Dr Gleb Ivanov MD PhD MRCP FRCPath Consultant Haematologist WHEN THE BLOOD IS NOT QUITE
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1 Dr Gleb Ivanov MD PhD MRCP FRCPath Consultant Haematologist WHEN THE BLOOD IS NOT QUITE RIGHT
2 Profile East Surrey Hospital Crawley Hospital UCH Gatwick Park Hospital Specialist interests Lymphoma Coagulation/thrombosis
3
4 Haematological abnormalities What to refer? What not to refer? What can be done in primary care?
5 Neutropenia Causes: viral infection drugs autoimmune disorders anorexia sepsis bone marrow failure due to dysplasia, malignant infiltration or B12 / folate deficiency.
6 Neutropenia Investigations?Recent viral illness ( Reactive lymphocytes )?Well otherwise Repeat in a few weeks Consider discontinuation of potentially precipitating medication Blood film examination B12 and folate levels Autoimmune screen
7 Neutropenia Investigations NB Normal neutrophil count often <2 x 10 9 /L in individuals of Afro-Caribbean or Middle Eastern origin Repeat FBC in 4-6 weeks viral neutropenia is transient, but can persist
8 Consider an urgent referral: Neutropenia in association with: other cytopenia (Hb < 12g, Platelets < 100), lymphadenopathy, splenomegaly Neutrophil count < 1 x 10 9 /L
9 Thrombocytopenia Clumping!!! Alcohol/hypersplenism ITP/other autoimmune Drugs Any cause of bone marrow failure (aplasia, malignant infiltration, myelodysplasia, B12 / folate deficiency)
10 Thrombocytopenia Investigation Blood film examination will exclude platelet clumping artefact Alcohol history B12 and folate levels Consider discontinuation of potentially precipitating medications Repeat FBC in 4-6 weeks
11 Refer Platelet count < 50 Platelet count in association with: other cytopenia (Hb < 12, Neutrophils < 1) Splenomegaly Lymphadenopathy Pregnancy Upcoming surgery
12 Very Urgent Referral Patients with platelets <20 or active bleeding should be discussed with the on-call Haematologist/Medical Take Registrar to arrange an appropriate direct assessment
13 Thrombocytosis Reactive Secondary to infection, inflammation, chronic bleeding (!) or neoplasia Post-splenectomy Essential thrombocythaemia/other myeloproloferative disorder
14 Urgent Referral Platelet count > 1000 Platelet count in association with: recent arterial or venous thromboembolism neurological symptoms abnormal bleeding
15 Investigation of thrombocytosis Blood film examination Ferritin treat and investigate iron deficiency Look for reactive causes: infection, inflammation, neoplasia Jak-2 mutation (discuss with a Haematologist)
16 Polycythaemia Wide differential diagnosis Relative polycythaemia resulting from plasma depletion commonest cause(s)? Secondary causes (such as hypoxic lung disease and erythropoietin-secreting tumours) Primary proliferative polycythaemia (polycythaemia vera)
17 Investigation of polycythaemia Confirm with repeat FBCs over time (uncuffed blood samples, if possible) Modify known associated lifestyle factors: smoking, alcohol, consider changing thiazides to non-diuretic anti-hypertensive agents
18 Refer if: Elevated PCV (Male >0.52, Female >0.48) in association with: Past history of arterial or venous thrombosis Splenomegaly Pruritus Elevated white cell or platelet counts Persistent unexplained elevated PCV (Male >0.52, Female >0.48)
19 Jak2 mutation and polycythaemia Present in up to 95% of patients with polycythaemia vera Changed the way we investigate polycythaemia: - History and examination - FBC/film - Jak-2 mutation - Serum ferritin - U&Es, LFTs
20 Macrocytosis MCV >98fl B12 and folate deficiency Excess alcohol consumption Myelodysplastic syndrome (MDS) Reticulocytosis Hypothyroidism? Antimetabolites!
