Gynecological bleeding in women with congenital bleeding disorders: A comprehensive cohort from Iran.

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.

Molecular and clinical profile of rare bleeding disorders: A single-center retrospective study.

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.

Genotype-phenotype analyses of Iranian patients with hemophilia B (Leyden -) and hemophilia B (Leyden +): A single-center study.

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.

Congenital Bleeding Disorders and COVID-19-A Systematic Literature Review.

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.

Health-related quality of life in persons with haemophilia in Afghanistan.

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.

Associations of multiple genetic variations with plasma levels of Von Willebrand Factor and clinical phenotype in Iranian patients with Von Willebrand disease type 1.

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.

Bleeding disorder of unknown cause: Results from Iranian study.

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.

Genotyping of blood groups in alloimmunized patients with ß-thalassemia major by T-ARMS-PCR and multiplex-aso-pcr.

INTRODUCTION: Beta-thalassemia major is a severe hemolytic anemia requiring life-long blood transfusion. Planned random donor blood transfusion is associated with alloimmunization against incompatible antigens. Determination of the minor blood group systems phenotype or genotype, and administration of the compatible blood components can significantly reduce the rate of alloimmunization. The present study aimed to determine the prevalence of alloimmunization, and genotype/phenotype characteristics of the minor blood groups systems in patients with ß-thalassemia major. MATERIAL AND METHODS: This study was conducted on 1147 ß-thalassemia major patients. Initially, antibody screening and antibody identification were performed. Then, phenotyping and genotyping for the Rh, Kell, Kidd, and Duffy blood groups were done in alloimmunized patients using monoclonal antibodies and Multiplex-Allele Specific Oligonucleotide-Polymerase Chain Reaction (Multiplex-ASO-PCR) and Tetra-primer amplification refractory mutation system-PCR (T-ARMS-PCR), respectively. Any phenotype/genotype discrepancy was assessed by direct sequencing. RESULTS: Ninety-seven (8.5 %) out of 1147 patients had alloantibodies against the minor blood group antigens (44 males, 45.4 %, and 53 female, 54.6 %). The most common alloantibodies were against the RH (n: 47, 48.5 %), and the Kell (n: 23, 23.7 %) blood groups systems. Twenty-three (2.1 %) genotype/phenotype discrepancies out of 1067 tests, including 9 in the Rh (9.3 %), 8 in Duffy (34.8 %), and 6 in Kidd (26.1 %) blood groups were detected. No discrepancy was found in the Kell blood group system. Direct sequencing revealed that the results of molecular methods were correct. CONCLUSION: Multiplex-ASO-PCR and T-ARMS-PCR molecular methods are fast, reliable and cost-benefit molecular methods for the minor blood group genotyping in multi-transfused ß-thalassemia major patients.

Tailored prophylaxis in children with severe hemophilia: A four-year Iranian study.

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.

Premarital Screening Program for Congenital Factor XIII Deficiency in Iran.

BACKGROUND: Factor XIII deficiency is one of the most severe congenital bleeding disorders with high rate of life-threatening bleeding including central nervous system bleeding, umbilical cord bleeding, and recurrent miscarriages. Due to the highest global incidence of the disorder in Iran, this study aimed to design a premarital screening program in Iran. METHODS: This descriptive study was performed on 30 couples with a positive family history of factor XIII deficiency. Underling F13A gene mutation was determined in the family members, and all the selected couples underwent molecular testing mutations by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), tetra primer-amplification refractory mutation system-PCR (T-ARMS-PCR), and sequencing. RESULTS: The probability of affected childbirth existed for ten couples. Three couples decided not to marry, while seven got married and three of them decided to have a baby. The genotypes of the fetuses were determined and revealed that none of them was a homozygote for the F13A gene mutation. CONCLUSIONS: Because of the importance of factor XIII deficiency diagnosis, it can be helpful to control the incidence of factor XIII deficiency by implementing preventive programs such as premarital screening.

A Comprehensive Overview of Coagulation Factor V and Congenital Factor V Deficiency.

Coagulation factor (F) V is a glycoprotein that plays an essential role in the formation of the prothrombinase complex, which is critical for progressing clot formation. FV deficiency is a rare bleeding disorder with an estimated incidence of one per 1 million in the general population. The disorder is manifested with a wide array of clinical bleeding events. The most common bleeding features of FV deficiency are mucosal bleedings. Life-threatening manifestations are rarely seen in this disorder. FV deficiency is diagnosed using routine coagulation tests and FV activity assay. A wide spectrum of mutations including missense, nonsense, and frameshift is observed throughout the F5 gene. Although fresh frozen plasma is the dominant therapeutic choice, a newly introduced plasma-derived FV concentrate was found effective in in vitro correction of prothrombin time, activated partial thromboplastin time, and thrombin generation parameters in severe FV deficiency and should provide more targeted treatment for patients with FV deficiency in the future.

