A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A.

BACKGROUND: The development of neutralizing anti-factor VIII alloantibodies (inhibitors) in patients with severe hemophilia A may depend on the concentrate used for replacement therapy. METHODS: We conducted a randomized trial to assess the incidence of factor VIII inhibitors among patients treated with plasma-derived factor VIII containing von Willebrand factor or recombinant factor VIII. Patients who met the eligibility criteria (male sex, age <6 years, severe hemophilia A, and no previous treatment with any factor VIII concentrate or only minimal treatment with blood components) were included from 42 sites. RESULTS: Of 303 patients screened, 264 underwent randomization and 251 were analyzed. Inhibitors developed in 76 patients, 50 of whom had high-titer inhibitors (≥5 Bethesda units). Inhibitors developed in 29 of the 125 patients treated with plasma-derived factor VIII (20 patients had high-titer inhibitors) and in 47 of the 126 patients treated with recombinant factor VIII (30 patients had high-titer inhibitors). The cumulative incidence of all inhibitors was 26.8% (95% confidence interval [CI], 18.4 to 35.2) with plasma-derived factor VIII and 44.5% (95% CI, 34.7 to 54.3) with recombinant factor VIII; the cumulative incidence of high-titer inhibitors was 18.6% (95% CI, 11.2 to 26.0) and 28.4% (95% CI, 19.6 to 37.2), respectively. In Cox regression models for the primary end point of all inhibitors, recombinant factor VIII was associated with an 87% higher incidence than plasma-derived factor VIII (hazard ratio, 1.87; 95% CI, 1.17 to 2.96). This association did not change in multivariable analysis. For high-titer inhibitors, the hazard ratio was 1.69 (95% CI, 0.96 to 2.98). When the analysis was restricted to recombinant factor VIII products other than second-generation full-length recombinant factor VIII, effect estimates remained similar for all inhibitors (hazard ratio, 1.98; 95% CI, 0.99 to 3.97) and high-titer inhibitors (hazard ratio, 2.59; 95% CI, 1.11 to 6.00). CONCLUSIONS: Patients treated with plasma-derived factor VIII containing von Willebrand factor had a lower incidence of inhibitors than those treated with recombinant factor VIII. (Funded by the Angelo Bianchi Bonomi Foundation and others; ClinicalTrials.gov number, NCT01064284; EudraCT number, 2009-011186-88.).

Cost-effectiveness analysis of low-dose prophylaxis versus on-demand treatment for moderate-to-severe hemophilia A in India.

AIM: Hemophilia A (HA) is an inherited bleeding disorder caused by a deficiency of clotting factor VIII in the blood. In resource-limited settings like India, affordability is a significant challenge in managing patients with severe HA. This study aims to assess the cost-effectiveness of intermediate-dose prophylaxis versus on-demand factor therapy in adult and pediatric populations with moderate-to-severe congenital HA without inhibitors in India. METHOD: We conducted a prospective cost-effectiveness analysis from a societal perspective, categorizing patients into a base state and a joint disease state (patients with Hemophilia suffering extensive bleeds leading to chronic joint disease). Using targeted literature search and primary market research, we developed a Markov model measuring the total cost of Hemophilia treatment and health outcomes, including life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-utility ratio (ICUR), and incremental cost-effectiveness ratio (ICER). The model extended over a lifetime horizon of 70 years with a one-year cycle length. Sensitivity analyses assessed study robustness. RESULTS: Low-dose prophylactic therapy was cost-effective for adults (>18 years) and pediatric populations (<18 years), yielding better health outcomes (adults: 0.15 LYs and 2.43 QALYs gained; pediatric: 0.40 LYs and 3.12 QALYs gained). Intermediate-dose prophylaxis showed positive net monetary benefits in terms of Quality-Adjusted Life Years (QALYs) for both adult and pediatric populations, with dominant ICER and ICUR values in both cases. CONCLUSION: Using intermediate-dose prophylactic factor VIII therapy is a cost-effective approach that improves clinical outcomes compared to on-demand therapy in the Indian adult and pediatric HA populations without inhibitors.

WITHDRAWN: Mutational analysis of the F8 gene and phenotypic characterization of Hemophilia A.

This article has been withdrawn as the request of the author(s) and/or Editors. The Publisher apologizes for any inconvenience this may cause.

Comparative analysis of oral health and treatment necessities in hemophilia individuals of Davangere population - A case control study.

BACKGROUND: The integrated approach towards the oral care of individuals with special needs requires proper motivation and prophylactic guidance by primary health care professionals, including musculoskeletal support to psychological therapy. In developing countries like India, oral care is not of primary importance as oral hygiene practices are less performed by compromised individuals suffering from hemophilia. Here, primary health care professionals play a significant role. The present study was commenced to evaluate oral health and treatment necessities in hemophilic individuals of Davangere population, Karnataka. OBJECTIVE: The present study was conducted to assess and compare the oral hygiene, dentition status, and treatment needs of individuals with hemophilia. METHODS: Simplified Oral Hygiene Index (OHI-S), decayed, missed, filled tooth (DMFT) indices and treatment needs in 50 hemophiliac patients registered at Karnataka hemophilia society were evaluated along with an Oral health-related quality of life (OHR-QoL) questionnaire. They were matched with healthy controls of the same age and gender. The data was analyzed using t test and Chi square test. RESULTS: The oral hygiene was fair in both hemophilic and healthy individuals with a mean value of 1.82 ± 0.79 and 1.83 ± 0.73, respectively. All the parameters such as OHIS, DMFT indices, and teatment needs were not statistically significant. The spontaneous oral bleeding was the only significant factor in OHR-Qol questionnaire. CONCLUSION: The present study concluded that oral hygiene, dental caries prevalence, and treatment needs were similar in both hemophiliac and control groups. With proper guidance, motivation, and preventive care by primary health care professionals, it was relatively easy for individuals with congenital blood disorder (CBD) to maintain oral health-related quality of life in Davangere population, Karnataka.

"Antihemophilic factor is not the only answer for all factor VIII deficiencies." Case report of odontogenic infection in a patient with hemophilia A, complicated by factor VIII inhibitors, and managed by transfusion of antihemophilic factor and factor VIII inhibitor bypass activity.

Dental extraction in hemophiliacs with acquired inhibitors is always a risky procedure, which often presents a lot of problems associated with bleeding. A known case of hemophilia A complicated with factor VIII inhibitors and having odontogenic infection was successfully managed by transfusion of factor VIII inhibitor bypass activity (FEIBA) and antihemophilic factor. Past medical history was significant for multiple factor VIII transfusions. Bethesda assay done to identify inhibitors revealed low titer factor VIII inhibitors. Extraction of the involved tooth was done after transfusion of FEIBA with low-dose protocols. Minimal bleeding was noted after extraction which was controlled by local measures. FEIBA was proven to be highly effective, and no side effects of the product were observed.