Venous Thromboembolism After Spinal Cord Injury

Article Outline

• Abstract
• Methods
• Results
  • Pharmacologic Agents for Deep Venous Thrombosis Prophylaxis
    • Unfractionated heparin for prophylaxis
    • Unfractionated heparin for prophylaxis: conclusions
    • Low-molecular-weight heparin for prophylaxis
    • Heparin analogs for prophylaxis
    • Low-molecular-weight heparin versus unfractionated heparin for prophylaxis
    • Low-molecular-weight heparin versus unfractionated heparin for prophylaxis: conclusions
    • Low-molecular-weight heparin for prophylaxis after spinal cord injury
    • Low-molecular-weight heparin for prophylaxis after spinal cord injury: conclusions
  • Prevention of Deep Venous Thrombosis through Mechanical Methods
    • Conclusions
  • Prevention of Deep Venous Thrombosis with Combined Measures
    • Conclusions
  • Vena Cava Filtration
    • Conclusions
  • Treatment of Acute Venous Thromboembolism in Spinal Cord Injury
    • Conclusions
• Discussion
• Conclusions
• References
• Copyright

Abstract 

Teasell RW, Hsieh JT, Aubut JL, Eng JJ, Krassioukov A, Tu L, for the Spinal Cord Injury Rehabilitation Evidence Review Research Team. Venous thromboembolism after spinal cord injury.

Objective

To review systematically the published literature on the treatment of deep venous thromboembolism after spinal cord injury (SCI).

Data Sources

MEDLINE/PubMed, CINAHL, EMBASE, and PsycINFO databases were searched for articles addressing the treatment of deep venous thromboembolism post-SCI. Randomized controlled trials (RCTs) were assessed for methodologic quality using the Physiotherapy Evidence Database Scale, while non-RCTs were assessed using the Downs and Black evaluation tool.

Study Selection

Studies included RCTs, non-RCTS, cohort, case-control, case series, pre-post, and postinterventional studies. Case studies were included only when no other studies were available.

Data Extraction

Data extracted included demographics, the nature of the study intervention, and study results.

Data Synthesis

Levels of evidence were assigned to the interventions using a modified Sackett scale.

Conclusions

Twenty-three studies met inclusion criteria. Thirteen studies examined various pharmacologic interventions for the treatment or prevention of deep venous thrombosis in patients with SCI. There was strong evidence to support the use of low-molecular-weight heparin in reducing venous thrombosis events, and a higher adjusted dose of unfractionated heparin was found to be more effective than 5000 units administered every 12 hours, although bleeding complications were more common. Nonpharmacologic treatments were also reviewed, but again limited evidence was found to support these treatments.

Key Words: Rehabilitation, Spinal cord injuries, Venous thrombosis

List of Abbreviations: APTT, activated partial thromboplastin time, ASIA, American Spinal Injury Association, CT, computed tomography, DVT, deep venous thrombosis, IPC, intermittent pneumatic compression, IU, international units, IVC, inferior vena cava, LMWH, low-molecular-weight heparin, PE, pulmonary embolism, PEDro, Physiotherapy Evidence Database Scale, RCT, randomized controlled trial, s/c, subcutaneous, SCI, spinal cord injury, SCIRE, Spinal Cord Injury Rehabilitation Evidence Review, UFH, unfractionated heparin, VT, venous thrombosis

DEEP VENOUS THROMBOSIS and subsequent PE remain significant causes of morbidity and mortality in patients with SCI. The incidence of DVT in patients with acute SCI was reported to be greater than 50% in early prospective studies,¹, ², ³, ⁴, ⁵ with the incidence of fatal PE estimated as high as 5%.¹, ⁶, ⁷, ⁸ The prevalence of DVT in acute SCI has been found to range from 14% to 100%⁹ and from 9% to 90%.¹⁰ Various test methods exist for diagnosing DVTs in patients; however, venography has been considered the criterion standard.¹¹

