A 21-year-old woman comes to the physician because of a 1-day history of right leg pain. The pain is worse while walking and improves when resting. Eight months ago, she was diagnosed with a pulmonary embolism and was started on warfarin. Anticoagulant therapy was discontinued two months ago. Her mother had systemic lupus erythematosus. On examination, her right calf is diffusely erythematous, swollen, and tender. Cardiopulmonary examination shows no abnormalities. On duplex ultrasonography, the right popliteal vein is not compressible. Laboratory studies show an elevated serum level of D-dimer and insensitivity to activated protein C. Further evaluation of this patient is most likely to show which of the following?

Mutation of coagulation factor V

Elevated coagulation factor VIII levels

A 48-year-old man comes to the emergency department because of sudden right flank pain that began 3 hours ago. He also noticed blood in his urine. Over the past two weeks, he has developed progressive lower extremity swelling and a 4-kg (9-lb) weight gain. Examination shows bilateral 2+ pitting edema of the lower extremities. Urinalysis with dipstick shows 4+ protein, positive glucose, and multiple red cell and fatty casts. Abdominal CT shows a large right kidney with abundant collateral vessels and a filling defect in the right renal vein. Which of the following is the most likely underlying cause of this patient's symptoms?

Malignant erythropoietin production

Increased lipoprotein synthesis

A 23-year-old woman with no significant past medical history currently on oral contraceptive pills presents to the emergency department with pleuritic chest pain. She states that it started today. Yesterday she had a trip and returned via plane. Her temperature is 98°F (36.7°C), blood pressure is 117/66 mmHg, pulse is 105/min, respirations are 14/min, and oxygen saturation is 98% on room air. Physical exam reveals tachycardia, a normal S1 and S2, and clear breath sounds. The patient’s lower extremities are non-tender and symmetric. Chest pain is not reproducible with position changes or palpation but is worsened with deep breaths. Which of the following is the most appropriate next test for this patient?

Ultrasound of the lower extremities

A 62-year-old man comes to the physician because of a 5-day history of swelling in his left arm. Two months ago, he was diagnosed with a deep venous thrombosis in the left calf. He has had a 7-kg (15-lb) weight loss in the last 3 months. He has smoked 1 pack of cigarettes daily for the past 25 years. His only medication is warfarin. Physical examination shows warm edema of the left forearm with overlying erythema and a tender, palpable cord-like structure along the medial arm. His lungs are clear to auscultation bilaterally. Duplex sonography shows thrombosis of the left basilic and external jugular veins. Which of the following is the most appropriate next step to confirm the underlying diagnosis?

Transesophageal echocardiography

Serum antiphospholipid antibody level

A 67-year-old woman presents with right leg pain and swelling of 5 days’ duration. She has a history of hypertension for 15 years and had a recent hospitalization for pneumonia. She had been recuperating at home but on beginning to mobilize and walk, the right leg became painful and swollen. Her temperature is 37.1°C (98.7°F), the blood pressure is 130/80 mm Hg, and the pulse is 75/min. On physical examination, the right calf is 4 cm greater in circumference than the left when measured 10 cm below the tibial tuberosity. Dilated superficial veins are present on the right foot and the right leg is slightly redder than the left. There is some tenderness on palpation in the popliteal fossa behind the knee. Which of the following is the best initial step in the management of this patient’s condition?

Wells’ clinical probability tool

International normalized ratio (INR)

Computerized tomography (CT) with contrast

Activated partial thromboplastin time (aPTT)

A 24-year-old male was in a motor vehicle accident that caused him to fracture his femur and pelvis. After 2 days in the hospital, the patient became delirious, tachypneic, and a petechial rash was found in his upper extremities. Which of the following is most likely responsible for this patient’s symptoms?

Fat microglobules in the microvasculature

Thrombotic clot in the pulmonary artery

Aspiration of oropharyngeal contents

Alveolar foamy exudates with disc shaped cysts seen with methenamine silver stain

Type I and type II pneumocyte damage due to neutrophils

A 25-year-old woman comes to the physician because of recurrent episodes of reddish discoloration of her urine. She also has a 3-month history of intermittent abdominal pain, yellowish discoloration of the skin and eyes, and fatigue. Physical examination shows pallor and scleral icterus. The spleen is not palpable. Her hemoglobin concentration is 7.8 g/dL, leukocyte count is 2,000/mm3, and platelet count is 80,000/mm3. Serum LDH and unconjugated bilirubin concentrations are elevated. Addition of a serum containing anti-human globulins to a blood sample shows no agglutination. A urine dipstick shows blood; urinalysis shows no RBCs. A CT scan of the abdomen shows a thrombus in a distal branch of the superior mesenteric vein. Which of the following is the most likely cause of this patient's condition?

