Phenotype and genotype of a cohort of families historically diagnosed with type 1 von Willebrand disease in the European study, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD).

Type 1 von Willebrand disease (VWD) is characterized by a personal and family history of bleeding coincident with reduced levels of normal plasma von Willebrand factor (VWF). The molecular basis of the disorder is poorly understood. The aims of this study were to determine phenotype and genotype and their relationship in patients historically diagnosed with type 1 VWD. Families were recruited in 9 European countries based on previous type 1 VWD diagnosis. Bleeding symptoms were recorded, plasma phenotype analyzed, and VWF mutation analysis performed in all index cases (ICs). Phenotypic and molecular analysis stratified patients into those with or without phenotypes suggestive of qualitative VWF defects (abnormal multimers) and with or without mutations. A total of 105 of 150 ICs (70%) had mutations identified. A subgroup with abnormal multimers (38% of ICs, 57 of 150) showed a high prevalence of VWF gene mutations (95% of ICs, 54 of 57), whereas in those with qualitatively normal VWF, fewer mutations were identified (55% of ICs, 51 of 93). About one third of the type 1 VWD cases recruited could be reconsidered as type 2. The remaining group could be considered "true" type 1 VWD, although mutations were found in only 55%.

Surgery in hemophilia. The general view: patient selection, timing, and preoperative assessment.

Although often overlooked, the life of the patient with severe hemophilia is characterized by both intermittent and chronic pain. Bleeds into joints and muscles cause extensive pressure on sensory nerves and, following recurrent bleeds, joint destruction, and synovial reaction is accompanied by constant pains that are frequently mistaken for further bleeding. The orthopedic surgeon may break the vicious cycle of chronic synovitis by excising inflamed and hypertrophic synovium or severely damaged cartilage and adjacent bone ends, and implanting an artificial joint. Numerous technical solutions are now available and orthopedic surgery is increasingly on offer to those hemophilia patients who, since childhood, have been victims of insufficiently treated bleeds because no or limited treatment was available, and because the concept of prophylaxis had not yet been developed. Nonetheless, orthopedic surgery in patients with hemophilia requires much more effort and planning than surgery in non-hemophilic patients. In this overview, we will address issues related to surgery in hemophilic patients, as well as some practical issues related to the timing of surgery, preoperative testing, perioperative hemostasis, and patient rehabilitation.