Predicting the risk of recurrent venous thromboembolism

2013 ◽  
Vol 33 (03) ◽  
pp. 201-209 ◽  
Author(s):  
L. Eischer ◽  
P. A. Kyrle
Keyword(s):  
Venous Thromboembolism ◽  
Vena Cava ◽  
Factor V Leiden ◽  
Recurrence Risk ◽  
Clotting Factor ◽  
Factor V ◽  
Vein Thrombosis ◽  
Increased Risk ◽  
Thrombophilia Screening ◽  
Recurrent Vte

SummaryVenous thromboembolism (VTE) is a disease, which often recurs. The recurrence risk is highest in patients with unprovoked proximal deep-vein thrombosis (VT) or pulmonary embolism. Men have a higher risk than women. The risk is low in patients with VTE related to a temporary risk factor such as surgery or estrogen use. Other risk factors include overweight, post-thrombotic syndrome, history of VTE, residual VT or a vena cava filter.Both factor V Leiden and the prothrombin mutation confer a negligible increase in recurrence risk. High clotting factor levels, deficiency of a natural coagulation inhibitor, or hyperhomocysteinaemia are also associated with an increased risk. Reasons why routine laboratory thrombophilia screening however is no longer warranted are addressed in this article. Prediction rules combining clinical characteristics and coagulation assays have recently been developed. One such model, the Vienna Prediction Model, allows predicting recurrent VTE on the basis of VTE location, sex and D-dimer. This article describes strategies to distinguish between patients with high risk of recurrent VTE from those with a lower risk, who might not benefit from long-term antithrombotic therapy.

"ProC Global": A functional screening test that predicts recurrent venous thromboembolism

2005 ◽  
Vol 93 (03) ◽  
pp. 600-604 ◽  
Author(s):  
Shannon Bates ◽  
Marilyn Johnston ◽  
Simon McRae ◽  
Jeffrey Ginsberg ◽  
Anne Grand’Maison
Keyword(s):  
Venous Thromboembolism ◽  
Protein C ◽  
Specific Inhibitor ◽  
Factor V Leiden ◽  
First Episode ◽  
Functional Screening ◽  
Factor V ◽  
Increased Risk ◽  
Global Result ◽  
Recurrent Vte

SummaryAbnormalities of the Protein C (PC) pathway are found in the majority of patients with thrombophilia. ProC Global is a coagulation assay that reflects the net effect of the PC pathway by measuring the activated partial thromboplastin time (APTT) of patient and control plasma, before and after activation of endogenous PC by Protac, a snake venom. Previous studies have suggested that abnormalities in this test are associated with an increased risk of venous thromboembolism (VTE). A retrospective analysis was performed using frozen plasma samples from 140 patients with confirmed VTE to determine whether an abnormal ProC Global result (in the presence and in the absence of known abnormalities in the PC pathway) is a predictor of initial and recurrent VTE. Patients were tested for the presence of activated protein C resistance, Factor V Leiden, PC and protein S (PS) deficiency, and non-specific inhibitor positivity. Mean ProC Global results were significantly lower in patients with recurrent VTE than in patients without recurrent VTE. The association between abnormal ProC Global result and recurrent VTE showed a strong trend, before (odds ratio, OR 3.6) and after (OR 3.1) exclusion of known thrombophilic abnormalities. Patients with a first episode of idiopathic VTE also expressed significant lower ProC Global results than those with secondary VTE. After exclusion of known PC pathway abnormalities, there was a statistically significant association between abnormal ProC Global and initial idiopathic VTE (p=0.04). These results suggest that ProC Global may serve as a predictor of recurrent VTE and potentially for first episode of idiopathic VTE. ProC Global may help identify patients at increased risk of initial and recurrent VTE.

