Thrombosis

Etiology

100

These are the features of the Virchow triad. 

What are is a combination of pathophysiological factors that promote thrombus formation, including endothelial damage (e.g., inflammation, trauma), venous stasis (e.g., varicosis, immobilization), and hypercoagulability (e.g., increased platelet adhesion, thrombophilia)?

200

These hormone-related factors are thought to play a role in DVT.

What are estrogen-related factors 

• Pregnancy
• Use of OCPs or HRT

300

The following 2 are prothrombotic chronic illnesses that can cause DVT.

• Active cancer 
• Nephrotic syndrome  
• Autoimmune disorders
  • APLA syndrome
  • Inflammatory bowel disease
• Hereditary thrombophilia
  • Factor V Leiden
  • Antithrombin III deficiency, protein C deficiency, and protein S deficiency
  • Prothrombin mutation

400

These are the non-thrombotic causes of PE.

What are:

• Fat embolism
• Air embolism
• Amniotic fluid embolism
• Others: bacterial embolism, pulmonary tumor embolism, pulmonary cement embolism

500

The following are 2 transient and 2 chronic patient-factor causes of DVT.

What are transient causes:

• Obesity
• Smoking
• IV drug use 
• Nonadherence to VTE prophylaxis.

What are chronic causes:

• Age > 60 years
• Personal or family history of DVT or PE  [9]
• Anatomic predisposition to venous stasis (e.g., compression of the iliac veins due to pelvic malignancy, May-Thurner syndrome)

Pathophysiology and Clinical Features

100

This is the mechanism of PE formation.

What is thrombus formation → deep vein thrombosis in the legs or pelvis (most commonly iliac vein) → embolization to pulmonary arteries via inferior vena cava  → partial or complete obstruction of pulmonary arteries?

200

These are localized unilateral symptoms of DVT.

• Typically affects deep veins of the legs, thighs, or pelvis 
• Swelling, feeling of tightness or heaviness
• Warmth, erythema, and possibly livid discoloration 
• Progressive tenderness, dull pain 
  • Homans sign: calf pain on dorsal flexion of the foot 
  • Meyer sign: Compression of the calf causes pain.
  • Payr sign: pain when pressure is applied over the medial part of the sole of the foot
• Distention of superficial veins 
• Distal pulses are normal.

300

These are the common clinical features of PE.

• Acute onset of symptoms
• Dyspnea (> 75% of cases) 
• Tachycardia and tachypnea (up to 50% of cases) 
• Sudden pleuritic chest pain (∼ 20% of cases) 
• Cough and hemoptysis
• Associated features of DVT: e.g., unilaterally painful leg swelling

400

Elaborate on the three main pathophysiological components of thrombus formation aka the Virchow triad.

• Endothelial injury disrupts the protective barrier of blood vessels, exposing subendothelial collagen and tissue factors, which trigger platelet activation and adhesion, as well as activation of the coagulation cascade.
• Venous stasis slows down blood flow, allowing activated clotting factors to accumulate and promoting the formation of thrombi, particularly in areas where blood flow is most sluggish, such as the valves of deep veins.
• Hypercoagulability increases the propensity for clot formation by augmenting the production of clotting factors, decreasing the levels of natural anticoagulants, or impairing fibrinolysis, leading to an imbalance in the hemostatic system that favors thrombus formation.

500

This is the pathophysiologic response of the lung to arterial obstruction (2/3).

• Infarction and inflammation of the lungs and pleura
  • Causes pleuritic chest pain and hemoptysis
  • Leads to surfactant dysfunction → atelectasis → ↓ PaO2  [3]
  • Triggers respiratory drive → hyperventilation and tachypnea → respiratory alkalosis with hypocapnia (↓ PaCO2)
• Impaired gas exchange
  • Mechanical vessel obstruction → ventilation-perfusion mismatch  → arterial hypoxemia (↓ PaO2) and elevated A-a gradient.
• Cardiac compromise
  • Elevated pulmonary artery pressure (PAP) due to blockage → right ventricular pressure overload → forward failure with decreased cardiac output  → hypotension and tachycardia

Evaluation

100

This is the Wells criteria or pretest probability for DVT (risk for DVT).

