By Brooks Crowe, MD
Peer Reviewed
A 73-year-old female presents to the emergency room with four days of fever, cough, and progressive dyspnea. Chest x-ray reveals multifocal pneumonia. She is subsequently intubated for worsening respiratory failure and admitted to the ICU. While obtaining collateral history, an accompanying family member mentions she recently was at an outside hospital with a lower gastrointestinal bleed requiring a blood transfusion, but is unable to provide any further details.
What is the appropriate method for venous thromboembolism (VTE) prophylaxis in this patient?
The 2012 Chest Physician Guidelines for prevention of VTE in nonsurgical patients recommends pharmacologic thromboprophylaxis for acutely ill hospitalized patients who are at increased risk of thrombosis.[1] Hospital admission for an acute medical illness can increase a person’s risk of VTE by eight fold.[2] For critically ill patients, the estimated incidence of deep vein thrombosis (DVT) ranges from 13-31%, and the reported mortality for ICU patients sustaining a pulmonary embolism (PE) can be as high as 30%.[3] For nonsurgical patients with active bleeding or at increased risk for major bleeding, mechanical prophylaxis with graduated compression stockings (GCS) or intermittent pneumatic compression (IPC) devices are the preferred prophylactic methods.[1] IPCs are thought to enhance blood flow in the deep veins of the lower extremities.[5] In addition, IPCs stimulate endogenous fibrinolytic activity likely through a decrease in plasminogen activator inhibitor-1 (PAI-1) and a subsequent increase in tissue plasminogen activator (tPA) activity.[6] However, at the time of publication of the 2012 Chest guidelines, no studies existed examining IPCs in hospitalized medical patients and instead were extrapolated based on analysis of mechanical prophylaxis in surgical patients.[3,4]
More recently there have been efforts to evaluate the use of IPCs – the primary method of mechanical prophylaxis at our institution – specifically in non-surgical patients, as compared to pharmacologic thromboprophylaxis with low molecular weight heparin (LMWH) or unfractionated heparin (UFH).
Gaspard et al. retrospectively examined mechanical prophylaxis (IPC) directly against pharmacologic prophylaxis (LMWH or UFH) in nonsurgical patients.[4] By analyzing only patients who were mechanically ventilated, the authors hoped to minimize non-compliance. Of the 329 patients receiving pharmacologic prophylaxis, there was one DVT and no PE events in comparison to 12 DVTs and one PE among the 419 patients in the IPC group (p <.01). Overall mortality was also significantly higher in the mechanical group compared to the pharmacologic group (50.6% and 34.3% respectively, p <.01). Controlling for various characteristics and comorbidities, multivariate analysis showed that patients treated with IPC were significantly more likely to develop VTE (OR 9.9, p = .028).
The CLOTS3 trial randomized 2876 patients admitted following an acute stroke to mechanical VTE prophylaxis versus no VTE prophylaxis.[7] Lower extremity duplex ultrasound was performed once between days 7-10 and again between days 25-30 with a primary endpoint of proximal DVT seen on duplex or symptomatic proximal DVT within 30 days of randomization. The primary outcome occurred in 8.5% of patients using IPCs as compared to 12.1% of patients without VTE prophylaxis. After excluding those patients who died before the primary outcome could be measured at days 25-30, and those who did not receive screening duplex studies, IPC use led to a significant reduction in proximal DVT compared to control with an adjusted odds ratio of 0.65 (95% CI 0.51-0.84, p<.01).
