Low-Molecular-Weight Heparin versus Low-Dose Unfractionated Heparin as Prophylaxis

Several studies have been found which examined LMWH alone or compared different dosages or types of LMWHs.

Discussion

Several studies have examined the thromboprophylactic effectiveness of LMWH compared to that of LDUH on the incidence of DVT and PE in the acute phase (<3 months) of SCI. Two studies evaluated the efficacy of Logiparin compared to LDUH. One RCT by Green et al. (1990) included individuals who were within 72 hours of sustaining SCI, and who were randomly assigned to receive 5000 IU LDUH every 8 hours or 3500 anti-Xa U Logiparin once daily. Significantly more individuals receiving LDUH (24%) developed DVT/PE compared to individuals receiving LMWH (0%, p=0.02). Green et al. (1994) studied 48 individuals who were given 3500 anti-Xa U Logiparin once daily for 8 weeks, beginning within 72 hours of injury. These individuals, combined with 20 individuals receiving the same regimen in the previously mentioned study (1990), were compared to individuals receiving LDUH (also from the previously mentioned study by Green et al. (1990)). Although not significant, a trend was reported in terms of fewer thrombotic events occurring for LMWH, which compared favourably to LDUH for VTE prophylaxis.

Several studies evaluated the efficacy of Enoxaparin compared to LDUH. In a case control study, Arnold et al. (2010) retrospectively reviewed individuals who were admitted greater than 72 hours post-SCI, and who received either 5000 U LDUH three times a day or Enoxaparin (30 mg twice daily or 40 mg once daily). A significant difference between groups in incidence of DVT was not observed (p=0.357). Thumbikat et al. (2002) also conducted a case control study in which individuals were studied, on average, 12 days post-injury. Participants received either 5000 IU LDUH twice daily, or 20 or 40 mg Enoxaparin. The authors reported that 13% of individuals receiving LDUH and 18% of individuals receiving Enoxaparin developed VTE, with peak incidences occurring at 20 to 30 days and 90 to 100 days following injury for both groups overall; however, no statistical analyses were reported.

In an RCT by the Spinal Cord Injury Thromboprophylaxis Investigators (2003a), individuals were randomly assigned to receive either 5000 IU LDUH every 8 hours along with IPC, or 40 mg of Enoxaparin every 12 hours without IPC. All individuals studied had sustained an SCI within 72 hours, were monitored for approximately two weeks, and were screened for DVT/PE. 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). Further to the previous study, the Spinal Cord Injury Thromboprophylaxis Investigators (2003b) investigated the effect of 6 more weeks of pharmacological prophylaxis following the initial 2-week protocol. Individuals previously receiving 5000 IU LDUH every 8 hours continued to do so, but without concurrent IPC. Individuals previously receiving Enoxaparin continued this regimen, but at a dose of 40 mg once daily. Screening for DVT and PE was performed at the conclusion of the additional 6-week protocol. In individuals receiving LDUH, the incidence of DVT was 18.3% which was not significantly different from 6.8% of individuals receiving Enoxaparin (p=0.067). The incidence of PE was also not significantly different between groups (3.3% and 1.7% of individuals receiving LDUH and Enoxaparin, respectively, p=0.576).

Finally, a case control by Worley et al. (2008) evaluated the efficacy of Dalteparin compared to LDUH. Individuals in acute care (time post-injury otherwise not specified) were retrospectively reviewed; individuals received either 5000 U LDUH twice daily or 5000 U Dalteparin daily. No significant difference in DVT incidence was found between the groups (p=0.7054).

A systematic review by Chen and Wang (2013) examining 18 studies with 2578 individuals compared the effect of different pharmacological VTE prophylactic options. It was concluded that LMWH is similar to LDUH in VTE prevention but has less bleeding complications. There was no difference in VTE prophylaxis using various types and/or doses of LMWH, including enoxaparin, tinzaparin, and dalteparin. Despite the conflicting results presented by Chen and Wang (2013), there is still strong evidence based on five studies that LMWH is more effective than LDUH.

Conclusions

There is level 1b evidence (from one RCT: Green et al. 1990) that Logiparin (low molecular weight heparin) is more effective than low-dose unfractionated heparin as prophylaxis for venous thromboembolism in acute SCI individuals.

There is level 1b evidence (from one RCT: Spinal Cord Injury Thromboprophylaxis Investigators 2003a) that Enoxaparin (low molecular weight heparin) is more effective than low-dose unfractionated heparin as prophylaxis for pulmonary emboli in acute SCI.

There is level 1b evidence (from one RCT: Spinal Cord Injury Thromboprophylaxis Investigators 2003a; one prospective controlled trial: Spinal Cord Injury Thromboprophylaxis Investigators 2003b; and two case controls: Arnold et al. 2010; Thumbikat et al. 2002) that Enoxaparin (low molecular weight heparin) is equally as effective as low-dose unfractionated heparin as prophylaxis for deep venous thrombosis in acute SCI.

There is level 3 evidence (from one case control: Worley et al. 2008) that Dalteparin (low molecular weight heparin) is equally as effective as low-dose unfractionated heparin as prophylaxis for venous thromboembolism in acute SCI individuals.