The clinical diagnosis of DVT and PE are often unreliable, and diagnostic testing is necessary to confirm the diagnosis. Diagnostic testing varies from center to center, but 3 tests for DVT have become important: venous ultrasound, venography, and the D-dimer assay. For PE, 2 commonly used tests are the ventilation/perfusion scan and the spiral CT scan. Venography is considered the definitive test for DVT but is an invasive study. Venous ultrasound is cheap and noninvasive, and it can be done as a screen or serially to monitor the patient. Sensitivity is only 73% for distal clots, but 95% for the more dangerous proximal clots. The D-dimer assay is a rapid, noninvasive, and inexpensive test¹² and measures a fibrin degradation product, D-dimers, because fibrin is the main component of thrombosis formation. The D-dimer test is highly sensitive, but it lacks specificity because D-dimers are found in other disease states, reducing the specificity of the test.¹³A positive diagnosis of DVT can be made only if the venogram is positive or if the venous ultrasound is positive for 2 or more sites of proximal vein. Nuclear ventilation/perfusion scans are often used to diagnose a PE, and the likelihood of a positive diagnosis increases with the size, shape, and number of deflects on perfusion scanning with a normal ventilation scan. A spiral CT scan is a quick CT scan of the entire thorax in 1 breath-hold and is most accurate when the PE is large.

The high risk of DVT in patients with acute SCI is a consequence of the simultaneous presence of all 3 components of the Virchow triad: hypercoagulability, stasis, and intimal (venous inner wall) injury,¹⁰ with stasis being the greatest concern. VT most commonly begins with a calf DVT.¹⁴, ¹⁵, ¹⁶ Although only 20% of DVTs extend into the proximal veins,¹⁷, ¹⁸, ¹⁹ these result in over 80% of symptomatic DVTs.²⁰ Distal calf DVTs that do not extend proximally rarely are a source of PEs, so they are much less worrisome.¹⁷ Nonetheless, even those who caution against overtreatment of distal DVTs concede that there is a need for randomized trials to assess the usefulness of diagnosing and treating distal DVTs.²¹

Proximal (ie, at the level of the knee or above) DVTs continue to be the primary source of concern.¹⁷ PE is reported in 8% to 14% of patients with an acute SCI,⁸, ⁹ with most asymptomatic or unrecognized. Symptomatic PEs tend to be relatively large, with reported mortality rates of up to 5%.⁸, ⁹, ¹⁰

This article reviews various interventions used when treating venous thromboemboli in patients with SCI and is part of the SCIRE, the details of which are available at http://www.icord.org/scire.

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Methods 

A systematic review was conducted of all relevant literature published from 1980 to 2007 using multiple databases (MEDLINE/PubMed, CINAHL, EMBASE, and PsycINFO) and SCIRE methodology.²² This search involved reviewing over 17,000 titles and 8400 abstracts, and the final analysis of approximately 700 articles. Studies were included for analysis only if at least 50% of subjects had an SCI, there were at least 3 subjects, and there was a definable intervention being studied. A quality assessment was conducted for each article using either the PEDro scoring system or the Downs and Black methodology for randomized and nonrandomized studies, respectively.²³, ²⁴ The PEDro tool consists of 11 questions but uses only questions 2 through 11 to assess study quality. The maximum score yielded by any RCT was 10, with higher scores indicating better study quality. The following cutpoints were used to categorize studies by quality: excellent (9–10), good (6–8), fair (4–5), and poor (<4). The Downs and Black tool consists of 27 questions that evaluate the quality of data reporting, external validity, and internal validity (both bias and confounding). Because of ambiguity in the last question, a slight modification was made; thus, the total score any reviewed article could receive was 28 (1 question was scored out of 2), with a higher score indicating higher methodologic quality.²⁴ Tables provided in this article include the PEDro or Downs and Black scores, inclusion and exclusion criteria, the type of study, a brief summary of the interventions and outcome measures, and study results. Levels of evidence were assigned to the studies for each intervention using a modified Sackett approach.²⁵ Sackett's levels of evidence were modified and collapsed into the following: level 1 evidence came from RCTs with a PEDro score of higher than 6; level 2 evidence was applied to RCTs with PEDro scores of 5 or less or nonrandomized prospective controlled or cohort studies; level 3 evidence came from case-control studies; level 4 evidence was assigned to pre-post/posttest/case series; and level 5 evidence included those studies that were observational or case reports.²², ²⁵

