Introduction & Objective: FACTOR V LEIDEN and prothrombin mutation are not common but they are involved in pediatric thrombosis. The aim of this study was to evaluate the frequency of FACTOR V LEIDEN & prohtrombin mutation in healthy population of Shiraz, south of Iran.Materials & Methods: In this cross-sectional study 195 healthy people (97 female and 98 male) were randomly selected. Peripheral white blood cells obtained from 5 ml blood contained 1-2 mg/ml K2- EDTA. Genomic DNA extraction was performed following the protocol described by Miller et al. PCR amplification was carried out in 25μl reaction volume containing 0.5 units Taq polymerase, 200μM dNTP, 500 μM of each of the previously described primers. After initial denaturation, 35 cycles at 95◦c for 30s, and 72◦c for 20s and followed extention by 72 for 10 min were performed. About 10μl of PDR product was digested with MNI I or Mbo restriction enzymes.Results: In this study we determined FACTOR V LEIDEN in 8 (4.1%) and prothrombin mutation in 6 individual (3.07%) of 198 cases in heterozygous form. No homozygous was seen for any of the mutations. Only one case presented a double heterozygous for FACTOR V and prothrombin in this cohort. Conclusion: Several studies of FACTOR V LEIDEN and prothrombin mutations in the East of Asia showed the higher frequency of these mutations in Iran.

Introduction: FACTOR V LEIDEN thrombophilia is an inherited disorder of blood clotting. Women with FACTOR V LEIDEN have a substantially increased risk of clotting in pregnancy in the form of DVT and pulmonary embolism. They are also having an increased risk of preeclampsia, as well as miscarriage and stillbirth due to clotting in the placenta, umbilical cord, or the fetus. Methods: FACTOR v LEIDEN is a common gentic mutation that predisposes its carries to venous thromobembolism. When combined with the hypercoagulable state that is characteristic of pregnancy, there is an increased risk of sever and recurrent pregnancy complication. FACTOR V LEIDEN carriage has consistently been shown to increase the risk of early onset gestational hypertension and HELP syndrome in pregnancy.Maternal carriage of FACTOR V LEIDEN is also associated with severs placental abruption and fetal growth disturbance. Some studies have found that having the FACTOR V LEIDEN mutation means an increased risk of recurrent miscarriages. Possibly because of tiny blood clots blocking the flow of nutrients to the placenta. Women with the mutation have a higher rate of miscarriage than women without it.Therapeutic heparin is required for acute thromboemblism events in pregnancy. Some doctors believe in using heparin and or low-dose aspirin to treat women who have FACTOR V LEIDEN gene and a history of miscarriages. The role of anthithrombotic therapy in the prevention of severs pregnancy complications remains unclear.Conclusion: FACTOR V LEIDEN is a common gene mutation, which results in a genetic predisposition to thromoboembolic complications. when combined with the prothrombotic influences of pregnancy, women who are carries of FACTOR V LEIDEN are faced with an increased risk of stillbirth, early onset pre-eclampsia, sever abruption and possibly fetal growth restriction .it is unclear whether heparin therapy reduces thes pregnancy complication or improves pregnancy out come .women with FACTOR V LEIDEN and a personal or family history of thrombosis probably benefit from thromboprophylaxis in pregnancy.

Background: FACTOR V G1691A (FV LEIDEN), FII GA20210, and methylenetetrahydrofolate reductase (MTHFR) C677T mutations are the most common genetic risk FACTORs for thromboembolism in the Western countries. However, there is rare data in Iran about cerebral venous and sinus thrombosis (CVST) patients. The aim of this study was to evaluate the frequency of common genetic thrombophilic FACTORs in CVST patients.Materials and Methods: Forty consequently CVST patients from two University Hospital in Isfahan University of Medical Sciences aged more than 15 years from January 2009 to January 2011 were recruited. In parallel, 51 healthy subjects with the same age and race from similar population selected as controls. FV LEIDEN, FII GA20210, MTHFR C677T, and FV Cambridge gene mutations by polymerase chain reaction technique were evaluated in case and control groups.Results: FV LEIDEN, FII GA20210, and FV Cambridge gene mutations had very low prevalence in both case (5%, 2%, 0%) and control (2.5%, 0%, 0%) and were not found any significant difference between groups. MTHFR C677T mutations was in 22 (55%) of patients in case group and 18 (35.5%) of control group (P=0.09).Conclusion: This study showed that the prevalence of FV LEIDEN, FII GA20210, and FV Cambridge were low. Laboratory investigations of these mutations as a routine test for all patients with CVST may not be cost benefit.

