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The article presents information on an article that involves the molecular genetic analysis of Iranian patients with congenital factor XIII deficiency.

ABSTRACT The purpose of this paper is to define a thermo-mechanical fatigue criterion in order to predict the failure of aluminum alloys components issued with the lost foam casting process and used in particular in the automotive industry. The microstructure of the studied materials (A356-A319 aluminum alloys) is clearly affected by the lost foam casting process which can directly affect the mechanical properties, the damage mechanisms and the fatigue failure of specimens and components. The major problem in defining a predictive fatigue criterion in this case is the fact that it should be applicable for the component which is submitted to complex multiaxial thermo-mechanical loadings. Since many years, energy-based criteria have been used to predict fatigue failure of this class of materials. Then, different energy-based criteria are tested in order to take into account different types of triaxiality and mean stress effects corrections. The fatigue lifetime results predicted by both of them show a good agreement with experimental results. [ABSTRACT FROM AUTHOR]

Background: Hemophilia B, or Christmas disease, is a hemorrhagic inherited disorder. Previous studies have reported measurement discrepancies in factor VIII activity between clot-based and chromogenic assays in approximately one-third of patients with non-severe hemophilia A. However, similar discrepancies in hemophilia B have been less extensively studied. This research compares clot-based and chromogenic assays in 33 patients with non-severe hemophilia B and investigates the mutations associated with these discrepancies., Methods: Citrate and EDTA samples were collected from 33 patients with non-severe hemophilia B at Iran's hemophilia comprehensive care center. Clinical information was also gathered. Both clot-based and chromogenic assays were performed on these patients. DNA was extracted from the EDTA samples for those with discrepancies in the test results, and PCR was conducted to sequence their genes to find mutations., Results: Among 33 plasma samples from patients with non-severe hemophilia B, 7 showed a measurement discrepancy according to the definition of ISTH (<0.5, >2.0, or an absolute difference >10), which includes both reverse and classic types of discrepancies. In this study, mutations that previously did not show contradictory results now exhibit discrepancies. A difference in classification was observed in 21 % of the patients., Conclusions: The findings indicate that the impact of specific mutations varies depending on the assay conditions. In addition to mutations, other factors also play a role in this discrepancy. Both types of assays are essential for the accurate diagnosis and classification of hemophilia B., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: One of the major problems for patients with severe hemophilia A (HA) is the development of neutralizing antibodies against factor VIII. This study aimed to analyze the molecular and clinical profiles of patients with severe HA and to determine if certain genetic variants predispose to inhibitor development in these patients., Methods: A single-center study was conducted among patients with severe HA between March 20, 2000, and June 31, 2023. Demographic data and laboratory results of patients were collected. The inverse-shifting PCR (IS-PCR) technique was initially used to screen patients for intron 22 and 1 inversions (Inv-22 and Inv-1)., Results: A total of 480 patients with severe HA (408 without inhibitors and 72 with inhibitors) were enrolled in this study. The median age of the patients at the time of diagnosis was 6 months (IQR: 3 months to 18 months). Inv-22 was observed in 199 (41.5 %) of the cases. Among those patients who developed inhibitors, 53 (73.6 %) were classified as high-titer and 19 (26.4 %) as low-titer. Inv-22, positive family history of inhibitor formation, and history of intense injections revealed a statistically significant association with the risk of inhibitor development., Conclusion: The results of this study confirm the important role of different genetic variants, family history of inhibitor formation, and history of intense injections for the formation of inhibitors in patients with severe HA. This would allow us to stratify the patients which can have important clinical implications, especially in terms of their management and outcome., Competing Interests: Conflicts of interest