Hemophilia Advisory Panel

Transcription

1 HEMOPHILIA TREATMENT IN NEW YORK STATE STATUS REPORT AND RECOMMENDATIONS The New York State Department of Health Hemophilia Advisory Panel Richard A Lipton, M.D., Chairman Third Edition 2001

2 Requests for copies of this publication may be directed to: Blood and Tissue Resources Program Wadsworth Center New York State Department of Health Empire State Plaza P.O. Box 509 Albany, NY

3 Hemophilia Treatment in New York State Status Report and Recommendations The New York State Department of Health HEMOPHILIA ADVISORY PANEL Richard A. Lipton, M.D., Chairman Third Edition 2001

4 TABLE OF CONTENTS Introduction I. Acknowledgments... 1 II. New York State Hemophilia Advisory Panel A. Members... 2 B. Mission... 2 III. Hemophilia A. Definition... 3 B. Clinical Picture... 3 C. Genetic Inheritance... 4 IV. Other Clotting Disorders... 4 V. Modern Hemostatic Therapy for Hemophilia A. Historical Perspective... 6 B. The Comprehensive Hemophilia Treatment Center Model... 8 C. Blood Derivatives... 9 D. Other Treatments... 9 VI. Complications of Hemophilia A. Joint Disease B. Liver Disease 1. Hepatitis A Hepatitis B Hepatitis C C. HIV Infection D. Inhibitors VII. Cost of Care A. Clotting Factor Concentrates B. Financial Subsidy of Comprehensive Hemophilia Centers VIII. Concerns/Challenges A. Discrimination B. Health Insurance C. Child Health Plus D. Physically Handicapped Children s Program E. Medicaid F. Medicare G. Supplemental Security Income H. Hospital Inpatient Care IX. Research in New York State X. New York State Hemophilia Advisory Panel Highlights XI. Conclusions XII. Recommendations for Action... 22

5 XIII. Appendices A. Hemophilia Treatment Centers in New York State B. Statewide Hemophilia Data Table 1. Prevalence of Hemophilia A and B in the State by Severity and Region Table 2. Causes of Death in Persons with Hemophilia Table 3. Race of Persons with Hemophilia by Region Table 4. Age of Persons with Hemophilia by Region Table 5. Primary Source of Insurance Coverage by Region of Residence C. Emergency Room Poster D. Department of Health Emergency Care Medical Advisory E. Voluntary Hemophilia Organizations in the State F. Biographical Information on Members of the Hemophilia Advisory Panel XIV. Glossary... 32

6 INTRODUCTION The New York State Hemophilia Advisory Panel was established in 1983 to promote optimal health care for all patients in New York State with hemophilia and related genetic bleeding disorders. It is committed to maintenance of a safe, adequate, and affordable supply of blood and blood products for these patients. Through Statewide statistical monitoring of demographic, geographic, medical care source and reimbursement data, educational materials have been developed to enhance professional knowledge and public awareness. The Panel supports and promotes non-discriminatory access to comprehensive hemophilia care for all persons with hemophilia in the State. This report offers a comprehensive look at the care and treatment of approximately 1,400 individuals with hemophilia living in New York State. Written in non-technical language, it attempts to highlight the major issues affecting this population. While the report in part offers a historical perspective, the Hemophilia Advisory Panel recognizes that much of the information presented is of a temporal nature. The Panel is committed to updating this document to keep the reader informed about current issues related to the care and treatment of persons with hemophilia. This report depicts the historical evolution of hemophilia, its associated complications, and the many advances in its treatment since The focus is the interface between ideal contemporary treatment and the challenges to its provision posed by the complex health care system currently in place. The challenges of the new millennium encompass barriers to access to specialized care, as well as the escalating costs of medical care and the inadequacy of medical insurance coverage.

7 I. Acknowledgments The New York State Hemophilia Advisory Panel gratefully acknowledges the pioneering efforts of the Metropolitan Chapter of the National Hemophilia Foundation, Inc., now known as the Hemophilia Association of New York (HANY), which successfully worked for establishment of the Hemophilia Program within the New York State Department of Health. We also acknowledge the leadership of the Commissioner of Health, Antonia Novello, M.D., M.P.H., Dr.P.H, and former Commissioner Barbara DeBuono, M.D., and the dedication of Department staff, particularly Jeanne V. Linden, M.D., M.P.H.; Marcia H. Kolakoski, M.S.; and Judith Bartholomew, R.N., B.S.N. 1

8 A. Members Richard A. Lipton, M.D., M.P.H., Chairman Wayne S. Cook, Jr. Rita Epstein Diane M. Groth, R.N., C.P.N.P. Thomas D. Harrington Rosemary Holmberg, R.N., B.S.N. Jennifer Pearce, M.D. II. NEW YORK STATE HEMOPHILIA ADVISORY PANEL New York State Department of Health Staff Jeanne V. Linden, M.D., M.P.H. Marcia H. Kolakoski, M.S. B. Mission The New York State Hemophilia Advisory Panel recognizes that optimal hemophilia care is ensured when modern treatment methods are applied within the setting of specialized comprehensive hemophilia treatment centers. The Panel is particularly concerned that a significant number of persons with hemophilia in the State are unaware of or denied access to comprehensive care. Employing the resources of the New York State Department of Health, the Panel: Monitors demographic and geographic distribution of persons with hemophilia, and gathers data regarding sources of medical care. Promotes development of educational materials for health professionals and the general public. Enhanced professional and public awareness enables more persons with hemophilia to participate in comprehensive care. Recognizes the critical role that adequate medical insurance plays in enhancing the quality of life of these individuals. Remains committed to maintenance of a safe, adequate, and affordable supply of blood and blood products for persons with hemophilia, as well as the public at large. The Panel is concerned that proposals to amend the State s blood shield law could have the unintended result of making important medications needed in obstetrics, surgery, immunology, and hemophilia treatment more costly and/or less available. Promotes high standards in provision of care to persons with hemophilia for HIV-related morbidity. Remains firm in its commitment to combat discrimination against persons with hemophilia, regardless of their HIV status. Recommends the availability of genetic counseling and testing for the State's hemophilia population and their at-risk family members. 2

9 III. HEMOPHILIA A. Definition Hemophilia is a rare, hereditary bleeding disorder that results from a deficiency in blood proteins known as clotting factors. Without these clotting factors, which are necessary for formation of clots, individuals experience prolonged bleeding. Hemophilia is transmitted genetically as a sex-linked disorder, affecting males almost exclusively. However, an increasing awareness has emerged that many women who are carriers of hemophilia have a mild but still clinically significant bleeding disorder. Approximately 30 percent of cases occur in the absence of a familial history, reflecting a spontaneous mutation rate. The disease takes two forms: factor VIII deficiency, also known as classical hemophilia or hemophilia A, and factor IX deficiency, also known as hemophilia B or Christmas disease. Factor VIII and factor IX deficiencies were not recognized as separate disorders until Factor VIII deficiency is four times more common than factor IX deficiency. B. Clinical Picture Although bleeding episodes may be precipitated by injury or surgery, internal bleeding can occur spontaneously in more severely affected individuals. Most bleeding takes place in the large hinge joints, e.g., ankles, knees, hips and elbows, but can also occur in the muscles and/or vital organs. Recurring bleeding episodes can cause severe joint damage, resulting in crippling arthritis and limited range of motion. Individuals with bleeding disorders do not bleed any more rapidly than persons with normal clotting factors, but they bleed for longer periods. Although the blood may not be visible, bleeding episodes in the head, oral cavity or vital organs may be lifethreatening. Health care providers are concerned about the potential danger to persons with an undiagnosed congenital bleeding disorder, since the diagnosis might first come to medical attention following trauma or surgery. Hemophilia A Case Study James, now 17 years old, has severe factor VIII-deficient hemophilia. He was diagnosed as a newborn after emergency surgery to correct pyloric stenosis (blockage to the stomach outlet) which was complicated by excessive post-operative bleeding. The family consists of an older brother and sister, but there is no prior family history of hemophilia. James received commercial clotting factor concentrate postoperatively on one occasion in April 1983, but because of growing concerns about transfusion safety, the treatment plan was changed to cryoprecipitate. Several soft tissue hemorrhages were treated in the emergency room with cryoprecipitate during the summer and fall of After 1985, his hemorrhages were managed with heattreated factor VIII concentrate. He experienced particular difficulties from recurring hemorrhages into the right knee joint. A program of scheduled factor infusions was begun, and he had no further knee hemorrhages. By the age of five, his mother had learned how to administer clotting factor concentrate at home. While at hemophilia summer camp, James learned how to self-infuse clotting factor. He is now in the 11th grade and doing well academically. He enjoys basketball, bike riding, and hunting and fishing with his father. He has an after school job three days a week. He used 400,000 units of factor VIII concentrate in The cost to his health insurance carrier for clotting factor was approximately $220,000. 3

