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USMLE Step 1 High‐Yield Hematology/Oncology Topics

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Hematology/Oncology

High Yield USMLE Step 1 Notes

Welcome to the Hematology/Oncology High-Yield Notes for Step 1.

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 1 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

Anemia

1. A 28-year-old woman presents with fatigue. Labs show Hb 9.5 g/dL, MCV 72 fL, ferritin 8 ng/mL, and TIBC elevated. What best explains these findings?
➔ Iron deficiency anemia (IDA)

  • Note: High RDW is specific for IDA
  • In elderly men with IDA, chronic GI blood loss, suspect colon cancer until proven otherwise ➔ Order a colonoscopy

2. A pregnant woman has mild anemia. Labs show low MCV, normal ferritin, and no improvement with oral iron therapy. What is the next diagnostic step?
➔ Hemoglobin electrophoresis

  • Note: Microcytic anemia not responding to iron, suspect thalassemia

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3. A newborn dies shortly after birth. Hemoglobin electrophoresis reveals only Hb Barts (γ4 tetramers). What best explains these findings?
➔ Alpha thalassemia major (hydrops fetalis)

  • Note: In alpha thalassemia, no α chain can be made (α chain is an essential component of all types of hemoglobin).
  • Deletion of all four α-globin genes results in nonviable hemoglobin (Hb Barts, Hemoglobin with just γ without α), causing severe hypoxia and fetal demise.
  • In normal adults: (HbA (α₂β₂) → ~95–98%; HbA₂ (α₂δ₂) → ~2–3.5%; HbF (α₂γ₂) → <1%). In newborns: HbF at birth (~80%) and transitions to HbA by 6 months.

4. 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).
  • Note: Hb electrophoresis shows increased HbF and HbA2, with little or no HbA. The child is usually transfusion-dependent by 6 months of age. Iron overload from transfusions is common, requiring chelation therapy.
  • Beta-thalassemia minor presents with mild microcytic anemia with normal iron studies, usually discovered incidentally. it has elevated HbA2.
ConditionHbA (%)HbA2 (%)HbF (%)
Normal>95%<3.5%<2%
Beta Thalassemia Minor↓ (~85-95%)↑ (>3.5%)Normal or ↑
Beta Thalassemia MajorAbsent↑ (>3.5%)↑↑

5. A child has developmental delay, constipation, and microcytic anemia. What would a Peripheral smear show?
➔ Basophilic stippling

  • Note: Lead poisoning is common in children living in old homes (usually before 1978). Treat with chelation (e.g., dimercaprol, EDTA) if levels are high.
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6. A patient being treated for tuberculosis develops microcytic anemia. What is the treatment?
➔ B6 supplementation

  • Note: Sideroblastic anemia caused by isoniazid (INH inhibits pyridoxine (B6), a cofactor in heme synthesis. Bone marrow shows ringed sideroblasts. Iron studies show increased serum iron and ferritin, decreased TIBC.

7. 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.

8. A vegan presents with paresthesia and elevated methylmalonic acid. What is the most likely explanation for this presentation?
 ➔ Vitamin B12 deficiency

  • Note: Neurologic signs include peripheral neuropathy, ataxia, and loss of vibration/proprioception.
  • Labs show macrocytic anemia, ↑ homocysteine, and ↑ methylmalonic acid. Diagnosis confirmed with low serum B12.

9. 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.
  • Findings include atrophic gastritis and ↑ the risk of gastric cancer.

10. An alcoholic patient has macrocytic anemia. What is the treatment?
 ➔ Folate

  • Note: Folate deficiency; Alcohol impairs folate absorption and metabolism. Presents with anemia but without neurologic symptoms.
  • 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

11. A patient on methotrexate develops 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. Regular CBC monitoring is needed.

12. A female with SLE presents with low hemoglobin and a positive direct Coombs test. What is the diagnosis?
 ➔ Warm autoimmune hemolytic anemia (AIHA)

  • Note: IgG-mediated hemolysis at body temperature. Common in SLE and CLL. Labs show spherocytes, ↑ LDH, ↑ bilirubin, and ↓ haptoglobin.
  • 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.

13. A patient presents with jaundice, anemia, splenomegaly, and elevated MCHC. What are the complications?
 ➔ Pigmented gallstones

  • Note: Hereditary spherocytosis; an Autosomal dominant defect in RBC membrane proteins (ankyrin, spectrin). Splenomegaly due to sequestration of spherocytes. 
  • Labs show ↑ MCHC, spherocytes on smear, negative Coombs test. Confirm with osmotic fragility or EMA binding test. Treat with folate to avoid macrocytic anemia and splenectomy in severe cases.

14. A patient develops dark urine after taking TMP-SMX. What condition best explains these findings?
➔ G6PD deficiency

  • Note: X-linked disorder causing RBC susceptibility to oxidative stress. Triggers include sulfa drugs (TMP-SMX), antimalarials, and fava beans. Avoid those triggers
  • Peripheral smear shows bite cells and Heinz bodies.

15. A patient reports red urine and fatigue in the morning, with 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, anti C5 monoclonal antibody.

16. A child presents with low hemoglobin and absent thumbs. What is the treatment?
 ➔ Treat with a stem cell transplant

  • Note: Fanconi anemia; an Autosomal recessive or X-linked disorder causing DNA repair defects. Associated with aplastic anemia, congenital anomalies (absent/radial thumbs, short stature), café-au-lait spots, and increased cancer risk (esp. AML).

17. A patient complains of fatigue, has a low RBC count, and elevated 2,3-BPG. What is the most likely explanation for this presentation?
 ➔ Pyruvate kinase deficiency

  • Note: Hemolytic anemia due to decreased ATP production. RBCs are rigid and removed by the spleen. ↑ 2,3-BPG shifts the oxygen dissociation curve right

18. A child with sickle cell disease develops left upper quadrant pain, anemia, and elevated retic count. What is the diagnosis?
 ➔ Splenic sequestration crisis

  • Note: Pooling of blood in the spleen ➞ hypovolemic shock, splenomegaly, and high RC.
  • Aplastic crisis due to parvovirus presents with low reticulocytes and no splenomegaly

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19. 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: Triggered by infection. treat with oxygen, antibiotics, transfusion, and pain control.

20. A child with known sickle cell disease presents with acute neurologic deficits (e.g., stroke). How could we have prevented his symptoms?
 ➔ Prevention with hydroxyurea or chronic transfusion

  • Note: Vaso-occlusive crisis; Caused by sickled RBCs blocking small vessels. Other signs include dactylitis, pain crises, and priapism.

21. A sickle cell patient with fever, sepsis signs, and Howell-Jolly bodies on smear. What is your next step?
➔ Require vaccination and prophylactic antibiotics

  • Note: Autosplenectomy; Chronic infarction of spleen leads to functional asplenia. Howell-Jolly bodies are nuclear remnants seen in asplenic patients.
  • These patients are at high risk for infections by encapsulated organisms (e.g., S. pneumoniae, H. influenzae, N. meningitidis).

22. A patient with sickle cell trait presents with painless hematuria. What is the most likely explanation for this presentation?
 ➔ Renal papillary necrosis

  • Note: Sickle cell trait is usually asymptomatic but can cause ischemic necrosis of renal papillae. Urinalysis shows hematuria without casts or proteinuria.
  • NSAIDs can cause papillary necrosis

23. A neonate develops severe jaundice within the first 24 hours of life. What is the diagnosis?
 ➔ Rh incompatibility

  • Note: Occurs when an Rh-negative mother forms anti-D antibodies against an Rh-positive fetus, leading to hemolytic anemia and jaundice in the first day. It can cause hydrops fetalis.
  • Prevented with Rho(D) immune globulin during pregnancy and postpartum.
  • It affects the second pregnancy VS ABO incompatibility affects the first.