Coinheritance of the HR2 Haplotype in the Factor V Gene Confers an Increased Risk of Venous Thromboembolism to Carriers of Factor V R506Q (Factor V Leiden)

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 3062-3066 ◽  
Author(s):  
E.M. Faioni ◽  
F. Franchi ◽  
P. Bucciarelli ◽  
M. Margaglione ◽  
V. De Stefano ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Family Members ◽  
Factor V Leiden ◽  
Protein S ◽  
Fold Increase ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Multicenter Cohort Study ◽  
Vein Thrombosis ◽  
Increased Risk

With the aim of establishing whether the HR2 haplotype in factor V affects the risk of venous thromboembolism, a retrospective multicenter cohort study was performed in 810 family members identified through 174 probands who suffered from at least 1 episode of deep vein thrombosis and/or pulmonary embolism and had an inherited defect associated with thrombophilia (antithrombin, protein C, or protein S deficiency; factor V R506Q or prothrombin G20210A). Fifty-eight percent (468/810) of the family members had an inherited defect and 10% (47/468) were symptomatic. The HR2 haplotype was found in association with factor V R506Q more frequently in family members with venous thromboembolism (18%) than in those without (8%). Double heterozygosity for factor V R506Q and HR2 conferred a 3- to 4-fold increase in the relative risk of venous thromboembolism compared with factor V R506Q alone. The median age at first event was lower when the 2 defects were associated (46v 52 years). No increase in risk of venous thromboembolism could be demonstrated when the HR2 haplotype was associated with inherited thrombophilic defects other than factor V R506Q. Because both factor V R506Q and the HR2 haplotype are very frequent, the effect of their coinheritance on the risk of venous thromboembolism might represent a clinically relevant issue, and screening for HR2 in carriers of factor V R506Q should be considered.

Inherited Thrombophilia and First Venous Thromboembolism during Pregnancy and Puerperium

2002 ◽  
Vol 87 (05) ◽  
pp. 791-795 ◽  
Author(s):  
Valerio De Stefano ◽  
Emanuela Taioli ◽  
Katia Paciaroni ◽  
Elena Rossi ◽  
Mannucci Pier ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Factor V Leiden ◽  
Protein S ◽  
First Episode ◽  
Factor V ◽  
Inherited Thrombophilia ◽  
Vein Thrombosis ◽  
Increased Risk ◽  
Prothrombin Mutation ◽  
Heterozygous Carriers

SummaryVenous thromboembolism is a rare but threatening complication of pregnancy. Little conclusive information is available on the actual risk of venous thromboembolism during pregnancy or puerperium in women with inherited thrombophilia, particularly in carriers of factor V Leiden and of the G20210A prothrombin gene mutation. To determine the pregnancy-related and puerperium-related risk of venous thromboembolism in women with inherited thrombophilia, we performed a case-control study on 119 women who had a first episode of deep vein thrombosis and/or pulmonary embolism during pregnancy or puerperium and 232 healthy women who had at least one pregnancy without thrombosis. Inherited thrombophilia was diagnosed in 47 patients (39.5%) and 15 controls (6.5%). The relative risk of venous thromboembolism was 10.6 (95% CI, 5.6-20.4) for heterozygous carriers of factor V Leiden, 2.9 (95% CI, 1.0-8.6) for heterozygous carriers of the prothrombin mutation and 13.1 (95% CI, 5.0-34.2) for those with antithrombin, protein C or protein S deficiency taken together. Sixty-eight of the 119 women (57%) had thrombosis after delivery, confirming the puerperium as a particularly high-risk period. When women were divided into two groups of those with antenatal or postnatal thrombosis, the relative risks associated with each type of inherited thrombophilia were of similar magnitude. In conclusion, women with inherited thrombophilia have an increased risk of venous thromboembolism during pregnancy. Among thrombophilic abnormalities, the prothrombin mutation was the weakest risk factor. Thrombosis occurred more frequently in puerperium than in pregnancy, whether or not thrombophilia was diagnosed.

scholarly journals Risk Factor Profiles in Patients with Different Clinical Manifestations of Venous Thromboembolism: A Focus on the Factor V Leiden Mutation

1996 ◽  
Vol 76 (04) ◽  
pp. 510-513 ◽  
Author(s):  
Bert Manten ◽  
Rudi G J Westendorp ◽  
Ted Koster ◽  
Pieter H Reitsma ◽  
Frits R Rosendaal
Keyword(s):  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Clinical Manifestations ◽  
Factor V Leiden ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Vein Thrombosis ◽  
Increased Risk ◽  
Deep Vein

