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. Apply diagnostic reasoning to determine the 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.
Q6
A 55-year-old man with chronic kidney disease (GFR 25 mL/min) develops deep vein thrombosis. He is started on low molecular weight heparin (LMWH) and warfarin. After 5 days, his INR is 2.8, but before stopping LMWH, laboratory studies show: platelet count decreased from 280,000/μL to 85,000/μL. He has no bleeding. Peripheral smear shows no schistocytes. Analyze the most likely diagnosis and appropriate action.
Q7
A 32-year-old woman presents with fatigue and dyspnea. Labs show hemoglobin 7.2 g/dL, MCV 68 fL, ferritin 8 ng/mL, and total iron binding capacity 450 μg/dL. She was started on oral ferrous sulfate 325 mg three times daily. After 4 weeks, her hemoglobin is unchanged at 7.3 g/dL. She reports taking the medication as prescribed. What factor most likely explains the lack of response?
Q8
A 65-year-old man with atrial fibrillation on warfarin (INR goal 2-3) presents to the emergency department after a fall with head trauma. His INR is 8.5. CT head shows a small subdural hematoma with no midline shift. He is alert and neurologically intact. Blood pressure is 145/85 mmHg. What is the most appropriate immediate management?
Q9
A 28-year-old woman with menorrhagia presents with easy bruising and epistaxis. Platelet count is 18,000/μL. PT and aPTT are normal. Peripheral smear shows decreased platelets with normal morphology. Bone marrow biopsy reveals increased megakaryocytes. She was treated with prednisone 1 mg/kg for 4 weeks without response. What is the most appropriate next step?
Q10
A 45-year-old African American man presents with fatigue and jaundice. Laboratory studies show hemoglobin 8.5 g/dL, MCV 88 fL, reticulocyte count 8%, total bilirubin 4.2 mg/dL (predominantly indirect), and LDH 650 U/L. Peripheral blood smear shows spherocytes and polychromasia. Direct Coombs test is positive. He recently started taking methyldopa for hypertension. What is the most appropriate next step in management?
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. Apply diagnostic reasoning to determine the 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.
Question 6: A 55-year-old man with chronic kidney disease (GFR 25 mL/min) develops deep vein thrombosis. He is started on low molecular weight heparin (LMWH) and warfarin. After 5 days, his INR is 2.8, but before stopping LMWH, laboratory studies show: platelet count decreased from 280,000/μL to 85,000/μL. He has no bleeding. Peripheral smear shows no schistocytes. Analyze the most likely diagnosis and appropriate action.
A. Warfarin-induced thrombocytopenia; stop warfarin and continue LMWH
B. Disseminated intravascular coagulation; begin supportive care
C. Heparin-induced thrombocytopenia (HIT); stop all heparin and start argatroban (Correct Answer)
D. Immune thrombocytopenic purpura; start prednisone
E. Uremic platelet dysfunction; initiate desmopressin therapy
Explanation: ***Heparin-induced thrombocytopenia (HIT); stop all heparin and start argatroban***
- The patient exhibits a **>50% drop in platelet count** within 5-10 days of starting heparin, which is a classic presentation of **HIT Type II** mediated by **anti-platelet factor 4 (PF4)** antibodies.
- Because HIT is a **prothrombotic state**, all heparin must be stopped immediately and a non-heparin anticoagulant like **argatroban** must be started; argatroban is ideal here as it is **metabolized hepatically**, making it safe for a patient with a **GFR of 25 mL/min**.
*Warfarin-induced thrombocytopenia; stop warfarin and continue LMWH*
- **Warfarin** is not typically a cause of isolated, acute thrombocytopenia; its most severe early complication is **skin necrosis** due to **Protein C deficiency**.
- Continuing **LMWH** in the setting of a massive platelet drop would be dangerous, as it would likely worsen the **HIT-mediated thrombosis**.
*Uremic platelet dysfunction; initiate desmopressin therapy*
- **Uremic platelet dysfunction** involves impaired platelet **aggregation and adhesion** rather than a significant reduction in the absolute **platelet count**.
- **Desmopressin (DDAVP)** is used to improve surgical bleeding risk in uremia but does not address the underlying cause of **acute thrombocytopenia** following heparin exposure.
*Disseminated intravascular coagulation; begin supportive care*
- **DIC** is characterized by the consumption of clotting factors and platelets, but it typically presents with **schistocytes** on peripheral smear and prolonged **PT/PTT**, which are not seen here.
- The clinical context lacks a clear trigger for DIC (like sepsis or trauma) and instead correlates perfectly with the timing of **heparin administration**.
*Immune thrombocytopenic purpura; start prednisone*
- **ITP** is a diagnosis of exclusion that usually presents as isolated thrombocytopenia without an obvious drug trigger or systemic illness.