A Unique Factor XIII Mutation in Southeastern Iran with an Unexpectedly High Prevalence: Khash Factor XIII.

Congenital factor XIII (FXIII) deficiency is an extremely rare hemorrhagic disorder characterized by a deficiency of FXIII and associated with a high rate of morbidity and mortality. The disorder is more frequent in Iran, especially in Khash, a city in the southeast of the country. As identified in the current report, the prevalence of FXIII deficiency in this city is 1 homozygote per approximately 500 population (which is ∼4,000 times higher than the worldwide prevalence) with 3.5% heterozygotes. The disorder is accompanied by a high rate of mortality in rural areas of Khash, given an averaged observed rate of approximately three deaths per each family with FXIII deficiency, mostly due to late-diagnosis and/or misdiagnosis, and fetal consequences of both umbilical cord and central nervous system bleeding. Almost all patients with FXIII deficiency in the southeast Iran have a unique mutation in F13A gene (Trp187Arg), which leads to a severe FXIII deficiency. This mutation is used for pre-marriage and prenatal diagnosis, as well as for carrier detection and diagnostic confirmation. Fibrogammin P has been used worldwide for about one decade, along with different therapeutic regimens for prophylaxis treatment, major and minor surgeries, and successful delivery. Due to the rapid increase in the number of patients identified to have congenital FXIII deficiency, and the high rate of related morbidity and mortality, a comprehensive regional preventive program is necessary to prevent further expansion of this condition and decrease the burden on the health care system. The area of Khash city provides novel insights into severe FXIII deficiency due to its high prevalence in this region. This report also provides a review of FXIII deficiency, its diagnosis, prevalence, molecular basis, clinical manifestations, management, and treatment, with a particular focus on Iran, representing a hotspot for this disorder.

Intracranial Hemorrhage: A Devastating Outcome of Congenital Bleeding Disorders-Prevalence, Diagnosis, and Management, with a Special Focus on Congenital Factor XIII Deficiency.

Intracranial hemorrhage (ICH) is a medical emergency. In congenital bleeding disorders, ICH is a devastating presentation accompanied with a high rate of morbidity and mortality. The prevalence of ICH is highly variable among congenital bleeding disorders, with the highest incidence observed in factor (F) XIII deficiency (FXIIID) (∼30%). This life-threatening presentation is less common in afibrinogenemia, FVIII, FIX, FVII, and FX deficiencies, and is rare in severe FV and FII deficiencies, type 3 von Willebrand disease and inherited platelet function disorders (IPFDs). In FXIIID, this diathesis most often occurs after trauma in children, whereas spontaneous ICH is more frequent in adults. About 15% of patients with FXIIID and ICH die; the bleeding causes 80% of deaths in this coagulopathy. Although in FXIIID, the bleed most commonly is intraparenchymal (> 90%), epidural, subdural, and subarachnoid hemorrhages also have been reported, albeit rarely. As this life-threatening bleeding causes neurological complications, early diagnosis can prevent further expansion of the hematoma and secondary damage. Neuroimaging plays a crucial role in the diagnosis of ICH, but signs and symptoms in patients with severe FXIIID should trigger replacement therapy even before establishment of the diagnosis. Although a high dose of FXIII concentrate can reduce the rate of morbidity and mortality of ICH in FXIIID, it may occasionally trigger inhibitor development, thus complicating ICH management and future prophylaxis. Nevertheless, replacement therapy is the mainstay of treatment for ICH in FXIIID. Neurosurgery is performed in patients with FXIIID and epidural hematoma and a hemorrhage diameter exceeding 2 cm or a volume of ICH is more than 30 cm3. Contact sports are not recommended in people with FXIIID as they can elicit ICH. However, a considerable number of safe sports and activities have been suggested to have more benefits than dangers for patients with congenital bleeding disorders, and are hence suitable for these patients.

Inherited Platelet Function Disorders (IPFDs).

BACKGROUND: Inherited platelet function disorders (IPFDs) are a wide spectrum of qualitative platelet disorders with variable bleeding tendency, ranging from mild bleeding to severe life-threatening episodes. Diagnosis and classification of IPFDs is a challenge worldwide. The present study aims to present a proper classification, describe the molecular basis and clinical presentations as well as some diagnostic clues for these disorders. METHODS: All relevant publications were searched using appropriate keywords. RESULTS: IPFDs can be divided into four major groups including defects of platelet surface glycoproteins, platelet granules and secretion disorders, platelet signaling defects, and transcription-related platelet disorders. Some of these disorders, such as Glanzman thrombasthenia, are more common, with severe bleeding, while most of these disorders are extremely rare with mild bleeding. CONCLUSIONS: A proper classification, accompanied by familiarity with diagnostic clinical and laboratory features of IPFDs, can be helpful in in-time and exact diagnosis of these complicated bleeding disorders.

