Cyclophosphamide vs rituximab for eradicating inhibitors in acquired hemophilia A: A randomized trial in 108 patients.

BACKGROUND: Acquired hemophilia A (AHA) is a rare autoimmune disorder due to autoantibodies against Factor VIII, with a high mortality risk. Treatments aim to control bleeding and eradicate antibodies by immunosuppression. International recommendations rely on registers and international expert panels. METHODS: CREHA, an open-label randomized trial, compared the efficacy and safety of cyclophosphamide and rituximab in association with steroids in patients with newly diagnosed AHA. Participants were treated with 1 mg/kg prednisone daily and randomly assigned to receive either 1.5-2 mg/kg/day cyclophosphamide orally for 6 weeks, or 375 mg/m2 rituximab once weekly for 4 weeks. The primary endpoint was complete remission over 18 months. Secondary endpoints included time to achieve complete remission, relapse occurrence, mortality, infections and bleeding, and severe adverse events. RESULTS: Recruitment was interrupted because of new treatment recommendations after 108 patients included (58 cyclophosphamide, 50 rituximab). After 18 months, 39 cyclophosphamide patients (67.2 %) and 31 rituximab patients (62.0 %) were in complete remission (OR 1.26; 95 % CI, 0.57 to 2.78). In the poor prognosis group (FVIII < 1 IU/dL, inhibitor titer > 20 BU mL-1), significantly more remissions were observed with cyclophosphamide (22 patients, 78.6 %) than with rituximab (12 patients, 48.0 %; p = 0.02). Relapse rates, deaths, severe infections, and bleeding were similar in the 2 groups. In patients with severe infection, cumulative doses of steroids were significantly higher than in patients without infection (p = 0.03). CONCLUSION: Cyclophosphamide and rituximab showed similar efficacy and safety. As first line, cyclophosphamide seems preferable, especially in poor prognosis patients, as administered orally and less expensive. FUNDING: French Ministry of Health. CLINICALTRIALS: gov number: NCT01808911.

Prednisolone treatment induced temporary factor IX normalization in mild hemophilia B who required an epidural infiltration: A case report.

A 31-year-old man with mild hemophilia B developed a herniated disc treated with prednisolone for back pain. Surprisingly, hemostasis result tests performed before epidural infiltration were a normal activated partial thrombin time at 36.1 s. (normal range 27.9-37.7 s.) and factor IX (FIX) level 76% (normal range>70%), 13 days after prednisolone introduction. After a second control with a normal FIX level and a second genetic confirmation of hemophilia, no FIX concentrates was administered to perform the infiltration, which occurred without hemorrhagic complication. This new case of FIX normalization showed the necessity to have a perfect knowledge of patient's treatment to avoid misdiagnosis and a temporary normal hemostasis permit to perform epidural infiltration without replacement therapy.

The new haematology analyzer DxH 800: an evaluation of the analytical performances and leucocyte flags, comparison with the LH 755.

INTRODUCTION: The analytical performance and the abnormality messages on differential (flags) of the new analyzer Beckman Coulter DxH 800 were compared with those of the LH 755. METHODS: First, we evaluated the accuracy of the results of the DxH 800, in comparison with the LH 755, in 125 samples without alarm using unflagged sample results on both analyzers. Second, flagged samples on the LH 755 but not flagged by the DxH 800 were evaluated by flow cytometry for accuracy of the DxH 800 results. Finally, we evaluated the sensitivity and specificity of abnormality messages on differential given by the analyzers, in comparison with manual blood smears. RESULTS: The correlation coefficients (R) for complete blood count parameters and differential demonstrated that the DxH 800 results were similar to that of LH 755. Excellent correlation coefficients between DxH 800 and flow cytometry results were found for white blood cell count (R = 0.985, n = 31), platelet count (R = 0.976, n = 51) and nucleated red blood cells (R = 0.966, n = 37). The overall performance showed an increased sensitivity (0.892) and specificity (0.864) of the flags on DxH 800 when compared to the LH 755 (0.846 and 0.733, respectively). CONCLUSION: The DxH 800 provides reliable results and increases laboratory efficiency by reducing working time and costs associated with the optical validation of the results.

[Protein Z, polymorphisms in the protein Z gene and thrombosis]. / Protéine Z, polymorphismes du gène de la protéine Z et thromboses.

Protein Z (PZ) is a vitamin K dependent protein acting as the cofactor of the protein Z dependent inhibitor (ZPI), in the inhibition of activated factor X bound on the phospholipids. Normal plasma protein Z concentrations have wide variations among individuals, partly explained by a genetic control. Several protein Z gene polymorphisms influence plasma concentration, separately and in combination. The role of PZ in blood coagulation regulation has been demonstrated in vitro. The responsibility of low PZ level in the occurrence of thrombosis has been questioned. However, the roles of PZ plasma level and PZ gene polymorphisms remain debated with conflicting results in arterial, venous, or placental thrombosis. These discrepancies can be explained by the heterogeneity of populations chosen as control, by the PZ interindividual variability, by the small size of the cohorts in mainly retrospective studies and perhaps by the lack of real important influence of this protein on coagulation. PZ measurement is not actually considered as a biological marker of thrombophilia. Large prospective studies remain to be done to investigate its possible role in thrombosis.

The G79A polymorphism of protein Z gene is an independent risk factor for cerebral venous thrombosis.

BACKGROUND AND PURPOSE: Protein Z (PZ), a vitamin Kdependent protein, plays a role in inhibiting coagulation. Its plasma level or PZ gene polymorphisms have been discussed as risk factors for stroke with conflicting results reported between various studies. Only one of these polymorphisms was studied in a cohort of patients suffering from cerebral venous thrombosis (CVT). METHODS: We performed a retrospective genetic study comparing 100 healthy controls to 54 patients referred to our hemostasis unit after CVT occurrence. We compared the distribution of three PZ gene polymorphisms that may influence PZ plasma levels: A-13G in the promoter and G79A in intron F were tested using previously described techniques, and we developed a technique to evaluate the G-103A in intron A. RESULTS: The G79A polymorphism was significantly more frequent in patients than in controls (p = 0.012): the presence of at least one A allele led to an odds ratio of 2.57 with a 95 % confidence interval of 1.23-5.34. The A-13G polymorphism also showed a nonsignificant trend towards a higher prevalence in patients. CONCLUSION: The G79A polymorphism of the PZ gene was shown to be a new independent risk factor for cerebral venous thrombosis. Nevertheless, these results have to be confirmed by a prospective study including plasma PZ evaluation.