24. A type O mother delivers a baby with jaundice in the first 24 hours. What is the diagnosis?
 ➔ ABO incompatibility

  • Note: Most common cause of hemolytic disease in newborns. Affects first pregnancy. Less severe than Rh incompatibility. Coombs test is positive.
  • Treat with phototherapy.

25. 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.

26. A man presents with blisters on sun-exposed areas. What condition is mostly associated with his symptoms?
➔ Hepatitis C

  • Note: Porphyria cutanea tarda (PCT); Presents with chronic blistering photosensitivity, skin fragility, and hyperpigmentation.
  • Treat with phlebotomy and low-dose hydroxychloroquine.
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Coagulation & Bleeding disorders

27. A female presents with bruises, prolonged bleeding time, and platelet count of 50,000. What condition best explains these findings?
 ➔ Immune thrombocytopenic purpura (ITP)

  • Note: Often follows viral illness or associated with HIV/HCV. Autoantibodies against platelets lead to increased destruction.
  • Labs show thrombocytopenia, prolonged bleeding time, normal PT, and PTT.
  • First-line treatment is corticosteroids. Splenectomy is second for steroid-resistant ITP.

28. A child has bruises, normal platelets, prolonged bleeding time, and no agglutination with ristocetin. What is the 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.

29. A patient with chronic kidney disease has 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.

30. A boy presents with hemarthrosis and prolonged PTT, with normal PT. What is the diagnosis?
 ➔ Hemophilia A or B

  • Note: X-linked recessive disorders. Hemophilia A = factor VIII deficiency, Hemophilia B = factor IX deficiency. PTT is elevated, and PT is normal.
  • Classic signs include joint bleeding, muscle hematomas. Positive family history is common.

31. A neonate born at home presents with bleeding from the umbilical stump. What is the treatment?
 ➔ Vitamin K, for both treatment and prevention

  • Note: Vitamin K deficiency; Common in neonates who do not receive prophylactic vitamin K. Causes bleeding from mucosa, umbilicus, or intracranial. Labs show ⇑ PT and ⇑ PTT, normal platelets.
  • Vitamin K is a fat-soluble vitamin (A, D, E, K). it decreases in conditions with fat malabsorption as Crohn’s disease

32. A female with menorrhagia, epistaxis, bleeding after dental extraction, and labs showing ⇑ BT and ⇑ PTT with normal PT.what is the treatment?
 ➔ Desmopressin 

  • Note: Von Willebrand disease; Most common inherited bleeding disorder. Defective platelet adhesion due to ↓ vWF. vWF also stabilizes factor VIII → ↑ PTT. Ristocetin test is abnormal.

33. A patient with sepsis develops bleeding from catheter and IV sites. What condition best explains these findings?
 ➔ Disseminated intravascular coagulation (DIC)

  • Note: Triggered by infection, trauma, malignancy, or obstetric complications. Consumptive coagulopathy. Labs show ⇑ PT, ⇑ PTT, ⇑ BT, ⇑ D-dimer, ⇓ fibrinogen, ⇓ platelets. Schistocytes may be seen.
  • Treat the underlying cause and fresh frozen plasma.

34. A postpartum woman develops shortness of breath and bleeding from IV sites. What are the lab findings?
 ➔ ↑ PT/PTT/BT/D-dimer, ↓ fibrinogen and platelets

  • Note: Disseminated intravascular coagulation (DIC) due to amniotic fluid embolism: Amniotic fluid in maternal circulation triggers massive coagulation and fibrinolysis. Presents with respiratory distress, hypotension, and bleeding.

35. A female with SLE presents with DVT and prolonged PTT that does not correct with mixing study. What is the diagnosis?
 ➔ Antiphospholipid syndrome

  • Note: presents as recurrent pregnancy loss, arterial or venous thrombosis are key features. Part of SLE or primary.
  • Positive for anticardiolipin, beta-2 glycoprotein I, or lupus anticoagulant. Requires lifelong anticoagulation. Lupus anticoagulant prolongs PTT but no bleeding.

36. A patient with nephrotic syndrome develops DVT or renal vein thrombosis. What is the diagnosis?
 ➔ Antithrombin III deficiency

  • Note: Nephrotic syndrome leads to urinary loss of antithrombin III, increasing clot risk. May also be congenital.
  • Heparin may not be effective, “no elevation in PTT”. Consider direct thrombin inhibitors.

37. A patient has recurrent venous clots. What is the most likely etiology?
 ➔ Factor V Leiden mutation

  • Note: Most common inherited thrombophilia. Mutation makes factor V resistant to inactivation by protein C. Leads to increased risk of DVT, PE. Normal PT/PTT.
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Heme Pharmacology

38. How do you monitor heparin therapy? What is the reversal agent?
 ➔ Monitor with PTT. Reverse with protamine sulfate

  • Note: Heparin binds to antithrombin III (ATIII), inhibiting Thrombin (Factor IIa) → ↓ fibrin formation and Factor Xa → ↓ conversion of prothrombin to thrombin.
  • Warfarin is teratogenic; heparin is safe in pregnancy

39. A patient on heparin develops a 50% drop in platelet count. What is the diagnosis?
 ➔ Heparin-induced thrombocytopenia (HIT)

  • Note: Type II hypersensitivity. IgG antibodies form against the heparin-platelet factor 4 complex. The risk of thrombosis is high.
  • Stop heparin and start a direct thrombin inhibitor (e.g., argatroban or dabigatran)

40. What is the mechanism of warfarin?
 ➔ Inhibits vitamin K epoxide reductase ➞ ⇓ synthesis of factors II, VII, IX, X, and protein C, S. we use PT/INR for monitoring

  • Note: The toxicity of warfarin leads to bleeding. FFP provides immediate clotting factors. Vitamin K takes several hours to reverse the effect.

41. 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.

42. What is the mechanism and advantage of rivaroxaban?
 ➔ Factor Xa inhibitor

  • Note: Direct oral anticoagulant (DOAC). No routine monitoring needed. Fewer food and drug interactions. Andexanet alfa is the reversal agent.

43. What is the mechanism of aspirin?
 ➔ Irreversibly inhibits COX-1 and COX-2 → ↓ thromboxane A2

  • Note: Inhibits platelet aggregation.
  • clopidogrel inhibits ADP receptor (P2Y12) on platelets ➞ ⇓ aggregation. Used in patients with aspirin allergy or in dual antiplatelet therapy after MI.

44. What is the mechanism and contraindications of thrombolytics like tPA?
 ➔ Convert plasminogen to plasmin → degrades fibrin

  • Note: The contraindications are active bleeding, recent stroke or surgery, or severe hypertension >180/110.
  • The reversal agent of TPA is aminocaproic acid and tranexamic acid, an antifibrinolytic agent.
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Leukemia & Lymphoma

45. A child presents with bone pain, fatigue, pallor, lymphadenopathy, and a mediastinal mass. What condition best explains these findings?
➔ T-cell acute lymphoblastic leukemia (T-ALL)

  • Note: T-ALL often presents with a mediastinal mass due to thymic involvement. Common in adolescent males. Poor prognosis with t(9;22); better with t(12;21). Labs may show elevated WBCs and lymphoblasts with TdT+.