Factor XIII deficiency in Iran: a comprehensive review of the literature.

Factor XIII deficiency (FXIIID) is a rare bleeding disorder with an estimated prevalence of 1 in 2-million population worldwide. In Iran, a Middle Eastern country with a high rate of consanguineous marriages, there are approximately 473 patients afflicted with FXIIID. An approximately 12-fold higher prevalence of FXIIID is estimated in Iran in comparison with overall worldwide frequency. In this study, we have undertaken a comprehensive review on different aspects of FXIIID in the Iranian population. The distribution of this disease in different regions of Iran reveals that Sistan and Baluchestan Province has not only the highest number of patients with FXIIID in Iran but the highest global incidence of this condition. Among Iranian patients, umbilical cord bleeding, hematoma, and prolonged wound bleeding are the most frequent clinical manifestations. There are several disease causing mutations in Iranian patients with FXIIID, with Trp187Arg being the most common mutation in FXIIID in Iran. Traditionally, the management of FXIIID in Iran was only based on administration of fresh frozen plasma or cryoprecipitate, until 2009 when FXIII concentrate became available for patient management. Various studies have evaluated the efficacy and safety of prophylactic regimens in different situations with valuable findings. Although the focus of this study is on Iran, it offers considerable insight into FXIIID, which can be applied more extensively to improve the management and quality of life in all affected patients.

Genetic risk factors in patients with deep venous thrombosis, a retrospective case control study on Iranian population.

BACKGROUND: Venous thromboembolism (VTE) could be manifested as deep venous thrombosis (DVT) or pulmonary embolism (PE). DVT is usually the more common manifestation and is usually formation of a thrombus in the deep veins of lower extremities. DVT could occur without known underlying cause (idiopathic thrombosis) which could be a consequence of an inherited underlying risk factor or could be a consequence of provoking events, such as trauma, surgery or acute illness (provoked thrombosis). Our aim in this study was to assess the impact of some previously reported genetic risk factors including, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, plasminogen activator inhibitor-1(PAI-1) 4G/5G, prothrombin 20210 and FV Leiden on occurrence of DVT in a population of Iranian patients. METHODS: This long-term study was conducted on 182 patients with DVT and also 250 age and sex matched healthy subjects as control group. The diagnosis of DVT was based on patient's history, clinical findings, D-dimer test, and confirmed by Doppler ultrasonography. After confirmation of DVT, both groups were assessed for the five mentioned mutations. The relationship between mutations and predisposition to DVT was calculated by using logistic regression and expressed as an OR with a 95 % confidence interval (CI). RESULTS: Our results revealed that FV Leiden (OR 6.7; 95 % CI = 2.2 to 20.3; P = 0.001), MTHFR C677T (OR 6.0; 95 % CI = 2.2 to 16.4; P < 0.001), MTHFR A1298C (OR 8.3; 95 % CI = 4.4 to 15.8; P < 0.001), and PAI-1 4G/5G (OR 3.8; 95 % CI = 2.1 to 7.2; P < 0.001) mutations were all significantly associated with an increased risk of DVT. Prothrombin 20210 was found in none of the patients and controls. CONCLUSION: Our findings suggest that genetic risk factors have a contributory role on occurrence of DVT.

Congenital factor V deficiency: comparison of the severity of clinical presentations among patients with rare bleeding disorders.

BACKGROUND: Factor V deficiency (FVD) is a rare bleeding disorder (RBD) mostly present in regions with a high rate of consanguinity. FVD after FXIII deficiency is the next more prevalent RBD in Sistan and Baluchistan (S&B) in southeastern Iran. The aim of this study was to evaluate the clinical manifestations and severity of bleeding diathesis in patients with FVD. METHODS: This descriptive study was conducted on 23 patients with FVD in S&B province. FVD was diagnosed by clinical findings and routine laboratory tests. Bleeding diatheses were classified into three grades (I-III) depending on the severity of symptoms. The severity of bleeding episodes in our patients was compared with other RBDs. RESULT: Based on residual plasma FV activity, 6 (26%), 16 (69.5%) and 1 (4.5%) patients had mild, moderate and severe factor deficiency, respectively. 24% of the patients had grade III life-threatening bleeding episodes which in comparison with FVII deficiency (17.4%) and FI deficiency (21%) had a higher incidence, and in comparison with FX deficiency (41.7%) and FXIII deficiency (63.1) had a lower incidence. Grade II and grade I bleeding diathesis were observed in 56.2 and 16.7% of the patients, respectively. CONCLUSION: FVD is the second most common type of RBD in S&B province and grade II bleeding episodes were the major bleeding presentation and observed in more than half of the patients.

Falsely prolonged prothrombin time test in a patient with erythrocytosis: a case report.

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.