A 19-year-old college student returns from a mission trip to Kenya. Three weeks later, he develops fatigue, dark urine, and jaundice. Labs show: hemoglobin 8.1 g/dL (baseline 14 g/dL), MCV 92 fL, reticulocyte count 9%, total bilirubin 4.8 mg/dL (indirect), LDH 720 U/L. Peripheral smear shows bite cells and Heinz bodies. Malaria smears are negative. He reports taking primaquine for malaria prophylaxis. Which of the following is the most likely underlying condition?
Q2
A 35-year-old woman with lupus anticoagulant and history of two miscarriages is now 10 weeks pregnant. She had a DVT 3 years ago. She is currently asymptomatic. Her obstetrician requests recommendations for antithrombotic management throughout pregnancy and postpartum period. Synthesize the optimal comprehensive management strategy.
Q3
A 45-year-old woman presents with confusion and fever. Labs show: hemoglobin 7.8 g/dL, platelets 15,000/μL, creatinine 2.8 mg/dL, LDH 890 U/L, total bilirubin 3.1 mg/dL (indirect), undetectable haptoglobin. Peripheral smear shows numerous schistocytes. ADAMTS13 activity is 8% (normal >67%). She has no diarrheal illness. Coagulation studies (PT/aPTT) are normal. Evaluate the most appropriate immediate therapeutic intervention.
Q4
A 70-year-old man with metastatic pancreatic cancer on chemotherapy develops sudden dyspnea and hypoxia. CT pulmonary angiogram confirms bilateral pulmonary emboli. Platelet count is 45,000/μL (down from 180,000/μL two weeks ago). He has normal renal and liver function. Oncologist reports he has an estimated survival of 6-8 months. Evaluate the optimal long-term anticoagulation strategy.
Q5
A 24-year-old African American woman presents with severe bone pain and fever. She has sickle cell disease. Temperature is 39.2°C (102.6°F), blood pressure 110/65 mmHg. Hemoglobin is 6.1 g/dL (baseline 8.5 g/dL), reticulocyte count 0.5%, WBC 3,200/μL. Chest X-ray is clear. Blood cultures are pending. Analyze the clinical presentation and determine the priority intervention.
Hematology (anemias, clotting disorders) US Medical PG Practice Questions and MCQs
Question 1: A 19-year-old college student returns from a mission trip to Kenya. Three weeks later, he develops fatigue, dark urine, and jaundice. Labs show: hemoglobin 8.1 g/dL (baseline 14 g/dL), MCV 92 fL, reticulocyte count 9%, total bilirubin 4.8 mg/dL (indirect), LDH 720 U/L. Peripheral smear shows bite cells and Heinz bodies. Malaria smears are negative. He reports taking primaquine for malaria prophylaxis. Which of the following is the most likely underlying condition?
A. Glucose-6-phosphate dehydrogenase (G6PD) deficiency (Correct Answer)
B. Paroxysmal nocturnal hemoglobinuria
C. Acute malaria with hemolytic crisis despite negative smear
D. Hereditary spherocytosis unmasked by oxidative stress
E. Autoimmune hemolytic anemia triggered by infection
Explanation: ***Glucose-6-phosphate dehydrogenase (G6PD) deficiency***
- The presence of **bite cells** and **Heinz bodies** (denatured hemoglobin) on a peripheral smear is pathognomonic for **G6PD deficiency** specifically triggered by oxidative agents like **primaquine**.
- This X-linked disorder results in an inability to maintain **reduced glutathione**, leading to **acute hemolytic anemia** with elevated **indirect bilirubin**, high **LDH**, and **reticulocytosis**.
*Acute malaria with hemolytic crisis despite negative smear*
- While common in travelers to Kenya, **malaria** is unlikely given the **negative smears** and the specific finding of **bite cells**, which are not characteristic of Plasmodium infection.
- Malaria-induced hemolysis typically presents with **parasitemia** on blood films rather than the morphological changes associated with oxidative stress.