21 Investigation of Macrocytosis B12 and folate levels (plus intrinsic factor and GPC Abs in B12 deficiency) Blood film examination and reticulocyte count Liver and thyroid biochemistry Lipids/cholesterol levels Alcohol history and appropriate lifestyle modification
22 Refer to Haematology Suspected myelodysplastic syndrome (based on blood film report) MCV > 100 fl with accompanying cytopenia (excluding B12 / folate deficiency) Persistent unexplained MCV > 105 fl B12 deficiency of uncertain cause requiring further investigation
23 Case 1 36 y.o. male Referred urgently by Ophthalmology SpR?Roth s spots?sbe Hb 6.6 WBC 1.7 Neut 0.6 Plts 83 MCV 129 Retics 18
24 Previous counts Oct 2012 Aug 2011 July 2011 Hb MCV WBC Neut Plts Final diagnosis: Hypoplastic myelodysplasia with monosomy 7
25 Case 2 60 y.o. male Progressively SOBOE Hb 8.9 MCV 108 WBC 5.4 Neut 3.3 Plts 358 Retics 255 (50-100)
26 Case 2 Bilirubin 24 LDH 5552 Normal B12/folate/ferritin Further tests?
27 Case 2 Haptoglobin Haemopexin DCT (DAGT) Blood film: undetectable low negative
28 Case 2 Mechanical haemolysis secondary to MR post-mvr
29 Raised Ferritin Indicates iron excess, but: Raised with any inflammation (like CRP) Raised with hepatic cytolysis (are LFTs normal?) Alcohol excess (what is GGT?) Polymetabolic syndrome
30 Haemochromatosis Very common (6-8%) Autosomal recessive HFE gene mutation C282Y or H63D homo or heterozygosity or double heterozygosity Extremely variable clinical phenotype
31 Polymetabolic Syndrome Increased BMI Hypertension NIDDM Hyperlipidaemia Hyperuricaemia Ferritin mcg/l Normal transferrin saturation (<45%)
32 Investigations in Hyperferritinaemia Repeat ferritin measurement in 4-6 weeks Transferrin saturation (fasting!) Fasting glucose and lipids Check liver biochemistry Careful alcohol history
33 Refer if Persistent unexplained raised ferritin >600 mcg/l, and transferrin saturation >50%. Consider genetic counselling / screening of first degree relatives of hereditary haemochromatosis cases
34 Case 3 78 y.o. lady Hb 8.7 MCV 108 WCC 3.5 Neut 1.8 Plt 156
35 Case 4 48 y.o. woman Hb 15.0 PCV 0.51 MCV 100 fl, round macrocytosis WCC 13.2 Neutrophils 12.1 Plts 112
36
37 Case 5 34 y.o. nurse Hb 5.5 MCV 56 MCH 18 MCHC 28.1 (low) WCC 9.0 Plt 483
38 Case 6 56 y.o banker presenting with gout Hb 18.6 PCV 0.56 WCC 15.0 Neut 12.3 Plt 507
39 Case 7 68 y.o. man feeling tired Hb 6.6 MCV 128 WCC 3.2 Neut 1.1 Plts 88 Bilirubin 70
40 Anaemia Careful history focussing on duration, symptoms, bleeding, diet, drug and family history Blood film examination and reticulocyte count Ferritin, B12 and folate Haemolysis screen (DAGT, LDH, haptoglobin) Protein electrophoresis/urine BJP Monitor FBC for evidence of progression over time
41 Questions 1. What is the most informative haematological investigation (according to Dr Ivanov)? 2. What is the best way of getting advice on a patient with an abnormal blood test?
42 Some FAQs Abnormal protein electrophoresis Polyclonal gammaglobulinaemia Raised alpha 1/ alpha2 globulins Polyclonal increase in gamma globulins Paraproteins??!Myeloma
43 Paraproteins (M-bands) A monoclonal band detected on electrophoresis of serum or urine (BJP) MGUS Myeloma NHL/CLL Waldenstrom s (IgM) Amyloidosis
44 Serum electrophoresis
45 Serum electrophoresis Normal Monoclonal spike
46 Common patterns of SPE
47 Common patterns of SPE Polyclonal gammaglobulinaemia commonly seen in liver disease,infection, rheumatological and autoimmune disorders
48 Paraprotein (M-protein)
49 IgG lambda paraprotein
50 MGUS Very common 1% of the population older than 25 3% over the age of 50 5% over the age of 80 14% over the age of 90 Risk of progression 1% per year
51 Out of patients with paraprotein Malmo study (n=930) MGUS 72% Myeloma 19% WM 2% Other LPD 6% AL-amyloidosis 1%
52 First line investigations in patients with paraproteins U&E Calcium FBC Spot urine for urinary protein and UPE (BJP) White universal no preservative! Serum immunoglobulin levels?skeletal survey
53 Risk of transformation from MGUS About 1% per year for IgG MGUS Higher for non-igg paraproteins (IgM, IgA, IgE, IgD) Positive correlation with paraprotein level at presentation Higher in patients with abnormal free light chain (FLC) ratio
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