Ischemic stroke in a young patient with protein C deficiency and prothrombin gene mutation G20210A

1998 ◽  
Vol 9 (8) ◽  
pp. 757-760 ◽  
Author(s):  
Y. S. Arkel ◽  
D. H. Ku ◽  
D. Gibson ◽  
X. Lam
Keyword(s):  
Ischemic Stroke ◽  
Young Patient ◽  
Gene Mutation ◽  
Protein C ◽  
Protein C Deficiency ◽  
Prothrombin Gene Mutation ◽  
Prothrombin Gene

Prevalence of Inherited and Acquired Thrombophilia in Females Post Multiple Assisted Reproductive Technology (ART) Attempts

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3535-3535
Author(s):  
Hind Rafei ◽  
Hisham Eissa ◽  
Sherif Amin ◽  
Amira Ramzy ◽  
Dalia Mobarek
Keyword(s):  
Gene Mutation ◽  
Protein C ◽  
Protein S ◽  
Homozygous Mutation ◽  
Protein C Deficiency ◽  
Egyptian Women ◽  
Prothrombin Gene Mutation ◽  
Prothrombin Gene ◽  
Homozygous Mutations ◽  
Prophylactic Anticoagulation

Abstract Introduction: A link between thrombophilia and female infertility has been previously reported and the role of thrombophilia in multiple ART failures has been debated. Most meta-analyses of existing studies yield inconclusive and contradictory results that no antithrombotic therapy could, to-date, be indicated in thrombophilia patients with ART failure(s) without clinical thrombosis. As analysis of a large cohort is therefore warranted, we embarked on this study to identify the true prevalence of thrombophilia in a large number of women who presented for infertility and recurrent ART failures evaluation to detect the true prevalence of thrombophilia. Methods: This is an IRB-approved retrospective cohort analysis of Egyptian women with 3 or more ART attempts referred to our center NSA-Diagnostic Laboratories from 1/1/2009 to 1/1/2015. Females with known venous thromboembolism (VTE) prior to infertility evaluation were excluded. Aspirin use and results of thrombophilia testing were collected on all patients. Thrombophilia testing included Factor V Leiden mutation (FVL), prothrombin gene mutation, Plasminogen Activator Inhibitor-1 (PAI-1), Factor XIII level, b-Fib, HPA, ACE, ApoB, ApoE, anticardiolipin IgG and IgM (ACLG, ACLM respectively), Protein C deficiency, Protein S deficiency, antithrombin (AT), lupus anticoagulant (LA), CD16, CD56, methylenetetrahydrofolate reductase (MTHFR) A or C, and homocysteine level. Thrombophilia was categorized into simple and complex reflecting 1 and >1 homozygous mutations detected, respectively. Demographic characteristics and the prevalence of the different mutations were analyzed. Statistical analysis was performed using SPSS software version 20.0. Results: Inclusion criteria and all data were available in 2585 female subjects. Age range was 21-43. While all subjects had at least one or more mutation(s) of any kind, 305 subjects (11.8%) did not have any homozygous mutations. Simple thrombophilia (one homozygous mutation) was found in 894 patients (34.6%). Complex thrombophilia (more than one homozygous mutation) with 2, 3, 4, and 5 concomitant abnormalities was encountered: in 35.8%, 13.5%, 3.9% and 0.4%, respectively. Prevalence of homozygous and heterozygous mutations was as follows: FVL (2.9%; 21.9%), prothrombin gene mutation (0.1%; 4.0%), PAI (17.4%; 67.5%), factor XIII (1.2%; 23.7%), b-Fib (39.2%; 2.7%), HPA (10%; 30%), ACE (49.6%; 49.2%), ApoB (0.1%; 0%), ApoE (62.7%; 21.3%). ACLG was positive in 1.2%, ACLM in 3.6%, Protein C deficiency in 0.4%, Protein S deficiency in 0.2%, AT in 1.0%, LA in 1.8%, CD16 in 0.1%, CD56 in 1.1% and hyperhomocysteinemia in 0.7%. Heterozygous and homozygous MTHFR A (45.1%; 9.8%), MTHFR C (35.3%; 7.7%) mutations were noted. When compared to historical controls in the literature, similar prevalence was found for Protein C/S deficiencies, higher prevalence for FVL and Prothrombin gene mutation, and a lower prevalence for hyperhomocysteinemia in our cohort. No VTE was reported in subjects from the time of testing until data collection and follow up. Prophylactic anticoagulation with low molecular weight heparin and low dose aspirin in subjects were noted. All subjects with successful pregnancies post identification of thrombophilia were prescribed prophylactic anticoagulation with low molecular weight heparin through pregnancy and for 6 weeks postpartum. Low dose aspirin and first trimester steroids were also used. Analysis of full term pregnancy as an outcome is underway. Discussion: Thrombophilia prevalence in infertile Egyptian women presenting to our center with multiple failed ART attempts is higher for certain mutations than reported in the literature. Our cohort is unique in that women did not have a history of clinically evident VTE and had a higher prevalence of complex homozygous mutations. Our study has implications on the evaluation of female patients with infertility and helps set up the stage for future prospective and interventional trials using antithrombotic therapy. Disclosures No relevant conflicts of interest to declare.

