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USMLE Step 2 CK High-Yield Hematology/Oncology Topics
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Hematology/Oncology
High Yield USMLE Step 2 CK Notes
Welcome to the Hematology/Oncology High-Yield Notes for Step 2 CK.
These are the most commonly tested topics on the exam—ideal for quick review in your last 2 weeks before the exam, when you’re short on time, or when you’re just starting out and want to focus on what is high yield. Created and peer-reviewed by physicians who scored 260+ on Step 2 CK in a Q&A style to reinforce active learning.
How to use this file
- Read the question ➔ cover the answer ➔ self-quiz before revealing.
- Review the NOTES ➔ they include high-yield details you don’t want to miss.
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Table of Contents
Hemostasis and coagulation
1. A 3-day-old full-term male develops persistent bleeding after circumcision and has a large cephalohematoma. He received vitamin K at birth. Labs: Normal PT/INR, normal platelets, prolonged PTT.
➔ Hemophilia A (Factor VIII Deficiency)
- Note: X-linked recessive disorders affect boys. Positive family history is common. Hemophilia A = factor VIII deficiency, Hemophilia B = factor IX deficiency.
- Presentation: Prolonged bleeding (e.g., post-circumcision), large hematomas, joint bleeding, and muscle hematomas.
- ↑ PTT (intrinsic pathway), normal PT, platelets. Treated with Factor VIII or desmopressin.
2. A 5-day-old newborn presents with bleeding from the nose and intraventricular hemorrhage. He was born at home. What is the risk factor for his bleeding?
➔ Vitamin K Deficiency Bleeding
- Note: Vitamin K deficiency is common in neonates who do not receive prophylactic vitamin K as those born at home. Also, with those with fat malabsorption as Crohn’s disease or Cystic Fibrosis as Vitamin K is a fat-soluble vitamin (A, D, E, K).
- ↓ synthesis of factors II, VII, IX, X, and proteins C & S, causing bleeding from the mucosa, umbilicus, or intracranial.
- Labs show ↑ PT and ↑ PTT, normal platelets, and bleeding time. Treated and prevented with vitamin K, and Fresh frozen plasma (FFP) for active bleeding.
3. A 24-year-old woman with heavy menstrual bleeding and recurrent epistaxis presents with a 6-hour nosebleed. Labs: Platelets 20,000/mm³, normal WBC, Hb 9.8 g/dL.
➔ Immune Thrombocytopenia (ITP)
- Note: Often follows viral illness is associated with HIV/HCV. Autoantibodies against platelets lead to increased destruction.
- Presents with mucocutaneous bleeding, petechiae, and menorrhagia.
○ Labs show thrombocytopenia, ↑ megakaryocytes, prolonged bleeding time, normal PT, and PTT. - Treatment:
○ Children: observation if cutaneous symptoms only, while steroids/ IVIG if bleeding.
○ Adults: observation if cutaneous symptoms and platelets >30000, while steroids/ IVIG if bleeding or platelets <30000. Splenectomy is a second-line option.
4. A 13-year-old girl has bruises. She has normal platelets, prolonged bleeding time, and no agglutination with ristocetin. What is the most likely diagnosis?
➔ Bernard-Soulier syndrome
- Note: GP1b deficiency → impaired platelet adhesion. Platelet count is normal, but high bleeding time, normal PT, and PTT.
- Glanzmann thrombasthenia: deficiency of GPIIb/IIIa ➞ defective platelet aggregation. Platelet count is normal, but prolonged bleeding time, normal PT, and PTT.
5. A female with heavy menstrual bleeding, epistaxis, and bleeding after dental extraction, and labs showing ↑ BT and ↑ PTT with normal PT. What is the next step in management?
➔ Desmopressin
- Note: Von Willebrand disease is the most common inherited bleeding disorder. Defective platelet adhesion due to ↓ vWF. vWF also stabilizes factor VIII → ↑ BT and normal or ↑ PTT. The Ristocetin test is abnormal.
- VWD is AD while Hemophilia is X-linked recessive, affecting only boys.
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6. A patient with sepsis develops bleeding from the IV sites. What condition best explains these findings?
➔ Disseminated intravascular coagulation (DIC)
- Note: Triggered by infection, trauma, malignancy, or obstetric complications as amniotic fluid embolism, triggering massive coagulation and fibrinolysis.
- Labs show ↑ PT, ↑ PTT, ↑ BT, ↑ D-dimer, ↓ fibrinogen, and ↓ platelets. Schistocytes may be seen.
- Treat the underlying cause and fresh frozen plasma.
7. A patient with chronic kidney disease complains of mucosal bleeding despite a normal platelet count. What is the most likely explanation for this presentation?
➔ Uremic platelet dysfunction
- Note: Platelet adhesion and aggregation are impaired due to uremic toxins. Bleeding time is prolonged. Normal platelet count, PT, and PTT.
- Desmopressin improves platelet function temporarily.
8. A female with SLE presents with DVT and prolonged PTT that does not correct with a mixing study. What is the most likely diagnosis?
➔ Antiphospholipid syndrome
- Note: It presents as recurrent pregnancy loss, arterial or venous thrombosis. It can be primary or part of SLE.
- Positive for anticardiolipin, beta-2 glycoprotein I, or lupus anticoagulant. Requires lifelong anticoagulation.