46. A patient presents with fatigue and petechiae. Peripheral smear shows Auer rods. What is the 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.

47. An elderly patient presents with fatigue, lymphadenopathy, and a smear showing smudge cells. What is the diagnosis?
 ➔ Chronic lymphocytic leukemia (CLL)

  • Note: Most common adult leukemia. Smudge cells result from fragile lymphocytes. CD5+, CD20+, CD23+ B cells on flow cytometry.

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48. A patient presents with fatigue, splenomegaly, elevated basophils, and low leukocyte alkaline phosphatase (LAP). What is the most likely associated gene mutation?
➔ BCR-ABL fusion, Associated with t(9;22), CML, leukocytosis with left shift and basophilia. Low LAP

  • Note: Targeted therapy with imatinib, a tyrosine kinase inhibitors is effective
  • Note: Leukemoid reaction is a benign response to infection or stress, with toxic granulations and Dohle bodies. = high LAP, polyclonal cell activation

49. A patient has pancytopenia, massive splenomegaly, and a dry tap on bone marrow aspiration. What is the 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.

50. A patient presents with cervical lymphadenopathy, night sweats, and itching after alcohol intake. What would smear show?
➔ Reed-Sternberg cells (CD15+, CD30+)

  • Note: Hodgkin lymphoma has bimodal age distribution. Symptoms include B-symptoms: fever, night sweats, and weight loss.
  • Note: lymphocytic-rich has the most favorable prognosis. In contrast, the lymphocyte-depleted subtype has the worst prognosis.

51. An African boy has a jaw mass. Biopsy shows “starry-sky” appearance. What is the 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.

52. A patient with H. pylori infection develops gastric MALT lymphoma. What is the most likely etiology?
 ➔ Marginal zone lymphoma

  • Note: May regress with H. pylori eradication using PPI + antibiotics.
  • Follicular lymphoma presents with painless waxing and waning lymphadenopathy. t(14;18) causes overexpression of bcl-2, inhibiting apoptosis.

53. An HIV-positive patient presents with a solitary ring-enhancing brain lesion. What is the diagnosis?
 ➔ Primary CNS lymphoma

  • Note: Associated with EBV, mostly single nodule VS toxoplasmosis, which is multiple.

54. A patient develops scaly skin patches, nodules, and lymphadenopathy. What condition best explains these findings?
 ➔ Mycosis fungoides (cutaneous T-cell lymphoma)

  • Note: Malignant CD4+ T cells infiltrate the skin. Pautrier microabscesses on biopsy. Can progress to Sezary syndrome (leukemic phase with cerebriform nuclei on smear).

55. An elderly patient presents with back pain, hypercalcemia, and anemia. What is the diagnosis?
 ➔ Multiple myeloma

  • Note: Plasma cell malignancy, Common in older adults. CRAB criteria: hyperCalcemia, Renal failure, Anemia, Bone lesions. 
  • Associated with high serum protein and rouleaux formation. M-spike (IgG or IgA), , elevated ESR, Bence-Jones proteins in urine. Bone marrow shows >10% clonal plasma cells.

56. A patient presents with headaches, blurry vision, and peripheral neuropathy. 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).

57. A child with ALL on chemotherapy develops flank pain, hyperkalemia, and hypocalcemia. What lab findings are most likely be there?
 ➔ ↑ 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.
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Oncology Pharmacology

58. A cancer patient on methotrexate develops stomatitis and pancytopenia. What reverses this toxicity?
 ➔ Leucovorin (folinic acid), can also cause liver toxicity and stomatitis

  • Note: Bypasses the inhibited enzyme. Given to reduce toxicity without decreasing efficacy.
  • Inhibits dihydrofolate reductase ➞ ⇓ dTMP synthesis ➞ inhibits DNA replication.

59. A cancer patient on 6-mercaptopurine develops toxicity after starting allopurinol. What is the explanation?
 ➔ 6-MP is degraded by xanthine oxidase → allopurinol inhibits this enzyme

  • Note: The dose of 6-MP should be reduced when combined with allopurinol.

60. What is the major toxicity of cyclophosphamide?
 ➔ Hemorrhagic cystitis and bladder cancer

  • Note: Prevented with MESNA, which binds toxic metabolites like acrolein.

61. Which drugs cause pulmonary fibrosis?
 ➔ Busulfan, Bleomycin, Methotrexate, and Amiodarone

  • Note: Monitor with pulmonary function tests during therapy.

62. What is the mechanism and toxicity of vincristine?
 ➔ Inhibits microtubule formation → prevents mitotic spindle formation

  • Note: Causes peripheral neuropathy

63. What is the major toxicity of doxorubicin?
 ➔ Dilated cardiomyopathy

  • Note: Prevented with dexrazoxane, an iron-chelating agent that reduces free radicals. trastuzumab also causes reversible dilated cardiomyopathy.

64. A chemotherapy patient develops pancytopenia and fever 101.8°F. What is the diagnosis?
 ➔ Neutropenic fever

  • Note: Stop the drug and start empiric IV broad-spectrum antibiotics immediately.
  • It also causes aplastic anemia due to damage to hematopoietic stem cells.

65. What is the mechanism and use of bortezomib?
 ➔ Proteasome inhibitor → induces apoptosis → used in multiple myeloma

  • Note: Inhibits degradation of pro-apoptotic factors.

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🏁 Final Thoughts

You made it to the end—well done! These high-yield notes are designed to save you time and keep you focused on what actually matters for Step 1. Review these vignettes regularly—steady practice beats cramming.

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Disclaimer

Version 1.0 May 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.

Prefer a narrative review instead of Q&A style? Scroll down to the section below for high-yield concepts in paragraph format (they cover the same concepts).

Narrative Format

High-Yield Hematology/Oncology Topics

USMLE Step 1 Hematology/Oncology: Master high-yield facts on anemias, hemolysis, leukemias, lymphomas, myeloma, myeloproliferative disorders, hemostasis & chemo.

Table of Contents

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Microcytic Anemias (MCV <80 fL)

Iron Deficiency Anemia (IDA) – Most Common

  • Chronic blood loss (GI bleed especially cancers, menorrhagia), pregnancy, Celiac disease.
  • ↓ Iron, ↓ Ferritin, ↑ TIBC, ↑ RDW, Microcytic, and hypochromic RBCs with central pallor.
  • Symptoms: Fatigue, pallor, pica (craving for ice, dirt), koilonychia (spoon nails), glossitis.
  • Treatment: Oral iron (ferrous sulfate) + Vitamin C to enhance absorption.

How it is tested: 1. Arrows q for iron studies.  2. An old with iron def anemia→ colonoscopy.  3. A woman with pica (ice craving) → screen IDA.

Thalassemias – Defective Globin Synthesis “normal Fe studies”

α-Thalassemia: Gene deletions

  • 1 deletion: Silent carrier
  • 2 deletions: α-thalassemia trait (mild anemia)
  • 3 deletions: HbH disease (β₄ tetramers, severe anemia)
  • 4 deletions: Hydrops fetalis (Hb Barts, γ₄)

β-Thalassemia: Point mutations

  • Minor: Mild anemia or asymptomatic, ↑ HbA₂ (>3.5%) on electrophoresis
  • Major: Absent β-globin → Severe anemia, crew-cut skull, chipmunk facies, hepatosplenomegaly, B19 aplastic crisis. Target cells on blood smear. ↑ HbA₂, ↑ HbF, ↓ HbA1 Treatment: Lifelong transfusions + Iron chelation (Deferoxamine)

How it is tested: 1. a pregnant with microcytic anemia with “normal Fe studies” → Hb electrophoresis. 2. For a patient with microcytic anemia that did not respond to iron, next step is Hb electrophoresis looking for thalassemia. 3. Arrows q for ↓HBA1, ↑HBA2, ↑HBF.

