Idiopathic venous thromboembolism and thrombophilia (original) (raw)
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Arteriosclerosis, Thrombosis, and Vascular Biology, 1999
The inherited thrombophilias-deficiencies of protein C, protein S, and antithrombin III-and the prothrombotic polymorphisms factor V G1691A and factor II G20210A predispose patients toward venous thromboembolism (VTE). The aim of this study was to determine the prevalence of single and combined prothrombotic factors in patients with idiopathic VTE and to estimate the associated risks. The study group consisted of 162 patients referred for work-up of thrombophilia after documented VTE. The controls were 336 consecutively admitted patients. In all subjects factor V G1691A, factor II G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T were analyzed by specific polymerase chain reactions and restriction enzymes. Activities of antithrombin III and protein C, free protein S antigen, and lupus anticoagulant were determined in a subset of 109 patients who were not receiving oral anticoagulants. The prevalences of heterozygotes and homozygotes for factor V G1691A and factor II G20210A among patients and controls were 40.1% versus 3.9% and 18.5% versus 5.4%, respectively (Pϭ0.0001). The prevalence of homozygotes for MTHFR C677T in patients was 22.8% and in controls, 14.3% (Pϭ0.025). Heterozygous and homozygous factor V G1691A, factor II G20210A, and homozygous MTHFR C677T were found to be independent risk factors for VTE, with odds ratios of 16.3, 3.6, and 2.1, respectively. Two or more polymorphisms were detected in 27 of 162 patients (16.7%) and in 3 of 336 controls (0.9%). Logistic regression analysis disclosed odds ratios of 58.6 (confidence interval [CI], 22.1 to 155.2) for joint occurrence of factor V and factor II polymorphisms, of 35.0 (CI, 14.5 to 84.7) for factor V and MTHFR polymorphisms, and of 7.7 (CI, 3.0 to 19.6) for factor II and MTHFR polymorphisms. Among 109 patients in whom a complete thrombophilic work-up was performed, 74% had at least 1 underlying defect. These data indicate that in most patients referred for evaluation of thrombophilia due to idiopathic VTE, 1 or more underlying genetic predispositions were discernible. The presence of Ͼ1 of the prothrombotic polymorphisms was associated with a substantial risk of VTE. (Arterioscler Thromb Vasc Biol. 1999;19:511-518.) Key Words: thrombophilia Ⅲ factor V G1691A (Leiden) Ⅲ factor II G20210A Ⅲ methylenetetrahydrofolate reductase Ⅲ venous thromboembolism
Antiphospholipid antibodies and recurrent thrombosis after a first unprovoked venous thromboembolism
Blood, 2018
The same type of APA on 2 occasions or >1 type of APA on the same or different occasions is associated with recurrent VTE. l APA and D-dimer levels seem to be independently associated with recurrence after a first unprovoked VTE. It is uncertain whether antiphospholipid antibodies (APAs) increase the risk of recurrence after a first unprovoked venous thromboembolism (VTE). We tested for anticardiolipin antibodies, anti-b2 glycoprotein 1 antibodies, and lupus anticoagulant on 2 occasions ∼6 months apart in 307 patients with a first unprovoked VTE who were part of a prospective cohort study. We then determined if APAs were associated with recurrent thrombosis in the 290 patients who stopped anticoagulant therapy in response to negative D-dimer results. Compared with those without an APA, the hazard ratios for recurrent VTE were 1.8 (95% confidence interval [CI], 0.9-3.7; P 5 .09) in the 25.9% of patients with an APA on ‡1 occasions, 2.7 (95% CI, 1.1-.7; P 5 .03) in the 9.0% of patients with the same APA on 2 occasions, and 4.5 (95% CI, 1.5-13.0; P 5 .006) in the 3.8% of patients with 2 or 3 different APA types on either the same or different occasions. There was no association between having an APA and D-dimer levels. We conclude that having the same type of APA on 2 occasions or having >1 type of APA on the same or different occasions is associated with recurrent thrombosis in patients with a first unprovoked VTE who stop anticoagulant therapy in response to negative D-dimer tests. APA and D-dimer levels seem to be independent predictors of recurrence in patients with an unprovoked VTE. This trial was registered at www.clinicaltrials.gov as #NCT00720915.