- Lupus anticoagulant prolongs PTT, but no bleeding.
9. A patient with nephrotic syndrome develops DVT or renal vein thrombosis. What is the most likely diagnosis?
➔ Antithrombin III deficiency
- Note: Nephrotic syndrome leads to urinary loss of antithrombin III, increasing clot risk. It may also be congenital.
- Heparin may not be effective, “no elevation in PTT” since it works by binding to ATIII. Consider direct thrombin inhibitors.
10. A patient has recurrent venous clots. What is the most likely etiology?
➔ Factor V Leiden mutation
- Note: The most common inherited thrombophilia. Mutation makes factor V resistant to inactivation by protein C, leading to increased risk of recurrent thrombosis or thrombosis without predisposing risk factors.
- It has normal PT/PTT.
- In the absence of a clear risk factor for DVT as surgery or immobilization, patients with a first episode of DVT should be referred for age-appropriate cancer screening.
11. A 57-year-old woman with metastatic colon cancer develops right arm DVT 10 days after port placement. After starting IV heparin, her platelet count drops from 260,000 to 61,000 within 2 days. What is the diagnosis?
➔ Heparin-Induced Thrombocytopenia (HIT)
- Note: IgG antibodies to heparin-platelet factor 4 (PF4) complexes → platelet activation → thrombosis + thrombocytopenia → ↓ Platelet count >50%.
- Stop heparin and start a direct thrombin inhibitor (e.g., argatroban or dabigatran).
12. A patient develops skin necrosis shortly after starting warfarin. What could have prevented his symptoms?
➔ Prevented by bridging with heparin
- Note: Protein C deficiency; Warfarin initially lowers protein C faster than clotting factors, creating a transient hypercoagulable state.
- Warfarin is monitored by PT/INR, while Heparin is monitored by PTT.
13. A 45-year-old previously healthy man presents with a 2-day history of headache and confusion. Exam shows mild jaundice, anemia, thrombocytopenia, renal impairment, and schistocytes on peripheral smear. What is the most likely diagnosis?
➔ Thrombotic Thrombocytopenic Purpura (TTP)
- Note: Pathophysiology: Anti-ADAMTS13 antibodies → ↑ vWF multimers → platelet aggregation mostly in renal and cerebral vessels→ MAHA + thrombocytopenia + renal failure + neuro changes + fever (not always present).
- Labs: ↓ Platelets, ↑ Creatinine/BUN, Normal PT/PTT, and schistocytes on smear.
- Treatment: plasma exchange (PEX).
- Schistocytes cause: TTP, HUS, DIC, Scleroderma renal crisis, HELLP syndrome, and Prosthetic heart valves.
14. A 3-year-old boy presents with fatigue, pallor, scleral icterus, edema, and bruising after a recent diarrheal illness treated with anti-diarrheal medication. Labs show anemia, thrombocytopenia, and a normal coagulation profile. Dx?
➔ Hemolytic Uremic Syndrome (HUS)
- Note: Trigger: Shiga toxin-producing E. coli (e.g., O157:H7): Shiga toxin → endothelial damage → platelet activation → microthrombi.
- Triad:
○ Hemolytic anemia (schistocytes, ↑ LDH, ↑ indirect bilirubin).
○ Thrombocytopenia.
○ Acute kidney injury (edema, ↑ BUN/Cr). - Treatment: Supportive care (IV fluids, transfusions, dialysis if needed), avoid Antibiotics & antimotility drugs (↑ risk of HUS).
15. A child with autism and a diet limited to chocolate milk and crackers presents with worsening leg pain, petechiae, and gingival bleeding. She refuses to walk, and examination shows tender thighs and perifollicular hemorrhages. What is the diagnosis?
➔ Vitamin C deficiency (Scurvy)
- Note: Etiology: Malnutrition in picky eaters (e.g., autism); lack of fruits/vegetables
- Symptoms:
○ Gingival swelling & bleeding
○ Petechiae, perifollicular hemorrhages
○ Bone/muscle pain due to subperiosteal bleeding
○ Poor wound healing. - Labs: (Microcytic anemia (iron deficiency), and normal coagulation studies)
- Diagnosis: Low ascorbic acid level, treated with Vitamin C supplementation.
16. A 35-year-old woman with no bleeding history undergoes a core needle biopsy for a thyroid nodule. After the procedure, she develops an expanding hematoma at the biopsy site. TSH is normal, and there is no personal or family history of bleeding or easy bruising. What is the diagnosis?
➔ Insufficient hemostasis (not a bleeding disorder)
- Note: Key exclusions based on history:
○ No mucocutaneous bleeding → unlikely platelet dysfunction or ITP
○ No family history → von Willebrand disease and hemophilia unlikely
○ Female patient, no childhood bleeding → rules out factor VIII deficiency (hemophilia A)
○ No signs of malnutrition → rules out vitamin C/K deficiency
17. A 30-year-old man, hospitalized for 3 weeks for third-degree burns, develops fever and purulent drainage at an IV catheter site on the left wrist. The overlying vein is erythematous, tender, indurated, and fluctuant. What is the diagnosis?
➔ Catheter-associated septic thrombophlebitis
- Note: Infected thrombus at catheter site; often due to S. aureus, gram-negatives, or Candida → Fever, localized vein induration, erythema, tenderness, purulent drainag
- Diagnosis: Clinical exam; duplex ultrasound
- Management:
○ Immediate catheter removal
○ Surgical excision of the affected vein
○ IV broad-spectrum antibiotics.