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Results 

Pharmacologic Agents for Deep Venous Thrombosis Prophylaxis 

Heparin acts as an anticoagulant by forming a complex with antithrombin, catalyzing the inhibition of several activated blood coagulation factors: XIIa, XIa, IXa, Xa, and thrombin. Heparin's onset of action is immediate, and for that reason it is often used for acute conditions. Bleeding is the most common adverse effect of heparin. Osteoporosis has been associated with the prolonged use of high doses of heparin, although its occurrence is relatively infrequent. Thrombocytopenia is another uncommon but serious side effect of treatment²⁶ (table 1).

Table 1. Efficacy of Unfractionated Heparin Versus Placebo as Prophylaxis Against Venous Thromboembolism in Spinal Cord Injuries

Abbreviations: D&B Score, Downs and Black quality assessment scale score²²; ES, electrical stimulation.

Historically, UFH has been the standard treatment for the prevention of venous thromboembolism acutely post-SCI. Merli et al⁶ evaluated 53 patients with acute SCI who were randomly assigned to 1 of 3 treatment arms: (1) placebo saline (n=17), (2) 5000 IU heparin (n=16), and (3) heparin plus electrical stimulation of the tibialis anterior and gastrocnemius muscles (n=15) over 28 days. There was no difference between the placebo saline and heparin groups in the incidence of DVT, but there was a significant improvement in the heparin and electrical stimulation group. The study was prematurely discontinued because of the apparent benefit of the heparin plus electrical stimulation. Frisbie and Sasahara²⁷ conducted a non-RCT of 32 patients with SCI comparing 5000 IU heparin given subcutaneously every 12 hours until day 60 post-SCI versus no heparin. VT was uncommon in both the control (1 of 17) and heparin groups (1 of 15).

Green et al²⁸ studied 75 patients with SCI randomized to receive 5000 IU subcutaneously every 12 hours of either fixed-dose or adjusted-dose heparin. The dose was adjusted based on the APTT, to a maximum of 15,000 IU subcutaneously every 12 hours. Patients on the adjusted-dose regimen received a mean of 13,200 IU subcutaneously every 12 hours. Thromboembolism was detected in 9 (31%) of 29 on the fixed-dose regimen but only 2 (7%) of 29 on the adjusted-dose regimen. No bleeding complications were noted with the fixed-dose regimen; however, 7 had bleeding complications with adjusted dosing. In this study, higher doses decreased the risk of venous thromboemboli but increased the risk of bleeding complications.

Typically, prophylactic treatment involves 5000 IU heparin given subcutaneously every 12 hours. One RCT and 1 controlled study examining the efficacy of this dose versus placebo identified no difference in the incidence of venous thrombosis. Interestingly, Merli et al⁶ found that heparin plus electrical muscle stimulation significantly reduced the incidence of venous thrombosis relative to heparin alone.

There is level 2 evidence (based on 1 low-quality RCT and 1 non-RCT) that 5000 IU of unfractionated heparin given subcutaneously every 12 hours is no more effective than placebo as prophylaxis against venous thrombosis post-SCI. There is level 1 evidence (based on 1 RCT) that an adjusted (higher) dose of subcutaneous heparin is more effective as prophylaxis against venous thromboembolism than the administration of 5000 IU subcutaneous heparin every 12 hours; however, the adjusted dose appears to be associated with a higher incidence of bleeding complications.