Sideroblastic Anemia (↓ALA synthase → ↓Heme Synthesis)

  • Causes: Lead poisoning, alcohol, B6 deficiency (INH therapy).
  • ↑ Iron, ↑ Ferritin, ↓ TIBC, ringed sideroblasts, and Basophilic stippling.
  • Treatment: Pyridoxine (B6, cofactor for ALA synthase).

How it is tested:   A patient treated from TB with microcytic anemia, Treatment is B6.

Normocytic Anemias (MCV 80–100 fL)

  1. Hemolytic Anemias

Intravascular hemolysis (schistocytes, ↓ haptoglobin, ↑ LDH, ↑ free Hb, hemoglobinuria):

  • Microangiopathic hemolytic anemia (DIC, HUS, TTP), Mechanical destruction (prosthetic valves), and Paroxysmal nocturnal hemoglobinuria (PNH).

Extravascular hemolysis (spherocytes, normal haptoglobin, jaundice, splenomegaly):

  • Hereditary spherocytosis and Autoimmune hemolytic anemia.

Sickle Cell Disease (SCD)

  • Mutation in β-globin gene (Glu → Val substitution) → Sickling triggered by Hypoxia, dehydration, and acidosis.
  • Sequestration crisis: congestion of spleen by sickle cells “acute anemia”. How it is tested: A patient with acute LUQ pain and acute anemia with high reticulocytes.
  • Painful vaso-occlusive crises: dactylitis (painful swelling of hands/feet), priapism, acute chest syndrome (How it is tested: respiratory distress, new pulmonary infiltrates on CXR), avascular necrosis of bones, stroke (How it is tested: a S.C.D patient with stroke).
  • Sickling in renal medulla → Renal papillary necrosis (also in sickle cell trait).
  • Autosplenectomy: ↑risk of infection by encapsulated organisms (pneumococcus, meningococcus, and h.influenza). Howell-Jolly bodies on blood smear. (How it is tested: sepsis in a S.C.D patient )
  • Aplastic crisis with parvovirus B19 “acute anemia”.
  • Sickled RBCs, Howell-Jolly bodies (asplenia), ↑ Reticulocytes, ↓↓ HBA1, ↑HBA2, ↑↑HBS. How it is Tested: Arrows q for HBA, HBA, HBF, and HBS.
  • Treatment: Hydroxyurea (↑ HbF), hydration, pain control, and folic acid.
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G6PD Deficiency (X-Linked recessive)

  • ↓ G6PD → ↓ NADPH → ↓ Glutathione → Oxidative stress → Hemolysis, triggered by Fava beans, sulfa drugs, antimalarials, infections. Heinz bodies, and bite cells on smear.

How it is tested: A man complains of dark urine and fatigue. He had a recent UTI treated with TMP-SMX → G6PD deficiency.

Autoimmune Hemolytic Anemia (AIHA)

Warm AIHA (IgG-mediated, at body temperature, extravascular hemolysis)

  • The most common type, is associated with SLE, CLL, and drugs (penicillin).
  • Treatment: → Steroids, rituximab, splenectomy if refractory.

Cold AIHA (IgM-mediated, cold exposure)

  • Seen in Mycoplasma pneumoniae and IMN.
  • Causes acrocyanosis (painful, blue fingers/toes in cold temperatures). Avoid cold.

Coombs Test is positive, with spherocytes in warm AIHA and agglutinated RBCs in cold AIHA.

How it is tested: 1. A patient with hemolytic anemia plus a positive Coombs test. 2. A patient with hemolytic anemia after being treated with penicillin“TMP-SMX and Nitrofurantoin “G6PD def”.

Hereditary Spherocytosis (HS)

AD RBC membrane defect (ankyrin, spectrin, band 3, or protein 4.2) → spherocytes and hemolysis in the spleen → anemia, jaundice, splenomegaly, and ↑ pigmented gallstones.

  • ↑ MCHC, Spherocytes (NO central pallor). EMA and Osmotic fragility test positive (lysis in hypotonic solutions)
  • Ttt: Folic acid (to prevent folic deficiency anemia) and Splenectomy.

How it is tested: 1. A patient with anemia, ↑ Reticulocytes, splenomegaly, or gallstones. 2. A patient with anemia and ↑ MCHC.

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Acquired mutation in PIGA gene → Defective GPI-anchor proteins (CD55, CD59) → Loss of complement regulation → Complement-mediated intravascular hemolysis.

  • Hemolysis → hemoglobinuria (in the morning, due to complement activation at night).
  • Thrombosis → Budd-Chiari syndrome (hepatic vein thrombosis), portal vein thrombosis.
  • Flow cytometry → Absence of CD55 & CD59 on RBCs, negative Coombs test.
  • Ttt: Eculizumab (Anti-C5 monoclonal antibody, prevents complement activation).

How it is tested: 1. A patient complains of morning fatigue and dark urine. 2. a patient with sudden RUQ pain and hepatomegaly (hepatic vein thrombosis).

Pyruvate Kinase Deficiency:

↓ ATP in RBC membrane → hemolysis and ↑ 2,3BPG.

How it is tested:  A patient with hemolytic anemia and ↑ 2,3BPG

Non- Hemolytic Anemias

Anemia of Chronic Disease (ACD)

  • Associated with chronic inflammation (RA, CKD, MM, TB) → ↑ Hepcidin, which inhibits iron release from macrophages and iron absorption from the intestine → ↓ Iron, ↑ Ferritin, ↓TIBC.
  • Treatment: Treat underlying disease, consider EPO in CKD.

How it is tested: 1. A patient with RA and low iron but high ferritin, ttt of his anemia → methotrexate. 2. Arrows q for iron studies.

Aplastic Anemia

Pancytopenia (↓ RBCs, WBCs, platelets) due to stem cell destruction or suppression:

Idiopathic (most common), autoimmune, Drugs: “Chloramphenicol, carbamazepine, methimazole, PTU, and chemotherapy”, Viruses: (B19, EBV, HIV), Fanconi anemia (DNA repair defect, presents with thumb abnormalities, short stature, and café-au-lait spots).

  • Fatigue, pallor – Frequent infections – Mucosal bleeding, petechiae – NO hepatosplenomegaly or lymphadenopathy (VS leukemia).
  • (↓ RBCs, ↓ WBCs, and ↓ platelets), Low Reticulocyte count, ↑ Erythropoietin (EPO).
  • Bone marrow biopsy → Hypocellular, fat-filled marrow (“dry tap”).
  • Ttt: Bone marrow transplant, G-CSF (Filgrastim) to boost neutrophils.

How it is tested: A patient presents with anemia and Low Reticulocyte count. Further investigations would show → pancytopenia with hypocellular marrow on biopsy.

