VTE Prophylaxis

Venous thromboembolism (VTE) Prophylaxis

OVERVIEW

• Venous thromboembolism (VTE) may contribute to up to 12% of deaths in ICU and is the No.1 preventable cause of hospital death
• asymptomatic events range from 10-80% in various medical and surgical groups
• silent DVT is present in 5-10% of ICU patients despite thromboprophylaxis
• importance of asymptomatic DVT uncertain -> if seen on Doppler then significantly higher chance of embolism
• even small PEs may be tolerated poorly by the critically unwell
• ICU doctors often have a skewed perception of the risk of bleeding in ICU patients, predisposing them to avoiding anticoagulation

RISK FACTORS

SLOMM-COM-Throm! = essentially all ICU patients

Major (relative risk 5-20) – SLOMMM

• Surgery and trauma – major abdominal/pelvic, hip/knee replacements, TBI
• Lower limb problems – fractures, varicose veins
• Obstetrics – late pregnancy, C-section, puerperium
• Malignancy – abdominal/pelvic, advanced/metastatic
• Mobility – hospitalization, institutional care
• Miscellaneous – previous VTE

Minor (relative risk 2-4) – COM

• Cardiovascular – congenital heart disease, CHF, HTN, superficial venous thrombosis, CVL
• Oestrogens – OCP, HRT
• Miscellaneous – COPD, neurological disability, occult malignancy, thrombotic disorder, long distance travel, obesity, other (IBD, nephrotic syndrome, dialysis, myeloproliferative disorders, paroxysmal nocturnal haemoglobinuria, Bechet’s disease)

Thrombophillias

• Factor V Leiden mutation
• Prothombin gene mutation (G20210A)
• hyperhomocysteinemia
• Antiphospholipid antibody syndrome (lupus anti-coagulant & anti-cardiolipin antibodies)
• Deficiency of antithrombin III, protein C or protein S
• High concentrations of factor VIII or XI
• Increased lipoprotein (a)

-> test in those < 50y with recurrent or a strong FHx

MANAGEMENT

• many different strategies
• risk should be considered
• reviews and recommendations are widely published -> data quality is low
• good placebo controlled RCT’s are rare

Non-pharmacological

• TED stockings (simple, widespread use, effective for low risk patients but less so than pharmacological methods)
• hydration (physiological basis only)
• intermittent pneumatic compression (recommended but limited evidence, useful where anticoagulation contraindicated)
• passive mobilisation (not well studied)
• early mobilisation (not well studied)
• minimisation of intraoperative duration
• optimal cardiac output
• clinical and imaging surveillance
• elective insertion of an IVC filter (procedure risks, increase risk of DVT even if anticoagulated, only removed from 20% of patients, only recommended in high risk patients)

Pharmacological

• regional anaesthesia (low quality data)
• adequate analgesia
• aspirin 100-300mg OD
• heparin 5000IU SC BD
• enoxaparin 40mg or 0.5 mg/kg SC OD (20mg OD if has renal impairment, similar or better than heparin, with less thrombocytopaenia, only slight increase in bleeding)
• IV heparin titrated to an APTT of 60-80 seconds
• pentasaccharides (new, showing promise)
• hirudin (new, showing promise)
• dextran (old, not used)
• warfarin (less frequently used)
• fondaparinux (2.5mg od, better than LMWH in meta-analysis of post-orthopedic surgery patients, no HITS)
• other controversies include cost-benefit and side-effect profiles

CONTRA-INDICATIONS

Pharmacological

• active bleeding objectively confirmed
• suspected active bleeding without objective confirmation (e.g. falling Hb)

Minor bleeding is not a contra-indication

Mechanical

• bilateral leg trauma
• skin, muscle or bone grafting to lower limbs
• major lower limb surgery
• lower limb ischemia or peripheral vascular disease
• not tolerated by patient

Theoretical risk of dislodging a DVT that is already present with delayed application of IPCs
-> if >24h without VTE prophylaxis perform lower limb ultrasound prior to starting IPCs

SPECIAL SITUATIONS

Trauma

• GCS/IPC if active bleeding or solid organ injury (48h)
• if CI then IVC filter if 2 of:
  (1) spinal injury,
  (2) pelvic injury,
  (3) multiple lower limb long bone fractures

Ocular trauma

• discuss with opthalmologist

TBI

• no haemorrhage, repeat CTH
  -> LMWH at 24-48h
• petechiae, repeat CTH
  -> LMWH at 48-72h
• significant haemorrhage, repeat CTH
  -> LMWH at day 7

spinal cord injury

• discuss with spinal surgeon

stroke

• ischaemic: LMWH in most situations
• intracerebral haemorrhage: GCS/IPC for 3-4 days then LMWH

EVIDENCE

• DVT rate in ICU with prophylaxis = 5-10%
• LMWH as good as SC heparin BD

PROTECT trial 2011

• MCRCT
• ~4000 patients
•  LMWH dalteparin vs unfractionated heparin
• primary outcome: proximal leg DVT incidence
• no statistically significant difference between the two modalities BUT significantly less PEs with dalteparin (? wrong primary outcome choice)
• which called into question what we should be using as our main outcome measure for VTE.
• no difference in  complications (bleeding, HIT)

AN APPROACH

• routinely used non-pharmacological techniques (GCS, IPCs, hydration, mobilise)
• LMWH 40mg SC or 20mg SC in renal failure (once daily dosing, heparin not superior, bleeding not an issue, cheap, does not accumulate at prophylactic doses in ESRF, possible trend to decreased PE in the PROTECT trial)
• review daily

References and Links

Journal articles

• Geerts WH, Pineo GF, Heit JA, Bergqvist D, Lassen MR, Colwell CW, Ray JG. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):338S-400S. PMID: 15383478.
• PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med. 2011 Apr 7;364(14):1305-14. PMID: 21417952.
• Sachdeva A, Dalton M, Amaragiri SV, Lees T. Elastic compression stockings for prevention of deep vein thrombosis. Cochrane Database Syst Rev. 2010 Jul 7;(7):CD001484. doi: 10.1002/14651858.CD001484.pub2. Review. PubMed PMID: 20614425.

FOAM and web resources

• ICN — Podcast 50. Good Housekeeping (2012)
• Maryland CCP — VTE Prophylaxis in TBI (2013)