Venous Thromboembolism

Meet the patient

A 67-year-old man, day 5 after a total hip replacement, sits up to use the bedpan and is stopped by stabbing right-sided pain every time he breathes in. Heart rate 112, saturations 92 percent on air, right calf 4 cm bigger than the left and tender along the deep veins. He is normotensive.^[1]

The two questions that decide the next hour: is this PE from that calf? and is the right ventricle failing? If he is haemodynamically stable, this is an anticoagulation-and-imaging problem, not a lytic one.^[1][2]

One disease, one continuum

DVT and PE are one thrombus read along its length. ESC 2019 frames VTE as globally the third most frequent acute cardiovascular syndrome behind myocardial infarction and stroke. Annual incidence: PE 39–115 per 100 000, DVT 53–162 per 100 000. Incidence is almost eight times higher at age 80 or over than in the fifth decade. ASH 2020 quotes about 1 to 2 events per 1000 each year in the United States.^[1][2]

^{[1] [2] [11] [5]}

Virchow's triad

Every risk factor sits on stasis, endothelial injury, or hypercoagulability. Provoked VTE has a transient trigger (surgery, immobility, pregnancy, oestrogen, hospitalisation). Unprovoked VTE is the prompt for longer anticoagulation and a cancer/thrombophilia work-up in selected patients.^[1][2]

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Severity — the acute decision

ESC 2019 defines haemodynamic instability as cardiac arrest, obstructive shock (systolic BP under 90 mmHg or vasopressors to reach 90 mmHg despite adequate filling plus end-organ hypoperfusion), or persistent hypotension (systolic BP under 90 mmHg or a drop of 40 mmHg or more for over 15 minutes, not caused by new arrhythmia, hypovolaemia or sepsis). That is high-risk PE. In suspected high-risk PE, a RV/LV diameter ratio over 1.0 is the main bedside imaging clue.^[1]

Normotensive PE with RV dysfunction and/or troponin rise is intermediate-risk. PEITHO randomised that group to tenecteplase plus heparin versus heparin: death or haemodynamic decompensation 2.6 vs 5.6 percent, but extracranial bleeding 6.3 vs 1.2 percent and stroke 2.4 percent with tenecteplase. Rescue lysis, embolectomy or catheter-directed therapy is reserved for those who become unstable.^[10][1]

Low-risk PE is identified with PESI / simplified PESI. Jiménez: simplified-PESI low-risk 30-day mortality 1.0 percent versus 10.9 percent high-risk. ESC table: 0 points = 30-day mortality 1.0 percent. Simplified items include age over 80, cancer, chronic heart or lung disease, pulse 110 or over, systolic BP under 100 mmHg, and oxygen saturation under 90 percent.^[20][1]

Probability first — Wells, PERC, then D-dimer

D-dimer rules out; it never rules in. Wells 1997 (DVT): among outpatients, DVT was present in 3 percent (low), 17 percent (moderate) and 75 percent (high) pretest probability. Wells 2001 (PE, emergency department): PE in 1.3 percent (low), 16.2 percent (moderate) and 37.5 percent (high) — not "60 percent high". Use the named Wells clinical model; do not invent point tables that are not in the fetched abstracts.^[23][22]

Christopher (van Belle, JAMA 2006): dichotomised Wells ("PE unlikely" vs "likely"), D-dimer, then CT. PE-unlikely plus a normal D-dimer occurred in 32.0 percent; among those untreated, subsequent nonfatal VTE was 0.5 percent. The algorithm allowed a management decision in 97.9 percent.^[13]

PERC (Kline): with gestalt suspicion under 15 percent and all of — age under 50, pulse under 100, saturations at least 95 percent, no haemoptysis, no oestrogen, no surgery/trauma needing hospitalisation within 4 weeks, no prior VTE, no unilateral leg swelling — the false-negative rate was 1.0 percent (16 of 1666, about 20 percent of outpatients). That is the rule that spares a D-dimer cascade, not a licence to skip imaging in anyone who "looks well".^[19]

Age-adjusted D-dimer (ADJUST-PE): cutoff age × 10 in patients 50 or older (ESC writes age × 10 µg/L for those over 50). It increased the yield of a negative D-dimer in the elderly versus a fixed 500 µg/L cut-off.^[21][1]

Imaging: compression ultrasound for DVT (non-compressibility); CTPA for PE; V/Q when contrast or radiation is a problem; bedside echo when the patient is too unstable for the scanner.^[1]

Anticoagulation — a DOAC by default

ASH 2020: preference for DOACs over VKA for primary treatment, INR 2.0 to 3.0 if a VKA is used, and indefinite anticoagulation for recurrent unprovoked VTE. ESC: NOACs first choice if the patient is eligible.^[2][1]

^{[4] [7] [8] [6] [15]}

Renal impairment raises DOAC exposure; Hokusai halved edoxaban to 30 mg when clearance was 30 to 50 mL/min or weight under 60 kg. In severe impairment prefer a VKA or UFH rather than guessing an untested DOAC dose.^[15][2]

LMWH — pregnancy and cancer

ASH pregnancy 2018: VTE complicates about 1.2 per 1000 deliveries. Strong recommendation for LMWH over UFH for acute VTE in pregnancy; once- or twice-daily LMWH both acceptable. Do not withhold indicated imaging.^[3]

CLOT: dalteparin 200 IU/kg daily for one month then about 150 IU/kg versus a coumarin (INR target 2.5): recurrence at six months 9 vs 17 percent.^[14]

Caravaggio: apixaban (same AMPLIFY load) versus dalteparin in cancer-associated VTE — recurrence 5.6 vs 7.9 percent, major bleeding 3.8 vs 4.0 percent. ESC 2019: edoxaban or rivaroxaban may be considered instead of LMWH, with caution in gastrointestinal cancer. Do not teach "LMWH is always preferred over every DOAC in cancer" — that predates Caravaggio.^[9][1]

