A study of 20 Jewish and four non-Jewish kindreds transmitting factor XI deficiency (164 individuals) confirmed inheritance to be autosomal with severe deficiency in homozygotes (mean factor XI level 3.8 u/dl, SD 2.91) and partial deficiency in heterozygotes (mean factor XI level 57 u/dl, SD 10.42; normal mean factor XI level 96 u/dl, SD 11.6). The probability of an individual being heterozygous can be predicted from the factor XI level using a graph derived from this data. The accuracy is increased by including the prior probability derived from the pedigree. A high frequency of heterozygote to heterozygote mating was observed in the Jewish families consistent with an estimated gene frequency of 13.4% in this racial group. The relationship between factor XI level and bleeding tendency is poor; a third of heterozygotes had bled excessively after surgery, including six with factor XI levels above 50 u/dl, showing this condition to have clear signs of expression in heterozygotes. The lower limit of the normal range (2 SDs from the mean) was found to be 72 u/dl.

SUMMARYWith the advent of standard flow cytometric methods using two-colour fluorescence on satnpies of whole blood, it is possible to establish the ranges of CD3, CD4 and CD8 T lymphocyte subsets in the routine laboratory, and also to assist the definition of HIV-l-re!ated deviations from these normal values. In 676 HIV-I-seronegative individuals the lymphocyte subset percentages and absolute counts were determined. The samples taken mostly in the morning. The groups included heterosexual controls, people with various clotting disorders but without lymphocyte abnormalities as well as seronegative homosexual men as the appropriate controls for the HIV-I-infected groups. The stability of CD4"/ values was demonstrated throughout life, and in children CD4 values <25% could be regarded as abnormal. The absolute counts ofall Tcell subsetsdeereased from birth until the age of ID years. In adolescents and adults the absolute numbers {mean±s.d.) of lymphocytes, CD3. CD4 and CD8 eells were I 90 + 0-55. I 45 + 046. 083+029 and 056 + 0 23 X iO'*//, respectively. In patients with haemophilia A and B the mean values did not differ signifieantly. In homosexual men higher CD8 levels were seen compared with heterosexual men and 27"/;. had an inverted CD4/CD8 ratio but mostly without CD4 lymphopenia {CD4<04x 107/), However, some healthy uninfected people were 'physiologieally' lymphopenic without having inverted CD4/CD8 ratios. When the variations "within persons" were studied longitudinally over a 5-year period, the absolute CD4 counts tended to be fixed al different levels. As a marked contrast, over 60% of asymptomatic HIV-I ' patients exhibited low CD4 counts <04x 10"//together with inverted CD4/CD8 ratios. Such combined changes among the heterosexual and HIV-1-seronegative homosexual groups were as rare as 14% and 3%. respectively. For this reason, when the lymphoeyte tests show < 0-4 X IO**// CD4 eount and a CD4/CD8 ratio ofless than unity, the individuals need to be investigated further for ehronicity of this disorder, the signs of viral infections sueh as HIV-I and other eauses of immunodeficiency.

Factor VIII was purified from cryoprecipitate by ion exchange chromatography on solid phase polyelectrolyte E-5 (PE-E5). The product was highly purified (3.5 u VIII:C/mg protein) compared to conventional concentrate (0.3 u VIII:C/mg protein) with low fibrinogen, low isoagglutinin titre, and a ratio of factor VIII coagulant activity (VIII:C) to factor VII related antigen (VIIIR:Ag) of 16:1. Trial infusions of this material (PE VIII) were given to three patients with severe haemophilia A and one patient with homozygous von Willebrand's disease. These patients also each received separate infusions of intermediate purity concentrate (IPC) for comparison. There were no adverse effects. The mean half life of VIII:C after PE VIII infusion in the haemophiliacs was 10.9 h and after IPC was 12.1 h, a statistically insignificant difference. The survival of factor VIII coagulant antigen (VIII:CAg) was similar to that of VIII:C. In contrast, the half life of VIII:C and of VIII:CAg was very short after infusion of PE VIII in the patient wih von Willebrand's disease (2.4 h). IPC when infused in this patient produced a typical secondary rise of VIII:C. Two bleeding episodes in severe haemophiliacs were satisfactorily treated with PE VIII. PE-E5 deserves further study as a means of preparing clinical concentrates of factor VIII.

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After a first exposure to factor VIII concentrates, 9/9 British patients treated with U.S.A.-derived commercial products, and 10/12 treated with British volunteer (NHS) products, developed acute non-A, non-B (NANB) hepatitis. Hepatitis following commercial products was more severe, and of shorter incubation. High previous exposure to NHS blood products seemed to prevent NHS but not commercial factor VIII-induced hepatitis; the latter was also not attenuated by administration of U.S.A.-derived commercial immune serum globulin (ISG). After a first exposure to NHS factor IX concentrates without ISG, 4/4 patients developed short incubation NANB hepatitis; one also contracted prolonged incubation hepatitis B. One patient treated with ISG and factor IX of proven infectivity did not develop hepatitis, suggesting protection by ISG. Observed differences between concentrates might be attributable to their content of different NANB agents, but dose-related effects could provide alternative explanations. This data provides a basis for comparative assessment of new products of possible reduced infectivity in only small numbers of patients.