Should Patients with Venous Thromboembolism Be Screened for Thrombophilia?
The American Journal of Medicine, 2008
In the mid-19th century, Virchow identified hypercoagulability as part of the triad leading to venous thrombosis, but the specific causes of hypercoagulability remained a mystery for another century. The first specific cause to be identified was antithrombin III deficiency. Many other causes of thrombophilia, both genetic and acquired, have been discovered since then. The 2 most common genetic causes of thrombophilia are the Leiden mutation of factor V and the G20210A mutation of prothrombin. The most common acquired cause is antiphospholipid syndrome. These factors increase the relative risk of an initial episode of venous thromboembolism (VTE) by a factor of 2 to 10, but the actual risk remains relatively modest. Therefore, thrombophilia screening to prevent initial episodes of VTE is not indicated, except possibly in women with a family history of idiopathic VTE who are considering oral contraceptive therapy. Some physicians screen for thrombophilia to aid decision making concerning the duration of anticoagulant therapy. However, several studies have demonstrated that, with the exception of antiphospholipid syndrome, thrombophilia does not significantly increase the risk of recurrent VTE. On the other hand, idiopathic VTE significantly increases the risk of recurrence in patients with or without thrombophilia.
Antiphospholipid antibodies and venous thromboembolism
Blood, 1995
The clinical relevance of antiphospholipid antibodies (APLA) in patients without systemic lupus erythematosus who have venous thromboembolism (VTE) in unknown. Limited evidence suggests that there is an association between the presence of APLA and both initial and recurrent episodes of VTE and that patients with APLA and VTE are resistant to warfarin therapy. Unselected patients with a first episode of clinically suspected deep vein thrombosis or pulmonary embolism were evaluated with objective tests for VTE and with laboratory tests for APLA; the latter included tests for the lupus anticoagulant (LA) and anticardiolipin antibodies (ACLA). Patients with VTE were treated with anticoagulant therapy and observed during and after discontinuation of anticoagulants for symptomatic recurrence of VTE. There was a strong association between LA and VTE (odds ratio, 9.4; 95% confidence interval [CI], 2.1 to 46.2) and 9 to 65 (14%; 95% CI, 7% to 25%) patients with VTE had LA. There was no assoc...
Blood Reviews, 2018
Direct oral anticoagulants (DOACs) are indicated in the treatment and prevention of venous thromboembolism (VTE). However, the use of DOACs in unusual VTE, including cerebral venous thrombosis (CVT) and splanchnic venous thrombosis (SVT), and in patients with biological thrombophilia including minor thrombophilia (Factor V Leiden and prothrombin G20210A), major innate thrombophilia (protein C and S deficiency, and antithrombin) and major acquired thrombophilia (antiphospholipid syndrome [APS]), remains controversial due to the paucity of available data. There are some reports of DOACs use in the initial treatment or long-term maintenance of patients with either CVT or SVT, but their efficacy remains unclear. The efficacy of DOACs may be suitable in patients with biological minor or major thrombophilia. The use of DOACs for the long-term maintenance of patients with APS is more contentious. Randomized clinical trials, which are currently underway, should offer definitive insight into the efficacy and safety profiles of DOACs in these patient populations.