LMWH is derived from standard heparin. Standard heparin has a molecular weight of 5000 to 30,000 d, whereas the molecular weight of LMWH ranges from 1000 to 10,000 d. LMWH binds less strongly to protein, has enhanced bioavailability, interacts less with platelets, and yields a very predictable dose response. The clinical advantages of LMWH include its predictability, dose-dependent plasma levels, long half-life, and reduced bleeding for a given antithrombotic effect. Thrombocytopenia has not been associated with the short-term use of LMWH. LMWH is administered once or twice daily and is used both during the high-risk period when prophylaxis for DVT is recommended, and while waiting for oral anticoagulation to take effect in the treatment of DVT. It is not necessary to monitor the APTT or adjust the dose of the drug.²⁹

Danaparoid sodium (Orgaran) is an alternative anticoagulant for patients who have developed heparin-induced thrombocytopenia. Danaparoid is a low-molecular-weight heparinoid. Its active components consist of heparin sulfate, dermatan sulfate, and chondroitin sulfate; however, it exerts effects similar to other LMWHs and acts by deactivating thrombin.

The most commonly studied LMWH for the prophylaxis of venous thromboembolism post-SCI is enoxaparin. Enoxaparin has a plasma half-life of 4.4 hours, versus 0.35 hours for UFH, and its subcutaneous bioavailability is 50% versus 20% for UFH.³⁰ Four trials have compared UFH and LMWH (table 2).

Table 2. Low-Molecular-Weight Heparin Versus Unfractionated Heparin as Prophylaxis Against Venous Thromboembolism in Spinal Cord Injury

Abbreviations: CI, confidence interval; D&B Scores, Downs and Black quality assessment scale scores²²; GES, gradient elastic stockings; SCD, sequential pneumatic compression device.

The SCI thromboprophylaxis investigators³¹ conducted a non-RCT comparing low dose UFH (5000 IU s/c every 8 hours) and enoxaparin (40mg once daily) during a 6-week rehabilitation phase in patients with SCI. Venous thromboembolism was detected in 21.7% of UFH and 8.5% of enoxaparin patients, a difference that approached statistical significance (P=.052).

The SCI thromboprophylaxis investigators³² also conducted an RCT involving 476 patients with SCI assigned to receive thromboprophylaxis with either a combination of low-dose UFH (5000 IU s/c every 8 hours) plus IPC at least 22 hours each day, or enoxaparin 30mg given subcutaneously every 12 hours. Three hundred sixty-nine patients were excluded from the study because of protocol deviations, bleeding or other clinical events, withdrawal of consent, intercurrent illness, thrombocytopenia, or other adverse laboratory findings. Among 107 assessable patients, the incidence of VT was 63.3% with UFH/IPC versus 65.5% with enoxaparin (P=.81). The incidence of PE was 18.4% in the UFH/IPC group versus 5.2% with enoxaparin (P=.03). The incidence of major bleeding was 5.3% with UFH/IPC versus 2.6% with enoxaparin (P=.14). This was the only study in which the incidence of venous thromboemboli was not significantly less with LMWH relative to UFH, an effect likely attributable to the addition of the pneumatic compression. Pulmonary emboli still were less common in the LMWH group, but the difference did not achieve significance.

Thumbikat et al³³ retrospectively compared 1 group of patients with SCI (n=101) who received a combination of UFH followed by warfarin and another group (n=72) who received enoxaparin (LMWH). Four patients in the UFH/warfarin group (4%) and 13 patients in the LMWH group (18.1%) developed venous thromboembolic episodes. Of the 72 patients on enoxaparin, 2 (15%) of 13 on 40mg daily and 10 (17%) of 59 on 20mg once daily developed DVT/PE. One patient on UFH and 6 on LMWH developed DVT postmobilization with discontinuation of anticoagulation.

