A 17-year-old girl is admitted with jaundice, confusion and 5 days of tiredness. She takes no medicines, and her hemoglobin was 12.6 g/dL [126 g/L] a month ago. Results: Hb 8.1 g/dL [81 g/L], reticulocytes 8.5%, DAT negative, no schistocytes or bite cells on the film, total bilirubin 18.6 mg/dL [318 µmol/L] with direct bilirubin 8.2 mg/dL [140 µmol/L], AST 214 U/L and ALT 74 U/L (reference for both < 40 U/L), alkaline phosphatase 22 U/L (reference 40-150 U/L) and INR 2.4. Tests for viral hepatitis and acetaminophen are negative. Which test is most likely to identify the cause of both the hemolysis and the liver failure?

Anti-smooth muscle antibody and IgG

A 19-year-old man presents with petechiae and fatigue 10 weeks after an episode of hepatitis for which no viral cause was found. Results: WBC 1.5 × 10^3/µL [1.5 × 10^9/L], absolute neutrophils 0.3 × 10^3/µL [0.3 × 10^9/L], Hb 7.0 g/dL [70 g/L], MCV 102 fL, reticulocytes 0.1% (absolute 2 × 10^3/µL [2 × 10^9/L]), platelets 9 × 10^3/µL [9 × 10^9/L] and a normal LD. B12 and folate are normal, and the film shows no blasts, dysplasia or teardrop cells. The marrow biopsy is 5% cellular and mostly fat, with no fibrosis or abnormal cells, and the karyotype is normal. Flow cytometry finds a 1.2% GPI-deficient (FLAER-negative) neutrophil clone. The most likely diagnosis is:

Paroxysmal nocturnal hemoglobinuria

Hypoplastic myelodysplastic neoplasm

A 2-year-old boy, previously well, has become pale over 3 weeks after a cold. Results: Hb 5.8 g/dL [58 g/L] (reference for age 10.5-13.5 g/dL), MCV 79 fL (reference for age 70-86 fL), reticulocytes 0.1% (absolute 2 × 10^3/µL [2 × 10^9/L]), WBC 7.6 × 10^3/µL [7.6 × 10^9/L] and platelets 410 × 10^3/µL [410 × 10^9/L]. Bilirubin and LD are normal, and the DAT is negative. Hb F (1.0%) and red cell adenosine deaminase are normal, parvovirus B19 PCR is negative, and he has no physical anomalies. The marrow is normocellular, with normal granulocytes and megakaryocytes but almost no erythroid precursors. The most likely diagnosis is:

Transient erythroblastopenia of childhood

A family has mild, compensated hemolysis. Results: MCHC 37.5 g/dL (375 g/L), target cells and some stomatocytes, DAT negative, osmotic fragility decreased, and a falsely high potassium when samples wait before separation. Which disorder is most likely?

Overhydrated hereditary stomatocytosis

Eight months after a mechanical aortic valve replacement, a patient reports fatigue. Results: hemoglobin 9.4 g/dL (94 g/L), platelets 245 × 10^3/µL (245 × 10^9/L), schistocytes 3%, LD raised, haptoglobin < 10 mg/dL (< 0.1 g/L), DAT negative, ferritin low, urine hemosiderin positive, INR in the warfarin target range. The most likely explanation is:

Valve-related mechanical hemolysis

Warm autoimmune hemolytic anemia

Thrombotic thrombocytopenic purpura

Disseminated intravascular coagulation

Normocytic anemias: hereditary and acquired hemolytic, aplastic

30 ASCP MLS practice questions on Normocytic anemias: hereditary and acquired hemolytic, aplastic, part of Hematology. The first 25 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