- Given the recent initiation of **heparin**, HIT is a far more likely cause of the sudden platelet drop than a new-onset **autoimmune destruction** of platelets.
Question 7: A 32-year-old woman presents with fatigue and dyspnea. Labs show hemoglobin 7.2 g/dL, MCV 68 fL, ferritin 8 ng/mL, and total iron binding capacity 450 μg/dL. She was started on oral ferrous sulfate 325 mg three times daily. After 4 weeks, her hemoglobin is unchanged at 7.3 g/dL. She reports taking the medication as prescribed. What factor most likely explains the lack of response?
A. Celiac disease causing malabsorption
B. Anemia of chronic disease coexisting with iron deficiency
C. Concurrent calcium supplement intake
D. Thalassemia trait misdiagnosed as iron deficiency
E. Ongoing blood loss exceeding replacement (Correct Answer)
Explanation: ***Ongoing blood loss exceeding replacement***
- In a patient with confirmed **iron deficiency anemia** (low ferritin, high TIBC), the most common reason for a failure of hemoglobin to rise despite compliance is **occult gastrointestinal** or **menstrual bleeding** that outpaces iron intake.
- While reticulocytes may increase, the **hemoglobin remains stable or drops** because the rate of red cell loss is greater than or equal to the rate of new red cell production.
*Concurrent calcium supplement intake*
- **Calcium supplements** and dairy products can inhibit the absorption of non-heme iron by competing for transport or altering the local environment, but they rarely cause a total lack of response if dosing is frequent.
- While this can diminish the **efficacy of oral iron**, physician-led investigation usually prioritizes rule-out of active bleeding or primary malabsorption first.
*Celiac disease causing malabsorption*
- **Malabsorption syndromes** like Celiac disease affect the **duodenum**, the primary site of iron absorption, and can lead to refractory iron deficiency.
- However, given the options, **active blood loss** is statistically a more frequent cause for a static hemoglobin in a young woman with severe depletion.
*Anemia of chronic disease coexisting with iron deficiency*
- **Anemia of chronic disease (ACD)** is characterized by **high ferritin** (an acute phase reactant) and **low TIBC**, which is the exact opposite of this patient's laboratory findings.
- Although inflammation increases **hepcidin** (blocking iron absorption), the specific lab values provided here (ferritin 8 ng/mL) are pathognomonic for **absolute iron deficiency**.
*Thalassemia trait misdiagnosed as iron deficiency*
- **Thalassemia trait** presents with microcytosis but typically features a **normal or high RBC count** and **normal ferritin** levels.
- Since the patient has a **ferritin of 8 ng/mL**, the diagnosis of iron deficiency is correct, and her lack of response is due to iron kinetics rather than a misdiagnosis of a hemoglobinopathy.
Question 8: A 65-year-old man with atrial fibrillation on warfarin (INR goal 2-3) presents to the emergency department after a fall with head trauma. His INR is 8.5. CT head shows a small subdural hematoma with no midline shift. He is alert and neurologically intact. Blood pressure is 145/85 mmHg. What is the most appropriate immediate management?
A. Administer prothrombin complex concentrate (PCC) and vitamin K 10 mg IV (Correct Answer)
B. Administer platelets and cryoprecipitate
C. Administer vitamin K 10 mg IV and fresh frozen plasma
D. Observe and repeat INR in 6 hours
E. Give vitamin K 5 mg PO only
Explanation: ***Administer prothrombin complex concentrate (PCC) and vitamin K 10 mg IV***
- Immediate reversal of anticoagulation is mandatory in the setting of **warfarin-associated intracranial hemorrhage**, even with a small **subdural hematoma**, to prevent expansion.
- **PCC** is the treatment of choice over FFP due to its ability to achieve **rapid INR correction** with a smaller volume, alongside **IV Vitamin K** for sustained reversal.
*Administer vitamin K 10 mg IV and fresh frozen plasma*
- **Fresh frozen plasma (FFP)** requires a large volume and **time for thawing and cross-matching**, which delays the critical stabilization of the patient.
- While it provides clotting factors, **4-factor PCC** is significantly faster and more effective at normalizing the **INR** in emergency settings.
*Give vitamin K 5 mg PO only*
- **Oral Vitamin K** takes approximately **24 hours** to reach its full effect, which is unacceptably slow for an active **intracranial bleed**.
- This approach is typically reserved for high **INR** without significant bleeding, not for patients with confirmed **subdural hematoma**.
*Administer platelets and cryoprecipitate*
- **Platelets** are not indicated for warfarin reversal unless there is concurrent **thrombocytopenia** or antiplatelet use, as warfarin affects clotting factors, not platelet count.
- **Cryoprecipitate** is primarily used to replace **fibrinogen** and is not the standard of care for reversing **vitamin K antagonist** overdose.
*Observe and repeat INR in 6 hours*
- Observation alone is contraindicated in a patient with a **supratherapeutic INR of 8.5** and evidence of **acute traumatic intracranial bleeding**.