scholarly journals Laboratory Investigation of Thrombophilia

2001 ◽  
Vol 47 (9) ◽  
pp. 1597-1606 ◽  
Author(s):  
Armando Tripodi ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Gene Mutation ◽  
Protein C ◽  
Solid Phase ◽  
Factor V Leiden ◽  
Laboratory Diagnosis ◽  
Factor V Leiden Mutation ◽  
Vitamin Deficiencies ◽  
Increased Risk ◽  
Prothrombin Gene Mutation ◽  
Prothrombin Gene

Abstract Until recently, laboratory diagnosis of thrombophilia was based on investigation of the plasmatic anticoagulant pathways to detect antithrombin, protein C, and protein S deficiencies and on the search for dysfibrinogenemia and anti-phospholipid antibodies/lupus anticoagulants. More recently, laboratory investigations have been expanded to include activated protein C (APC) resistance, attributable or not to the presence of the factor V Leiden mutation; hyperprothrombinemia attributable to the presence of the prothrombin gene mutation G20210A; and hyperhomocysteinemia attributable to impairment of the relevant metabolic pathway because of enzymatic and/or vitamin deficiencies. All of the above are established congenital or acquired conditions associated with an increased risk of venous and, more rarely, arterial thrombosis. Testing is recommended for patients who have a history of venous thrombosis and should be extended to their first-degree family members. Because most of the tests are not reliable during anticoagulation, it is preferable to postpone laboratory testing until after discontinuation of treatment. Whenever possible, testing should be performed by means of functional assays. DNA analysis is required for the prothrombin gene mutation G20210A. Laboratory diagnosis for anti-phospholipid antibodies/lupus anticoagulant should be performed by a combination of tests, including phospholipid-dependent clotting assays and solid-phase anti-cardiolipin antibodies. Hyperhomocysteinemia can be diagnosed by HPLC methods or by fluorescence polarization immunoassays.

scholarly journals Association of G20210A Prothrombin Gene Mutation and Cerebral Ischemic Stroke in Young Patients

Cureus ◽  
2020 ◽  
Author(s):  
Sujan Poudel ◽  
Mehwish Zeb ◽  
Varshitha Kondapaneni ◽  
Sai Dheeraj Gutlapalli ◽  
Jinal Choudhari ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Gene Mutation ◽  
Young Patients ◽  
Prothrombin Gene Mutation ◽  
Cerebral Ischemic Stroke ◽  
Prothrombin Gene ◽  
Cerebral Ischemic ◽  
Stroke In Young

Relationship between Uteroplacental Blood Flow snd Thrombophilia in Women eith Late Complicated Pregnancies.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4016-4016
Author(s):  
Delphine Pranger ◽  
Veronique Deneys ◽  
Corinne Hubinont ◽  
Pierre Bernard ◽  
Frederic Debieve ◽  
...  
Keyword(s):  
Blood Flow ◽  
Gene Mutation ◽  
Pregnancy Complications ◽  
Protein C ◽  
Late Pregnancy ◽  
Anticardiolipin Antibodies ◽  
Obstetrical Complications ◽  
Uteroplacental Blood Flow ◽  
Prothrombin Gene Mutation ◽  
Prothrombin Gene