Green et al³⁴ randomized 41 patients with SCI to either standard heparin or LMWH. Five patients in the standard heparin group (n=21) had thrombotic events, including 2 patients with fatal pulmonary emboli. Two other patients had bleeding severe enough to necessitate withdrawal of the heparin. The cumulative event rate in the standard heparin group was 34%, while the LMWH group had neither thrombotic events nor bleeding episodes. The difference between the 2 groups was significant (P=.006). Green et al³⁵ also studied 60 patients with acute SCI with complete motor paraplegia, all of whom received a daily dose of 3500 IU of LMWH subcutaneously. Forty-eight of those recruited were able to complete the study; however, 12 were unable to complete the study because of discharge from care, transfer to other facilities, or death. Treatment began within 72 hours of injury and continued for 8 weeks. Forty patients completed the 8 weeks of prophylaxis uneventfully, while 8 had a thrombotic event (17%). Of the thrombotic events, 2 were pulmonary emboli, 4 were proximal DVTs, and 2 were distal calf DVTs. The differences in bleeding between standard heparin and LMWH, when combined with data from a previous study (68 LMWH [20 from previous study] and 79 UFH), significantly favored LMWH (P=.04), with a trend toward fewer thrombotic events with LMWH (P=.15).

There is convincing evidence that LMWH, in particular enoxaparin, is more effective than standard UFH at preventing venous thromboembolism. The evidence provided by RCTs in favor of LMWH outweighs the conflicting conclusions of the nonrandomized study by Thumbikat et al³³ (see table 2).

There is level 1 evidence (based on 2 RCTs) that LMWH, in particular enoxaparin, is more effective than standard subcutaneous heparin at reducing venous thromboembolic events. Moreover, the incidence of bleeding complications appears to be less with LMWH.

Three studies were found that examined the effects of LMWH. The studies looked at the effects of LMWH given independently, given in different doses, or given as a combination of different LMWH medications. From the previous discussion, it is clear that LMWH is superior to UFH, both as prophylaxis against venous thromboembolism and at reducing the risk of bleeding complications (table 3).

Table 3. Low-Molecular-Weight Heparin Alone in Prophylaxis Against Venous Thromboembolism After Spinal Cord Injury

Abbreviations: D&B Scores, Downs and Black quality assessment scale scores²²; NS, not significant.

Harris et al³⁶ retrospectively examined 105 subjects (66 had had an SCI) given 30mg of enoxaparin subcutaneously every 12 hours, beginning at the time of hospital admission. If a patient was scheduled for surgery, the drug was withheld on the morning of the operation, resumed 24 hours later, and continued until the patient's discharge. No patient developed clinical evidence of venous thromboemboli, and none of the 60 venous ultrasound examinations demonstrated a DVT.

The optimal dose of enoxaparin has not yet been established. Hebbeler et al³⁷ reported a nonrandomized trial involving 129 patients with acute SCI who received prophylactic enoxaparin either 40mg once daily or 30mg twice daily. The incidence of symptomatic thromboemboli did not differ between the 2 groups, with DVT occurring in only 1 patient in each group. There also was no difference in the incidence of bleeding complications between the 2 groups.

Many new LMWHs are becoming available and studies comparing their efficacy are starting to appear in the literature. Chiou-Tan et al⁹ randomized 95 patients with acute SCI into 1 of 2 groups: 1 received enoxaparin (30mg s/c q12h) while the other received 5000 IU of dalteparin daily. There were no significant differences between the 2 groups in terms of DVTs or bleeding complications. The cost of enoxaparin was noted to be greater than that of dalteparin.

There is level 4 evidence that 40mg daily enoxaparin, used prophylactically, is no more effective than 30mg daily at reducing the incidence of deep venous thrombosis; the 2 doses also appear similar with respect to bleeding complications. There is level 1 evidence (based on 1 RCT) that enoxaparin is no more effective than dalteparin at reducing the risk of DVT, and again, there was no difference in the rate of bleeding complications.

Prevention of Deep Venous Thrombosis through Mechanical Methods 

Although pharmacologic measures generally have been the preferred mode of venous thromboembolism prophylaxis post-SCI, mechanical means of limiting venous stasis also can reduce the incidence of DVT post-SCI. Mechanical treatments are designed to limit stasis in the paralyzed lower extremities; however, the use of these devices should be accompanied by twice-daily inspection for skin discolorations or breakdown. Furthermore, pneumatic compression devices are not suitable for patients with severe arterial insufficiency (table 4).