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RBC
18. A woman presents with a 3-month history of fatigue and craving for non-food substances. Exam: pale conjunctivae. Labs: Hemoglobin 9 g/dL. Blood smear: hypochromic microcytic cells. What is the diagnosis?
➔ Iron Deficiency Anemia
- Note: Risk factors of IDA:
○ Chronic blood loss: (peptic ulcers, colorectal cancer, hookworm as Ancylostoma)- heavy menstrual bleeding.
○ Low intake as infants consuming >24 ounces/ 700 ml of cow milk.
○ High demand as pregnancy
○ Decreased absorption as celiac disease or PPI. - Blood smear shows microcytic, hypochromic RBCs. Labs: ↓ Serum ferritin, ↑ TIBC, ↓ Serum iron, and ↑RDW.
- Treatment: Oral iron supplementation (ferrous sulfate)
- In elderly men with IDA, chronic GI blood loss, suspect colon cancer until proven otherwise.
19. A woman presents with 1 year of fatigue. Past history includes anemia during pregnancy. Labs: Hemoglobin 11.6 g/dL, MCV 66 fL, reticulocyte count 0.3%. Hemoglobin electrophoresis shows: HbA2 = 5%, HbF = 2%. What best explains these findings?
➔ Beta-Thalassemia minor
- Note: Key diagnostic clue: ↑ HbA2 (above 3.5%) on electrophoresis
- Retic count: Low → decreased RBC production, smear may show target cells.
- Other scenarios for thalassemia trait:
○ Persistent microcytic anemia despite iron therapy.
○ Microcytic anemia with normal iron studies. - Asymptomatic or mild anemia → No treatment required.
Target cells
Mikael Häggström, M.D. Author info – Reusing images- Conflicts of interest: None Mikael Häggström, M.D.Consent note: Consent from the patient or patient’s relatives is regarded as redundant, because of absence of identifiable features (List of HIPAA identifiers) in the media and case information (See also HIPAA case reports guidance). (https://commons.wikimedia.org/wiki/File:Micrograph_of_a_target_cell.jpg), „Micrograph of a target cell“, https://creativecommons.org/publicdomain/zero/1.0/legalcode
20. A child presents with chipmunk facies, massive hepatosplenomegaly, and elevated HbA2 levels. What are the lab findings?
➔ Increased HbF and HbA2, no HbA
- Note: Beta-thalassemia major (they can’t make the chain β, so they can’t make HbA).
- Hb electrophoresis shows increased HbF and HbA2, with little or no HbA. The child is transfusion-dependent by 6 months of age. Target cells on blood smear.
- Iron overload from transfusions is common, requiring chelation therapy.
| Condition | HbA (%) | HbA2 (%) | HbF (%) |
|---|---|---|---|
| Normal | >95% | <3.5% | <2% |
| Beta Thalassemia Minor | ↓ (~85-95%) | ↑ (>3.5%) | Normal or ↑ |
| Beta Thalassemia Major | Absent | ↑ (>3.5%) | ↑↑ |
21. A 4-year-old child is brought to the clinic due to chronic constipation, developmental delays, and irritability. The parents report that the family lives in an older home built before 1978 and that the child often plays near chipping paint. What is the most likely finding on the peripheral blood smear?
➔ Basophilic stippling
- Note: Key Signs: (Microcytic anemia, Developmental delay, Constipation)
- Peripheral Smear: Basophilic stippling (due to ribosomal RNA aggregates)
- Common Source: Ingestion of lead-based paint or contaminated dust (old homes built before 1978)
- Treatment:
○ Mild: Remove the source of lead
○ Moderate-severe: Chelation therapy with dimercaprol + EDTA or succimer.
22. A 36-year-old man with TB on RIPE therapy develops microcytic anemia (Hb 7, MCV 77) with elevated serum iron and low/normal TIBC. Blood smear shows dimorphic RBCs. What best explains these findings?
➔ Isoniazid-induced sideroblastic anemia
- Note: Isoniazid (INH) → inhibits pyridoxine (vitamin B6) → defective protoporphyrin synthesis → ineffective heme synthesis, iron trapped in mitochondria → ring sideroblasts.
- Labs: ↓ MCV, ↑ serum iron, ↓/normal TIBC, dimorphic RBCs (normochromic + hypochromic)
- Management: Give pyridoxine (vitamin B6)
23. A 3-year-old boy presents with increasing lethargy and jaundice. Family history reveals the father had a splenectomy at age 6. Exam: scleral icterus, splenomegaly, systolic murmur. Labs: Hb 8.3 g/dL, reticulocyte count 10%, bilirubin 5 mg/dL, Coombs-negative. What is the diagnosis?
➔ Hereditary Spherocytosis
- Note: Mutation in RBC membrane proteins (e.g., spectrin, ankyrin); autosomal dominant → Normocytic, normochromic RBCs with spherocytes → trapped in spleen → hemolysis
- Key: Hemolytic anemia (↑ indirect bilirubin, ↑ reticulocytes), ↑ MCHC (the only common cause of increased MCHC), Splenomegaly, Family history of hemolytic anemia/splenectomy, and Gallstones.
- Diagnosis: Confirmed with osmotic fragility or eosin-5-maleimide (EMA) test.