Macrocytic Anemias (MCV >100 fL)

(Impaired DNA Synthesis, Hypersegmented Neutrophils)

Vitamin B12 Deficiency (Cobalamin):

  • Pernicious anemia (autoimmune, anti-parietal cell Abs), gastrectomy, vegan diet, Crohn’s, chronic pancreatitis, and Diphyllobothrium latum → ↑ Methylmalonic acid, ↑ Homocysteine.
  • Neurologic defects (subacute combined degeneration, ataxia, paresthesia, dementia).
  • Treatment: IM B12 (if we give folate, anemia resolves while neuro symptoms worsen).

How it is tested: 1. A vegan or Crohn’s patient with neuropathy and fatigue. 2. Arrow questions for ↑ Methylmalonic acid, ↑ Homocysteine. 3. A patient with abdominal pain and anemia→ Pernicious anemia.

Folate Deficiency:

  • Alcoholism, pregnancy, hemolytic anemia, drugs as “methotrexate, TMP, phenytoin”→ Normal methylmalonic acid, ↑ Homocysteine → Anemia with no neurologic symptoms. Treated with Folate supplementation.

How it is tested: 1. An alcoholic with macrocytic anemia. 2. Arrow questions for normal Methylmalonic acid, ↑ Homocysteine.

Hemolytic Disease of the Newborn

Rh Incompatibility (Severe, Preventable)

  • Rh-negative mother exposed to Rh-positive fetal blood (during delivery, abortion, trauma) → Mother develops anti-D IgG antibodies → In subsequent pregnancies, maternal IgG crosses placenta → Attacks Rh+ fetal RBCs → Severe hemolysis → Hydrops fetalis: (severe anemia → high-output heart failure, ascites, pleural/pericardial effusion, anasarca).
  • Coombs test positive.

Prevention: Rh-negative mothers get Rh(D) immune globulin (RhoGAM) at 28 weeks & postpartum.

ABO Incompatibility (Mild, Common, Can Occur in First Pregnancy)

  • Type O mother performs anti-A and anti-B IgG antibodies. If fetus is A, B, or AB, maternal antibodies cross placenta → Mild hemolysis, mild jaundice in the first 24 hours of life.

Treatment: Phototherapy or Exchange transfusion if severe.

1 Lead Poisoning

inhibits ferrochelatase and ALA dehydratase, decreasing heme synthesis → Microcytic, hypochromic anemia with basophilic stippling (rRNA aggregates). Exposure at battery factory, ammunition, and old houses before 1978 or a child with pica-eating pencils.

2 LEAD:

  1. Lead lines on gingivae (Burton lines) and on metaphyses of long bones.
  2. Encephalopathy (headache, irritability, growth delay), p.neuropathy, and Erythrocyte basophilic stippling.
  3. Abdominal colic and sideroblastic Anemia.
  4. Drop wrist and Drop foot. EDTA, Dimercaprol, and succimer for chelation.
  • ↑ Blood lead levels, ↑ Zinc protoporphyrin, ↑ ALA (Aminolevulinic acid) in urine.

How is it tested: 1. A child with developmental delay, irritability, and constipation. Blood smear would show → basophilic stippling. 2. A patient with tingling and burning in his hands, constipation and fatigue. DX → Lead Poisoning.

2 Acute Intermittent Porphyria (AIP)

Deficiency of porphobilinogen deaminase → buildup of porphobilinogen and ALA → (“5 P’s”):

Painful abdomen (severe, colicky), Port wine-colored urine (darkens with air exposure).

Polyneuropathy (motor neuropathy, autonomic dysfunction), Psychiatric disturbances (hallucinations, anxiety, confusion). Precipitated by P450 inducers, alcohol, starvation. Treated by IV glucose & hemin (inhibit ALA synthase).

How is it tested: a woman with recurrent abdominal pain, dark urine, and irritability, especially after fasting → AIP.

3. Porphyria Cutanea Tarda (PCT)

Deficiency of uroporphyrinogen decarboxylase (UROD) → Buildup of uroporphyrin → Blistering photosensitivity and Hyperpigmentation in sun-exposed areas). Associated with Hepatitis C.

How is it tested: a man with Hep C, alcohol use, and blistering skin lesions on sun-exposed areas, treat with phlebotomy.

Ttt: Phlebotomy (reduces iron load, decreases porphyrin production). Hydroxychloroquine (enhances porphyrin excretion), and Avoidance of sun exposure.

Leukemias

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General leukemia symptoms;

Infiltration of bone marrow decreasing RBCS “anemia”, platelets “bleeding tendency”, WBCS “infections” , cytokines release “ fever, night sweats, weight loss”, lymphadenopathy, and hepatosplenomegaly often.

Acute Lymphoblastic Leukemia (ALL): General Sx +

  • Most common childhood leukemia, associated with Down syndrome (after age 5), (TdT+).
  • B-ALL (CD10+, CD19+, CD20+) →invades brain and scrotum, t(12;21) (good prognosis), t(9;22) (poor prognosis, Philadelphia chromosome).
  • T-ALL (CD2–CD8, NO CD10) → Mediastinal mass (SVC syndrome, edema in upper body).

How it is tested: A 6-year-old boy with bone pain, fever, fatgue and lymphadenopathy, CXR shows a mediastinal mass→ ALL, T type.

Chronic Lymphocytic Leukemia (CLL): General Sx +

  • Most common adult leukemia (>60 years), Smudge cells on peripheral smear.
  • Richter transformation → Can progress to Diffuse Large B-cell lymphoma.

How it is tested: A 64-year-old patient with fatigue, bruises, and painless lymphadenopathy, blood smear shows smudge cells → CLL.

Acute Myeloid Leukemia (AML): General Sx +

  • ↑ Myeloblasts with Auer rods (myeloperoxidase/MPO+ granules).
  • t(15;17), PML-RARA fusion → Treat with ATRA (all-trans retinoic acid): induces maturation and differentiation of abnormal cells. DIC is a common complication in AML.

How it is tested: A 45-year-old patient with fatigue, bruising, and lymphadenopathy, with a blood smear showing Auer rods → AML, check for t(15;17).

Chronic Myeloid Leukemia (CML): General Sx +

  • t(9;22) Philadelphia chromosome (BCR-ABL, ↑ Tyrosine kinase activity), ttt: Imatinib (tyrosine kinase inhibitor).
  • Basophilia (hallmark), left shift (immature WBCs), eosinophilia, and low LAP score (vs. leukemoid reaction; high LAP, low basophils and esinophils).

How it is tested: 1. A patient with General Sx, basophilia, and low LAP → CML, treat with imatinib.

2. A patient with monoclonal cell activation of WBCs following an infection while leukomoid reaction shows polyclonal activation.

Hairy Cell Leukemia: General Sx +

  • Massive splenomegaly (red pulp expansion), Pancytopenia, TRAP +, dry tap on bone marrow aspiration, ttt: Cladribine (adenosine analog, inhibits adenosine deaminase).

How it is tested: A middle-aged man with splenomegaly and pancytopenia. Blood smear shows hairy cells. Bone marrow biopsy would show → fibrosis and no marrow cells.

Myeloproliferative neoplasms

Polycythemia Vera (PV)

  • JAK2 mutation → Uncontrolled RBC production leading to hyperviscosity (headache, blurry vision, thrombosis – Budd-Chiari), pruritus after hot shower. ↓ EPO (secondary polycythemia has ↑ EPO).
  • Treatment: Phlebotomy and hydroxyurea.

How it is tested: 1. A patient with headaches, itching after hot showers, and ↑ Hb/Hct → Polycythemia Vera, low EPO. 2. Arrows questions for HCT and EPO.