The authors declare no potential conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Gynecological bleeding including menorrhagia and postpartum hemorrhage (PPH) face women's quality of life constantly with difficulties, especially those suffering from inherited bleeding disorders. In this study, we aim to evaluate gynecological bleeding particularly menorrhagia among Iranian women patients with inherited bleeding disorders admitted to the Iranian Comprehensive Hemophilia Care Center (ICHCC)., Methods: This study was conducted on 156 females aged ≥ 12 diagnosed with an inherited bleeding disorder in ICHCC. Demographic and laboratory data were documented for all patients. Bleeding questionnaires (the International Society on Thrombosis and Hemostasis bleeding assessment tool (ISTH-BAT), Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand disease (MCMDM-1), and Pictorial blood loss assessment chart (PBAC)) were filled out for all patients. For comparing metric and categorical parameters, Mann-Whitney was performed. Spearman's rho test was used for analyzing correlation., Results: The mean age of patients was 33. Von Willebrand disease (VWD), Factor (F) VII deficiency and combined factor deficiency were the most diagnosed disorders. The median of ISTH-BAT, MCMDM-1, and PBAC was 7,7, and 517, respectively. Menorrhagia was the most common reason for diagnosis. Menorrhagia and PPH domain scores ≥ 2 were recorded in 82 and 34 patients, respectively, and PBAC scores > 100 were seen in 118 patients. Significant positive correlations were observed between bleeding scores and menorrhagia and PPH scores. No significant correlations were recorded for VWF: Ag and VWF: RCo with menorrhagia and PPH scores; however, significant correlations were seen for VWF: Ag and VWF: RCo with bleeding score questionnaires., Conclusion: Menorrhagia is the most common problem in females affected by different types of inherited bleeding disorders, particularly VWD. Increased awareness among gynecologists and hematologists about bleeding disorders in cases with unexplained menorrhagia is an essential step for optimal management., Competing Interests: Conflict of interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Background: There is a high prevalence of inherited bleeding disorders in Iran, such as hemophilia A (HA) and hemophilia B (HB). This study aimed to analyze the molecular and clinical profiles of patients with HB., Methods: A single-center study was conducted among patients with severe HB between March 20, 2000, and June 31, 2023. The polymerase chain reaction (PCR) amplification was used for all of the major regions, such as the promoter, the exons, the adjacent intronic regions, and the untranslated regions of the F9 gene. Finally, Sanger sequencing was performed on the PCR products., Results: A total of 111 HB patients (17 with HB [Leyden +] and 94 with HB [Leyden -]) were enrolled in this study. Among 94 patients with HB (Leyden -), 59 (62.8 %) had missense, 21 (22.3 %) had nonsense, and 8 (8.5 %) had frameshift mutations. Moreover, the most frequent pathogenic variant in HB (Leyden +) was c.-17 A>G in this study., Conclusion: The results of this study confirm that HB is caused by a wide range of molecular defects in Iran. Thus, by knowing the genotypes and phenotypes, we would be able to stratify the patients which is important in terms of their management and outcome., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Hypercoagulability is a prominent feature of coronavirus disease 2019 (COVID-19) and can lead to fatal consequences. Although the impact of COVID-19 on several disorders is well-established, its effect on congenital bleeding disorders (CBDs) is not well-documented. To address this ambiguity, a systematic review was conducted on the available studies to determine the impact of COVID-19 and vaccination aimed to prevent COVID-19 on patients with CBDs. We performed a systematic literature review using relevant keywords and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol. We conducted our search on the PubMed, Scopus, and Web of Science databases until July 2023. Out of 31 included studies, 12 case series covering 770 patients with CBD and COVID-19 were further analyzed. The majority of the patients had hemophilia A ( n  = 352, ∼46%) or hemophilia B ( n  = 74, ∼10%), while the remaining patients had von Willebrand disease ( n  = 43, 5.6%) or rare bleeding disorders (n = 27, 3.5%). A total of 25 deaths (3.2%) and 22 intensive care unit admissions (2.8%) were recorded. Bleeding complications were reported in the majority of the 12 case series ( n  = 