Venous thromboembolism and post-operative management of anticoagulation

Venous thromboembolism (VTE) = deep vein thrombosis (DVT) and/or pulmonary embolism (PE). Almost 60% of all VTE events occur in people over 65.

Incidence rises exponentially with age — from <1 per 1000 person-years below 50 years to about 8 per 1000 person-years above 80.

Older patients are under-represented in trials; most VTE treatment trials excluded those with increased bleeding risk, renal failure or recent stroke, so evidence is extrapolated. Cohorts and registries (RIETE, EPICA, SWITCO65+) fill part of this gap.

Virchow's triad — stasis, endothelial injury and hypercoagulability. In the elderly all three are amplified by immobility, surgery, and age-related increases in fibrinogen and platelet reactivity.

Acquired: immobility and hospitalisation, surgery (especially hip, knee and pelvis), fracture, malignancy, heart failure, stroke with paresis, infection and sepsis, dehydration, obesity, long travel, oestrogens, central venous catheters, nephrotic syndrome and frailty.

Inherited thrombophilia is present in up to 50% of venous thromboses, becoming manifest under the above circumstances: factor V Leiden (commonest inherited defect — a single base substitution at position 1691 causing resistance to activated protein C), prothrombin G20210A, and deficiencies of antithrombin, protein C and protein S. Antiphospholipid syndrome is the important acquired thrombophilia.

Testing caveat: levels of antithrombin, protein C and protein S fall during acute thrombosis, and are further reduced by heparin (antithrombin) and warfarin (proteins C and S) — so test only when the patient is neither acutely thrombosed nor anticoagulated. A positive result should prompt family screening.

DVT algorithm: assess clinical probability with the two-level modified Wells score. If "DVT likely" → complete venous ultrasonography. If "DVT unlikely" → D-dimer; if negative, no DVT and no treatment; if positive, proceed to ultrasound.

PE algorithm (haemodynamically stable): assess probability with the revised Geneva score or Wells score. Low/intermediate probability → D-dimer; if negative, exclude PE. High probability or positive D-dimer → CT pulmonary angiography.

Age-adjusted D-dimer is essential in the elderly, because specificity falls with age. Use a cut-off of age × 10 µg/L in patients over 50 — validated in the ADJUST-PE study; this safely increases the proportion of older patients in whom PE can be excluded without imaging.

Note that asymptomatic DVT is common on admission in older medical inpatients, and that clinical signs and risk factors have different diagnostic value in the elderly than in the young.

DOACs are first choice for acute VTE in the elderly in the absence of cancer or severe renal insufficiency, mainly because of lower intracranial bleeding risk than vitamin K antagonists.

Regimens (Pathy's Table 37.3): Dabigatran — LMWH/UFH/fondaparinux for at least 5 days, then 150 mg twice daily. Rivaroxaban — no lead-in: 15 mg twice daily for 21 days, then 20 mg once daily; extended phase 10 mg once daily. Apixaban — no lead-in: 10 mg twice daily for 7 days, then 5 mg twice daily; extended phase 2.5 mg twice daily. Edoxaban — LMWH lead-in for at least 5 days, then 60 mg once daily, reduced to 30 mg once daily if creatinine clearance 30–50 mL/min, body weight ≤60 kg, or concomitant strong P-glycoprotein inhibitors.

Duration: Pathy's recommends three to six months of anticoagulation in elderly patients with acute VTE, because bleeding risk is higher and the recurrence risk is no greater than in younger patients. Extended treatment is not routinely indicated and any such decision must be carefully justified. Existing recurrence-prediction rules are unhelpful in the elderly — HERDOO2 automatically classes those ≥65 as high risk, DASH is not validated, and the Vienna model lacks discrimination.

Prognosis: 30-day mortality doubles in those ≥65 compared with younger patients (11% versus 4%), and remains higher at one year (31% versus 14%). Use PESI/sPESI to identify low-risk PE suitable for early discharge. The strongest predictors of long-term mortality are systolic BP <100 mmHg, active cancer and age. The main causes of death in the first three months are cancer (38%), PE (26%), infection (13%) and bleeding (6%).

Bleeding: patients ≥65 have an almost twofold higher risk of major and clinically relevant non-major bleeding; age ≥75 at least doubles the risk of intracranial haemorrhage. Low physical activity level and polypharmacy (>4 drugs) predict major bleeding.

Pre-operative interruption. Warfarin — stop 5 days before surgery; check INR the day before; give low-dose vitamin K if INR remains high. Heparin bridging is not required for most patients (BRIDGE trial showed no benefit and more bleeding); reserve bridging for very high thrombotic risk — mechanical mitral valve, recent (<3 months) VTE or stroke, or CHA₂DS₂-VASc ≥7. DOACs — follow the PAUSE protocol, based on drug, renal function and procedural bleeding risk: stop 1 day before a low-bleeding-risk procedure and 2 days before a high-bleeding-risk procedure for apixaban, rivaroxaban and edoxaban; for dabigatran, stop 1–2 days (CrCl ≥50) or 2–4 days (CrCl <50). No bridging and no routine DOAC level testing. The ASRA guidance requires a longer interval — at least 72 hours — before neuraxial anaesthesia and deep nerve blocks; where the two conflict, follow the anaesthetic guidance. No interruption is needed for minor dental procedures, cataract surgery or most skin procedures.

Post-operative resumption and prophylaxis. Restart warfarin on the evening of surgery or the first post-operative day at the usual maintenance dose, once haemostasis is secure and enteral intake has returned. Restart DOACs 24 hours after low-bleeding-risk and 48–72 hours after high-bleeding-risk procedures, since the DOAC reaches full anticoagulant effect within hours. In the interval, give prophylactic-dose LMWH where the thrombotic risk is high and haemostasis is adequate. Continue mechanical prophylaxis (early mobilisation, graduated compression stockings, intermittent pneumatic compression) throughout. For major orthopaedic surgery (hip and knee replacement, hip fracture), give extended thromboprophylaxis for up to 35 days after hip and 14 days after knee surgery, using LMWH, a reduced-dose DOAC or aspirin per protocol. Two safety points: parenteral vitamin K should not be used for non-life-threatening bleeding in patients with mechanical prosthetic valves, because of the risk of inducing a hypercoagulable state; and after cardiac surgery, oral anticoagulation should be restarted as soon as intestinal function permits.