Act Before the RBCS in your Patient’s Vein Reach a Dead End

Venous thromboembolism (VTE) is an umbrella term for various degrees of deep vein thrombosis (DVT) and pulmonary embolism (PE). The risk statistics are alarming: One in every five cases of VTE is related to either cancer and/or its treatment. Cancer Surgery has a 7-fold higher risk of perioperative PE compared to similar surgery for benign disease.  In the absence of routine thromboprophylaxis in surgical cancer patients, a majority (40-80%) develop postoperative isolated or asymptomatic calf vein thrombosis, 10-20% develop proximal DVT, 4-10% acquire symptomatic PE, and unfortunately, 1-5% exhibit fatal PE. It’s no wonder that VTE-prophylaxis is a vital element of the ERAS-Protocol. There exist all three elements of the Virchow’s triad namely, hypercoagulability (cancer, major surgery), vascular damage (multiple venepunctures, arterial line, central venous pressure lines, ports, PICC lines, chemotherapy) and venous stasis (frail, bedridden patients; venous compression by large tumours or bulky lymph nodes) in surgical cancer patients.

Before your patient’s RBCs reach a dead end, let’s check out the cafeteria choice of mechanical and pharmacological thromboprophylactic measures available to us.

Mechanical thromboprophylaxis

This includes elastic graduated compression stockings, intermittent pneumatic calf compression or sequential compression devices and foot pumps. It is extremely important to achieve the right amount of pressure for compression stockings ie 18-23 mmHg for primary VTE prophylaxis at ankle and 30-40 mmHg to prevent or treat post-thrombotic syndrome after an established DVT. Mechanical monotherapy offers a 67% risk reduction for perioperative DVT, but is much less efficacious in preventing perioperative PE. Hence, in high-risk patients a combination therapy with pharmacological thromboprophylaxis is required. Intraoperative intermittent pneumatic compression is achieved by alternate inflation-deflation of plastic/fabric sleeves, wrapped around the leg, secured with Velcro and wired to an electric pump.

Inferior venacava (IVC) filters (temporary or permanent) have very specific and limited indications and should not be indiscriminately used because of significant complications.

Pharmacological thromboprophylaxis

Low-dose Unfractionated Heparin (UFH) effectively reduces the incidence of asymptomatic DVT by 67% and fatal PE by 68% reducing total perioperative mortality by 21%. Low-Molecular-Weight Heparin (LMWH) is obtained by fractionation of UFH and has a longer elimination half-life of 4-6 h (Kidneys). with a similar efficacy and safety profile, LMWHs have an additional advantage of a ten times reduced risk of heparin induced thrombocytopenia (HIT) and osteopenia, coupled with the convenience of fixed once daily injections. Enoxaparin is the most commonly used LMWH in our institution.

Heparinoids like danaparoid, being heparin-free, are useful in surgical patients where heparin is contraindicated (allergy; HIT). Fondaparinux is a synthetic pentasaccharide that produces a 50% greater reduction in the incidence of VTE in major orthopaedic/abdominal surgery, compared to enoxaparin.

Vitamin-K antagonists (VKAs) like warfarin, although efficacious for perioperative VTE prophylaxis, have limited clinical utility owing to a slow onset of action (2-3 days) and a narrow therapeutic window that necessitates regular INR monitoring and frequent dose adjustments.

Directly acting intravenous thrombin inhibitors like lepirudin (recombinant hirudin) in a dose of 2 × 15 mg s/c per day provide primary VTE prevention after hip/knee arthroplasty. Argatroban is the drug of choice in HIT since it does not resemble heparin, averting any cross-reaction with HIT antibodies. Unlike lepirudin, argatroban does not induce formation of alloantibodies that can alter its clearance.

Aspirin is a notable exception in most guidelines for VTE prophylaxis which is probably industry driven. For general surgery, aspirin is NOT recommended as VTE prophylaxis but its use could be interesting in low-income countries.

Contraindications to pharmacological thromboprophylaxis include an INR>2, thrombocytopenia (< 50000/mm3), known bleeding disorders, any active bleeding, uncontrolled hypertension (BP> 230/120 mmHg), neuraxial block (lumbar puncture, subarachnoid block, epidural), performed within the last 4h (last 24h if traumatic) or expected to be instituted within next 12h and new onset stroke (ischemic/haemorrhagic).

Which hospitalized patients with cancer should receive anticoagulation for VTE prophylaxis?

The three prerequisites for pharmacologic thromboprophylaxis include active malignancy, acute medical illness or reduced mobility and absence of bleeding or other contraindications. Anticoagulation is contraindicated in patients admitted solely for minor procedures, chemotherapy or those undergoing stem-cell or bone marrow transplant.

Should ambulatory cancer patients receive anticoagulation for VTE prophylaxis during systemic chemotherapy?

Routine pharmacologic thromboprophylaxis should not be offered to all outpatients with cancer. The three prerequisites include high VTE risk (Khorana score ≥ 2 before a new systemic chemotherapy regimen), absence of significant risk factors for bleeding and no drug-drug interactions (CYP-3A4; P-gp). Apixaban, rivaroxaban or LMWH may be utilized for VTE prophylaxis after educating these patients about relative benefits and harms, drug cost and duration of prophylaxis.

Should surgical cancer patients receive perioperative VTE prophylaxis?

All cancer patients undergoing major surgery should receive pharmacologic thromboprophylaxis with UFH/LMWH unless contraindicated. A combined regimen (pharmacologic + mechanical) has enhanced efficacy in high-risk patients. Mechanical methods monotherapy is resorted to if pharmacologic methods are contraindicated. Ideally commenced preoperatively, the duration is 7 to 10 days postoperatively. Extended prophylaxis with LMWH (4 weeks) is recommended for major open/ laparoscopic/ robotic abdominal or pelvic surgery patients with high-risk features (restricted mobility, obesity, history of VTE). For lower-risk surgical settings, decision on a case-by-case basis is required.

Future directions

Future research should be directed at improving VTE-risk scores, developing and incorporating new biomarkers, oncogenes and machine learning, introducing risk scores for concurrent bleeding risk and improving prophylactic therapy by conducting clinical trials on new compounds like Factor-XI inhibitors (Abelacimab).

To conclude, the risk of VTE should be balanced against the risk of bleeding.

Dr. Shagun Bhatia
Sr. Consultant – Anaesthesia Department
Guest Editor