Myelofibrosis

  • JAK2 mutation → Atypical megakaryocytes → Excess fibroblast activity → Bone marrow fibrosis → Extramedullary hematopoiesis (splenomegaly). Teardrop RBCs (dacrocytes), dry tap on bone marrow biopsy.
  • Treatment: Ruxolitinib (JAK2 inhibitor).

How it is tested: A patient with massive splenomegaly, tear-drop RBCs, and dry tap → Myelofibrosis.

Essential Thrombocythemia

  • JAK2 mutation → ↑ Platelets, megakaryocytes ↑ risk of thrombosis & bleeding, ttt: Hydroxyurea, aspirin (if thrombosis risk).

Lymphomas

Hodgkin Lymphoma (HL)

  • Reed-Sternberg cells (CD15+, CD30+ B-cells, “Owl-eye nuclei”), Bimodal age distribution (young and elderly), Localized L.N groups, contiguous spread. EBV association.
  • Constitutional B symptoms (fever, night sweats, weight loss), and pruritus with alcohol.
  • Subtypes: Nodular Sclerosis is the most common, Lymphocytic-rich has the best prognosis, while Lymphocytic-depleted has the worst prognosis.

How it is tested: A young adult with painless cervical lymphadenopathy, night sweats, and pruritic with alcohol → Hodgkin Lymphoma, “Reed-Sternberg cells”.

Non-Hodgkin Lymphoma (NHL)

B-cell Neoplasms:

Follicular Lymphoma

  • t(14;18), BCL-2 overexpression (anti-apoptotic), waxing and waning painless lymphadenopathy.

How it is tested: A middle-aged patient with fluctuating lymphadenopathy → Follicular Lymphoma.

Burkitt Lymphoma

  • t(8;14), c-MYC activation → increased transcription.
  • Starry-sky appearance (macrophages among lymphoma cells).
  • Endemic in Africa (jaw mass, EBV-associated) vs. Sporadic (abdominal mass).

How it is tested: A child with a jaw mass in Africa → Burkitt Lymphoma.

Mantle Cell Lymphoma

  • t(11;14), Cyclin D1 overexpression. Aggressive with poor prognosis.

Marginal Zone Lymphoma (MALT Lymphoma)

  • Associated with untreated chronic inflammation (H. pylori, Sjögren, Hashimoto, and celiac disease). It may regress with treating the underlying cause.

How it is tested: A patient with chronic H. pylori infection and gastric lymphoma. ttt → H pylori regimen.

Primary CNS Lymphoma:

HIV patient infected with EPV → Ring-enhancing brain mass elevating intracranial pressure, while toxoplasmosis multiple rings.

How it is tested: HIV patient with headache, vomiting, and papilledema. Brain MRI shows a ring-enhancing lesion → Primary CNS Lymphoma

T-cell neoplasms:

Cutenous T-cell lymphoma: “mycosis fungoids”

Erythematous skin patches, and lymphadenopathy.

Plasma Cell Neoplasm

  1. Multiple Myeloma (MM) :

Malignant proliferation of monoclonal plasma cells in the bone marrow → Excessive IgG or IgA production→  Monoclonal M spike (IgG) on Serum protein electrophoresis (SPEP)→ CRAB:

C – HyperCalcemia (osteoclasts activated by cytokines → bone lysis → fractures, confusion).

R – Renal failure (Bence Jones proteins → Cast nephropathy).

A – Anemia (BM infiltration → ↓ RBCs).  B – Bone lytic lesions ” punched out” on x-ray.

  • Peripheral smear: Rouleaux formation (stacked RBCs), Bone marrow biopsy: >10% clonal plasma cells.
  • ↑ Infections (↓ normal Ig production). Amyloidosis (AL type).
  • Treated by Bortezomib: Proteasome inhibitors leading to abnormal protein accumulation inside the cells activating apoptosis.

How it is tested: An elderly patient with back pain, anemia, hypercalcemia→ Multiple Myeloma.

2. Waldenström Macroglobulinemia (WM): “Excess IgM production”

  • Hyperviscosity Syndrome:

Blurry vision, headaches, retinal hemorrhages, and Neuropathy (demyelination).

  • SPEP: IgM monoclonal M spike, Bone marrow: >10% small lymphoplasmacytic cells.

How it is tested: A patient with blurred vision, headaches, and IgM spike → Waldenström Macroglobulinemia.

Langerhans Cell Histiocytosis (LCH)

  • Clonal proliferation of Langerhans cells (CD1a+, S100+, Birbeck granules on EM).
  • Lytic bone lesions, rash, recurrent otitis media (mastoid involvement).

How it is tested: A child with lytic skull lesions, rash, and otitis media → Langerhans Cell Histiocytosis.

Tumor lysis syndrome

Massive tumor cell lysis, leading to the release of intracellular contents into the bloodstream spontaneously or after chemotherapy.

  • ↑ Phosphate → binds calcium, leading to hypocalcemia, causing tetany and seizures.
  • ↑ Uric acid due to purine breakdown → Forms crystals and causes acute kidney injury.
  • ↑ Potassium (Hyperkalemia) → arrhythmias and muscle weakness.

How it is tested: 1. A child with ALL started on chemotherapy develops flank pain, hematuria, high BUN, and Cr → urate crystals of TLS. 2. Arrows q for K, Ca, and P.

4. Prevention & Treatment

  • Aggressive IV hydration (prevents uric acid crystallization in kidneys).
  • Allopurinol (Xanthine oxidase inhibitor, prevents uric acid formation).
  • Rasburicase (Recombinant uricase, converts uric acid to allantoin for renal excretion).

Physiology of Coagulation & Platelet Plug Formation

Primary Hemostasis (Platelet Plug Formation – “Adhesion, Activation, Aggregation”)

Endothelial injury → Exposure of collagen & vWF → Platelet adhesion: vWF binds to GpIb receptor on platelets → Platelet activation: Release of ADP (induces GpIIb/IIIa expression), TXA₂ (vasoconstriction, aggregation) → Platelet aggregation → GpIIb/IIIa binds fibrinogen → Platelet plug forms.

Secondary Hemostasis (Coagulation Cascade – Fibrin Clot Formation)

  • Intrinsic Pathway (PTT – Heparin) → Activated by subendothelial collagen (Factor XII).
  • Extrinsic Pathway (PT – Warfarin) → Activated by tissue factor (Factor VII).
  • Final Common Pathway: Factor Xa converts prothrombin (II) → thrombin (IIa), which converts fibrinogen → fibrin clot.
  • Fibrinolysis: tPA converts plasminogen → plasmin → Cleaves fibrin, breaks clots.

How it is tested: PTT monitors Heparin, and PT/INR monitors Warfarin.

Coagulation disorders

Hemophilia (X-Linked Recessive, boys)

Hemophilia A (Factor VIII Deficiency), (B: Factor IX deficiency), (C: Factor XI Deficiency).

  • ↑ PTT, normal PT, normal platelet count.
  • Symptoms: Hemarthrosis (bleeding into joints), deep muscle bleeds, post-op bleeding.
  • Treatment: Factor VIII, Desmopressin (↑ vWF & Factor VIII release from endothelium).

How it is tested: A boy with easy bruising, joint swelling after minor trauma or intracranial bleeding after minor head trauma→ Hemophilia A.

