A 74-year-old woman has tiredness, and her fingertips turn blue in cold weather. Results: Hb 8.8 g/dL [88 g/L], reticulocytes 7.2%, LD 410 U/L (reference 100-225 U/L), indirect bilirubin 2.4 mg/dL [41 µmol/L] (reference 0.2-0.8 mg/dL) and haptoglobin < 10 mg/dL [< 0.1 g/L]. Her plasma is clear, and urine dipstick blood and urine hemosiderin are negative. Her EDTA sample shows red cell agglutinates at room temperature that disperse at 37 °C. The DAT is negative with anti-IgG and positive with anti-C3d, and the cold agglutinin titer is 2,048 with anti-I specificity. Where are most of her red cells being destroyed?

On fibrin strands in small vessels

Inside vessels by complement lysis

Splenic macrophages binding IgG

A patient with anemia and a raised reticulocyte count has total bilirubin 4.2 mg/dL [72 µmol/L], direct bilirubin 0.4 mg/dL [7 µmol/L], negative urine bilirubin and urine urobilinogen 4.0 EU (reference < 1.0 EU). What is the indirect bilirubin, and what does the pattern show?

3.8 mg/dL [65 µmol/L]; fits hemolysis

3.8 mg/dL [65 µmol/L]; fits bile obstruction

4.6 mg/dL [79 µmol/L]; fits hemolysis

0.4 mg/dL [7 µmol/L]; normal handling

Destruction: red cell lifespan and hemolysis

10 ASCP MLS practice questions on Destruction: red cell lifespan and hemolysis, part of Hematology. The first 10 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 74-year-old woman has tiredness, and her fingertips turn blue in cold weather. Results: Hb 8.8 g/dL [88 g/L], reticulocytes 7.2%, LD 410 U/L (reference 100-225 U/L), indirect bilirubin 2.4 mg/dL [41 µmol/L] (reference 0.2-0.8 mg/dL) and haptoglobin < 10 mg/dL [< 0.1 g/L]. Her plasma is clear, and urine dipstick blood and urine hemosiderin are negative. Her EDTA sample shows red cell agglutinates at room temperature that disperse at 37 °C. The DAT is negative with anti-IgG and positive with anti-C3d, and the cold agglutinin titer is 2,048 with anti-I specificity. Where are most of her red cells being destroyed?
1. ALiver macrophages binding C3b
2. BOn fibrin strands in small vessels
3. CInside vessels by complement lysis
4. DSplenic macrophages binding IgG
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Answer: A · Liver macrophages binding C3b
The cold-reacting IgM autoantibody binds red cells in the cooler peripheral circulation and fixes complement, coating the cells with C3b. Most C3b-coated cells are taken up by liver macrophages, which carry complement receptors, so the hemolysis is mainly extravascular: clear plasma, no hemoglobinuria or hemosiderinuria, a raised indirect bilirubin and reticulocytosis, with haptoglobin that can still be low. Cells that escape have their C3b cleaved to C3d, which is why the DAT detects C3d on the surviving cells. Fc-receptor clearance in the spleen is the main route for IgG-coated cells, and no IgG is found here. Full complement lysis inside the vessels happens only in severe flares, because red cell CD55 and CD59 limit the membrane attack complex.
- B: Fragmentation on fibrin strands produces schistocytes, which are not described here.
- C: The plasma is clear and urine hemosiderin is negative, so lysis inside the vessels is minor.
- D: The DAT shows no IgG, so Fc-receptor clearance in the spleen is not the main route.
Question 2 · Medium
A 38-year-old woman being investigated for anemia has raised plasma free hemoglobin, haptoglobin < 10 mg/dL [< 0.1 g/L] (reference 30-200 mg/dL), a positive urine dipstick for blood with 0 to 1 RBC/HPF, and positive urine hemosiderin. Where are her red cells mainly being destroyed?
1. AInside the blood vessels
2. BIn the liver's Kupffer cells
3. CIn the splenic macrophages
4. DIn the marrow before release
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Answer: A · Inside the blood vessels
When red cells break open in the circulation, free hemoglobin enters the plasma and quickly uses up haptoglobin. Unbound hemoglobin dimers pass through the glomerulus, giving a positive blood test with few or no red cells in the sediment. Tubular cells absorb some of it and store the iron as hemosiderin, which shows up in shed cells. These findings mark intravascular hemolysis; extravascular hemolysis mainly raises unconjugated bilirubin.
- B: Removal by Kupffer cells is extravascular and does not cause hemoglobinuria.
- C: Splenic removal does not release free hemoglobin into the urine.
- D: Destruction in the marrow (ineffective erythropoiesis) does not cause hemoglobinuria.
Question 3 · Hard
A patient with anemia and a raised reticulocyte count has total bilirubin 4.2 mg/dL [72 µmol/L], direct bilirubin 0.4 mg/dL [7 µmol/L], negative urine bilirubin and urine urobilinogen 4.0 EU (reference < 1.0 EU). What is the indirect bilirubin, and what does the pattern show?
1. A3.8 mg/dL [65 µmol/L]; fits bile obstruction
2. B4.6 mg/dL [79 µmol/L]; fits hemolysis
3. C3.8 mg/dL [65 µmol/L]; fits hemolysis
4. D0.4 mg/dL [7 µmol/L]; normal handling
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Answer: C · 3.8 mg/dL [65 µmol/L]; fits hemolysis
