Von Willebrand disease combined with coagulation defects in Iran.

BACKGROUND: Although Von Willebrand disease (VWD) is the most common inherited bleeding disorder, few cases of VWD combined with coagulation defects have been reported. This study sought to determine the clinical and laboratory features of VWD combined with other coagulation defects and to evaluate the prevalence of this combination in Iran. MATERIAL AND METHODS: A total of 3,120 cases were evaluated to confirm a suspected diagnosis of VWD. Clinical and laboratory phenotypes, including bleeding scores (BS), were also obtained. RESULTS: A diagnosis of VWD was established for 130 patients. Following their further characterisation, a subgroup of 25 patients with a dual or triple combination of VWD with coagulation defects (FXII, FXI, FIX, FVII, FV, and lupus anticoagulant) was identified. Their laboratory and clinical data were compared with those of healthy controls (n=25) and VWD-only patients (n=25). No differences were observed for VWF-related laboratory measurements between the combined deficient cases and those with VWD only, results being expectedly lower than in healthy controls. The median BS of combined patients was 4, higher than for VWD-only and control groups (median BS 3 and 1; p=0.55 and p<0.001, respectively). DISCUSSION: The prevalence of combined coagulation defects was 19.2% among all the VWD cases. The co-occurrence of VWD with clotting factor deficiencies may lead to more severe clinical presentations. To ensure adequate treatment, combined defects should be considered in VWD patients presenting with a more severe bleeding phenotype than expected or with a poor response to treatment.

Discrepancy between the results of one-stage and chromogenic factor VIII: C assays in patients with mild/moderate hemophilia A.

: Diagnosis of hemophilia A is generally based on the measurement of plasma factor VIII activity (FVIII:C) using the one-stage assay (OSA) or the two-stage chromogenic substrate assay (CSA). The results of these methods show considerable discrepancy in about one-third of non-severe hemophilia A patients. The aim of this study was to assess the prevalence of FVIII:C assay discrepancy in non-severe hemophilia A patients in Iran and the relationship between the bleeding tendency with the level of FVIII:C by each method. Patients registered as mild or moderate hemophilia A in hemophilia clinic of Imam Khomeini Hospital were included. In each patient, FVIII:C level was assessed using one-stage (FVIII:C1) and chromogenic (FVIII:CR) methods. Assay discrepancy was defined as a two-fold or greater difference between the results of two assays. Bleeding tendency of the patients was recorded based on 'ISTH-BAT'. Sixty male patients were eligible for the study. The levels of FVIII:C1 was higher than FVIII:CR in 90% of patients. Assay discrepancy was seen in 41 (68%) patients. The classification of hemophilia A in 23 (38%) patients was modified by chromogenic method. No significant correlation was noted between the results of ISTH BAT with FVIII:C levels of each method. Regarding the prevalence of FVIII:C assay discrepancy in 2/3 of our non-severe hemophilia A patients, high rate of disease severity modification by chromogenic method and no significant relation between the clinical bleeding phenotype with any method, the authors highly recommend to perform both FVIII:C assays for the diagnosis and classification of non-severe hemophilia A.

Are Iranian patients with von Willebrand disease type 2N properly differentiated from hemophilia A and do they receive appropriate treatment?

: The defect function of the von Willebrand factor (VWF) in carrying factor VIII (FVIII) leads to von Willebrand disease type 2N (VWD 2N) which could be easily misdiagnosed as hemophilia A. Differentiating of VWD 2N from hemophilia A is crucial for patient treatment and genetic counseling. As a retrospective study, we aimed to evaluate the current diagnostic work-up of Iranian patients with mild/moderate deficiency of FVIII levels and the possibility of misdiagnosis of VWD 2N as hemophilia A. All patients who referred to the reference coagulation laboratory at the Iranian Blood Transfusion Organization in a 10-months period for bleeding diathesis work-up with the request of FVIII activity level were included. Clinical and laboratory phenotypes including International Society on Thrombosis and Hemostasis - Bleeding Assessment Tool, FVIII activity, VWF antigen, VWF ristocetin cofactor, and FVIII binding capacity of VWF were assessed on suspected cases for VWD 2N. In total, the results of 896 patients for investigation of VWD 2N were evaluated and five new patients were identified within unrelated families with abnormal VWF:FVIIIB levels. Four were heterozygous for VWD 2N and one homozygous whom all were misdiagnosed as hemophilia A and underwent inappropriate treatments. The median bleeding score of the VWD 2N population was nine (4-13). In Iran, probably a significant number of VWD 2N patients are misdiagnosed as hemophilia A due to insufficient test panel for subtyping of von Willebrand disease. This study also emphasized the need for inclusion of the VWF:FVIIIB in suspected hemophilia A to achieve an optimal treatment strategy.