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  1. Tubog, Tito D.

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Venous thromboembolism (VTE) is a significant cause of morbidity and mortality worldwide (Heit, 2015; Kakkos et al., 2016). Deep vein thrombosis (DVT) commonly occurring in the lower extremities and its complication, pulmonary embolism (PE), are collectively known as VTE (Kakkos et al., 2016). The risk of developing VTE dramatically increases in patients who are 50 years and older (Mackman, 2012). Other risk factors include but are not limited to prolonged hospitalization, immobility, genetic hypercoagulable states, cancer, neuromuscular diseases causing leg paresis, obesity, orthopaedic surgery, and pregnancy (Mackman, 2012). Associated with the development of VTE are concerns of long-term complications and recurrence. It is estimated that 50% of the patients with VTE will have a postthrombotic syndrome, a significant complication that includes swelling, pain, discoloration, and scaling in the affected limb (Beckman, Hooper, Critchley, & Ortel, 2010). About 33% of patients with VTE will have a recurrence within 10 years (Beckman et al., 2010).


The proposed mechanism of VTE is complex and multifactorial. Blood stasis, procoagulant changes in the blood, and the activation of the endothelial lining comprise Virchow's triad for thrombogenesis (Mackman, 2012). Reduced blood flow and blood stasis induced thrombin, a significant clotting factor in the physiologic clotting mechanism, to concentrate in deep veins leading to thrombosis. The hypercoagulable state brought by various mechanisms such as variant genetic factors, pregnancy, obesity, cancer, and surgical procedures increases the incidence of thrombus formation. Activation of the endothelium leads to expression of procoagulants from the surface of the endothelium lining predisposing the vessel to thrombosis.


The economics and public health burden of VTE prompted many organizations to increase awareness for VTE prevention. Some professional societies advocate for similar VTE prevention measures (Maynard, 2016). Pharmacological and mechanical prophylaxis used alone or in combination are the two most common preventive measures recommended by many professional organizations (Maynard, 2016). A combination of mechanical and pharmacological prophylaxis is highly recommended in high-risk patients; however, the quality of evidence supporting this recommendation is moderate and requires further studies to include patients at moderate risks, cost-effectiveness, and other patient population (Kakkos et al., 2016).



The primary objective of the systematic review and meta-analysis was to evaluate the efficacy of the combined intermittent pneumatic leg compression (IPC) device and pharmacological prophylaxis technique compared to a single modality preventing VTE (Kakkos et al., 2016). This review is an update of the meta-analysis published in 2008.



Kakkos and colleagues conducted an extensive search, which yielded a total of 22 clinical studies comprising of 9,137 patients (Kakkos et al., 2016). Only patients requiring VTE prevention at risk of developing VTE in the intensive care unit, after trauma or undergoing surgery, were included. Besides, only studies examining the effects of a combined modality (IPC + pharmacological agent) compared to a single intervention (IPC or pharmacological agent used alone) were included. The pharmacological agents used were unfractionated heparin, low-molecular-weight heparin, warfarin, edoxaban, fondaparinux, and aspirin with varying doses and routes of administration. The IPC used in the included studies were foot pumps and devices inflating calf or calf and thigh sleeves.


The primary outcome was the incidence of VTE subcategorized as DVT and PE, and the secondary outcomes were bleeding and fatal PE. The rate of DVT and PE was assessed using ascending venography, I-125 fibrinogen uptake test and ultrasound scanning and pulmonary angiography or scintigraphy, computed tomography, angiography, and autopsy, respectively. Bleeding was operationalized based on the author's definition of major or fatal bleeding. For dichotomous outcomes, effect sizes were estimated by calculating the pooled odds ratio (OR) or risk ratio with 95% confidence interval (CI). Using the I2 statistic to assess variation between studies, the authors considered I2 values more than 50% as evidence of substantial heterogeneity. When the I2 was less than 50%, the data were pooled with a fixed-effect model; otherwise, the random-effects model was used.


Each study was assessed for methodological quality according to the Risk of Bias guidelines. The authors rated the overall quality of evidence using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach.



