Neurologic Uses of Low Molecular Weight Heparins

ABSTRACT & COMMENTARY
Source: Weitz JI. Low-molecular-weight heparins. N Engl J Med 1997;337:688-698.

Low molecular weight heparins (lmh) (mw @ 5000) vs. unfractionated heparin (UFH; contains heterogenous chains of mw 3000-30,000) have been evaluated and tested for almost 20 years, especially in Euro-Asiatic countries. Although costing 10-20 times per dose more than UFH, LMH has increasingly been used in the United States on an outpatient basis to prevent venous thrombosis, making it cost-effective under such conditions. Compared to LMH, UFH produces more predictable anticoagulant responses, has better bioavailability and length of action, has fewer antithrombocyte effects, and possesses better dose-independent clearance by the kidney. It also has less risk of producing unwanted bleeding.

Currently, despite its individual dosage costs, LMH can be recommended under several circumstances for preventing venous thrombosis. One group consisted of non-hemorrhagic major trauma, in which low-dose UFH was compared to LMH, each started before 36 hours post-injury. LMH compared to UFH reduced the rate of venous thrombosis from 44% to 31% (P = 0.014) and reduced proximal venous thrombosis from 15% to 6% (P = 0.09). However, five of six persons with major bleeding had received LMH.

Acute spinal injury provides a second high-risk group for potential venous thrombosis, the incidence of a venous thrombosis being reported as 14.5% and 4.5% pulmonary embolism (Waring, Karunas. Paraplegia 1991;29:8-16). Small trials suggest higher effectiveness of LMH, but numbers remain few. Untreated ischemic stroke carries about a 40% risk of venous thrombosis in the plegic leg (Clagett, et al. Chest 1995;Suppl 108:312S-334S); several small studies promote LMH as the prophylactic measure of choice. The data, however, are few and not strongly indicative of an advantage over UFH. One large study in Hong Kong, however, treated 312 acute strokes as outpatients and reported that among patients surviving or becoming functionally independent, 55% received LMH twice daily and 48% received LMH once daily. Severe morbidity-mortality among controls was 65% (Kay, et al. N Engl J Med 1995;333: 1588-1593; Neuro Alert 1996;14:42-43).

COMMENTARY

Weitz’s informative review adds additional points relevant to general physicians. For neurologists, the principal advantage of LMH compared to UFH is that it is highly safe, has fewer unwanted side effects, has a longer and more steady effect, and does not require blood testing for each successive dose. Its therapeutic value over UFH is relatively small, however, making the latter the preferred agent for the prophylaxis/treatment of hospitalized patients at risk for or suffering from venous thrombosis. LMH, however, despite its unit costs, provides an effective drug for venous thrombosis in outpatients, thereby eliminating the costs and risks of hospitalization. —fp