Heme Board Review

Multiple Choice

A 34-year-old woman is evaluated for a rash on her lower extremities that appeared 3 days ago. She also reports easy bruising for the past week and bleeding when she brushes her teeth. Her medical history is otherwise unremarkable, and she takes no meds.

On examin, vital signs are normal. Petechiae are noted on the lower extremities, and ecchymoses are present on her right thigh and on her abdomen. No hepatomegaly, splenomegaly, or lymphadenopathy is noted.

Laboratory studies:

Hemoglobin 12.8 g/dL (128 g/L)

Leukocyte count 6600/µL (6.6 × 10⁹/L) with a normal differential

Mean corpuscular volume 82 fL

Platelet count 28,000/µL (28 × 10⁹/L)

Hepatitis C antibody Negative

Large and giant platelets seen on the peripheral blood smear, but no schistocytes or platelet clumping is noted.

Which of the following laboratory tests should be performed?

• Antiplatelet antibodies

• HIV testing

• Lupus anticoagulant

• Vitamin B12 level

ITP

​TL;DR

Immune thrombocytopenic purpura can be idiopathic, triggered by medications, or associated with other disorders, such as systemic lupus erythematosus, chronic lymphocytic leukemia, lymphoma, HIV, hepatitis C, or Helicobacter pylori nfection.

Multiple Choice

A 42-year-old man is admitted to the hospital with an acute change in mental status and fever of 2 days' duration. Medical history is noncontributory, and he takes no medications.

On physical examination, temperature is 38.2 °C (100.8 °F), blood pressure is 108/70 mm Hg, pulse rate is 104/min, and respiration rate is 18/min. Oxygen saturation is 96% breathing ambient air. He is agitated and disoriented to place and time. Petechiae are noted on his shins. The remainder of the examination is normal.

Laboratory studies:

Haptoglobin 20 mg/dL (200 mg/L)

Hemoglobin 10.2 g/dL (102 g/L)

Leukocyte count 9800/µL (9.8 × 10⁹/L)

Platelet count 44,000/µL (44 × 10⁹/L)

Reticulocyte count 6.8% of erythrocytes

Creatinine 1.4 mg/dL (123.8 µmol/L)

Lactate dehydrogenase 1600 U/L

The direct antiglobulin (Coombs) test is negative.

Therapy should be immediately initiated pending results of which of the following studies?

• ADAMTS13 activity

• Coagulation studies

• Peripheral blood smear

• Stool culture and testing for shiga toxin

TTP

​TL;DR

In the proper clinical setting, a peripheral blood smear showing schistocytes in a patient with thrombocytopenia and hemolytic anemia establishes a presumptive diagnosis of thrombotic thrombocytopenic purpura and confirms the need to initiate early, life-saving therapy.

Multiple Choice

18M evaluated in the ED for abdominal cramping and bloody diarrhea of 6 days' duration. Medical history is unremarkable, and he takes no meds.

On exam, temperature is 37.0 °C (98.6 °F), blood pressure is 98/60 mm Hg, pulse rate is 100/min, and respiration rate is 16/min. Oxygen saturation is normal breathing ambient air. His abdomen is tender, without guarding or organomegaly. The exam is otherwise unremarkable.

Laboratory studies:

Haptoglobin Undetectable

Hemoglobin 6.1 g/dL (61 g/L)

Leukocyte count 6800/µL (6.8 × 10⁹/L)

Platelet count 37,000/µL (37 × 10⁹/L)

Reticulocyte count 9.8% of erythrocytes

Creatinine 3.6 mg/dL (318 µmol/L)

Urinalysis 3+ blood; 3+ protein; 0-2 erythrocytes/hpf; 0-2 leukocytes/hpf; several granular casts

The peripheral blood smear shows schistocytes and scant platelets without clumps. The direct antiglobulin (Coombs) test is negative.

What is the most likely diagnosis?

• Atypical hemolytic uremic syndrome

• Hemolytic uremic syndrome

• Immune hemolytic anemia and thrombocytopenia

• Rapidly progressing glomerulonephritis

HUS

​TL;DR

Classic hemolytic uremic syndrome is a diarrhea-associated syndrome of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury caused by Shiga toxin–producing E. coli and, less commonly, Shigella dysenteriae.

