Haemophilia B is extremely rare in females and so far 20 cases have been reported. A 9-year-old girl with severe haemophilia symptoms is described, who shows a very low level of factor IX activity (1.5%) and antigen (less than 10%), normal XX female karyotype and negative family history of bleeding tendency or consanguinity. This case is probably the fourth report of sporadic female haemophilia B without chromosomal aberration and the first one with quantitative analysis by immunoradiometric assay and enzyme-linked immunosorbent assay of factor IX antigen. This very low factor IX level and severe bleeding tendency of the patient would be consistent with the homozygous state, but since a double mutation is extremely rare the patient's laboratory findings can be more easily explained by extreme lyonization of the normal X-chromosome of a heterozygous carrier.

We describe a patient with haemophilia A and factor VIII inhibitor who underwent surgical excision of a large pseudotumour in the left femoral region. Haemostasis was successfully maintained with bolus doses of recombinant factor VIIa at 2-h intervals and anti-fibrinolytic therapy, and the pseudotumour was removed. Subsequently, the dose interval was gradually prolonged to 8 h for a total of 18 days. Although a spontaneous haemorrhage was observed on postoperative day 8, haemostasis was achieved by reducing the dosage interval. No adverse event occurred during the course of treatment.

We evaluated the medium-term follow-up results, effectiveness, and suitability of arthroplasty for hemophilic arthropathy. We performed 26 total knee and 9 total hip arthroplasty operations on hemophilic patients between 1988 and 1998 under general anesthesia and appropriate hemostatic management. Postoperative treatment for hemophilic arthropathy is the same as that for osteoarthritis and rheumatoid arthritis. After their operations, patients experienced relief from pain and intra-articular bleeding in affected joints but only marginal improvement in the range of motion. In general, total joint arthroplasty is not indicated for young patients. However, arthropathy can have a severe impact on the active life of patients during their youth. For severe hemophilic arthritis, total knee and hip arthroplasty can lead to a pain-free and improved quality of life. We believe total knee and hip arthroplasty is a good solutions for hemophiliac arthropathy before severe deformity occurs. Although treated relatively young hemophilic patients, age was not considered to be a contraindication.

Recently, the gene structure for human F.VIII protein was clarified, and F.VIII DNA probes have been used for carrier detection and prenatal diagnosis ofhaemophilia A. In order to make sure that the phenomena are universal, we have analysed the RFLPs of F.VIII gene in 16 Japanese families with haemophilia A, including a female haemophiliac case, using an intragenic F.VIII DNA probe(F8A) and an extragenic(linked) DNA probe(Stl4-1). The probe F8A revealed two variant bands after digestion by Bel I. Of normal 60 X chromosomes (females) examined, about 85% bore the 879-bp fragment and 15%the 1165-bp fragment. Five of sixteen mothers of hemophiliacs, definite carriers, were found to be heterozygous for Bel I polymorphism. Since the relationship between Bel I alleles and hemophilia gene has been identified in the 5 families in which the mothers were heterozygous, we could diagnose the carrier status of two women whose brothers are hemophiliacs. Onthe other hand, we could identify that one "haemophilic woman" with less than 10% of F.VIII:C was a carrier status when we analysed the Bel I alleles in theother members of the family. The probe DNA(ST 14-1) revealed seven variant bands ranging from 5.5 kb to 3.4 kb after digestion by Taq I. In 6 out of 16 families, the RFLPs of ST 14 locus were informative for carrier detection. From these data, it was concluded that the Bel I polymorphism of F.VIII gene and the Taq I polymorphism of ST 14 locus were informative for carrier detection in 8 out of 16 families with haemophilia A

The nature of sugar chain of factor VIII/von Willebrand factor in plasma of normal subjects and patients with von Willebrand's disease (vWd) was examined by crossed affinoimmunoelectrophoresis using anti-human factor VIII rabbit serum, with inserted Ricinus communis agglutinin-120 (RCA-120) agarose layer (RCA - CIE). Molecular weights of factor VIII-related antigen (VIIIR:Ag) were estimated by SDS polyacrylamide gel electrophoresis - crossed affinoimmunoelectrophoresis (SDS PAGE - RCA - CIE). VIIIR:Ag, in normal plasma and in classical form of vWd, showed two precipitin peaks on RCA - CIE. The slower moving component of VIIIR:Ag with molecular weights over 3 x 10(6) daltons from normal subjects and patients with classical form of vWd showed a high affinity for RCA-120. The faster moving component of VIIIR:Ag below 3 x 10(6) daltons from the above-mentioned subjects and patients with a variant form (Type IIA) showed a very weak affinity for RCA-120. These results suggested that all of VIIIR:Ag in these variant cases may have a deficiency of galactose residues reactive with RCA, in addition to an incomplete polymerization of VIIIR:Ag, similar to that of the faster moving component of normal subjects.

3 young Japanese sisters with congenital α2-plasmin inhibitor (α2-PI) deficiency are reported. They have mild umbilical bleeding and/or repeated prolonged bleeding after minor trauma, but rarely spontaneous bleedings. The most characteristic hemostatic findings were shortened whole blood clot lysis time and euglobulin lysis time. Activities of all hemostatic factors except α2-PI were within normal range. Both functional and immunological absence of α2-PI were found in the plasma, and this failure to detect α2-PI was not corrected by the addition of the patient’s plasma of the first described case of α2-PI deficiency. Clinical and laboratory data revealed that these patients were probably homozygous for α2-PI deficiency and born of heterozygous parents, but not of consanguineous ones. Bleeding episodes due to deficiency of (α2-PI in these patients were well controlled by an antifibrinolytic agent, tranexamic acid.

A surgical case is described of a 40-year-old hemophilia A patient with a potent factor VIII inhibitor (40 Bethesda units) suffering from a chronic cystic haematoma in the right thigh. Surgery was performed after extensive plasmapheresis and administration of a large amount of factor VIII concentrate (42,500 U on the day of operation). During the five post-operative days, the factor VIII level was maintained above 25%, which allowed control of hemorrhage. However, two serious problems, i.e., hemolytic anemia and anamnestic response of factor VIII inhibitor titer, occurred on the 6th post-operative day. The hemolytic anemia was circumvented by administering prothrombin complex concentrate every 8 hours for 12 days until the sutures were removed. There was no bleeding although the inhibitor titer rose to 460 Bethesda units.

A 17-year-old hemophilia A patient with an intracranial bleeding and a high titre of factor VIII inhibitor was treated with repeated infusion of an activated prothrombin complex concentrate (FEIBA). A good effect was achieved clinically, but laboratory tests on 8th day of the treatment revealed no shortening effect on non-activated partial thromboplastin time and on r-value of thrombelastograph. A prolongation of prothrombin time and thrombin time, a decrease in fibrinogen and antithrombin III, and an increase in serum FDP were also observed. These findings returned to normal after FEIBA was stopped. It was suggested that repeated and massive infusion of FEIBA might cause a decrease in natural inhibitors which lead to DIC.