Association of FXII 5�UTR 46C>T polymorphism with FXII activity and risk of thrombotic disease

Objective: Thrombotic diseases are caused by genetic and environmental factors. There are a number of well-characterized genetic defects that lead to increased risk of thrombosis. Results from previous studies have indicated that FXII is involved in the pathogenesis of thrombophilic diseases. However, the results in this regard are highly controversial. One of the most important determinants of Plasma FXII level is 46CgT polymorphism in the FXII gene. In the present study, the risk of thrombophilic diseases related to this polymorphism was investigated in a case-control study. Material and Methods: One hundred and sixty subjects were studied: 120 patients diagnosed with thrombophilia (96 venous thromboembolism, 24 arterial thrombosis), and 40 age-gender-matched controls. For each subject, FXII activity level was measured by a one-step clotting assay with FXII-deficient plasma, and 46CγT polymorphism was genotyped using a restriction fragment length polymorphism (RFLP) method. Results: In this study, the previous observation that individuals with different genotypes for the 46 CγT polymorphism show significant differences in FXII activity levels was confirmed. Most importantly, FXII activity �68 was associated with an increased risk of venous thrombosis with an adjusted odds ratio (OR) of 4.7 (95 confidence interval CI: 1.03-21.1, p=0.04). However, it was not a risk factor for arterial thrombosis with adjusted OR of 5 (95% CI: 0.91-27.1, p=0.09). In CT and TT genotype, the adjusted ORs were 2 (95% CI: 0.9-4.4, p=0.11) and 2.3 (95% CI: 0.45-11, p=0.48), respectively, for patients with venous thrombosis compared with the controls. Similarly, the adjusted ORs in arterial thrombosis were 1.2 (95% CI: 0.4-3.6, p=0.76) for CT and 1.8 (95% CI: 0.2-14.9, p=0.59) for TT genotype. Thus, we did not find any association of the mutated T allele in the heterozygous or homozygous state with an increased risk of venous or arterial thrombosis. Conclusion: Lower FXII activity is not a risk factor; rather, it simply represents a risk marker for thrombosis

Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren’s syndrome

Sjögren’s syndrome is a common autoimmune disease (~0.7% of European Americans) typically presenting as keratoconjunctivitis sicca and xerostomia. In addition to strong association within the HLA region at 6p21 (Pmeta=7.65×10−114), we establish associations with IRF5-TNPO3 (Pmeta=2.73×10−19), STAT4 (Pmeta=6.80×10−15), IL12A (Pmeta =1.17×10−10), FAM167A-BLK (Pmeta=4.97×10−10), DDX6-CXCR5 (Pmeta=1.10×10−8), and TNIP1 (Pmeta=3.30×10−8). Suggestive associations with Pmeta<5×10−5 were observed with 29 regions including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2, and PHIP amongst others. These results highlight the importance of genes involved in both innate and adaptive immunity in Sjögren’s syndrome

"Prevalence of inhibitors in a population of 1280 Hemophilia A patients in Iran "

Development of inhibitor to factor VIII is the most serious complication of hemophilia therapy. To determine the prevalence of inhibitors in Iran hemophilia A patients exposed to blood products, 1280 hemophilia A patients (age range 9 months-84 years) were evaluated. All patients received several blood products such as fresh frozen plasma (FFP), cryoprecipitate, and factor VIII. 635 of 1280 patients (49.6%), 277 patients (21.6%) and 368 patients (28.8%) had severe, moderate and mild disease, respectively. 184 of 1280 patients (14.4%) developed inhibitor. The prevalence of inhibitor for severe, moderate and mild in hemophilia A patients was 22.8%, 9.4%, and 3.5% respectively. 41 patients (22.2%) and 143 patients (77.8%) were high responder and low responder respectively. Among 184 patients with inhibitor, 67 patients (36.4%) had blood group O and for B, A, AB blood groups, number of patients with inhibitor was 55 (29.9%), 50 (27.2%), 12(6.5%) respectively and 153 patients (83.1%) had Rh blood group

Molecular and clinical profile of type 2 von Willebrand disease in Iran: a thirteen-year experience