Table 4. Evaluating Physical Methods for the Prevention of Deep Venous Thrombosis

Abbreviations: D&B Scores, Downs and Black quality assessment scale scores²²; GES, gradient elastic stockings; IPG, impedance blood plethysmography; SCD, sequential pneumatic compression device.

Winemiller et al³⁸ retrospectively examined the hospital records of 285 patients with an SCI. Of these, 84 were diagnosed with a DVT or PE, while the remaining 201 were used as a comparison group. Multivariate analysis demonstrated that the use of sequential pneumatic compression devices or gradient elastic stockings was associated with a reduced risk of a diagnosed venous thromboembolism. Multivariate analysis also revealed a greater decreased risk of venous thromboembolism in patients with SCI treated with heparin within the first 14 days, with lesser effect from 14-42 days. Although the risk reduction with heparin was approximately twice that of sequential pneumatic compression devices/gradient elastic stockings, the difference was not statistically significant.

Becker et al⁵ studied whether rotating treatment tables prevent the development and progression of DVT in patients with acute SCI. The authors noted that, up to that time, rotating treatment tables had been used with patients with acute SCI to maintain spinal alignment while facilitating nursing care, allowing for the even distribution of ventilation and preventing pressure ulcers. It was hypothesized that, because these appliances rotate continuously, they may serve to inhibit thrombosis formation by reducing venous stasis. This RCT involved 15 patients with acute SCIs. Four of the 5 control (nonrotated) patients developed distal and/or proximal thrombi, as assessed by I¹²⁵ fibrinogen scanning and impedance plethysmography, while only 1 of the 10 treated (rotated) patients with SCI developed either distal and proximal venous thrombi (P=.007).

There is level 4 (limited) evidence that the use of sequential pneumatic compression devices or gradient elastic stockings reduces the risk of venous thromboemboli post-SCI. There is level 1 evidence (based on 1 small RCT) that rotating treatment tables reduces the incidence of venous thrombi in patients with acute SCI.

Prevention of Deep Venous Thrombosis with Combined Measures 

Pharmacologic approaches have been examined in combination with several mechanical methods (table 5).

Table 5. Combined Pharmacologic and Physical Measures for the Prophylaxis of Venous Thromboembolism After Spinal Cord Injury

Abbreviations: ASA, acetylsalicylic acid; D&B Scores, Downs and Black quality assessment scale scores²²; EPCC, external pneumatic calf compression; PAR, platelet aggregation ratio.

Merli et al³⁹ studied 36 patients with SCI, of these 17 patients served as controls and received no treatment while 19 received 2 weeks of prophylaxis with external sequential pneumatic compression devices plus gradient elastic stockings and low-dose heparin 5000 IU subcutaneously every 12 hours. Results from the current study indicated that 17 of the 19 patients treated had negative fibrinogen scans on completion of the study, while the 2 remaining patients developed a positive fibrinogen scan on days 6 and 8 of the study. In comparison, 6 of 17 patients in the control group developed positive I¹²⁵ fibrinogen scans, all of which were confirmed by venography. The incidence of thrombosis was significantly higher in the control group than in the treatment group (P=.04).

Aito et al¹⁰ studied 275 patients with SCI, 99 of whom were treated within 72 hours of injury, while 176 were treated more than 8 days post-SCI. Treatment involved continuous gradient elastic stockings, subcutaneous LMWH 0.4mL once daily, and external sequential pneumatic compression of the lower limbs 3 hours a day, given in 2 applications. There was also early mobilization of the lower limbs. The complete prophylactic treatment lasted at least 30 days post-SCI; LMWH and external sequential pneumatic compression were continued for 2 more months, depending on the patient's progress. In those treated earlier, DVT incidence was 2%, while the incidence in those treated later was 26%. Of the DVTs that occurred, 60% were detected at time of later admission (8–28d posttrauma), while the remaining 40% developed within 6 weeks of hospitalization. Sixty-five percent of detected DVTs did not exhibit any obvious clinical signs. ASIA grade A patients were more likely to develop a DVT (36%), while only 7% of ASIA grade D patients did so on admission.