- Treatment: folate supplementation to prevent folic acid deficiency anemia. Splenectomy if severe or symptomatic.
24. A child with sickle cell disease develops left upper quadrant pain, hypotension, anemia, and elevated retic count. What is the most likely diagnosis?
➔ Splenic sequestration crisis
- Note: Pooling blood in the spleen → hypovolemic shock and splenomegaly.
- Sickle-shaped RBCs on blood smear. ↑HbS, ↑HbF, ↑HbA2, ↓HbA
- Aplastic crisis due to parvovirus presents with low reticulocytes and no splenomegaly.
- Chronic sickling causes atrophy of the spleen:
○ Predisposing the body to infection with encapsulated organisms as pneumococci, meningococci, and H. influenzae, requires vaccination for those organisms.
○ Howell-Jolly bodies on blood smear.
Sickle cells
Erhabor Osaro (Associate Professor) (https://commons.wikimedia.org/wiki/File:Sickle_Cell_Anaemia_(SCA).jpg), „Sickle Cell Anaemia (SCA)“, https://creativecommons.org/licenses/by-sa/3.0/legalcode
Howell Jolly bodies
Gusloureiro (https://commons.wikimedia.org/wiki/File:Howell-Jolly-Arrows.jpg), „Howell-Jolly-Arrows“, https://creativecommons.org/licenses/by-sa/3.0/legalcode
25. A child with sickle cell disease presents with joint pain, fever, chest pain, and a new infiltrate on chest X-ray. What is the diagnosis?
➔ Acute chest syndrome
- Note: New chest infiltrate on CXR, hypoxia, and chest pain. Triggered by infection. treat with oxygen, antibiotics, transfusion, and pain control.
- Other sickling scenarios include dactylitis, bone pain crises, priapism, and renal papillary necrosis.
- Sickle cell disease is the most common cause of pediatric stroke. The next step is hemoglobin electrophoresis to confirm the diagnosis.
- Vaso-occlusive crisis episodes can be prevented by hydroxyurea.
- Hydroxyurea can cause macrocytic anemia and myelosuppression.
26. A patient with rheumatoid arthritis presents with hemoglobin 9.5, high ferritin, and low TIBC. What is the treatment for his anemia?
➔ Methotrexate
- Note: Anemia of chronic disease is common in chronic conditions as Multiple Myeloma and Rheumatoid Arthritis, and resolves by treating the underlying disease.
- IL-6 increases hepcidin, trapping iron in macrophages and reducing iron absorption. Labs show low serum iron, low TIBC, and normal/high ferritin.
- Anemia of chronic disease due to chronic kidney disease is treated with EPO. EPO can cause an HTN emergency.
27. A female with abdominal pain, anemia, and neurologic symptoms like paresthesia. What best explains these findings?
➔ Pernicious anemia (autoimmune B12 deficiency)
- Note: Caused by antibodies against intrinsic factor or parietal cells. Leads to decreased B12 absorption in the terminal ileum. Associated with other autoimmune diseases.
- It is associated with atrophic gastritis and ↑ the risk of gastric cancer.
- Labs show macrocytic anemia, ↑ homocysteine, and ↑ methylmalonic acid. Diagnosis confirmed with low serum B12.
- Neurological signs include peripheral neuropathy, ataxia, loss of vibration/proprioception, and spastic paralysis.
28. A patient with rheumatoid arthritis stable on methotrexate complains of recent fatigue. Labs show macrocytic anemia. What is the most likely explanation for this presentation?
➔ Folate deficiency
- Note: Methotrexate inhibits dihydrofolate reductase, blocking folate metabolism. Supplement with folinic acid (leucovorin) or folic acid to prevent this side effect.
○ Labs show ↑ homocysteine and normal methylmalonic acid. Both are high with B12 deficiency.
○ If you treat a B12 deficiency patient with folate, anemia may resolve, but neuro symptoms worsen.
○ Other risk factors for folate deficiency are hemolytic anemia, alcoholism, and phenytoin.
29. A female with SLE presents with fatigue and shortness of breath. Labs show low hemoglobin and a positive direct Coombs test. What best explains these findings?
➔ Warm autoimmune hemolytic anemia (AIHA)
- Note: IgG-mediated hemolysis at body temperature. Labs show spherocytes, ↑ LDH, ↑ bilirubin, and ↓ haptoglobin. A positive Coombs test is an important key.
- Triggered by antibiotics as penicillin and cephalosporin, and conditions as SLE and CLL.
- Treat with steroids first-line; refractory cases may need rituximab or splenectomy.
- Cold AIHA (cold agglutinin disease): IgM-mediated hemolysis is triggered by cold temperatures. Commonly secondary to Mycoplasma pneumoniae or EBV. Avoid the cold.
30. A patient develops fatigue and dark urine after taking TMP-SMX for a recent UTI. What condition best explains these findings?
➔ G6PD deficiency
- Note: X-linked disorder causing RBC susceptibility to oxidative stress. Triggers include sulfa drugs (TMP-SMX), nitrofurantoin, dapsone, primaquine, antimalarials, and fava beans. Avoid those triggers.
- Peripheral smear shows bite cells and Heinz bodies. Negative Coombs test.
- Hemolytic anemia after TMP-SMX is G6PD deficiency, while Hemolytic anemia after cephalosporin is AIHA.