Question 1 · Hard
A 17-year-old girl is admitted with jaundice, confusion and 5 days of tiredness. She takes no medicines, and her hemoglobin was 12.6 g/dL [126 g/L] a month ago. Results: Hb 8.1 g/dL [81 g/L], reticulocytes 8.5%, DAT negative, no schistocytes or bite cells on the film, total bilirubin 18.6 mg/dL [318 µmol/L] with direct bilirubin 8.2 mg/dL [140 µmol/L], AST 214 U/L and ALT 74 U/L (reference for both < 40 U/L), alkaline phosphatase 22 U/L (reference 40-150 U/L) and INR 2.4. Tests for viral hepatitis and acetaminophen are negative. Which test is most likely to identify the cause of both the hemolysis and the liver failure?
1. AOsmotic fragility test
2. BRed cell G6PD activity
3. CAnti-smooth muscle antibody and IgG
4. DCeruloplasmin and urine copper
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Answer: D · Ceruloplasmin and urine copper
Acute liver failure with a DAT-negative hemolytic anemia in a young patient, an AST much higher than the ALT and a strikingly low alkaline phosphatase for the bilirubin level is the classic presentation of acute Wilson disease. Dying liver cells release large amounts of free copper into the blood, and the copper damages red cell membranes and enzymes by oxidation, causing hemolysis. Serum ceruloplasmin (usually low) and 24-hour urine copper (high) are the first tests, with an eye examination for Kayser-Fleischer rings. Autoimmune hepatitis does not explain a DAT-negative hemolysis, and G6PD deficiency or hereditary spherocytosis would not cause liver failure. Recognizing the pattern matters, because the patient may need urgent liver transplantation.
- A: Hereditary spherocytosis causes lifelong hemolysis, not sudden liver failure, and her count was normal.
- B: G6PD deficiency causes hemolysis but not liver failure, and no oxidant drug was taken.
- C: Autoimmune hepatitis does not explain a DAT-negative hemolytic anemia.
Question 2 · Hard
A 19-year-old man presents with petechiae and fatigue 10 weeks after an episode of hepatitis for which no viral cause was found. Results: WBC 1.5 × 10^3/µL [1.5 × 10^9/L], absolute neutrophils 0.3 × 10^3/µL [0.3 × 10^9/L], Hb 7.0 g/dL [70 g/L], MCV 102 fL, reticulocytes 0.1% (absolute 2 × 10^3/µL [2 × 10^9/L]), platelets 9 × 10^3/µL [9 × 10^9/L] and a normal LD. B12 and folate are normal, and the film shows no blasts, dysplasia or teardrop cells. The marrow biopsy is 5% cellular and mostly fat, with no fibrosis or abnormal cells, and the karyotype is normal. Flow cytometry finds a 1.2% GPI-deficient (FLAER-negative) neutrophil clone. The most likely diagnosis is:
1. AParoxysmal nocturnal hemoglobinuria
2. BHypoplastic myelodysplastic neoplasm
3. CAcquired aplastic anemia
4. DMegaloblastic anemia
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Answer: C · Acquired aplastic anemia
Pancytopenia with a very low reticulocyte count and a marrow that is 5% cellular and fatty, without fibrosis, blasts, dysplasia or abnormal cells, defines aplastic anemia. Onset weeks after a hepatitis with no viral cause is a recognized pattern of immune-mediated acquired aplastic anemia. Small GPI-deficient clones are found in many patients with aplastic anemia and do not make a diagnosis of PNH when there is no hemolysis; here the LD is normal and reticulocytes are almost absent. Hypoplastic myelodysplastic neoplasm would usually show dysplasia or a clonal karyotype. Mild macrocytosis is common in aplastic anemia, whereas megaloblastic anemia has a hypercellular marrow.
- A: A small GPI-deficient clone is common in aplastic anemia; PNH needs hemolysis, which is absent here.
- B: Hypoplastic MDS usually shows dysplasia or an abnormal karyotype, and neither is present.
- D: B12 and folate are normal, and a megaloblastic marrow is hypercellular, not empty.
Question 3 · Hard
A 2-year-old boy, previously well, has become pale over 3 weeks after a cold. Results: Hb 5.8 g/dL [58 g/L] (reference for age 10.5-13.5 g/dL), MCV 79 fL (reference for age 70-86 fL), reticulocytes 0.1% (absolute 2 × 10^3/µL [2 × 10^9/L]), WBC 7.6 × 10^3/µL [7.6 × 10^9/L] and platelets 410 × 10^3/µL [410 × 10^9/L]. Bilirubin and LD are normal, and the DAT is negative. Hb F (1.0%) and red cell adenosine deaminase are normal, parvovirus B19 PCR is negative, and he has no physical anomalies. The marrow is normocellular, with normal granulocytes and megakaryocytes but almost no erythroid precursors. The most likely diagnosis is:
1. AAcquired aplastic anemia
2. BTransient erythroblastopenia of childhood
3. CParvovirus B19 aplastic crisis
4. DDiamond-Blackfan anemia
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Answer: B · Transient erythroblastopenia of childhood
Severe normocytic anemia with almost no reticulocytes, normal white cells and platelets, no hemolysis and a marrow lacking erythroid precursors shows an isolated failure of red cell production. In a previously well 2-year-old after a viral illness, with normal Hb F and red cell adenosine deaminase and no physical anomalies, this is transient erythroblastopenia of childhood, which recovers on its own within 1 to 2 months. Diamond-Blackfan anemia usually presents in the first year of life, with macrocytosis, raised Hb F and adenosine deaminase, and often thumb or other anomalies. A parvovirus aplastic crisis causes anemia this severe mainly in children with a hemolytic disorder, and the PCR is negative. Acquired aplastic anemia lowers all three cell lines.