Vitamin K deficiency:

  • Vitamin K is needed for γ-carboxylation of clotting factors II, VII, IX, X & proteins C, S
  • Deficiency: Newborns (↓ gut bacteria, sterile gut → No Vitamin K synthesis). Prolonged broad-spectrum antibiotics (gut flora disruption). Malabsorption (fat-soluble vitamin loss): Cystic fibrosis, celiac disease, IBD, liver disease. Warfarin use (inhibits vitamin K epoxide reductase).
  • Neonatal hemorrhagic disease → GI bleeding, umbilical stump bleeding, intracranial hemorrhage “IVH”.

↑ PT “more reliable”, ↑ PTT, and normal bleeding time & platelet count.

Treatment: Vitamin K supplementation and Fresh Frozen Plasma (FFP) for acute bleeding (replenishes clotting factors immediately).
Prevention: Neonates get IM vitamin K at birth to prevent hemorrhagic disease.

How it is tested: 1. A neonate to a mother who had a home birth without prenatal care, is brought with altered mental status and lethargy, head USG show inerventricular hemorrhage → Vitamin K deficiency. 2. A patient with Crohn’s disease develops easy bruising and prolonged PT

Platelet Disorders (Mucocutaneous Bleeding “petechiae, purpura”)

Bernard-Soulier Syndrome (GpIb Deficiency)

  • Defective platelet adhesion (GpIb defect → ↓ vWF binding). Large platelets, ↑ Bleeding Time, normal platelet count. No aggregation with ristocetin test.

How it is tested: A child with mucosal bleeding, normal platelet count but ↑ Bleeding Time→ Bernard-Soulier.

Glanzmann Thrombasthenia (GpIIb/IIIa Deficiency)

  • Defective platelet aggregation. ↑ Bleeding Time, normal platelet count. No platelet clumping on smear, normal ristocetin test.

How it is tested: A child with mucosal bleeding, normal platelet count but ↑ Bleeding Time→ Glanzmann.

Immune Thrombocytopenic Purpura (ITP)

  • Autoimmune IgG against GpIIb/IIIa → Splenic macrophage destruction. ↓Platelets, ↑megakaryocytes, ↑Bleeding Time, normal PT/PTT. Common post-viral, SLE, HIV, HCV.
  • Treatment: Steroids, IVIG, splenectomy (if refractory).

How it is tested: A patient with mucosal bleeding, low platelet count and ↑ Bleeding Time, he has no other pathology→ ITP.

Thrombotic Microangiopathy

Thrombotic Thrombocytopenic Purpura (TTP)

  • Deficiency of ADAMTS13 (vWF cleaving protease) → Large vWF multimers → Platelet microthrombi → Thrombocytopenia, microangiopathic hemolytic anemia (MAHA, schistocytes), fever, neurologic symptoms, renal failure.
  • ↓ Platelets, ↑ Bleeding Time, normal PT/PTT, schistocytes, ↑ LDH.
  • Treatment: Plasma exchange.

How it is tested: A woman with fever, thrombocytopenia, neurologic symptoms, and schistocytes → TTP, start plasma exchange.

Hemolytic Uremic Syndrome (HUS)

  • Shiga toxin-producing E. coli O157:H7following bloody diarrhea in children → Endothelial injury → platelet microthrombi in small vessels → Platelets consumed in thrombi + RBCs sheared → schistocytes → Fatigue, pallor, petechiae
  • Narrowing of renal vessels → ↓ GFR → ↑ BUN/Cr → Oliguria, edema, and hypertension.

Labs

  • ↓ Hb(hemolytic anemia), ↑ LDH, ↑ indirect bilirubin, ↑ retic, schistocytes on peripheral smear. Normal PT/PTT , and ↓ platelets
  • ↑ BUN and Cr

Management

  • Supportive only; IV fluids, electrolytes, dialysis if needed. No antibiotics, no antidiarrheals

How it is tested:

A child with bloody diarrhea 5 days ago, now presents with pallor, petechiae, and low urine output. Labs show anemia, thrombocytopenia, ↑ BUN, and schistocytes.

Mixed platelet and coagulation disorders

Von Willebrand Disease (AD – Most Common Inherited Bleeding Disorder)

  • Genetic deficiency of vWF or acquired with AS or angiodysplasia → (impaired platelet adhesion + ↓ Factor VIII) → ↑ Bleeding Time, normal/↑ PTT, normal PT.
  • Mucosal bleeding, prolonged menstrual bleeding, prolonged bleeding after surgery.
  • Treatment: Desmopressin (releases vWF from endothelium).

How it is tested: A young woman with easy bruising, prolonged menstrual bleeding, and ↑ PTT → VWD, treat with desmopressin.

Disseminated Intravascular Coagulation (DIC)

  • Widespread activation of coagulation → clotting factors consumption → Bleeding + Thrombosis → ↑ PT/PTT, ↓ Platelets, ↓ Fibrinogen, ↑ D-dimer, ↑ thrombin, ↑ plasmin, schistocytes.
  • Triggered by Sepsis (endotoxin), trauma, malignancy (AML-M3), obstetric complications, snake bites. Treat underlying cause, FFP, cryoprecipitate.

How it is tested: 1. A septic patient with bleeding from catheter sites, thrombocytopenia, ↑ PT/PTT, and ↑ D-dimer → DIC. 2. Arrow questions asking about ↑ PT, ↑ PTT, ↑ BT, ↑ Thrombin, ↑Plasmin.

Hereditary Thrombophilias (Hypercoagulable State)

Factor V Leiden Mutation (Most Common)

  • Mutated Factor V →no longer inhibited by Protein C. ↑ DVT, PE (especially in young), recurrent pregnancy loss. Normal PT/PTT.

How it is tested: A young patient with recurrent DVTs with normal PT/PTT → Factor V Leiden.

Antithrombin III Deficiency

  • Inherited or acquired due to nephrotic syndrome → hypercoagulability. No prolongation of PTT after heparin administration.

How it is tested: A nephrotic syndrome patient presents with sudden flank pain and hematuria→ renal vein thrombosis due to ATIII loss.

Protein C or S Deficiency (↓ Inactivation of Factors V/VIII)

  • Warfarin can cause warfarin-induced skin necrosis due to early Protein C depletion.

How it is tested: A patient with skin necrotic patches. History of DVT treated with warfarin → Protein C deficiency

Pharmacology

Anticoagulants

Heparin

  • Activates antithrombin III → Inhibits thrombin (Factor IIa) & Factor Xa → ↑PTT, ↑ Thrombin time, normal PT. Used for: DVT, PE, acute MI, prophylaxis in hospitalized patients, safe in pregnancy (does not cross placenta). 
  • AE: 1. Bleeding, Antidote: Protamine sulfate (binds heparin chemically). 2. Heparin-Induced Thrombocytopenia (HIT); IgG against heparin platelet factor 4 (PF4) → removal by spleen → thrombosis and platelet count < 50% → stop heparin, give argatroban or fondaparinux.

How it is tested: 1. A patient with acute DVT was started on Heparin 5 days ago. today, her labs show decreased platelet count <50% since admission / new thrombi scenario→ HIT, give Argatroban. 2. Arrow questions asking about the mechanism of Heparin: ↓Xa, ↑X, ↓IIa.

