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Combined Mechanical and Pharmacological Modalities

Evaluation of Combined Pharmacological and Mechanical Modalities for Thromboprophylaxis in Acute SCI

Discussion

Eight studies have examined the prophylactic effectiveness of various combinations of mechanical and pharmacological methods on the incidence of DVT and PE in acute SCI individuals. Two studies investigated the combined effect of LDUH with mechanical methods for VTE prophylaxis. In a RCT by the Spinal Cord Injury Thromboprophylaxis Investigators (2003a), individuals were randomly assigned to either receive 5000 IU LDUH every 8 hours along with IPC, or 40 mg of Enoxaparin every 12 hours. All individuals studied had sustained SCI within 72 hours, and were monitored for a duration of approximately 2 weeks of acute treatment, at the end of which screening for DVT and PE was performed. In individuals receiving LDUH, the incidence of DVT was 44.9%, which was not significantly different from 60.3% of individuals receiving Enoxaparin (p=0.11). The incidence of PE was significantly higher (18.4%) in individuals receiving LDUH compared to Enoxaparin (5.2%, p=0.03). Merli et al. (1992) conducted a case control study in which individuals received external pneumatic compression with GES and 5000 U LDUH every 12 hours, and were compared to a control group of individuals receiving no intervention. All individuals were studied beginning within 48 hours of injury for the initial 2 week duration following injury. The incidence of DVT was found to be significantly lower in individuals receiving mechanical and pharmacological prophylaxis as compared to the group of control individuals (p=0.04).

One study by Maxwell et al. (2002) compared LDUH and LMWH, each in combination with mechanical methods of prophylaxis. Individuals hospitalized for an average of 23 days after injury were retrospectively reviewed in terms of their use of SCD in combination with either 5000 IU LDUH every 12 hours or 30 mg Enoxaparin every 12 hours. The incidence of DVT and PE in individuals using SCD and LDUH was 11.1% and 2.8%, respectively. The incidence of DVT in individuals using SCD and Enoxaparin was 6.9%; no PE was observed in this group of individuals. There were no significant differences in incidence rates for DVT or PE between groups.

Five studies investigated LMWH in combination with mechanical methods of prophylaxis. Pierfranceschi et al. (2013) studied individuals who had received graduate compressive stockings in combination with either 4000 U Enoxaparin daily or 5000 U Dalteparin daily. Treatment was administered within 72 hours of admission after surgery, which occurred 48-72 hours after injury. The authors found that 23.4% of individuals developed VTE events, 90.9% of which occurred within the first 3 months after SCI. Halim et al. (2014) conducted a RCT in which individuals were randomly assigned to receive either only physical modalities of prophylaxis (not specified further), or 40 mg Enoxaparin once daily along with the same form of physical prophylaxis. Individuals enrolled in this study had sustained a SCI no more than 5 days prior to entering the study, and were monitored for the initial 2-week duration following injury. The incidence of DVT was significantly higher in individuals receiving only mechanical prophylaxis (21.6%) compared to individuals receiving a combination of mechanical and pharmacological prophylaxis (5.4%, p=0.041). PE occurrences were nonexistent. Germing et al. (2010) enrolled individuals within the first 36 hours of admission in a pre-post study; all individuals received 40 mg Enoxaparin together with compression stockings. The cumulative incidence of DVT was reported to be 45.3%, with 38% of DVT events occurring within the first 36 hours of admission; no statistical analysis was reported. A case series by Deep et al. (2001) retrospectively investigated individuals on admission to a spinal injuries unit. On admission or at the time of injury, individuals received anti-thromboembolic stockings and 40 mg Enoxaparin once daily. Of this study population, 2.2% and 0.7% of individuals developed DVT and PE, respectively. Finally, in a pre-post study by Aito et al. (2002), individuals, who were classified as either early admitted (i.e., 72 hours post injury) or late admitted (mean=12 days post injury), received a combination of permanently dressed GES, external sequential pneumatic compression, as well as Nadroparine. The incidence of DVT was 2% and 26% for early admitted and late admitted individuals, respectively; no statistical analysis was reported.

Conclusion

There is level 1b evidence (from one RCT; Spinal Cord Injury Thromboprophylaxis Investigators 2003a) that low-dose unfractionated heparin in combination with intermittent pneumatic compressionis as effective as Enoxaparin as prophylaxis for deep vein thrombosis in acute SCI individuals.

There is level 3 evidence (from one case control; Merli et al. 1992) that pneumatic compression in combination with gradient elastic stockings and low-dose unfractionated heparin is effective in reducing the incidence of deep vein thrombosis in acute SCI individuals.

There is level 1b evidence (from one RCT; Halim et al. 2014) that Enoxaparin in combination with physical measures is more effective than physical measures alone as prophylaxis for deep venous thrombosis in acute SCI individuals; However, there is level 4 evidence (from one case series; Maxwell et al. 2002) that Enoxaparin plus sequential compression devices, low-dose unfractionated heparin plus sequential compression devices, and sequential compression devices alone are similarly effective as venous thromboembolism prophylaxis in acute SCI individuals.   

  • A combination of low-dose unfractionated heparin with intermittent pneumatic compression seems equally as effective as low-molecular-weight heparin alone at reducing this risk.

  • There is conflicting evidence regarding the effectiveness of the combination of low- molecular-weight heparin with physical measures at reducing the risk of venous thromboembolism compared to physical measures alone during the acute phase post SCI.