LA JOLLA- An anticoagulant compound derived from the deadly Malayan pit viper appears to offer a useful therapeutic alternative to heparin in certain high-risk patients, reported Canadian researchers at the 13th Annual Conference on Clinical Hematology and Oncology.

Heparin is used in a variety of clinical settings where anticoagulation is important, including deep vein thrombosis, pulmonary embolism and frostbite. However, in some cases heparin can cause a potentially life-threatening thrombocytopenia (an abnormal decrease in blood platelets. The incidence of heparin induced thrombocytopenia (HIT) is increasing, leading researchers to focus on how best to treat the condition, or better yet, prevent it from happening in the first place.

Heparin is being used for an increasing number of indications. As a result of this trend, the incidence of heparin induced thrombocytopenia is increasing. For example, hospitals in Hamilton, Ontario (which serve a population of two million people) saw about ten cases of HIT per year a few years ago. In 1992 this jumped to 60 cases and has jumped again to 125 cases per year, reported John Kelton, M.D., Chief of Medicine at Cheooke- McMaster Hospitals in Hamilton, Ontario.

Heparin induced thrombocytopenia is essentially an allergic reaction. IgG antibodies form against a complex of heparin and platelet factor 4 (PF4). Platelets are activated and this results in thrombocytopenia and thrombotic complications.

A higher incidence of HIT has been reported with bovine heparin than other forms. As a result most medical centers have switched to porcine heparin. HIT is seen more often at therapeutic heparin doses, but has been reported with minute doses administered by various routes.

One third of patients with HIT will go on to develop thrombotic complications. These complications may include venous thrombi, arterial thrombi including thrombosis of the limbs, myocardial infarction and stroke. Skin necrosis at the site of heparin injection may be another manifestation of HIT.

If thrombocytopenia develops in a patient receiving prophylactic heparin therapy, for example, for prevention of deep vein thrombosis, the heparin is stopped immediately. These patients may be at increased risk for thrombotic complications and alternative antithrombotic therapies are then considered, explained Kelton.

Many patients receive ongoing heparin therapy to maintain an anticoagulated state. These patients may be candidates for an alternative defibrinogenating agent called ancrod. Ancrod is extracted from the venom of the Malayan pit viper. Components in the viper's venom have a potent anti-clotting effect which keep the bite wound of the victim open while the toxin is administered.

"We have had extensive experience with ancrod. The drug is administered intravenously over eight to 12 hours. With this approach, the fibrinogen level slowly drops and the patient becomes effectively anticoagulated. Our experience with this drug has been very satisfactory," noted Dr. Kelton.

Ancrod acts via an enzymatic action on fibrinogen, forming a product which cannot be clotted by the action of thrombin. Other clotting factors including factors V and VIII are not affected by ancrod. Ancrod also does not cause platelet aggregation, nor does it degrade plasminogen. Ancrod gradually reduces viscosity, an effect attributable to decreasing fibrinogen levels. Together with decreased red blood cell aggregation, this leads to improved blood flow and perfusion of the microcirculation, he explained.

Ancrod is now being used to treat deep vein thrombosis, central retinal and branch vein thrombosis, pulmonary hypertension of embolic origin and embolism following prosthetic cardiac valve insertion. It is also indicated for prevention of rethrombosis after vascular surgery or thrombolytic surgery, as well as for the prophylaxis of deep vein thrombosis following the repair of fractures of the femur neck. The drug is also used for the treatment of moderate to severe circulatory disorders involving the peripheral arteries.

Heparin is found in the natural state in the liver, lungs and other tissues. It is produced by mast cells and leukocytes. Heparin inhibits coagulation by preventing the conversion of prothrombin to thrombin as well as by preventing the release of thromboplastin from platelets. Heparin for therapeutic use comes in two forms, standard unfractionated heparin and low molecular weight heparin.

Dr. Kelton presented his data on Feb. 20, 1995, at the 13th Annual Conference on Clinical Hematology and Oncology, sponsored by the Scripps Clinic and Research Foundation.

Transmitted: 95-03-03 19:01:41 EST