Hemolytic anemias: membrane defects and immune

15 DOH Abu Dhabi (HAAD) lab licensing practice questions on Hemolytic anemias: membrane defects and immune, part of Hematology. The first 15 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

1. Question 1 · Hard

   A 24-year-old woman had a splenectomy for hereditary spherocytosis at age 9. Afterwards her hemoglobin stayed normal, her platelets ran at about 500 × 10^9/L, and every film showed Howell-Jolly bodies. Over the past year she has become tired and jaundiced again. Results: hemoglobin 102 g/L (10.2 g/dL), reticulocytes 8% (her baseline after splenectomy 2%), indirect bilirubin 46 µmol/L (2.7 mg/dL), platelets 290 × 10^9/L, DAT negative, and serum B12 and folate normal. The film shows many spherocytes and polychromasia, but Howell-Jolly bodies are no longer seen. What is the most likely cause of the returning hemolysis?

   1. AWarm autoimmune hemolytic anemia
   2. BRegrowth of an accessory spleen
   3. CParvovirus B19 aplastic crisis
   4. DFolate deficiency from ongoing hemolysis

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   Answer: B · Regrowth of an accessory spleen

   Howell-Jolly bodies are nuclear remnants that the spleen normally removes from red cells, so their constant presence after splenectomy showed that no splenic tissue was working. Their disappearance, with a fall in the platelet count from the post-splenectomy level and the return of hemolysis, shows that splenic tissue is again filtering the blood, most often an accessory spleen (splenule) that has enlarged. The spherocytes are trapped and destroyed there, so the anemia returns. A negative DAT excludes autoimmune hemolysis, a reticulocyte count of 8% excludes an aplastic crisis, and normal folate rules out folate deficiency. A scan with heat-damaged labelled red cells can locate the splenule before surgery.

   • A: The DAT is negative.
   • C: An aplastic crisis lowers the reticulocyte count; hers has risen to 8%.
   • D: Folate is normal, and folate deficiency would lower, not raise, the reticulocyte count.

2. Question 2 · Hard

   A 71-year-old man with untreated chronic lymphocytic leukemia (CLL) has become breathless. Two months ago his hemoglobin was 128 g/L. Today: hemoglobin 71 g/L (7.1 g/dL), MCV 104 fL, MCHC 368 g/L (reference 320-360), reticulocytes 9.5% (reference 0.5-2.5%), WBC 46 × 10^9/L with 90% lymphocytes and many smudge cells, platelets 152 × 10^9/L, LD 690 U/L (reference 125-220), indirect bilirubin 49 µmol/L (2.9 mg/dL) and haptoglobin undetectable. The film shows many spherocytes and polychromasia but no schistocytes. DAT: anti-IgG 3+, anti-C3d negative, and the eluate reacts with all panel cells at the antiglobulin phase. The most likely cause of the fall in hemoglobin is:

   1. AMarrow failure from CLL infiltration
   2. BWarm autoimmune hemolysis due to CLL
   3. CLate-presenting hereditary spherocytosis
   4. DCold agglutinin disease from the CLL clone

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   Answer: B · Warm autoimmune hemolysis due to CLL

   A rapid fall in hemoglobin with a high reticulocyte count, raised LD and indirect bilirubin, undetectable haptoglobin and many spherocytes shows extravascular hemolysis. A DAT positive with anti-IgG and an eluate that reacts with all panel cells identify a warm IgG autoantibody, and CLL is one of the commonest causes of secondary warm autoimmune hemolytic anemia. Marrow infiltration would lower the reticulocyte count and usually the platelets, which are normal here. Cold agglutinin disease gives a DAT positive for C3d only, and hereditary spherocytosis has a negative DAT and would not appear suddenly at 71. The raised MCV reflects the large number of reticulocytes.

   • A: Marrow failure lowers the reticulocyte count; here it is 9.5%.
   • C: Hereditary spherocytosis has a negative DAT and is present from childhood.
   • D: Cold agglutinin disease gives a DAT positive for C3d, not IgG alone.

