Thromboprophylaxis for the critically ill patient

Question 2 from the first paper of 2003 and Question 10 from the first paper of 2010 discuss thromboprophylaxis in the ICU. One question was a straightforward "critically evaluate" piece, and the other was related more to the setting of neurotrauma. The delicate issue of giving chemical anticoagulants to somebody who has bled into the brain is discussed in the separate chapter on thromboprophylaxis in neurosurgical patients. The summary below is derived largely from the excellent LITFL page on this subject, as well as from a nice recent article (Boonyawat and Crowther, 2015).

Rationale for the use of thromboprophylaxis in ICU patients

  • DVT develops in a large proportion of ICU patients in the absence of DVT prophylaxis:
    • up to 30% of general medical/surgical ICU patients
    • 50-65% of trauma patients
    • 20%-50% of neurosurgical patients
    • 80% of spinal cord injury patients
  • VTE is a significant cause of ICU mortality and morbidity
  • Even small emboli may be disastrous

The table of undifferentiated risk factors for VTE is reproduced below:

Risk Factors for Pulmonary Embolism

Inherited risk factors

  • Antithrombin III deficiency
  • Protein C deficiency
  • Protein S deficiency
  • Factor V Leiden mutation
  • Hyperhomocysteinaemia

Acute risk factors

  • Surgery
  • Trauma
  • Pregnancy 
  • Burns
  • CVC, Swan-Ganz
  • Spinal injury with paralysis
  • Immobility

Chronic risk factors

  • Smoking
  • Obesity
  • Oral contraception
  • Hormone replacement
  • therapy
  • Malignancy
    Heart failure
  • Lupus anticoagulant
  • Increasing age

If one finds this loosely assembled list of risk factors satisfying, it may be because it does not in any way describe the relative contribution of risk for each risk factor. A mch better list (but one which is more difficult to remember) can be generated from the 30-item Caprini inventory. This is discussed in greater detail in the chapter on DVT in ICU. 

Risk Factors for VTE - Caprini Model from Obi et al (2015)
(1 point) (2 points) (3 points) (5 points)

- Age <41
- Minor surgery
- Varicose veins
- Inflammatory bowel disease
- Obesity (BMI >25)
- Pneumonia
- Sepsis
- Bed rest

- Age 41-60
- Arthroscopy
- Malignancy
- Major surgery
- Laparoscopy
- confined to bed for > 72 hrs
- CVC device
- Age 61-74
- History of DVT
- Inherited thrombotic disorder
- Age >75
- Arthroplasty
- Lower limb fracture
- Stroke
- Multitrauma
-Acute spinal cord injury

Female-specific risk factors:

  • Oral contraceptive
  • Postpartum or peripartum
  • Has recently had an unexplained miscarriage

Therapeutic options to prevent venous thromboembolism

The main options are:

  • Unfractionated heparin
  • Low molecular weight heparin
  • Compression stockings
  • Sequential pneumatic compression devices
  • Early mobilisation
  • IVC filters should probably be included in this list, as they prevent embolism, but not thrombosis (in fact if anything they probably worsen the conditions of venous stasis). In any case, their use is discussed in the chapter on inferior vena cava filters.

The limitations of these options:

  • Risk of bleeding with chemical methods, particularly if there are high risk features:
    • Low platelets (less than 50)
    • Active gastric ulcer bleeding
    • Recent bleeding of ay sort within the last 3 months
  • Risk of DVT dislodgement with pneumatic compression
  • Risk of falls with early mobilisation
  • Risk of limb ischaemia with compression stockings
  • Compression stockings may be contraindicated in lower limb surgery or trauma
  • There is a failure rate: 5-15% of patients still get DVT or PE in spite of being on regular unfractionated heparin (Ribic et al, 2009)


  • Omission of thromboprophylaxis is independently associated with an increased ICU and in-hospital mortality (Ho et al, 2011)
  • Beyond the abovementioned high-risk groups, for the generic patient population there does not appear to be any great increase in the risk of bleeding with chemical VTE prophylaxis (according to the massive IMPROVE study  from 2011)
  • The recommendation for early mobilisation is based on the knoweldge that immobility is associated with DVT, rather than on any sort of prospective trial evidence.
  • Heparin of any sort is protective against DVT (16 studies with a combined n=34,369) - the risk of DVT appears to be halved.
  • No difference between LMWH and UHF (PROTECT trial), which is the most recent large entry into the DVT prophylaxis arena. It was negative- there was no difference between LMWH and UFH. However, a significant reduction in the incidence of PE was found with LMWH, which has led some authors to recommend it as the first choice in renally normal patients.
  • Unfractionated heparin is inferior to low molecular weight heparin in the context of ICU thromboprophylaxis, but may be preferable in the ICU population  because it can be easily reversed with protamine in case of bleeding (whereas only about a third of the anticoagulant effect of enoxaparin would be reversed by protamine). In any case, the evidence to support the "superiority" of LMWH comes from just one study (the PROTECT trial again),
  • Chemical anticoagulation is more effective than mechanical thromboprophylaxis.
  • Intermittent compression stockings are better than nothing according to a recent prospective cohort study.
  • Compression stockings in the ICU are purely decorative according to the same study, but in the general hospital population they are better than nothing, and have a cumulative benefit when used together with other methods of DVT prophylaxis.
  • Authors trend towards the suggestion that a combination of chemical and mechanical methods is the best practice.


LIFL have an excellent page on VTE prophylaxis in the ICU.

Cook, Deborah, et al. "Dalteparin versus unfractionated heparin in critically ill patients." The New England journal of medicine 364.14 (2011): 1305-1314.

Attia, John, et al. "Deep vein thrombosis and its prevention in critically ill adults." Archives of Internal Medicine 161.10 (2001): 1268-1279.

Arabi, Yaseen M., et al. "Use of Intermittent Pneumatic Compression and Not Graduated Compression Stockings Is Associated With Lower Incident VTE in Critically Ill Patients Mechanical Prophylaxis in Critically Ill Patients A Multiple Propensity Scores Adjusted Analysis." CHEST Journal 144.1 (2013): 152-159.

Sachdeva, Ashwin, et al. "Elastic compression stockings for prevention of deep vein thrombosis." Cochrane Database Syst Rev 7.7 (2010).

Alikhan, Raza, Rachel Bedenis, and Alexander T. Cohen. "Heparin for the prevention of venous thromboembolism in acutely ill medical patients (excluding stroke and myocardial infarction)." status and date: New search for studies and content updated (no change to conclusions), published in 5 (2014). Cochrane Database of Systematic Reviews 2014, Issue 5.

Boonyawat, Kochawan, and Mark A. Crowther. "Venous thromboembolism prophylaxis in critically ill patients." Seminars in thrombosis and hemostasis. Vol. 41. No. 1. 2015.

Ribic, Christine, et al. "Low-molecular-weight heparin thromboprophylaxis in medical-surgical critically ill patients: a systematic review." Journal of critical care 24.2 (2009): 197-205.

Ho, Kwok M., Shaila Chavan, and David Pilcher. "Omission of early thromboprophylaxis and mortality in critically ill patients: a multicenter registry study." CHEST Journal 140.6 (2011): 1436-1446.

Decousus, Hervé, et al.  "Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators." CHEST Journal 139.1 (2011): 69-79.