10 C. Genetic Inheritance At least ten proteins must work in a precise sequence to make blood clot. A defect in any of these clotting factors may lead to abnormal bleeding. The genes involved in factor VIII and factor IX production are both located on the X chromosome; therefore, hemophilia is frequently referred to as a sex-linked trait. A mutation in one of these genes can cause a clotting factor to be defective. The gene associated with hemophilia may be passed on to the subsequent generation by either parent. Women who carry the gene that causes hemophilia are called "carriers." All affected members of a given family feature the same defect in their factor VIII or factor IX gene. Factor deficiency severity is usually the same in different members of the same family. In two-thirds of hemophilia cases, there is a family history of the disorder. However, hemophilia arises as a spontaneous mutation with no familial history in approximately one-third of families. Females have two X chromosomes, while males have one X and one Y chromosome. Each parent contributes one of these sex chromosomes to each offspring. In Figure 1 on page 5, the first chart (Figure 1a) illustrates transmission of normal genes, resulting in children who are not affected. In the case of a female carrier, there is a chance that any given daughter will be a carrier and that any given son will have hemophilia (Figure 1b). The third chart depicts a hemophilic father who only has an altered X chromosome, which he will pass on to all of his daughter(s), thus making them carriers (Figure 1c). His son(s), however, will not be affected. It is possible for some carrier females to have low factor VIII or factor IX activity and be symptomatic; thus, they are called symptomatic carriers. Symptomatic carriers often require treatment following traumatic injury or prior to surgery, including dental surgery. It is possible, but rare, that both parents may carry affected genes. Sons born to a hemophilic father and a carrier mother stand a chance of hemophilia. Daughters also have a chance, since both parents have an X chromosome with the hemophilia gene. In this case, daughter(s) who do not have hemophilia are carriers. Hemophilia's inheritance pattern and its clinical pattern of bleeding have been known for many centuries. The earliest description of hemophilia is attributed to the medieval physician and rabbi Maimonides. He understood the pattern of sex-linked inheritance, and recommended against ritual circumcision in males whose brothers or male cousins had hemorrhaged during the procedure. The best-known cases of hemophilia are those among male descendants of England's Queen Victoria in the nineteenth and twentieth centuries. IV. OTHER CLOTTING DISORDERS Another important related inherited disorder of hemostasis, von Willebrand disease, is transmissible as a dominant or a recessive genetic disorder affecting either sex. Women with von Willebrand disease are particularly at risk for anemia due to menstrual blood loss. Furthermore, women with undiagnosed von Willebrand disease are likely to suffer morbidity from unneeded gynecologic procedures, including hysterectomy. Several other less common hemorrhagic disorders are inherited as recessive genetic conditions. 4

11 Figure 1. Hemophilia Inheritance Patterns Normal Normal Carrier Normal Mother Father Mother Father 100% probability - normal child 25% probability - carrier female 25% probability - hemophilic male 50% probability - normal male or female Figure 1a. Figure 1b. Normal Mother Hemophilic Father 50% probability - normal male 50% probability - carrier female Figure 1c. 5

12 V. MODERN HEMOSTATIC THERAPY FOR HEMOPHILIA A. Historical Perspective Whole blood and plasma transfusions were performed as part of hemophilia care prior to the 1960s but proved ineffective given the unpredictability of bleeding episodes, unavailability of blood products, and traveling distance to hospitals. Moreover, unless the missing clotting factor could be concentrated into a smaller injection volume, its level could not be sufficiently increased in the recipient s blood stream. Persons with hemophilia seldom lived beyond the age of 30. Those surviving were usually disabled with crippling musculoskeletal dysfunction. Surgery was extremely hazardous. The hemophilic individual was often prevented from pursuing educational and vocational objectives. A life of pain, unmet goals, and the continuing threat of hemorrhage took their toll on the psychological health of the affected individual and his family. The 1960s saw the development of procedures to isolate cryoprecipitate, the first practical clotting factor concentrate, for use in treating bleeding episodes. Cryoprecipitate could be produced in blood banks during routine blood component preparation and was soon readily available nationwide. Still, its major disadvantage was that it needed to be stored frozen and was not easily adaptable to ambulatory self-treatment. Advances in plasma protein processing in the 1960s and the 1970s triggered emergence of the commercial plasma derivative industry. These companies engaged in bulk fractionation of human plasma from thousands of blood donors into albumin, immune globulins, and clotting factor concentrates. The advantage of commercially derived concentrates was that they could be freeze-dried in convenient dosage bottles for storage at room temperature and be self-administered following reconstitution. A significant disadvantage of these products, also shared by cryoprecipitate, had been their potential for virus transmission, exposing many hemophilic individuals to hepatitis and other viral contaminants. Moreover, their availability was dependent on supply and demand in the albumin and immune globulin market. In the 1980s, hemophilia patients were struck a devastating blow when it was learned that clotting factor concentrates could become contaminated with the human immunodeficiency virus (HIV). Many hemophilic persons who received these products prior to 1985 were exposed to HIV. Approximately 80 percent of persons with severe hemophilia in New York State at that time were thought to have become infected with HIV. Since 1984, methods utilizing heat and certain solvents and detergents were developed for treating clotting factor concentrate to inactivate HIV and other viruses. Therefore, no children presently age 15 and younger have become HIV-infected from clotting factor concentrates. During the 1990s, technology for manufacturing purer clotting factor concentrate continued to advance. Using specific monoclonal antibodies and techniques such as chromatography, factors VIII and IX were separated from other plasma proteins. However, these production methods are more expensive, and treatment costs escalated. Factor VIII and factor IX concentrates may also be prepared through recombinant DNA technology. These products hold the promise of eliminating the risk of transfusion-associated diseases. While they may be subject to less price fluctuation than plasma-derived factor concentrates, these new products are presently more expensive. The timeline on the following page depicts significant events in hemostatic therapy for hemophilia. Today, hemophilia patients and their families are optimistic that hemophilia can eventually be cured with advances in gene therapy research. 6

13 7 Pre-1960s Whole blood and plasma transfusions Ineffective due to length of time for blood processing and travel time to hospitals. Disability and early death common Modern Hemostatic Therapy for Hemophilia Historical Perspective 1960s Cryoprecipitate extracted from pooled plasma of many blood donors 1970s Human plasma clotting factor concentrates commercially prepared 1980s Factor concentrates found to be infected with HIV and hepatitis 1990s Monoclonal and genetically engineered factor products developed Product could be prepared in blood banks and was readily available nationwide Convenient freeze-dried dosage bottles could be stored at room temperature until needed Heat, solvents and detergents were used to inactivate HIV and hepatitis viruses Genetic engineering reduces risk of virus transmission, but methods are expensive and costs escalated 2000s Gene therapy research Possible cure for hemophilia?

14 B. The Comprehensive Hemophilia Treatment Center Model By 1970, it became apparent to hematologists treating hemophilia that merely offering effective hemostatic therapy during a bleeding crisis was insufficient to improve patient prognosis. Several major hospitals and organizations in the United States, including Los Angeles Orthopedic Hospital, The New York Hospital and The Rochester Chapter of the National Hemophilia Foundation, developed what were to become models for a national network of comprehensive hemophilia treatment centers. These pioneering institutions documented a substantial improvement in quality of life for persons with hemophilia when the venue of care moved from the hospital emergency room to a designated hemophilia treatment center emphasizing preventive care. These early successes attracted the attention of federal health planners, who recognized that comprehensive care for a complex and chronic illness such as hemophilia could serve as a useful model for dealing with rare, potentially high-cost, multi-faceted illnesses. In 1973, federal funds became available to establish a national network of comprehensive hemophilia treatment centers, including four in New York State. These centers were encouraged to establish satellites or affiliations with other medical centers within the region. At hemophilia centers, a team of dedicated medical and nursing specialists addresses the full range of long-term needs of persons with hemophilia and other congenital clotting disorders, such as von Willebrand disease. The centers provide comprehensive, multi-disciplinary services, including hematology care, dental care, orthopedic care, physical therapy, psychosocial support, infectious disease care, and financial, vocational and genetic counseling. The hemophilia nurse specialist plays a pivotal role in patient care management. Typically, the hemophilia nurse has been the professional responsible for training patients and their family members in home administration of clotting factor concentrates. Comprehensive care, such as that in federally funded hemophilia treatment centers, epitomizes the standard of care for individuals with hemophilia, as recommended by the Medical and Scientific Advisory Council of the National Hemophilia Foundation. Hemophilia treatment centers are now reaching out to women with undiagnosed bleeding disorders due to von Willebrand disease or by virtue of being "carriers" of hemophilia. The prevalence of all cases of hemophilia and related disorders at any given time is difficult to estimate. It has been estimated that there are 13,320 cases of hemophilia A and 3,640 cases of hemophilia B in the United States. Approximately 67 percent (11,364 patients) are enrolled in 134 hemophilia centers nationwide. These centers and their affiliates provide family-centered, multi-disciplinary services to individuals with hemophilia, von Willebrand disease and other bleeding disorders. Approximately 1,000 of the 1,428 persons with hemophilia (70 percent) residing in New York State receive some care in the hemophilia treatment center setting. Three comprehensive hemophilia treatment centers are located in the New York City area. In the upstate area, the Mary M. Gooley Hemophilia Center, Inc., in Rochester operates autonomous associated facilities in Buffalo, Syracuse, Johnson City, and Albany (see Appendix A). 8

