Introduction Overweight increases the secretion of pro‐inflammatory cytokines and serves as a major risk factor for arthropathy and cardiovascular diseases (CVD). This condition is becoming increasingly prevalent among patients with haemophilia (PWH). Different forms of exercise training could favourably modify weight‐related complications, cardiovascular risk factors and the inflammation. Aim To investigate the effects of resistance, aerobic and combined exercises on the pro‐inflammatory and anti‐inflammatory markers in overweight patients with moderate haemophilia A. Methods Forty‐eight patients with moderate haemophilia A, aged 35‐55 years, and body mass index (BMI) of 25‐30 kg/m2 were randomly assigned to resistance training (RT, n = 12), aerobic (AT, n = 12), combined training (CT, n = 12) and control (n = 12) groups. The patients participated in 45‐minutes exercise sessions three times a week for 6 weeks. Waist circumference (WC), waist‐to‐hip ratio (WHR), fat mass, fat‐free mass, interleukin‐10 (IL‐10), adiponectin, tumour necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6) and high sensitive C‐reactive protein (hs‐CRP) were measured before and after the 6 weeks of training. Results There was significant decrease in WC, WHR, BMI and weight in the AT, RT and CT groups as compared to the control group. Total HJHS scores decreased in the AT, RT, CT groups compared to the control groups (P ≤ 0.001). The decrease in hs‐CRP, IL‐6 and TNF‐α in the CT group was significant compared to the control group (P ≤ 0.02). The increase in IL‐10 and adiponectin was not significant in the RT, AT and CT groups compared to the control group. Conclusion CT was the most effective training mode for decreasing the pro‐inflammatory cytokines and increasing anti‐inflammatory markers in overweight patients with haemophilia A.

Background Type 3 von Willebrand's disease (VWD) patients present markedly reduced levels of von Willebrand factor and factor VIII. Because of its rarity, the bleeding phenotype of type 3 VWD is poorly described, as compared to type 1 VWD. Aims To evaluate the frequency and the severity of bleeding symptoms across age and sex groups in type 3 patients and to compare these with those observed in type 1 VWD patients to investigate any possible clustering of bleeding symptoms within type 3 patients. Methods We compared the bleeding phenotype and computed the bleeding score (BS) using the MCMDM‐1VWD bleeding questionnaire in patients enrolled in the 3WINTERS‐IPS and MCMDM‐1VWD studies. Results In 223 unrelated type 3 VWD patients, both the BS and the number of clinically relevant bleeding symptoms were increased in type 3 as compared to type 1 VWD patients (15 versus 6 and 5 versus 3). Intracranial bleeding, oral cavity, hemarthroses, and deep hematomas were at least five‐fold over‐represented in type 3 VWD. A more severe bleeding phenotype was evident in patients having von Willebrand factor antigen levels < 20 IU/dL at diagnosis in the two merged cohorts. In type 3 patients, there was an apparent clustering of hemarthrosis with gastrointestinal bleeding and epistaxis, whereas bleeding after surgery or tooth extraction clusters with oral bleeding and menorrhagia. Conclusions In the largest cohort of type 3 VWD patients, we were able to describe a distinct clinical phenotype that is associated with the presence of a more severe hemostatic defect.

Episodic CFC replacement over a large range of doses does not alter the natural course of bleeding in haemophilia or the musculoskeletal deterioration and should not be recommended as a long term option for treatment. Prophylaxis is the only way to preserve musculoskeletal function in haemophilia.

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Introduction Congenital fibrinogen disorders (CFDs) comprise the quantitative and qualitative fibrinogen molecule abnormalities that are caused by fibrinogen gene mutations. The objective of this cohort research was to study the molecular and clinical profiles of patients with CFDs. Materials and methods Genomic DNA Sanger sequencing of 14 Iranian patients was performed to determine CFDs‐causing mutations. The disorders were diagnosed by routine and specific (fibrinogen antigen and functional assay) coagulation tests, and clinical data were obtained from medical records. Molecular dynamics (MD) simulations were performed to investigate the effect of missense mutation on the protein structure. Results Thirteen out of 14 patients had afibrinogenemia while the remaining patient had dysfibrinogenemia. Umbilical cord bleeding was the most common clinical presentation (n: 9, ~70%) which led to the diagnosis of afibrinogenemia, while menorrhagia led to the diagnosis of dysfibrinogenemia. Six homozygous mutations were identified in afibrinogenemia: three previously described variants in FGA (p.Trp52Ter, p.Ser312AlafsTer109 and p.Gly316GlufsTer105), one in FBG (p.Gly430Asp), and two novel mutations in FGB (p.Gly430Arg) and FGG (p.His366ThrfsTer40), while the FGA (p.Arg38Thr) heterozygous mutation was identified in dysfibrinogenemia. MD simulation indicated that the FGA p. Arg38Thr mutation probably interferes with polymerization of fibrin monomers. Conclusions In Iran, with its high rate of consanguinity, autosomal recessive afibrinogenemia with severe clinical presentations is relatively common due to heterogeneous molecular defects.