Clot prevention after spinal cord injury
ACP J Club. 1991 Jan-Feb;114:9. doi:10.7326/ACPJC-1991-114-1-009
Green D, Lee MY, Lim AC, et al. Prevention of thromboembolism after spinal cord injury using low-molecular-weight heparin. Ann Intern Med. 1990;113:571-4. [PubMed ID: 2169216]
To examine the safety and effectiveness of low-molecular-weight heparin compared with standard heparin for prophylaxis of deep venous thrombosis in patients with recent spinal cord injury and complete motor paralysis.
Randomized, unblinded trial of 8 weeks' duration.
Regional spinal cord unit in Chicago, Illinois, USA.
Consecutive patients referred with complete motor spinal cord injury sustained within the preceding 72 hours were considered. Patients were excluded if they had bleeding injuries not accessible to hemostatic control, severe trauma to the head or lower extremities, coagulopathy, evidence of thrombosis, cardiovascular instability, or pregnancy. Of 87 consecutive patients with spinal cord injury, 41 proved eligible and were randomized.
21 patients received standard heparin, 5000 units subcutaneously every 8 hours, and 20 received low-molecular-weight heparin, 3500 anti-Xa units subcutaneously once daily. During the trial, prophylactic measures for thrombosis such as calf-compression boots, elastic stockings, and aspirin were withheld.
Main outcome measures
Patients were examined daily for symptoms and signs of deep-venous thrombosis, pulmonary embolism, and bleeding. Impedance plethysmography, Doppler flow measurements, and duplex ultrasonography were done on a decreasing schedule for 8 weeks. Clinical findings suggestive of deep-venous thrombosis, or positive or borderline findings from venous flow studies, were confirmed by contrast venography.
Of 21 patients on standard heparin, 7 had either bleeding or thrombosis (35%; 95% CI 13.7% to 55.2%), whereas no patient in the low-molecular-weight heparin group had either bleeding or thrombosis (CI 0% to 14%, P = 0.006). In patients given standard heparin, 2 bled severely enough to require discontinuation of therapy and 2 patients died suddenly while being turned in bed, both with massive pulmonary embolus. 5 patients on standard heparin had abnormal venous flow studies, and in 2, the diagnosis was confirmed by venography. In the low-molecular-weight heparin group, 2 patients had abnormal venous flow studies, but these could not be confirmed by venography.
Low-molecular-weight heparin is more effective, safer, and easier to administer than standard heparin for preventing thromboembolism in selected patients with spinal cord injury and complete motor paralysis.
Source of funding: National Institute of Disability and Rehabilitation Research.
Address for article reprint: Dr. D. Green, 345 E. Superior Street, Room 1407, Chicago, IL 60611, USA.
This is a well-designed clinical trial, and the data appear to support the conclusions. Several laudatory features of the methods should be mentioned: The size of the study was determined by a power calculation; details of the eligible and ineligible patients were provided, allowing the reader to consider whether the results can be generalized; cause of death was determined by autopsy; and details of patients who switched treatment groups or dropped out of the study were included. There are some troublesome details, however: The treatment groups were small; it was not clear whether risk factors for deep venous thrombosis other than spinal cord injury were equally distributed after randomization; the pulmonary embolism case fatality rate was surprisingly high in the heparin group; and, if abnormal flow studies are used as proxies for thrombus, the difference between the 2 groups was not significant (5 of 21 vs 2 of 20 patients, P > 0.28 by Fisher exact test). Thus, other studies would be desirable to confirm the validity of the findings.
Daniel M. Becker, MD
University of Virginia School of MedicineCharlottesville, Virginia, USA