False-negative coagulation factor activity results due to the presence of antiphospholipid antibodies in a case of autoimmune hemolytic anemia

An 88-year-old female was admitted with autoimmune hemolytic anemia (AIHA). Coagulation test revealed severe prolongation of activated partial thromboplastin time (APTT). APTT cross-mixing test with patient plasma and normal plasma demonstrated an inhibitory pattern. Several intrinsic coagulation factor activities, particularly factor IX, showed remarkable decreases, and the inhibitor titers for coagulation factors VIII and IX were elevated. Although AIHA with existing antiphospholipid (aPL) antibodies was diagnosed initially, purpura developed on extremities intermittently during the clinical course. Considering the possibility of coexisting acquired hemophilia, APTT cross-mixing test with patient’s plasma and equal amount of the recombinant factor VIII product instead of normal plasma was performed. The APTT value on equal mixing samples with patient plasma and recombinant factor VIII product was decreased to within the normal range, and coagulation factor IX activity was restored. These results indicate that the recombinant factor VIII product had a neutralizing effect on aPL antibodies. We concluded that recombinant factor VIII product may lead to the repair of incorrect results from the APTT-dependent diagnostic system in the presence of aPL antibodies.

Extended Stability and Sterility of Antihemophilic Factor Human

OBJECTIVES Antihemophilic factor human is a factor VIII product used to supplement those with hemophilia. Recent data show treatment benefit and cost saving opportunities if factor products are administered as a continuous infusion rather than conventional bolus dose. This method has not been widely used given the lack of evidence for safe and effective use beyond 3 hours from preparation. The objectives of this study were to determine the physical and chemical stability and sterility of antihemophilic factor human over a 7-day period. METHODS Antihemophilic factor human was obtained from the manufacturer. Baseline stability and sterility were determined by factor activity levels along with bacterial and fungal cultures. These tests were also evaluated over a span of 7 days at room temperature and under refrigeration. RESULTS Each sample was inspected at the time of delivery and showed no visible signs of physical changes. Factor activity levels were maintained between 88% and 102% of baseline measurements. No growth was observed for bacterial or fungal cultures in any sample after 4 weeks of incubation. CONCLUSIONS Antihemophilic factor human maintained physical stability and chemical stability and remained sterile for the 7-day period, allowing extended stability and continuous infusions to be considered.

Rationale for Investigator-Assigned Prophylaxis Dosing Frequency in the Leopold I Study

The LEOPOLD I study (part B) in severe hemophilia A was a multicenter, phase II/III, open-label trial to assess the safety, tolerability, and efficacy of prophylaxis treatment with BAY 81-8973, an unmodified recombinant factor VIII product. Dose and dose frequency of the prophylaxis regimen during the study were at the investigators' discretion. A questionnaire was sent to sites poststudy to determine what elements led to the assignment of patients to a twice-weekly regimen rather than 3 times weekly. Seventeen specific questions were posed, plus 1 labeled as "other," allowing the investigator to insert a rationale not otherwise specified. Responses to the questionnaire were received for 13 of 17 patients (76%) assigned to twice-weekly prophylaxis. The 2 most frequent responses were "treatment options were discussed with the patients" (67%) and "patient preference" (61%). Additional responses in descending frequency included "prophylaxis regimen was adapted to the patient's physical activity and schedule" (28%) and "already on a twice-weekly regimen before the study," "sedentary lifestyle," "noncompliance with a 3-times-weekly regimen," and "other" (17% each). "Minimal arthropathy," "no target joints," and "patient's age" were included at 11% each. These results demonstrate that discussions between patient and doctor are appropriately considered paramount to treatment decisions. The other elements mentioned are known parameters thought to contribute to bleeding phenotype in hemophilia. Disclosures Humphries: Bayer: Employment. Church:Bayer: Employment. Lalezari:Pfizer: Honoraria; Bayer: Honoraria; TEVA pharmaceuticals: Consultancy. Poulsen:Bayer: Membership on an entity's Board of Directors or advisory committees, Other: Investigator for Clinical Trials; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Other: Investigator for Clinical Trials, Mentor, Speakers Bureau; SOBI: Speakers Bureau; Ferring: Speakers Bureau; Pfizer: Consultancy. Yoon:Bayer Inc: Employment. Maas Enriquez:Bayer Pharma AG: Employment.