Haematology in 1 hour

1. Haematology in 1 hour Dr Simon Watt Research SpR, MRI

2. Topics to be covered • Anaemia • Iron deficiency • Causes of macrocytosis and treatment • Haemoglobinopathies • Haemolytic anaemia • Polycythaemia • Leukaemia • Chronic v acute • Consequences of leukaemia • Bone marrow failure • Tissue infiltration • Myeloma

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

8. 23 y male from Cyprus • Hb 13.0 • WCC 5.4 • PLT 196 • MCV 68.7 • MCH 23 • MRCP question: Which is the best test to perform next?

9. Laboratory features • Mild anaemia with reduced MCV and MCH (27pg) • RDW normal (c.f. iron deficiency) • Raised Hb A2 (>3.5%) is diagnostic: higher levels seen with b0 or severe b+ • Raised Hb F in 1/3 – ½ cases (2-7%) • Normal A2 and iron = probable alpha thal

10. 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

11. 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)

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

13. 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 • % Hb S is constant and bears no relation to acute crisis • Patients have functional asplenia

14. Blood film appearances Sickle cell Howell Jolly body Target cell

15. 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?

16. 20 yr old vegan • Hb 9.8 • MCV 110 • Plt 115 • WCC 3.0

17. Management of low B12 • History • Diet, previous surgery, GI disease • IF antibodies • Schilling test (distinguishes intrinsic factor def from malabasorption) • 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

18. 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

19. Classification of leukaemias Acute Chronic Myeloid origin Acute Myeloid Leukaemia (AML) Chronic Myeloid Leukaemia (CML) Lymphoid origin Acute Lymphoblastic Leukaemia (ALL) Chronic Lymphocytic Leukaemia (CLL)

20. 25 year old male. Recurrent upper respiratory infections with fever & nausea. Submandibular swelling for several months Noted that cuts on his hands did not heal well. On examination: Submandibular adenopathy. No organomegaly. HGB 9.9 g/dL HCT 28.7 % MCV 106.3 fL WBC 7.9 x 10[9]/L. PLT 50 x 10[9]/L Automated differential was: N 4% L 16% M 1 E 0 B 0 Flag!!! Immature Granulocytes ?? Blasts ??

21. 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

22. 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

23. Chronic lymphocytic 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

24. What is Myeloproliferation?

25. Stem cells Proliferating/maturing cells Mature cells monocytes neutrophils megakaryocytes red cells This is normal myeloid cell production (hopelessly simplified) Myeloproliferation arises when normal blood cell production goes wrong!

26. 39 year old female. • Fibrocystic breast disease. • Routine work-up prior to breast biopsy. • Physical Exam: • Moderate splenomegaly. • RBC 4.28 x 10[12]/L HGB 13.4 g/dL • HCT 41.2 % MCV 96.3 fL • WBC 133.6 x 10[9]/L • N seg 52% N band 15% • N meta 13% N myelo 4 % • N pro 3 % Lymph 3 % • Mono 4 % Eosino 1 % • Baso 5 %

27. CML is a classic example in haematology • Distinctive natural history • First “chromosomal” malignancy • Massive research interest – some understanding of how it forms • Real effectiveness of biological therapies: bone marrow transplant; interferon; donor lymphocyte infusion • First targeted malignancy: Glivec

28. The Philidelphia Chromosome (described Nowell and Hungerford in 1960 Material is exchanged between chromosomes 9 and 22 Reciprocal translocation

29. The BCR-ABL tyrosine kinase (described 1983) The chromosomal translocation causes the formation of a fusion between two gene: BCR and ABL. This activates ABL activating many signalling pathways:

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

31. 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)

32. 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

33. 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)

34. 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.

35. 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 malignancy)

36. 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. • Remember differential may be metastatic malignancy!