Background: Activated protein C (APC) inactivates FACTOR V (FV) by cleavage of its heavy chain at Arg306, Arg506, Arg679, and Lys994. Mutational changes, which abolish APC cleavage sites, may predispose thrombosis by altering the inactivation process of FV. FV LEIDEN (FVL) (Arg506Glu) has been demonstrated as a strong risk FACTOR for thrombosis. In the current study, we have studied whether mutations in the cleavage sites of FV for APC, not due to FVL, would have a role in presenting APC resistance (APCR) and initiation of a cerebral thrombotic event. Methods: A group of 22 patients with a history of cerebral venous thrombosis (CVT), who were not carriers of FVL enrolled in the study. The patients who had conditions associated with acquired APCR were excluded from the study. APCR test was performed on the remaining 16 patients, which showed APCR in 4 plasma samples. DNA sequencing was performed on four exons of FV of APCR patients, encoding Arg306, Arg506, Arg679, and Lys994. Results: Mutations were not found within nucleotides encoding the cleavage sites; neither was found within their close upstream and downstream sequences. Conclusion: Our results show that polymorphisms affecting cleavage sites of FV other than Arg506Glu it would be less likely to be the basis for APCR and its increased thrombosis susceptibility. In addition, it emphasizes on the importance of screening for APCR in the patients diagnosed with CVT.

Normal hemostasis requires balanced regulation of prothrombotic and antithrombotic FACTORs. Inherited alteration of FACTOR V and prothrombin gene, the G20210A mutation, increases the resistance of FACTOR V to degradation and booster production of prothrombin respectively. These alterations can increase hypercoagulability leading to thrombotic consequences. We aimed to assess the frequencies of these mutations in a group of the population of southern Iran. In total, 198 healthy volunteers with the age range of 1-64 years were selected and screened for FACTOR V LEIDEN and prothrombin mutations using polymerase chain reaction and restriction fragment length polymorphism techniques. The carrier frequencies for FACTOR V LEIDEN and prothrombin mutation in the studied cohort were 4.1% and 3.07%, respectively. In the studied area, the allele frequency of FACTOR V is higher than the prothrombin G20210A mutation (0.0204 v 0.0153). According to the data and Hardy-Weinberger equation, the total risk of thrombosis caused by homozygosity and heterozygosity of FACTOR V LEIDEN, prothrombin G20210A mutation and compound heterozygosity of these mutations are about 1 in 500 individuals.

Background: Behcet’s disease (BD) is a multisystemic inflammatory disease with unknown origin characterized by recurrent oral aphtous ulcers, genital, ocular and skin lesions. A single point mutation 1691G to A in the FACTOR V gene increases the risk of venous thrombosis. This study designed to determine FACTOR V LEIDEN mutation in Behcet’s disease, and to find out it's relationship with the clinical manifestations in Khuzestan province, Iran.Methods: One hundred patients with Behcet's Disease (44 males and 56 females) based on international diagnostic criteria and 70 healthy subjects were included in the study. Patients and controls were tested for the presence of FACTOR V LEIDEN mutation using polymerase chain reaction method.Results: The prevalence of FACTOR V LEIDEN mutation was significantly higher in BD (10 out of 100, 10%) compared with healthy control subjects (1 out of 70, 1.4%), (p=0.025). Vascular lesions in this study were deep vein thrombosis (DVT) (7%), subcutaneous thrombophlebitis (5%), stroke (1%) and retinal vasculitis (39%). It was found that there was no association between venous thrombosis and the FACTOR V LEIDEN mutation in Khuzestanian patients. Also, no association between other vascular lesions and the FACTOR V LEIDEN mutation was recognized. On the other hand there was a significant association between DVT and anterior uveitis (p=0.033).Conclusion: In this study we did not find any association between clinical manifestations in BD patients and FACTOR V LEIDEN mutation in Khuzestan province, Iran but in BD patients with DVT, FACTOR V LEIDEN mutation might be a risk FACTOR for the development of anterior uveitis.

Context: Thrombophilia is an inherited or acquired predisposition in developing thrombosis. The two common thrombophilia polymorphisms are FACTOR V LEIDEN (FVL) and FACTOR II/ prothrombin G20210A (PT) gene mutations which can contribute to negative pregnancy outcomes such as miscarriage, in-vitro fertilization (IVF) failure, preeclampsia, intrauterine growth restriction (IUGR), placental abruption, stillbirth, and pregnancyassociated venous thromboembolism. This review study sought to describe the effects of FVL and PT mutations on pregnancy complications. Evidence Acquisition: In this review study, a comprehensive search was performed on Iranian and international databases including MEDLINE, PubMed, Scopus, Web of Sciences, Proquest and Google Scholar for articles published during 1996-2018. Out of 220 reviewed articles, 80 papers were ultimately selected. Results: According to these 80 selected papers, the possible relations of PT and FVL with recurrent pregnancy loss (RPL) have been widely evaluated. Several studies indicated higher risk of recurrent early miscarriages, implantation failure and fetal loss after IVF among women with FVL and PT mutations. Conclusion: Observational studies have suggested the benefits of screening patients for thrombophilic polymorphisms in identification of women with higher risk of developing thromboembolic events and other related pregnancy complications. Based on such screening programs, prophylactic therapy can be limited to a selected group of women who truly need it.