Absence of protective factors against destruction by complement

Activation and consumption of platelets and coagulation factors

Replacement of a single amino acid in a β-globin chain

Formation of IgG antibodies against glycoprotein IIb/IIIa

Endothelial cell dysfunction from bacterial toxin production

A 27-year-old woman presents to the emergency department complaining of a left-sided headache and right-sided blurry vision. She states that 2 weeks ago she developed dark urine and abdominal pain. She thought it was a urinary tract infection so she took trimethoprim-sulfamethoxazole that she had left over. She planned on going to her primary care physician today but then she developed headache and blurry vision so she came to the emergency department. The patient states she is otherwise healthy. Her family history is significant for a brother with sickle cell trait. On physical examination, there is mild abdominal tenderness, and the liver edge is felt 4 cm below the right costal margin. Labs are drawn as below: Hemoglobin: 7.0 g/dL Platelets: 149,000/mm^3 Reticulocyte count: 5.4% Lactate dehydrogenase: 3128 U/L Total bilirubin: 2.1 mg/dL Indirect bilirubin: 1.4 mg/dL Aspartate aminotransferase: 78 U/L Alanine aminotransferase: 64 U/L A peripheral smear shows polychromasia. A Doppler ultrasound of the liver shows decreased flow in the right hepatic vein. Magnetic resonance imaging of the brain is pending. Which of the following tests, if performed, would most likely identify the patient’s diagnosis?

Glucose-6-phosphate-dehydrogenase levels

Thromboembolic disease for USMLE Step 3: High-Yield Pathology Lessons

Virchow's Triad - The Clotting Culprits

Three primary factors predispose to thrombus formation. 📌 Mnemonic: SHE (Stasis, Hypercoagulability, Endothelial injury).

Endothelial Injury: The most critical factor. Disruption exposes thrombogenic subendothelial collagen.
- Causes: Trauma, surgery, vasculitis, atherosclerosis.
Abnormal Blood Flow (Stasis/Turbulence): Allows platelet-coagulation factor contact; prevents dilution.
- Causes: Immobilization, atrial fibrillation, aneurysms.
Hypercoagulability: Imbalance in clotting/anti-clotting pathways.
- Primary: Factor V Leiden, Prothrombin gene mutation.
- Secondary: Malignancy, pregnancy, OCP use.

⭐ Factor V Leiden is the most common inherited thrombophilia in Caucasians, resistant to Protein C cleavage.

Clots on the Move - Thrombi & Emboli Types

Thrombus: A stationary intravascular clot attached to the vessel wall.
Embolus: An intravascular solid, liquid, or gaseous mass that travels from its origin. A thromboembolus is a dislodged thrombus.
Types of Emboli (📌 Mnemonic: FAT BAT)
- Fat: Associated with long bone fractures or liposuction. Classic triad: hypoxemia, neurologic abnormalities, petechial rash.
- Air: Caused by decompression sickness or iatrogenic procedures (e.g., central line placement). Requires >100 cc of air for symptoms.
- Thrombus: The most common source (>95%), typically from deep vein thrombosis (DVT).
- Bacteria: Septic emboli from infective endocarditis.
- Amniotic fluid: Rare complication of labor, causing DIC.
- Tumor: Fragments of malignant neoplasms.

⭐ A patent foramen ovale (PFO) or atrial septal defect (ASD) can allow a venous embolus to enter the systemic circulation, causing a "paradoxical embolus" and subsequent stroke.

A Clot's Life - Fate of the Thrombus

📌 PED-O

Propagation: Thrombus enlarges, causing further obstruction.
Embolization: Dislodges and travels to a distant site.
Dissolution: Fibrinolysis, mediated by plasmin, breaks down the clot.
Organization & Recanalization: Ingrowth of granulation tissue; new capillary channels form to re-establish flow.

⭐ For most thrombi, organization and subsequent recanalization is the most common outcome, leading to the thrombus being incorporated into the vessel wall.

Clinical Crises - DVT, PE, & Strokes

Deep Vein Thrombosis (DVT):
- Presents with unilateral leg swelling, pain, and warmth.
- Dx: Begin with Wells score; Doppler ultrasound is the primary imaging test.
Pulmonary Embolism (PE):
- Classic presentation: sudden-onset dyspnea, pleuritic chest pain, tachypnea.
- Dx: CT pulmonary angiography (CTPA) is the imaging of choice. ECG may show S1Q3T3.
Ischemic Stroke:
- Often from atrial fibrillation (cardioembolic) or paradoxical emboli (via PFO).

⭐ A saddle embolus lodging at the pulmonary artery bifurcation can cause acute right heart failure and sudden death.

High‑Yield Points - ⚡ Biggest Takeaways

Virchow's triad (stasis, hypercoagulability, endothelial injury) is the cornerstone of thrombosis pathogenesis.

Pulmonary embolism (PE), most often from a lower extremity deep vein thrombosis (DVT), is the most feared complication.

Factor V Leiden represents the most common inherited hypercoagulable state.

Antiphospholipid syndrome is a critical acquired cause of recurrent arterial and venous thrombosis.

Lines of Zahn are characteristic of pre-mortem thrombi.

D-dimer is a sensitive test used to rule out venous thromboembolism.

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