- A: Aplastic anemia lowers all three cell lines; here white cells and platelets are normal.
- C: The parvovirus PCR is negative, and he has no underlying hemolytic disorder.
- D: Diamond-Blackfan anemia starts in infancy, with macrocytosis and raised Hb F and adenosine deaminase.
Question 4 · Hard
A family has mild, compensated hemolysis. Results: MCHC 37.5 g/dL (375 g/L), target cells and some stomatocytes, DAT negative, osmotic fragility decreased, and a falsely high potassium when samples wait before separation. Which disorder is most likely?
1. AOverhydrated hereditary stomatocytosis
2. BHereditary elliptocytosis
3. CHereditary spherocytosis
4. DHereditary xerocytosis
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Answer: D · Hereditary xerocytosis
Hereditary xerocytosis (dehydrated stomatocytosis), usually from PIEZO1 gain-of-function mutations, lets potassium and water leak out of red cells. The dehydrated cells have a high MCHC like spherocytes, but they resist hypotonic lysis, so osmotic fragility is decreased rather than increased. Potassium leaking from cells in stored samples causes pseudohyperkalemia. Telling it apart from HS matters because splenectomy helps little and raises the risk of thrombosis.
- A: Overhydrated cells have a low MCHC, a high MCV and increased fragility.
- B: Elliptocytosis shows oval cells and does not cause pseudohyperkalemia.
- C: HS also raises the MCHC, but its osmotic fragility is increased, not decreased.
Question 5 · Hard
Eight months after a mechanical aortic valve replacement, a patient reports fatigue. Results: hemoglobin 9.4 g/dL (94 g/L), platelets 245 × 10^3/µL (245 × 10^9/L), schistocytes 3%, LD raised, haptoglobin < 10 mg/dL (< 0.1 g/L), DAT negative, ferritin low, urine hemosiderin positive, INR in the warfarin target range. The most likely explanation is:
1. AWarm autoimmune hemolytic anemia
2. BThrombotic thrombocytopenic purpura
3. CDisseminated intravascular coagulation
4. DValve-related mechanical hemolysis
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Answer: D · Valve-related mechanical hemolysis
Turbulent, high-shear flow through or around a prosthetic valve, especially with a paravalvular leak, fragments red cells. This macroangiopathic hemolysis produces schistocytes but leaves the platelet count normal, which separates it from TTP and other thrombotic microangiopathies. Chronic intravascular hemolysis loses iron in the urine as hemoglobin and hemosiderin, so iron deficiency often develops and worsens the anemia. Echocardiography looks for a leak or valve dysfunction.
- A: Warm AIHA shows spherocytes and a positive DAT, not schistocytes.
- B: TTP causes marked thrombocytopenia, not a normal platelet count.
- C: DIC lowers the platelet count and disturbs the clotting tests.
Question 6 · Hard
A 4-year-old has bloody diarrhea, then 5 days later becomes pale and passes little urine. Results: hemoglobin 7.1 g/dL (71 g/L), platelets 38 × 10^3/µL (38 × 10^9/L), schistocytes on the film, creatinine 3.4 mg/dL (301 µmol/L), PT and aPTT normal, DAT negative. Which is the most likely diagnosis?
1. AShiga toxin-associated HUS
2. BDisseminated intravascular coagulation
3. CThrombotic thrombocytopenic purpura
4. DEvans syndrome
Answer and explanation in LearnFree account
Question 7 · Hard
A 7-year-old with short stature, café-au-lait spots and an absent thumb has pancytopenia, macrocytic red cells and a hypocellular marrow. Which test confirms the most likely diagnosis?
1. ADEB chromosome breakage test
2. BFlow cytometry for CD55 and CD59
3. CRed cell adenosine deaminase activity
4. DTelomere length by flow-FISH
Answer and explanation in LearnFree account
Question 8 · Hard
A day after surgery for a perforated bowel, a patient develops fever and shock. Hemoglobin falls from 12.8 to 6.0 g/dL (128 to 60 g/L), the plasma is red, many spherocytes are seen and the DAT is negative. Blood cultures grow large gram-positive rods. The most likely cause of the hemolysis is:
1. AParoxysmal nocturnal hemoglobinuria
2. BClostridium perfringens alpha toxin
3. CDisseminated intravascular coagulation
4. DDelayed hemolytic transfusion reaction
Answer and explanation in LearnFree account
Question 9 · Hard
A 7-year-old with known hereditary spherocytosis has a fever, then grows pale over a week. Hemoglobin has fallen from 10.5 to 5.8 g/dL (105 to 58 g/L), reticulocytes are 0.2%, bilirubin is lower than usual and the spleen is unchanged. The most likely cause is:
1. AParvovirus B19 infection
2. BAcute folate deficiency
3. CSplenic sequestration
4. DA hyperhemolytic crisis
Answer and explanation in LearnFree account
Question 10 · Easy
Aplastic anemia is pancytopenia caused by:
1. AA hypocellular, fatty bone marrow