Abstract There is a growing body of evidence that thrombophilia is linked to several obstetrical complications, most likely through uteroplacental vascular insufficiency. Very few studies have however evaluated whether alterations of the uteroplacental blood flow, as assessed functionally by Doppler ultrasound analysis, are associated with thrombophilic abnormalities in women with late pregnancy complications. Forty-nine non-smoking women followed during their whole pregnancy in the High Risk Pregnancy Clinic of the Cliniques Universitaires Saint-Luc, Brussels, in 2003 were enrolled in this retrospective study. They all had an unexplained late pregnancy complication (intrauterine growth retardation (IUGR) (n=34), intrauterine fetal death (IUFD) (n=4), preeclampsia (n=11)). They were not treated with anti-thrombotic agents. They all had a complete thrombophilic work-up (functional antithrombin, protein C and S assays, homocystein level, antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies), activated protein C resistance, G20210A prothrombin gene mutation). Doppler evaluation of the uterine arteries (assessed by the presence of bilateral notches after 26 weeks) and umbilical arteries (assessed by resistance index above 90th percentile) was performed. Thrombophilic abnormalities were identified in 8 of 49 (16%) women (factor V Leiden (FVL) (n=4), G20210A prothrombin gene mutation (n=2) and isolated anticardiolipin antibodies (n=2)). Of the 49 women, 20 had an abnormal Doppler (uterine (n=5) and umbilical (n=15)) including IUGR (n=13), IUFD (n=2) and preeclampsia (n=5). Four women with thrombophilia were found to have Doppler abnormalities (4/20; 20%) while most women with Doppler alterations had no thrombophilia. In conclusion, abnormal uteroplacental Doppler findings are frequently found in women with late pregnancy complications. They do not seem to be correlated with the presence of thrombophilic abnormalities even if thrombophilia seems to be more frequent in obstetrical complications.

Abstract 223: Acute Ischemic Stroke in a 23-Year-Old Patient with Verrucous Endocarditis, Prothrombin Heterozygote Mutation, and a Patent Foramen Ovale: A Case Report and Literature Review

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
George Samuel ◽  
Qi Shi ◽  
Lisa Thomas ◽  
Timothy Burke ◽  
Huimin Wu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Case Report ◽  
Acute Ischemic Stroke ◽  
Gene Mutation ◽  
Patent Foramen Ovale ◽  
Anticoagulation Therapy ◽  
The United States ◽  
Foramen Ovale ◽  
Prothrombin Gene Mutation ◽  
Prothrombin Gene

Background Stroke is the third leading cause of death and the leading cause of severe, long-term disability in the United States. Since the etiology of stroke in young adults is more heterogeneous, making a diagnosis is often a challenge requiring extensive clinical investigation. We report a case of acute ischemic stroke in a 23 year-old patient with multiple risk factors. Case Report A 23 year-old Spanish female with a history of tobacco abuse was brought to the Emergency room after she had a sudden onset of left-side weakness, slurring of speech, and lost of consciousness for a couple of minutes. Physical examination: left upper and lower extremities were completely flaccid with left facial weakness. MRI of head confirmed a right middle cerebral artery regional acute ischemic stroke. Transesophageal Echocardiogram revealed small granular densities on the mitral leaflets that consistent with atypical verrucous endocarditis and a patent foramen ovale (PFO). Hypercoagulable evaluation confirmed prothrombin gene mutation heterozygote. The erythrocyte sedimentation rate (ESR) was 75 mm/hour. All other tests were either negative or in normal range. Anticoagulation therapy was started with Heparin and then switched to Coumadin with an INR target of 2.5. Aspirin was also initiated. Discussion The differential diagnosis in young people (under 50 years) for potential etiology of ischemic stroke is broader than that for older adults. Atypical causes are more prevalent in this population, including cardiogenic cerebral embolus, hypercoagulable states, and autoimmune disease. Verrucous endocarditis is small thrombotic and nonbacterial lesions on the heart valves and endocardium, occurring frequently in systemic lupus erythematosus (SLE). However, hypercoagulable states and malignancy are often associated with the formation of verrucous endocarditis. Lesions are usually clinically silent. An embolic stroke may be the first feature to suggest the diagnosis. Since there was no evidence in malignancy, SLE, and antiphospholipid syndrome for our patient, hypercoagulable states should be considered as one of the risks for verrucous endocarditis. About 1-2% of the general population is heterozygous for the prothrombin gene mutation. In contrast, in Spain rates of 6% have been reported. It carries a 2 to 4 times increase in venous thrombosis and also increases the risk of arterial thrombosis (stroke and heart attack). Additionally, studies also show that inherited thrombophilic disorders in the pathogenesis of ischemic stroke might relate to congenital heart diseases such as Prothrombin G20210A variant and Factor V Leiden G1691A mutation might be associated with PFO. The prevalence of PFO in patients who have stroke of unknown cause may be about 40%. PFO also increases the rate of paradoxical thromboembolic stroke. This is particularly true in patients who have had a stroke at an age less than 50 years. Since our patient presents multiple risks for recurrent ischemic stroke, life-long anticoagulant therapy should be considered. Conclusion Acute ischemic stroke in a 23-years-old patient with verrucous endocarditis, prothrombin heterozygote mutation, and a PFO, but absent SLE has been rarely reported. Beside, the authors conclude that hypercoagulable testing and echocardiogram should be performed in young patients with stroke in order to provide us a better understanding of the etiology and the best treatment options.