Summary Background. Patients with venous thromboembolic disease may present with different clinical manifestations. Factor V Leiden mutation leading to resistance to activated protein C is associated with a sevenfold increased risk for presenting with deep-vein thrombosis. It is not yet established whether carriers of the mutation have a similarly increased risk for manifesting with pulmonary embolism. Methods. From an Anticoagulation Clinic monitoring coumarin therapy, a consecutive series of patients with a first thromboembolic event (objectively proven by current radiological methods) were enrolled. All patients were interviewed and blood was drawn for geno-typing. From the hospital charts and the personal interview, information was obtained on acquired risk factors and the signs and symptoms on hospital admission. Results. 45 patients presented with symptoms of pulmonary embolism only, 211 had only symptoms of deep-vein thrombosis whereas 23 had clinical features of both. In about half of the patients acquired risk factors for venous thromboembolism were present which did not differ between the three groups of patients. Recent surgery had been performed more often in patients presenting with pulmonary embolism than in other patients (33.3% vs. 18.5%, p <0,05). Factor V Leiden was present in 9% of the patients presenting with pulmonary embolism (relative risk: 3.3 95% Cl: 1.0-10.6) and 17% of the patients presenting with deep-vein thrombosis (relative risk: 6.9 95% Cl: 3.6-12.8). The prevalence of factor V Leiden was intermediate in patients with both clinical characteristics. Conclusion. These data suggest that patients with venous thromboembolism have different clinical presentation depending on the risk factor profile. Factor V Leiden may preferentially lead to manifest deep-vein thrombosis. Differences in structure of venous thrombi could underlie differences in embolic tendency.

Coinheritance of the HR2 Haplotype in the Factor V Gene Confers an Increased Risk of Venous Thromboembolism to Carriers of Factor V R506Q (Factor V Leiden)

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 3062-3066 ◽  
Author(s):  
E.M. Faioni ◽  
F. Franchi ◽  
P. Bucciarelli ◽  
M. Margaglione ◽  
V. De Stefano ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Family Members ◽  
Factor V Leiden ◽  
Protein S ◽  
Fold Increase ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Multicenter Cohort Study ◽  
Vein Thrombosis ◽  
Increased Risk

Abstract With the aim of establishing whether the HR2 haplotype in factor V affects the risk of venous thromboembolism, a retrospective multicenter cohort study was performed in 810 family members identified through 174 probands who suffered from at least 1 episode of deep vein thrombosis and/or pulmonary embolism and had an inherited defect associated with thrombophilia (antithrombin, protein C, or protein S deficiency; factor V R506Q or prothrombin G20210A). Fifty-eight percent (468/810) of the family members had an inherited defect and 10% (47/468) were symptomatic. The HR2 haplotype was found in association with factor V R506Q more frequently in family members with venous thromboembolism (18%) than in those without (8%). Double heterozygosity for factor V R506Q and HR2 conferred a 3- to 4-fold increase in the relative risk of venous thromboembolism compared with factor V R506Q alone. The median age at first event was lower when the 2 defects were associated (46v 52 years). No increase in risk of venous thromboembolism could be demonstrated when the HR2 haplotype was associated with inherited thrombophilic defects other than factor V R506Q. Because both factor V R506Q and the HR2 haplotype are very frequent, the effect of their coinheritance on the risk of venous thromboembolism might represent a clinically relevant issue, and screening for HR2 in carriers of factor V R506Q should be considered.

The Risk Of Recurrence In Women With Venous Thromboembolism While Using Estrogens: A Prospective Observational Cohort Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1123-1123
Author(s):  
Paul A Kyrle ◽  
Lisbeth Eischer ◽  
Sabine Eichinger
Keyword(s):  
Venous Thromboembolism ◽  
Conflicts Of Interest ◽  
Oral Anticoagulants ◽  
Hormone Replacement ◽  
Factor V Leiden ◽  
Recurrence Risk ◽  
Cumulative Probability ◽  
Carrier Status ◽  
Factor V ◽  
Recurrent Vte