Warfarin necrosis, HIT, and reversal

Start a VKA with a parenteral anticoagulant until the INR is therapeutic (RE-COVER's oral dabigatran followed a median 9-day heparin lead-in; warfarin itself still needs overlap). Warfarin-induced skin necrosis typically appears in the first few days, with painful haemorrhagic lesions that can necrose; it is associated with protein C or S deficiency and high-dose warfarin without heparin bridging.^[6][24]

If platelets fall and new thrombosis appears on heparin, stop all heparin and switch to a non-heparin anticoagulant — do not "just change to LMWH".^[2]

Idarucizumab 5 g IV: median maximum dabigatran reversal 100 percent (RE-VERSE AD). Andexanet alfa: excellent or good haemostasis in 82 percent at 12 hours (ANNEXA-4).^[16][17]

High-risk PE — lyse on haemodynamics

ASH 2020 strongly recommends thrombolytic therapy for PE with haemodynamic compromise. ESC prefers rtPA 100 mg over 2 hours to prolonged streptokinase or urokinase infusions, and lists an accelerated 0.6 mg/kg over 15 minutes (maximum 50 mg). Do not send an unstable patient to CT if echo already shows a failing RV and the bedside mimics (tamponade, tension pneumothorax, STEMI) are out.^[2][1]

MAPPET-3 tested heparin plus 100 mg alteplase over 2 hours in submassive (stable) PE — it reduced treatment escalation, not a licence to lyse every intermediate-risk patient. Chatterjee meta-analysis: thrombolysis associated with lower all-cause mortality (OR 0.53; 2.17 vs 3.89 percent) at the cost of more major bleeding (9.24 vs 3.42 percent).^[12][18]

How long?

• Provoked by a transient factor — the DOAC trials treated for 3, 6 or 12 months (EINSTEIN) or 6 months (AMPLIFY). If the trigger has gone, stopping after a finite course is the default.
• First unprovoked — AMPLIFY-EXT: after 6 to 12 months, placebo 8.8 percent recurrent VTE or VTE death in 12 months versus 1.7 percent on apixaban 2.5 mg or 5 mg twice daily; major bleeding 0.2 percent (2.5 mg) and 0.1 percent (5 mg) versus 0.5 percent placebo. ESC: consider reduced-dose apixaban or rivaroxaban after the first 6 months.
• Recurrent unprovoked — ASH strong recommendation for indefinite anticoagulation.
• Cancer — CLOT and Caravaggio treated for 6 months, then continue while cancer is active.^{[4][5][2][1][9][14]}

CTEPH — the late, curable complication

Pengo (first PE, no prior VTE): symptomatic CTEPH 1.0 percent at 6 months, 3.1 percent at 1 year, 3.8 percent at 2 years. Unexplained dyspnoea after PE earns a V/Q scan, not another chest X-ray.^[11]

The trials that changed practice

^{[7] [8] [4] [5] [6] [9] [10]}

How VTE patients come to harm

• Anticoagulating aortic dissection mistaken for PE.
• Sending high-risk PE to the scanner instead of reperfusion.
• Skipping PERC and chasing a false-positive D-dimer into unnecessary CTPA — or skipping imaging in a high-probability patient because the D-dimer is only mildly raised.
• Giving a full-dose DOAC in severe renal failure.
• Teaching LMWH forever in every cancer VTE as if Caravaggio did not exist — or ignoring ESC's GI-cancer bleeding caution with edoxaban/rivaroxaban.
• Starting warfarin without heparin in protein C deficiency.
• Routine tenecteplase in intermediate-risk PE after PEITHO.^{[1][2][10][24]}

The mantra

Virchow first, Wells next, D-dimer to rule out, DOAC to treat — lyse only if the blood pressure has collapsed — and never anticoagulate a dissection.^[1][2]

Ward-round test

Stem 1 — day-5 hip replacement (answer)ShowHide

The 67-year-old, day 5 after hip replacement, pleuritic pain, heart rate 112, saturations 92 percent, swollen calf, normotensive. Next step and first drug? Model: Provoked PE from proximal DVT until proven otherwise. He is stable, so no thrombolysis. Score Wells (clinical signs of DVT, PE the likely diagnosis), exclude dissection at the bedside, then CTPA (Christopher algorithm). Start anticoagulation — apixaban 10 mg twice daily if no bleed contraindication — and ultrasound the leg.^[13][4]

Stem 2 — syncope with clear lungs (answer)ShowHide

A 72-year-old collapses, BP 78/50, saturations 88 percent, JVP raised, lungs clear, T inversion V1–V3, echo shows a dilated RV. Next 15 minutes? Model: High-risk PE. Do not send her to CT. ASH strongly recommends thrombolysis for haemodynamic compromise; ESC prefers rtPA 100 mg IV over 2 hours. Support BP, then confirm once stable. Chatterjee: mortality OR 0.53 versus anticoagulation alone, with more major bleeding.^[2][1][18]

Stem 3 — intermediate-risk and the PEITHO trap (answer)ShowHide

Normotensive PE, RV strain on CT, troponin positive. The registrar wants "the PEITHO lytic". What did PEITHO actually randomise, and what happened? Model: Tenecteplase plus heparin versus heparin, not alteplase 100 mg. Death or decompensation 2.6 vs 5.6 percent, extracranial bleeding 6.3 vs 1.2 percent, stroke 2.4 percent. No significant day-7 mortality difference. Anticoagulate and watch; rescue reperfusion if she becomes unstable.^[10][1]

References24ShowHide

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