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Haematology in Primary Care: The Full Blood Count

Haematology in Primary Care: The Full Blood Count. Charles Crawley George Follows. C ambridge H aematology P artners. The FBC. Haemoglobin. Low haemoglobin defines anaemia Males 13-18g/l Females 11.5-16g/l Variations: Children Neonates – 14-24g/l 2 months – 8.9-13.2g/l

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Haematology in Primary Care: The Full Blood Count

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  1. Haematology in Primary Care:The Full Blood Count Charles Crawley George Follows Cambridge Haematology Partners www.cambridgehaematology.com

  2. The FBC www.cambridgehaematology.com

  3. Haemoglobin • Low haemoglobin defines anaemia • Males 13-18g/l • Females 11.5-16g/l • Variations: • Children • Neonates – 14-24g/l • 2 months – 8.9-13.2g/l • 9-12ys - 11.5-15.4g/l • Pregnancy • 3rd Trimester – 9.8-13.7g/l • Age • 5-7th decade – falls in men rises in women • Exercise • Increases Hb • Altitude • Smoking www.cambridgehaematology.com

  4. MCV • Mean Cell Volume: average size of RBC • Normal adult : 76 (80) - 100 fL • MCV < 76 fL (microcytic) • MCV > 100 fL (macrocytic) • MCV 80 - 100fL (normocytic) www.cambridgehaematology.com

  5. Practical Classification of Anaemia • Reticulocyte count: In the investigation of anaemia • Reduced: Failure of erythropoiesis • Increased: Appropriate BM erythroid response www.cambridgehaematology.com

  6. 35 year Male • Hx: Lethargy, SOB • Sx: Pale • FBC: Hb 6.4 g/dL MCV 71 fL RDW 0.19 WCC 5.2 Platelets 375 • Film: Severe hypochromasia and microcytosis www.cambridgehaematology.com

  7. Commonest Causes Iron Deficiency www.cambridgehaematology.com

  8. Blood Film www.cambridgehaematology.com

  9. Differential Diagnosis • Causes of microcytic hypochromic anaemia • Iron deficiency • Blood loss • Malabsorption - Coeliac disease; gastrectomy • Increased utilisation - parasites • Dietary deficiency - rare • Haemoglobinopathy • Anaemia of chronic disease www.cambridgehaematology.com

  10. Fe Deficiency vs Anaemia of Chronic Disease GIT studies: endoscopy etc www.cambridgehaematology.com

  11. 26 year Female • Hx: Antenatal visit; First trimester • FBC: Hb 11.0 g/dL MCV 73 fL MCH 27 pg RDW 0.14 WCC 8.5 x 109/L Platelets 164 x 109/L • Film: Microcytic RBC www.cambridgehaematology.com

  12. Fe Deficiency vs Hbinopathy Check iron status: Ferritin Family history / ethnicity: Thalassaemia / haemoglobinopathy Need to determine risk to fetus of severe thalassaemic syndrome (in 1st rimester): Homozygous thalassaemia (α or β) Homozygous Hb S (sickle cell disease) Severe compound heterozygous states E.g.: HbS/β; HbE/β; HbSC Determine need to check partner www.cambridgehaematology.com

  13. Red Cell Distribution Width (RDW) • The degree of variation in size of RBC: N <14 • Increased RDW corresponds with anisocytosis: • Iron deficiency (increased RDW is the earliest lab feature: anisocytosis precedes the anaemia) • Megaloblastic anaemia (can be very high >20) • Anaemia with bone marrow erythroid response (i.e. reticulocytosis) • RDW useful in DDx of microcytic anaemias. • Most cases of iron deficiency: raised RDW • Most cases thalassaemia trait: normal RDW www.cambridgehaematology.com

  14. MCH • Mean Cell Haemoglobin (27-32 pg) • The mean haemoglobin per red blood cell • MCH usually rises or falls as the MCV is increased or decreased. • MCH < 25 pg used as a guide to the presence of thalassaemia or haemoglobinopathy. • MCH usually markedly reduced in thalassaemia (e.g. beta thalassaemia trait MCH 19 pg) www.cambridgehaematology.com

  15. Haemoglobin Studies 1. Normal adult 2. HPFH (heterozygote)3. Hb S--HPFH 4. Hb C--HPFH 5. Normal newborn A/F/S/C control www.cambridgehaematology.com