7, 58.3%) and in most of the case reports ( n  = 8, ∼57%), while thrombotic complications were only reported in two studies (16.6%). The mortality rate ranged from 0% in five studies (41.6%) to 5.7% and the rate of hospitalization ranged from 0 to 40%. Bleeding complications were reported in a range of 0 to 81%, while the thrombotic complication rate in one study was 6.9%. The mortality rate varied from 0 to 5.7%, and the hospitalization rate ranged from 0 to 40%. Bleeding complications were reported in a range of 0 to 81%, while the rate of thrombotic complications in one study was 6.9%. Vaccination was reported in five case series, which included 821 patients with CBDs with the majority having hemophilia A ( n  = 479; 67.2%) and hemophilia B ( n  = 85; ∼12%). The most frequently reported side effects were myalgia (6.5%), flu-like symptoms (4.8%), fever (4.7%), and headache (4%). COVID-19 in patients with CBDs appears to provoke thrombotic complications and bleeding events more frequently, as well as a higher rate of hospitalization, which may be partially due to the increased risk of bleeding events. Although it seems that patients with CBD have lower mortality rates, further studies are necessary to fully understand this, especially considering comorbidities and low number of available studies., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction: Due to their low frequency, there is little information on the molecular pathologies of rare bleeding disorders (RBD). Therefore, this study aimed to analyze the molecular and clinical profiles of patients with RBD., Methods: A retrospective single-center study was conducted among patients with factor (F) II, FVII, FX, and FXIII deficiencies between March 20, 2000, and June 31, 2023. Data on patient demographics, genetic analysis, and laboratory results were documented for all patients. The disease severity was classified according to the clotting factor activity (except FXIII) as follows: >5%: mild, 1-5%: moderate, and <1%: severe., Results: A total of 79 patients were enrolled in this study. Three of the cases had FII (3.7%), 40 had FVII (50.6%), 20 had FX (25.3%), and 16 had FXIII deficiency (20.2%). The median age of the patients at the time of diagnosis was six months for FII, 6.5 years for FVII, five months for FX, and 5.75 months for FXIII deficiencies, respectively. The major clinical manifestations were bruising, epistaxis, oral cavity bleeding, ecchymosis, and hemarthrosis. Consanguinity was present in 60 (76%) of patients. The majority of the patients had missense mutations. FVII mutations occurred primarily in exon 6, FX mutations affected mainly exons 2 and 7, and the majority of FXIII mutations occurred in exons 3 and 4., Conclusion: The diagnosis of the causative mutations in patients with RBD provides an insight into the underlying molecular basis of these disorders and probably explains their variable clinical manifestations., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: β-thalassemia is a group of inherited blood disorders that affect the production of β-globin chains, leading to the reduction or absence of these chains. One of the complications observed in patients with β-thalassemia major (β-TM) is thrombosis, especially in those who receive frequent blood transfusions. This may be due to a decrease in the levels of the natural anticoagulants: protein C (PC), total protein S (PS), and antithrombin (AT)., Methods: In this case-control study, patients with β-TM, who had received at least 20 packed cell transfusions during their lifetime, were included. Patients with other underlying diseases like bleeding or thrombotic disorders were excluded. Totally, 118 patients with β-TM and 120 healthy individuals were included., Results: The mean level of PC and AT was significantly lower in patients with β-TM (48.2 ± 65.4 and 57.42 ± 13.6, respectively) compared to the control group (97.1 ± 21.46 and 81.79 ± 14.3, respectively), with P value of 0.001 and 0.01, respectively. Although the difference was not statistically significant (P = 0.1), a similar trend was observed for total PS (61.12 ± 21.12 for patients versus 72.2 ± 35.2 for the control group). Of note, the decrease in PC, AT, and total PS levels compared to the control group was 50.36%, 27.5%, and 15.34%, respectively., Conclusions: It seems that β-TM patients who receive prolonged blood transfusions frequently are at an increased risk of decreased in natural anticoagulants levels and therefore potentially are at risk of thrombosis., Competing Interests: The authors declare no conflict of interest., (Copyright 2024, Ahmadi et al.)

