Hypercoagulability How to Expect the Unexpected. Beth Saft, DO VOMA Conference 2012

Transcription

1 Hypercoagulability How to Expect the Unexpected Beth Saft, DO VOMA Conference 2012

2 Who is at Risk Most Common Hypercoagulability Objectives + When to Test What to do with the Test Results

3 Who gets a DVT General Population: 1 in :100 if > age 80yrs Hip Replacement: 5 in 1000 Knee Replacement: 10 in ,000 to 600,000 DVTs per year 60,000 to 100,000 deaths attributable to PE.

4 All Cause Death in US VTE

5 Cancer Incidence VTE.

6 30-50% DVTs have Genetic Cause DVT Causes Unknown Factor V Leiden Prothrombin Antithrombin III Protein C Protein S Fibrinolysis Dysfibrinogenemia

7 Primary Hypercoagulability Mutation General Population DVT population Factor V Leiden 2-5% 30% Prothrombin % (6% Spain) 6% Homocystinemia % Heat Variant 10-20% 0% Antithrombin III 0.02%-1% 4% Protein C 0.2% 1-3% Protein S 0.1% 1-5% Factor VIII? Fibrinolysis rare Dysfibrinogenemia rare

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9 Protein C Protein S Thrombomodulin

10 Antithrombin III

11 DVT Risk Factors Genetic Acquired Transient Acquired Family History Advanced age >40-60 Pregnancy Factor V Leiden Antiphospholipid antibody Oral Contraceptives Prothrombin G20210A Cancer/Chemotherapy Hormone Therapy Protein C defic/dysfunc Chronic disease Hospitalization Protein S defic/dysfunc Obesity >30 Surgery Antithrombin III defic Smoking Trauma Sickle cell trait Previous hx DVT Immobilization New Gene SNPs Beckman et al. 2010

12 Thrombophilic State Relative Risk of Venous Thrombosis Normal 1 (1:1000 annual incidence) 4 Factor V Leiden, Heterozygous Homozygous 80 >100 Prothrombin Gene Mutation, Hetero Homozygous Protien C defic, hetero 7 Homozygous Protein S defic, hetero 6 Homozygous Antithrombin Defic, hetero 5 Homozygous Hyperhomocysteinemia 2-4 Hyperhomocysteinemia + Factor V hetero 3 16?possible risk of arterial thrombosis Severe thrombosis at birth Severe thrombosis at birth Fetal demise 20 Oral Contraceptives

13 Combining Multiple Risk Factors Primary Risk Secondary Risk Relative Risk DVT Factor V Leiden OCP HRT 15 Pregnancy 7 Antithrombin Defic Surgery 60 (0.3/100pt-yr ->20/100pt-yr Prothrombin OCP 16 None OCP 4 None HRT 2 None Obesity 2.4 None Smoking 1.6 Pregnancy 10 DVT (Unprovoked) 10-20%

14 Combining Multiple Risk Factors Pregnancy risk 1: x age matched pt Obesity 2.4 Obesity + OCP 24 Smoking 1.6 Smoking + OCP 8.8 Age + HRT increased risk Recurrent DVT after unprovoked DVT 10-20%.

15 Cancer OCPs/HRT Protein C Protein S Thrombomodulin Pregnancy

16 DVT Prevention Who to given Anticoagulation Risk: 3% bleeding on Warfarin 0.6% (1/5 of bleeds) -> Fatal bleeding Benefit: When clotting risk >3-9%

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18 CHEST 2012 New ACCP Antithrombotic Guidelines Prevention, Diagnosis and Treatment Added Patient Values Added Factor Xa inhibitors for HIP and KNEE Repl.

19 2012 ACCP Guidelines Major Orthopedic Surg: EVERYONE gets antithrombotic prophylaxis min, 35 days suggested LMWH or LDUH Fondaparinux Apixaban Dabigatran Rivaroxaban Warfarin ASA IPCD not preferred

20 2012 ACCP Guidelines General Abdominal Surgery Very Low Risk ambulate Low Risk IPC Moderate Risk LMWH or LDUH High Risk LMWH + IPC High Risk + Cancer LMWH x 4 weeks (ASA, fondaparinux, IPC alterative opt)

21 2012 ACCP Guidelines Depends on Risk Level for: Thoracic Surgery Neurosurgery Hospitalized Acutely ill Hospitalized Critically ill Trauma, lower leg vs major Travel long distance stockings

22 Risk Prediction Scores Rogers Score Surgery type, physical status, work RVUs, Cancer, Lab values (Na, bili, albumin), etc. Caprini Score 2005 Surgery type, Hx or FHx DVT, HIT, thrombophilia, BMI, OCP, pregnancy, varicose veins

23 New ACCP Guidelines Cancer Outpatient + Risk Factors/Chemo: LMWH or LDUH NOT Warfarin

24 2012 ACCP Guidelines No Prophylaxis: Knee Arthroscopy Lower Leg immobilization Chronically immobilized patients Asymptomatic Thrombophilia

25 Caprini Score

26 Points Rogers Score Risk Factors 9 Respiratory Surgery 7 Thoraco-abdominal aneurysm surg, embolectomy, thrombectomy, venous reconstruction, endovascular repair 4 Other aneurysm, mouth, palate, stomach, intestines 3 Integument surg, >17 RVUs 2 Hernia surg, ASA physical status class 3-5, Cancer, chemo, Na 145, Transfusion >4u PRBC, Ventilator, RVU Each wound class, ASA phys status class 2, Hct <38, Bili >1, dyspnea, alb <3.5, emergency Rogers SO Jr, Kilaru RK, Hosokawa P, Henderson WG, Zinner MJ, Khuri SF. J Am Coll Surg Jun;204(6): Multivariable predictors of postoperative venous thromboembolic events after general and vascular surgery: results from the patient safety in surgery study.

