haematology dr dániel erdélyi 2nd dept pediatrics semmelweis university

Haematology

Dr Dániel Erdélyi2nd Dept PediatricsSemmelweis University

Haematology topics for final exam

• Coagulopathies• Leukaemia• Hodgkin’s disease, Non-Hodgkin’s lymphoma• Diseases with hepatomegaly, splenomegaly• Lymphnodes enlargement - DD and

treatment• Anaemias• Iron deficiency anaemia

1st case presentation

6 mo. old boy C/O ↑crying, progressively over recent days.O/E well developed and hydrated, CVS stable,Abdo distended, liver 1.5–2 cms below costal margin,Exam unremarkable otherwiseWBC 14.3 G/L, Neutro 13%, Lymph 76%Hb 102 g/L, Plt 379 G/LCreat 25 umol/L, U&Es-CRP normalIdeas, please!

Lab values normal for adults would be very worrying in a baby!

1. LAB NORMAL RANGES

Normal Hb in infancy & childhoodHb (g/L)

Age

100

150

200

boysgirls

3 mo 6 mo 10 y

Hb (g/L)

Age

100

200

3 mo 6 mo

Age Hemoglobin (g/l)

3 mo - 2 years < 100

< 110

6 - 14 years < 120

Adult women < 120

Adult men < 130

2 - 5 years

Anaemia, thresholds

Normal WBC in infancy & childhood

15

WBC (G/L)

Age

10

30

3 mo 6 mo

5

10 y

Differential count in children1 wk

4 y

10 y

Neutrophils Lymphocytes

Normal platelets in childhoodPlt (G/L)

Age

150

300

„Adult type” FBC in 6 mo baby(case presentation – to interpret)

• Hb 140 g/l• WBC 4.5 G/L• Neutrophils 70%

2nd case presentation

18 mo. girl Pale, GP requested FBCWBC 12.5 G/L, Neutro 26%, Hb 82 g/L, MCV 59 fl, RDW 18%, Plt 530 G/L,Physical exam unremarkableInterpretation, DD, please!

Classification of anaemia

1. Blood loss

•acute•chronic – iron deficiency later

•external•internal

2A. Haemolytic - intrinsic•membrane-defects (sphaerocytosis, elliptocytosis, stomatocytosis, PNH)•hemoglobinopathy (sickle cell anaemia, thalassaemia, rare others)•enzyme-defects (pyruvate kinase defect, glucose-6-phosphate dehydrogenase def., other rare forms)

2B. Haemolytic – extrinsicImmune Autoimmune haemolytic anaemiaAlloimmune (neonatal)Autoimmune diseasesTransfusion reactionsNon-imm. Infections (malaria, mycoplasma, EBV)

+/- immune mechanismsHypersplenismMicroangiopathic (HUS, TTP, DIC,

Kassabach-Merritt syndrome)

Not typically called as haemolytic anaemia

3. Hyporegenerative•Haematinics: Fe, Cu, folate, B6, B12, protein...•Primary or idiopathic: congenital anaemias, SAA•Temporary, by external causes:

viral infections (Parvo B19, EBV, CMV, else) drugs (ibuprofen, metamizol; chemotherapy)

•Bone marrow space ↓leukaemia, neuroblastoma, osteopetrosis...

•Secondary other: chronic infections,renal, hepatic, endocrine disordersautoimmune (SLE)

2. DIAGNOSTICS

Microcytic Normocytic Macrocytic

Iron deficiency Blood loss B12 folate deficiency

Chronic disease Haemolysis/AIHA Liver diseaseThalassaemia Bone marrow Aplastic

failure MDSLead intox. Renal failure Congen dyserythr. aB6 deficiency Hypothyroidosis

