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Haematology in 1 hour

Haematology in 1 hour. Approach to low blood count. Consider cause Is it a lack of production = bone marrow problem (intrinsic or extrinsic) Is it excess destruction = immune or other causes Is it excess consumption = sepsis, haemorrhage, large spleen etc Always consider Drugs

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Haematology in 1 hour

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  1. Haematology in 1 hour

  2. Approach to low blood count • Consider cause • Is it a lack of production = bone marrow problem (intrinsic or extrinsic) • Is it excess destruction = immune or other causes • Is it excess consumption = sepsis, haemorrhage, large spleen etc • Always consider Drugs • Consider inheritedvsacquired

  3. Approach to the investigation of Anaemia

  4. Microcytic anaemia -questions • Is it iron deficiency or thalassaemia? • or both? • If iron deficiency: • what is the cause? • what further investigations are required? • What is the treatment? • What if the patient fails to respond to oral iron?

  5. Iron deficiency • Produces a drop in MCV proportional to the degree of anaemia • RDW increases, reflecting anisocytosis • Beware effect of acute disease in interpretation of Ferritin and TIBC results • Beware of counteracting effect of drugs/alcohol causing macrocytosis on MCV in iron deficiency – look at previous results • Treatment dose is 200 mg Fe/day (=200mg tds of Feso4, look up other Fe preparations in BNF

  6. Failure to respond to oral iron • Insufficient dose • Thalassaemia traits • Non compliance • Continuing losses • Malabsorption (coeliac disease, post gastrectomy)

  7. Thalassaemia traits • Produce microcytic, hypochromic indices • Clinically asymptomatic • Mild anaemia, MCH<27pg • Look for steady state Hb in notes – will tell if additional problem • Do not give iron unless iron deficiency proven • b thalassaemia trait causes raised Hb A2 • a thal traits by exclusion of other causes • In antenatal context identification of b thal trait in women mandates partner screening

  8. Haemolytic anaemia questions • How is diagnosis of haemolytic anemia made? • Clinical – jaundice, dark urine, splenomegaly • Lab-normocytic anemia, unconjugated hyperbilirubinaemia, reticulocytosis • Further tests: direct antiglobulin test (Coombs), blood film, Hb screen

  9. Haemolytic anaemia • Consider cause • Inherited: haemoglobinopathy, membrane disorder • Acquired: drugs, transfusion reaction, immune disorders • Treatment directed at cause • Transfuse if symptomatic (problems with cross match)

  10. Sickle cell disease: clinical problems • Anaemia • Infections • Painful crises • Stroke • Leg ulcers • Visual loss • Chronic organ damage • Kidneys, lungs, joints, heart

  11. Sickle cell basic facts • Not exclusive to black races • Hb SS steady state Hb 7-9g/dl • Transfuse only for certain indications • Milder forms may have normal Hb so always do Hb Screen if suspicion or pre op • % Hb S is constant and bears no relation to acute crisis • Patients have functional asplenia, therefore high risk of infection

  12. Macrocytic anaemia - questions • Is it a new problem? • Is it due to alcohol? • Is it due to diet /haematinic deficiency • Is it due to drugs? • When to refer to the haematologist?

  13. Management of low B12 • History • Diet, previous surgery, GI disease • IF antibodies • Schilling test no longer available • Symptoms/signs - give i.m. B12 with folic acid • levels unhelpful and unnecessary after this • Asymptomatic - ?dietary can give oral B12 and reassess levels after a few weeks • Failure to respond to haematinics may indicate MDS n.b. if normal Hb, MCV can take several weeks to fall

  14. Polycythaemia • Raised haematocrit (in well hydrated patient) • Consider cause • primary (uncommon) v secondary (common) • cause of secondary • Hypoxia (respiratory disease, smoking, cardiac disease R – L shunt) • Excessive EPO (renal /hepatic disease/tumours) • Increased thrombotic risk

  15. Polycythaemia • Investigations, if not apparent from history • CXR, Arterial gas, lung function, EPO level • Refer to haematology if no obvious secondary cause • Management: Venesection to Hct as defined for underlying cause • Chemotherapy (primary cause)

  16. Raised WBC questions • Is it confined to one type of cell or all white cells? • Are abnormal cells present? • What are appearances of blood film? • Common cause is reactive (neutrophilia, L shift, in context of infection/inflammation/malignancy) • CRP may be a pointer to reactive cause

  17. Leukaemia • Clonal proliferations of one of more types of white cells • Mature cells = chronic leukaemia • CLL lymphocytes • CML Mature + immature Myeloid cells • Immature cells = acute leukaemia • characterised by presence of blasts and immature cells in blood/BM • e.g AML, ALL