15 C. Blood Derivatives Plasma-derived factor concentrates are produced for the relatively few hemophilic persons worldwide, in part because these concentrates can be prepared easily from a byproduct of plasma procured for manufacturing more widely used derivatives such as albumin and immune globulins. Absent such a linkage, it is possible that clotting factor concentrate would not be available at a reasonable cost. Plasma derivative manufacturers obtain plasma primarily by plasmapheresis from paid donors. Plasma collected from 5,000 to 40,000 donors is pooled and processed together. In fractionation plants, physically resembling breweries or dairies, large containers of plasma are processed sequentially into clotting factor concentrate, albumin, and immune globulins. Prior to development of an HIV test in 1985, albumin and immune globulins had been sufficiently treated by heating during manufacturing to render them virus-free. Clotting factor concentrates could not be subjected to the same amount of heat without destroying their potency. Eventually, methods were developed to inactivate HIV and hepatitis virus during the manufacturing process, but not before many hemophilic individuals who had received clotting factor concentrates between 1979 and 1985 became infected with hepatitis B virus (HBV), hepatitis C virus (HCV), and/or HIV. Now, viral inactivation techniques and donor screening render factor concentrates significantly safer from the risk of HIV and hepatitis virus infection. No cases of HIV transmission due to infusion of clotting factor concentrates have been reported in the United States since March The incidence of transfusion-associated diseases has been significantly reduced by the advent of stringent blood donor screening for HIV, and the viruses causing hepatitis B and hepatitis C through detailed donor health history and sensitive blood tests. Mandatory blood and plasma donor testing for HBV, HIV and HCV in 1972, 1985 and 1990, respectively, and advances in clotting factor production technology all have contributed to the safety of factor concentrates. The safety of hemophilia products is further ensured through advances in purification and virus inactivation by physical and chemical treatments. However, present virus inactivation methods may not completely eliminate the risk of all forms of hepatitis. It is recommended that all previously unexposed potential transfusion recipients receive hepatitis B vaccination. On rare occasions, clotting factor concentrates have been contaminated with hepatitis A, and vaccination for hepatitis A is now recommended. Several effective but expensive methods of purifying clotting factor concentrates are in use. Clotting factor may be concentrated by isolation from plasma using monoclonal antibodies. Another method involves physical/chemical separation by a process known as chromatography, and then virus-inactivation by heating, using certain solvents and detergents, filtration, or combinations of these methods. High-purity clotting factor concentrates are sold at two to four times the price of concentrates with a higher plasma protein content--the higher the protein content, the less pure the product. D. Other Treatments Genetically engineered factor VIII concentrate, commonly called recombinant factor VIII, and albumin-free recombinant factor IX are licensed for use by the federal Food and Drug Administration (FDA). In fact, 60 to 70 percent of all factor IX product dispensed is recombinant. Recombinant products hold the promise of eliminating most concerns about transfusion-associated disease, but costly production methods raise other considerations about costs, and, therefore, their availability to many hemophilic individuals may be limited. 9

16 In selected patients with mild factor VIII deficiency, symptomatic female carriers of hemophilia, and some forms of von Willebrand disease, the drug desmopressin (DDAVP), which stimulates the body to release more of its own factor VIII, reduces or eliminates the need for blood products. DDAVP can be administered intravenously or as a nasal spray. Several medications are available as important adjuncts to hemophilia dental treatment, reducing the quantity of clotting factor concentrate needed. These drugs, called anti-fibrinolytic agents, prevent clots, once formed, from dissolving prematurely. VI. COMPLICATIONS OF HEMOPHILIA The complications of hemophilia include joint and liver disease, HIV immunosuppression, and development of inhibitors. A. Joint Disease The most common and debilitating complication of hemophilia, affecting approximately 80 percent of the hemophilia population, results from recurrent hemorrhages within the joints. The synovial membrane that lines all joints secretes a clear fluid that functions as a natural lubricant. Repeated bleeding, whether spontaneous or due to trauma, causes inflammation of the synovial lining (synovitis). Cells that mediate the body s inflammatory response digest not only unwanted blood in the joint, but also begin to digest the cartilage at the ends of bones. Without the protection of this cartilage, upon movement, friction between bones causes pain. Continued destruction results in scar tissue, pain, and stiffness, leading to arthritis. 10

17 B. Liver Disease 1. Hepatitis A In the United States, hepatitis A is generally considered to be transmitted by the fecal/oral route via infected food handlers or drinking water. Although several outbreaks of hepatitis A from clotting factor concentrates have been reported in Europe, only a few cases associated with solvent-detergent treated methods have occurred in the U.S. The manufacturing process for factor concentrates has been enhanced by filtration or a heating process to help eliminate hepatitis A virus. 2. Hepatitis B When clotting factor concentrate became widely available in the early 1970s, most persons with hemophilia were exposed to the hepatitis B and hepatitis C viruses. While some individuals experienced episodes of acute hepatitis, most never noted acute illness. However, most persons with hemophilia exhibited serologic (blood test) evidence of prior exposure; laboratory testing of liver function enzymes often showed abnormalities. Some individuals manifested clinical signs of chronic liver disease from hepatitis virus infection. About 15 percent of those exposed to hepatitis B exhibit persistent viral protein in the blood. For some, these findings may be associated with increased likelihood of developing significant liver disease such as cirrhosis and liver cancer. Safe and effective vaccines against hepatitis B virus are available and should be strongly considered for hemophilic individuals or other persons receiving blood or plasma derivatives who have not been previously exposed to the virus. Hepatitis B vaccination is now routine for most children. 3. Hepatitis C Hepatitis C occasionally arises in multiply-transfused individuals: however, more than 90 percent of hemophilic persons have been exposed to the virus. In most cases this exposure leads to chronic infection. The single most common reason for patients to require a liver transplant in the United States is hepatitis C infection. At its onset, this infection does not cause any symptoms, but, as the decades pass, those infected are placed at increased risk of cirrhosis and liver cancer. Several medical therapies are in use or under development to eradicate chronic hepatitis C, but these efforts to date, particularly in hemophilic individuals, have not been very effective. A laboratory test has been developed 11

18 and is in use for screening blood donors for the virus; however, a vaccine for hepatitis C is not yet available. Hemophilia Complicated by Hepatitis C Richard is a 45-year-old male with mild hemophilia and limited exposure to clotting factor concentrates. Fortunately, he is HIV-negative, but he acquired a chronic infection with hepatitis C after exposure to cryoprecipitate for trauma-related hemorrhages in late childhood. Richard is married, and his wife is employed. He has health insurance coverage through his wife's employer. He operates a commercial refrigeration repair business from his home. During the past five years, he has become increasingly weakened by progression of his hepatitis C infection to cirrhosis. Unable to meet the physical demands of repairing large refrigeration units, he is rapidly losing hard-sought clients, and his business will soon fold. Richard has been placed on the waiting list for a liver transplant. A small hepatoma (liver cancer lesion) was noticed on his abdominal CAT scan, lending urgency to the transplant. Ultimately, if he receives a donor liver and the procedure is successful, his hemophilia will have been "cured," because the donor liver should produce sufficient amounts of factor VIII. C. HIV Infection While they represent only 1.1 percent of AIDS patients reported to the Centers for Disease Control and Prevention (CDC), persons with hemophilia are a unique patient group with special needs and problems requiring special resources. As of June 30, 2000, CDC had recorded 5,357 cases of acquired immune deficiency syndrome (AIDS) among individuals with hemophilia or other congenital coagulation disorders, and no other risk factor; 236 of these were children under 13 years old at the time of diagnosis. While these numbers appear relatively low compared to the more than 753,000 total AIDS cases in the United States, the proportion of men with hemophilia exposed to HIV through factor concentrates is very high. Several serological surveys suggest that from 1979 to 1985 an estimated 80 percent of persons with severe hemophilia became infected with HIV. Persons with hemophilia, cared for at comprehensive hemophilia treatment centers, receive counseling about HIV exposure and its effects. HIV testing, as well as clinical and laboratory immunologic surveillance, are essential aspects of comprehensive hemophilia care. Past studies have indicated that from five to 20 percent of sexual partners of HIV-infected men with hemophilia may have become infected as well. Because of concerns about increased heterosexual and maternal-fetal transmission of HIV, specific risk reduction programs have been developed for sexually active individuals. The hemophilia treatment centers continue to facilitate access to specialized counseling services, support groups and other regional resources. Results of recent clinical trials suggest that the onset of AIDS in HIV-positive individuals can be postponed by early intervention with complex and expensive combinations of anti-hiv medications. In some instances, these medical treatments have significantly improved the quality 12

