Cerebral sinus thrombosis in a patient with active ulcerative colitis and double heterozygosity for Factor V Leiden and prothrombin gene mutations

SummaryHomozygous carriers of factor V Leiden have an approximately 80-fold increased risk of venous thrombosis. Also double heterozygous carriers of both the factor V Leiden and the prothrombin gene mutations are at high thrombotic risk. The magnitude of the risk of venous thrombosis in pregnant women with the two severe thrombophilic conditions has not been estimated so far. We performed a multicenter retrospective family study in women with homozygous factor V Leiden, double heterozygous factor V Leiden and the prothrombin gene mutation, and women with normal coagulation. Only relatives of index patients with thrombosis formed the study cohort. Fifteen homozygous and 39 double heterozygous women were compared to 182 women with normal coagulation. Venous thrombosis occurred in 3 of 19, 2 of 50 and 1 of 221 pregnancies, respectively. One thrombotic episode occurred in the third trimester, the remaining 5 in the postpartum. The prevalence of venous thrombosis was 15.8% (95% CI 3.4-39.6) for homozygotes, 4.0% (95% CI 0.5-13.7) for double heterozygotes and 0.5% for women with normal coagulation. The relative risk of pregnancy-related venous thrombosis was 41.3 (95% CI 4.1-419.7) for homozygous and 9.2 (95% CI 0.8-103.2) for double heterozygous carriers. In conclusion, homozygous carriers of factor V Leiden and, to a lesser extent, double heterozygous carriers of factor V Leiden and of the prothrombin mutation have an increased risk of venous thrombosis during pregnancy, particularly high during the postpartum period. On the basis of these findings we recommend that these women receive anticoagulant prophylaxis at least in the postpartum, that should perhaps be extended to the whole pregnancy in homozygous carriers.

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Factor V Leiden and prothrombin gene mutations in Egyptian cases with unexplained recurrent pregnancy loss

Hematology ◽

10.1179/102453311x12902908411959 ◽

2011 ◽

Vol 16 (1) ◽

pp. 59-63 ◽

Cited By ~ 5

Author(s):

Ahmad Settin ◽

Rabab Abo Alkasem ◽

Ehab Ali ◽

Rizk ElBaz ◽

Abdel Megid Mashaley

Keyword(s):

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Gene Mutations ◽

Factor V Leiden ◽

Factor V ◽

Prothrombin Gene

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Selected genetic causes of miscarriages

Postępy Higieny i Medycyny Doświadczalnej ◽

10.5604/01.3001.0014.7758 ◽

2021 ◽

Vol 75 ◽

pp. 116-121

Author(s):

Ewelina Łazarczyk ◽

Magdalena Pasińska ◽

Katarzyna Osmańska-Załuska ◽

Olga Haus

Keyword(s):

De Novo ◽

Chromosomal Abnormalities ◽

Gene Mutations ◽

Factor V Leiden ◽

Factor V ◽

Robertsonian Translocations ◽

Monogenic Diseases ◽

Structural Aberrations ◽

Prothrombin Gene Mutation ◽

Prothrombin Gene

Approximately 15–25% of pregnancies end in spontaneous abortion, which is an expulsion from the mother body of the fetus weighing less than 500 g or before the 20th week of gestation. Determining abortions etiology is difficult due to its multifactorial character. Chromosomal abnormalities cause 38.6–80% of miscarriages. The largest group (93%) of chromosomal aberrations found in miscarried fetuses are numerical changes – aneuploidies and polyploidies. Much rarer (7%) are unbalanced structural aberrations, which can arise de novo or can be inherited from a carrier parent. In couples with spontaneous abortions, reciprocal chromosomal translocations (RCT) occur the most frequently, next are Robertsonian translocations and inversions. More complex chromosome abnormalities, e.g. double aneuploidies are found in 3.8% of fetuses. Another group of causes responsible for abortions are monogenic diseases of embryo or fetus resulting from autosomal dominant, autosomal recessive or X-linked mutations. Among mutations which may contribute to pregnancy loss are factor V Leiden gene mutations (c.1601G>A, earlier 1691G>A) and prothrombin gene mutation (c.97G>A, earlier 20210G>A). The research on mutations in candidate genes, eg.: ALOX15, CR1, CYP1A1, CYP17, CYP2D6, FOXP3, HLA-G, IL-6, KHDC3L, NLRP7, NOS3, PLK4, SYCP3, TLR3, TNF, TP53 and VEGFA is still ongoing.