scholarly journals Prothrombin Gene G20210A Mutation in Acute Deep Venous Thrombosis Patients with Poor Response to Warfarin Therapy

2009 ◽  
Vol 3 (1) ◽  
pp. 147-151 ◽  
Author(s):  
F.M. Attia ◽  
D.P. Mikhailidis ◽  
S.A. Reffat
Keyword(s):  
Family History ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Gene Mutation ◽  
Protein C ◽  
Poor Response ◽  
G20210a Mutation ◽  
History Of ◽  
Prothrombin Gene Mutation ◽  
Prothrombin Gene

Aim: The pathogenesis of deep venous thrombosis (DVT) involves an interaction between hereditary and acquired factors. Prothrombin gene mutation is one of the hereditary risk factors. We evaluated the frequency of the prothrombin gene mutation in patients with DVT and its relation to oral warfarin anticoagulant therapy response.Methods: Prothrombin gene mutation was looked for in 40 DVT patients with poor response to warfarin. The results were compared with 40 DVT patients with a normal response to warfarin and 30 healthy blood donors. Blood samples were also assessed for protein C, protein S, anti-thrombin III and anticardiolipin antibodies (ACA) levels.Results: Prothrombin gene mutation was found in normal and poor DVT responders (6/40 and 13/40, respectively; p = NS) as well as in healthy controls (1/30). Patients with recurrent DVT or a family history of DVT were significantly (p<0.0001) more likely to have the prothrombin mutation than other DVT patients. Non prothrombin abnormalities (protein C, anti-thrombin III and ACA) were more common in poor responders than controls (p<0.0037) as were ACA (p<0.034).Conclusions: Prothrombin gene mutation is present in several DVT patients, especially those with recurrent DVT or a family history of DVT. This mutation may contribute to a poor response to warfarin.

scholarly journals Protein C Gene Mutation in an Older Adult Patient with Clostridium perfringens Septicemia-Related Visceral Vein Thrombosis

TH Open ◽  
2021 ◽  
Vol 05 (02) ◽  
pp. e171-e173
Author(s):  
Kiyoko Kanosue ◽  
Satomi Nagaya ◽  
Eriko Morishita ◽  
Masayoshi Yamanishi ◽  
Shinsaku Imashuku
Keyword(s):  
Gene Mutation ◽  
Clostridium Perfringens ◽  
Protein C ◽  
Later Life ◽  
Heterozygous Mutation ◽  
Protein C Deficiency ◽  
Vein Thrombosis ◽  
Thrombosis Risk ◽  
Japanese Male ◽  
Old Japanese

AbstractA 78-year-old Japanese male with Clostridium perfringens septicemia and cholecystitis was found to have thrombosis in the left branch of intrahepatic portal vein as well as superior mesenteric vein. Visceral vein thrombosis (VVT) in this case was associated with protein C deficiency, due to a heterozygous mutation, p. Arg185Met. Our experience emphasizes that VVT, or other thromboembolic events, may occur in later life, triggered by environmental thrombosis risk factors, together with underlying hereditary protein C gene mutation.

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