Annals of vascular surgery, 2017
Superficial vein thrombosis is a common venous condition. Recent studies have shown that SVT is associated with high frequency of thromboembolic complications: from 22 to 37 % for deep venous thrombosis and up to 33% for pulmonary embolism. To assess the prevalence of major hereditary and acquired thrombophilic factors in patients with SVT. 66 patients presenting with primary ST underwent evaluation for thrombophilia: molecular testing for the factor V Leiden and factor II G20210A (prothrombin) mutations, protein C, protein S, antithrombin deficiency, presence of lupus anticoagulant, as well as anti-cardiolipin antibody titers. Patients under 18 years old, with confirmed deep vein thrombosis, and pregnant women were excluded. 95.5% were caucasian and 62.1% of female gender. Age ranged from 21 to 88 years. Molecular testing showed that 34.2% of patients were heterozygous for factor V Leiden, 23.6% were heterozygous for the factor II mutation, 7.8% had antithrombin deficiency, 2.6% ha...
Antiphospholipid Antibodies in Venous Thromboembolism Patients Younger than 50 Years Old
2010
Background: Antiphospholipid antibodies are among the most important risk factors of arterial and venous thrombosis. Various studies have demonstrated that these antibodies are seen in patients with deep vein thrombosis (DVT) and pulmonary embolism (PE) more than normal individuals but there are a few studies about prevalence of these antibodies in patients younger than 50 years old with venous thromboembolism (VTE). This study aimed to evaluate these antibodies in this age group. Materials and Methods: This was a case-control study. Fifty patients younger than 50 years old with venous thromboembolism (DVT, PE or both) who were diagnosed according to the standard criteria were compared with 48 subjects in the control group. Subjects in the control group were age and sex matched with patients and had no history of venous thromboembolism. Both groups had no history of malignancy or other chronic diseases. Lupus anti-coagulant and serum anticardiolipin antibodies (IgG and IgM) were measured in both groups. Data were analyzed using SPSS version 11.5 software. Results: Fifty VTE patients younger than 50 years of age enrolled in this study (28 males and 22 females; mean age: 38.14±6.5 yrs). Forty-eight subjects were selected as healthy controls (27 males and 21 females; mean age: 38.35±5.06 yrs). Mann-Whitney test showed a significant difference between serum IgM anticardiolipin antibody levels of VTE patients (8.04 MPL units/ml) and those of healthy subjects (1.85 MPL units/ml) (P=0.001).Also, a significant difference was found between serum IgG anticardiolipin antibody levels of VTE patients (8.29 GPL units/ml) and those of healthy subjects (3.51 GPL units/ml) (P=0.001). In VTE group, 7 patients (M/F = 4/3) had an IgG level >10 GPL units/ml and 6 patients (M/F =2/4) had an IgM level >10 MPL units/ml while none of the healthy subjects had IgG or IgM levels higher than 10 (PIgM=0.015 and PIgG=0.007). Lupus anti-coagulant was positive in four (8%) but negative in all healthy subjects (P=0.04). Conclusion: This study demonstrated that antiphospholipid antibodies were more prevalent in VTE patients younger than 50 years old compared to healthy subjects. Considering the fact that these patients need stronger and longer treatment, it seems necessary to evaluate every VTE patient younger than 50 yrs for antiphospholipid syndrome.
Risk factors associated with thrombosis in patients with antiphospholipid antibodies
The Journal of rheumatology, 2001
To define risk factors associated with thrombosis in patients with antiphospholipid antibodies (aPL). Ninety-nine patients with aPL, most of whom had prior thrombosis, were evaluated for the presence of acquired and inherited thrombophilic states. Genomic testing was performed for factor V(R506Q), 3' prothrombin (PTG) and methylene tetrahydrofolate reductase (MTHFR) polymorphisms. Clinical records were reviewed for the presence of acquired risk factors (RF) for thrombosis and events associated with aPL. Univariate statistical analysis was performed using Fisher's exact testing. A neural network statistical model was also used to identify which thrombophilic risk factors were most important in development of arterial and venous thrombosis. For arterial thrombosis, hypertension, tobacco use, hyperlipidemia, and diabetes mellitus were the most important predictors of thrombosis. By contrast, tobacco use, the 3' PTG and factor V(R506Q) polymorphisms, and previous cardiac sur...