Abstract Objective Because of the high recurrence risk, guidelines recommend indefinite anticoagulation in women with a first unprovoked proximal deep-vein thrombosis (DVT) and/or pulmonary embolism (PE). The optimal duration of anticoagulation in women who had venous thromboembolism (VTE) while using estrogens is unknown. We therefore compared the risk of recurrent VTE between women who used estrogens at the time of first VTE and women who did not. Methods This analysis was performed within the frame of the Austrian Study on Recurrent Venous Thromboembolism (AUREC), an on-going prospective observational study. Patients with a first objectively confirmed DVT of the leg and/or PE who had received anticoagulants for 3 to 18 months were included. Exclusion criteria were: age < 18 years; VTE associated with surgery, trauma, cancer or pregnancy; long-term anticoagulation; natural inhibitor deficiency; lupus anticoagulant; homozygosity or double heterozygosity for factor V Leiden and/or the prothrombin mutation. Women were advised to refrain from further estrogen use and were excluded in case of non-adherence. The study end point was recurrent symptomatic DVT and/or PE verified by imaging. The local ethics committee approved the study and all patients gave written informed consent. Results We followed 630 women (mean age 46 +/- 17 years) who had been treated with oral anticoagulants for 7 (+/- 3) months for an average of 69 (+/- 52) months. Recurrent VTE was recorded in 71 patients (11%). Recurrent VTE occurred in 22 (7%) of 333 estrogen users and in 49 (17%) of 297 non-users. After 1, 2 and 5 years, the cumulative probability of recurrence was 1% (95% CI 0-2), 1% (95% CI 0-2) and 6% (95% CI 3-9) among estrogen users and 5% (95% CI 2-7), 9% (95% CI 6-13) and 17% (95% CI 12-22) among non-users, respectively (p < 0.001, Figure). Compared to non-users, estrogen users had a relative risk (RR) of recurrent VTE of 0.4 (95% CI 0.2-0.8) after adjustment for age, site of first VTE and factor V Leiden carrier status. Compared to non-users in the respective age groups, the RR of recurrent VTE was 0.4 (95% CI 0.2-0.8) among estrogen containing contraceptive users and was 0.7 (95% CI 0.3-1.5) among women using estrogen containing hormone replacement therapy. Conclusion Women who had their first VTE while using estrogens have a low risk of recurrent VTE. The recurrence risk is particularly low in estrogen containing contraceptive users. We therefore propose that these women should receive anticoagulant therapy for no longer than 3 months. Disclosures: No relevant conflicts of interest to declare.

The Risk of Recurrent Venous Thromboembolism in Patients with and without Factor V Leiden

1997 ◽  
Vol 77 (04) ◽  
pp. 624-628 ◽  
Author(s):  
Sabine Eichinger ◽  
Ingrid Pabinger ◽  
Andreas Stümpfien ◽  
Mirko Hirschl ◽  
Christine Bialonczyk ◽  
...  
Keyword(s):  
Oral Anticoagulant Therapy ◽  
Oral Anticoagulants ◽  
Factor V Leiden ◽  
Multicenter Trial ◽  
Observation Time ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Factor V ◽  
Increased Risk ◽  
Recurrent Vte

SummaryThromboprophylaxis with oral anticoagulants up to six months is established in patients after a first venous thromboembolic event (VTE). The risk of recurrent VTE is still considerable thereafter, and it is uncertain whether some patients might benefit from extended anticoagulation. We performed a prospective, multicenter trial (4 thrombosis centers) and evaluated in 380 patients with a first or recurrent VTE (patients with a deficiency of antithrombin, protein C, protein S or plasminogen; cancer; or an antiphospholipid antibody syndrome were excluded) the risk of recurrence after discontinuation of secondary thromboprophylaxis with oral anticoagulants. It was the aim of the study to evaluate whether patients with factor V Leiden are at an increased risk of recurrent VTE. 112 (29.5%) patients were carriers of factor V Leiden (26.9% heterozygous, 2.6% homozygous). After a median observation time of 19.3 months the overall recurrence rate of VTE was 9.9%. Recurrent deep vein thrombosis and/or pulmonary embolism occurred in 26 of 268 patients without factor V Leiden (9.7%) and in 10 of 112 patients with factor V Leiden (8.9%). The probability of recurrent VTE two years after discontinuation of oral anticoagulants was 12.4% (95% Cl 7.8-17) in patients without factor V Leiden and was 10.6% (95% Cl 3.8-17.4) in carriers of the mutation. This difference was statistically not significant. Patients with factor V Leiden are not at a higher risk of recurrent VTE within two years after discontinuation of oral anticoagulants than patients without factor V Leiden. Balancing the risk of recurrent VTE and bleeding from oral. anticoagulants, patients with factor V Leiden are not likely to benefit from oral anticoagulant therapy extended beyond six months.

