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USMLE Step 2 (Fach) / Hematology/Oncology (Lektion)

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• Cryoglobulinemia Immune complex deposition in small- to medium-size blood vessels, leading to endothelial injury and end-organ damage. Type I- Disease associations: Lymphoproliferative or hematologic (eg, multiple myeloma)- Asymptomatic- Hyperviscosity (eg, blurry vision), thrombosis (eg, Raynaud phenomenon)- Skin: Livedo reticularis, purpura- Complement: normal Mixed (types II & III)- Disease associations: Chronic HCV, HIV, SLE- Systemic: Fatigue, arthralgias- Renal: Glomerulonephritis, HTN- Pulmonary: Dyspnea, pleurisy- Skin: Palpable purpura, LCV- Cold-precipitable immune complexes- Complement: Low C4
• Diamond-Blackfan anemia Pathogenesis: Congenital erythroid aplasia Clinical findings:- Congenital malformations (50%): Microcephaly, hypertelorism, flat nasal bridge, micrognathia, short stature, webbed neck, cleft palate, triphalangeal thumbs- Pallor in infancy- Increased risk of malignancy Laboratory findings:- Macrocytic anemia- Reticulocytopenia- Normal platelets, white blood cells Treatment:- Corticosteroids- Red blood cell transfusions
• Acute severe anemia in sickle cell disease Aplastic crisis:- ↓ Reticulocytes- Transient arrest of erythropoiesis- Secondary to infection (e.g., parvovirus B19) Splenic sequestration crisis:- ↑ Reticulocytes- Splenic vaso-occlusion → rapidly enlarging spleen- Occurs in children prior to autosplenectomy
• Causes of macrocytic anemia - Folate deficiency - Vitamin B12 deficiency - Myelodysplastic syndromes - AML - Drug-induced (e.g., hydroxyurea, zidovudine, chemotherapy agents) - Liver disease - Alcohol abuse - Hypothyroidism
• Therapy characterizations Neoadjuvant: Treatment given before the standard therapy Adjuvant: Treatmnet given in addition to standard therapy Induction: Initial dose of a treatment to rapidly kill tumor cells and send the patient into remission (< 5% tumor burden). A typical example is induction chemotherapy for acute leukemia. Consolidation: Typically given after induction therapy with multidrug regimens to further reduce tumor burden. A typical example is multidrug therapy after induction therapy for acute leukemia. Maintenance therapy: Usually given after induction and consolidation therapy (or initial standard therapy) to kill any residual tumor cells and keep the patient in remission. An example is daily antiandrogen therapy for prostate cancer. Salvage therapy: Treatment for a disease when standard therapy fails, such as radiation therapy for PSA recurrence after radical prostatectomy for prostate cancer.
• Acute traumatic coagulopathy An acute disorder of coagulation that occurs acutely following severe injuries. Diagnostic criteria: PT/PTT > 1.5x normal in an acute trauma patient without pre-existing coagulopathy. - Sometimes associated with a drop in platelets, but this is not required for diagnosis. ATC is associated with greater transfusion requirements, longer ICU stays, and increased mortality. Treatment: Matched transfusion of blood products (pRBC, FFP, and platelet concentrate) in a 1:1:1 ratio