Green et al⁴⁰ randomized 28 patients with a complete SCI to either external pneumatic calf compression alone or external pneumatic calf compression combined with acetylsalicylic acid 300mg twice daily and dipyridamole 7mg twice daily. Twenty-seven subjects completed the study. DVT was detected in only 9 (33%) of 27 patients, an incidence significantly less than the 78% recorded in 37 patients (from a previous study) who had not received any prophylactic treatment (P<.001). Thrombi developed in 6 (40%) of 15 patients treated solely with external pneumatic calf compression compared with 3 (25%) of 12 receiving acetylsalicylic acid/dipyridamole in combination with external pneumatic calf compression (P<.10). The authors concluded that the early application of pharmacologic plus mechanical treatment reduces the risk of DVT complications compared with mechanical treatments alone, even though study numbers were small and most intergroup differences did not achieve statistical significance.

The quality of evidence is not strong for combined DVT prophylaxis measures. Given the additive effects of the Virchow triad, different measures designed to treat different risk factors should have an additive effect and be more effective than individual treatments.¹⁰

There is level 4 evidence that comprehensive prophylactic treatment combining external pneumatic compression, gradient pressure stockings, and low-dose heparin reduces venous thrombosis risk post-SCI. There is level 4 evidence that a comprehensive prophylactic regimen of pharmacologic and physical measures is more effective at preventing venous thrombosis post-SCI when instituted earlier rather than later. In a single, small RCT, a trend is noted (P<.10), suggesting that pneumatic compression plus antiplatelet agents (acetylsalicylic acid and dipyridamole) is more effective than pneumatic compression alone.

Vena Cava Filtration 

Vena cava filtration involves inserting a mechanical filter in the IVC to prevent emboli, initially formed in the lower extremities, from traveling to the lungs. This is a highly invasive procedure, that is associated with significant morbidity. Routine use of IVC filters in the prophylaxis of PE post-SCI has been the subject of observational trials and case series (table 6).

Table 6. Prophylactic Vena Cava Insertion in Patients With Traumatic Spinal Cord Injury

Abbreviations: D&B Score, Downs and Black quality assessment scale score²²; PGF, prophylactic Greenfield filter.

Jarrell et al⁴¹ studied 21 patients with acute SCI in whom a Kim-Ray Greenfield filter^a was inserted in the IVC. Although 1 patient died of a PE perioperatively, on follow-up, no additional PEs were noted. Two patients did develop thrombosis within the IVC, a presumed complication of the IVC filter.

In a retrospective chart audit, Wilson et al⁴² studied 22 patients with acute traumatic SCI who were treated with IVC filter insertion. No complications were associated with IVC insertion. No patient developed venous thrombosis during the acute hospitalization (median, 22d), and no patient developed a PE after filter insertion.

Khansarinia et al⁴³ in a case-control study compared 108 patients who had sustained multiple trauma, were at high risk for PE (including patients with SCI), and had received a prospectively placed prophylactic Greenfield filter, versus 216 historically matched control patients. No patient in the prospectively placed prophylactic Greenfield filter group had a pulmonary embolism, compared with 13 patients (4.2%) in the control group (P<.009), 9 of whom died (P<.03). The overall mortality rate was less in the prospectively placed prophylactic Greenfield filter group (18 of 108, 16%) than in controls (47 of 216, 22%), but this difference was not statistically significant.

