Borderline cytopenias Dr Taku Sugai Consultant Haematologist
Borderline cytopenias Neutropenia Thrombocytopenia Anaemia with normal haematinics Two recent cases of cytopenias
Neutropenia ANC of more than 2SD below a normal mean Hillingdon normal range 1.8 7.7 x 10 9 /l Ethnic variation Caucasian: less than 1.5 x 10 9 /l Afro caribbean: less than 1.2 x 10 9 /l
Neutrophil maturation
Common causes of Neutropenia Decreased neutrophil productions Vitamin B12/Folate deficiency Drugs Antibiotics(Penicillins/Cephalosporins/choloramphenicol) Anti epileptic(carbamazepine/phenytoin) Psychiatric drugs(phenothiazine) Anti inflammatory(gold/phenylbutazone) Anti Thyroid drugs(carbimazole/methylthiouracil) Diuretics(Hydrochlorothiazide/bumetanide) Cytotoxic agents Alcohol Viral infections e.g HIV, CMV, EBV, Parvovirus, Hep B MDS/Aplastic Anaemia/Bone marrow infiltration Increased peripheral destructions Hypersplenism Autoimmune disease(sle/ra)
Neutrophil morphology
Neutropenia Which cases to refer? ANC less than 0.5 x 10 9 /l Any neutropenia with history of infections Any cases with other cytopenias Drug induced neutropenia is the commonest cause of isolated neutropenia.
Thrombocytopenia Platelets Below 100x 10 9 /l No significant bleed until below 20 x 10 9 /l Inverse relationship between platelets count and skin bleeding time
Bleeding associated with significant thrombocytopenia Findings Disorder of coagulation Disorder of platelets/ Thrombocytopenia Onset of bleeding Delayed after trauma Immediate after trauma Mucosal bleeding Rare Common Petechiae Rare Characteristics Deep haematomas Characteristics Rare Haemarthrosis Characteristics Rare Bleeding from superficial cuts and scratches Minimal Persistent, often profuse
Platelets clumping
Megakaryopoiesis
Common causes of Thrombocytopenia Decreased platelets productions Vitamin B12/Folate deficiency Drugs Ranitidine Thiazide diuretics Isotretinoin Quinine Heparin Valproic acid Montelukast Interferon Teicoplanin Abciximab/Oral GpIIb/IIIa inhibitors Alcohol Viral infections e.g HIV, ToRCH(HHV6), EBV, Parvovirus, Hep C, Mycoplasma, Helicobacter Haem neoplasm MDS/Aplastic Anaemia/Bone marrow infiltration Increased peripheral destructions Hypersplenism Autoimmune disease(sle/antiphospholipid syndrome) ITP HUS/TTP
Thrombocytopenia Which cases to refer? Platelets count less than 50 x 10 9 /l Any thrombocytopenia with bleeding history Any cases with other cytopenias Drug history and virology screen would be helpful
Anaemia WHO definition (Blanc et al, 1968) Age or Gender Group Children (0.5 5.0) 11 Children (5 12yr) 11.5 Teens (12 15yr) 12.0 Women, nonpregnant(>15yr) Hb threshold (g/dl) 12.0 Women, pregnant 11.0 Men (>15yr) 13.0
Anaemia with normal haematinics Haematological malignancies* Solid organ malignancies Haemolytic anaemia Anaemia of chronic disease* Anaemia 2ndary to renal disease Anaemia 2ndary to liver disease
Anaemia of chronic disease Hb is not less than 9g/dl MCV is normal or mildly reduced(77 82fl) MCH is usually normal Serum iron is reduced Total iron binding capacity(transferrin) reduced Transferrin Saturation mildly reduced Serum Ferritin normal or increased CRP and ESR usually raised(hepcidin increased)
Anaemia of chronic disease Iron metabolism
Anaemia of chronic disease Pathogenesis Reduction in iron granules in bone marrow RBC precursors Direct inhibition by TNFa/IL 1/IL 6 Relative lack of Erythropoietin for the level of haemoglobin(il 1a inhibits Epo secretion)
Anaemia of chronic disease Treatment Treatment of underlying chronic disease Epo treatment Trial of iron for 3 months in selected cases
Anaemia Which cases to refer Unexplained anaemia with significant weight loss Unexplained anaemia with other cytopenias
Case 1 Investigations Hb 15.9 MCV 86.8 WBC 3.0* (4 11) Neu 1.7* (1.8 7.7) Lym 0.7*(1 4.8) Plt 88* (140 400) Na 134 K4.3 U1.7 Cr57 Bil 17 ALP 74 ALT 21 Alb 37 AST34*(8 20)
Diagnosis?
Case 1 Diagnosis HIV positive Hepatitis B positive
Case 2 Mr KS is 32 year old Caucasian male Routine blood test in 2008 No history of infection/mouth ulcers No history of bruising Drinks 4 units/week
Case 2 Investigations 2008 Hb 14.2 MCV 102.6*(80 100) WBC 3.1* (4 11) Neu 0.9* (1.8 7.7) Lym 1.9*(1 4.8) Plt 72* (140 400) Na 142 K3.8 U5.2 Cr90
Case 2 Feb2012 4 weeks history of SOB on exertion 12 months history of lethargy Recent history of easy bruising No history of infections Evidence of clinical anaemia No organomegaly
Case 2 Investigations Feb 2012 Hb 7.6* WBC 1.6* Neu 0.2* Lymp 1.2 Plt 24* Normal clotting Normal renal function/lfts Normal Folate/B12
Diagnosis?
Case 2
Case 2 Blood film
Bone marrow aspiration and trephine biopsy
Case 2 Bone marrow aspirate
Case 2 Bone marrow trephine
Cytogenetics
FISH for Chromosome 7
Diagnosis Myelodysplastic syndrome Refractory Anaemia Excess Blasts 2(Almost AML) Monosomy 7 Small PNH clone
Myelodysplastic Syndrome Clonal disorder of haemopoiesis Incidence 3 5 per 100,000/ year Incidence >20 per 100,000/year over the age of 70 years. 60% of patients over the age of 70 More common in male 1.4M to 1.0F 15% of MDS related to previous chemo T R MDS common after 5 7 years
Incidental 20% MDS Clinical features Lethergy due to anaemia 80% Infections or bleed 20%
MDS Laboratory features Pancytopenia 30 50% Hb <10g/dL Neutrophils <1.8 x 10 9 /L Platelets <100 x 10 9 /L Anaemia & thrombocytopenia/neutro 20% Isolated thrombocytopenia/neutropenia5%
Summary Cases to refer Unexplained anaemia with significant weight loss Unexplained anaemia with other cytopenias Neutropenia <0.5 x 10 9 /l Neutropenia with Hx of infections Thrombocytopenia with Hx of bleeding Multiple cytopenias Detailed Drug history is essential prior to referral
Thank you Any Questions?