  18. Effects of leukaemia • Bone marrow failure • anaemia • thrombocytopenia - bleeding risk • neutropenia - infection risk • Tissue infiltration • Tumour deposits e.g skin, nodes, gums,CNS, liver or spleen • Immune suppression - infection • Death usually due to infection or bleeding

  19. How does acute leukaemia present? • Infection • Symptoms of anaemia • Bruising/bleeding • Tissue infiltration • Blood film shows cytopenias with blasts • Confirm on Bone marrow and immunophenotyping/cytochemistry. Chromosomes • Treatment: intensive chemotherapy • Prognosis: depends on characterisitcs and patient comorbidity. e.g childhood ALL very good prognosis, elderly AML, poor

  20. Chronic leukaemia • May be incidental finding e.g CLL • Associated with symptoms/signs of marrow infiltration • Increased infections (bacterial/fungal) • Lymphadenopathy • Autoimmune features eg AIHA in CLL • Diagnosis on film/marrow/special investigations • Treatment variable: observation only to intensive chemotherapy • Prognosis very variable eg. CLL

  21. What are lymphomas • neoplasms of lymphoid origin, typically causing lymphadenopathy • leukaemia vs lymphoma • lymphomas are clonal expansions of cells at certain developmental stages

  22. Category Survival of untreated patients Curability To treat or not to treat Non-Hodgkin lymphoma Indolent Years Generally not curable Generally defer Rx if asymptomatic Aggressive Months Curable in some Treat Very aggressive Weeks Curable in some Treat Hodgkin lymphoma All types Variable – months to years Curable in most Treat A practical approach to lymphomas

  23. Clinical manifestations • Variable • severity: asymptomatic to extremely ill • time course: evolution over weeks, months, or years • Systemic manifestations • fever, night sweats, weight loss, anorexia, pruritis • Local manifestations • lymphadenopathy, splenomegaly most common • any tissue potentially can be infiltrated

  24. Other complications of lymphoma • bone marrow failure (infiltration) • CNS infiltration • immune hemolysis or thrombocytopenia • compression of structures (eg spinal cord, ureters) by bulky disease • pleural/pericardial effusions, ascites

  25. Stage I Stage II Stage III Stage IV Staging of lymphoma A: absence of B symptoms B: fever, night sweats, weight loss

  26. Investigation of suspected lymphoma • Biopsy of affected node/mass • ESSENTIAL as dictates treatment and prognosis • Staging CT scans/Bone marrow • FBC, Biochemistry, LDH, etc

  27. Three types of lymphoma you will most commonly meet • Follicular lymphoma • Diffuse large B-cell lymphoma • Hodgkins lymphoma

  28. Neutropenia questions • Is it isolated or associated with other cytopenias? • Is it recent or longstanding? • Is it associated with history of infection? • Common causes of isolated neutropenia: • Viral infection (acute and chronic eg HIV) • Drug related (look up list) • Ethnic (longstanding, asymptomatic, no other cause)

  29. Severe neutropenia • Infection risk increased if neuts<1.0 x 109/l • High risk of infection of neuts<0.5 • Risk is also related to duration of neutropenia and neutrophil function • Consider prophylaxis of infection if neuts<0.5 • Fever in Neutropenic patient is a medical emergency – investigate and treat empirically with broad spectrum antibiotics pending micro results. Hospital should have a protocol.

  30. Paraproteins • Common incidental finding, esp in elderly • Due to clonal proliferation of plasma cells • Is it significant? • Causes: • secondary: (autoimmune disorders/infections) • Malignant: myeloma/lymphoma • Uncertain: MGUS (20% evolve into clonal disorder)

  31. Myeloma • Clinical features due to combinations of: • Marrow failure • immunsuppression • Paraprotein (renal disease) • Bone disease (pain, fractures, lytic lesions/hypercalcaemia) • Investigation of PP • History • FBC, Biochem, Serum electrophoresis • Bone X rays • Bone marrow • MGUS is defined by lack of evidence for malagnancy or reactive cause.

  32. Haemostasis and thrombosis Physiology of haemostasis Bleeding disorders (congenital) Massive blood loss DIC Anticoagulant drugs

  33. Haemostasis needs… Platelets Vessel Wall Clotting Factors

  34. PT The starter motor…….. Switched off by Tissue Factor Pathway Inhibitor Provides initial Thrombin burst Factors measured in Prothrombin Time

  35. The engine………….. Thrombin from initial burst back activates “intrinsic system” APTT TT Fibrin then cross linked by XIII

  36. Natural anticoagulants Protein C (activated by thrombin/thrombomodulin) Protein S - cofactor for protein C Protein C and S cleave factors V and VIII Antithrombin inhibits Thrombin and Xa TAT complexes removed by liver Activity increased 000’s by heparin

  37. APTT : Kallikrein, HMWK, XII, XI, IX, VIII, X, V, II, I • “intrinsic system” • PT : VII, X, V, II, I • “extrinsic system” • TT : I • 50:50 mix with normal plasma will distunguish a lack of clotting proteins from an inhibitor of function Global coagulation tests