3. Question 3 · Hard

   A 45-year-old man has hemoglobin 80 g/L (8.0 g/dL), down from 145 g/L a year ago. Reticulocytes are 10%, LD is raised, haptoglobin is undetectable and the film shows many spherocytes but no schistocytes. The tube DAT is negative with polyspecific and monospecific reagents, and the hemolysis responds to corticosteroids. The best explanation is:

   1. AWarm autoantibody below the tube DAT detection limit
   2. BMicroangiopathic hemolysis from small-vessel disease
   3. CCold agglutinin disease with a weak cold antibody
   4. DHereditary spherocytosis from a new mutation

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   Answer: A · Warm autoantibody below the tube DAT detection limit

   A small proportion of warm AIHA cases are DAT negative by the tube method, because the red cells carry fewer IgG molecules than the test can detect, or the antibody is IgA or low-affinity IgG that washes off. Acquired spherocytic hemolysis with a good steroid response strongly suggests this. More sensitive methods, such as a column agglutination or flow cytometric DAT, or an anti-IgA reagent, often show the antibody. HS is unlikely because the hemoglobin was normal a year earlier.

   • B: Microangiopathic hemolysis produces schistocytes, and none are seen.
   • C: Cold agglutinin disease gives a C3-positive DAT, and spherocytes are not its main feature.
   • D: HS is present from birth, and this man had a normal hemoglobin a year ago.

4. Question 4 · Hard

   A 32-year-old woman with no diarrhea develops acute kidney injury, with creatinine 362 µmol/L (4.1 mg/dL). Results: hemoglobin 74 g/L (7.4 g/dL), platelets 52 × 10^9/L, schistocytes 4%, haptoglobin undetectable, DAT negative, PT and APTT normal, ADAMTS13 activity 62% (severe deficiency is below 10%), stool Shiga toxin PCR negative and C3 low. The most likely diagnosis is:

   1. AComplement-mediated (atypical) HUS
   2. BDisseminated intravascular coagulation
   3. CImmune thrombotic thrombocytopenic purpura
   4. DShiga toxin-associated HUS

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   Answer: A · Complement-mediated (atypical) HUS

   Schistocytes, thrombocytopenia, a negative DAT and normal clotting times point to a thrombotic microangiopathy. ADAMTS13 activity well above 10% makes TTP unlikely, and the absence of diarrhea with a negative Shiga toxin test argues against STEC-HUS. Severe kidney injury with a low C3 fits uncontrolled activation of the alternative complement pathway, called complement-mediated or atypical HUS. It is treated with complement inhibitors such as eculizumab.

   • B: DIC prolongs the PT and APTT, and these are normal.
   • C: Immune TTP has severely reduced ADAMTS13 activity, usually below 10%.
   • D: STEC-HUS follows diarrhea, usually bloody, and the Shiga toxin test is positive.

5. Question 5 · Hard

   A 30-year-old woman has hemoglobin 82 g/L (8.2 g/dL), reticulocytes 9%, MCHC 365 g/L (reference 320-360) and many spherocytes. Osmotic fragility is increased and the DAT is positive with anti-IgG. Her hemoglobin was normal a year ago and no relative has anemia. What is the best interpretation?

   1. AWarm AIHA; immune spherocytes are also fragile
   2. BMicroangiopathic hemolysis with fragmented cells
   3. CHereditary spherocytosis, shown by the fragility test
   4. DCold agglutinin disease with secondary spherocytes

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   Answer: A · Warm AIHA; immune spherocytes are also fragile

   Osmotic fragility reflects the shape of the cells, not the cause, so any spherocyte, inherited or immune, lyses early. A positive IgG DAT, recent onset and no family history point to warm autoimmune hemolytic anemia. HS is lifelong and DAT negative, and the fragility test cannot separate the two, so the DAT should always be done first. An eluate and a search for causes such as SLE or lymphoma should follow.

