Assessment for evidence of non A-non B hepatitis in patients given n-heptane-suspended heat-treated clotting factor concentrates.

Nineteen patients, (2 adults, 17 children) with inherited bleeding disorders were infused with n-heptane-suspended-heated clotting factor concentrates. Twelve of the nineteen were previously untreated. Six patients were infused with Profilnine Heat-Treated and 13 with Profilate Heat-Treated. Five separate centers participated and were given various lots of concentrates for use. Blood from the seventeen children was sampled prior to entry, at infusion, 2 weeks, 6 weeks, 12 weeks and 6 months after the first infusion. The two adults were sampled every 2 weeks. Twelve of the 19 patients were followed beyond six months. Three patients demonstrated a rise in ALT during the first six months of observation with levels above 2.5 times the upper limit of normal. One of these patients showed a parallel increment in a-CMV IgM titer and a second patient, an adult, had previously received many units of single donor blood components. During the second 6 month observation interval, two patients showed a rise in ALT. One of these patients had been exposed to only one lot of concentrate with no other viral cause being determined. Two additional patients had a moderate increase in ALT up to 98 U/L (normal less than 50). No patients were clinically ill or showed jaundice during these episodes. The hepatitis episode at 11 months in the patient using one lot of concentrate, might suggest a non-viral mechanism in this instance. This study indicates that these concentrates may be associated with episodes of ALT above 2.5 times the upper limit of normal in approximately 20% of the patients treated, but the etiology of the raised ALT may not always be Non A-Non B hepatitis.

Evaluation of human viral disease transmission through plasma products.

Alpha's Wet Heat-Treatment process is being applied to both Factor VIII (AHF) and Factor IX Complex (PTC). Twelve hemophilia A, five hemophilia B, and one von Willebrands patient have been followed for at least 6 months for evidence of non-A, non-B hepatitis. No ALT elevations were seen in the hemophilia B patients. There have been four cases of ALT elevation, three in hemophilia A patients and one in the von Willebrand's patient. A subset of these patients have been followed for over one year for anti-HTLV-III status. No patient, either hemophilia A, hemophilia B, or von Willebrand's seroconverted to anti-HTLV-III positive status. Intravenous gamma globulin was studied in 11 normal patients given a single infusion and in 23 immune deficient patients with multiple infusions and evaluations of liver enzymes over a two year period. No elevated ALT or AST values were seen in either group.

Trials with an adenosine analogue as antianginal medication.

The potential antianginal effects of orally administered ethyl-adenosine-5-carboxylate hydrochloride (EACH) were assessed in 9 patients with stable angina pectoris who underwent two standardized exercise tests for 3 consecutive days. The first daily exercise performed after placebo revealed no daily variation. The second test was preceded by placebo, 26 mg EACH or 33 mg EACH administered in a double-blind fashion with the use of crossover design. After the completion of the study in the first 6 patients, the 33-mg dose of EACH had to be discontinued because 3 patients had severe angina and another one had nausea and diffuse numbness after this dose. In the remaining 3 patients a 6-mg dose of EACH was used instead of 33 mg, after which the study was terminated because no difference could be determined. EACH, 26-mg and 6-mg, had no significant effect on resting and exercise heart rate, on blood pressure, on onset or duration of angina and positive-exercise electrocardiogram, or on exercise duration. Our study revealed that EACH had no potential antianginal effect and that at a dosage of 33 mg it may induce angina.