Recent advances in hemophilia.

ABSTRACT

Classical sex-linked hemophilia (Hemophilia A) has been described as due to deficiency in the synthesis of Factor VIII procoagulant activity (VIIIC). The availability of immunological techniques provided the means of identifying Factor VIII-Related Antigen(VI-IIRAg) detectable by rabbit antibodies to F VIII, which is distinct from VIIIC detected by human anti-F VIII available from multitransfused patients. Hemophilia A is lacking in VIIIC but not VIIIRAg. Recently, a third function of the F VIII "complex" was discovered with the help of ristocetin (von Willebrand's Factor, VIIIR RCo). This activity is reduced in von Willebrand's syndrome. Estimation of the titers of VIIIC and VIIIRAg provides a method for more accurate detection of hemophilic carriers. Newly available chromogenic substrates perhaps will give rise to more simplified assays of VIIIC. The development of cryoprecipitates and stable lyophilized concentrates of F VIII has greatly simplified and intensified maintenance therapy, and has opened a new era in treatment. Prophylactic therapy has been shown to be very helpful in certain "high risk" cases. The impact and benefits of home care and self-administration has been tremendous. However, the varying quality of cryoprecipitates and the high cost of more purified concentrates are still stumbling blocks in treatment regimes. Other problems exist. Spontaneous bleeding, especially central nervous system bleeding, account for the majority deaths by haemorrhage. Inhibitor kinetics have been well characterized. It is clear that there exists "low" and "high" responders. For the "high" responders, plasmapheresis, immunosuppressives and the infusion of Factor IX concentrates have been utilized with varying success. The prevention of hemophilic arthropathy and its progression by maintenance therapy seems to be still inadequate. The results of trials with more vigorous regimes are awaited. The complications of therapy still remain to be solved. Apart from the well-known complications wuch as hepatitis, haemolytic disease and F VIII inhibitors, the existence of previously unnoticed complications as splenomegaly, hypertension, renal disease and paradoxal bleeding have been recently realized. The role of altered fibrinogen, fibrin degradation products (FDP) and unclassified fibrinogen derivatives (UFD) present in cryoprecipitates and F VIII concentrates in the above complications needs to be further clarified. In conclusion, tremendous progress in various aspects of hemophilia has been achieved in developed countries. Comprehensive care can now be carried out in various centers. On the other hand, developing countries still face a number of basic problems. The concept that hemophilia is a "manageable" disease and that chronic crippling and death from exsanguination can be prevented, should be disseminated widely by various means...