19 of life of infected individuals. In New York State, the death rate from AIDS is declining in this population. D. Inhibitors Approximately 25 percent of patients with hemophilia will, at some point in their lives, develop an immune response against the clotting factor protein contained in clotting factor concentrates. The emergence of an "inhibitor" as it is called, significantly increases long-term morbidity for many of those so affected. A. Clotting Factor Concentrates VII. COST OF CARE Clotting factor concentrates were initially made available only through a hemophilia center or a hospital pharmacy or blood bank. Beginning in the 1980s, commercial home care companies increasingly replaced hospitals as distributors of clotting factor concentrates. These for-profit entities serve a useful purpose in areas where treatment centers or hospitals are unable to provide clotting factor for home use. Regardless of the source, most clotting factor concentrate (90 percent) is administered at home, with its final price dependent upon the nature of the distribution system and how much health insurers are willing to pay. Fully developed distribution systems provide medical treatment coordination, shipment of concentrates and collection of used injection materials for medical waste disposal. Clotting factor replacement therapy represents the most costly aspect of hemophilia treatment. Annual expenditures for clotting factor concentrate distributed by the Hemophilia Consortium (see page 14) rose from approximately $5 million in 1987 to approximately $65 million by the end of More than $550 million were spent nationwide. Hemophilia B Complicated by an Inhibitor Alan is a thirteen-year-old boy with factor IX-deficient hemophilia. In the first year of life, he was found to have an inhibitor (an antibody) to factor IX infusions, making his hemorrhages untreatable with factor IX clotting factor concentrate. He is treated with a special clotting factor called prothrombin complex concentrate; however, this material is less effective in arresting hemorrhages, resulting in progressive musculoskeletal disabilities from recurrent bleeding into his right knee joint. Alan has been unable to extend his knee fully because of the resulting hemophilic arthritis. He frequently misses school, and often must use crutches or a wheelchair. A long-term treatment program to eradicate Alan's inhibitor was begun in 1997 and continued for 18 months. This treatment, called immune tolerance therapy, consists of a daily infusion of factor IX. Predictably, in the beginning of this treatment the strength of the inhibitor increases. However, the long-range goal is to fatigue the patient s immune system so that he becomes tolerant of the factor. This effect often occurs several months after immune tolerance therapy begins and is indicated by diminished strength of antibody measured in a special laboratory test called an inhibitor assay. Unfortunately, this therapy was not successful in Alan's case. While the inhibitor's strength diminished, it was never fully eradicated. During the immune tolerance therapy program, approximately $750,000's worth of clotting factor concentrate was required. The year prior to this treatment program, Alan had needed about $400,000 in prothrombin complex concentrate. An adolescent with factor IX deficiency without an inhibitor, on scheduled, twiceweekly factor infusions to prevent joint damage, would require approximately $150,000 to $200,000 of the concentrate annually. 13

20 However, self-treatment at home has been tremendously successful in reducing the cost of care, limiting disability and decreasing unemployment. Analyses by the National Hemophilia Foundation have shown that hemophilia treatment centers have saved federal and state governments, as well as commercial insurers, hundreds of millions of dollars by reducing the need for hospitalization, and decreasing clinic or emergency room visits. Clotting factor concentrate prices are not determined only by the plasma industry s costs of production and marketing. Acquisition and distribution of concentrates by intermediaries result in highly variable wholesale and retail prices. Although acquisition costs from manufacturers have stabilized, the final prices to patients or third party insurance payors are increasing because of inflated distribution costs by wholesale pharmacies and commercial home care companies. Nearly 30 percent of clotting factor distribution is handled by for-profit home care organizations, resulting in differences between acquisition and final prices often exceeding 150 percent. Home care agency profits are sufficient to offer hemophilia centers billing and collection services. A significant markup from acquisition costs also may be incurred if hospital pharmacies or blood banks distribute concentrates. This profit may go into a hospital's general operating budget or directly supplement the institution s costs for hemophilia care. These arrangements arise due to inadequate federal support of regional hemophilia centers and because health insurers, with few objections, are willing to pay inflated final prices. Hemophilia treatment centers in New York State are working to keep the costs of clotting factor down. Upstate New York treatment centers have developed center-owned clotting factor programs for their patients in Buffalo, Rochester and Albany. In metropolitan New York City, the three hemophilia centers, together with the Hemophilia Association of New York, have formed the Hemophilia Consortium, Inc., a not-for-profit corporation which is the country's largest bulk purchaser of clotting factor concentrate. The Consortium's buying leverage and a generic purchasing philosophy results in prices considerably below the national average. In 1992, Congress passed the Veterans' Health Care Act, requiring discounted acquisition costs for outpatient pharmaceuticals. Federally designated hemophilia treatment centers are covered entities under the Act. For three upstate hemophilia centers, acquisition costs have decreased by 15 percent. The Hemophilia Consortium similarly obtains discounts due to both the Act's provisions and the high volume of purchases. The Hemophilia Consortium has played an important role in allocating an expensive resource in times of scarcity. During 1988 and part of 1989, the nation experienced a dangerous shortage in clotting factor concentrate, directly threatening the health and safety of persons with hemophilia in the State. The shortage, continuing into the summer of 1989, was due in part to manufacturers dedicating plasma stores to producing monoclonal antibody-purified concentrate, since this complex process yields less clotting factor from each liter of plasma. Another reason for the shortage was that factor VIII production from plasma was linked to supply and demand in the world albumin market. An oversupply of albumin restrained the manufacturers' willingness to increase supplies of clotting factor concentrate until its price rose dramatically. In 1988, prices increased from approximately 10 cents to nearly 65 cents per factor VIII unit for several high purity products. Despite rapidly rising prices and a severe shortage, the Consortium was able to ensure availability of an adequate supply of clotting factor, but only after Consortium physicians agreed to cancel elective surgical procedures and sharply restrict the amount of products released for home 14

21 use. By 1990, the shortage had eased, with some reduction in the average price. In 1997, a worldwide shortage of porcine factor VIII concentrate arose. The Consortium s inventory was made available to physicians around the country on a priority basis, lessening the hoarding seen in prior shortages. Shortages continue today in the wake of product quarantines, recalls, and market withdrawals associated with quality control issues and lookback efforts resulting from increased surveillance by the industry and the FDA. B. Financial Subsidy of Comprehensive Hemophilia Centers In 1973, the federal government began subsidizing regional hemophilia centers and encouraged their growth, thereby making the special medical services needed by people with hemophilia more available. Federal grants in 1999 for hemophilia services, including HIV services, reached approximately $7.1 million for 134 hemophilia centers and their affiliates. The grants fund operational expenses and staff salaries, although payments for specific medical services and clotting factor concentrates are not included. Presently, government grants cover about 11 percent of the nation's hemophilia centers' operating budgets totaling about $65 million. The inadequacy of federal support has caused many regional hemophilia centers to become involved in home distribution of clotting factor concentrates, whereby processing and handling fees can significantly augment operational funding. These arrangements also underwrite otherwise uncompensated care of indigent patients. VIII. CONCERNS/CHALLENGES The medical needs of hemophilia patients are emergent, episodic and ongoing. However, some patients continue to receive nearly all medical treatment in the hospital emergency room despite the fact that comprehensive care is available at comprehensive treatment centers. While the primary care physician might be contacted by telephone, unless hospitalized, the patient might not be seen by a physician with hemophilia experience. In New York State, such fragmented, crisis-oriented care still persists for many individuals with hemophilia. A. Discrimination The hemophilic person and his family are at significant risk of discrimination at work and school. Anecdotes of overt as well as subtle discrimination are sometimes relayed to the Hemophilia Advisory Panel. Several dramatic instances of discrimination reported widely in the media have generated fear among hemophilic individuals. Often, any actions a person with hemophilia might take against a discriminatory act are tempered by the realization that the publicity resulting from this action may be ultimately counterproductive. The Panel has received reports of instances of some medical and dental professionals refusing to care for HIV-infected individuals. B. Health Insurance In recent years, the driving force within the health insurance industry has been cost containment, posing a challenge for carriers, providers and patients alike. Most health insurance coverage provided by employers involves managed care arrangements that attempt to limit access to specialty care by using patients' primary care physicians as gatekeepers to these services. Since they are encouraged to practice medicine more economically, primary care physicians may face ethical dilemmas associated with financial incentives designed to decrease specialty service utilization. New York State s hemophilia treatment centers are challenged by the multiplicity of HMOs with which they must have arrangements in place in order for all patients to access the centers' specialized care. It is critical for a patient's hemophilia center to be included in his HMO's provider network. 15