*Autoimmune hemolytic anemia triggered by infection*
- This condition would typically show **spherocytes** on the peripheral smear and would require a **positive Direct Antiglobulin Test (Coombs test)** for diagnosis.
- AIHA is not classically triggered by **primaquine** and does not produce the characteristic **Heinz bodies** seen in enzymatic deficiencies.
*Paroxysmal nocturnal hemoglobinuria*
- Characterized by a **triad** of hemolytic anemia, **pancytopenia**, and **venous thrombosis** due to a stem cell mutation in the PIGA gene.
- Diagnosis is confirmed via **flow cytometry** for CD55 and CD59; it does not present with **bite cells** or specifically after oxidative medication exposure.
*Hereditary spherocytosis unmasked by oxidative stress*
- HS is defined by a defect in **membrane proteins** leading to **spherocytes** and an increased **MCHC**, rather than the **normocytic** indices and Heinz bodies seen here.
- While stressors can worsen hemolysis, HS typically presents with **splenomegaly** and a history of jaundice, and is not specifically linked to **primaquine** ingestion.
Question 2: A 35-year-old woman with lupus anticoagulant and history of two miscarriages is now 10 weeks pregnant. She had a DVT 3 years ago. She is currently asymptomatic. Her obstetrician requests recommendations for antithrombotic management throughout pregnancy and postpartum period. Synthesize the optimal comprehensive management strategy.
A. Therapeutic dose LMWH throughout pregnancy and 6 weeks postpartum
B. Warfarin with INR 2-3 after first trimester, then switch to LMWH at term
C. Prophylactic dose LMWH throughout pregnancy, continue 6 weeks postpartum
D. Prophylactic LMWH plus aspirin throughout pregnancy, therapeutic LMWH postpartum (Correct Answer)
E. Aspirin 81 mg daily only throughout pregnancy
Explanation: ***Prophylactic LMWH plus aspirin throughout pregnancy, therapeutic LMWH postpartum***
- Patients with **Antiphospholipid Syndrome (APS)** who have a history of **venous thromboembolism (VTE)** plus obstetric complications require a combined regimen of **aspirin** and **anticoagulation** to prevent further pregnancy loss.
- Management of a patient with a prior **provoked or remote DVT** (and not on long-term anticoagulation) involves **therapeutic-dose LMWH postpartum** for 6 weeks, as the postpartum period carries the highest risk for thrombotic recurrence.
*Prophylactic dose LMWH throughout pregnancy, continue 6 weeks postpartum*
- This regimen lacks **low-dose aspirin**, which is a critical component for improving live-birth rates in women with **obstetric APS**.
- It fails to address the need for **therapeutic-intensity** anticoagulation in the postpartum period for a patient with a known history of **DVT** and established APS.
*Therapeutic dose LMWH throughout pregnancy and 6 weeks postpartum*
- **Therapeutic-dose LMWH** throughout the entire pregnancy is typically reserved for those with **multiple recent DVTs** or those who are already on lifelong anticoagulation.
- This approach is associated with a higher risk of **maternal bleeding complications** and bone density loss compared to prophylactic or intermediate dosing in the antepartum period.
*Aspirin 81 mg daily only throughout pregnancy*
- **Aspirin monotherapy** is statistically inferior to combination therapy for preventing **recurrent pregnancy loss** in patients with confirmed **Lupus Anticoagulant**.
- It provides no significant protection against **maternal venous thrombosis**, leaving the patient at high risk for a recurrent DVT during the hypercoagulable state of pregnancy.
*Warfarin with INR 2-3 after first trimester, then switch to LMWH at term*
- **Warfarin** is generally avoided throughout pregnancy because it crosses the placenta and can cause **fetal hemorrhage** or CNS abnormalities even after the first trimester.
- **LMWH** is the preferred agent throughout all trimesters because it does not cross the placenta and has a more predictable safety profile for the fetus.