For the incidence of DVT, dual prophylaxis did not decrease the rate of DVT compared to pharmacological intervention alone (OR [95% CI] = 0.42 [0.18, 1.03]) but combined modality was effective when compared to IPC alone (OR [95% CI] = 0.52 [0.33, 0.82]).


For the incidence of PE, dual therapy decreased the rate of PE compared to pharmacological intervention (OR [95% CI] = 0.39 [0.23, 0.64]); however, combined modality was not effective when compared to IPC alone (OR [95% CI] = 0.49 [0.18, 1.34]).


When an anticoagulant was added to an IPC, more patients experienced bleeding (4.0%) compared to IPC alone (0.66%). Similarly, more patients had major bleeding in the combined modality (1.5%) than IPC alone (0.15%). However, when IPC was added to anticoagulant therapy, bleeding was not detected.


In the subgroup analysis, there was no difference between nonorthopaedic and orthopaedic patients for the incidence of DVT and PE. Table 1 summarizes the outcomes of the meta-analysis.

Table 1 - Click to enlarge in new windowTable 1. Summary of Effect Size of Outcomes in the Systematic Review and Meta-analysis Examining the Efficacy of Combined Intermittent Pneumatic Leg Compression and Pharmacological Prophylaxis for the Prevention of Venous Thromboembolism


The most important findings of the review were the efficacy of combined IPC and pharmacological prophylaxis compared to IPC alone in reducing the incidence of DVT and combined IPC and pharmacological prophylaxis compared to pharmacological intervention alone in mitigating the incidence of PE. Also, the addition of an anticoagulant in an IPC modality increased bleeding. Conversely, dual modality was ineffective in preventing PE when compared to IPC alone and preventing DVT when compared to pharmacological intervention alone.


The combined modality approach to the prevention of DVT and PE targets the factors predisposing patients to VTE as described by Virchow's triad for thrombogenesis. Intermittent mechanical compression reduces the risk of blood stasis whereas anticoagulants such as unfractionated heparin and low-molecular-weight heparin antagonize factor X (Kakkos et al., 2016). The different targets of mechanical and anticoagulants in Virchow's triad contribute to the efficacy of the preventive measures.


The overall quality of the evidence for the incidence of DVT, PE, bleeding, and major bleeding is moderate. The reasons for this judgment were based on the likelihood of type 2 error, the risk of attrition bias, and reporting bleeding outcomes varied with each study.


Implications to Practice

Nursing plays a pivotal role in the implementation of any evidence-based practice initiatives in a healthcare organization. Some clinical implications emerged from this review. First, nurses must actively participate in any quality improvement projects to prevent VTE. Nurses collaborate with an interdisciplinary group to identify the framework for improvement and common barriers in the implementation of the VTE prevention protocol. Second, provide patient advocacy by working with physicians to adjust pharmacological thromboprophylaxis in patients with low risk for bleeding. Third, monitor compliance and adherence to the prevention protocol. Vigilance in signs and symptoms of bleeding should be part of the VTE prevention protocol instituted in any healthcare organization. In a systematic review and meta-analysis of eight randomized control trials, 25% of surgical patients did not have proper placement of the compression device (Craigie et al., 2015). Nurses play a significant role in making sure that adherence to the measures is carried out by clinicians and patients.




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Craigie S., Tsui J. F., Agarwa A., Sandset P. M., Guyatt G. H., Tikkinen K. A. (2015). Adherence to mechanical thromboprophylaxis after surgery: A systematic review and meta-analysis. Thrombosis Research, 136(4), 723-726. doi:10.1016/j.thromres.2015.06.023 [Context Link]


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Kakkos S. K., Caprini J. A., Geroulakos G., Nicolaides A. N., Standsby G. P., Reddy D. J., Ntouvas I. (2016). Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism. Cochrane Database of Systematic Reviews, 9, CD005258. doi:10.1002/14651858.CD005258.pub3 [Context Link]


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Maynard G. (2016). Preventing hospital-associated venous thromboembolism: A guide for effective quality improvement. Retrieved from https://www.ahrq.gov/sites/default/files/publications/files/vteguide.pdf[Context Link]