   • B: No schistocytes are described, and microangiopathic hemolysis has a negative DAT.
   • C: Fragility is increased in any spherocytic anemia, and HS would be lifelong with a negative DAT.
   • D: Cold agglutinin disease gives a C3-only DAT, not an IgG-positive one.

6. Question 6 · Easy

   Warm autoimmune hemolytic anemia occurring together with immune thrombocytopenia is called:

   1. AHELLP syndrome
   2. BKasabach-Merritt syndrome
   3. CEvans syndrome
   4. DFelty syndrome

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7. Question 7 · Medium

   Which set of results fits microangiopathic hemolytic anemia caused by a thrombotic microangiopathy?

   1. AAgglutinates, normal platelets, C3-only DAT, high MCHC
   2. BSchistocytes, low platelets, negative DAT, high LD
   3. CSpherocytes, normal platelets, IgG DAT, high LD
   4. DBite cells, normal platelets, negative DAT, Heinz bodies

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8. Question 8 · Easy

   Which red cell index is often raised in hereditary spherocytosis?

   1. AMCH
   2. BHematocrit
   3. CMCHC
   4. DMCV

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9. Question 9 · Medium

   Primary chronic cold agglutinin disease is most often caused by:

   1. AA polyclonal IgG warm autoantibody to Rh proteins
   2. BMonoclonal IgM kappa from a small B-cell clone
   3. CPolyclonal IgM made after Mycoplasma pneumonia
   4. DA biphasic IgG antibody with anti-P specificity

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10. Question 10 · Medium

    In warm autoimmune hemolytic anemia, spherocytes form mainly because:

    1. ASplenic macrophages remove bits of IgG-coated membrane
    2. BFibrin strands cut the red cells in small vessels
    3. CAn inherited membrane protein defect weakens cells
    4. DComplement lyses the red cells inside blood vessels

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11. Question 11 · Medium

    In hereditary spherocytosis the osmotic fragility curve is shifted to the right. This means the cells:

    1. ADo not lyse even in distilled water
    2. BStart to lyse at higher saline concentrations
    3. CLyse at normal concentrations, but more slowly
    4. DStart to lyse only at lower saline concentrations

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12. Question 12 · Hard

    A 10-year-old girl with hereditary spherocytosis has become paler over 6 weeks. Compared with her usual results: hemoglobin 68 g/L (usual 105), reticulocytes 1.2% (usual 8%), MCV 106 fL (usual 86), WBC 3.2 × 10^9/L and platelets 110 × 10^9/L, with hypersegmented neutrophils. Parvovirus B19 IgM is negative. The most likely cause is:

    1. ASplenic sequestration crisis
    2. BParvovirus B19 aplastic crisis
    3. CFolate deficiency from high marrow demand
    4. DIncreased hemolysis with an infection

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13. Question 13 · Easy

    Hereditary spherocytosis is usually caused by a defect in which red cell membrane proteins?

    1. AProtein 4.1 or glycophorin C
    2. BAnkyrin, band 3 or spectrin
    3. CRh-associated glycoprotein
    4. DCD55 and CD59

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14. Question 14 · Medium

    Which blood film finding is expected after splenectomy for hereditary spherocytosis?

    1. ASpherocytes still present, plus many bite cells
    2. BSpherocytes replaced by many schistocytes
    3. CSpherocytes still present, plus Howell-Jolly bodies
    4. DNo spherocytes, as the membrane defect is cured

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15. Question 15 · Hard

    A 62-year-old man with metastatic gastric adenocarcinoma has bruising and fatigue. Results: hemoglobin 79 g/L (7.9 g/dL), platelets 38 × 10^9/L, schistocytes 3%, nucleated red cells and myelocytes on the film, PT 19 s (reference 11-14), APTT 42 s (reference 25-35), fibrinogen 1.1 g/L (reference 2.0-4.0), D-dimer markedly raised and DAT negative. The most likely cause of the anemia is:

    1. AImmune thrombotic thrombocytopenic purpura
    2. BHypersplenism from liver metastases
    3. CCancer-associated microangiopathy with DIC
    4. DWarm autoimmune hemolytic anemia

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