Thrombophilic Genotypes in Subjects with Idiopathic Antiphospholipid Antibodies – Prevalence and Significance

1998 ◽  
Vol 79 (01) ◽  
pp. 46-49 ◽  
Author(s):  
Catello Tommasino ◽  
Giovanna D’Andrea ◽  
Luigi Iannaccone ◽  
Vincenzo Brancaccio ◽  
Maurizio Margaglione ◽  
...  
Keyword(s):  
Antiphospholipid Antibodies ◽  
Healthy Subjects ◽  
Methylenetetrahydrofolate Reductase ◽  
Thrombotic Event ◽  
Significant Proportion ◽  
Factor V ◽  
Vein Thrombosis ◽  
History Of ◽  
Fv Leiden

SummaryTo evaluate the significance of common thrombophilic genotypes in subjects with idiopathic antiphospholipid antibodies (aPL) we determined the methylenetetrahydrofolate reductase C677→ (MTHFR) and factor V A506→ G (FV Leiden) polymorphisms in 49 subjects with idiopathic aPL (57% of whom suffered spontaneous vein thrombosis), in 70 subjects with a history of spontaneous vein thrombosis and in 193 healthy subjects. The prevalence of MTHFR C677→+/+ (homozygotes) was 25%, 18% and 17% respectively amongst aPL thrombotics, non aPL thrombotics and controls and that of MTHFR C677→+/– (heterozygotes) was 53%, 59% and 53% respectively in the same groups. The prevalence of FV Leiden was higher in aPL thrombotics (14%) and in non aPL thrombotics (18%) than in controls (4%) (p ≤ = 0.05). APL thrombotics with MTHFR C677→+/+ had a lower mean age at first thrombotic event (22 ± 6 years) than aPL thrombotics with MTHFR C677→+/– and non mutated considered together (38 ± 14 years, p = 0.0004) and than non aPL thrombotics with MTHFR C677→+/+ (38 ± 14 years, p = 0.003). FV Leiden may con tribute to the hypercoagulability of a small, albeit significant proportion of thrombotic aPL subjects, whereas the association between MTHFR C677→+/+ and aPL may have an impact on age at first occlusive event and suggests a possible pathogenetic interaction.

scholarly journals Molecular Analysis of Prothrombotic Gene Variants in Venous Thrombosis: A Potential Role for Sex and Thrombotic Localization

2020 ◽  
Vol 9 (4) ◽  
pp. 1008
Author(s):  
Gustavo Cernera ◽  
Alessandro Di Minno ◽  
Felice Amato ◽  
Ausilia Elce ◽  
Renato Liguori ◽  
...  
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Large Population ◽  
Thrombotic Event ◽  
Factor V Leiden ◽  
Cerebral Vein ◽  
Gene Variants ◽  
Clinical Context ◽  
Vein Thrombosis ◽  
Superficial Vein Thrombosis ◽  
History Of

Background: Requests to test for thrombophilia in the clinical context are often not evidence-based. Aim: To define the role of a series of prothrombotic gene variants in a large population of patients with different venous thromboembolic diseases. Methods: We studied Factor V Leiden (FVL), FVR2, FII G20210A, Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, beta-fibrinogen -455 G>A, FXIII V34L, and HPA-1 L33P variants and PAI-1 4G/5G alleles in 343 male and female patients with deep vein thrombosis (DVT), 164 with pulmonary embolism (PE), 126 with superficial vein thrombosis (SVT), 118 with portal vein thrombosis (PVT), 75 with cerebral vein thrombosis (CVT) and 119 with retinal vein thrombosis (RVT), and compared them with the corresponding variants and alleles in 430 subjects from the general population. Results: About 40% of patients with DVT, PE and SVT had at least one prothrombotic gene variant, such as FVL, FVR2 and FII G20210A, and a statistically significant association with the event was found in males with a history of PE. In patients with a history of PVT or CVT, the FII G20210A variant was more frequent, particularly in females. In contrast, a poor association was found between RVT and prothrombotic risk factors, confirming that local vascular factors have a key role in this thrombotic event. Conclusions: Only FVL, FVR2 and FII G20210A are related to vein thrombotic disease. Other gene variants, often requested for testing in the clinical context, do not differ significantly between cases and controls. Evidence of a sex difference for some variants, once confirmed in larger populations, may help to promote sex-specific prevention of such diseases.