Park et al. performed a meta-analysis to study pharmacologic versus mechanical prophylaxis based on 12 RCTs across a mixed ICU population (8,622 medical, trauma, and surgical patients).[3] Across all types of patients, those treated with IPCs did not have a statistically significant lower risk of DVT compared to control population (no prophylaxis or only treated with GCS). By comparison, those treated with LMWH or UFH had a significantly lower risk of DVT compared to control; OR 0.38 (95% CI 0.18, 0.72) and 0.45 (95% CI 0.22, 0.83), respectively. However a randomized control study included in this meta-analysis looked specifically at 162 medical patients in the ICU and compared IPC vs control (no mechanical or chemical prophylaxis).[8] The IPC group had lower rates of DVT (3.80% vs 19.28%, P<.01), PE (0 vs. 9.64%, P<.01) and non-sudden cardiac death (1.26% vs. 7.23%, P<.01).
While the majority of patients admitted to the medical ICU and general medicine floors have no contraindication to pharmacologic DVT prophylaxis, a small percentage will have an absolute or relative contraindications and will instead be managed with mechanical prophylaxis. While IPCs are well studied in surgical patients, based on the recent studies in medical patients detailed above, IPCs do appear to reduce the risk of VTE compared to no prophylaxis, but seem to lack efficacy in comparison to pharmacologic prophylaxis. This makes it particularly important for providers to assess a patient’s VTE risk in order to best determine the necessity for pharmacologic prophylaxis. Tools like the Padua Score, which estimates 90-day risk of symptomatic VTE based on a twenty-point scale for those patients receiving no anticoagulation during hospitalization,[9] and the GENEVA risk score, which estimates 30 day risk of symptomatic VTE or VTE related mortality,[10] can help providers assess risk of VTE and associated complications. Ultimately, for those patients with a relative contraindication to pharmacologic prophylaxis, careful consideration should be given in regards to whether the risk of VTE would outweigh the risk of significant bleeding events if trialed with pharmacologic prophylaxis.
Dr. Brooks Crowe is a 2019 graduate of the NYU Langone Internal Medicine Residency
Peer reviewed by David Green, MD, Chief of Anticoagulation Services, NYU Langone Health
Image courtesy of Flickr Commons, Threthny
References
[1] Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in Nonsurgical Patients Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 suppl):e195S–e226S.
[2] Al Yami MS, Silva MA, Donovan JL, Kanaan AO. Venous thromboembolism prophylaxis in medically ill patients: a mixed treatment comparison meta-analysis. Journal of Thrombosis and Thrombolysis. Epub ahead of print: Oct 17, 2017. https://link.springer.com/article/10.1007/s11239-017-1562-5. Accessed November 10, 2017.
[3] Park J, Lee JM, Lee JS, Cho YJ. Pharmacological and Mechanical Thromboprophylaxis in Critically Ill Patients: a Network Meta-Analysis of 12 Trials. J Korean Med Sci 2016;31:1828-1837.
[4] Gaspard D, Vito K, Schorr C, Hunter K, Gerber D. Comparison of Chemical and Mechanical Prophylaxis of Venous Thromboembolism in Nonsurgical Mechanically Ventilated Patients. Thrombosis 2015;2015:1-6.
[5] Roberts VC, Sabri S, Beeley AH, Cotton LT. The effect of intermittently applied external pressure on the haemodynamics of the lower limb in man. Br J Surg 1972;59(3):223-226.
[6] Comerota AJ, Chouhan V, Harada RN, et al. The fibrinolytic effects of intermittent pneumatic compression: mechanism of enhanced fibrinolysis. Ann Surg 1997;226(3):306-313.
[7] CLOTS Trials Collaboration. Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke (CLOTS 3): a multicentre randomised controlled trial. Lancet 2013;382:516–24.
[8] Zhang C, Zeng W, Zhou H, et al. The efficacy of intermittent pneumatic compression in the prevention of venous thromboembolism in medical critically ill patients. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2011;23(9):563-5.
[9] Barber S, Noventa F, Rossetto V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost 2010;8(11):2450-7.
[10] Nendaz M, Spirk D, Kucher N, et al. Multicenter validation of the Geneva Risk Score for hospitalized medical patients at risk of venous thromboembolism. Explicit Assessment of Thromboebolic Risk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE). Thromb Haemost 2014;111(3):531-8.