Borderline cytopenias Dr Taku Sugai Consultant Haematologist
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 109/l
• Ethnic variation– Caucasian: less than 1.5 x 109/l– Afro‐caribbean: less than 1.2 x 109/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 109/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 109/l
• No significant bleed until below 20 x 109/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 scratchesMinimal Persistent, often profuse
Platelets clumping
Megakaryopoiesis
Common causes of Thrombocytopenia
• Decreased platelets productions– Vitamin B12/Folate deficiency– Drugs
• Ranitidine
Valproic acid• Thiazide diuretics
Montelukast• Isotretinoin
Interferon• Quinine
Teicoplanin• Heparin
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 109/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 Hb threshold (g/dl)
Children (0.5‐5.0) 11
Children (5‐12yr) 11.5
Teens (12‐15yr) 12.0
Women, non‐ pregnant(>15yr)
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
MDS Clinical features
• Incidental 20%
• Lethergy due to anaemia 80%
• Infections or bleed 20%
MDS Laboratory features
• Pancytopenia 30‐50%– Hb <10g/dL– Neutrophils <1.8 x 109
/L
– Platelets <100 x 109
/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 109/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?