  16. 73 year male • Hx: Tiredness • FBC: Hb 4.0 g/dL MCV 102 fL RDW 0.24 WCC / Plt Normal • Film: Macrocytes, fragmented red cells, occasional NRBC www.cambridgehaematology.com

  17. Blood Film73 yr old male www.cambridgehaematology.com

  18. Severe Macrocytic Anaemia • Megaloblastic anaemia • Liver disease: end-stage failure • Red cell aplasia: • Parvovirus; thymoma, other malignancy • Bone marrow failure or infiltration: • Myelodysplasi • Multiple myeloma www.cambridgehaematology.com

  19. Investigations 1. Serum vitamin B12 Red cell folate (serum folate) 2. Reticulocyte count (BM erythroid function) 3. Liver function 4. Parvovirus serology 5. Bone marrow examination www.cambridgehaematology.com

  20. Don’t Forget the Alcohol www.cambridgehaematology.com

  21. Other Causes of Macrocytic Anaemia • Severe liver disease • Excess alcohol • Haemorrhage / haemolysis: reticulocytosis • Drug therapy: esp. cytotoxics • Hypothyroidism • Myelodysplasia • Marrow infiltration • Bone marrow examination may be indicated www.cambridgehaematology.com

  22. Myelodysplasia (MDS) • Clonal disorder • Ineffective haematopoiesis • Incidence increases with age • Age 50yrs - 1 per 100,000 • Age 70yrs – 25 per 100,000 • RBC, WCC, and platelets affected www.cambridgehaematology.com

  23. Myelodysplasia Bone Marrow Peripheral Blood www.cambridgehaematology.com

  24. Myelodysplasia • Prognosis • Number of cytopenias • BM Blast percentage • Cytogenetics • Age • Survival • Varies 11.7 yrs – 0.4yrs • Management • Supportive • Stem cell transplantation • New drugs www.cambridgehaematology.com

  25. Normocytic Anaemia • Multiple aetiologies • Primary marrow production defect • Myelodysplasia • Marrow infiltration • Haematinic deficiencies • Reduced red cell survival • Blood loss • Intrinsic defects (eg. Enzyme; membrane) • Extrinsic defects (eg. Plasma problems) www.cambridgehaematology.com

  26. Approach to Normocytic Anaemia • History: • Acute blood loss ; jaundice; dark urine • Exclude treatable causes: • Check ferritin, folate, vitamin B12 • Renal and hepatic function • Acute phase reactants • Consider haemolysis The blood film may have the answer ! www.cambridgehaematology.com

  27. 78 year male • Hx: Chest pain • PMHx: Myocardial infarct • FBC: Hb 7.2 g/dL MCV 97 fL WCC 4.5 x 109/L Platelets 320 x 109/L Reticulocytes: 320 (10-100) www.cambridgehaematology.com

  28. Blood Film www.cambridgehaematology.com

  29. Blood Film • RBC: Spherocytes Polychromasia Nucleated red cells Spherocytic haemolytic anaemia: Auto-immune haemolytic anaemia Hereditary spherocytosis www.cambridgehaematology.com

  30. Other Investigations • Biochemistry: • Bilirubin 100 μmol/L (<20) • Other LFT Normal • LDH 1,500 U/L (120-240) • Haptoglobin <0.1 • Haematology: • Reticulocyte count • Direct anti-globulin (Coombs) test: Positive • Enzymes, • Hereditary spherocytosis screen www.cambridgehaematology.com

  31. Primary Red Cell Problem: Red cell membrane: Hereditary spherocytosis Enzyme defect: G6PD deficiency Haemoglobin defect: thalassaemia Abnormal red cells: dyserythropoiesis (MDS) Secondary Red Cell Destruction Autoimmune Severe hepatic dysfunction Red cell fragmentation: DIC; HUS; TTP Infections: malaria; clostridium Haemolytic Anaemia www.cambridgehaematology.com