Multiple Choice

What is the most likely diagnosis?

• ALL

• AML

• CLL

• Pyruvate kinase deficiency

AML

​TL;DR

This peripheral blood smear shows an immature granulocyte with a rod-shaped inclusion body (Auer rod) characteristic of acute myeloid leukemia. Auer rods represent linear collections of granules and are virtually diagnostic of acute myeloid leukemia.

Multiple Choice

80F is evaluated for fatigue and exertional dyspnea developing over several months. Medical history is significant for longstanding hypertension, but she has not been adherent with her medications.

On physical examination, vital signs are normal except for blood pressure of 180/110 mm Hg. She is frail, with pallor of mucous membranes and nail beds. The remainder of the examination is normal.

Laboratory studies:

Hemoglobin 9 g/dL (90 g/L)

Leukocyte count 8700/µL (8.7 × 10⁹/L), with a normal differential

Mean corpuscular volume 85 fL

Platelet count 380,000 (380 × 10⁹/L)

Reticulocyte count 1% of erythrocytes

Creatinine 1.8 mg/dL (159 µmol/L)

Folate 8 ng/mL (18.1 nmol/L)

Ferritin 120 ng/mL (120 µg/L)

Iron 70 µg/dL (13 µmol/L)

Total iron-binding capacity 250 µg/dL (44.8 µmol/L)

Vitamin B₁₂ 540 pg/mL (399 pmol/L)

Peripheral blood smear shows normal erythrocyte morphology.

On kidney ultrasonography, kidneys are small bilaterally, with echographic features suggesting CKD.

Which of the following is the most likely cause of this patient's anemia?

• Erythropoietin deficiency

• Inflammation

• Iron deficiency

• Myelodysplastic syndrome

AML

​TL;DR

Normocytic anemia with a low reticulocyte count and normal erythrocyte morphology in a patient with underlying chronic kidney disease is usually caused by erythropoietin deficiency and will respond to therapy with an erythropoiesis-stimulating agent; however, normalization of the blood count is not advised.

Multiple Choice

Which of the following diagnoses is most compatible with this bone marrow biopsy specimen?

• AML

• Aplastic anemia

• Graft vs host disease

• Immune thrombocytopenia

• Pure red cell aplasia

Aplastic anemia

​TL;DR

The biopsy specimen shows profound hypocellularity. Fat and marrow stroma are the major components present, and there is no evidence of malignant cells or fibrosis. This is consistent with a diagnosis of aplastic anemia. Aplastic anemia is characterized by diminished or absent hematopoietic precursors in the bone marrow, most frequently resulting from injury to the pluripotent stem cell. Such injury may occur secondary to drugs, radiation, infection, or immune disorders or may be idiopathic. The most common peripheral blood pattern seen in aplastic anemia is pancytopenia, with the simultaneous presence of neutropenia, thrombocytopenia, and anemia.

Multiple Choice

56M is brought to the emergency department after being found lying unresponsive in the local train station. Medical history is significant for chronic alcohol dependence. He is homeless. The patient is a frequent visitor to the emergency department for minor trauma and ailments; his last visit was 6 months ago. Until that time, the patient lived in various shelters and received at least one nutritious meal per day. His whereabouts and living circumstances since that time are unknown. His medical history is otherwise not significant, and at his last visit to the emergency department, he was taking no medications.

On physical examination, vital signs are normal. The patient is disheveled, cachectic, and malodorous. He moans in response to painful stimuli and moves all extremities. He has poor dentition. Hepatomegaly is noted.

Laboratory studies:

Hemoglobin 7.4 g/dL (74 g/L)

Leukocyte count 4200/µL (4.2 × 10⁹/L)

Mean corpuscular volume 110 fL

Platelet count 97,000/µL (97 × 10⁹/L)

Reticulocyte count 1% of erythrocytes

Blood alcohol level 500 mg/dL (108 mmol/L)

Hypersegmented neutrophils are seen on the peripheral blood smear.

