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Effectiveness of Initiating Deep Vein Thrombosis Prophylaxis in Patients With Stroke

An Integrative Review

Dizon, Mark Angel M.; De Leon, Josephine M.

Journal of Neuroscience Nursing: October 2018 - Volume 50 - Issue 5 - p 308–312
doi: 10.1097/JNN.0000000000000385
Article

ABSTRACT Venous thromboembolism (VTE) is a frequent and potentially fatal complication of immobility caused by cerebrovascular disease. This review examines the efficiency of deep vein thrombosis (DVT) prophylaxis methods. Patients with stroke initiated on DVT prophylaxis were compared with those who did not have any prophylaxis. Integrative review research design was used and included articles from 2010 to 2016. Search terms such as “DVT prophylaxis” and “stroke” were used to identify scientific publications. Of 173 studies identified, 12 articles were included and rated using the Canadian Medical Association and Center for Evidence-Based Medicine Level of Evidence ranking system. Of DVT prophylaxis methods identified, intermittent pneumatic compression device was superior to antiembolic stockings. Current data showed that the stockings were insufficient in preventing VTE. Heparin and low–molecular-weight heparin were efficient chemoprophylaxis in reducing the incidence of VTE. The combination of chemical and mechanical DVT prevention is recommended.

Questions or comments about this article may be directed to Mark Angel M. Dizon, BSN, at markangeldizon2013@gmail.com. He is an Assistant Nurse Unit Manager at the NeuroCritical Care and Epilepsy Monitoring Units, St. Lukes Medical Center, Quezon City, Philippines.

Josephine M. De Leon, PhD MAN BSN, is Associate Professor, School of Nursing and Graduate School, Centro Escolar University, Manila, Philippines.

The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.jnnonline.com).

Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is a frequent, potentially fatal but preventable complication in immobile patients with acute stroke.1 Reported rates of VTE after stroke have decreased over the last 4 decades, possibly because of the implementation of stroke units, early mobilization and hydration, and increased early use of antiplatelets. Additional means of thromboprophylaxis in stroke include mechanical methods such as pneumatic compression device to prevent venous stasis and chemoprophylaxis including antiplatelets, heparins, and heparinoids.2

The incidence of VTE is approximately 1 per 1000 annually in adult population. Approximately two-thirds of episodes manifest as DVT; and one-third, as PE with or without DVT. This is associated with impaired quality of life. Mortality rate is at 30%. Death occurs a month after having DVT.3

Stroke places patients at a high risk for VTE. Immobility is a key risk factor, and as many as two-thirds of patients will be immobile or require assistance with walking immediately after their stroke. A third will be nonambulatory or require assistance at 3 months. Immobility due to stroke may be compounded by deconditioning and by comorbidities including dementia, arthritis, and peripheral vascular disease. Systemic inflammation from cerebral injury and infectious complications may also contribute to thrombosis risk.4

Venous thromboembolism is a disease of aging, affecting 1 per 10,000 annually before the age of 40s, escalating after the age of 45 years, and approaching 5 to 6 per year at the age of 80 years. Morbidity impact to the older adults is greater, with an accelerated rise in incidence of PE than DVT.5

The weighing of the benefits of thromboprophylaxis against the risks of hemorrhage is an ever-present challenge for those involved in poststroke care and necessitates a careful assessment of the available evidence. Thus, this review aimed to find out which among the varied methods of DVT prophylaxis is efficient in preventing DVT among patients with stroke.

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Methodology

The review used the integrative review design, which included articles from the year 2010 to 2016. It used the Patient Intervention Comparator Outcome (PICO) framework to describe all the components related to the identified problem and to structure the research question: “Which among the varied DVT prophylaxis methods is efficient in preventing DVT in patients with stroke?” After the research question was formulated, search terms, or descriptors, were identified relating to each component of the PICO framework. Search terms such as “DVT prophylaxis” and “stroke” were used for the indexation of articles in the databases. Search results from a PICO framework for questions using different combinations of PICO elements were then compared. Patients with stroke initiated on DVT prophylaxis were taken as the population of the study. “DVT prophylaxis” was selected as the intervention. There were no restrictions regarding studies that described different types of DVT prophylaxis. The comparison was with those patients who did not have any DVT prophylaxis in the different studies. The desired outcome is to prevent VTE. The research design adapted the PRISMA flow diagram (Fig 1).