The prothrombin time (PT) test is commonly used to monitor deficiencies in coagulation factors. A prolonged PT may indicate a deficiency of factors II, V, VII, X, and fibrinogen, or the presence of an inhibitor. However, further tests are required to differentiate between a true factor deficiency and the presence of an inhibitor. It is important to note that falsely prolonged PT can lead to misdiagnosis and inappropriate clinical intervention that can have life-threatening consequences. A 19-year-old woman with elevated hematocrit levels and prolonged PT was diagnosed with secondary erythrocytosis due to cyanotic congenital heart disease with ventricular septal defect (VSD). However, further investigation revealed that the prolonged PT result was false. Excess citrate in the blood sample, caused by polycythemia, led to this misleading outcome, resulting in unnecessary and potentially harmful treatment. This incident emphasizes the importance of laboratory personnel and clinicians being aware of the test's limitations. Not only should specialists in thrombosis and hemostasis possess this knowledge, but it is also pertinent for general laboratory staff, as well as laboratory directors and specialists. The significance of accurate laboratory testing for the proper diagnosis and treatment of patients is highlighted in this case., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Definite diagnosis of patients with mild to moderate bleeding is challenging. Some studies reported that even more than 50% of their patients remained undiagnosed which is classified as a Bleeding disorder of unknown cause (BDUC). This study aims to document the clinical characteristics and proportion of patients with BDUC in the Iranian Comprehensive Hemophilia Care Center (ICHCC) one of the referral centers for diagnosis of congenital bleeding disorder in Iran., Methods: This study was conducted on 397 patients who were referred with a bleeding manifestation to ICHCC from 2019 to 2022. Demographic and laboratory data were documented for all patients. Bleeding questionnaires including ISTH-Bleeding Assessment tool (ISTH-BAT) and the Molecular and Clinical Markers for the Diagnosis and Management of Type 1 (MCMDM-1 (ISTH-BAT, MCMDM-1, and the Pictorial Bleeding Assessment Chart (PBLAC) were filled out for all patients. The data were analyzed by the statistical package for social science (SPSS version 22, SPSS, Chicago, Illinois, USA)., Results: BDUC was diagnosed in 200 patients and 197 patients reached the final diagnosis. Hemophilia, von Willebrand disease (VWD), factor (F) VII deficiency, and platelet functional disorders (PFDs) were confirmed in 54, 49, 34, and 15 of the patients, respectively. No significant difference was found in bleeding scores between patients with BDUC and those with confirmed disease. In contrast, after setting cut-off (ISTH-BAT for males ≥ 4 and females ≥ 6 and MCMDM-1 for males ≥ 3 and females ≥ 5) clinically significant difference was found. There was no association between having a positive consanguineous marriage and setting a diagnosis; however, significant associations were seen for having a positive family history of bleeding. Age (OR =0.977, 95% CI.965-0.989), gender (BDUC female, 151/200; final diagnosis female, 95/197) (OR=3.3, 95% CI 2.16-5.06), family history (OR = 3.19, 95% CI 1.99-5.11), and consanguineous marriage (OR=1.59, 95% CI 1.03-2.45) were considered as a risk factor for categorizing the patients with BDUC or final diagnosis., Conclusion: The findings are mainly in line with previous studies about BDUC patients. The large number of patients with BDUC underlines the incompleteness of available routine laboratory tests and shows the necessity of progress in the development of reliable diagnostic tools to identify underlying bleeding disorders., Competing Interests: Conflict of interest None, (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Genetic variations influence the Von Willebrand Factor plasma level and function. This study aims to evaluate the frequency and clinical phenotype effects of eight single nucleotide polymorphism candidates in four genes (VWF, STXBP5, CLEC4M, and ABO) in Iranian patients with VWD type 1., Method: The study recruited 50 patients with VWD type 1 and 100 healthy individuals. The demographic data from all participants were collected, and the High-Resolution Melting technique was used to determine the frequency of specific single nucleotide polymorphisms. Bleeding scores were also obtained from all patients to assess how these genetic variations might affect the severity of their bleeding symptoms., Results: The study found notable variations in the occurrence of certain SNPs (rs7853989 and rs8176743 for ABO gene and rs1063856 and rs1063857 for VWF gene) between the control group and the patients. Additionally, the study discovered that two SNPs (rs868875 for CLEC4M gene and rs9390459 for STXBP5 gene) were significantly linked to the severity of bleeding, and two others (rs868875 for CLEC4M gene and rs8176746 for ABO gene) were associated with reduced levels of VWF antigen in the patients., Conclusion: According to this study, the above-selected SNPs can cause variations in VWF plasma levels in patients with VWD type 1. Furthermore, the effects of SNPs on bleeding phenotype prove the role of these SNPs in the severity of bleeding manifestations in patients., Competing Interests: Conflict of interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Rare bleeding disorders (RBDs), including factor (F) I, FII, FV, FVII, combined FV and FVIII (CF5F8), FXI, FXIII and vitamin-K dependent coagulation factors (VKCF) deficiencies, are a heterogeneous group of hemorrhagic disorder with a variable bleeding tendency. RBDs are due to mutation in underlying