Janet Harrison

Prothrombin complex concentrate (Konyne) in the treatment of hemophilic patients with factor VIII inhibitors

Two prothrombin complex concentrates, Auto-Factor IX and Proplex, have been reported to be effective in controlling bleeding in hemophilic patients with factor VIII inhibitors. A third PCC, Konyne, was used to treat 64 bleeding episodes (130 infusions) in five hemophilic patients with factor VIII inhibitors. Prompt control of bleeding was observed in each instance with doses of 15 to 100 units of factor IX/kg; no complications were encountered. Konyne resulted in in vivo and in vitro shortening of the partial thromboplastin time of patients with factor VIII inhibitors, but the mechanism of action is unknown. If further studies confirm the efficacy and safety of PCC in the treatment of such patients, its use for this purpose could lead to significant saving of factor VIII concentrates.

Early treatment of hemophilic hemarthroses withminimal dose of new factor VIII concentrate

Studies of in vivo recovery and longevity of factor VIII following infusions of a new factor VIII concentrate (Koate, Cutter Laboratories) yielded results similar to those reported using other sources of factor VIII. Of 51 episodes of early joint bleeding treated with single infusions of approximately 10 units per kilogram of factor VIII, 49 resolved without further replacement therapy. Koate is an effective source of factor VIII and early hemarthroses can be treated successfully with a single infusion of factor VIII in a dose of 10 units per kilogram.

Assessment of thrombogenicity of prothrombin complex concentrates in a porcine model

Infusion of prothrombin complex concentrates into pigs resulted in evidence of disseminated intravascular coagulation manifested by positive fibrin monomer tests, depletion of coagulation factors and platelets, and the presence of fibrin in small blood vessels at autopsy. All of the nine prothrombin complex concentrates were found to be thrombogenic. The response appeared to be dose-related, and the two activated materials were more thrombogenic than the non-activated products. In contrast, a purified factor IX concentrate resulted in minimal transient changes in only 2 of 5 animals tested, and autopsy findings were negative for fibrin deposition in all. Four of these animals received 200 factor IX units/kg, which was twice the dose used for any of the other products. Control animals received human plasma or albumin with no evidence of coagulation changes or fibrin deposition at autopsy. The porcine model is more sensitive than other animal models for detection of the thrombogenic effects of prothrombin complex concentrates and may be useful for testing new products found to be non-thrombogenic in other test procedures.

Plasmodium knowlesi Malaria in the Rhesus Monkey

Twelve Rhesus monkeys were inoculated intravenously with about 500 000 malaria parasites, Plasmodium knowlesi. Acute hemolysis occurred 5 days later, and all animals died on the 6th or 7th day after inoculation. All organs were gray-green to gray-brown because of deposition of hemoglobin and malaria pigments. This deposition was particularly striking in the lung, brain, abdominal fat and serous surfaces. Microscopic changes indicative of acute hypoxia were found in the liver (centrilobular necrosis) and kidneys (acute tubular necrosis). Terminal intravascular coagulopathy was evidenced by widely distributed, recently formed, fibrin thrombi.

Activities of Trimethoprim against Infections with Pyrimethamine Susceptible and Resistant Strains of Plasmodium cynomolgi

Summary A systematic comparison of the capacity of trimethoprim to control established infections with the drug susceptible RO and primethamine resistant RO/PM strains of P. cynomolgi showed that the above pyrimidine has a significant order of activity against infections with the RO strain but, at the maximum tolerated dose, little capacity to control infections with the RO/PM. Thus contrary to expectations, based on results of earlier studies in bacterial systems and in human infections with P. falciparum, there is a considerable degree of cross resistance between trimethoprim and pyrimethamine.