FIGURE 1

FIGURE 1

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Search Strategy

The search strategy aimed to find all the relevant published studies. First, an initial limited search was undertaken using Google Scholar and the ProQuest database. This was followed by an analysis of the text words contained in the title and abstract and of the index terms used to describe the article. A second search was undertaken in MEDLINE, CINAHL, ERIC, Scopus, EBSCO, PsycINFO, and PubMed from the period of 2010 to 2016 using search keywords and the index terms identified, including “DVT prophylaxis” and “stroke” (Supplemental Digital Content 1, available at http://links.lww.com/JNN/A127).

The search period is critical to include recent and up-to-date literature and studies. The first and second searches used “AND” to combine the key word groups, whereas “OR” was used within each group of the key words. The searches were limited to English-language, peer-reviewed, and scholarly articles. Large databases including abstracts written in English-language, peer-reviewed, and scholarly articles were considered to be of high standards of writing, content, and research quality. The reference lists of all identified reports and articles were screened to identify additional publications that might have been missed in the original and subsequent searches and might be relevant to this review purpose.

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Data Abstraction

The review consisted of 12 articles. These were yielded from databases such as Cochrane, PubMed, IHI, and Clinical Key and web-based linkages such as Google. The 12 individual articles were then rated using the Canadian Medical Association and Center for Evidence-Based Medicine ranking system (Table 1).

TABLE 1

TABLE 1

The results were used to formulate recommendations and conclusions. The other 161 articles were excluded because of the following reasons: (1) time of the study (studies from 2009 below were excluded), (2) population (studies pertaining to children were excluded), (3) poor level of evidence, (4) small population size, (5) bias that was seen especially in the methodology, and (6) major methodological concerns (Supplemental Digital Content 2, http://links.lww.com/JNN/A128).

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Results

The 12 included articles clearly determined what methods are effective in preventing occurrences of DVT as a complication of stroke. Of these, 5 studies comprised systematic reviews and meta-analyses of randomized controlled trials (RCTs) and 4 RCTs that were of good quality researches. In addition, a retrospective study and 2 cohort studies were included in the study. The studies pointed out that effective DVT prophylaxis include use of heparin, low–molecular-weight heparin (LMWH), antiembolic stockings, and pneumatic compression device.

Neither intermittent pneumatic compression device nor antiembolic stockings were insufficient in preventing DVT.6 The research revealed that both DVT mechanical methods were insufficient in preventing DVT (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.70–1.04) or deaths (OR, 1.12; 95% CI, 0.87–1.45). Use of antiembolic stockings based on 2 clinical trials conducted in 2615 patients did not show a significant decrease of DVT (OR, 0.88; 95% CI, 0.72–1.08) or deaths (OR, 1.13; 95% CI, 0.87–1.47). Use of intermittent pneumatic compression did not merit a significant reduction of DVT either (OR, 0.45; 95% CI, 0.19–1.10), with no evidence of an effect on deaths (OR, 1.04; 95% CI, 0.37–2.89).6

This was negated in other studies in which antiembolic stockings, especially those of thigh length, are preferred. Proximal DVT occurred more often in patients wearing below-knee stockings (138 patients, 8.8%) compared with those who are wearing thigh-length stockings (98 patients, 6.3%).7,8

Mixed methods of preventing DVT were also introduced. These include both chemical methods (use of unfractionated heparin [UFH], heparinoids, and LMWH) and mechanical methods (use of antiembolic stockings and intermittent pneumatic compression device).9–15 Field and Hill10 (2012) discussed that intermittent pneumatic compression device, UFH, daparanoids, and LMWH were helpful in preventing DVT whereas antiembolic stockings were found out to be ineffective. It was further supported by the study conducted by Bembenek and Czlonkowska11 in 2013 and the study conducted by the European Stroke Organization.12 The recommended prophylactic anticoagulation with UFH (5000 U 2× or 3× daily) or LMWH or heparinoid should be considered in immobile patients with ischemic stroke in whom the benefits of reducing the risk of VTE are high enough to offset the increased risks of intracranial and extracranial bleeding associated with their use.12 Where a judgment has been made that prophylactic anticoagulation is indicated, LMWH or heparinoid should be considered instead of UFH because of its greater reduction in the risk of DVT, greater convenience, reduced staff costs, and patient comfort associated with single versus multiple daily injections, but these advantages should be weighed against the higher risk of extracranial bleeding, higher drug costs, and risks in elderly patients with poor renal function associated with LMWH and heparinoids. Weaknesses of the research include limiting the population to patients with ischemic stroke and a spurt of new anticoagulants in the market. Bembenek and Czlonkowska11 also supported the research by Field and Hill. Heparins are recommended as a method of choice to prevent thromboembolism in patients with stroke. However, they point out that there is no criterion standard for all patients with stroke to prevent VTE. Clinical practice and recommendations thus vary.