Indirect (unconjugated) bilirubin = total - direct = 4.2 - 0.4 = 3.8 mg/dL [72 - 7 = 65 µmol/L]. A rise in unconjugated bilirubin with a negative urine bilirubin points to more heme breakdown than the liver can conjugate, as in hemolysis. The raised urine urobilinogen reflects more bilirubin reaching the gut. In biliary obstruction the direct fraction rises, urine bilirubin turns positive and urobilinogen falls.
- A: Obstruction raises direct bilirubin and makes urine bilirubin positive.
- B: 4.6 mg/dL adds the direct fraction to the total instead of subtracting it.
- D: 0.4 mg/dL is the direct (conjugated) fraction, not the indirect.
Question 4 · Easy
Healthy adult red cells survive in the circulation for about how long?
1. A120 days
2. B30 days
3. C60 days
4. D10 days
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Answer: A · 120 days
Normal red cells circulate for about 120 days. With age they lose enzyme activity and membrane, become less deformable and are removed, mainly by macrophages in the spleen. To keep the count steady, the marrow replaces about 1% of the red cells each day, which fits a normal reticulocyte count of 0.5 to 2.5%. A shorter survival with a raised reticulocyte count is the hallmark of hemolysis.
- B: About 30 days is the half-life of chromium-labeled red cells, not their lifespan.
- C: Newborn red cells survive about 60 to 90 days; adult cells live longer.
- D: About 10 days is the lifespan of platelets.
Question 5 · Easy
In intravascular hemolysis, once haptoglobin is used up, which plasma protein binds free heme?
1. AFerritin
2. BCeruloplasmin
3. CTransferrin
4. DHemopexin
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Answer: D · Hemopexin
Haptoglobin binds free hemoglobin first. When it is exhausted, hemoglobin breaks down and the released heme is bound by hemopexin, which carries it to the liver. Low hemopexin therefore also indicates significant intravascular hemolysis. Any heme left over binds albumin as methemalbumin.
- A: Ferritin stores iron inside cells.
- B: Ceruloplasmin carries copper.
- C: Transferrin carries iron, not heme.
Question 6 · Easy
Haptoglobin falls in hemolysis. What does it bind and remove from plasma?
1. AFree hemoglobin
2. BUnconjugated bilirubin
3. CFree heme
4. DFree iron
Answer and explanation in LearnFree account
Question 7 · Hard
After a 40 km march, a soldier passes red-brown urine. Results: urine dipstick blood 3+, 0 to 2 RBC/HPF, pink plasma, haptoglobin < 10 mg/dL [< 0.1 g/L] and CK only mildly raised. What is the most likely cause of the urine color?
1. ABilirubinuria from extravascular hemolysis
2. BHematuria from bleeding in the urinary tract
3. CMyoglobinuria from muscle breakdown
4. DHemoglobinuria from intravascular hemolysis
Answer and explanation in LearnFree account
Question 8 · Medium
Which condition destroys red cells mainly inside the blood vessels?
1. ABeta-thalassemia major
2. BHereditary spherocytosis
3. CABO-incompatible transfusion
4. DWarm autoimmune hemolytic anemia
Answer and explanation in LearnFree account
Question 9 · Medium
Urine hemosiderin usually becomes detectable a few days after an episode of intravascular hemolysis, not at once. The reason is that:
1. AHaptoglobin must first be fully regenerated
2. BTubular cells must store the iron and then shed
3. CHemosiderin forms slowly from urine in the bladder
4. DThe liver must first excrete it into the bile
Answer and explanation in LearnFree account
Question 10 · Easy
Splenic macrophages recognize aged red cells partly because the cells expose which molecule on their outer surface?
1. AHemoglobin A2
2. BGlycophorin A
3. CSpectrin
4. DPhosphatidylserine
Answer and explanation in LearnFree account

Destruction: red cell lifespan and hemolysis

A 38-year-old woman being investigated for anemia has raised plasma free hemoglobin, haptoglobin < 10 mg/dL [< 0.1 g/L] (reference 30-200 mg/dL), a positive urine dipstick for blood with 0 to 1 RBC/HPF, and positive urine hemosiderin. Where are her red cells mainly being destroyed?

A patient with anemia and a raised reticulocyte count has total bilirubin 4.2 mg/dL [72 µmol/L], direct bilirubin 0.4 mg/dL [7 µmol/L], negative urine bilirubin and urine urobilinogen 4.0 EU (reference < 1.0 EU). What is the indirect bilirubin, and what does the pattern show?

Healthy adult red cells survive in the circulation for about how long?

In intravascular hemolysis, once haptoglobin is used up, which plasma protein binds free heme?

Haptoglobin falls in hemolysis. What does it bind and remove from plasma?

After a 40 km march, a soldier passes red-brown urine. Results: urine dipstick blood 3+, 0 to 2 RBC/HPF, pink plasma, haptoglobin < 10 mg/dL [< 0.1 g/L] and CK only mildly raised. What is the most likely cause of the urine color?

Which condition destroys red cells mainly inside the blood vessels?

Urine hemosiderin usually becomes detectable a few days after an episode of intravascular hemolysis, not at once. The reason is that:

Splenic macrophages recognize aged red cells partly because the cells expose which molecule on their outer surface?