scholarly journals Idiopathic pulmonary embolism in a case of severe family ANKRD26 thrombocytopenia

2017 ◽  
Vol 9 (1) ◽  
pp. e2017038 ◽  
Author(s):  
Jérôme Guison ◽  
Gilles Blaison ◽  
Oana Stoica ◽  
Remy Hurstel ◽  
Marie Favier ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Heterozygous Mutation ◽  
Severe Thrombocytopenia ◽  
Factor V ◽  
Vein Thrombosis ◽  
First Case ◽  
History Of ◽  
Fv Leiden ◽  
Deep Vein

Venous thrombosis affecting thrombocytopenic patients is challenging. We report the case of a thrombocytopenic woman affected by deep vein thrombosis and pulmonary embolism leading to the discovery of a heterozygous mutation in the gene encoding ankyrin repeat domain 26 (ANKRD26) associated with a heterozygous factor V (FV) Leiden mutation. This woman was diagnosed with left lower-limb deep vein thrombosis complicated by pulmonary embolism. Severe thrombocytopenia was observed. The genetic study evidenced a heterozygous FV Leiden mutation. Molecular study sequencing was performed after learning that her family had a history of thrombocytopenia. Previously described heterozygous mutation c-127C>A in the 5′ untranslated region (5′UTR) of the ANKRD26 gene was detected in the patient, her aunt, and her grandmother. ANKRD26-related thrombocytopenia and thrombosis are rare. This is, to our knowledge, the first case reported in the medical literature. This mutation should be screened in patients with a family history of thrombocytopenia.

Factor V Leiden Is Associated with Repeated and Recurrent Unexplained Fetal Losses

1997 ◽  
Vol 77 (05) ◽  
pp. 0822-0824 ◽  
Author(s):  
Elvira Grandone ◽  
Maurizio Margaglione ◽  
Donatella Colaizzo ◽  
Marina d'Addedda ◽  
Giuseppe Cappucci ◽  
...  
Keyword(s):  
Protein C ◽  
Strong Association ◽  
Activated Protein C ◽  
Fetal Loss ◽  
Factor V Leiden ◽  
Factor V ◽  
Significant Difference ◽  
History Of ◽  
Fv Leiden ◽  
Caucasian Women

SummaryActivated protein C resistance (APCR) is responsible for most cases of familial thrombosis. The factor V missense mutation Arg506>Gln (FV Leiden) has been recognized as the commonest cause of this condition. Recently, it has been suggested that APCR is associated with second trimester fetal loss. We investigated the distribution of FV Leiden in a sample (n = 43) of Caucasian women with a history of two or more unexplained fetal losses. A group (n = 118) of parous women with uneventful pregnancies from the same ethnical background served as control. We found the mutation in 7 cases (16.28%) and 5 controls (4.24%; p = 0.011). A statistically significant difference between women with only early fetal loss vs those with late events (p = 0.04) was observed. Our data demonstrate a strong association between FV Leiden and fetal loss. Furthermore, they indicate that late events are more common in these patients.

The Natural History of Idiopathic Erythrocythosis: A Cohort Study of 74 Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1506-1506
Author(s):  
Finazzi Guido ◽  
Ruggeri Marco ◽  
Marconi Monica ◽  
Rodeghiero Francesco ◽  
Barbui Tiziano
Keyword(s):  
Cohort Study ◽  
Deep Vein Thrombosis ◽  
Natural History ◽  
Thrombotic Event ◽  
Previous History ◽  
Full Blood Count ◽  
Vein Thrombosis ◽  
History Of ◽  
Thrombotic Complications ◽  
Deep Vein

