Hemophilia and von Willebrand Disease in Developing Countries

In the last decade great progress has been made in the diagnosis and management of patients with hemophilia and those with von Willebrand disease (vWD). Patients with hemophilia can expect a near-normal life expectancy without the once devastating joint deformities due to intraarticular bleedings. They are full participants in the work force and enjoy a relatively uncomplicated life style. This is, unfortunately, not the case for patients in developing countries where major problems still exist regarding diagnosis and adequate treatment.

This issue of Seminars in Thrombosis and Hemostasis reviews the problems that still exist in developing countries and delineates multiple avenues that can and should be taken to improve the health care for these patients.

In the first article, Evatt reports on the status of population statistics concerning hemophilia. The World Federation of Haemophilia (WFH) is actively involved in gathering data from developed and emerging countries. Such data are important for health planers to address specific problems, disseminate information, garner governmental support, and develop local healthcare systems. Although the number of hemophilic patients is well established in developed countries, their numbers are grossly underestimated, for a variety of reasons, in developing countries. There appears to be a direct link between the economic capacity of these countries and the status of care for hemophilic patients. Lack of diagnostic facilities, lack of adequate and safe treatment options, and lack of knowledge on behalf of healthcare providers, patients, their families, and the population in general influence the status of these patients. It is thus not surprising that, in contrast to developed countries, the life expectancy of hemophiliacs is markedly lower in developing countries.

In the next article, Srivastava and collaborators review the status of hemophilia care in seven emerging countries. They describe the overall incidence of hemophilia, the availability and protocols used for treatment, the management of patients with inhibitors, and the available adjunct therapies. There is wide variability in the types of factor replacement available and the way that dosing is used. The authors point to the need of greater awareness of this disorder, a better coordination of treatment modalities, and improved therapies.

Chandy next discusses the management of hemophilia in developing countries by focusing on minimal use of factor concentrates but extensive use of adjuvant modalities. The three major problems facing hemophiliacs in these countries are lack of education for patients, their relatives, and healthcare providers; unavailability of basic laboratories that can establish the proper diagnosis; and limited supplies of factor concentrates because they are expensive and unaffordable by most patients.

Kasper elaborates on the strategies that may be used by developing countries to procure factor replacement. The production of domestic plasma and cryoprecipitate is one possibility, but depends heavily on a reliable blood transfusion service. Domestic plasma fractionation is another possibility, but this could be expensive. A third possibility is contract fractionation, where an existing fractionation unit abroad performs these services on domestically procured plasma. Lastly, concentrates can be imported, but this is very costly in most instances. The advantages and disadvantages of these options are discussed expertly.

Heijnen and Buzzard review the role of physical therapy and rehabilitation for hemophiliacs in developing countries. The use of factor concentrates and their prompt administration has widely reduced the sequelae of joint bleedings (i.e., hemophilic arthropathies) in developed countries. Joint deformities have become exceedingly rare. In countries that do not have ready access to these concentrates, joint deformities are still common, and for these patients physical therapy and rehabilitation efforts are of the greatest importance. The authors outline available modalities and make valuable recommendations on how to reduce these serious complications.

Rodrigues-Merchan and Heim discuss the orthopedic options available for hemophilic joint bleedings. The problems start in infancy and prophylactic treatment of these children with factor concentrates has markedly reduced hemophilic arthropathies. Both conservative and operative treatment options are reviewed and the importance of a team approach to the management of hemophiliacs is stressed.

Yee and Lee discuss the transfusion-transmitted infections in hemophiliacs in emerging countries. The main infections that face hemophiliacs are hepatitis B and C viruses and human immunodeficiency virus. The incidence of these infections varies greatly between countries and largely depends on the safety of the blood supply. Several steps are outlined in this review that can be taken to reduce the overall incidence of virus infections. In addition, the nature of the viruses, their impact on hemophiliacs, and the challenges that exist in delivering antiviral treatment modalities in developing countries are reviewed expertly.

Mathews and coworkers review the issue of surgeries in hemophilic patients in developing countries. With the availability of factor concentrates, almost all forms of surgery currently can be performed safely in these patients. Lack of concentrates, however, presents a major problem when surgeries are needed in hemophilic patients. The authors, forced by their local circumstances, developed several treatment protocols and observed that substitution of factor VIII (FVIII) and FIX with lower than recommended doses was equally successful. They also observed that there was no difference in outcome when these lower doses were administered as bolus or by continuous infusion. These findings should encourage clinicians to revisit the dosing schemes that are recommended presently in developed countries.

Peyvandi addresses the issue of carrier detection for hemophilia. Given that treatment options are limited in many emerging countries, detection of carriers and genetic counseling are of great importance. The author reviews the present status of the genetics of hemophilia A and B, and describes the genetic defects presently identified and the frequency with which they occur. In addition, the technical aspects of gene mutation identification are summarized. Some of these tests can be adapted in developing countries at a reasonable cost. The prenatal identification of gene defects for these bleeding disorders is also described.

Giangrande and Black describe the programs that the WFH has initiated for developing countries. The WFH was founded in 1963 and currently includes 107 national member organizations. Its main goal is to improve hemophilia care throughout the world; many educational programs and workshops are offered to assist in this endeavor. Marked progress has been made in the last few years and undoubtedly improvements in the life of patients with hemophilia have been accomplished.

O'Mahony and Black report on the role of the WFH in addressing the issues related to hemophilia. They elaborate on the reasons for the gross underreporting, underdiagnosing, and inadequate treatment of hemophiliacs in developing countries and offer, through the WFH, many opportunities to improve these conditions. The main focus is again on education, establishment of local hemophilia support groups, and governmental awareness and assistance. The WFH attempts to develop the necessary infrastructure for improving hemophilia care throughout the world.

Srivastava and Rodeghiero discuss the epidemiology of vWD in developing countries. Two surveys were taken. The data indicate that vWD is probably even more underdiagnosed and untreated than the two hemophilias, and most reports on vWD describe only the severe forms. In some countries consanguinity and marriages in small communities were found to be associated with vWD. In addition, the diagnostic capabilities are limited in many developing countries. Despite the underreporting, the data obtained indicate that vWD is probably four times more frequent than hemophilia A. Considerable efforts are needed to address these problems, especially because most forms of vWD respond to desmopressin acetate (DDAVP), which is easy to obtain and affordable.

Michiels and collaborators provide an overview of the classification, characterization, and treatment of vWD. vWD presents in a multitude of different forms that are genetically determined and very complex in nature. The authors describe all of the presently recognized variants, their genetic basis (if known), their clinical presentation, and the treatment modalities available at present. Suggestions for a new classification are presented and discussed in the context of their earlier nomenclature.

In the last article, Mannucci discusses the management of vWD in general and for developing countries in particular. Almost all patients with type I vWD, and these comprise the majority (60 to 80%), respond to the antidiuretic hormone vasopressin (DDAVP). This should be the treatment of choice for minor bleeding problems and for prophylactic use. This compound is affordable for most developing countries. DDAVP also does not transmit blood-borne infectious agents. Another treatment modality for patients in developing countries is fresh frozen plasma and cryoprecipitate. Concentrates containing FVIII and von Willebrand factor are certainly more effective, also in the other types of vWD (types II and III), but they are costly and are rarely available in developing countries. The author also reviews ancillary treatment modalities (i.e., antifibrinolytic agents and hormones). Issues of monitoring therapy are also presented.

My thanks and appreciation are due to all authors and their collaborators for the interesting contributions; special thanks are extended to Drs. Srivastava and Michiels for assembling this informative and timely issue.