Clinical efficacy of heparin fractions: issues and answers

Abstract

The recent development of heparin fractions and fragments for clinical use has created the prospect of some new agents at our disposal for the treatment of thrombotic disorders. The development of a drug that will block thrombosis but will not impair hemostasis now appears to be a possibility. Due to lack of understanding of all of the mechanisms of the pathology of thrombosis, we are not certain what the properties of the ideal anticoagulant should be. Of the heparins and heparin fractions, fragments, and heparinoids now available to us, we have yet to fully understand the mechanism of their pharmacologic activity. It has been amply demonstrated that decreasing the average molecular weight decreases the antithrombin activity while retaining the anti-Xa activity of heparin derivatives. Studies on animal models have proven the antithrombotic potency of some of these low molecular weight heparins to be equal to that of unfractionated heparin. There has been some evidence that these fractions are less likely than unfractionated heparin to cause hemorrhage in animal models as well as in at least one human clinical trial. A recently published human clinical trial revealed an unexpected incidence of hemorrhage following major surgery when a certain heparin fraction was given as prophylaxis against thrombosis. We are desperately in need of heparin derivatives, heparinoids or other anticoagulants that can be used in place of standard heparin in patients who are allergic to heparin or who have heparin-induced thrombocytopenia. Patients with these problems not infrequently require cardiopulmonary bypass surgery in which the use of heparin has been mandatory. There is now evidence from animal and human studies that such a procedure is possible with a heparin fraction or a heparinoid. This is true for hemodialysis as well. Studies in progress offer hope that a low molecular weight fragment with potent anti-Xa activity will not cause thrombocytopenia in patients with heparin-induced thrombocytopenia. Whether this agent, a pentasaccharide, will have sufficient antithrombotic potency for clinical use remains an important question. An important property of some of the newer heparin fractions is a prolonged duration of action which may permit fewer doses, thus reducing the cost as well as patient discomfort and inconvenience.