27 Risk Evaluation for Outpatient Surgery N=250,000 Limited by Database(ASC-NSQIP): Personal and Family History of VTE, and known Thrombophilia NOT included. (Pannucci et al, Ann Surg 2012;255: )

28 Primary + Secondary Risk Factors = DVT

29 When do you Suspect Genetics? Age <50 Family History of DVT Recurrent DVT Unusual Site for DVT mesenteric, cerebral, hepatic, upper extremity Frequent Miscarriage or IUGR Unprovoked DVT FPNotebook.com

30 What do you test? Common: CBC, PT, PTT Lupus Anticoag, ANA, Antiphospholipid Ab Anticardiolipin Ab or B2 Glycoprotein Ab Factor V Leiden or APC Resistance (costs less) G20210A mutation Homocysteine Level? Less Common: Protein C, S, AntiThrombin, Factor VIII excess

31 ? TREATS study 2006 Universal screening before HRT Universal screening before OCPs, Pregnancy, Ortho surgery Selective screening based on History Personal and/or Family History

32 DVT Diagnosis Wells Score/Criteria Probability of suspected DVT actually being a DVT (possible score 2 to 9) Active cancer (treatment within last 6 months or palliative): +1 point Calf swelling 3 cm compared to asymptomatic calf (measured 10 cm below tibial tuberosity): +1 point Swollen unilateral superficial veins (non-varicose, in symptomatic leg): +1 point Unilateral pitting edema (in symptomatic leg): +1 point Previous documented DVT: +1 point Swelling of entire leg: +1 point Localized tenderness along the deep venous system: +1 point Paralysis, or recent cast immobilization of lower extremities: +1 point Recently bedridden 3 days, or major surgery requiring regional or general anesthetic in the past 12 weeks: +1 point Alternative diagnosis at least as likely: 2 points

33 DVT Treatment options Home vs hospital Serial Imaging not recommended Thrombolysis and thrombectomy - optional Reduces post-thrombotic syndrome >1yr life expectance Iliofemoral DVT <7days of symptoms

34 Common Treatment Medications Anticoagulant Risk Monitoring Antidote Half-live Heparin LMWH Bleeding HIT Bleeding HIT aptt Protamine <60min Factor Xa Protamine (0-60% effective) Warfarin 3% Bleeding PT/INR Vitamin K FFP Fondaparinux (Arixtra) Bleeding Factor Xa None 15h Variable Several days Argatroban Bleeding Factor Xa None 30-60min Rivaroaban (Xarelto) Dabigatran (Pradaxa) ASA 81mg? Bleeding Factor Xa None 11h Bleeding Thrombin None 12-14h 5h

35 WARFASA Trial 402 patients, ASA 100mg or Placebo x 2yrs DVT Risk after unprovoked DVT ASA reduces risk 36-54% VKA reduces risk 60-90% 0 ASA Placebo

36 Coming Soon ASPIRE Aspirin to Prevent Recurrent Venous Thromboembolism (VTE): 3000 patients over 3yrs Aspirin EC 81mg to prevent recurrent symptoms in patients with VTE who have been treated with warfarin for a period of three to 12 months.

37 heparin Rivaroxaban Fondaparinux et. al. Antithrombin III Dabigatran

38 Factor Xa inhibitors Review 8/2012: 22 Randomized Controlled trials 32,000 patients Reduce DVT more than LMWH in total knee or hip replacement rivaroxaban (8 RCTs); edoxaban (4 RCTs); apixaban (4 RCTs); YM150 (2 RCTs); and betrixaban, razaxaban, TAK442, and LY517717

39 Factor Xa inhibitors Outcomes Number of trials included in analyses (n) Weighted event rates Factor Xa inhibitors At 5 wk unless otherwise stated LMWH RRR (95% CI) NNT (CI) Mortality ( 10 wk) 10 (21 993) 0.24% 0.25% 5% ( 63 to 45) Not significant DVT 12 (21 030) 0.27% 0.58% 54% (30 to 70) 321 (247 to 578) RRI (CI) NNH (CI) Nonfatal PE 20 (26 998) 0.27% 0.25% 7% ( 35 to 73) Not significant Major bleeding 21 (31 424) 0.84% 0.66% 27% ( 2 to 64) Not significant Bleeding leading to reoperation 14 (26 312) 0.15% 0.10% 62% ( 18 to 218) Not significant

40 Hot off the Presses Ann Intern Med Aug 28. Adam SS et al. Comparative Effectiveness of Warfarin and New Oral Anticoagulants for the Management of Atrial Fibrillation and Venous Thromboembolism: A Systematic Review. 6 Trials Reviewed. Factor Xa and Direct Thrombin Inhibitors Non-inferior

41 Summary Genetic Acquired Transient Acquired Family History Advanced age Pregnancy Factor V Leiden Antiphospholipid antibody Oral Contraceptives Prothrombin G20210A Cancer Hormone Therapy Protein C defic/dysfunc Chronic disease Hospitalization Protein S defic/dysfunc Obesity Surgery Antithrombin III defic Smoking Trauma Sickle cell trait Immobilization Beckman et al. 2010

42 Feb 2012 ACCP Guidelines 9 th ed. Updated March 2012