Which of the following is the most likely cause of this patient's anemia?

• Cobalamin deficiency

• Folate deficiency

• Inflammatory anemia

• Iron deficiency anemia

Folate deficiency

​TL;DR

Folate deficiency should be suspected in patients with macrocytic anemia, malnutrition, and alcohol dependence. It's not B12 because it takes longer to deplete those stores.

Multiple Choice

A 56-year-old man is evaluated in the emergency department for a 4-week history of progressive fatigue, increased sleepiness, dyspnea on exertion, and chest pain with moderate activity. He also notes an inability to perform all his duties as a construction worker. Family and medical history are noncontributory, and he takes no medication.

On physical examination, temperature is 36.7 °C (98.2 °F), blood pressure is 123/69 mm Hg, pulse rate is 98/min, and respiration rate is 16/min. The patient has scleral icterus and no lymphadenopathy. Abdominal examination discloses splenomegaly.

Laboratory studies:

Hemoglobin 8.1 g/dL (81 g/L)

Leukocyte count 4900/µL (4.9 × 10⁹/L) with a normal differential

Platelet count 159,000/µL (159 × 10⁹/L)

Reticulocyte count 5.4% of erythrocytes

Direct antiglobulin (Coombs) test IgG, strongly positive; C3, weakly positive

A complete blood count from 1 year ago was normal. The peripheral blood smear is shown.

Which of the following is the most likely diagnosis?

• Cold agglutinin disease

• G6PD deficiency

• Warm autoimmune hemolytic anemia

• Hereditary spherocytosis

Warm autoimmune hemolytic anemia

​TL;DR

Warm autoimmune hemolytic anemia is characterized by insidious symptoms of anemia, jaundice, splenomegaly, spherocytes on the peripheral blood smear, and direct antiglobulin (Coombs) test results that are strongly positive for IgG and negative or weakly positive for complement. (In cold agglutinin: DAT IgG would be negative; G6PD should have bite cells; HS should have family history and negative DAT)

Multiple Choice

A 30-year-old man is evaluated for worsening exertional dyspnea. One week ago, he developed fever, sore throat, and cough. Those symptoms have resolved, but he has become more easily fatigued and short of breath. He had cholecystectomy 2 years ago because of symptomatic cholelithiasis; at that time, he was noted to be anemic and was diagnosed with hereditary spherocytosis. His only medication is a folate supplement.

On physical examination, he is pale but in no distress. Temperature is 37.0 °C (98.7 °F), blood pressure is 100/60 mm Hg, pulse rate is 116/min, and respiratory rate is 16/min. Oxygen saturation is 98% breathing ambient air. The spleen is palpable 3 cm below the left costal margin. Other examination findings are normal.

Laboratory studies:

Hemoglobin 7 g/dL (70 g/L)

Leukocyte count 5600/µL (5.6 × 10⁹/L), with a normal differential

Mean corpuscular hemoglobin concentration 40 g/dL (400 g/L)

Platelet count 213,000/µL (213 × 10⁹/L)

Reticulocyte count 1% of erythrocytes

Bilirubin Total

6.2 mg/dL (106 µmol/L)

Bili Indirect

5.6 mg/dL (95.8 µmol/L)

Spherocytes are seen on the peripheral blood smear. A direct antiglobulin test is negative.

Which of the following is the most appropriate management?

• EPO-stimulating agent

• Prednisone

• Splenectomy

• Observation

Transient aplastic crisis in the setting of HS

​TL;DR

Acute viral infections may trigger a transient aplastic crisis in patients with hereditary spherocytosis. If more severe, can consider splenectomy. If this was WAIHA, can consider steroids. EPO is probably really high in this patient, so EPO-stimulating agents are not helpful.

Multiple Choice

A 22-year-old man with sickle cell anemia (SCA) is seen 1 week after hospitalization for acute chest syndrome that required critical care and treatment with exchange transfusion and noninvasive assisted ventilation. He has not had any previous pulmonary or any other major complications from his SCA and typically has two to three episodes of acute pain events yearly. He reports he has returned to his usual level of activity and has no pulmonary symptoms and no pain. His only medication is folate, 1 mg/d.