Heinz bodies & Bite cells
Martínez-Pérez PA, Hyndman TH, Fleming PA (https://commons.wikimedia.org/wiki/File:Some_erythrocytic_morphologies_and_intraerythrocytic_inclusions_found_in_peripheral_blood_smears_of_quokkas_on_Rottnest_Island_
(also_found_in_quokkas_on_mainland_Western_Australia).png), https://creativecommons.org/licenses/by/4.0/legalcode
31. A 40-year-old patient reports red urine and fatigue in the morning. He has a history of unexplained thrombosis. What condition best explains these findings?
➔ Paroxysmal nocturnal hemoglobinuria (PNH)
- Note: PIGA gene mutation → deficient CD55/CD59 → complement-mediated lysis. Presents with hemolysis (dark urine in morning), pancytopenia, and venous thrombosis (esp. hepatic, portal, cerebral).
- Diagnose with flow cytometry. Treated with eculizumab. Treated with eculizumab, anti anti-C5 monoclonal antibody.
32. A 70-year-old man with a mechanical aortic valve presents with 6 months of fatigue and dyspnea. The exam shows pallor, hepatosplenomegaly. Labs show anemia, ↑ reticulocytes, and thrombocytopenia. What is the next step?
➔ Transthoracic echocardiogram to assess valve dysfunction
- Note: Mechanical valve → chronic hemolysis→ Fatigue, dyspnea, (Anemia with ↑ reticulocytes), Thrombocytopenia from mechanical destruction, and hepatosplenomegaly from extravascular hemolysis.
- Peripheral smear: schistocytes
33. A full-term neonate is born to a healthy mother after an uncomplicated vaginal delivery. Within the first 12 hours of life, the baby develops significant jaundice and scleral icterus. Labs reveal anemia and a positive direct Coombs test. What is the most likely diagnosis?
➔ Rh incompatibility
- Note: Occurs when an Rh-negative mother forms anti-D antibodies against an Rh-positive fetus, “husband is RH positive”, leading to hemolytic anemia and jaundice on the first day. It can cause hydrops fetalis.
- Prevented with Rho(D) immune globulin during pregnancy and postpartum.
- It affects the second pregnancy, whereas ABO incompatibility affects the first.
34. A term neonate is born to a mother with blood type O. Within the first 24 hours of life, the infant develops noticeable jaundice. The baby is feeding well, and vital signs are stable. Labs show elevated unconjugated bilirubin and a mild anemia. A direct Coombs test is weakly positive. What is the most likely diagnosis?
➔ ABO incompatibility
- Note: The most common cause of hemolytic disease in newborns. It affects the first pregnancy. Coombs test is positive.
- Less severe than Rh incompatibility. Treat with phototherapy.
- Bilirubin >25 or failed phototherapy = urgent exchange transfusion to prevent kernicterus.
35. A woman presents with abdominal pain, dark urine after fasting or certain drugs. What condition best explains these findings?
➔ Acute intermittent porphyria (AIP)
- Note: This is a case of Acute intermittent porphyria (AIP). Defect in porphobilinogen deaminase → buildup of ALA.
- Symptoms: abdominal pain, neurologic dysfunction, psychiatric symptoms, dark urine (porphyrins).
- Triggered by fasting and alcohol. Treat with glucose and hemin to downregulate ALA synthase.
36. A patient with hepatitis C presents with blisters on sun-exposed areas. What condition is mostly associated with his symptoms?
➔ Porphyria cutanea tarda (PCT)
- Note: Porphyria cutanea tarda (PCT) presents with chronic blistering, photosensitivity, skin fragility, and hyperpigmentation in sun-exposed areas.
- Treat with phlebotomy and low-dose hydroxychloroquine.
37. A 1-year-old boy presents with persistent epistaxis, petechiae, ecchymoses, pallor, and tachycardia. The exam shows no hepatosplenomegaly. Labs show low RBCs, WBCs, and platelets. What is the diagnosis?
➔ Aplastic anemia
- Note: Bone marrow failure due to destruction of hematopoietic stem cells → pancytopenia
- Common triggers: idiopathic, viral (parvovirus, hepatitis), drugs, toxins
- Diagnosis: confirmed by bone marrow biopsy → hypocellular, fatty marrow.
- No hepatosplenomegaly or lymphadenopathy → rules out leukemia and lymphoma. Normal cell morphology on smear.
Transfusion reactions
38. A 43-year-old man develops sudden shortness of breath and back pain during a packed RBC transfusion on postoperative day 1 after splenectomy for trauma. He is diaphoretic, with normal oxygen saturation, and clear lungs. Vitals are stable. No skin findings. What best explains these findings?
➔ Acute hemolytic transfusion reaction (AHTR)
- Note: Type II hypersensitivity due to ABO incompatibility, caused by the recipient’s preformed anti-A or anti-B IgM antibodies. Positive direct Coombs test.
- Presents with fever, chills, dyspnea, back/flank pain, and hemoglobinuria. Rapid intravascular hemolysis → risk of DIC, renal failure, and death.