Gravidity

Various: corpuscular haemolytic anaemias

RDW: red cell distribution width

• Normal: 11-14%• Increased: iron deficiency, cong. membrane

disorders, burns, microangiopathic

Hypochrome / Hyperchrome

• Usually correlate with micro/normo/macrocytic featire

• Sphaerocytosis: ↓ MCV ↑ MCHC

Reticulocyte count

• Normal: 0.5 – 1.5 %, but consider anaemia• High: bleed, haemolysis• Low: hyporegenerative

Other lab tests to identify haemolysis:• Billirubin• LDH, haptoglobin• Consider intra/extravascular haemolysis

Blood film

Iron deficiency

Thalassaemia

Sphaerocytosis

Elliptocytosis

Megaloblastic anaemia

Fragmentocytes

Sickle cell disease

Lead intoxication

Bone marrow cytology/histopath.• For hyporegenerative anaemias only

Antibodies• For haemolytic anaemias only• Coombs: direct (DAT) / indirect antibodies • Cold and warm antibodies• Specific antibodies

Miscellaneous others

• Haemoglobin electrophoresis / HPLC• Osmotic fragility / cryoresistance• ADAMTS13 activity• D-dimer, coagulation factors• Haemoglobinuria• Erythropoietin

3. CLINICAL COURSE @ THERAPY

• Prelatent / latent deficiency / anaemia• Causes• Symptoms: haematology, others• Lab signs; DD chronic disease related a.• Therapy– iron salts (ferrous sulphate II, III)– iron carbohydrate complex– iv iron

• Follow up

Iron deficiency anaemia

Haemolytic anaemias

Clinical signs:•Pallor, collapse•Icterus•Splenomegaly•Gall stones•Possibly emergencies:

rapid haemolysis, aplastic crisis

Immune-haemolytic anaemia

• Course of AIHA• Therapy:– glucocorticoids– IVIG– other immunosuppressive therapies, rituximab– splenectomy– transfusion only when life-threatening

www.wikipedia.org

Haemoglobinopathies

Sickle cell anaemia – special points

• Painful cryses• Sequestration• Hydration• Analgaesia• Hyposplenism• Transfusion policy• Exchange transfusion• Transcranial Doppler-US• Hydroxyurea, allo-HSCT

Congenital aplastic/hypoplastic anaemias

• Fanconi anemia• Dyskeratosis congenita• Shwachmann-Diamond sy• Constitucional aplastic anemia• Diamond-Blackfan anaemia• ...

• DNA repair defect• Mean age at diagnosis 9

years, pancytopenia• Multiple anomalies

possible: short stature, bone, kidney, heart, malformations, skin pigmentation, hypogonadism, learning difficulties

Fanconi anaemia

• Ribosomal defect• Isolated red cell aplasia, presents at few

months of age• Most children without other

abnormalities

Diamond-Blackfan anaemia

Treatment of congenital aplastic / hypoplastic anaemias

• Symptomatic: transfusions, kelating agents • Steroids• Allogenic stem cell transplant

4. LEARNING POINTS

Frequent, important...

Anaemia - most important:•Iron deficiency: dietary, cow-milk protein allergy, malabsorption•Anaemia in chronic diseases

2nd line•B12 and folate deficiency•Corpuscular (e.g. sphaerocytosis) and autoimmune haemolytic anaemias•In Hungary, haemoglobinopathies are rare

Bleeding - most important:•ITP, DD of thrombocytopenia•Haemophylia A, B•von Willebrand’s

2nd line•DIC, HUS•Lupus anticoagulans and other inhibitors

Haemat. malignancies – most important:•ALL >> AML >> CML •Hodgkin’s•Non-Hodgkin:–Burkitt’s– Lymphoblastic lymphoma

Specific to / different in children

Alloimmune cytopenias in newborns+ thrombocytopenia from maternal ITP

Vitamin K deficiency in infantsPresenting symptoms of congen. coagulopathiesFrequency of malignanciesApproach to polycytaemia, thrombocytosis

5. ELSE

• New leukaemic patient• New malignancy• Febrile neutropenia