2. BIneffective, dysplastic hematopoiesis
3. CMarrow replacement by fibrosis
4. DMarrow infiltration by leukemic blasts
Answer and explanation in LearnFree account
Question 11 · Easy
Paroxysmal nocturnal hemoglobinuria is caused by an acquired mutation in which gene?
1. APIGA
2. BJAK2
3. CANK1
4. DPKLR
Answer and explanation in LearnFree account
Question 12 · Medium
Which flow cytometry test is used to screen for hereditary spherocytosis?
1. AFLAER binding to GPI anchors
2. BEosin-5'-maleimide (EMA) binding
3. CAnti-HbF staining of red cells
4. DCD55 and CD59 expression
Answer and explanation in LearnFree account
Question 13 · Hard
A 28-year-old has mild anemia, proliferative retinopathy and avascular necrosis of the hip. The film shows many target cells, a few sickle cells, and dense crystals with blunt, finger-like projections. The solubility test is positive. Which condition is most likely?
1. ASickle cell trait
2. BHemoglobin C disease
3. CSickle cell anemia (Hb SS)
4. DHemoglobin SC disease
Answer and explanation in LearnFree account
Question 14 · Medium
Patients with pyruvate kinase deficiency often feel better than their hemoglobin suggests, mainly because:
1. ARaised 2,3-BPG improves oxygen release
2. BRaised ATP strengthens the membrane
3. CHemoglobin binds oxygen more tightly
4. DFetal hemoglobin stays high for life
Answer and explanation in LearnFree account
Question 15 · Medium
Which blood film finding is most characteristic of homozygous hemoglobin C disease?
1. ABite cells and blister cells
2. BTeardrops and nucleated red cells
3. CTarget cells with hexagonal crystals
4. DSickle cells, Howell-Jolly bodies
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Question 16 · Medium
What is the leading cause of death in untreated paroxysmal nocturnal hemoglobinuria?
1. AAcute leukemia
2. BSplenic rupture
3. CThrombosis
4. DIron overload
Answer and explanation in LearnFree account
Question 17 · Hard
A 2-year-old with sickle cell anemia, never transfused, becomes suddenly pale and listless. Hemoglobin falls from 8.0 to 4.2 g/dL (80 to 42 g/L), platelets drop, reticulocytes rise to 18%, and the spleen is now palpable well below the costal margin. The most likely event is:
1. ADelayed hemolytic transfusion reaction
2. BAcute chest syndrome
3. CAcute splenic sequestration
4. DTransient aplastic crisis
Answer and explanation in LearnFree account
Question 18 · Medium
Rigid oval red cells, many with one or two transverse slits or bars, in a person with little or no anemia are typical of:
1. AHereditary stomatocytosis
2. BHereditary elliptocytosis
3. CSoutheast Asian ovalocytosis
4. DHereditary pyropoikilocytosis
Answer and explanation in LearnFree account
Question 19 · Easy
G6PD protects red cells from oxidant damage mainly by generating which molecule?
1. ANADPH
2. BNADH
3. CATP
4. D2,3-bisphosphoglycerate
Answer and explanation in LearnFree account
Question 20 · Hard
A child of related parents has lifelong hemolysis. The DAT is negative, osmotic fragility is normal, no Heinz bodies form after an oxidant challenge and there is no basophilic stippling. After splenectomy, many small echinocytes (prickle cells) appear. Which enzyme is most likely deficient?
1. APyruvate kinase
2. BGlutathione synthetase
3. CG6PD
4. DPyrimidine 5'-nucleotidase
Answer and explanation in LearnFree account
Question 21 · Hard
A 60-year-old man starting chemotherapy for lymphoma is given rasburicase. Within 48 hours his hemoglobin falls from 13.2 to 8.1 g/dL (132 to 81 g/L), his plasma is pink and his urine dark, bite and blister cells appear, methemoglobin is 8% and the DAT is negative. The most likely cause is:
1. ATumor lysis with renal failure
2. BG6PD deficiency unmasked by rasburicase
3. CDrug-induced immune hemolysis
4. DThrombotic microangiopathy
Answer and explanation in LearnFree account
Question 22 · Medium
Schistocytes and severe thrombocytopenia are found with a normal PT, aPTT and fibrinogen. Which condition fits best?
1. AThrombotic thrombocytopenic purpura
2. BImmune thrombocytopenia
3. CWarm autoimmune hemolytic anemia
4. DDisseminated intravascular coagulation
Answer and explanation in LearnFree account
Question 23 · Medium
Hereditary hemolytic anemia with coarse basophilic stippling in many red cells and a normal blood lead level points to a deficiency of:
1. AHexokinase
2. BPyruvate kinase
3. CGlucose-6-phosphate dehydrogenase
4. DPyrimidine 5'-nucleotidase
Answer and explanation in LearnFree account
Question 24 · Easy
In microangiopathic hemolytic anemia, red cells are broken into fragments mainly by:
1. AOxidized hemoglobin precipitating in cells
2. BComplement attack on GPI-deficient cells
3. CMacrophages removing coated membrane
4. DFibrin and platelet thrombi in small vessels
Answer and explanation in LearnFree account
Question 25 · Medium
A patient with advanced alcoholic cirrhosis develops brisk hemolysis, and the blood film shows many acanthocytes. What is the most likely cause?
1. AAbetalipoproteinemia
2. BMcLeod syndrome
3. CSpur cell anemia
4. DPyruvate kinase deficiency
Answer and explanation in LearnFree account