- Management: Stop transfusion, IV fluids, and supportive care, and notify the blood bank.
| Transfusion Reaction | Clinical Features & Timing | Mechanism |
|---|---|---|
| Febrile nonhemolytic | Fever, chills – Starts within 1–6 hours. | Most common reaction. Caused by cytokines from donor WBCs. Prevent with leukoreduction |
| Acute hemolytic | Fever, flank pain, hemoglobinuria, DIC, hypotension – Starts within 1 hour | ABO incompatibility → type II hypersensitivity. Positive Coombs test. Emergency: Stop transfusion, supportive care |
| Delayed hemolytic | Mild fever, jaundice, anemia – Occurs 2–10 days post-transfusion | Anamnestic IgG response to minor RBC antigens. Positive Coombs test and new antibody screen |
| Anaphylactic | Shock, angioedema, urticaria, respiratory distress – Starts within seconds to minutes | Seen in IgA-deficient recipients – Caused by anti-IgA antibodies – Treat with epinephrine – Use washed RBCs |
| Urticarial / Allergic | Urticaria, itching, flushing, angioedema – Starts within 2–3 hours | Type I hypersensitivity is caused by recipient IgE reacting to donor plasma allergens. Treat with antihistamines |
| TRALI (Transfusion-Related Acute Lung Injury) | Dyspnea, hypoxia, and noncardiogenic pulmonary edema. Starts within 6 hours | Caused by donor anti-leukocyte antibodies. Neutrophil activation → capillary leak – Leading cause of transfusion death |
39. A 24-year-old woman is in hemorrhagic shock after a motor vehicle accident. She has a right hemothorax (1.5 L blood in chest tube), positive FAST exam (abdominal bleeding), and left femur fracture. Vitals: BP 80/50, HR 138, cold extremities, decreased consciousness. What is the next step?
➔ Transfuse group O, Rh D-negative blood
- Note: Signs of hemorrhagic shock: (SBP <90 mm Hg, HR >120/min, Altered mental status, and Cold, clammy extremities).
- Likely blood loss sites: (Chest “hemothorax”, Abdomen “hemoperitoneum”, and pelvis).
- Resuscitation priority:
○ Crystalloids limited to 1 L max initially.
○ Group O, Rh D-negative blood to avoid Rh sensitization.
○ Early massive transfusion if needed (1:1:1 PRBCs: FFP: platelets). - Avoid:
○ Excess crystalloids (worsens acidosis, coagulopathy).
○ Vasopressors (reduce perfusion in volume-depleted patients).
40. A 55-year-old man is admitted with upper gastrointestinal bleeding. On exam, he is pale and hypotensive (BP 85/60), HR 112/min. He has no focal neurological signs. Labs show: (Hemoglobin: 6.9 g/dL- Platelets: 38,000/mm³- INR: 2.4- PTT: 40 sec- BUN: 40 mg/dL- Creatinine: 1.1 mg/dL). What blood products should be given to this patient?
➔ RBCs + Platelets + FFP
- Note: Packed RBC transfusion:
○ Indicated if Hb <7 g/dL in stable patients. Hb >10 g/dL not indicated.
○ Use a threshold of <10 g/dL in active bleeding, symptomatic anemia, or unstable patients. - Platelet transfusion:
○ Indicated if platelets <50,000/mm³ with active bleeding or prior to surgery.
○ Transfuse always if platelets <10,000/mm³. - Fresh Frozen Plasma (FFP):
○ DIC, warfarin-induced bleeding, and Vitamin K deficiency bleeding.
○ Massive resuscitation.
41. A 27-year-old man presents with recurrent epistaxis. On physical exam, he has multiple ruby-colored papules on his lips that partially blanch with pressure and digital clubbing. CBC shows elevated hematocrit (60%). What is the diagnosis?
➔ Hereditary hemorrhagic telangiectasia (AD)
- Note: Telangiectasias: on lips, tongue, face, GI tract/ Recurrent epistaxis/ Pulmonary AVMs: Right-to-left shunt → hypoxemia → reactive polycythemia/ Digital clubbing: Secondary to chronic hypoxia
- Labs: Isolated polycythemia (high hematocrit); platelets and WBCs normal
- Complications:
○ Brain abscess or stroke (from paradoxical emboli via AVMs).
○ Brain hemorrhage and stroke in children.
42. A 64-year-old woman with CKD on a new erythropoiesis-stimulating agent (ESA) presents with headache, nausea, BP 210/121, and retinal hemorrhages. What is the diagnosis?
➔ Hypertensive emergency due to EPO-induced hypertension
- Note: EPO: vasoconstriction (↑ α-receptor sensitivity, ↓ NO, direct smooth muscle stimulation) → hypertensive emergency.
- Risk ↑ with rapid Hb rise or high ESA dose
- Management: control BP, adjust EPO dose to slow Hb rise.
- Those treated with EPO should take iron to avoid IDA risk.
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WBCs
43. A 3-year-old boy with systemic-onset juvenile idiopathic arthritis presents with fever (104°F), petechiae, hepatosplenomegaly, lymphadenopathy, pancytopenia, and elevated liver enzymes. What is the diagnosis?
➔ Acute lymphoblastic leukemia (ALL)
- Note: Key findings:
○ Pancytopenia: ↓ Hct, WBC, platelets
○ Pallor, petechiae, fever, lymphadenopathy, hepatosplenomegaly in a child. - Next step: Bone marrow biopsy: >20% lymphoblasts in bone marrow.
- T-ALL often presents with a mediastinal mass due to thymic involvement, leading to superior vena cava syndrome, which can also be caused by non-Hodgkin lymphoma and lung cancer.