  32. Blood Film blister or helmet cells Glucose-6-phosphate dehydrogenase deficiency www.cambridgehaematology.com

  33. Normocytic Anaemia • Blood film may have the answer: • Normal red cell morphology • Dimorphic (high RDW): 2x RBC populations • Marked anisocytosis: marrow dysfunction/MDS • Is there polychromasia? • Yes: Anaemia with marrow response • No: Impaired marrow response • Anaemia of Chronic Disease • BM failure • Red cell aplasia: Parvovirus; aplastic anaemia www.cambridgehaematology.com

  34. Polycythaemia • Pseudopolycythaemia • Primary • Polycythemia vera • Secondary • Hypoxia • Altitude • Cardiac/Pulmonary disease • Cirrhosis • Abnormal Haemoglobins • Chronic CO exposure • Inappropriate erythropoietin • Renal lesions • Tumours • Drug www.cambridgehaematology.com

  35. Clinical Features • Hyperviscosity • Headaches • Blurred vision • Breathlessness • Confusion • (Plethora) • Thrombosis • Venous + arterial • Bleeding • Other • Pruritis • Gout www.cambridgehaematology.com

  36. Polycythaemia investigations • FBC + Film • CXR • Cardiac assessment • Red Cell mass • Blood gasses • Major advance – JAK 2 mutation screens www.cambridgehaematology.com

  37. JAK2 • Presence of the V617F mutation indicates that the patient has an acquired, clonal hematological disorder and not a reactive or secondary process. • Absence of the JAK2 V617F mutation does not exclude a MPD as up to 50% of patients with ET and IMF will have wildtype JAK2. • The V617F mutation does not help in sub-classifying the type of MPD of a given patient www.cambridgehaematology.com

  38. Pathogenesis: Deregulated Tyrosine Kinases in MPD CML BCR-ABL CMML TEL-PDGFRB CEL FIP1L1-PDGFRA SM KIT D816V PV JAK2 V617F ET JAK2 V617F IMF JAK2 V617F www.cambridgehaematology.com

  39. Questions so far? www.cambridgehaematology.com

  40. Platelets • Too many (thrombocytosis) • Too few (thrombocytopenia) • Dysfunctional • When should we worry? www.cambridgehaematology.com

  41. Thrombocytosis • > 450 x 109/l • Causes • Reactive (almost anything!) • Common – bleeding, infection, malignancy • Tend to be less than 1000 x 109/l • Primary bone marrow disorder • Myeloproliferative disorders (up to 3000+) (essential thrombocythaemia, myelofibrosis, polycythaemia, chronic myeloid leukaemia) www.cambridgehaematology.com

  42. Thrombocytosis • History, examination should guide investigations and referrals • Should the patient be on aspirin? • Only firm evidence is MPDs • Reactive often given if > 1000, but little evidence for this www.cambridgehaematology.com

  43. Thrombocytosis • Essential Thrombocythaemia (ET) • Long term management balancing thrombotic vs bleeding risk • Aspirin for intermediate risk • Cytoreduction + aspirin for higher risk (beware the pseudohyperkalaemia!!) www.cambridgehaematology.com

  44. Thrombocytopenia • Is it real??? • Poor sample • Clumped in EDTA – blood film **If at all possible confirm with a repeat sample www.cambridgehaematology.com

  45. Thrombocytopenia Pancytopenia vs Isolated low platelets • Pancytopenia – • always serious (marrow failure) • Isolated • may be relatively unimportant www.cambridgehaematology.com

  46. Thrombocytopenia • Decreased production • Rare in isolation • Viral infections • Increased consumption • Autoimmune – ITP • Drugs • Pregnancy • Large spleen / portal hypertension • Infections (HIV) • RARE but serious TTP – HUS - DIC www.cambridgehaematology.com

  47. Thrombocytopenia • Investigations depend on clinical suspicion • Platelet volume may be helpful (small - think marrow) • <8.0 and >10.5 • BM often not required www.cambridgehaematology.com

  48. Thrombocytopenia (not joint bleeds!) www.cambridgehaematology.com

  49. Thrombocytopenia • How real is the bleeding risk? • Cause of low platelets • Wet vs dry purpura • Platelet transfusions often not useful www.cambridgehaematology.com

  50. ITP – a few useful reminders • Children • Acute, post viral, • spontaneous resolution (often no therapy) • Adult • More insidious onset • Chronic = common • Many (not all!) cases do require treatment • Steroids – splenectomy • Novel therapies www.cambridgehaematology.com

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