Rogers et al⁴⁴ in a chart audit, pre-post and in comparison with historical controls, studied 63 of the 3151 patients admitted to the trauma service who had received a prophylactic vena cava filter. Fifteen of these patients had head injuries, 25 had SCIs, and 23 had pelvic fractures. The mean time to insertion of the vena cava filter was 4.3 days postadmission. Overall, 19 patients (30%) with prophylactic vena cava filters developed a DVT. When the incidence of pulmonary embolism in high-risk patients was compared before and after the prophylactic vena cava filter policy was instituted, there was a significant reduction (P<.001) in the incidence of PE in the group receiving filters. It was unclear how many of these 19 patients who had developed a DVT had an SCI.

Performing a retrospective chart audit, Maxwell et al⁴⁵ studied 111 patients with SCI to determine whether they differed from other trauma patients in DVT and PE incidence, and concluded that they did not differ. Maxwell noted, “there are high risk patients with SCI … that probably deserve prophylactic IVC filter placement. They include patients that have failed DVT prophylaxis or have contraindications to anticoagulation. SCI patients with long bone fractures also appear to be at extreme risk for DVT and may also benefit from IVC filter placement.”^45(p902)

There is level 3 evidence that IVC filters reduce the risk of PE in high-risk patients with SCI.

Treatment of Acute Venous Thromboembolism in Spinal Cord Injury 

Research has focused on the prevention of venous thromboemboli. Little research has examined the treatment of newly diagnosed venous thromboembolism in patients with SCI. The standard treatment of newly diagnosed venous thromboembolism post-SCI has been anticoagulation, generally beginning with intravenous unfractionated heparin, followed by the gradual transition to warfarin, which generally is maintained for 3 to 6 months. Increasingly, unfractionated heparin is being replaced by LMWH. In this regard, we found only 1 small study comparing UFH with LMWH (table 7).

Table 7. Unfractionated Heparin Versus Low-Molecular-Weight Heparin as Treatment of Acute Venous Thromboembolism in Spinal Cord Injury

Abbreviation: D&B Scores, Downs and Black quality assessment scale score²²; IV, intravenous; PTT, partial thromboplastin time.

Tomaio et al³⁰ studied 6 patients with SCI with acute DVT, half of whom were treated with intravenous heparin followed by warfarin, with the remainder treated with subcutaneous enoxaparin followed by warfarin. Although the study was small, the authors performed a careful cost analysis. Even though more research is needed, subcutaneous enoxaparin was regarded to be a safe, cost-effective, and less labor-intensive treatment of DVT in patients with SCI.

There is level 4 evidence that enoxaparin, administered subcutaneously, is safe, cost-effective, and less labor-intensive than intravenous heparin for acute DVTs post-SCI.

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Discussion 

Venous thromboembolism after SCI is a source of significant morbidity and mortality. Virtually all of the research into treatment has focused on prophylaxis to prevent venous thromboembolism in this high-risk population. Guidelines based on best evidence for DVT prophylaxis in SCI include the use of sequential compression devices for 2 weeks and anticoagulants for 8 to 12 weeks after injury.⁴⁵ There is evidence in the literature that 5000 IU UFH delivered subcutaneously every 12 hours may not be sufficient in this population to provide adequate protection. The research suggests that LMWH is more effective and should be considered the standard of treatment, particularly given the lower risk of bleeding complications. Physical measures, in particular gradient pressure stockings and intermittent pneumatic compression, are designed to reduce the impact of stasis that results from the SCI patient's lower extremities being immobilized for a prolonged period; to date, such devices have been shown to have a positive, but limited, impact. There is an intuitive benefit to combining treatments (ie, pharmacologic with mechanical treatment) and limited evidence supporting this has emerged; however, the current evidence suggests that pharmacologic measures are the more important of the two.

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Conclusions 

A systematic review of the treatment of venous thromboembolism in patients with SCI has provided reasonably good evidence supporting pharmacologic prophylaxis, while research into nonpharmacologic prophylaxis or treatment of venous thromboembolism specifically in patients with SCI is lacking.

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• a Kim Ray Medical Associates, 53 NW 42^nd St, Oklahoma City, OK.