- Poor prognosis with t(9;22); better with t(12;21). Labs may show elevated lymphoblasts with TdT+.
44. A 32-year-old man presents with fatigue and easy bruising. He reports frequent nosebleeds and has noticed red spots on his legs. Physical examination shows pallor and petechiae over the lower extremities. Peripheral blood smear shows numerous myeloblasts with Auer rods. What is the most appropriate initial treatment?
➔ Treated with all-trans retinoic acid (ATRA), which induces blast maturation
- Note: Acute myeloid leukemia (AML): Characterized by myeloblasts with Auer rods (fused lysosomes). t(15;17) indicates acute promyelocytic leukemia (APL).
- The risk of DIC is high in APL.
Auer rods
The Armed Forces Institute of Pathology (AFIP) (https://commons.wikimedia.org/wiki/File:Two_myeloblasts_with_Auer_rods.jpg), „Two myeloblasts with Auer rods“, marked as public domain, more details on Wikimedia Commons: https://commons.wikimedia.org/wiki/Template:PD-US
45. A patient with progressive fatigue and weight loss over 3 months has splenomegaly and marked leukocytosis with marked basophilia and thrombocytopenia. What is the diagnosis?
➔ Chronic myelogenous leukemia (CML)
- Note: Pathophysiology: BCR-ABL → constitutive ABL kinase activation → ↑ proliferation, ↓ apoptosis→
○ WBC ↑ (36,000), platelets ↓ (70,000), normal Hct
○ Basophilia and eosinophilia.
○ Bone marrow: 100% cellular, all lines increased.
○ Fatigue, weight loss.
○ Splenomegaly (tip 8 cm below the costal margin). - Treatment: Tyrosine kinase inhibitors (imatinib).
- Leukemoid reaction is a benign response to infection or stress, with toxic granulations and Dohle bodies. high LAP, polyclonal cell activation
46. A 70-year-old man presents with fatigue and unintentional weight loss. He also reports occasional night sweats. On physical examination, he has non-tender cervical and axillary lymphadenopathy. Labs show low RBCs, WBCs, and platelets. What is the most likely finding on blood smear?
➔ Smudge cells
- Note: Chronic lymphocytic leukemia (CLL) is the most common leukemia in the elderly.
- Smudge cells result from fragile lymphocytes. CD5+, CD20+, CD23+ B cells on flow cytometry.
- Can trigger autoimmune hemolytic anemia AIHA.
Smudge cells
Mikael Häggström, M.D. Author info – Reusing images- Conflicts of interest: None Mikael Häggström, M.D.Consent note: Consent from the patient or patient’s relatives is regarded as redundant, because of absence of identifiable features (List of HIPAA identifiers) in the media and case information (See also HIPAA case reports guidance). (https://commons.wikimedia.org/wiki/File:Smudge_cell_in_a_peripheral_blood_smear.jpg), „Smudge cell in a peripheral blood smear“, https://creativecommons.org/publicdomain/zero/1.0/legalcode
47. A patient presents with progressive fatigue and unintentional weight loss. Physical examination reveals pallor and a massively enlarged spleen. Labs show low RBCs, WBCs, and platelets. Blood smear shows atypical lymphoid cells with cytoplasmic projections. What is the most appropriate treatment?
➔ Treated with cladribine (purine analog). Inhibits adenosine deaminase
- Note: Hairy cell leukemia; B-cell neoplasm. Cells have “hairy” cytoplasmic projections. Bone marrow is fibrotic → dry tap. Positive for TRAP stain.
48. A patient presents with several weeks of painless swelling on the left side of his neck. He reports night sweats, unintentional weight loss, and intense itching after drinking alcohol. Examination reveals a firm, non-tender cervical lymph node. What would a lymph node biopsy show?
➔ Reed-Sternberg cells (CD15+, CD30+)
- Note: Hodgkin lymphoma has a bimodal age distribution. Symptoms include B-symptoms: fever, night sweats, and weight loss.
- Lymphocytic-rich has the most favorable prognosis. In contrast, the lymphocyte-depleted subtype has the worst prognosis.
- Painless lymphadenopathy, particularly in the cervical, supraclavicular, and mediastinal LN. Lymph node biopsy confirms the diagnosis.
49. A 47-year-old woman with long-standing SLE presents with 1 month of fatigue, low-grade fever, 10 lb weight loss, and cervical and axillary lymphadenopathy. Labs show normal CBC except mild anemia, and elevated LDH (828 U/L). what is the diagnosis?
➔ Non-Hodgkin lymphoma (NHL)
- Note: Chronic autoimmune diseases increase NHL risk due to B-cell stimulation and immune dysregulation.
- NHL features: (painless lymphadenopathy, B symptoms → fever, weight loss, fatigue, and elevated LDH → marker of tumor burden).
- HIV infection increases the risk of NHL by reactivation of the Epstein-Barr virus in B-lymphocytes.
50. A boy from Africa is brought to the clinic with a rapidly enlarging, painless mass in the right jaw. He has no fever or weight loss. Biopsy of the lesion reveals sheets of medium-sized lymphocytes with scattered tangible body macrophages. What is the most likely diagnosis?
➔ Burkitt lymphoma
- Note: Associated with EBV. t(8;14) leads to c-myc activation.
- The endemic form affects jaw; the sporadic form affects abdomen.
