AA

Low-Dose Unfractionated Heparin (LDUH) as Prophylaxis

Heparin acts as an anticoagulant by forming a complex with anti-thrombin, catalyzing the inhibition of several activated blood coagulation factors: XIIa, XIa, IXa, Xa and thrombin. Heparin’s onset of action is immediate. It is most often used in acute conditions, and must be given parenterally. Although low-molecular-weight heparin has become more popular in the treatment of DVT, the effects of intravenous heparin can be reversed rapidly. Bleeding is the most common adverse effect of heparin. Osteoporosis is associated with the prolonged use of high doses of heparin, although its occurrence is infrequent. Thrombocytopenia, a decreased platelet level in the blood, is an uncommon but serious side-effect of heparin treatment (Pineo & Hull 2004).

Table 3 Efficacy of Unfractionated Heparin vs. Placebo as Prophylaxis

Table 4 Fixed vs. Adjusted Dose Heparin in Prophylaxis of Thromboembolism in SCI

Discussion

Unfractionated heparin has been the standard treatment for venous thromboembolism post SCI for years. Evidence for its effectiveness, however, is unclear. Despite the use of LDUH, a high rate of DVTs and PEs has been shown to occur in acute SCI patients (Kulkarni et al. 1992). Three studies have examined the effect of treatment with LDUH versus placebo. Agarwal and Mathur (2009) randomly divided patients between treatment and control groups. The treatment group received 5000 IU of low-dose unfractionated heparin (LDUH) subcutaneously two times a day from admission to three months post injury while the control group received no treatment. The study found no significant difference in DVT incidence between the two groups (3.0% vs. 1.8%, respectively).

Merli et al. (1988)evaluated 53 acute SCI patients who were randomly assigned to one of three groups: placebo saline (n=17), 5000 IU LDUH (n=16), or 5000 IU LDUH 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 while there was a significant improvement in the heparin and electrical stimulation group. The study was prematurely discontinued because of the benefit of the heparin plus electrical stimulation group and lack of efficacy in the control group.

Frisbie and Sasahara (1981) conducted a non-randomized trial of 32 SCI patients receiving either no treatment or 5000 IU of LDUH until day 60 post SCI. Incidence of DVT was rare in both the control (1/17) and the LDUH group (1/15).

Green et al. (1988) studied 75 SCI patients who were randomized to receive either a fixed dose or an adjusted dose of unfractionated heparin. The fixed dose heparin was 5000 IU; the adjusted heparin group started off at 5000 IU and was adjusted according to aPTT (activated Partial Thromboplastin Time) to a maximum of 15000 IU (mean = 13200 IU). Thromboembolism was detected in 9/29 on fixed-dose regimen with no bleeding complications while 2/29 on the adjusted-dose regimen developed thromboembolism and 7/29 had bleeding complications.

Typically prophylactic treatment involves 5000 IU of heparin. Two RCTs and one controlled study examining the efficacy of this dose and a placebo found no difference in the incidence of venous thrombosis in both the treatment and the placebo groups. Interestingly, Merli et al. (1988) found that heparin plus electrical muscle stimulation significantly reduced the incidence of venous thrombosis when compared to heparin alone. Finally, one RCT (Green et al. 1988) has shown that while 5000 IU of heparin was not an effective dose in reducing the incidence of thromboembolism, higher doses were more effective but had a higher risk of bleeding complications. In a recent systematic review and meta-analysis, Chen and Wang (2013) conclude that among patients with acute SCI, LDUH has no thromboprophylaxis effect compared with placebo or no treatment.

Conclusions

There is level 2 evidence (from 2 RCTs and 1 prospective controlled trial; Merli et al. 1988; Agarwal & Mathur 2009; Frisbie & Sasahara 1981) that 5000 IU of low-dose unfractionated heparin is no more effective than placebo in the prophylaxis of venous thrombosis post SCI.

There is level 1b evidence (from 1 RCT; Green et al. 1988) that adjusted (higher) dose unfractionated heparin is more effective in prophylaxis of venous thromboembolism than 5000 IU low-dose unfractionated heparin but has a higher incidence of bleeding complications.

  • 5000 IU subcutaneously every 12 hours of unfractionated heparin does not prevent venous thrombosis post SCI while higher dose, adjusted unfractionated heparin is more effective, although risk of bleeding complications is higher.