Abstract Patients with absolute erythrocytosis not due to a detectable cause and not fulfilling the criteria for diagnosis of polycythemia vera (PV) are descriptively classified as Idiopathic Erythrocytosis (IE). Based on scanty and retrospective data, this disease is considered to be an heterogeneous entity, including “early” PV, unrecognized secondary erythrocytosis and other miscellaneous conditions. However, appropriate prospective studies to evaluate the natural history of patients with IE are not available. We report here the results of a cohort study of 74 patients with IE (66 males, 8 females, median age 56 years, range 14–82) followed in two Italian institutions. By definition, at baseline all IE patients had increased hematocrit (median 54%, range 48–68%) and increased red blood cell mass (> 25% above mean normal predicted value), but normal leukocyte (median values 8.1 x 109/L, range 2.3–12) and platelet counts (median values 197 x 109/L, range 117–467), as well as normal erythropoietin level, arterial O2 saturation, chest X ray and abdominal ultrasound scanning (i.e. no splenomegaly). Granulocyte PRV-1 expression was also normal in 29 patients (39%) analyzed. At diagnosis, 12 patients (16%) reported a previous history of major thrombosis (7 ischemic cardiopathies, 4 cerebral ischemic events and 1 deep vein thrombosis). All IE patients were treated with phlebotomy to maintain a target hematocrit <45% and 24 patients (32%) were given aspirin, 100 mg/die, for previous thrombosis or microvascular symptoms. No cytotoxic drugs were given. The IE cohort was followed in the outpatient clinic with physical examination and full blood count at least every three months for a median period of 3.5 years (range 1–23). Twentythree patients (31%) were followed for more than 8 years. No patient was lost to follow-up. During the observation period, no disease potentially associated with secondary eryhtrocytosis emerged and no hematological transition into overt PV, myelofibrosis or acute leukemia occurred; two patients had a major thrombotic event (1 cerebral ischemia and 1 deep vein thrombosis) with an estimated incidence of thrombotic complications of 0.8% patient-year. The incidence of thrombosis was significantly lower than observed in 205 patients with overt PV followed during the same period in one of the two institutions (Bergamo, 3.49% patient-year, p<0.05). This study indicates that: a. the natural history of patients with IE, at least in the first years, is characterized by a remarkable and unexpected homogeneity without appearance of overt PV or diseases associated with secondary erythrocythosis; b. the diagnosis of IE identifies a group of absolute erythrocythoses at lower risk of thrombotic complications not requiring cytotoxic drug therapy; c. the diagnostic work-up of patients with absolute erythrocythosis should carefully distinguish IE from PV because the natural history and management of the two diseases is different.

Findings of Thrombophilia Evaluation and Impact On Management in Asymptomatic Children with a Proximate Family History of Early Thromboembolism: An Institutional-Based Prospective Inceptional Cohort Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1289-1289
Author(s):  
Meghan J. Calhoon ◽  
Elizabeth Pounder ◽  
Marilyn J. Manco-Johnson ◽  
Neil A. Goldenberg
Keyword(s):  
Cohort Study ◽  
Family History ◽  
Laboratory Evaluation ◽  
Antiphospholipid Antibody ◽  
Factor V ◽  
Oral Contraceptive Pills ◽  
Asymptomatic Children ◽  
History Of ◽  
Fv Leiden ◽  
Thrombophilia Testing

Abstract Abstract 1289 Poster Board I-311 ABSTRACT Background and Objective Although the overall incidence of venous thromboembolism (VTE) is low in children, risk is greatly increased by a proximate family history of early TE. The principal aims of the present study were to determine among such children: (1) the prevalence of thrombophilia; and (2) the frequency of recommended changes in management resulting from thrombophilia evaluation. Methods Laboratory thrombophilia investigation was performed in 56 children (≤ 18 years of age) with a first- or second-degree family history of TE before age 55 years, but without personal history of TE, who were consecutively enrolled in an institutional-based prospective inceptional cohort study of pediatric thrombosis/thrombophilia between March 1, 2006 and June 1, 2009. VTE risk factors, family history, thrombophilia findings, and management recommendations were systematically collected. Results The frequencies of all thrombophilia traits were higher than expected for the general population; factor V (FV) Leiden, elevated factor VIII activity, elevated lipoprotein(a) concentration, and antiphospholipid antibody positivity were most common (Figure 1). Among 32 children who underwent complete laboratory evaluation, 34% had ≥2 traits (Figure 2). Thrombophilia testing led to a change in recommended management in 71% of subjects, principally consisting of transient anticoagulant prophylaxis during periods of heightened clinical risk for VTE. Furthermore, recommendation against future use of estrogen-containing oral contraceptive pills was made in 32% of females based upon FV Leiden testing alone, as compared to 64% in whom additional laboratory evaluation was performed (P=0.02). Conclusions Multi-trait thrombophilia is common among asymptomatic children who have a proximate family history of early TE. In this cohort study, comprehensive thrombophilia testing in such children informed future use of estrogen-containing oral contraceptives among females, and often resulted in a recommendation for antithrombotic prophylaxis during high-risk situations. Future studies should evaluate the safety and efficacy of risk-stratified primary prevention strategies for pediatric VTE. Disclosures Manco-Johnson: Baxter BioScience: Honoraria; Bayer HealthCare: Honoraria; CSL Behring: Honoraria; NovoNordisk: Honoraria; Octapharma: Honoraria.

