Haemophilia & Other Inherited Bleeding Disorders

From The New England Journal of MedicineHemophilia is a relatively rare congenital disorder (80 severe cases per 1 million males), which medical students become acquainted with mainly as the prototype of an X-linked hereditary disease. Despite the rarity of the disorder, the bleeding manifestations (hemarthrosis, muscle bleeding, hematuria, intracranial hemorrhage, and bleeding during surgery) can involve many medical disciplines, and a single patient may see numerous physicians during his lifetime. This multiauthored book is a useful guide to the current management of hemophilia.During the past four decades, the care of patients with hemophilia has been an extraordinary mix of success and failure. The hemophilias were defined and the clotting factors were discovered in the 1950s through the collaboration of astute clinicians, who mixed plasma samples from patients with congenital bleeding disorders. If mixing the samples did not correct the clotting time, the patients had the same defect; if mixing corrected the clotting time, the defect was different, suggesting the possible existence of yet another clotting factor. The early discovery of the coagulation cascade remains an impressive example of patient-driven fundamental research. The 1960s and 1970s saw the development of clotting-factor concentrates and the concept of self-infusion of these materials ("home therapy"). The immediate arrest of an incipient hemarthrosis by self-administration of clotting factor has undoubtedly been most influential in changing hemophilia from a crippling disorder to a manageable disease, allowing persons with hemophilia to have nearly normal participation in educational, professional, and social activities. The 1980s witnessed the cloning of the genes involved in the disorder and the development of recombinant clotting products. During this period, the practice of prophylactic infusion of concentrate twice or three times a week in severely affected persons was initiated in some countries. The 1990s have focused on the possibilities of gene therapy for patients with hemophilia.Hemophilia, however, is also the paradigm of clinical failure. In the early 1980s, at the very moment that hemophilia seemed to have been nearly harnessed, transfusion-mediated infection with the human immunodeficiency virus suddenly took center stage. This has been a tragedy both for patients with hemophilia and for their physicians, who devoted their energies to caring for their patients and unwittingly infected them with the deadly virus. As illustrated in this book, the median age at the time of death for persons with hemophilia A in the United States increased from 40 years in the period from 1968 to 1970 to 57 years in the period from 1979 to 1981 but declined to 40 years in the period from 1987 to 1989. Moreover, most adults with hemophilia have chronic hepatitis C infection.Care for patients with hemophilia is also a failure in that the optimal therapy is extremely expensive. In some industrialized countries, patients with hemophilia have problems getting adequate health insurance coverage, and therapy is virtually unavailable for most patients in developing countries. Repeated infusion of costly concentrate remains an effective but hardly affordable halfway approach to care. Fortunately, there is hope that gene therapy may provide a more definitive and perhaps more economical answer to the problem of hemophilia.This book gives a valuable overview of various aspects of the care of patients with hemophilia, mainly from the perspective of physicians in the United Kingdom; of the 19 contributors, 16 are from the United Kingdom, and 3 are from the United States. As one might expect, the book starts with a useful summary of the current concepts of normal hemostasis. The genetics, clinical features, and management of hemophilia are well covered, as are transfusion-transmitted viral diseases, the possible development of neutralizing antibodies against (inhibitors