• Hemolytic uremic syndrome Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy in which microthrombi, consisting primarily of platelets, form and occlude the arterioles and capillaries. Epidemiology:- Mainly children < 5 years of age Etiology:- Shiga-like toxin (verotoxin) from enterohemorrhagic E. coli (EHEC) strain O157:H7→ Usually transmitted via contaminated foods, e.g., undercooked beef or raw leafy vegetables- Shiga toxin produced by Shigella dysenteriae- Streptococcus pneumoniae infection Clinical features:- A diarrheal illness (usually bloody) for the past 5-10 days precedes the onset of HUS symptoms in many children. 1. Low platelets (i.e., thrombocytopenia): Petechiae, purpura, mucosal bleeding, prolonged bleeding2. Microangiopathic hemolytic anemia: Fatigue, dyspnea, and pallor, jaundice3. Impaired renal function: Hematuria, proteinuria, oliguria, anuria Diagnostics:- ↓ Platelets, ↑ WBC count, ↓ Hemoglobin, ↑ Reticulocytes, ↓ Haptoglobin- Normal/slightly elevated prothrombin time (PT) and activated partial thromboplastin time (aPTT)- ↑ Fibrin degradation products and D-dimer levels- Large number of schistocytes on blood smear (up to 10% of RBCs) - ↑ LDH, ↑ indirect bilirubin (hemolytic anemia)- ↑ BUN and ↑ creatinine (impaired renal function)- Urinalysis: hematuria, proteinuria Treatment:- Supportive- RBC transfusions if Hb < 6 g/dL- Dialysis as indicated for AKI: Up to 50% of HUS patients require dialysis.- Only in refractory cases: plasma exchange therapy- Eculizumab: may be beneficial in HUS with neurological symptoms
• Essential thrombocythemia Genetics: JAK2 mutation in 50% of cases Clinical features: - 50% asymptomatic- Thromboembolic events- Increased risk of fetal loss- Vasomotor symptoms (headache, visual disturbances, acral paresthesias)- Acute gouty arthritis- Petechial bleeding Diagnostics:- Thrombocytosis (> 600,000/μL)- ↑ LDH and uric acid- Bone marrow aspiration: hyperplasia of megakaryocytes Treatment:- Prevent thromboembolisms: low dose aspirin- Reduce thrombocyte count: hydroxyurea or interferon alpha
• Anemia of chronic disease Description: anemia due to chronic inflammation Epidemiology: second most common anemia  Pathophysiology: inflammation → increase in cytokines and hepcidin → - Reduced iron release from macrophages in the reticuloendothelial system and reduced intestinal iron absorption → reduced iron available systemically- Reduced response (of production) to erythropoietin (EPO) and relative reduction of EPO levels → reduced RBC synthesis- Reduced erythrocyte survival and lifespan Etiology:- Inflammation (e.g., rheumatoid arthritis, systemic lupus erythematosus)- Malignancy (e.g., lung cancer, breast cancer, lymphoma)- Infection (e.g., tuberculosis) Diagnostics:- CBC: normocytic anemia (early phase) → microcytic anemia (later phase)- Low iron, low iron saturation, low TIBC (vs. iron deficiency anemia ↑ TIBC)- Elevated serum ferritin- Low reticulocyte count Treatment: treat the underlying cause
• Primary myelofibrosis Primary myelofibrosis encompasses any myeloproliferative neoplasm leading to bone marrow fibrosis, extramedullary hematopoiesis, and splenomegaly. Epidemiology: peak incidence between age 60–70 years Genetics: JAK2 mutation in 50% of cases Clinical features:- Weakness, fatigue, weight loss- Splenomegaly: left upper quadrant abdominal pain - Hyperproliferative phase (early phase): thrombocytosis (→ thromboembolic events) and leukocytosis- Pancytopenic phase (late phase): → Erythrocytopenia → anemia→ Thrombocytopenia → petechial bleeding→ Leukopenia → increased susceptibility to infections Diagnosis:- Laboratory studies: ↑ leukocyte alkaline phosphatase, LDH, and uric acid- Peripheral blood smear: dacrocytes- Bone marrow aspiration: punctio sicca  Treatment:- Curative: allogeneic stem cell transplantation (option for younger patients)- Hyperproliferative phase:→  Prevent thromboembolisms: antiplatelet drug (aspirin 100 mg)→ Control cell count: hydroxyurea, interferon alpha, cladribine- Pancytopenic phase:→  JAK2 inhibitor: ruxolitinib → Periodic transfusions → Low-dose thalidomide plus glucocorticoids