Question 3: A 45-year-old woman presents with confusion and fever. Labs show: hemoglobin 7.8 g/dL, platelets 15,000/μL, creatinine 2.8 mg/dL, LDH 890 U/L, total bilirubin 3.1 mg/dL (indirect), undetectable haptoglobin. Peripheral smear shows numerous schistocytes. ADAMTS13 activity is 8% (normal >67%). She has no diarrheal illness. Coagulation studies (PT/aPTT) are normal. Evaluate the most appropriate immediate therapeutic intervention.
A. High-dose corticosteroids and rituximab
B. Eculizumab for atypical hemolytic uremic syndrome
C. Platelet transfusion for severe thrombocytopenia
D. Supportive care and dialysis for renal failure
E. Immediate plasma exchange with FFP replacement (Correct Answer)
Explanation: ***Immediate plasma exchange with FFP replacement***
- The patient exhibits the classic pentad of **Thrombotic Thrombocytopenic Purpura (TTP)**: microangiopathic hemolytic anemia (**schistocytes**, high LDH, low haptoglobin), thrombocytopenia, fever, renal dysfunction, and confusion.
- **Plasma exchange (PEX)** is the definitive immediate treatment as it removes autoantibodies against **ADAMTS13** and restores the deficient enzyme levels to prevent further microthrombi formation.
*Platelet transfusion for severe thrombocytopenia*
- Platelet transfusions are generally **contraindicated** in TTP as they can "fuel the fire" by worsening **microvascular thrombosis** and exacerbating organ ischemia.
- This intervention is reserved only for patients with life-threatening **hemorrhage**.
*High-dose corticosteroids and rituximab*
- Although these are used to suppress the production of **ADAMTS13 autoantibodies**, they are **adjunctive therapies** and cannot replace the immediate need for PEX.
- Corticosteroids do not provide the necessary replacement of the **ADAMTS13 protease** required to break down large vWF multimers.
*Eculizumab for atypical hemolytic uremic syndrome*
- While atypical HUS shares features with TTP, the significantly low **ADAMTS13 activity (<10%)** confirms TTP, making eculizumab (a **C5 inhibitor**) inappropriate here.
- Atypical HUS is typically caused by **complement dysregulation**, whereas this case is driven by a protease deficiency.
*Supportive care and dialysis for renal failure*
- While the patient has elevated creatinine, dialysis is only a **supportive measure** for renal failure and does not address the systemic **microangiopathy** driving the TTP.
- Relying on supportive care alone in TTP is associated with a **mortality rate** exceeding 90%.
Question 4: A 70-year-old man with metastatic pancreatic cancer on chemotherapy develops sudden dyspnea and hypoxia. CT pulmonary angiogram confirms bilateral pulmonary emboli. Platelet count is 45,000/μL (down from 180,000/μL two weeks ago). He has normal renal and liver function. Oncologist reports he has an estimated survival of 6-8 months. Evaluate the optimal long-term anticoagulation strategy.
A. Low molecular weight heparin (LMWH) for cancer-associated thrombosis (Correct Answer)
B. Apixaban with dose reduction for thrombocytopenia
C. Unfractionated heparin infusion continued indefinitely
D. Inferior vena cava filter placement without anticoagulation
E. Warfarin with INR goal 2-3
Explanation: ***Low molecular weight heparin (LMWH) for cancer-associated thrombosis***
- **LMWH** is a preferred treatment for **cancer-associated thrombosis (CAT)**, specifically in **gastrointestinal malignancies** where other agents may increase the risk of intraluminal bleeding.
- In the setting of **thrombocytopenia** (45,000/μL), LMWH allows for easier **dose adjustments** or temporary suspension compared to long-acting oral agents.
*Unfractionated heparin infusion continued indefinitely*
- **UFH** is inappropriate for long-term therapy as it requires **continuous intravenous administration** and frequent monitoring of aPTT, which is impractical for outpatient care.
