Anaemias

Question 1

Sideroblastic anaemia

Answer 1

Ineffective erythropoiesis ->iron loading (bone marrow) causing haemosiderosis (organ damage from iron deposition)

Causes: myelodysplastic disorders, chemotherapy, alcohol excess, lead excess, anti-TB drugs or myeloproliferative disease

Diagnosis: Ring sideroblasts seen in the marrow (erythroid precursors with iron deposited in mitochondria in a ring around the nucleus)

Treatment: remove the cause; Pyridoxine (vitamin B6 promoted RBC production)

Question 2

Haemolytic anaemia bloods

Answer 2

Reticulocytosis
Raised unconjugated bilirubin
Raised urobilinogen
Raised LDH (lactate dehydrogenase released from red cell cytoplasm)

Question 3

What virus/crisis does haemolytic anaemia make you susceptible to

Answer 3

Parvovirus B19 -> aplastic crisis

Question 4

Hereditary spherocytosis

Answer 4

Autosomal dominant
Spectrin or ankyrin deficiency (membrane proteins)
Susceptibility to parvovirus B19 and often develop gallstones
Extravascular haemolysis = splenomegaly

Diagnosis: spherocytes, increased osmotic fragility (lysis in hypotonic solutions), DAT-ve, flow cytometry

Treatment: splenectomy, folic acid

Question 5

Hereditary eliptocytosis

Answer 5

Almost all AD - spectrin mutations
Elliptocytes on blood film
Severity ranges from foetal hydrops to asymptomatic

Question 6

Glucose-6-phosphate dehydrogenase deficiency

Answer 6

X-linked
Attacks - rapid anaemia and jaundice, with bite cells and Heinz bodies
Precipitated by oxidants (G6PD makes glutathione: protects from oxidant damage) - drugs, broad beans, acute stressors/infection
Intravascular haemolysis: dark urine

Diagnosis: enzyme assays 2-3 months after crisis

Treatment: avoid precipitants, transfuse if severe, genetic screening (some types indicate splenectomy)

Question 7

Pyruvate kinase deficiency

Answer 7

AR inheritance

severe neonatal jaundice, splenomegaly, haemolytic anaemia

Question 8

Sickle cell disease: mutation, features, diagnosis

Answer 8

Single base mutation, Glu->Val at codon 6 of B chain -> HbS instead for HbA

Manifests at 3-6mths (with decreasing HbF)
Decreased O2 tension -> HbS polymerisation -> sickling

Haemolysis: anaemia, splenomegaly, folate deficiency, gallstones, aplastic crisis
Vaso-oclusion + infarction:
Stroke
Infections (hyposplenism, CKD)
Crises (splenic, sequestration, chest and pain)
Kidney (papillary necrosis, nephrotic)
Liver (gallstones)
Eyes (retinopathy)
Dactilitis (impaired growth)
mesenteric ischaemia
priapism

Diagnosis: sickle cells and target cells, sickle solubility test, Hb electrophoresis, Guthrie test for pneumococcal prophylaxis

Question 9

Sickle cell: acute and chronic treatment

Answer 9

Acute:

• Opioid analgesia for painful crises
• Exchange blood transfusions in severe crises (particularly chest)

Chronic:

• All should be on penicillin V, pneumovax, HIB vax
• Some benefit from: folic acid/hydroxycarbamide (increases HbF), regular exchange transfusions, carotid doppler monitoring

Question 10

Beta thalassaemia

Answer 10

Point mutation -> ↓B-chain synthesis, excess of a-chains
↑ HbA2 and HbF

Skull bossing, maxillary hypertrophy, hairs on end skull X-ray
Hepatosplenomegaly

• β- thalassaemia minor (e.g. β+/ β+ or β0/ β+) → Asymptomatic carrier, mild anaemia
• β-thalassaemiaintermedia (e.g. β+/βorβ0/β) → Moderate
  anaemia, splenomegaly, bony deformity, gallstones
• β-thalassaemiamajor (β0/β0) → 3-6 mths severe anaemia, FTT, hepatosplenomegaly (extramedullary erythropoiesis), bony deformity, severe anaemia + heart failure

Diagnosis: Hb electrophoresis (Guthrie test at birth)

Tx: some none; blood transfusions with iron chelation to stop iron overload + folic acid

Question 11

Alpha thalassaemia

Answer 11

Deletion - reduced a-chain synthesis, excess B-chain

3 genes - silent carrier
2 genes - a-thalassaemia trait - asymptomatic, mild anaemia
1 genes - HbH disease - moderate anaemia, splenomegaly
0 genes - HbBarts; hydrops foetalis - incomparable with life

Question 12

Warm autoimmune haemolytic aneamia: temp, Ig, blood film, coombs test, causes, management

Answer 12

> 37C
IgG to Rh on RBCs
Positive Coombs
Spherocytes on film

Causes: Idiopathic, lymphoma, CLL, SLE, methyldopa, some Abx

Management: Steroids, splenectomy, immunosuppression

Question 13

Cold autoimmune haemolytic aneamia: temp, Ig, features, coombs test, causes, management

Answer 13

<37C
IgM to L, I, P on RBCs
Positive Coombs
Raynauds

Causes: Lymphoma, infections: EBV, mycoplasma, idiopathic

Management: treat underlying, avoid cold

Question 14

Paroxysmal cold haemoglobinuria (PCH)

Answer 14

Acute cold autoimmune haemolutic anaemia
Usually in children
Hb in urine usually caused by viral infection (measles, EBV, syphilis, VZV)
Donath-Landsteiner Abs -> stick to RBCs in cold -> complement mediated haemolysis on re-warming

Question 15

Paroxysmal nocturnal haemoglobinuria (PNH)

Answer 15

Acquired loss of protective surface GPI markers on RBCs (platelets+neutrophils) -> complement mediated lysis -> chronic intravascular haemolysis, esp at night

Morning haemoglobinuria, thrombosis, (+Budd Chiari syndrome)

Diagnosis: immunophenotype shows altered GPI, Ham’s test (in vitro acid-induced lysis)

Tx: Iron/folate, prophylactic vax/Abx, expensive mAbs (eculizumab) prevents complement binding RBCs

Question 16

What is MAHA, what is seen in blood film, causes

Answer 16

Mechanical RBC destruction (forced through fibrin/pit mesh in damaged vessels -> HUS, TTP, DIC, pre-eclampsia, eclampsia

Tx - usually plasma exchange

Question 17

Thrombotic thrombocytopenic pupura

Answer 17

Auto-antibodies against ADAMTS13 lead to strong strands of vWF that cut up RBCs in the blood
Pentad of symptoms: MAHA (with RBC fragmentation) + thrombocytopenia + AKI + fever + neurological Sx

Question 18

Haemolytic uraemic syndrome

Answer 18

Caused by E.coli: toxin damages endothelial cells, forms fibrin mesh
Triad: MAHA (fragmented RBCs) + impaired renal function + thrombocytopenia