Chapter 10

Venous thromboembolism (VTE) is the main cause of pulmonary embolism (PE), which is present in up to 27% of postmortem examinations, contributing to death in up to 12% of ICU patients. Of the deceased patients, there is a clinical suspicion for PE in only 30%.1

Virchow’s Triad identifies three predisposing factors for VTE. These are hypercoagulability, as in sepsis; vascular stasis as in prolonged major surgery, prolonged bed rest in the supine position, delayed ambulation and vessel injury as in trauma.

The main risks for Deep Vein Thrombosis (DVT) in the general population are well known, including hospital or nursing home confinement, surgery, trauma, malignant neoplasm, chemotherapy, neurologic disease with paresis, central venous catheter or pacemaker, varicose veins, smoking and use of some oral contraceptives. Difficulty in applying screening and the heterogeneity of the ICU population have resulted in few publications on this issue in the ICU population. Ansari et al. found that the most common risk factors in medical patients were bed rest > 72 hours, age > 60 years and age 4,060 years. Among surgical patients the risk factors were major surgery in 80.25%, central venous access and age 40–60 years.2 When assessing more specifically for ICU acquired risk factors for VTE/DVT, mechanical ventilation (OR 1.56), immobility (OR 2.14), femoral venous catheter (OR 2.24), sedatives (OR 1.52) and paralytic drugs (OR 4.81) were associated with higher risk. On the other hand, VTE heparin prophylaxis (OR 0.08), aspirin use (0.42) and thromboembolic disease stockings (OR 0.63) were associated with a decreased risk for VTE. Warfarin use (OR 0.07 P = 0.01) and intravenous heparin (OR 0.04 P < 0.01) were associated with a significantly decreased risk of VTE.³

VTE Prevention

As described by Hyers et al. in 1995, oral anticoagulants given after unfractionated heparin, prevents PE in 95% of the patients with proximal DVT.⁴

VTE prophylaxis regimens for non-ICU patients may not necessarily be extrapolated to more critically ill patients, mainly because the risk/benefit ratio in this population for thromboprophylaxis, differs significantly from that of non-ICU patients.^1,5 However, a large meta-analysis of 7,226 patients by Alhazzani et al. suggests that any type of heparin thromboprophylaxis decreases deep vein thrombosis and PE in critically ill patients, and low-molecular-weight heparin compared with twice daily unfractionated heparin decreases PE. Major bleeding events and mortality rates did not appear to be significantly influenced by heparin thromboprophylaxis in this study. Therefore the main issue, in the ICU population, is to assess the risk of thromboprophylaxis and the risk of VTE. In 2012, a large multicenter study from Asia, showed that the assessment for high risk for VTE in patients varies among physicians. When using their own clinical judgment, physicians categorized only 8.4% of ICU patients as having high risk for VTE. When applying a stratification objective scale as the Caprini risk stratification, 54.9% of the patients were included in the high risk for VTE group, suggesting that objective parameters should be applied when assessing ICU patients.⁶ The assessment of VTE risk and prevention was also described by the ENDORSE study published in 2008. After enrolling 68,183 patients from 32 countries they found 51.8% of the patients being at risk for VTE. In spite of this finding no more than 58.5% of the patients, were receiving adequate prophylaxis as recommended by published guidelines.⁷ Similar results were reported by Tapson et al. in 2007 after collecting data from 15,156 patients from 12 different countries, finding that only 60% of patients who needed prophylaxis, were actually receiving it.8 As previously discussed, ICU patients are at high risk of VTE and are prime candidates for prophylaxis. VTE prevention techniques include mechanical, chemical and inferior vena cava filters.