Warfarin

  • Inhibits Vitamin K Epoxide Reductase → ↓ Y carboxylation of Factors II, VII, IX, X, Proteins C & S → ↑ PT, ↑ INR. Slow onset, long half-life (used for long-term anticoagulation).
  • Used for atrial fibrillation, DVT/PE (after heparin bridging), and mechanical valves.
  • AE: 1. Bleeding, Antidote: Vitamin K + Fresh Frozen Plasma (FFP). 2. Teratogenicity. 3. Warfarin-induced skin necrosis (Protein C depletion first → hypercoagulability), prevented by Heparin bridge. 4. Metabolized by CYT P450.

How it is tested: 1. A patient with A-fib starts a new anticoagulant but develops skin necrosis → Warfarin → Protein C depletion → Hypercoagulability. 2. A patient presented with bleeding. she took PPI last week for her GERD, and she has a history of a mechanical valve and chronic warfarin therapy. “↓ warfarin metabolism.”

Direct Thrombin (IIa) Inhibitors:

  • Drugs: Bivalirudin, Dabigatran, Argatroban. Used for HIT, and A-fib.

Direct Factor Xa Inhibitors:

  • Drugs: RivaroXaban, ApiXaban, Edoxaban. Used for DVT/PE, and A-fib.
  • No monitoring. Antidot: Adenexate Alpha.

Antiplatelets

Aspirin (COX-1/COX-2 Inhibitor)

  • Irreversibly inhibits COX-1 & COX-2 → ↓ TXA2 (thromboxane A2) → ↓ platelet aggregation.
  • Uses: CAD, stroke prevention, acute MI.
  • Adverse Effects: GI ulcers, renal papillary necrosis, Reye’s syndrome in kids.

How it is tested: 1. A child presents with lethargy, weakness, jaundice, and ↑ AST, ALT. He had flu last week, for which he took an over-the-counter drug. 2. A patient on aspirin for CAD has IDA. 3. Aspirin toxicity asking for acid-base balance “mixed respiratory alkalosis and metabolic acidosis”.

ADP Receptor Blockers

  • Drugs: Clopidogrel, Prasugrel, Ticagrelor.
  • Mechanism: Block P2Y12 receptor → Prevent platelet aggregation. Uses like Aspirin.

GpIIb/IIIa Inhibitors

  • Drugs: Abciximab, Eptifibatide, Tirofiban.
  • Mechanism: Inhibit GpIIb/IIIa → Prevent fibrinogen cross-linking of platelets.

Thrombolytics (Plasminogen Activators)

  • Drugs: Alteplase (tPA), Streptokinase, Reteplase, Tenecteplase.
  • Convert plasminogen to plasmin → Fibrin degradation, ↑ PT, PTT. Uses: Acute stroke, MI, PE.
  • Contraindications: Active bleeding, recent surgery, severe HTN > 180.
  • Antidote: Aminocaproic acid (antifibrinolytic) and tranexamic acid. Also, FFP and PCC.

Chemotherapy Drugs

Antitumor Antibiotics

  • Doxorubicin, Daunorubicin → Generates free radicals, intercalates DNA → Dilated cardiomyopathy. (Dexrazoxane prevents cardiotoxicity).

How it is tested: A patient with a history of treated leukemia. Now has fatigue, shortness of breath, and cardiomegaly on imaging.

  • Bleomycin → DNA strand breaks via free radicals → Pulmonary Fibrosis.

How it is tested: A patient with a history of treated leukemia. Now has chronic dry cough.

Antimetabolites (S-phase specific)

  • Methotrexate (MTX) → Folicacid analog, inhibits DHFR → ↓DNA synthesis.

Uses: abortion, ectopic pregnancy, RA, Psoriasis, IBD, and leukemias.

AE: Myelosuppression (reversible with Leucovorin), hepatotoxicity, mouth ulcers, anemia, and pulmonary fibrosis.

How it is tested: Most questions ask about its adverse effects.

  • 5-Fluorouracil (5-FU) → Pyrimidine analog bioactivated to 5-FdUMP → Inhibits thymidylate synthase → ↓ DNA synthesis (enhanced with Leucovorin). AE: myelosuppression.

How it is tested: Questions comparing the effects of leucovorin on MTX vs 5-FU.

  • Hydroxyurea

Inhibits ribonucleotide reductase → ↓ DNA synthesis → S-phase arrest.

Uses: Sickle cell disease (↑ HbF production → reduces sickling), Polycythemia vera

AE: Myelosuppression.

How it is tested: A sickle cell patient is started on a medication that increases HbF. What is the mechanism of action?

  • Cytarabine

Pyrimidine analog → Incorporates into DNA → Inhibition of DNA polymerase.

AE: Pancytopenia, cerebellar toxicity (ataxia, confusion, nystagmus, dysarthria).

How it is tested: AML patient receives chemotherapy and develops pancytopenia + ataxia.

  • Cladribine

Purine analog → Inhibits adenosine deaminase (ADA) → Inhibition of DNA polymerase.

Uses: Hairy cell leukemia. AE: Myelosuppression.

How it is tested: A middle-aged man with splenomegaly and pancytopenia. Smear shows “hairy” lymphocytes. What’s the best treatment?

  • Thiopurines (6-Mercaptopurine & Azathioprine)

Purine analogs → Inhibit de novo purine synthesis. Azathioprine is activated to 6-MP by HGPRT.

Uses: IBD, RA, SLE, ALL. AE: Myelosuppression, hepatotoxicity.

Metabolized by xanthine oxidase → toxicity ↑ with XO inhibitors like allopurinol/febuxostat.

How it is tested: A patient treated with 6-MP has gout and is given allopurinol → ↓ 6-MP dose.

Alkylating Agents

  • Cyclophosphamide → Cross-links DNA. AE: Hemorrhagic cystitis (prevented with Mesna), bladder cancer.
  • Busulfan → Cross-links DNA. AE: Pulmonary fibrosis.

Microtubule Inhibitors (M-phase specific)

  • Vincristine → Blocks microtubule polymerization → Prevents mitotic spindle formation. AE: Peripheral neuropathy.

How it is tested: A woman with ovarian cancer on chemotherapy complains of tingling and burning in fingers and toes.

Topoisomerase Inhibitors

  • Etoposide (Topoisomerase II inhibitor) → ↓ DNA unwinding → ↓ DNA replication.

How it is tested: a woman with leukemia treated with a drug that ↓ DNA unwinding.

Anticancer Monoclonal Antibodies

Monoclonal Antibodies

  • Rituximab (CD20 Ab) → For B-cell cancers: CLL, NHL, ITP, TTP.
  • Bevacizumab (VEGF Ab) → AE: Hemorrhage and ↓ wound healing.
  • Trastuzumab (HER2 Ab, a tyrosine kinase) → AE: Dilated cardiotoxicity.
    How it is tested: A patient with a history of treated leukemia now presents with fatigue, shortness of breath, and cardiomegaly on imaging.

Anticancer Small Molecule Inhibitors

  • Imatinib: Targets BCR-ABL in CML and ALL.
  • Bortezomib: Inhibits proteasome → accumulation of abnormal proteins → apoptosis.
    Used for Multiple Myeloma. How it is tested: Questions like to ask about the mechanism of action.
  • Vemurafenib: Targets BRAF → Used for Melanoma.

Platinum Compounds (Cisplatin, Carboplatin)

Cross-link DNA. AE: Nephrotoxicity, prevented by Amifostine.

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Leukemia Cell Resistance to Chemotherapy

  • ↑ P-Glycoprotein (efflux pump) → Pumps drug out of the cell
  • Secretes antibodies that bind to programmed cell death ligand PDL1 on T cells → exhaustion.
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