22 Prompt access to essential and, in some reported instances, emergency clinical services has been hindered by problems associated with required determination of medical necessity prior to authorization for care. Many hemophilic individuals report limitations on the frequency of visits and/or reimbursement problems for specialized emergency and consultative services received at their hemophilia center. Annual and/or lifetime caps are frequently imposed on routine and preventive office-based services, as well as specialty and hospital-based care and clotting factor concentrates. Moreover, even when these services are available, they may be subject to high deductible payments. Coverage for clotting factor concentrates can be subject to co-payments that are unaffordable for many families. Coordination of care between the primary care physician and the specialist is imperative in order to maintain the standard of care for this chronically ill population and, therefore, maximize treatment outcomes. Children with chronic disabilities, especially those living in poverty, have special needs related to normal growth and development. Managed care arrangements have not sufficiently addressed these children's developmental vulnerabilities in defining covered benefits. By failing to provide medical services according to a standard of care, a child s covered benefits might not allow him to achieve his potential. Risk-adjusted capitation payments are needed; otherwise these children may be subject to discrimination when enrolling in health plans. Unfortunately, according to an issue brief provided by the American Academy of Pediatrics, no valid or reliable risk adjustment approaches are available for children. Because of inadequate health insurance coverage, many adult patients and parents of pediatric patients must choose between viable careers, and working in lower-paying positions or not working at all, in order to qualify for government assistance. C. Child Health Plus Congressional passage of Title XXI of the Social Security Act extends health insurance to uninsured children (19 years of age or younger) by providing funds to the states for that purpose. In New York, these funds are used to expand the eligibility and range of benefits offered by the State s Child Health Plus Program. However, Child Health Plus does not cover outpatient clotting factor concentrates. This limitation thwarts the envisioned seamless transition from Medicaid, which covers clotting factor concentrates, to Child Health Plus. Without coverage for clotting factor concentrate, a family affected by hemophilia would have considerable difficulty moving from welfare to work. D. Physically Handicapped Children's Program Administered and funded on a county-by-county basis, this program is of only sporadic benefit to persons with hemophilia in New York State. Children with hemophilia, residing in counties with limited budgets, have been excluded from participation because hemophilia-related expenditures have affected available resources significantly. E. Medicaid Many hemophilia patients do not qualify for Medicaid benefits simply because of their present ability to work. Significant concerns have been raised that restrictions in future health insurance benefits may lead to impoverishment of more persons with hemophilia and the need for expansion of Medicaid benefits. 16

23 New York's waiver application to the federal government for mandated Medicaid managed care was approved recently. The Hemophilia Advisory Panel is concerned about for-profit HMOs' implementation difficulties with Medicaid comprehensive benefit packages. Inadequate Insurance Coverage Robert is a nine-year-old boy with severe hemophilia. He was born in the West Indies. His parents are divorced, and, at the age of eight, he came to New York City to live with his father, stepmother and their children. Since infancy, Robert s bleeding episodes had been managed in his native country by hospitalizations and emergency room visits. Clotting factor concentrate was provided only for life-threatening hemorrhages. He has a painful arthritis in his right knee as a result of prior inadequate medical interventions. The medical treatment promoted by Robert's hemophilia treatment center was prompt administration of clotting factor concentrates for all hemorrhages, many of which occurred in his inflamed right knee. The long-term plan of care is to train a family member, and ultimately Robert, in home administration of clotting factor concentrate. This approach would shorten the time from hemorrhage to treatment, and lessen the acute pain and progression of his hemophilic arthritis. Home treatment would also reduce school absences and his parents' absenteeism from work. Struggling to stay employed, his parents do not have health insurance benefits and have enrolled their children in New York State s Child Health Plus program. Since Child Health Plus does not include clotting factor concentrates in its formulary, the medical recommendations of Robert's hemophilia treatment center have not been fully implemented. Most of the factor he has received to date has been either from the hospital emergency department or donated by philanthropic sources. Despite counseling and aggressive advocacy by the treatment center s social worker, a determination that Robert is eligible to receive Medicaid benefits has been delayed by more than a year. It may now be possible to begin home-based treatment for him. F. Medicare Most people with hemophilia are under 65 years of age and, as a result of hemophilia treatment, are not permanently disabled. Those under 65 with permanent disabilities are eligible for Medicare benefits after a two-year waiting period. Still, as HIV infection progresses, more infected adults become disabled. Medicare reimburses up to 80 percent of approved blood product costs incurred on an outpatient basis. Recent increases in clotting factor price make the 20-percent Medicare co-payment impossible for most beneficiaries to meet. Recently, many health plans have abandoned their Medicare Managed Care programs because of inadequate government reimbursement. G. Supplemental Security Income Eligibility requirements for Supplemental Security Income (SSI) as a means of accessing disability benefits have been tightened of late. Many people with hemophilia are likely to be adversely affected by such a change because their disabilities are made less evident through treatment. Yet, without this entitlement, they may not be able to continue to receive comprehensive treatment. 17

24 H. Hospital Inpatient Care Since 1997, New York State s hospitals have been able to negotiate inpatient rates directly with health plans. These contracts need to be skillfully crafted so as to not "over discount" certain high-cost services needed in the care of special populations. For example, clotting factor concentrates purchased at a discount by a federally designated hemophilia center should not be discounted further but, instead, should be carved out of a hospital s contract with a health plan. Hospitals providing in-patient services to people with hemophilia must be adequately reimbursed by all third parties for the cost of administered clotting factor concentrates. These costs must be carved out of contractual arrangements between the treating hospital, private health plans and government payors. Beginning in 1998, federal law has provided for a pass-through of clotting factor concentrate inpatient charges for Medicare patients. This provision allows the hospital to bill Medicare for actual charges for clotting factor concentrates administered to inpatients. These passthrough payments are also applicable to Tri-Care program patients. The Hemophilia Advisory Panel strongly recommends that New York State consider a similar inpatient pass-through for Medicaid patients' clotting factor charges. IX. RESEARCH IN NEW YORK STATE Since the early 1980s, the federal Maternal and Child Health Block Grant program has provided funding to hemophilia treatment centers. In 1993, CDC was mandated by Congress to determine the number of cases of hemophilia in the United States and assess the status of the hemophilia population's health. With this information in hand, CDC and other federal programs will be better equipped to meet the needs of the hemophilia community through research, education and health care programs. To fulfill this mandate, CDC issued a request for proposals (RFP) to announce the availability of federal grant funding to several state health departments for characterization of the statewide epidemiology of hemophilia A and B and associated complications. Five other states in addition to New York State were awarded cooperative agreement funds: Colorado, Georgia, Louisiana, Massachusetts and Oklahoma. Exhaustive case finding was conducted in an effort to identify every hemophilia case among the residents of these states. New York State field staff investigated every reported case to determine case eligibility according to CDC case definitions. If a case was deemed eligible for inclusion in this public health initiative, a retrospective review of medical records from all identified health care sources was performed for calendar years 1993 through 1998 utilizing a surveillance tool developed by CDC. Since cases were assigned a unique CDC identification number, the identity of cases remained confidential at the State level and anonymous at the federal level. New York State data comprise 40 percent of the federal database and are summarized in Appendix B tables. The aggregate data are being analyzed by CDC and will be available in a database for researchers, consumers, and health care providers to use worldwide. This is the first time that a hemophilia database of this magnitude has been constructed for international use. 18

25 X. NEW YORK STATE HEMOPHILIA ADVISORY PANEL HIGHLIGHTS In the mid-1980s, disturbed by the rising costs of clotting factor to the health care system, Hemophilia Advisory Panel members met with representatives of the New York State Medicaid Program. As a result, a Medicaid reimbursement ceiling was placed on clotting factor, making it difficult to collect on claims reflecting inflated prices. In 1984, the Panel recommended to the New York State Department of Health that essential genetic counseling and testing services for the State's hemophilia population are most efficiently and cost-effectively concentrated at recognized hemophilia centers of excellence, where the majority of the patients are treated and at-risk family members served. In 1985, the Panel designed a pamphlet describing hemophilia, how it is acquired, its treatment and sources of assistance. To date, more than 50,000 pamphlets have been distributed to educators, hemophilic persons and the general public. A poster was devised detailing emergency care for hemophilic individuals and emphasizing the unique triage priorities necessary to treat hemophilia emergencies effectively. Distributed in 1986 to all New York State hospitals for display in emergency rooms, the poster has gained national recognition and served as a model for similar educational efforts in other states. The poster was revised in March, 1989 and April, 2000 (Appendix C), updating information on comprehensive hemophilia treatment centers in the State, as well as crisis intervention procedures. The Panel's primary concern is the safety, purity and efficacy of blood products such as clotting factor concentrates, and appropriate reimbursement for such products. Technological advances often affect factor concentrate supply and demand, as well as price. In 1988, a nationwide shortage of clotting factor concentrates caused a dramatic surge in costs. (See page 13.) The Hemophilia Advisory Panel convened a meeting of health insurance industry and State regulatory agency representatives to discuss revision of reimbursement policies for hemophilia care. Based on its comprehensive study of hospital reimbursement rates, the Panel successfully sought establishment of a separate diagnosis-related group (DRG) for hemophilia. As a result, from 1990 until rate-setting ended in 1997, hospitals treating inpatients with hemophilia were more equitably reimbursed by third party insurance payors. The Panel was instrumental in development of an emergency medical services (EMS) advisory on emergency care of individuals with hemophilia. The advisory was endorsed by the Commissioner of Health and disseminated to EMS providers Statewide in 1997 (see Appendix D). This advisory recommends that, when transporting a person with hemophilia, emergency personnel not consider solely the proximity of a hospital emergency room, and officially sanctions transporting the patient to more distant specialized hemophilia treatment centers, since not all hospitals in the State routinely stock clotting factor concentrates. The policy was developed as the result of consumer advocacy and serves as a nationwide model for field care of individuals with hemophilia. The Panel also sponsored a booth on this subject at the Department's Bureau of Emergency Medical Services' Vital Signs '96, '97, '98 and '00 conferences. 19