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Normocytic anemias: hereditary and acquired hemolytic, aplastic

A family has mild, compensated hemolysis. Results: MCHC 37.5 g/dL (375 g/L), target cells and some stomatocytes, DAT negative, osmotic fragility decreased, and a falsely high potassium when samples wait before separation. Which disorder is most likely?

A 7-year-old with short stature, café-au-lait spots and an absent thumb has pancytopenia, macrocytic red cells and a hypocellular marrow. Which test confirms the most likely diagnosis?

A day after surgery for a perforated bowel, a patient develops fever and shock. Hemoglobin falls from 12.8 to 6.0 g/dL (128 to 60 g/L), the plasma is red, many spherocytes are seen and the DAT is negative. Blood cultures grow large gram-positive rods. The most likely cause of the hemolysis is:

A 7-year-old with known hereditary spherocytosis has a fever, then grows pale over a week. Hemoglobin has fallen from 10.5 to 5.8 g/dL (105 to 58 g/L), reticulocytes are 0.2%, bilirubin is lower than usual and the spleen is unchanged. The most likely cause is:

Aplastic anemia is pancytopenia caused by:

Paroxysmal nocturnal hemoglobinuria is caused by an acquired mutation in which gene?

Which flow cytometry test is used to screen for hereditary spherocytosis?

A 28-year-old has mild anemia, proliferative retinopathy and avascular necrosis of the hip. The film shows many target cells, a few sickle cells, and dense crystals with blunt, finger-like projections. The solubility test is positive. Which condition is most likely?

Patients with pyruvate kinase deficiency often feel better than their hemoglobin suggests, mainly because:

Which blood film finding is most characteristic of homozygous hemoglobin C disease?

What is the leading cause of death in untreated paroxysmal nocturnal hemoglobinuria?

A 2-year-old with sickle cell anemia, never transfused, becomes suddenly pale and listless. Hemoglobin falls from 8.0 to 4.2 g/dL (80 to 42 g/L), platelets drop, reticulocytes rise to 18%, and the spleen is now palpable well below the costal margin. The most likely event is:

Rigid oval red cells, many with one or two transverse slits or bars, in a person with little or no anemia are typical of:

G6PD protects red cells from oxidant damage mainly by generating which molecule?

A child of related parents has lifelong hemolysis. The DAT is negative, osmotic fragility is normal, no Heinz bodies form after an oxidant challenge and there is no basophilic stippling. After splenectomy, many small echinocytes (prickle cells) appear. Which enzyme is most likely deficient?

A 60-year-old man starting chemotherapy for lymphoma is given rasburicase. Within 48 hours his hemoglobin falls from 13.2 to 8.1 g/dL (132 to 81 g/L), his plasma is pink and his urine dark, bite and blister cells appear, methemoglobin is 8% and the DAT is negative. The most likely cause is:

Schistocytes and severe thrombocytopenia are found with a normal PT, aPTT and fibrinogen. Which condition fits best?

Hereditary hemolytic anemia with coarse basophilic stippling in many red cells and a normal blood lead level points to a deficiency of:

In microangiopathic hemolytic anemia, red cells are broken into fragments mainly by:

A patient with advanced alcoholic cirrhosis develops brisk hemolysis, and the blood film shows many acanthocytes. What is the most likely cause?