Obstetrical history of women with cerebral vein thrombosis: outcome of the pregnancies before and after the thrombotic event

2017 ◽  
Vol 12 (7) ◽  
pp. 941-945 ◽  
Author(s):  
Daniela Poli ◽  
Caterina Cenci ◽  
Sophie Testa ◽  
Oriana Paoletti ◽  
Elena Silvestri ◽  
...  
Keyword(s):  
Thrombotic Event ◽  
Cerebral Vein ◽  
Cerebral Vein Thrombosis ◽  
Vein Thrombosis ◽  
Before And After ◽  
History Of

Fibrinolysis in patients with the 1691 G→A mutation in factor V gene and history of deep vein thrombosis

1997 ◽  
Vol 11 (4) ◽  
pp. 201-207 ◽  
Author(s):  
M. Stegnar ◽  
P. Peternel ◽  
P. Uhrin ◽  
T. Cvelbar-Marinko ◽  
K. Goršič-Tomažic ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Factor V ◽  
Vein Thrombosis ◽  
History Of ◽  
Factor V Gene ◽  
V Gene ◽  
Deep Vein

Bilateral renal vein thrombosis and venous sinus thrombosis in a neonate with factor V mutation (FV Leiden)

1998 ◽  
Vol 132 (1) ◽  
pp. 159-161 ◽  
Author(s):  
Martin Pohl ◽  
Lothar B. Zimmerhackl ◽  
Florian Heinen ◽  
Anton H. Sutor ◽  
Reinhard Schneppenheim ◽  
...  
Keyword(s):  
Renal Vein ◽  
Sinus Thrombosis ◽  
Renal Vein Thrombosis ◽  
Venous Sinus ◽  
Factor V ◽  
Venous Sinus Thrombosis ◽  
Vein Thrombosis ◽  
Fv Leiden

scholarly journals Molecular Analysis of Factor V Leiden, Factor V Hong Kong, Factor II G20210A, Methylenetetrahydrofolate Reductase C677T, and A1298C Mutations Related to Turkish Thrombosis Patients

2007 ◽  
Vol 13 (4) ◽  
pp. 435-438 ◽  
Author(s):  
Bilgen Dölek ◽  
Serpil Eraslan ◽  
Sevim Eroğlu ◽  
Belgin Eroglu Kesim ◽  
Turgut Ulutin ◽  
...  
Keyword(s):  
Hong Kong ◽  
Methylenetetrahydrofolate Reductase ◽  
Factor V Leiden ◽  
Mthfr C677t ◽  
Enzyme Analysis ◽  
Restriction Enzyme Analysis ◽  
Factor V ◽  
Conformation Analysis ◽  
Factor Ii ◽  
Fv Leiden

Inherited gene disorders related to the hemostatic system have been documented as risk factors for thrombosis. The roles of factor V Hong Kong (FV Hong Kong), factor V Leiden (FV Leiden), factor II G20210A (FII G20210A), methylenetetrahydrofolate reductase (MTHFR) C677T, and MTHFR A1298C mutations in Turkish patients with thrombosis (270 patients) compared with healthy controls (114 subjects) were evaluated. Polymerase chain reaction—based restriction enzyme analysis was carried out to screen these mutations, and single-strand conformation analysis was established to identify variations using the primers selected for restriction enzyme analysis studies. As a result, a significant relationship was determined among FV Leiden, FII G20210A, and thrombosis. The FV Hong Kong mutation was observed in only 2 patients with pulmonary vein thrombosis who are FV Leiden/FV Hong Kong compound heterozygous for FV gene. MTHFR C677T and A1298C were equally distributed in the patient group compared with the control group. All named mutations were also identified with single-strand conformation analysis, but a new variant/polymorphism during studies was not found. Because some inherited abnormalities are associated with thromboembolic disorders, determining the mutations and gene-to-gene interactions in patients with thrombosis history has a great impact on diagnosis and treatment of these diseases.

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