- Long-term use of UFH is associated with a higher risk of **heparin-induced thrombocytopenia (HIT)** and **osteoporosis** compared to other options.
*Warfarin with INR goal 2-3*
- **Warfarin** is less effective than LMWH for preventing recurrent VTE in cancer patients and is difficult to maintain within the **therapeutic range** due to chemotherapy interactions and nausea.
- Frequent monitoring of the **INR** is required, which is burdensome for patients with advanced **metastatic pancreatic cancer** and poor nutritional status.
*Apixaban with dose reduction for thrombocytopenia*
- While **DOACs** are often first-line, they are associated with a higher risk of **major gastrointestinal bleeding** in patients with luminal GI or pancreatic cancers.
- There is no standardized "dose reduction" protocol for **thrombocytopenia** for DOACs; they are generally avoided if the platelet count is consistently below **50,000/μL**.
*Inferior vena cava filter placement without anticoagulation*
- An **IVC filter** is only indicated when there is an absolute **contraindication to anticoagulation**, typically a platelet count less than **25,000/μL** or active major bleeding.
- For this patient, the risk of **recurrent pulmonary embolism** remains high, and filter placement alone does not address the underlying **prothrombotic state** of malignancy.
Question 5: A 24-year-old African American woman presents with severe bone pain and fever. She has sickle cell disease. Temperature is 39.2°C (102.6°F), blood pressure 110/65 mmHg. Hemoglobin is 6.1 g/dL (baseline 8.5 g/dL), reticulocyte count 0.5%, WBC 3,200/μL. Chest X-ray is clear. Blood cultures are pending. Analyze the clinical presentation and determine the priority intervention.
A. Simple transfusion for aplastic crisis and broad-spectrum antibiotics (Correct Answer)
B. Immediate bone marrow transplant evaluation
C. Exchange transfusion for acute chest syndrome
D. Intravenous immunoglobulin for parvovirus B19
E. Hydroxyurea initiation and pain management
Explanation: ***Simple transfusion for aplastic crisis and broad-spectrum antibiotics***
- The patient exhibits **aplastic crisis**, characterized by a significant drop in hemoglobin from baseline and an inappropriately low **reticulocyte count (0.5%)**, indicating suppressed erythropoiesis.
- **Simple blood transfusion** is the life-saving priority for symptomatic anemia, and **broad-spectrum antibiotics** are mandatory in sickle cell patients with fever due to functional asplenia and risk of **encapsulated bacterial sepsis**.
*Exchange transfusion for acute chest syndrome*
- This patient's **Chest X-ray is clear**, which effectively rules out **Acute Chest Syndrome (ACS)** as the primary cause of her current distress.
- Exchange transfusion is indicated for severe **ACS** or stroke, but her main issue is suppressed red cell production requiring simple volume and cell replacement.
*Hydroxyurea initiation and pain management*
- While **Hydroxyurea** is essential for long-term reduction of vaso-occlusive crises, it is not used for acute management and can briefly worsen **myelosuppression** during an active crisis.
- Pain management is a supportive measure, but it does not address the physiological emergency of **marrow failure** and potential sepsis indicated by her vitals and labs.
*Immediate bone marrow transplant evaluation*
- **Aplastic crisis** in SCD is typically a transient event often triggered by **Parvovirus B19**, not a permanent state of marrow failure like aplastic anemia.
- Bone marrow transplant is a definitive cure for SCD but is never the priority intervention during an **acute life-threatening hematologic crisis**.
*Intravenous immunoglobulin for parvovirus B19*
- **IVIG** may be used in chronic or severe cases of persistent Parvovirus B19 infection in immunocompromised patients, but it is not the first-line emergency treatment for an acute drop in hemoglobin.
- Stabilization with **transfusion** takes precedence over treating the underlying viral trigger, as the crisis is usually self-limiting once the acute phase passes.