Prophylaxis methods may also be dependent on the type of stroke. Douds et al14 discussed in their cohort study analyzed data from 149,916 patients enrolled in the Get With The Guidelines-Stroke study that revealed that 3% did have DVT and is associated with a history of atrial fibrillation/flutter. Limitation of the study is that it only focused on patients with ischemic stroke. Nyquist et al (2016) tackled evidence-based approaches to prevent DVT in neurologically ill patients. In the ischemic type of stroke, intermittent pneumatic compression device and LMWH were effective in preventing DVT. In hemorrhagic stroke, both UFH and LMWH yielded the same results and thus were effective in preventing PE. In aneurysmal subarachnoid hemorrhage, VTE is double the mean length of stay, as much as cardiopulmonary complications. Deep vein thrombosis prophylaxis in this type of stroke varies depending on the condition of the aneurysm—whether it is secured or unsecured. Heparins must be used when aneurysm is secured; otherwise, patients are at risk for bleeding.10 This was further supported by a retrospective analysis by Liang et al15 stressing the proper timing of DVT prophylaxis to cases of aneurysmal subarachnoid hemorrhage, which is 2 weeks after the onset of symptoms.

New trends in healthcare may also reduce DVT; thus, further research is needed to provide evidence-based practices. Kappelle16 added new criteria for DVT prophylaxis: early mobilization and fluid hydration. Early mobilization after stroke may reduce VTE and PE, but no conclusive results are published yet because of an ongoing clinical trial: AVERT (A Very Early Rehabilitation Trial). Fluid hydration has not been evaluated in RCTs. Liu et al17 conveyed the use of clinical factors as determinants of DVT. Eight hundred twenty-six patients were included in this multicenter prospective cohort study: Incidence of Deep Vein Thrombosis after Acute Stroke in China. The overall incidence of DVT after stroke within 2 weeks was 12.4%. Risk factors included as determinants of DVT include female sex, age of 65 years or older, obesity with a body mass index of 25 kg or more, active cancer, intracerebral bleed, and muscle weakness with an NIHSS score of 2 or higher.

Neuromuscular electrical stimulation (NES) is also reviewed as a new method of DVT prophylaxis; however, further study is required to yield its effectiveness. There is no identified relevant RCT to prove the effectiveness of NES in preventing DVT.12

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Discussion

Varied DVT prophylaxes were tested for their effectiveness. Of the many methods presented, evidences shows that the efficient ones are the use of intermittent pneumatic compression (mechanical method), the use of UF (chemoprophylaxis), and the use of LMWH (chemoprophylaxis). Evidences also show that the use of antiembolic stockings was ineffective in preventing DVT in patients with stroke. Heparin and LMWH use must be necessitated by constant monitoring of the possible adverse effects such as hemorrhage.

Liu et al17 discussed the varied factors affecting the initiation of DVT protocols. Use of clinical factors such as female sex, age of 65 years or older, obesity with a body mass index of 25 kg or more, active cancer, intracerebral bleed, and muscle weakness with an NIHSS score of 2 or higher may result to DVT. Further studies are needed to test the claim that fluid hydration, use of NES, and early rehabilitation poststroke may reduce DVT.

This review contributes to poststroke nursing care. These patients are immobile and are afflicted with cognitive ailments predisposing them to complications. They need either partial or total assistance to meet their required activities of daily living. Having adequate knowledge of VTE prevention will aid in initiating means to prevent further suffering to these patients simply by using evidence-based strategies and researches. Cost-effectiveness and length of hospitalization must also be taken into consideration in future studies.

There are several recognized limitations. The review only included patients with stroke. Thus, it may not be applicable to patients with other medical conditions, excluding cerebrovascular disease.

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Implications for Research, Education, and Practice

Evidence-based strategies dictate using clinically proven devices or treatment methods, thus promoting safety, cost-effectiveness of care, and patient involvement. The review will also benefit nursing education. Internal and external trainings will provide nurses new knowledge about DVT prevention and management. Yearly or biannual nursing skills fair, use of unit-based teaching strategies and web-based technologies, and enrollment to a masteral or doctoral degree will definitely enhance nurses’ continuous professional education. Learnings can be shared through unit meetings and postconferences.

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Conclusions

Various methods are effective in preventing DVT in patients with stroke. Intermittent pneumatic compression device, UF, and LMWH are effective methods of DVT prophylaxis. Antiembolic stockings were proven to be inefficient in preventing DVT. The most recent guidelines do not recommend antiembolic stockings as DVT prophylaxis for patients with stroke.

