RESUMEN
The development of inhibitors against administered clotting factors may render replacement therapy ineffective for some hemophilia patients. Such patients are therefore at the highest risk of developing arthropathy. Elective orthopedic surgery (EOS) in hemophilic patients having such inhibitors remains a rare, expensive, and difficult surgery, whose management represents a significant challenge. We report the case of a 35-year-old man with a severe form of hemophilia A (factor VIII < 1%), who was suffering from repetitive spontaneous hemarthrosis, especially in his knee joints that had consequently become more susceptible to bleeding. The patient had a history of high levels of factor VIII inhibitor (> 5.0 Bethesda Unit [BU]/ml) as shown by the factor VIII inhibitor assay; therefore, we began treatment with factor VIIa for his mild-to-moderate bleeding (90 µg/kg intravenous bolus injections). The interval between injections varied with the severity of the hemorrhage in each bleeding episode. The inhibitor level reduced to 3.1 BU/ml after three months, to 1.6 BU/ml after six months, and disappeared completely after one year of treatment. We administered factor VIII at a dose of 50 IU/kg every eight hours during the first three post-operative days, then continued administration with a dose of 40 IU/kg every 12 hours for another four days, and observed a very good response to treatment with no bleeding. Recombinant activated factor VII (rFVIIa) is not an inhibitor-removal strategy, but an inhibitor-bypassing product. However, in our patient, the treatment of mild-to-moderate bleeding with short-term use of rFVIIa and no exposure to factor VIII caused a gradual reduction in the inhibitor level over a period of 1 year.
RESUMEN
BACKGROUND: Genetic variation in multiple genes associated with hemostasis and thrombosis is well documented to impact the rates of future venous thromboembolism; in addition, trauma and orthopedic surgery in lower limb and immobilization are important factors in increasing the incidence of thrombosis. Gene mutation can be predisposing factor for thrombosis in traumatic patients under anti-coagulant agent prophylaxis. The aim of this study is to evaluate the different gene mutations in these patients. MATERIALS AND METHODS: In this cross-sectional descriptive study, the sample consisted of 53 patients with deep venous thrombosis (DVT) and 32 traumatic patients without thrombosis as the control group. Two groups matched together according to sex, age, weight, and medications. DNA analysis for mutation of multivariate of genes in thrombosis was studied. RESULTS: Regarding gene variations, there was statistically significant difference only in Prothrombin (Factor II, G20210A) between the patients with thrombosis and control group (P = 0.01). But, there was no difference between two groups considering other gene mutations. Mutation of Prothrombin gene (G20210A) was a predictive factor for thrombosis with odds ratio of 1.1 (CI 0.3-1.9). CONCLUSION: According to the outcomes resulted from this study, genetic mutation in Prothrombin (Factor II [G20210A]) is one of the most important genetic variations involved in traumatic patients with DVT despite prophylaxis. Genetic mutation in Prothrombin appears to be predisposing factor for thrombosis associated with trauma.