- starry-sky” appearance: sheets of medium-sized lymphocytes with scattered tangible body macrophages.
- Follicular lymphoma is a common form of NHL. It presents with waxing and waning lymphadenopathy.
51. A 62-year-old woman presents with a 1-month history of mid-back pain, fatigue, cognitive changes, anemia (Hb 8), hypercalcemia (Ca²⁺ 12.4 mg/dL), renal insufficiency (Cr 2.4), and lytic skull lesions on x-ray. What is the best next step?
➔ Serum and urine protein electrophoresis, multiple myeloma
- Note: >40-year-old patient +
○ Anemia + renal failure + hypercalcemia + bone pain = CRAB criteria
○ Skull x-ray: lytic (“punched out”) lesions
○ Recurrent infection due to decreased production of functional antibodies. - Confirmatory test: Monoclonal spike (M-protein) on SPEP, RBC rouleaux formation on blood smear. Bone marrow biopsy for >10% clonal plasma cells
Rouleaux formation
Michail Charakidis, David Joseph Russell (https://commons.wikimedia.org/wiki/File:Rouleaux_formation.jpg), „Rouleaux formation“, https://creativecommons.org/licenses/by/2.0/legalcode
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52. A 65-year-old man presents with worsening headaches, blurry vision, and tingling in his hands and feet over the past several weeks. He also reports fatigue and occasional dizziness. Fundoscopy shows retinal vein engorgement. What condition best explains these findings?
➔ Waldenström macroglobulinemia
- Note: B-cell neoplasm with IgM monoclonal gammopathy. Hyperviscosity syndrome is common due to large IgM.
- Bone marrow shows <10% plasma cells (unlike multiple myeloma).
53. A patient presents with dizziness, memory loss, and diplopia, along with acute burning pain and cyanosis of the left great toe. He has had pruritus for 2 months. Labs show elevated hemoglobin (18.5), hematocrit (62%), and thrombocytosis. What is the diagnosis?
➔ Polycythemia Vera (PV), JAK2 mutation
- Note: Clinical clues:
○ Hyperviscosity symptoms: blurry vision, memory loss, dizziness
○ Erythromelalgia: burning toe pain + red/blue discoloration
○ Pruritus (esp. after warm showers)
○ Splenomegaly - Labs: ↑Hct, ↑Hb, ↑platelets, ↑uric acid, ↓ferritin
- Management: phlebotomy, Hydroxyurea, aspirin, JAK2 inhibitors (e.g., ruxolitinib)
54. A 7-year-old boy with acute lymphoblastic leukemia (ALL) is undergoing induction chemotherapy. Two days after starting treatment, he develops acute flank pain, nausea, and reduced urine output. Labs show hyperkalemia and hypocalcemia. What additional lab findings are most likely present in this patient?
➔ ↑ uric acid, ↑ phosphate, ↑ potassium, ↓ calcium
- Note: Tumor lysis syndrome; rupture of tumor cells releases intracellular contents. It can cause renal failure, arrhythmia, and seizures.
- Aggressive IV hydration is key. Allopurinol blocks xanthine oxidase to reduce uric acid. Rasburicase directly degrades uric acid. Monitor electrolytes and renal function closely.
55. A 54-year-old man with alcoholic cirrhosis, recently treated for SBP, presents with fever, chills, sore throat, and pharyngeal ulcers. He is on lactulose and TMP-SMX prophylaxis. Vitals stable. Labs show: (WBC: 1,500/mm³ and Neutrophils: 15% → ANC <500 ). What is the best next step?
➔ Drug-induced neutropenia from TMP-SMX
- Note: Other common causes of neutropenia:
○ Methimazole and propylthiouracil.
○ Clozapine.
○ Sulfasalazine.
○ Methotrexate.
○ Griseofulvin. - Scenarios for presentation: sepsis or fever + sore throat.
- Next step:
○ Stop the causative drug and give IV antibiotics.
56. A patient with a 4-month history of a right submandibular mass and occasional deep ear pain presents for evaluation. He has a heavy smoking history and no signs of infection or systemic symptoms. What is the diagnosis?
➔ Head and neck squamous cell carcinoma (SCC)
- Note: The most common cause of a solitary, firm, non-tender upper cervical lymphadenopathy in adults.
○ Often represents metastasis from mucosal SCC of the oropharynx, larynx, or hypopharynx.
○ Deep otalgia = referred pain via CN IX or X → suggests mucosal origin
○ Tobacco use is a major risk factor.
○ The next step is Laryngopharyngoscopy (endoscopic exam), looking for the primary tumor.
57. A 58-year-old woman with metastatic breast cancer is started on combination chemotherapy. Two months, she presents with progressive exertional dyspnea and lower extremity edema. Cardiac auscultation reveals S3 gallop. Chest x-ray shows cardiomegaly and pulmonary vascular congestion. What is the most likely cause of this patient’s cardiac findings?
➔ Dilated cardiomyopathy, caused by doxorubicin
- Note: Prevented with dexrazoxane, an iron-chelating agent that reduces free radicals.
- Trastuzumab also causes reversible dilated cardiomyopathy.
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Disclaimer
Version 1.0 August 2025. No part of this document may be reproduced or distributed without written permission. For personal study only. Medical information herein is for educational purposes and does not constitute clinical advice. Always confirm with current guidelines and your institution’s policies.
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