26 New York State Department of Health Hemophilia Advisory Panel Activities Timeline 1985 Public education need identified 1986 Emergency treatment deemed insufficient 1988 Clotting factor concentrates shortage and cost surge Diagnosis related groups needed for hemophilia 1997 Emergency treatment clotting factor not stocked in all NYS hospitals 1998 Medicaid managed care clotting factor selection by HMOs of concern 20 Hemophilia pamphlet developed explaining hemophilia, its treatment, and sources of assistance Emergency room care triage priorities poster designed and nationally recognized Meeting with State regulatory agency and health insurance representatives DRGs established for all inpatient hemophilia care Emergency medical services advisory developed Information on clotting factor concentrate provided to State Office of Medicaid Managed Care 50,000 copies distributed to educators, patients and the general public Distributed to all NYS hospitals and used as a model in other states Revision of reimbursement policies for hemophilia care DRGs implemented for more equitable reimbursement by insurance payors Advisory disseminated Statewide to EMS personnel Factor fully reimbursed by "carving out" cost of clotting factor

27 The Panel acts as a clearinghouse for hemophilia information, disseminating educational materials to persons with hemophilia throughout the State. Panel members have made presentations throughout the State to school nurse teachers. The Panel regularly meets with State Title V program staff, and the Panel chairman was a participant in the State's Medicaid Managed Care Task Force. The Panel continues to collaborate with the Department's Office of Managed Care on issues of quality of care and access to comprehensive hemophilia care. As Medicaid Managed Care began its implementation of the policy, information provided by the Panel resulted in a decision by the State to carve out the cost of clotting factor concentrate for full State reimbursement. This decision alleviated the Panel s concerns about potential adverse risk selection by HMOs. XI. CONCLUSIONS The comprehensive hemophilia treatment center is an integral and essential aspect of contemporary hemophilia care, and serves as a model health care system for other life-long conditions such as sickle cell anemia, cystic fibrosis and thalassemia (Cooley's anemia). Government support must be adequate to ensure that persons with hemophilia receive the full range of medical and counseling services necessary to treat the disease. The principal obstacle to accessing comprehensive hemophilia care in the year 2000 is unavailable or insufficient health insurance. Approximately 30 percent of people with hemophilia in New York State have nonexistent or inadequate health insurance coverage. In light of modern treatment modalities, a person with hemophilia need not be disabled or impoverished. Universal and unrestricted access to health insurance could prevent a lifelong medical condition from becoming a personal or societal catastrophe. In New York State, these insurance obstacles are highly significant -- transcending all other comprehensive care issues. The predominance of managed care arrangements raises serious issues regarding access to needed specialty hemophilia services. Needless, costly and often risky delays are incurred in accessing specialized hemophilia care because of gatekeeping and other requirements for specialized service authorization. These impediments may, in the end, be more costly to health plans and, in some instances, life-threatening to a person with hemophilia. At the present time, no publicly sponsored medical insurance plan addresses the hemophilic individual's requirement for lifelong treatment without prior assessment of financial need or designation of a disabling condition. Moreover, the State's Child Health Plus program does not include clotting factor concentrate in its outpatient formulary. Variations in medical benefits offered by private and public health plans prevent smooth transition of families undergoing changes in their hemophilia care eligibility and entitlements. Development of genetically engineered clotting factor products and changes in production methodology offer the hope of diminishing the incidence of transfusion-associated diseases, but at increased costs. Adequate supplies of clotting factor concentrates must be produced at affordable prices. 21

28 HIV infection and the threat of AIDS remain an alarming reality for many persons with hemophilia and their families. AIDS continues to reverse two decades of progress in hemophilia treatment, as many people with hemophilia become disabled and die of this unexpected complication. XII. RECOMMENDATIONS FOR ACTION Health Insurance: Legislative action is required to mandate that basic health insurance policies cover the cost of clotting factor concentrate administered outside the hospital setting. Whenever these costs are covered separately as a major medical benefit, lifetime ceilings provide only limited relief for a lifelong chronic hemophilia condition. Similar legislation already exists in New Jersey and is necessary to provide all citizens of New York State, including those with hemophilia, with comprehensive and affordable health insurance. The Hemophilia Advisory Panel regrets that New York State's Child Health Plus program has not taken favorable action regarding the Panel's recommendation that the cost of clotting factor concentrate be included as a specific benefit. This omission must be corrected. Hospital Reimbursement: Hospitals providing out-patient care to people with hemophilia must be sufficiently reimbursed for clotting factor concentrates to ensure continued appropriate out-patient services without financial penalty. Therefore, any proposed ambulatory case-payment method should be assessed as to its potential impact on the price and distribution of clotting factor concentrates for home use. The Panel recommends that the cost of clotting factor concentrates for inpatients be separately reimbursed for Medicaid patients, as it is for Medicare patients. Physically Handicapped Children's Program: The intrinsic autonomy of county health departments in matters of policy and budget holds the potential of excluding conditions such as hemophilia from the Physically Handicapped Children's Program benefits. Legislative and regulatory changes are required to ensure equitable and uniform delivery of children's services from county to county throughout the State. Adequate funds must be provided to county health departments to implement these services. C AIDS Services: Hemophilia treatment centers and their affiliates need State funds to support the psychosocial services necessary for outreach and counseling services related to testing, monitoring, and treating HIV-infected individuals and their partners. Expansion of testing services alone cannot stem the spread of AIDS; sufficient funds must be made available to ensure enhanced adjunct health care and counseling services. The State's AIDS Drug Assistance Program must be funded adequately so that its benefits may continue to be relevant to contemporary treatment of HIV-infected individuals, including those with hemophilia. New anti-viral agents, biologic modifiers and antibiotics must be covered. The New York State Department of Health should continue to develop and provide specialized laboratory services to assist the clinician in managing all HIV-infected patients, including hemophilia patients. 22

29 XIII. APPENDICES APPENDIX A Hemophilia Treatment Centers in New York State For more information regarding emergency management of hemophilia and other congenital bleeding disorders, including von Willebrand disease, the following regional hemophilia treatment centers may be contacted: Buffalo: *Hemophilia Center of Western N.Y., Inc. Pediatrics: Children's Hospital of Buffalo 219 Bryant Street Buffalo, New York (716) (8:30 a.m. - 5:00 p.m.) (716) (24-hour M.D. on call) Adults: Erie County Medical Center 462 Grider Street Buffalo, New York (716) (24 hours) Rochester: *The Mary M. Gooley HemoCenter 1415 Portland Avenue, Suite 425 Rochester, New York (716) (24-hour M.D. on call) Syracuse: Pediatrics: Center for Children's Cancers & Blood Disorders Upstate Medical University University Hospital 750 East Adams Street Syracuse, New York (315) (8:30 a.m. - 3:00 p.m.) (315) (24-hour pediatric hematologist on call) Adults: Regional Oncology Center Upstate Medical University University Hospital 750 East Adams Street Syracuse, New York (315) (8:30 a.m. - 5:00 p.m.) (8:30 a.m. - 4:30 p.m. Friday) (315) (24-hour M.D. on call) Binghamton/Southern Tier: UHSH Blood Disorders Center Wilson Memorial Regional Medical Center P.O. Box 540 Johnson City, New York (607) (24 hours) Albany and Adirondack Area: Albany Regional Comprehensive Center for Hemophilia and von Willebrand Disease at Albany Medical Center Albany Medical College, MSX-43 New Scotland Avenue Albany, New York (518) (8:00 a.m. - 4:30 p.m.) (518) (Answering Service - Adults) (518) (Answering Service - Pediatrics) Downstate Area: Regional Comprehensive Hemophilia Diagnostic and Treatment Center New York Presbyterian Hospital Weill Medical College of Cornell University 525 East 68th Street New York, New York Pediatrics: (212) (24-hour M.D. on call) Adults: (212) (24-hour M.D. - voice mail) Regional Comprehensive Hemophilia Diagnostic and Treatment Center Mount Sinai Medical Center 19 East 98th Street, Suite 9-D New York, New York (212) (24 hour hot line) Clinic (9:00 a.m. - 5:00 p.m.) Comprehensive Hemophilia Treatment Program Long Island Jewish Medical Center New Hyde Park, New York (718) (8:00 a.m. - 4:00 p.m.) (718) (24-hour ER hot line) * Denotes hemophilia treatment center operated by local National Hemophilia Foundation chapter 23

30 APPENDIX B STATEWIDE HEMOPHILIA DATA Table 1. Prevalence of Hemophilia A and B in New York State in 1998 by Severity and Region* Factor VIII <1% 1-5% 6-30% No. of Cases Upstate Downstate Total Rate/million pop Total Factor IX <1% 1-5% 6-30% Total Grand Total *The Downstate Region includes Dutchess, Sullivan, Ulster, Orange, Rockland, Putnam, Westchester, Nassau and Suffolk counties, and the five boroughs of New York City. The Upstate Region includes all other NYS counties. Table 2. Causes of Death in Persons with Hemophilia, New York State to 1998 (Percentage of Annual Deaths) Cause of Death Total AIDS (81) (81) (66) (50) (47) (40) (67%) Bleeding Viral Hepatitis Cancer Heart Disease Other* Total 0 (0) 0 (0) 5 (15) 0 (0) 1 (3) 32 (100%) 1 (2) 1 (2) 0 (0) 4 (9) 2 (5) 42 (100%) 1 (3) 2 (6) 5 (14) 2 (6) 2 (6) 35 (100%) 4 (20) 3 (15) 1 (5) 2 (10) 0 (0) 20 (100%) 2 (12) 3 (18) 1 (6) 0 (0) 3 (18) 17 (100%) 0 (0) 3 (30) 1 (10) 1 (10) 1 (10) 10 (100%) 8 (5%) 12 (8%) 13 (8%) 9 (6%) 9 (6%) 156 (100%) *Other causes of death include motor vehicle accidents (2), birth defects (2), drug overdose (1), non-hivrelated pneumonia (1) and renal failure (3). 24