Combined Effect of Factor V Leiden and Prothrombin 20210A on the Risk of Venous Thromboembolism

2001 ◽  
Vol 86 (09) ◽  
pp. 809-816 ◽  
Author(s):  
Frits Rosendaal ◽  
Marco Cattaneo ◽  
Maurizio Margaglione ◽  
Valerio De Stefano ◽  
Tony Cumming ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Odds Ratio ◽  
Large Population ◽  
Factor V Leiden ◽  
Pooled Analysis ◽  
Factor V ◽  
Case Control Studies ◽  
Vein Thrombosis ◽  
G20210a Mutation ◽  
Factor Ii

SummaryFactor V Leiden and factor II G20210A mutations are two frequent genetic risk factors involved in venous thromboembolism (VTE). The goal of this pooled analysis of 8 case-control studies, comprising a total of 2310 cases and 3204 controls, was to precisely estimate the risk of VTE in patients bearing both mutations (double heterozygotes). Odds ratios for VTE were 4.9 (95% CI; 4.1-5.9) for the factor V Leiden and 3.8 (3.0-4.9) for the factor II G20210A mutation. Fifty-one cases (2.2%) and none of the controls were double heterozygotes. The odds ratio for venous thrombosis in double heterozygotes was 20.0 (11.1-36.1). Twelve percent of patients heterozygous for factor V Leiden were also heterozygous for factor II G20210A and conversely 23% of patients heterozygous for factor II G20210A were also heterozygous for factor V Leiden. Furthermore, in this large population we analyzed the effect of oral contraceptive (OC) in women carrying one of these mutations. Odds ratio for VTE associated with OC was 2.29 (1.72-3.04). In factor V Leiden carriers using OC, the odds ratio for VTE was 10.25 (5.69-18.45). The odds ratio of the association of factor II mutation and OC use was 7.14 (3.39-15.04). Finally, we also confirmed that the frequency of factor V Leiden was lower in patients with pulmonary embolism than in patients with deep vein thrombosis without PE (odds ratio 0.69). Conversely, factor II G20210A mutation was equally balanced in both patient groups.

Is APC Resistance a Risk Factor for Venous Thromboembolism in Patients over 70 Years?

2002 ◽  
Vol 88 (10) ◽  
pp. 587-591 ◽  
Author(s):  
Karine Lacut ◽  
Grégoire Le Gal ◽  
Patrick Van Dreden ◽  
Luc Bressollette ◽  
Pierre-Yves Scarabin ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Odds Ratio ◽  
Dna Analysis ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Factor V ◽  
Apc Resistance ◽  
Increased Risk ◽  
History Of

SummaryActivated protein C (APC) resistance is the most common risk factor for venous thromboembolism (VTE). Previous studies mostly analysed patients under 70 years and reported a four-to sevenfold increased risk. This case-control study included consecutive patients referred for a clinical suspicion VTE to our medical unit: 621 patients with a well-documented diagnosis (cases) and 406 patients for which the diagnosis was ruled out and who had no personal history of VTE (controls). APC resistance related to factor V Leiden was defined by either a positive DNA analysis or a positive STA® Staclot APC-R assay. Under 70 years, APC resistance was associated with a threefold increased risk of VTE (odds ratio 3.2, 95% CI, 1.7 to 6.0), whereas in patients over 70 years, it appeared to be no longer a strong risk factor (odds ratio 0.8, 95% CI, 0.4 to 1.7). Age appeared as an effectmeasure modifier with a significant interaction (p = 0.005). Our data suggest that APC resistance is not a risk factor for VTE in elderly.

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