Venous Thromboembolism
From Wells score to thrombolysis: when to test, treat, and for how long
Risk factors and presentation
Virchow triad. Clots form with stasis, endothelial injury, and hypercoagulability. Major risk factors are surgery, immobilization, malignancy, estrogen (oral contraceptives, pregnancy), prior VTE, and inherited thrombophilia. Factor V Leiden, which makes factor V resistant to inactivation by activated protein C, is the most common inherited thrombophilia; others include the prothrombin G20210A mutation, protein C, protein S, and antithrombin deficiencies.
Deep vein thrombosis (DVT). Unilateral leg swelling, pain, warmth, and erythema; Homans sign is unreliable. Most clinically significant PEs arise from proximal DVT (popliteal, femoral, iliac); isolated calf DVT embolizes less often. Phlegmasia cerulea dolens is a limb-threatening massive proximal DVT with cyanosis, severe swelling, and compromised arterial inflow.
Pulmonary embolism (PE). Sudden dyspnea, pleuritic chest pain, tachycardia, and hypoxia; blood gases typically show respiratory alkalosis with a widened A–a gradient.
- ECG: sinus tachycardia is the most common finding; the classic S1Q3T3 pattern is uncommon.
- Chest radiograph: usually normal; occasionally a Hampton hump (wedge-shaped infarct) or Westermark sign (regional oligemia).
- Troponin and BNP rise with right ventricular strain and mark a worse prognosis.
The diagnostic pathway
| Criterion | Points |
|---|---|
| Clinical signs of DVT | 3 |
| PE is the most likely diagnosis | 3 |
| Heart rate >100 | 1.5 |
| Immobilization or surgery in the past 4 weeks | 1.5 |
| Prior DVT or PE | 1.5 |
| Hemoptysis | 1 |
| Active malignancy | 1 |
- Very low risk?If all 8 PERC criteria are met, no testing is needed.
- PE unlikely (Wells ≤4)Order a D-dimer; a negative result excludes PE.
- PE likely (Wells >4) or D-dimer positiveCT pulmonary angiography.
- High suspicion while awaiting imagingStart anticoagulation empirically if bleeding risk is low.
D-dimer rules out, never rules in. It is highly sensitive but nonspecific, so it is useful only to exclude VTE when pretest probability is low or intermediate. Use an age-adjusted cutoff (age × 10 ng/mL) after age 50. A positive result mandates imaging, and the test should not be ordered at all when pretest probability is high.
PERC rule. All eight must be present: age under 50, heart rate under 100, oxygen saturation ≥95%, no hemoptysis, no estrogen use, no prior VTE, no unilateral leg swelling, and no recent surgery or trauma requiring hospitalization.
Imaging. CT pulmonary angiography is the test of choice for PE. Use a V/Q scan when contrast is contraindicated (renal failure, contrast allergy) or in pregnancy with a normal chest radiograph. Compression ultrasound diagnoses DVT by showing a noncompressible vein. Echocardiography can show right heart strain but is not diagnostic; at the bedside of an unstable patient who cannot go to CT, RV dilation supports the diagnosis.
Anticoagulation: choice and duration
| Situation | Preferred agent | Why |
|---|---|---|
| Most VTE | DOAC: apixaban or rivaroxaban, no heparin lead-in | Effective, no INR monitoring; dabigatran and edoxaban need initial parenteral heparin |
| Cancer-associated VTE | LMWH or a DOAC (apixaban, edoxaban, rivaroxaban) | Continue while cancer is active |
| Pregnancy | LMWH | Warfarin is teratogenic; DOACs are not recommended |
| Antiphospholipid syndrome | Warfarin | TRAPS: rivaroxaban was inferior, especially in triple-positive patients |
| Severe renal failure or possible procedure | Unfractionated heparin | Not renally cleared; short-acting and reversible |
Warfarin needs a bridge. Warfarin lowers protein C before the procoagulant factors, so starting it alone is briefly prothrombotic (and can cause skin necrosis in protein C deficiency). Overlap it with heparin until the INR reaches 2–3.
Duration. Provoked VTE, triggered by a transient reversible risk factor such as surgery, is treated for 3 months. Unprovoked VTE, active cancer, or recurrent VTE warrants extended or indefinite anticoagulation, weighed against bleeding risk and reassessed periodically. After stopping treatment for unprovoked VTE, recurrence is roughly 10% in the first year.
Severe PE, filters, and special problems
| Category | Definition | Treatment |
|---|---|---|
| Massive (high-risk) | SBP <90 mmHg for ≥15 minutes or requiring pressors | Systemic thrombolysis (alteplase); embolectomy if lysis is contraindicated |
| Submassive (intermediate-risk) | RV strain on echo or CT, or raised troponin/BNP, with normal BP | Anticoagulate and monitor; thrombolysis case by case |
| Low-risk | Normal BP, no RV strain | Anticoagulation; selected patients can be treated as outpatients |
IVC filters are indicated when anticoagulation is contraindicated (such as active bleeding) or when VTE recurs despite therapeutic anticoagulation. Use a retrievable filter and remove it once anticoagulation is safe. Filters do not treat existing clot.
Thrombophilia testing. Do not test during the acute clot or while on anticoagulation: protein C, protein S, and antithrombin levels fall with acute thrombosis and warfarin, and DOACs distort clotting assays. Consider testing after therapy for unprovoked, young, recurrent, or unusual-site VTE. Antiphospholipid antibody testing is the main exception, because a positive result changes the anticoagulant.
Heparin-induced thrombocytopenia: a platelet fall of more than 50% at days 5–10 of heparin, caused by antibodies to heparin–PF4 complexes, often with new venous or arterial clots (clots are not required for the diagnosis). Stop all heparin (including flushes and LMWH) and start argatroban or fondaparinux. Do not start warfarin until platelets recover, and avoid platelet transfusion unless there is bleeding.