coagulation factors genes, except for CF5F8 and VKCF deficiencies. FVII deficiency is the most common RBD with >330 variants in the F7 gene, while only 63 variants have been identified in the F2 gene. Most detected variants in the affected genes are missense (>50% of all RBDs), while large deletions are the rarest, having been reported in FVII, FX, FXI and FXIII deficiencies. Most were located in the catalytic and activated domains of FXI, FX, FXIII and prothrombin deficiencies. Understanding the proper molecular basis of RBDs not only can help achieve a timely and cost-effective diagnosis, but also can help to phenotype properties of the disorders., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Haemophilia is the most common severe congenital bleeding disorder and can significantly influence patients' quality of life. The health-related quality of life (HRQoL) is a multi-dimensional concept that assess effect of different aspects of health status, including physical, mental, and social domains. Identification of the factors affecting the HRQoL of Persons with Haemophilia (PWH) can guide health care system to better management of patients., Aim: The aim of the present study is to evaluate HRQoL in PWH in Afghanistan., Methods: This cross-sectional study was conducted on 100 PWH in Kabul City, Afghanistan. Data were collected using 36-Item-Short-Form Health Survey (SF-36) questionnaire and analysed using correlation coefficients and regression analysis., Results: The mean scores for the SF-36 questionnaire 8 domains range from 33 ± 38.3 to 58.15 ± 20.5. The highest mean value belongs to physical function (PF) (58.15), whereas the lowest is related to restriction of activities due to emotional problems (RE) (33.00). A significant association (p < .005) was observed between all domains of SF-36 and patients' age except for PF (p = .055) and general health (GH) (p = .75). A significant association was also observed between all HRQoL domains and the severity of haemophilia (p < .001). The severity of haemophilia was the significant predictor for Physical Component Summary (PCS) and Mental Component Summary (MCS) (p < .001)., Conclusion: Due to the reduced HRQoL in Afghan PWH, special attention by health care system should be paid to improve patients' quality of life., (© 2023 John Wiley & Sons Ltd.)

Taking care of people who need constant care is essential and its cost is rising every day. Many intelligent remote health monitoring systems have been developed from the past till now. Intelligent systems explainability has become a necessity after the worldwide adoption of such systems, especially in the health domain to explain and justify decisions made by intelligent systems. Rule-based techniques are among the best in terms of explainability. However, there are several challenges associated with remote health monitoring systems in general and rule-based techniques, specifically. In this research, an adaptive platform based on Complex Event Processing (CEP) has been proposed for user behavior modeling to provide adaptive and personalized remote health monitoring. This system can manage a massive amount of data in real-time utilizing the CEP engine. It can also avoid human errors in setting rules thresholds by extracting thresholds from previous data using JRip rule-based classifier. Moreover, a feature selection method is proposed to decrease the high number of features while maintaining accuracy. Additionally, a rule adaption method has been proposed to cope with changes over time. Additionally, a personalized rule adaption method is proposed to address the need for responsiveness of the system to the special requirements of each user. The experimental results on both hospital and activity data sets showed that the proposed rule adaption method improves the accuracy by about 15 % compared to non-adaptive systems. Additionally, the proposed personalized rule adaption method has an accuracy improvement of about 3 % to 6 % on both mentioned datasets., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Antithrombin (AT), protein C (PC), and protein S (PS) are natural anticoagulant proteins that deficiency in each of them is associated with an increased risk of venous thromboembolism.The overlapping of plasma levels of AT, PC, and PS between healthy individuals and heterozygote carriers poses significant challenges in precise diagnosis. This study aimed to evaluate the effect of most influencing variables on plasma levels of these proteins and propose specific reference intervals to improve the interpretation of the laboratory results., Methods: This study was conducted on 1464 individuals who were referred to Massoud medical laboratory, Tehran, Iran, from 2019 to 2020. AT and PC were measured through chromogenic assay and PS plasma level with the clot-based assay. A multivariable linear regression model was performed to evaluate the effect of sex, age, oral contraceptive (OCP) intake, and menopause state. Normal deviate z value was used for different subgroups to justify the need for a separate reference interval., Results: 1200 verified healthy individuals (434 males and 766 females), aged between 18 and 69 years were included in the study. The mean ± SD age of the participants was 39.78 ± 11.79 years. The age-related effects for AT were found in men. In females, increasing age was associated with a rise in AT, PC, and PS plasma levels. No sex difference was found in AT plasma level. OCP-taking is associated with a decrease in AT and an increase in PC plasma levels., Conclusion: This is the largest study ever conducted on healthy individuals in the Iranian population, using specific reference interval results in accurate diagnosis of true AT, PC, and PS deficiency., (© 2022 John Wiley & Sons Ltd.)