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Heritable Thrombophilia in Venous Thromboembolism in Northern Pakistan: A Cross-Sectional Study

Advances in Hematology ◽

10.1155/2021/8317605 ◽

2021 ◽

Vol 2021 ◽

pp. 1-5

Author(s):

Maria Khan ◽

Chaudhry Altaf ◽

Hamid Saeed Malik ◽

Muhammad Abdul Naeem ◽

Aamna Latif

Keyword(s):

Venous Thromboembolism ◽

Protein C ◽

Gene Mutations ◽

Factor V Leiden ◽

Factor V ◽

Protein C Deficiency ◽

Factor V Leiden Mutation ◽

Inherited Thrombophilia ◽

At Deficiency ◽

Prothrombin Gene

Background. Venous thromboembolism (VTE) is referred to as formation of clots in a deep vein or lodging of thrombus towards the lungs which could be fatal yet preventable. The risk of developing VTE can be increased by various factors. Where there are innumerable acquired causes, the possibility of inherited thrombophilia cannot be ignored. In view of this, we have evaluated all patients with venous thromboembolism for inherited thrombophilia. Objective. To evaluate the frequencies of antithrombin (AT) deficiency, protein C and S deficiencies, Factor V Leiden, and prothrombin gene mutations in patients harboring venous thromboembolism. Materials and Methods. A study comprising of 880 patients who were presented with manifestations of venous thromboembolism was conducted from July 2016 to June 2017. A blood sample collected from patients was screened for thrombophilia defects encompassing AT, protein C and S deficiencies, Factor V Leiden, and prothrombin gene mutations. All acquired causes of thrombosis were excluded. Results. Of 880 patients who underwent screening for thrombophilia, 182 patients demonstrated VTE history. Their age ranged from 1 to 58 years. Males constituted a predominant group. About 45 (24.7%) patients had evidence of heritable thrombophilia. Of these, 20 (10.9%) had AT deficiency, 9 (4.9%) had Factor V Leiden mutation, 6 (3.2%) had protein C deficiency, whereas protein S deficiency and prothrombin gene mutation both were found in 5 (2.7%) patients. Conclusion. Our study illustrated the highest frequency of antithrombin deficiency among other investigated thrombophilia defects.

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Thrombophilia gene mutations in relation to recurrent miscarriage

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20180857 ◽

2018 ◽

Vol 7 (3) ◽

pp. 796 ◽

Cited By ~ 1

Author(s):

Tawfik Abdelsalam ◽

Tarek Karkour ◽

Magdy Elbordiny ◽

Dina Shalaby ◽

Ziad S. Abouzeid

Keyword(s):

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Recurrent Miscarriage ◽

Gene Mutations ◽

Factor V Leiden ◽

Mthfr C677t ◽

Factor V ◽

Total Prevalence ◽

History Of ◽

Prothrombin Gene

Background: Recurrent pregnancy loss is multifactorial involving clinical and biological risk factors. Evidence addressed the association of inherited thrombophilia with recurrent pregnancy loss and other serious pregnancy complications. However, the relation between thrombophilia associated gene mutations and adverse obstetric outcome is controversial and data in the literature are inconsistent. The aim of this study was to investigate the prevalence of thrombophilia associated gene mutations (factor V Leiden, prothrombin gene G20210A and methylene-tetrahydrofolate reductase MTHFR C677T) in relation to recurrent miscarriage.Methods: Case control study conducted on 200 women recruited from Elshatby Maternity Hospital clinics. The cases group included 100 women with history of three or more unexplained consecutive pregnancy losses, while 100 healthy age matched women with no history of recurrent miscarriages served as controls. Blood samples were collected from all women enrolled in the study for DNA extraction and genotype analysis. Factor V, prothrombin and MTHFR gene mutations were assayed based on polymerase chain reaction (PCR) and reverse-hybridization.Results: The prevalence of Factor V Leiden and prothrombin gene G20210A mutations did not differ significantly between cases and controls. However, MTHFR C667T mutations and the total prevalence of the three gene mutations were significantly increased in the patients group compared to controls (p=0.001, p=0.003 respectively). The prevalence of combined thrombophilia of Factor V Leiden and MTHFR C677T was significantly increased in the patients group compared to controls (p=0.032). Regarding homozygosity of each of the gene mutations, no homozygosity was detected in controls and heterozygotes were significantly increased in the patients group compared to homozygotes.Conclusions: MTHFR mutations and the total prevalence of the three gene mutations were significantly increased in the patients group compared to controls. There was a significant increase in the prevalence of combined thrombophilia (Factor V Leiden and MTHFR C677T) in the patients group compared to controls without involvement of prothrombin gene.