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References

1. Balogun I, Roberts LN, Patel R, Pathansali R, Kalra L, Arya R. Clinical and laboratory predictors of deep vein thrombosis after acute stroke. Thromb Res. 2016;142:33–39. doi:10.106/j.thromres.2016.04.002
2. Nyquist P, Bautista C, Jichici D, et al. Prophylaxis of venous thrombosis in neurocritical care patients: an evidence-based guideline: a statement for healthcare professionals from the neurocritical care society. Neurocrit Care. 2016;24(1):47–60. doi:10.1007/s12028-015-0221-y
3. Piazza G, Goldhaber SZ, Kroll A, Goldberg RJ, Emery C, Spencer FA. Venous thromboembolism in patients with prior stroke. Clin Appl Thromb Hemost. 2014;20(1):43–49. doi:10.117/1076029613487430
4. Attia J, Ray JG, Cook DJ, Douketis J, Ginsberg JS, Geerts WH. Deep vein thrombosis and its prevention in critically ill adults. Arch Intern Med. 2001;161(10):1268–1279.
5. Dennis M, Sandercock P, Graham C, et al. The Clots in Legs Or sTockings after Stroke (CLOTS) 3 trial: a randomised controlled trial to determine whether or not intermittent pneumatic compression reduces the risk of post-stroke deep vein thrombosis and to estimate its cost-effectiveness. Health Technol Assess. 2015;19(76):1–90. doi:10.3310/htal19760
6. Dennis M, Graham C, Smith J, Forbes J, Sandercock P; CLOTS Trial Collaboration. Which stroke patients gain most from intermittent pneumatic compression: further analyses of the CLOTS 3 trial. Int J Stroke. 2015;10(suppl A100):103–107. doi:10.1111/ijs.12598
7. Dennis M, Cranswick G, Deary A, et al. Thigh-length versus below-knee stockings for deep venous thrombosis prophylaxis after stroke: a randomized trial (CLOTS Trial Collaboration). Ann Intern Med. 2010;153(9):553–562. doi:10.7326/0003-4819-153-9-201011020-00280
8. Naccarato M, Chiodo Grandi F, Dennis M, Sandercock PA. Physical methods for preventing deep vein thrombosis in stroke. Cochrane Database Syst Rev. 2010;(8):CD001922. doi:10.1002/14651858.CD001922.pub3
9. Amarenco P, Bath P, Lees KR, et al. Effect of the neutral CLOTS 1 trial on the use of graduated compression stockings in the efficacy of nitric oxide stroke trial (ENOS). Neurol Neurosurg Psychiatry. 2013;84(3):342–347. doi:10.1136/jnnp-2012-303396
10. Field S, Hill MD. Prevention of deep vein thrombosis and pulmonary embolism in patients with stroke. Clin Appl Thromb Hemost. 2012;18(1):5–19. doi:10.1177/1076029611412362
11. Bembenek JP, Członkowska A. Venous thromboembolism prophylactic methods in acute stroke patients—current state of knowledge. Neurol Neurochir Pol. 2013;47(6):564–571. doi:10.5114/ninp.2013.39074
12. Dennis M, Caso V, Kappelle LJ, et al. European Stroke Organization (ESO) guidelines for prophylaxis for venous thromboembolism in immobile patients with acute ischemic stroke. Eur Stroke J. 2016;1(1):6–19. doi:10.1177/2396987316628384
13. Douds GL, Hellkamp AS, Olson DM, et al. Venous thromboembolism in the Get With The Guidelines-Stroke acute ischemic stroke population: incidence and patterns of prophylaxis. Stroke Cerebrovasc Dis. 2014;23(1):123–129. doi:10.1016/j.jstrokecerebrovasdis.2012.10.018
14. Liang CW, Su K, Liu JJ, Dogan A, Hinson HE. Timing of deep vein thrombosis formation after aneurysmal subarachnoid hemorrhage. J Neurosurg. 2015;123(4):891–896. doi:10.3171/2014.12.jns.141288
15. Kappelle LJ. Preventing deep vein thrombosis after stroke: strategies and recommendations. Curr Treat Options Neurol. 2011;13(6):629–635. doi:10.1007/s11940-011-0147-4
16. Liu LP, Zheng HG, Wang DZ, et al. Risk assessment of deep-vein thrombosis after acute stroke: a prospective study using clinical factors. CNS Neurosci Ther. 2014;20(5):403–410. doi:10.1111/cns.122227
Keywords:

DVT prophylaxis; stroke; stroke patients; thromboembolism

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