Congenital factor (F) XIII deficiency is a rare coagulation factor deficiency that is inherited in an autosomal recessive manner. FXIII deficiency presents various clinical manifestations, such as intracranial hemorrhage (ICH), which is the most common cause of morbidity and mortality. As ICH can occur in the neonatal period, prenatal diagnosis (PND) is an effective way to reduce neonatal ICH and its associated fatal consequences. In this study, we investigated a noninvasive prenatal diagnosis (NIPD) method, cell-free fetal DNA (cffDNA), for PND in FXIII deficiency. This study was conducted on seven pregnant women in the first trimester. After extraction of cffDNA from maternal plasma, PCR-restriction fragment length polymorphism (PCR-RFLP) was performed to find the underlying F13A gene mutations previously identified in the family members. PCR-RFLP was also performed on postnatal DNA samples. Sanger sequencing was performed to confirm the results. Four cases were heterozygous for F13A gene mutations, whereas three were unaffected. PCR- RFLP results for cffDNA and postnatal DNA samples were identical, and Sanger sequencing confirmed the results. cffDNA is a noninvasive and effective method for PND in congenital FXIII deficiency., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Prophylaxis the current standard care for patients with severe hemophilia should be planned to optimize the replacement therapy and minimize bleeding. We report our single-center experience of tailored prophylaxis in children affected by hemophilia A (HA) and hemophilia B (HB)., Methods: This study was conducted on 55 patients, under 15 years, with HA (PWHA, n: 46) and HB (PWHB, n: 9) between 2015 and 2019. According to the phenotype, three prophylaxis regimens: 25-50 unit/kg once, twice, or three-times a week for PWHA, and two: 30-50 unit/kg once or twice a week for PWHB were administered. Following the occurrence of > 3 joint bleeding, or > 4 soft tissue bleeding, or one spontaneous major bleeding in the last 3 months, the prophylaxis regimen is changed. Annualized bleeding rate (ABR), annualized joint bleeding rate (AJBR), target joints development, inhibitor development, and hemophilia joint health score (HJHS) also were assessed., Results: A mean ± SD of 2520 ± 1045 IU/kg/yr coagulation factor (F) VIII was used to reduce ABR and AJBR from 1.02 ± 1.11 and 0.8 ± 1.3 (in the first year of the study) to 0.27 ± 0.44 (P < 0.001) and 0.19 ± 0.38 (P = 0.004) (at the end of the study) in PWHA, respectively. Furthermore, in PWHB, in the first year of the study, with using 2168 ± 1216 IU/kg coagulation FIX, ABR and AJBR were 0.19 ± 0.39 and 0.06 ± 0.1. At the end of the study, ABR and AJBR were 0.02 ± 0.05 (p = 0.156) and 0.01 ± 0.03 (p = 0.361), respectively. During the study period, the mean number of the target joints and mean HJHS were 0.25 ± 0.57 and 7.6 ± 2.1 for PWHA and 0 and 6.3 ± 1.8 for PWHB, respectively. Finally, 5 PWHA (11 %) did not need dose-escalation in their prophylaxis regimen, whereas 31 (67 %) and 10 (21 %) PWHA needed two and three infusions a week, respectively. In PWHB, 7 (78 %) and 2 (22 %) were adjusted to receive a once and twice weekly regimen, respectively., Conclusion: Our results suggest that tailored prophylaxis is an effective strategy to reduce the rate of bleeding and optimize the replacement therapy in children with hemophilia., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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.)