- Waiting 6 hours to repeat the **INR** without intervention allows for a high risk of **hematoma expansion** and sudden neurological collapse.
Question 9: A 28-year-old woman with menorrhagia presents with easy bruising and epistaxis. Platelet count is 18,000/μL. PT and aPTT are normal. Peripheral smear shows decreased platelets with normal morphology. Bone marrow biopsy reveals increased megakaryocytes. She was treated with prednisone 1 mg/kg for 4 weeks without response. What is the most appropriate next step?
A. Intravenous immunoglobulin (IVIG)
B. Romiplostim (thrombopoietin receptor agonist)
C. Splenectomy
D. Increase prednisone to 2 mg/kg
E. Rituximab therapy (Correct Answer)
Explanation: ***Rituximab therapy***
- This patient has **Immune Thrombocytopenic Purpura (ITP)** and has failed first-line **corticosteroid** therapy; **Rituximab** is a preferred second-line monoclonal antibody directed against **CD20** on B-cells.
- It is effective in reducing the production of **anti-platelet antibodies** and is often chosen before surgical interventions like splenectomy in modern clinical practice.
*Splenectomy*
- While **splenectomy** is a valid second-line treatment, it is an invasive procedure generally deferred until pharmacological options like **Rituximab** or **TPO-receptor agonists** are considered.
- It carries a lifelong risk of **overwhelming post-splenectomy infection (OPSI)**, requiring preoperative vaccinations against encapsulated organisms.
*Intravenous immunoglobulin (IVIG)*
- **IVIG** is used for **acute management** to rapidly increase platelet counts in cases of severe bleeding or prior to surgery.
- Its effects are **temporary** (lasting only 1–2 weeks) and it is not an appropriate long-term strategy for patients who are steroid-refractory.
*Romiplostim (thrombopoietin receptor agonist)*
- **Romiplostim** is a second-line option that stimulates **megakaryocytes** via the **TPO receptor** to increase platelet production.
- Though effective, it requires weekly subcutaneous injections and is often ranked alongside or after **Rituximab** depending on patient preference and clinician experience.
*Increase prednisone to 2 mg/kg*
- Increasing the dose of **prednisone** beyond 1 mg/kg is not recommended as it significantly increases **systemic toxicity** without improving the remission rate.
- Failure to respond to 1 mg/kg after 4 weeks defines the patient as **steroid-refractory**, necessitating a switch to second-line agents rather than dose escalation.
Question 10: A 45-year-old African American man presents with fatigue and jaundice. Laboratory studies show hemoglobin 8.5 g/dL, MCV 88 fL, reticulocyte count 8%, total bilirubin 4.2 mg/dL (predominantly indirect), and LDH 650 U/L. Peripheral blood smear shows spherocytes and polychromasia. Direct Coombs test is positive. He recently started taking methyldopa for hypertension. What is the most appropriate next step in management?
A. Discontinue methyldopa and observe (Correct Answer)
B. Initiate rituximab therapy
C. Start prednisone 1 mg/kg daily
D. Begin plasmapheresis immediately
E. Perform splenectomy
Explanation: ***Discontinue methyldopa and observe***
- The patient presents with **drug-induced Warm Autoimmune Hemolytic Anemia (WAIHA)**, as evidenced by a **positive Direct Coombs test**, anemia, and jaundice shortly after starting **methyldopa**.
- Methyldopa induces the production of true **autoantibodies** against red blood cell antigens; the most appropriate and often curative first step is the **withdrawal of the offending drug**.
*Start prednisone 1 mg/kg daily*
- **Corticosteroids** are the first-line treatment for **primary (idiopathic) WAIHA**, but they are not the immediate priority when a clear drug-induced cause is identified.
- Most cases of **methyldopa-induced hemolysis** resolve gradually within weeks after the medication is stopped without requiring systemic steroids.
*Perform splenectomy*
- **Splenectomy** is a **second-line intervention** reserved for patients with WAIHA who are refractory to or dependent on high doses of corticosteroids.
- It is inappropriate in the initial management of **drug-induced hemolysis** where the trigger can be easily removed.
*Initiate rituximab therapy*
- **Rituximab**, an anti-CD20 monoclonal antibody, is utilized for **refractory AIHA** or cases where patients fail initial steroid therapy.
- It is an expensive treatment with potential side effects and is not indicated as the **next step** before assessing response to drug discontinuation.
*Begin plasmapheresis immediately*
- **Plasmapheresis** is generally ineffective in WAIHA because **IgG antibodies** are primarily located on the RBC surface and have a large volume of distribution.
- This procedure is typically reserved for extreme cases of **Thrombotic Thrombocytopenic Purpura (TTP)** or occasionally Cold Agglutinin Disease, but not drug-induced WAIHA.