Type 2 von Willebrand disease (VWD) is the most common congenital bleeding disorder, with variable bleeding tendency and a complex laboratory phenotype. In the current study, we report the clinical and molecular profile of a large number of Iranian patients with type 2 VWD. All exons, intron�exon boundaries, and untranslated regions were sequenced by Sanger sequencing for direct mutation detection. All identified mutations were confirmed in family members and by relevant bioinformatics studies. A total of 136 patients with type 2 VWD were diagnosed, including 42 (30.9), 32 (23.6), 38 (27.9), and 24 (17.6) patients with type 2A, type 2B, type 2M, and type 2N, respectively. Epistaxis (49), gum bleeding (30.2), ecchymosis (23.2), and menorrhagia (16.3) were the most common clinical presentations, while miscarriage (2.3) and umbilical cord bleeding (0.8) were the rarest. Thirty mutations were identified within the VWF gene, nine (30) being novel, with p.Arg1379Cys (n = 20), p.Val1316Met (n = 13), p.Arg1597Trp (n = 13), p.Arg1374Cys (n = 10), p.Ser1506Leu (n = 10), and p.Arg1308Cys (n = 9) the most common. Type 2 VWD is a hemorrhagic disorder with variable bleeding tendency and a heterogeneous molecular basis in patients in Iran. © 2020, Japanese Society of Hematology

Challenges and concerns of patients with congenital bleeding disorders affected by coronavirus disease 2019

Coronavirus disease 2019 (COVID-19) is a new medical challenge for all individuals, especially for those with underlying disorders, such as congenital bleeding disorders (CBDs). Therefore, the pandemic might significantly change the behaviour of patients with CBDs and results in some challenges. In the present study, we assessed the main challenges of COVID-19 infection to patients with CBDs. Data were collected from medical files and interviews of patients with CBDs who had COVID-19 infection. Follow-ups were performed on patients who had active severe acute respiratory syndrome coronavirus 2 infection between April and October 2020. All patients were interviewed by an expert in order to collect the pertinent data. Some questions were about patients' preventive behaviors and feelings prior to infection, and some were about the consequences of infection on patients' replacement therapy and bleeding management. Among 25 patients, infection and death of loved ones (n: 7, 28), and their own (n: 5, 20) or family members' (n: 1, 4) infection, and the resulting economic burden (n: 2, 8) were main concerns. Six patients experienced depression during the pandemic. The pandemic caused all severely affected patients but one (n: 11, 92) to abandon replacement therapy. However, two received on-demand therapy after exacerbation of their bleeding. Only one (25) of four patients on prophylaxis received in-home therapy, whereas the others (75) abandoned prophylaxis. It seems that COVID-19 infection has great consequences on the lives of patients with CBDs, causing some to take dangerous actions, such as abandonment of their treatment. Healthcare systems, and healthcare providers, should have an appropriate strategy for management of patients with CBDs that prevents infection and provides timely replacement therapy. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved

Challenges and concerns of patients with congenital bleeding disorders affected by coronavirus disease 2019

Coronavirus disease 2019 (COVID-19) is a new medical challenge for all individuals, especially for those with underlying disorders, such as congenital bleeding disorders (CBDs). Therefore, the pandemic might significantly change the behaviour of patients with CBDs and results in some challenges. In the present study, we assessed the main challenges of COVID-19 infection to patients with CBDs. Data were collected from medical files and interviews of patients with CBDs who had COVID-19 infection. Follow-ups were performed on patients who had active severe acute respiratory syndrome coronavirus 2 infection between April and October 2020. All patients were interviewed by an expert in order to collect the pertinent data. Some questions were about patients' preventive behaviors and feelings prior to infection, and some were about the consequences of infection on patients' replacement therapy and bleeding management. Among 25 patients, infection and death of loved ones (n: 7, 28%), and their own (n: 5, 20%) or family members' (n: 1, 4%) infection, and the resulting economic burden (n: 2, 8%) were main concerns. Six patients experienced depression during the pandemic. The pandemic caused all severely affected patients but one (n: 11, 92%) to abandon replacement therapy. However, two received on-demand therapy after exacerbation of their bleeding. Only one (25%) of four patients on prophylaxis received in-home therapy, whereas the others (75%) abandoned prophylaxis. It seems that COVID-19 infection has great consequences on the lives of patients with CBDs, causing some to take dangerous actions, such as abandonment of their treatment. Healthcare systems, and healthcare providers, should have an appropriate strategy for management of patients with CBDs that prevents infection and provides timely replacement therapy