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Factor V leiden and Prothrombin Gene Mutations: Differences by Gender

Blood ◽

10.1182/blood.v120.21.5135.5135 ◽

2012 ◽

Vol 120 (21) ◽

pp. 5135-5135

Author(s):

Camila Sahebi ◽

Alice J. Cohen ◽

Mirza Hamza Parvez Mughal

Keyword(s):

Lower Extremity ◽

Gene Mutation ◽

Gene Mutations ◽

Factor V Leiden ◽

Factor V ◽

Vein Thrombosis ◽

Time To Recurrence ◽

History Of ◽

Prothrombin Gene ◽

Deep Vein

Abstract Abstract 5135 Background: Factor V Leiden (FVL) and prothrombin gene mutation (PT) are the most common cause of inherited thrombophilia in Caucasian populations, accounting for 40 to 50 % of cases. The incidence of inherited thrombophilia in subjects with a deep vein thrombosis ranges from 24 to 37 %. Women with factor V Leiden or prothrombin gene mutation have a substantially increased risk of clotting in pregnancy and on estrogen -containing birth control pills or hormone replacement in the form of deep vein thrombosis (DVT) and pulmonary embolism (PE). There have been multiple studies done in regards to thrombophilia in women but few reports specific to the behavior of these mutations in men. Objective: To investigate the difference in clinical presentations of men vs women with Factor V Leiden and prothrombin gene mutations. Methods: A retrospective study of patients (pts) over the age of 18 years (yrs) with FVL and PT mutation with history of thrombosis was conducted. These pts were followed in Comprehensive Hemophilia and Thrombosis Disorder Center at Newark Beth Israel Medical Center (NBIMC). Results: 72 pts with symptomatic diagnoses of FVL or PT mutation were identified. The female to male ratio was (43/17) 2:1. Of the male patients 13/17 (76%) had FVL mutation and 4/17(24%) had PT gene mutation. The mean age was 32 yrs (range18–54 yrs). The majority, 15/17(88%) had a lower extremity DVT; 2/17(12%) had PE at presentation. 13/15(86%) of the DVTs were provoked: 5/13 (38%) had surgery, 5/13(38%) had history of recent travel, 3/13(24%) had history of trauma. Of the male pts 11/17 (65%) of the pts had a family history of thrombophilia. 9/17 (53%) had a second thrombotic event with a mean time of 10 yrs (range 1–30 years). Of the female pts 31/43(72%) were diagnosed with FVL gene mutation and 12/43(28%) with PT mutation. The mean age was 32 yrs (18–79 yrs). Of the females 13/43(30%) presented with pregnancy loss, 11/43(23%) with a provoked lower extremity DVT [ 3/43 (6%) had history of oral contraceptive pills use, 5/43(12%) with recent surgery, 2/43(5%) with pregnancy, 1/43(2%) with travel history], 5/43 (12%) had unprovoked DVT, and 13/43(30%) had other thrombotic events (2/43 (5%)CVA, 1/43 (2%)neck vein thrombosis, 1/43(2%) arteriovenous fistula thrombosis, 6/43 (14%) PE, 1/43(2%)with retinal artery thrombosis, 1/43 (2%) with mesenteric ischemia, and 1/43(2%) with portal vein thrombosis). In this group 21/43(49%) had a family history of thrombophilia. Second events occurred in 8/43(18%) with a mean time to recurrence of 7 yrs (range 1–41 yrs). Conclusion: Clinical presentations in patients with FVL and PT mutations differ between males and females including location, time to recurrence and associated conditions. First events in females included both arterial and venous thrombosis and were predominantly hormone related. In contrast, the most common site of thrombosis in our male pts was a provoked lower extremity venous thrombosis especially post surgery and prolonged travel. Additionally, males had higher recurrent events. Prospective long term outcome studies of patients and their asymptomatic family members are necessary to confirm these differences. Disclosures: No relevant conflicts of interest to declare.

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