P-selectin gene haplotypes modulate soluble P-selectin concentrations and contribute to the risk of venous thromboembolism

SummaryThe cell adhesion molecule P-selectin mediates the interaction of activated platelets or endothelial cells with leukocytes. In arterial and venous thromboembolism (VTE) increased soluble P-selectin (sP-selectin) concentrations have been found, and associations of P-selectin genotypes with thrombotic disease have been proposed. We assessed the effect of four single nucleotide polymorphisms (SNPs) [one in the promoter region (c.–2123C>G) and three (S290N, c.1087G>A; D562N, c.1902G>A; T715P, c.2363A>C) in the coding region] and the calculated haplotypes in the P-selectin gene (SELP) on sP-selectin concentrations and VTE risk. The analysis was carried out in 116 high-risk patients with a history of objectively confirmed recurrent VTE and 129 age- and sex-matched healthy individuals. Haplotypes were generated using computer-assisted haplotype reconstruction with Phase 2.1. sP-selectin (μg/l) was measured by ELISA. Frequencies of all four individual SNPs were not statistically significantly different between patients and controls. Tenhaplotypes were obtained for the control population, and nine for the patient group. The most frequent haplotype among controls was CGGA (major allele at all positions) (27.8%; frequency in patients 19.0%), which was used as reference for statistical analyses. Among patients GGAA was most frequent (23.3%; frequency in controls 17.5%). Haplotypes were significantly associated with sP-selectin concentrations in patients and in controls (p<0.001 and p=0.011). Compared to CGGA some but not all haplotypes conferred an increased risk for VTE with odds ratios (ORs) between 5.4 (95% CI: 2.5–12.2) for CAGA, 3.3 (1.2–9.2) for CGAC, and 2.4 (1.3–4.7) for GGAA. All ORs remained statistically significant after adjustment for the factor V Leiden mutation, located in close proximity to SELP on chromosome 1, as well as all other established risk factors for VTE. In conclusion, SELP haplotypes modulate plasma concentrations of sP-selectin and affect the risk of recurrent VTE.

Download Full-text

Factor V Leiden (G1691A) and Prothrombin Gene G20210A Mutations as Potential Risk Factors for Venous Thromboembolism after Total Hip or Total Knee Replacement Surgery

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613052 ◽

2002 ◽

Vol 87 (04) ◽

pp. 580-585 ◽

Cited By ~ 59

Author(s):

G. Larson ◽

T. L. Lindahl ◽

C. Andersson ◽

L. Frison ◽

D. Gustafsson ◽

...

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Factor V Leiden ◽

Composite Endpoint ◽

Factor V ◽

Factor V Leiden Mutation ◽

G20210a Mutation ◽

Symptomatic Pulmonary Embolism ◽

Increased Risk ◽

Prothrombin Gene

SummaryPatients (n = 1600) from 12 European countries, scheduled for elective orthopaedic hip or knee surgery, were screened for Factor V Leiden and prothrombin gene G20210A mutations, found in 5.5% and 2.9% of the populations, respectively. All patients underwent prophylactic treatment with one of four doses of melagatran and ximelagatran or dalteparin, starting pre-operatively. Bilateral ascending venography was performed on study day 8-11. The patients were subsequently treated according to local routines and followed for 4-6 weeks postoperatively. The composite endpoint of screened deep vein thrombosis (DVT) and symptomatic pulmonary embolism (PE) during prophylaxis did not differ significantly between patients with or without these mutations. Symptomatic venous thromboembolism (VTE) during prophylaxis and follow-up (1.9%) was significantly over-represented among patients with the prothrombin gene G20210A mutation (p = 0.0002). A tendency towards increased risk of VTE was found with the Factor V Leiden mutation (p = 0.09). PE were few, but significantly over-represented in both the Factor V Leiden and prothrombin gene G20210A mutated patients (p = 0.03 and p = 0.05, respectively). However, since 90% of the patients with these genetic risk factors will not suffer a VTE event, a general pre-operative genotyping is, in our opinion, of questionable value.

Download Full-text

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

Thrombosis and Haemostasis ◽

10.1160/th04-07-0445 ◽

2005 ◽

Vol 93 (03) ◽

pp. 600-604 ◽

Cited By ~ 7

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.

Download Full-text

Endogenous Thrombin Potential (ETP) for Assessing the Risk of Recurrent Venous Thromboembolism.