31 Table 3. Race of Persons With Hemophilia by New York State Region (1998) Race Upstate (% of upstate) Downstate (% of downstate) Total (% of all cases) White 431 (91.1) 336 (48.9) 767 (66.0) Black 20 (4.2) 140 (20.4) 160 (13.8) Hispanic 7 (1.5) 140 (20.4) 147 (12.7) Asian 2 (0.4) 13 (2.0) 15 (1.3) Native American 1 (0.2) 0 (0) 1 (0.1) Middle Eastern 3 (0.6) 34 (4.9) 37 (3.2) Mixed Race 8 (1.7) 21 (3.1) 29 (2.5) Unknown 1 (0.2) 3 (0.4) 4 (0.3) Total 473 (100) 687 (100) 1,160 (100) The Downstate Region includes Dutchess, Sullivan, Ulster, Orange, Rockland, Putnam, Westchester, Nassau and Suffolk counties, and the five boroughs of New York City. The Upstate Region includes all other NYS counties. Table 4. Age of Persons With Hemophilia in New York State by Region (1998) Age (Years) No. of Cases (% total upstate and downstate) Upstate Downstate Total (%) 0 to 4 41 (9) 76 (11) 117 (10%) 5 to (23) 213 (31) 322 (28%) 16 to (13) 86 (12) 146 (13%) 22 to (30) 176 (26) 320 (28%) 41 to (18) 105 (15) 188 (16%) >60 36 (8) 31 (5) 67 (6%) Total 473 (100%) 687 (100%) 1,160 (100%) 25

32 Table 5. Primary* Source of Insurance Coverage by Region of Residence (1998) Primary Source of Coverage Number of Cases (% of upstate and downstate) Total (%) Upstate Downstate Private Insurance/HMO/PPO 302 (63.8) 259 (37.7) 561 (48.4%) Medicaid 59 (12.5) 191 (27.8) 250 (21.6%) Medicare 10 (2.1) 8 (1.2) 18 (1.6%) Medicaid and Medicare 8 (1.7) 22 (3.2) 30 (2.6%) Child Health Plus 3 (0.6) 1 (0.1) 4 (0.3%) Physically Handicapped 2 (0.4) 0 (0) 2 (0.1%) Children Department of Corrections 1 (0.2) 3 (0.4) 4 (0.3%) Other** 3 (0.6) 0 (0) 3 (0.2%) No Coverage 10 (2.1) 3 (0.4) 13 (1.1%) Unknown 75 (15.9) 200 (29.1) 275 (23.7%) Total 473 (100%) 687 (100%) 1,160 (100%) * Only one (primary) source was listed per patient. ** Other sources of coverage included Worker s Compensation, U.S. Department of Veterans Affairs and pharmaceutical donations. 26

33 APPENDIX C EMERGENCY ROOM POSTER 27

34 APPENDIX D NEW YORK STATE DEPARTMENT OF HEALTH HEMOPHILIA EMERGENCY CARE MEDICAL ADVISORY 28

35 APPENDIX E VOLUNTARY HEMOPHILIA ORGANIZATIONS IN NEW YORK STATE The Hemophilia Association of New York and three chartered chapters of the National Hemophilia Foundation in the State are devoted to improving the health and welfare of New York State residents with hemophilia, von Willebrand disease and other bleeding disorders. These organizations are committed to enhancing the quality of life of all persons affected with these disorders so that each may fulfill his or her individual potential. Within its territorial boundaries, each organization delivers services directly to patients and their families. These organizations provide, participate in and/or support: C specialized, comprehensive hemophilia treatment facilities; C research into all aspects of hemophilia, its treatment and complications; C promotion of safe, effective, and equitable distribution of blood products; C patient, public, and professional education; C collaboration with federal research agencies and hemophilia treatment facilities to promote new directions and new funding sources for research; C maintenance of a hemophilia database and information clearinghouse; C sponsorship of activities such as blood drives, summer camps, local support groups, educational symposia, financial counseling, seminars, and direct individual assistance; and C provision of information and referral to other community services. Formal and informal linkages are maintained among these organizations: C to ensure maximum and uniform services to all clients/patients; and C to address issues affecting persons with hemophilia throughout the State. Representatives of many of the following organizations serve on the New York State Department of Health's Hemophilia Advisory Panel: Hemophilia Association of New York, Inc. 104 East 40th Street, Suite 506 New York, NY Tel: (212) Fax: (212) National Hemophilia Foundation 116 West 32nd Street, 11th Floor New York, NY Tel: (212) Fax: (212) Bleeding Disorders Association of NENY, Inc. P.O. Box 3707 Albany, NY Tel: (518) Fax: (518) *51 Blood Disorder Association of the Southern Tier, Inc. P.O. Box 854 Johnson City, NY Tel: (607) Fax: (607) The Mary M. Gooley HemoCenter, Inc Portland Avenue, Suite 425 Rochester, NY Tel: (716) Fax: (716) Hemophilia Center of Western New York, Inc. Erie County Medical Center 462 Grider Street, 1st Floor Buffalo, NY Tel: (716) (24 hours) Fax: (716) New York State Hemophilia Program Wadsworth Center New York State Department of Health Empire State Plaza P.O. Box 509 Albany, NY Tel: (518) Fax: (518)

36 APPENDIX F BIOGRAPHICAL INFORMATION - MEMBERS OF NYSDOH'S HEMOPHILIA ADVISORY PANEL Richard A. Lipton, M.D., M.P.H., F.A.C.P., is chairman of the Panel. After graduating from the Columbia University College of Physicians and Surgeons, and completing clinical training in internal medicine and hematology, he conducted blood coagulation research sponsored by the National Institutes of Health in Dr. Judith Pool's laboratory at Stanford University. Dr. Pool, a prominent hemophilia researcher, discovered cryoprecipitate, the first practical clotting factor concentrate used in treatment of hemophilia. Dr. Lipton is physician-in-charge at the Long Island Jewish Medical Center Regional Hemophilia Center. He has served on the Medical and Scientific Advisory Council of the National Hemophilia Foundation, as well as the Executive Committee and Blood Bank/Financial Task Force for the federal Department of Health and Human Services (HHS) Region II hemophilia centers. Dr. Lipton is also professor of clinical medicine at the Albert Einstein College of Medicine. Wayne S. Cook, Jr., has severe factor IX hemophilia complicated by chronic hepatitis B and C. He has worked for the General Electric Company for the past 10 years as a welder and inspector. In 1995, he became a member of the board of directors of the Bleeding Disorders Association of NENY, Inc. (formerly the Upper Hudson Valley Chapter - National Hemophilia Foundation, Inc.) and assumed its presidency in He has worked as an advocate for individuals with bleeding disorders at the local, State, and national level, dealing with legislative, employment, insurance and Worker's Compensation issues. He and his wife, Maureen, were instrumental in encouraging the NYS Department of Health to develop and adopt an Emergency Medical Services advisory for emergency field care of individuals with hemophilia. While his son does not have a bleeding disorder, his oldest daughter has been diagnosed with von Willebrand disease and his youngest daughter is a symptomatic carrier. Rita Epstein is the mother of a 14-year-old with severe factor VIII hemophilia. She is also a business woman who owns a private day care and elementary school in New Windsor, New York. For the last 30 years, Ms. Epstein has applied her post-graduate training in school administration and gifted education in both the public and private sectors. She is a licensed U.S. Coast Guard charter boat captain and lived for many years on a sailboat both in the United States and in the Virgin Islands. In the early years of the Parent Exchange Newsletter, she regularly wrote articles about her adventures as a mother of a young child with hemophilia. She continues to maintain contacts with parents of newly diagnosed children via the Internet. Diane M. Groth, R.N., C.P.N.P., has been a member of the Panel since She is a certified pediatric nurse practitioner employed by University Hospital at Syracuse, Division of Pediatric Hematology/Oncology. She is nurse coordinator of the Pediatric Hemophilia Center and serves as camp health director of Camp High Hopes, New York State's only summer camp for boys with hemophilia, which she helped establish in Thomas D. Harrington has been involved professionally with voluntary health agencies since 1962, serving the cause of hemophilia for 26 of those 39 years. He is currently chief staff officer of the Hemophilia Association of New York and a member of the Hemophilia Services Advisory Committee of HHS Region II. From 1991 to 1997, he served as a member of the NYS Department of Health's Council on Human Blood and Transfusion Services. He was formerly a member of the New York-New Jersey Regional Organ Transplant Program and the Diabetes Advisory Panel of the Metropolitan New York Regional Medical Program. In 1973, he received the American Society of Association Executives Award of Merit for Management Achievement for developing a model public health education program in diabetes awareness and detection. Rosemary Holmberg, R.N., B.S.N., has been affiliated with the Hemophilia Center of Western New York, Inc., since 1972, for which she served as executive director/nurse coordinator until She returned to the center in 1976 to work in a variety of capacities including research assistant, special projects coordinator, accountant, secretary and nurse coordinator. Since April 1996, she has served as the 30

