[[39]] For important considerations related to performing surgical

procedures in persons with hemophilia, please see “Surgery and Invasive Procedures”. Specific issues in relation to orthopedic surgery include: Orthopedic surgeons should have had specific training RAD001 mouse in surgical management of persons with hemophilia. [[3]] Performing multiple site elective surgery in a simultaneous or staggered fashion to use clotting factor concentrates judiciously should be considered. (Level 3) [[50]50] Local coagulation enhancers may be used. Fibrin glue is useful to control oozing when operating in extensive surgical fields. (Level 3) [[36, 51, 52]36,51,52] Postoperative care in patients with hemophilia requires closer monitoring of pain and often higher doses of analgesics in the immediate postoperative period. (Level 5) [[36]] Good communication with the postoperative rehabilitation CHIR-99021 team is essential [[39]]. Knowledge of the details of the surgery performed and intra-operative joint status will facilitate planning of an appropriate rehabilitation program. Postoperative rehabilitation should be carried out by a physiotherapist experienced in hemophilia management. Rehabilitation may have to progress more slowly in persons with hemophilia. Adequate pain control is essential to allow appropriate exercise and mobilization. These

principles also apply to fixation of fractures and excision of pseudotumors. Inhibitors” in hemophilia refer to IgG antibodies that neutralize clotting factors. In the current era in which clotting factor concentrates have been subjected to appropriate viral inactivation, inhibitors to FVIII Amino acid or FIX are considered the most severe treatment-related complication in hemophilia. The presence of a new inhibitor should be suspected in any patient who fails to respond clinically to clotting factors, particularly if he has been previously responsive. In this situation, the expected recovery and half-life of the transfused clotting factor are severely diminished. Inhibitors are more frequently encountered

in persons with severe hemophilia compared with those with moderate or mild hemophilia. The cumulative incidence (i.e., lifetime risk) of inhibitor development in severe hemophilia A is in the range of 20–30% and approximately 5–10% in moderate or mild disease. [[53, 54]] In severe hemophilia A, the median age of inhibitor development is 3 years or less in developed countries. In moderate/mild hemophilia A, it is is closer to 30 years of age, and is often seen in conjunction with intensive FVIII exposure with surgery. [[55, 56]] In severe hemophilia, inhibitors do not change the site, frequency, or severity of bleeding. In moderate or mild hemophilia, the inhibitor may neutralize endogenously synthesized FVIII, thereby effectively converting the patient’s phenotype to severe.