  38. CAUSES OF A PROLONGED PROTHROMBIN TIME • CONGENITAL • Coagulation factor deficiencies: VII, X, V, II, I • ACQUIRED • Hepatocellular disease • Vitamin K deficiency (II, VII, IX, X): obstructive jaundice, haemorrhagic disease of the newborn • Disseminated intravascular coagulation (DIC) • Massive blood transfusion • Warfarin (monitoring test based on PT) • Gross overheparinisation, some lupus anticoagulants

  39. CAUSES OF A PROLONGED ACTIVATED PARTIAL THROMBOPLASTIN TIME • CONGENITAL • Coagulation factor deficiencies: XII, XI, IX, VIII, X, V, II, I • ACQUIRED • Hepatocellular disease • Vitamin K deficiency • Disseminated intravascular coagulation • Massive blood transfusion • Heparin (monitoring test based on APTT) • Lupus anticoagulants

  40. CAUSES OF A PROLONGED THROMBIN TIME • CONGENITAL • Dys/hypofibrinogenaemia • ACQUIRED • Hepatocellular disease: dys/hypofibrinogenaemia • Disseminated intravascular coagulation: • hypofibrinogenaemia • FDPs • Heparin

  41. Haemophilia A = reduced VIII; B = reduced IX Both sex-linked recessive Queen Victoria Intronic rearrangements, point mutations, gene deletions Haemophilia A 1 in 10,000 male infants Prolonged APTT (normal PT and TT) Mild Rx: Tranexamic acid, DDAVP (not HB) Severe Rx: factor replacement recombinant or pooled donor Home prophylaxis Past problem with HIV, now HCV ??? CJD

  42. Von Willebrand’s Disease Functions of VWF: 1. Sticks to platelets (GPIb) 2. Sticks to collagen in subendothelium (Important in small blood vessel lesions; high shear stress) 3. Binds to and protects VIII (labile) Therefore in VWD see long APTT (low VIII) and bleeding where VWF platelet interaction important

  43. Von Willebrand’s Disease Treatment options DDAVP, antifibrinolytics NB DDAVP causes fluid retention. NOT for type 2B Intermediate purity VIII concentrate VWF concentrate (NB takes hours for VIII to follow so may need to give both) If severe bleeding consider platelet infusion and cryoprecipitate (NB type I may “auto-correct” in pregnancy)

  44. Massive blood loss Defined as loss of > one circulating volume in 24 hours Coagulopathy is multifactorial: Loss of factors only once 80% of volume replaced Dilution of factors during fluid resuscitation Inhibitory effect of some colloids on clotting factors DIC secondary to trauma Acidosis Hypothermia (enzymes) (blood warmer)

  45. Massive blood loss Regular checks of FBC and PT,APTT,TT and Fibrinogen Aim for platelets > 50x109/l or >100x109/l if polytrauma or CNS injury Aim for fibrinogen >1g/l Aim for PT and APTT <1.5x control times FFP 12-15ml/kg Cryoprecipitate 1-1.5 packs /10kg if fibrinogen fails to correct with FFP ? rVIIa

  46. Causes of DIC • sepsis/severe infection (any organism) • trauma (e.g. polytrauma, neurotrauma, fat embolism) • organ destruction (e.g. severe pancreatitis) • malignancy • massive blood loss with inadequate fluid replacement • vascular abnormalities (e.g. Kassbach-Merrit syndrome) • severe hepatic failure • severe toxic or immunological reactions (e.g. recreational drugs, transfusion reactions, transplant rejection)

  47. Management of DIC • TREAT THE CAUSE • Fluid resus as needed, antibiotics if sepsis • If bleeding or need surgery give FFP, Platelets, Cryoprecipitate (Aim Platelets>50x109/l, PT and APTT < 1.5x normal) • If thrombotic manifestations eg. Dermal ischaemia consider low dose heparin infusion.

  48. Heparin NB arterial lines !!!!!!!

  49. Heparin • Unfractionated • monitor with APTT (ratio 1.5-2.5 patient’s baseline) • reversal by stopping infusion and (very rapid with protamine sulphate) • can be hard to anticoagulate children due to low antithrombin levels • bolus then continuous infusion • Low molecular weight heparin • less monitoring • once or twice daily administration • more reliable pharmacokinetics (NB renal excretion) • anti-Xa levels - 4h post dose • Treatment 0.5-1; Prophylaxis 0.1-0.3 IU/ml

  50. Warfarin • II, VII, IX, X, protein C and S are vitamin K dependent. • NB C and S fall first so overlap with heparin (Warfarin induced skin necrosis) • Therapeutic range within 3-5 days • Monitor in anticoagulant clinic using INR • Most indications target INR 2-3

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