www.cambridgehaematology.com Fe Deficiency vs Anaemia of Chronic Disease Variable Fe deficiency Chronic disease Serum Iron Transferrin or Normal Transferrin Saturation Ferritin or Normal or normal CRPNormal GIT studies: endoscopy etc
www.cambridgehaematology.com 26 year Female Hx:Antenatal visit; First trimester FBC:Hb11.0 g/dL MCV73 fL MCH27 pg RDW0.14 WCC8.5 x 10 9 /L Platelets 164 x 10 9 /L Film: Microcytic RBC
www.cambridgehaematology.com Fe Deficiency vs Hbinopathy Check iron status: Ferritin Family history / ethnicity: –Thalassaemia / haemoglobinopathy –Need to determine risk to fetus of severe thalassaemic syndrome (in 1 st 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 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 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 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 73 year male Hx:Tiredness FBC:Hb4.0 g/dL MCV102 fL RDW0.24 WCC / PltNormal Film:Macrocytes, fragmented red cells, occasional NRBC
www.cambridgehaematology.com Blood Film 73 yr old male
www.cambridgehaematology.com 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 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 78 year male Hx:Chest pain PMHx:Myocardial infarct FBC:Hb7.2 g/dL MCV97 fL WCC4.5 x 10 9 /L Platelets320 x 10 9 /L Reticulocytes: 320 (10-100)
www.cambridgehaematology.com Polycythaemia investigations FBC + Film CXR Cardiac assessment Red Cell mass Blood gasses Major advance – JAK 2 mutation screens
www.cambridgehaematology.com 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 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 Platelets Too many (thrombocytosis) Too few (thrombocytopenia) Dysfunctional –When should we worry?
www.cambridgehaematology.com Thrombocytosis > 450 x 10 9 /l Causes –Reactive (almost anything!) Common – bleeding, infection, malignancy Tend to be less than 1000 x 10 9 /l –Primary bone marrow disorder Myeloproliferative disorders (up to 3000+) (essential thrombocythaemia, myelofibrosis, polycythaemia, chronic myeloid leukaemia)
www.cambridgehaematology.com 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 Thrombocytosis
www.cambridgehaematology.com Essential Thrombocythaemia (ET) –Long term management balancing thrombotic vs bleeding risk –Aspirin for intermediate risk –Cytoreduction + aspirin for higher risk (beware the pseudohyperkalaemia!!) Thrombocytosis
www.cambridgehaematology.com Thrombocytopenia Is it real??? –Poor sample –Clumped in EDTA – blood film **If at all possible confirm with a repeat sample
www.cambridgehaematology.com How real is the bleeding risk? –Cause of low platelets –Wet vs dry purpura –Platelet transfusions often not useful Thrombocytopenia
www.cambridgehaematology.com 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 Platelet Dysfunction Range of rare inherited causes –Family history –Refer the child that bleeds abnormally! Don’t forget the acquired dysfunction –Renal failure –Liver disease –ASPIRIN
www.cambridgehaematology.com Questions and break!
www.cambridgehaematology.com White Cells Important (and commonly problematic!) –Neutrophils –Lymphocytes Important (less commonly problematic) –Monocytes –eosinophils Less important –basophils
www.cambridgehaematology.com How worried should I be? Pancytopenia is ALWAYS worrying Many cases of isolated neutropenia are less serious What should I do with a neutropenic patient? How common is neutropenic sepsis?
www.cambridgehaematology.com Pancytopenia Referral usually required Bone marrow biopsy usually required
www.cambridgehaematology.com Isolated Neutropenia Not always easy to identify a cause! Always think drugs (idiopathic vs dose) Viral infection Auto-immune disease Marrow causes (sepsis / very ill elderly) Don’t forget –Racial variation –cyclical neutropenia (clinical and lab details) –If child, think congenital
www.cambridgehaematology.com Investigations will depend on clinical presentation –Chance finding vs ill patient –Viral serology may be indicated (hepatitis, EBV etc – Think HIV!) –Autoimmune (SLE, sjorgrens, RA – Felty’s) –Serial blood counts –Referral may be required Isolated Neutropenia
www.cambridgehaematology.com When to refer urgently –Cause of neutropenia –Is the patient acutely ill? Neutropenic fever vs sepsis –Incidence etc –Antibiotic policies etc. –Prophylactic antibiotics - controversial Isolated Neutropenia
www.cambridgehaematology.com Lymphocytes Lineage B vs T vs NK OriginRole
www.cambridgehaematology.com Priorities for investigation –Clinical picture –If other FBC abnormalities, speak to a haematologist –If in doubt, ask for an opinion on a blood film –Monospot test vs viral serology –Flow cytometry –Molecular tests Lymphocytosis
www.cambridgehaematology.com Lymphocytosis (>4 x 10 9 /l) Blasts vs more mature cells Clinical picture very important –Young sick child vs older well patient vs
www.cambridgehaematology.com Young patient with clinical picture of infectious mononucleosis –Monospot useful –Film useful (rule out ALL) –Flow cytometry less helpful –Serology as second line investigation –ID referral occasionally required –(worth thinking about acute HIV) Lymphocytosis
www.cambridgehaematology.com Acute lymphoblastic leukaemia –Children >> adults –Often presents very acutely –Range of clinical features –Laboratory features typical –Referral mandatory Lymphocytosis
www.cambridgehaematology.com Older patient with lymphocytosis –Blood film required (CLL vs LGL) –Flow cytometry usually required –? Refer Clinical picture Underlying diagnosis Lymphocytosis
www.cambridgehaematology.com CLL –Relatively common (300 + / year) –New entity of Monoclonal B Lymphocytosis (MBL) –Age –Clinical presentation Asymptomatic stage A VS Symptomatic stage C Lymphocytosis
www.cambridgehaematology.com Rarer lymphoproliferative disorders –LGL –PLL –Leukaemic phase of most lymphomas –Hairy cell leukaemia Lymphocytosis
www.cambridgehaematology.com Lymphopenia (<1.0 x 10 9 /l) Many cases reflect normal variants How hard should you chase a cause? More common causes –HIV / hepatitis / Hodgkin’s (steroids) Rarer causes –Autoimmune disease / sarcoidosis
www.cambridgehaematology.com Enlarged LN ? cause Clinical context is critical –? Symptom profile –(?spleen) Please do first line investigations –FBC may save a LN biopsy Neck nodes – ENT fast track referral Axillary and groin nodes –Much depends on the clinical context –Haematology review first? –Biopsy first? –CT first?
www.cambridgehaematology.com Monocytes High –Range of infectious and inflammatory stimuli –Primary BM conditions CMML (overlap between myelodysplasia and myeloproliferative disorder) CML Clinical picture and blood film important If no clear cause consider haematology referral
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