On physical examination, vital signs are normal. He appears pale. Cardiac examination reveals a grade 3/4 systolic flow murmur. The remainder of the examination, including pulmonary examination, is unremarkable.

Laboratory studies:

Hemoglobin 8.4 g/dL (84 g/L)

Leukocyte count 14,000/µL (14 × 10⁹/L)

Mean corpuscular volume 86 fL

Platelet count 325,000 (325 × 10⁹/L)

Reticulocyte count 8% of erythrocytes

Which of the following is the most appropriate management?

• Folate supplementation, 4mg/d

• Hydroxyurea

• Incentive spirometry

• Monthly exchange transfusions

• Monthly simple transfusions

Prevent complications of sickle cell disease

​TL;DR

In patients with sickle cell disease, hydroxyurea therapy has been shown to decrease vaso-occlusive episodes and acute chest syndrome, to decrease transfusion requirements and hospitalizations, and to prolong overall survival. His elevated MCV is from reticulocytosis, not folate deficiency. IS is helpful during crisis, not so much afterwards. No evidence for transfusions after recovery.

Multiple Choice

A 19-year-old man is admitted to the hospital with an acute pain crisis. He has sickle cell anemia. He experiences pain crises one to two times per year. Medications are hydroxyurea and folic acid, both started 5 months ago.

On physical examination, other than a pulse rate of 108/min, vital signs are normal. The patient has moderate pain in his upper and lower extremities. The remainder of the physical examination is normal.

Laboratory studies show a hematocrit of 21% and a mean corpuscular volume of 106 fL. A peripheral blood smear shows sickled erythrocytes and rare nucleated erythrocytes and macrocytes but is otherwise normal. Mean corpuscular volume was normal at his last hospitalization 6 months ago.

Which of the following is the most likely cause of this patient's macrocytosis?

• Cobalamin deficiency

• Hydroxyurea

• Myelodysplasia

• Sickle cell anemia

Diagnose hydroxyurea as a cause of macrocytic anemia.

​TL;DR

Hydroxyurea is an RNA-reductase inhibitor that causes macrocytosis because of its effect on DNA synthesis. In fact, adherence to hydroxyurea therapy can be confirmed by identification of an increased mean corpuscular volume (MCV).

Multiple Choice

A 71-year-old man is evaluated for headaches of 2 months' duration. He reports no shortness of breath and has a good energy level. Medical history is significant for hypertension, hypothyroidism, and hypogonadism; he has never smoked. Medications are lisinopril, levothyroxine, and testosterone injections.

On physical examination, vital signs are normal except for a blood pressure of 160/92 mm Hg; BMI is 19. He has facial plethora. Cardiopulmonary examination is normal. No hepatosplenomegaly is noted.

Laboratory studies:

Erythropoietin 40 mU/mL (40 U/L)

Hematocrit 56%

Hemoglobin 18.9 g/dL (189 g/L)

Leukocyte count 7000/µL (7 × 10⁹/L) with normal differential

Platelet count 300,000/µL (300 × 10⁹/L)

Which of the following is the most likely cause of this patient's findings?

• Levothyroxine

• Lisinopril

• Polycythemia vera

• Testosterone

Diagnose testosterone supplementation as a secondary cause for polycythemia.

​TL;DR

Polycythemia is a common adverse effect of testosterone injections, and testosterone supplementation should be interrupted if the hematocrit level exceeds 54%.

PV is EPO-independent! Lisinopril doesn't do this. Levothyroxine can't do it.

Multiple Choice

24M with progressive fatigue and intermittent dark urine over several months is evaluated in the ED for exertional dyspnea, abdominal pain, and red urine.

On exam, he is pale. T=37.0 °C (98.6 °F), BP 110/70 mm Hg, HR 112/min, RR 16/min. O2 98% room air. Scattered petechiae are visible on the skin. The abdomen is not distended and is diffusely tender to palpation without guarding. Bowel sounds are normal. The remainder of the examination is normal.

