MASAC Recommendation #96
MASAC Resolution on Genotyping of Persons with Inherited Bleeding Disorders
The following resolution was approved by the Medical and Scientific Advisory Council (MASAC) on November 6, 1999, and adopted by the NHF Board of Directors on December 21, 1999.
Since the genes for factors VIII and IX and von Willebrand disease were identified and sequenced in the 1980s, numerous gene defects have been identified in persons with these bleeding disorders. This information has led to increased understanding of the molecular biology of these genes and of so-called neutral polymorphisms and has established new correlations between a person’s genotype and phenotype, providing scientific insights into evolutionary biology and diseases outside of hemostasis.
More recently, genotyping has been utilized as a tool to further understand the basis of inhibitor development. With the emergence of experimental gene therapies, genotyping is thought to be important in predicting individuals who might be potential responders and those who might be at risk for inhibitor formation and in selecting the most appropriate form of gene therapy for each patient (i.e., correction of point mutations or homologous recombination requires genotyping). Further, genotyping of carriers would have benefits for their clinical management as well as for managing their unborn children at risk for bleeding in the perinatal period.
High throughput technology and strategies for cost efficient genotyping are continuing to evolve. Even with the present low throughput technology, genotyping is relatively inexpensive (under $1500), and some mutations can be identified for considerably less. In large part, these costs are borne either by patients or by research grants to core genotyping laboratories and are not widely accessible outside of specific research studies. On a per-patient basis, these costs are a small fraction of the yearly costs for medical care for persons with bleeding disorders. Private insurance rarely reimburses for the testing, and other sources of funding have not been accessed. Further, only one member of a kindred requires testing, since the gene defects in related individuals will be identical.
MASAC recommends the performance of genome-based diagnosis for persons with inherited coagulation factor deficiencies as a part of their overall comprehensive care. This strategy will enhance medical management of carriers and unborn children at risk, permit selection of candidates for different types of gene therapy clinical trials, identify persons at increased risk of inhibitor development, and extend scientific knowledge.
MASAC recommends that NHF undertake educational efforts designed to help the bleeding disorders community understand the purposes of genome-based diagnosis and the role it can play in improved medical management of inherited coagulation factor deficiencies.
MASAC further recommends that NHF identify public and private funding sources, including insurance companies, which can facilitate widespread genotyping efforts in the community.