37 executive director. She received a bachelor's degree in nursing from D'Youville College in Buffalo and a Masters Degree in Business Administration from the State University of New York at Buffalo. Jennifer Pearce, M.D., is associate professor of pediatric hematology/oncology at Albany Medical College. She is Principal Investigator for the Children's Oncology Group and serves as a member of the College's Cancer/Cancer Quality Assurance Committee as well as director of its Sickle Cell Program. She received her education at Johns Hopkins University and The University of Michigan Medical School. Her postgraduate and fellowship training were completed at the Children's Hospital of Philadelphia. 31

38 XIV. GLOSSARY Acquired immune deficiency syndrome (AIDS) is a disease that results from a long-standing infection with human immunodeficiency virus (HIV). This infection can gradually impair the function of cells concerned with immune defenses, leaving the infected person at risk of developing serious secondary infections or certain malignancies. AIDS - See Acquired immune deficiency syndrome. Albumin is the principal plasma protein, making up 60 percent of the protein content of plasma. It is purified commercially by plasma derivative manufacturers from pooled donated plasma. Albumin products are used medically to help treat surgical shock and protein-losing conditions such as burns, and do not carry any infectious disease risks. Antibody is a protein component of the immune system found in blood. Antibody production is stimulated by introduction of an antigen into the body. Antihemophilic factor (AHF) - See factor VIII. Blood components are derived from whole blood. At a blood bank, a single unit of donor whole blood can be separated into several useful components, including red blood cells, platelets, plasma and/or cryoprecipitate. Comprehensive hemophilia treatment centers are a network of federally designated hemophilia treatment programs and their affiliated centers, providing multi-specialty care for persons with hemophilia or other severe bleeding disorders. Cryoprecipitate is an important blood component containing factor VIII, which is obtained during separation of whole blood at a blood bank. One of the first plasma concentrates used to treat factor VIII-deficient hemophilia effectively, cryoprecipitate is rich in other important plasma proteins, namely fibrinogen and fibronectin, used to treat certain acquired bleeding problems encountered in obstetrics, cardiac surgery, and treatment of infections and burns. Diagnosis-related group (DRG) payment system refers to a federal method of hospital reimbursement, no longer in effect in New York State, which called for a schedule of payments based on a specific diagnosis. Reimbursement programs prior to DRGs were based on pre-negotiated per diem hospital rates. Dominant disorder is an inherited disease or condition resulting from the effects of a dominant gene. An affected individual need inherit the trait from only one parent. In contrast, a recessive disorder in order to be expressed generally requires that the affected individual inherit a gene for the trait from each parent. DRG - See Diagnosis-related group (DRG) payment system. Factor VIII, also known as antihemophilic factor (AHF), is a plasma protein involved in coagulation of blood. Factor VIII clotting factor concentrate or antihemophilic factor is therapeutic material made from pooled human plasma or its components, and used to treat factor VIII-deficient hemophilia (hemophilia A) or severe von Willebrand disease. Factor VIII deficiency, one of the most prevalent inherited bleeding disorders, is also known as hemophilia A or classical hemophilia. Factor VIII unit is a measure of factor VIII clotting activity and represents the factor activity present in one milliliter of normal human plasma. The dose of factor VIII concentrate necessary to treat hemophilia A is usually calculated in terms of units of factor VIII activity. The price of commercial clotting factor concentrate is determined by the purity of the material and the number of factor VIII units in a vial. 32

39 Factor IX, also known as plasmathromboplastin component (PTC) and antihemophilic factor B, is a plasma protein involved in coagulation of blood. Factor IX clotting factor (prothrombin complex) concentrate is therapeutic material made from pooled human plasma or its components, used to treat factor IX-deficient hemophilia (hemophilia B), patients with liver disease, or those needing prothrombin complex therapy for other reasons. Factor IX deficiency is a less common inherited bleeding disorder than hemophilia A, and is also known as hemophilia B or Christmas disease. Factor IX unit is a measure of factor IX clotting activity and represents the factor activity present in one milliliter of normal human plasma. The dose of factor IX concentrate necessary to treat hemophilia B is usually calculated in terms of units of factor IX activity. The price of commercial clotting factor concentrate is determined by the purity of the material and the number of factor IX units in a vial. FDA - See Food and Drug Administration. Food and Drug Administration (FDA) is the agency within the federal Department of Health and Human Services that regulates blood banks and plasma derivative manufacturers. Gatekeeper is the name given to the role of the primary care physician responsible to a health plan for prior authorization of specialty services and certain diagnostic tests. Genetic engineering uses recombinant deoxyribonucleic acid (DNA) technology. Bacterial, viral, or animal cells grown in culture are programmed to manufacture a useful protein or hormone by inserting the gene for that product into the genetic machinery of the organism or cell. Important drugs, such as insulin for the treatment of diabetes, previously produced only from animal sources (bovine and porcine pancreas), are now manufactured artificially by this recombinant DNA technique. Several clotting proteins have now been produced by this technique rather than by extraction from human blood, and are undergoing preliminary research or clinical trails. Eventually, these laboratory-made products should replace current plasma-derived materials to prevent risks of transfusion-associated diseases. Health maintenance organization (HMO) is a health care system in which subscribers pay an all-inclusive annual fee for comprehensive medical care. HMOs may maintain their own facilities and salaried professionals. Hemophilia is a rare, hereditary bleeding disorder caused by a deficiency in the ability to synthesize one or more coagulation proteins such as factor VIII or factor IX. Hemophilia A - See Factor VIII deficiency. Hemophilia B - See Factor IX deficiency. Hepatitis B is a form of viral hepatitis that can be transmitted by transfusion of blood products, needle sharing or sexual transmission. Hepatitis B infection can become chronic and lead to permanent liver damage, such as cirrhosis or hepatic cancer, and may even be fatal. Effective plasma-derived and genetically engineered vaccines are available to prevent hepatitis B infection. HIV - See Human immunodeficiency virus. HMO - See Health maintenance organization. Human immunodeficiency virus (HIV) is a pathogenic retrovirus transmitted in a fashion similar to hepatitis B. It infects many body tissues, including those concerned with the immune system and the bone marrow, gradually destroying a person's immunity and eventually leading to AIDS. 33

40 Immune globulins are a family of blood proteins, including humoral or circulating proteins in the immune system known as antibodies. Immune globulins are the principal components of an important product purified by plasma derivative manufacturers from pooled donated plasma, and are used to restore temporarily or enhance a patient's immune response. Inhibitors result from an immune response to clotting factor treatment. Inhibitors are antibodies directed against the factor in which a person with hemophilia is deficient. Occurring in approximately 25 percent of the hemophilia population, this complication renders factor treatment ineffective and often leads to increased disability. Monoclonal antibodies are immunochemically identical antibodies produced by clones of identical cells. Because these antibodies are highly target-specific, they can be used to identify or isolate specific proteins within a mixture of proteins. A monoclonal antibody made against factor VIII can separate this protein from plasma, thereby allowing its purification. In the future, monoclonal antibodies directed against cancer cells might be used routinely as treatment for certain cancers. Non-A, non-b hepatitis is viral hepatitis other than hepatitis A or hepatitis B, and may be associated with transfusion. One of the infectious agents causing this viral disease complex was recently identified and named the hepatitis C agent. Plasma is the liquid portion of blood, excluding its cellular elements but including its proteins. Plasma derivative manufacturers denote pharmaceutical companies and blood banks specializing in processing human plasma to obtain certain medically useful products, including albumin, immune globulins, and clotting factor concentrate. Plasmapheresis is a technique for harvesting large volumes of plasma safely from donors by collecting whole blood and returning the donor's red and white blood cells and platelets. Plasma derivative manufacturers use this method primarily to obtain plasma. Sex-linked recessive disorder is a disease carried genetically on the X chromosome. For example, females (XX) carrying the gene for hemophilia on one X chromosome are asymptomatic carriers, while their male children (XY) have a 50 percent chance of inheriting the gene for hemophilia on their single X chromosome and being affected with hemophilia. Color blindness and Duchenne's muscular dystrophy are other examples of sex-linked disorders. Synovitis is an inflammation of the synovium, the tissue that lines the joint space, which can occur from bleeding into a joint. von Willebrand's disease is an inherited deficiency of the plasma von Willebrand factor (vwf) component of the circulating factor VIII complex, which is made up of factor VIII (antihemophilic factor) and vwf. A relatively common disorder generally clinically milder than hemophilia, it is usually inherited as an incompletely dominant disorder and affects both males and females with equal frequency. 34

41 State of New York GEORGE E. PATAKI, GOVERNOR Department of Health ANTONIA C. NOVELLO, M D, M P H, DR P H, COMMISSIONER /01