What are the components of Virchow's triad and how is thrombosis managed?

Virchow's Triad: Components and Thrombosis Management

The Three Components of Virchow's Triad

Virchow's triad consists of three pathophysiological factors that predispose to thrombus formation: (1) stasis of blood flow, (2) endothelial injury or dysfunction, and (3) hypercoagulability of blood components. 1

1. Stasis of Blood Flow

• Reduced or turbulent blood flow allows prolonged contact between coagulation factors and the vessel wall, promoting thrombus formation 1, 2
• Occurs in conditions such as immobilization, atrial fibrillation (particularly in the left atrial appendage), venous insufficiency, and post-surgical states 1
• In pediatric congenital heart disease, nonpulsatile flow (after Fontan procedures) and vessel/chamber dilatation create static flow conditions 1
• Low shear rates in small vessels increase blood viscosity through red blood cell interactions 1

2. Endothelial Injury or Dysfunction

• Endothelial denudation is the most critical factor for arterial thrombosis, exposing subendothelial collagen and tissue factor 2
• Arterial thrombi typically form on ruptured or eroded atherosclerotic plaques in coronary, cerebral, and femoral arteries 2
• Endothelial dysfunction in atrial fibrillation is evidenced by elevated von Willebrand factor levels 1
• Central line placement, surgical trauma, and inflammatory conditions cause direct vascular injury 1

3. Hypercoagulability

• Inherited thrombophilias include protein C deficiency (odds ratio 11.1 for cerebral venous thrombosis), protein S deficiency, antithrombin III deficiency, Factor V Leiden, and prothrombin G20210A mutation 3, 4, 5
• Acquired hypercoagulable states include malignancy (4-7 fold increased VTE risk), pregnancy/postpartum, oral contraceptives, inflammatory conditions, and elevated fibrinogen levels 1, 3, 4
• Biochemical markers of activation include elevated fibrin D-dimer, thromboglobulin, and platelet factor 4 1

Management of Thrombosis

Venous Thromboembolism (DVT/PE)

Anticoagulation is the cornerstone of VTE treatment, with duration and intensity determined by thrombosis etiology and risk factors. 1, 6

Treatment Duration by Clinical Scenario:

• Provoked VTE (transient risk factor): 3 months of anticoagulation 6
• First unprovoked (idiopathic) VTE: 6-12 months minimum 6
• Recurrent VTE (≥2 episodes): Indefinite anticoagulation 6
• VTE with documented thrombophilia: 6-12 months, with indefinite therapy suggested for idiopathic cases 6
• VTE with antiphospholipid antibodies or multiple thrombophilic conditions: 12 months minimum, indefinite therapy suggested 6

Anticoagulation Regimen:

• Target INR of 2.5 (range 2.0-3.0) for warfarin therapy across all VTE treatment durations 6
• Initial heparin (unfractionated or LMWH) with 4-5 day overlap when transitioning to warfarin 6
• For pediatric patients, dabigatran is suggested over standard anticoagulants (LMWH, UFH, VKA, fondaparinux) due to reduced thrombus recurrence and improved resolution 1

Cerebral Venous Sinus Thrombosis (CSVT)

Anticoagulation is strongly recommended for pediatric CSVT without hemorrhage, even though this represents a hemorrhagic stroke risk. 1

• Intravenous heparin or subcutaneous LMWH is the initial treatment of choice 7
• MRI with MR venography is the mandatory diagnostic modality; CT venography serves as alternative 3, 7, 4
• Comprehensive thrombophilia screening is required for all patients: protein C, protein S, antithrombin III, Factor V Leiden, prothrombin mutation, lupus anticoagulant, anticardiolipin antibodies, and homocysteine 3
• For severe cases with mass effect or neurological deterioration, endovascular therapy or decompressive hemicraniectomy may be necessary 7

Atrial Fibrillation-Related Thromboembolism

Oral anticoagulation with warfarin targeting INR 2.0-3.0 is recommended for AF patients at high stroke risk. 1, 6

Risk Stratification:

• High-risk features requiring anticoagulation: Prior stroke/TIA/systemic embolism, age >75 years, heart failure, hypertension, or diabetes 6
• Intermediate risk (age 65-75 without other factors): Either warfarin or aspirin 325 mg daily 6
• AF with mitral stenosis or prosthetic valves: Anticoagulation mandatory, with higher INR targets for mechanical valves 6

Post-Myocardial Infarction

For high-risk post-MI patients (large anterior MI, heart failure, visible intracardiac thrombus, or prior thromboembolism), combined moderate-intensity warfarin (INR 2.0-3.0) plus aspirin is recommended. 6

• Treatment duration up to 4 years is supported for high-risk patients 6
• Most low-risk post-MI patients should receive aspirin alone rather than warfarin 6

Critical Management Pitfalls

Monitoring and Dose Adjustment

• PT/INR should be determined daily after warfarin initiation until stable in therapeutic range 6
• Subsequent monitoring intervals: 1-4 weeks once stable dosage achieved 6
• Anticoagulation clinics and self-monitoring achieve significantly better time in therapeutic range (56-93%) compared to usual care (33-64%) 6

Special Populations

• Lower warfarin initiation doses required for elderly/debilitated patients and those with CYP2C9 and VKORC1 genetic variations 6
• Pediatric VTE management requires consultation with pediatric hematologist given care complexity 1

Perioperative Management

• For minimal invasive procedures: Adjust warfarin to maintain INR at low end of therapeutic range rather than discontinuing 6
• When discontinuing warfarin: Carefully weigh benefits versus risks even for short periods 6
• PT/INR determination recommended immediately prior to any dental or surgical procedure 6

Diagnostic Delays to Avoid

• Median 7-day delay from symptom onset to CSVT diagnosis is common; maintain high suspicion for headache with seizures 3, 7
• Normal non-contrast CT does not exclude CSVT; proceed to CTV or MRV when clinical suspicion remains high 7
• Bilateral brain involvement can occur with CSVT unlike typical arterial stroke patterns 3
• Isolated headache without focal findings occurs in 25% of CSVT cases and should not exclude diagnosis 3