What are medical history (presence of active cancer, history of previous DVT), history of immobilization (paralysis or recent immobilization of a lower extremity, recent history of major surgery of remaining bedridden), and clinical symptoms (localized tenderness along the deep venous system, leg swelling, asymmetrical calf swelling, unilateral pitting edema, and presence of collateral, non-varicose superficial veins)?

Interpretation (pretest probability for DVT) 

• 0: low 
• 1–2: intermediate 
• ≥ 3: high 

200

This test is obtained if PTP is low.

Check D-dimer first for low PTP (initial D-dimer is not diagnostically helpful for intermediate and high PTP). 

• Negative (< 500 ng/mL): DVT ruled out
• Positive (≥ 500 ng/mL): Possible DVT; Proceed to venous US.

300

This test is ordered for intermediate or high PTP, or low PTP with positive D-Dimer.

What is US?

• Negative US
  • Intermediate and low PTP: DVT ruled out
  • High PTP: Repeat venous US within a week if no alternate diagnosis. 
• Positive US: DVT confirmed; Screen for an underlying cause if no risk factors for DVT are identified on initial evaluation.
• Inconclusive US: Consider venography, CT venography, or MR venography.

400

This is the preferred test for the diagnosis of acute PE.

What is CT pulmonary angiography (CTPA)?

Findings

• Direct finding of PE: intraluminal filling defects of pulmonary arteries 
• Pulmonary infarct: opacity with consolidated border; may be accompanied by pleural effusion
• Evidence of RV dysfunction

A wedge-shaped infarction with pleural effusion is almost pathognomonic for PE.

500

PE severity assessment includes an echocardiogram which could yield these findings.

What are

• Dilatation and hypokinesis of the right ventricle (RV) 
• Venous reflux with IVC dilation 
• Tricuspid regurgitation (tricuspid valve insufficiency) 
• ↑ PASP 
• Increased right atrial pressure

Treatment

100

This initial parenteral anticoagulation class is preferred in pregnant patients and patients with normal renal function, liver disease, or active cancer.

What is low molecular weight heparin (LMWH) (e.g., enoxaparin)?

200

This initial parenteral anticoagulation class is preferred in patients with a history of heparin-induced thrombocytopenia.

What is fondaparinux (factor Xa inhibitor)?

300

This long-term anticoagulation class is the first-line therapy in nonpregnant patients, including patients with active cancer.

What is a direct oral anticoagulant?

Oral anticoagulant that directly binds to clotting factors (e.g., thrombin, factor Xa). Examples include dabigatran, rivaroxaban, and apixaban.

Long-term anticoagulation

• Indication: all patients with DVT who cannot be managed expectantly and have no contraindications to anticoagulation.

400

These are the general principles for PE management (3)?

What are:

• Provide oxygen therapy for hypoxic patients.
• Treat PE based on severity and bleeding risk; start empiric anticoagulation for PE if indicated. 
• Provide analgesia; avoid NSAIDs if possible.

500

The use of a thrombolytic agent (which one?) in PE treatment is indicated in these conditions and has a single major complication.

• Indications
  • Massive PE (hemodynamic instability and/or right heart failure) with a low bleeding risk
  • Nonmassive PE with a low bleeding risk, if patients deteriorate despite anticoagulation 
  • Cardiac arrest in patients with suspected PE
• Common thrombolytic agents
  • Recombinant tissue plasminogen activator (tPA), e.g., alteplase (preferred)
  • Streptokinase
  • Urokinase
• Complication: hemorrhage during thrombolytic treatment

Complications

100

This is the number one feared complication of DVT.

What is PE?

200

This type of heart failure can be observed in PE.

What are right ventricular failure and secondary pulmonary arterial hypertension?

300

This DVT complication may occur in patients with a history of IV drug use using nonsterile needles.

What is septic thrombophlebitis?

400

Without anticoagulant treatment, the risk of PE recurrence is __% in the first year and ~ __% per year after.

What is... without anticoagulant treatment, the risk of recurrence is ∼ 10% in the first year and ∼ 5% per year after?

500

20% of the PE cases experience loss of lung volume caused by deflation of alveoli and subsequent collapse of part of the lung also known as:

What is atelectasis?