Laboratory studies:

Haptoglobin Undetectable

Hemoglobin 7.2 g/dL (72 g/L)

Leukocyte count 1200/µL (1.2 × 10⁹/L) with 70% neutrophils and 30% lymphocytes

Mean corpuscular volume 84 fL

Platelet count 23,000/µL (23 × 10⁹/L)

Reticulocyte count 8% of erythrocytes

Lactate dehydrogenase 500 U/L

Urinalysis 4+ blood; 0-1 erythrocytes/hpf; 0 leukocytes/hpf

The peripheral blood smear shows normal-appearing erythrocytes without spherocytes, schistocytes, agglutinated erythrocytes, or immature-appearing leukocytes.

Which of the following is the most appropriate next test?

• DAT

• Flow cytometry

• Methylmalonic acid measurement

• Quantitative and functional levels of C1 esterase inhibitor

Diagnose paroxysmal nocturnal hemoglobinuria.

​TL;DR

Diagnosis of paroxysmal nocturnal hemoglobinuria is based on flow cytometry results, which can detect CD55 and CD59 deficiency on the surface of peripheral erythrocytes or leukocytes.

DAT would be negative. C1 esterase inhibitor is for hereditary angioedema. MMA is for B12 deficiency.

Multiple Choice

A 52-year-old woman undergoes perioperative evaluation. She has osteoarthritis of the right hip since sustaining injuries in a motor vehicle accident 15 years ago and is scheduled for elective hip arthroplasty in the next few months. Medical history is otherwise notable for type 2 diabetes mellitus. She is up to date on routine health care. Her last menstrual period was 5 weeks ago. Medications are ibuprofen and metformin.

On physical examination, vital signs are normal. She has painful and limited range of motion in the right hip.

Laboratory studies:

Hemoglobin 10 g/dL (100 g/L)

Mean corpuscular volume 81 fL

Platelet count 223,000/µL (223 × 10⁹/L)

Creatinine 1 mg/dL (88.4 µmol/L)

Hemoglobin A_1c 7.5%

Which of the following is the most appropriate test to perform next?

• Hemoglobin electrophoresis

• Iron studies

• B12 level

• No further evaluation

Evaluate preoperative anemia.

​TL;DR

Patients scheduled for elective surgery who have anemia should be evaluated for iron deficiency; preoperative management of iron deficiency anemia includes oral iron replacement and evaluation to determine the source of blood loss. (Other answers: if you thought she has a hemoglobinopathy, smear would be the next thing to do. B12 is less likely than iron given low normal MCV. Don't just ignore it!)

Multiple Choice

78F is evaluated for increasing fatigue during the past 2 weeks. She has a 7-year history of chronic lymphocytic leukemia previously treated with bendamustine and rituximab with excellent results. One month ago, after presenting with persistent night sweats, she was diagnosed with relapsed chronic lymphocytic leukemia based on lymphocytosis on a complete blood count and results of peripheral blood flow cytometry. Her hemoglobin level at that time was 12.1 g/dL (121 g/L). She was started on oral ibrutinib.

On physical examination, vital signs are normal. Scleral icterus is noted. The spleen is palpable 3 cm below the costal margin. There is no peripheral lymphadenopathy.

Laboratory studies:

Hemoglobin 7.4 g/dL (74 g/L)

Leukocyte count 22,000/µL (22 × 10⁹/L) with 79% lymphocytes

Platelet count 122,000/µL (122 × 10⁹/L)

Reticulocyte count 11% of erythrocytes

Which of the following is the most appropriate management?

• Anti-parvovirus IgM antibody assay

• Bone marrow aspiration and biopsy

• DAT (Coombs) test

• Discontinue ibrutinib

• Splenectomy

Evaluate anemia in a patient with chronic lymphocytic leukemia.

​TL;DR

Autoimmune hemolytic anemia is common in patients with chronic lymphocytic leukemia; a direct antiglobulin (Coombs) test can confirm the diagnosis and guide treatment. Parvovirus can cause aplastic anemia, but would not expect her to be retic-ing so well. Bone marrow aspiration is too aggressive - do DAT first. Splenectomy likewise is more of a last resort thing.