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• Autoimmune hemolytic anemia (AIHA) – Cold Occurs in lower temperatures (0-5°C) and usually affects elderly women (≥ 70 years) Etiology: mostly IgM antibodies (bound to erythrocytes) that can cause both intravascular and extravascular hemolysis - Idiopathic (esp. in the elderly)- Secondary: Mycoplasma or EBV infection, malignancy (e.g. non-Hodgkin lymphoma, chronic lymphocytic leukemia) Clinical features:- Pallor, fatigue, weakness- Cyanosis of the extremities (acrocyanosis) Diagnosis:- Signs of hemolysis- Peripheral blood smear: spherocytes, polychromasia- Coombs test: positive- ↑ Cold agglutinins titer- ↓ C3 and ↓ C4 (due to complement activation) Prognosis: spontaneous remission within a few weeks is common Therapy:- Mild disease: avoid cold exposure- Moderate/severe disease: immunosuppressive therapy with rituximab
• Autoimmune hemolytic anemia (AIHA) – Warm Occurs at body temperature (37°C/98.6° F) Etiology: mostly IgG antibodies, that result in extravascular hemolysis mediated by the reticuloendothelial system of the spleenand liver- Idiopathic- Secondary: due to lymphoma, chronic lymphocytic leukemia, systemic lupus erythematosus, or a drug reaction (e.g., cephalosporins, penicillins, α-methyldopa)  Clinical features: - Often more severe and more acute than cold agglutinin disease- Signs of anemia (pallor, fatigue, weakness) Diagnosis:- Signs of hemolysis- Peripheral blood smear: spherocytes, polychromasia- Coombs test: positive Therapy:- Initial treatment of choice: glucocorticoids- If glucocorticoids are unsuccessful → Adults: splenectomy→ Children: rituximab
• Howell-Jolly body Single, round, blue inclusions within red blood cells on peripheral smear. = Retained RBC remants that are typically removed by the spleen. Found in:- Asplenia- Functional hyposplenism due to splenic autoinfarction (e.g., sickle cell disease)- Infiltrative disorders of the spleen (e.g., sarcoidosis)- Splenic congestion (e.g. thrombosis)
• Iron deficiency anemia in young children Risk factors:- Prematurity- Lead exposure- Age < 1→ Delayed introduction of solids (i.e., exclusive breastfeeding after 6 months)- Cow's, soy, or goat's milk- Age > 1→ > 24 oz/day cow's milk→ < 3 servings/day iron-rich foods Diagnosis:- Screening hemoglobin at age 1- Hemoglobin < 11 g/dL, ↓ MCV, ↑ RDS Treatment: Empiric trial of iron supplementation
• Cancer-related anorexia/cachexia syndrome (CACS) Hypercatabolic state associated with weight loss, anorexia, and an excessive reduction in skeletal muscle. Etiology:- Systemic inflammation - Caloric reduciton Treatment:- Progesterone analogues (e.g., megestrol acetate)- Corticosteroids
• Upper extremity deep venous thrombosis Risk factors:- Central venous catheters- Repetitive arm movements (e.g. baseball pitching)- Weight lifting- Malignancy Clinical features:- Acute arm edema, heaviness, pain & erythema- Dilated subcutaneous collateral veins in chest/upper extremity- Pulmonary embolism Diagnosis: Duplex or doppler ultrasonography Treatment:- 3 months of anticoagulation- Thrombolysis (non-catheter-related)
• Drugs/supplements that affect warfarin metabolism CYP450 Inhibitors (↑ Warfarin effect)- Acetaminophen, NSAIDs- Antibiotics/antifungals (e.g., metronidazole)- Amiodarone- Cimetidine- Cranberry juice, Ginkgo biloba, vitamine E- Omeprazole- Thyroid hormone- SSRIs (e.g., fluoxetine) CYP450 Inducers (↓ Warfarin effect)- Carbamazepine, phenytoin- Ginseng, St. John's wort- Oral contraceptives- Phenobarbital- Rifampin

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