—  Mechanical prophylaxis includes:

  1.  Intermittent pneumatic compression

  2.  Graduated compression stockings

—  Chemical prophylaxis includes:

  1.  Unfractionated heparin

  2.  Low-molecular-weight heparin

  3.  Fondaparinux

  4.  Warfarin

  5.  Aspirin

  6.  Dabigatran, Rivaroxaban

  7.  Inferior Vena Cava filters (IVC filters)

Megan et al. when analyzing 30 public hospital ICU’s from Australia and New Zealand, found that of 502 patients, 64% were receiving pharmacological prophylaxis, 80% mechanical prophylaxis and 44% receiving both. Patients who did not receive pharmacological prophylaxis were those having recent neurosurgery, intracranial hemorrhage or coagulopathy as well as other less frequent or not specified causes.⁹

Chemical prophylaxis is suggested in all high risk patients for VTE. ICU patients are all at high risk for VTE so they should receive chemical prophylaxis as soon as possible. The main concern when using chemical prophylaxis is the risk of bleeding, which should be assessed on a case by case basis by considering any possible source of bleeding, recent trauma or surgery etc. As to which chemical prophylactic agent to choose, the literature generally favors low molecular weight heparin while unfractionated heparin is considered as an effective agent, especially in the orthopedic literature.¹⁶

When chemical prophylaxis is not possible, mechanical prophylaxis should be initiated, most preferably with intermittent pneumatic compression devices (IPC) until chemical prophylaxis is possible and is then added to IPC. Although, using both chemical and mechanical prophylaxis has not been proven in the literature, the combination appears safe.^a

In spite of the strong evidence supporting the use of early thromboprophylaxis in the ICU patient as soon as possible, the literature shows as few as 33% of the patients actually receive adequate prophylaxis.10 This may be explained by ICU systems where there is no common protocol, with each physician prescribing what he/she considers appropriate. In addition, many patients fail to receive VTE prophylaxis because of the increased risk of bleeding and other complications associated with the surgery or intervention itself. Having strict protocols and quality assurance programs is necessary to ensure that the patients receive the needed prophylaxis. Regarding prevention of DVT/PE in the acutely ill patient, the use of relatively new anticoagulants such as the direct thrombin inhibitors, Rivaroxaban of Dabigatran is not recommended.

Some studies have shown that these drugs are efficient in preventing thromboembolic events in the short and long term, but the risk of bleeding increases when compared to LMWH.^11,12

Inferior vena cava filters have been very helpful in the prophylaxis of PE disease. First described buy Trousseau in 1865, it was not until 1973 with Greenfield’s percutaneous technique, that this device was considered in patients at high risk of PE but in whom anticoagulation was contraindicated. In 1990 with the availability of retrievable IVC filter devices, the use of IVC filters became more widespread in the ICU setting.¹³ Decousus et al. in 1998, randomized two groups among 400 patients at high risk for PE, one with and the other without IVC filter. At day 12, 1.1% of the filter group had PE, compared to 4.8% in the no filter group (OR 0.22). However, in the filter group, who did not receive anticoagulation, 20.8% had recurrent DVT, compared to 11.6% in those that did not receive an IVC filter but were anticoagulated (OR 1.87). There was no statistical significant difference in mortality between the two groups.¹⁴

Recommendations in the literature differ on the use of Inferior Vena Cava filters.

In 2006, Kaufman et al. of the Society of Interventional Radiology, suggested that any patient with high risk for developing VTE should have an IVC filter inserted.¹⁵ The 9th edition of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines for Diagnosis, Therapy and Prevention for VTE, with Level 1B recommended against IVC filter in addition to anticoagulants in patients with acute DVT of the leg.¹⁶ However, they did recommend the use of IVC filter in patients with acute DVT of the leg, in whom anticoagulation is contraindicated because of high bleeding risk, as occurs in many ICU patients.

Sarosiek et al. assessed more than 900 patients with IVC filter in a level 1 Trauma center and reported that as low as 8.5% of the patients with an IVC filter, had the filter successfully removed. They also reported that 48% of VTE events, occurred in patients with no thromboembolism at time of IVC filter insertion, and that many IVC filters were inserted in patients in whom the risk for bleeding was already low, and anticoagulation could have been initiated.13

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