Blood ◽

10.1182/blood.v106.11.1622.1622 ◽

2005 ◽

Vol 106 (11) ◽

pp. 1622-1622 ◽

Cited By ~ 2

Author(s):

Sabine Eichinger ◽

Gregor Hron ◽

Ansgar Weltermann ◽

Marietta Kollars ◽

Paul A. Kyrle

Keyword(s):

Venous Thromboembolism ◽

Factor V Leiden ◽

Factor Ix ◽

Clotting Factor ◽

Study Endpoint ◽

Cumulative Probability ◽

Computer Assisted ◽

Risk Of Recurrence ◽

Increased Risk ◽

Factor Ii

Abstract Venous thromboembolism (VTE) is a multifactorial chronic disease. The number and severity of risk factors determine the risk of recurrence. A laboratory method that measures the overall thrombophilia is required. In a prospective cohort study, we measured ETP in 778 patients with a first unprovoked VTE. Patients were followed after discontinuation of anticoagulants for an average of 49 months. The study endpoint was recurrent symptomatic VTE. ETP was determined by a commercially available (research use only) assay (Dade Behring, Marburg, Germany) in platelet poor plasma by use of a chromogenic substrate and automatic registration as well as computer assisted calculation of thrombin generation over time. Patients with recurrence had higher ETP than those without recurrence (104.2% ± 15.4% vs. 101.4% ±14.2%. Patients with ETP ≥ 100% had an almost two-fold higher relative risk (RR) of recurrence than patients with lower levels (RR 1.6, 95% CI 1.0 – 2.5). At 4 years, the cumulative probability of recurrence was 14.4% in patients with ETP ≥ 100% and 6.1% in those with lower levels (p = 0.05). Patients with ETP ≥ 100% had higher clotting factor levels (Table). ETP was significantly increased in heterozygous carriers of factor II G20210A as compared with patients with wild type factor II (128% ± 18% vs. 100 ± 12%, p < 0.001). Patients with a first unprovoked VTE and an ETP ≥ 100% have an increased risk of recurrence. Table Characteristics of 778 Patients with VTE ETP < 100% ETP ≥ 100% p-value Men, no. (%) 160 (42%) 174 (44%) n.s. Age at first VTE (yrs) 46 ± 17 47 ± 14 n.s. Factor V Leiden, no. (%) 124 (32%) 108 (28%) n.s. Factor II G20210A, no. (%) 4 (1%) 49 (13%) < 0.001 Factor VIII (IU/dL) 162 ± 46 168 ± 45 0.09 Factor IX (IU/dL) 113 ± 24 123 ± 27 < 0.001 Factor XI (IU/dL) 102 ± 21 110 ± 24 < 0.001

Download Full-text

High Levels of Soluble P-Selectin Are Associated with the Risk of Venous Thromboembolism and the P-Selectin Thr715 Variant.

Blood ◽

10.1182/blood.v108.11.384.384 ◽

2006 ◽

Vol 108 (11) ◽

pp. 384-384 ◽

Cited By ~ 1

Author(s):

Cihan Ay ◽

Lea V. Jungbauer ◽

Thomas Sailer ◽

Theres Tengler ◽

Silvia Koder ◽

...

Keyword(s):

Venous Thromboembolism ◽

Factor V Leiden ◽

Prothrombin G20210a ◽

Factor V ◽

Gene Variation ◽

Viii Level ◽

Risk Patients ◽

Recurrent Vte ◽

Soluble P ◽

The Difference

Abstract The cell adhesion molecule P-selectin, which is found in the alpha granula of platelets and in Weibel-Palade bodies of endothelial cells, has been shown to play an important role in the pathophysiology of thrombosis. However, the meaning of soluble P-selectin (sP-selectin) in venous thromboembolism (VTE) is still uncertain because clinical data are limited. The purpose of this study was to investigate whether sP-selectin is associated with the risk for VTE and to elucidate the association of sP-selectin and the P-selectin gene variation (SELP) Thr715Pro in high risk patients with recurrent VTE. We recruited cases and control individuals between January 2005 and November 2005 for an analysis of sP-selectin plasma levels and the SELP Thr715Pro. Patients with a history of objectively confirmed recurrent VTE and at least one event of an unprovoked deep venous thrombosis or pulmonary embolism were enrolled. Plasma was obtained at least 3 months after the most recent event of VTE. Age and sex-matched healthy individuals served as controls. sP-selectin levels were measured with a high sensitive ELISA. The variant for the P-selectin gene was determined by a mutagenically separated PCR followed by high resolution gel-electrophoresis. Hundred-sixteen patients (53 female / 63 male; mean age +/−SD: 56 +/−12 yrs) and 129 controls (66 female / 63 male; mean age +/−SD: 53 +/−11 yrs) were enrolled. Mean concentration (+/−SD) of sP-selectin (ng/mL) was significantly higher in patients than in controls (47.28 +/−15.00 vs. 36.77 +/−11.00, p<0.001). The unadjusted odds ratio (OR) of elevated sP-selectin (cut-off level 55.10 ng/mL representing the 95th percentile of the controls) was 8.5 (95% confidence interval (CI): [3.7–23.3], p<0.001) and increased after adjustment for factor V Leiden, prothrombin G20210A variant, elevated factor VIII level, hyperhomocysteinemia and BMI (OR=11.1, 95% CI [4.3–33.0], p<0.001). Carriers of the SELP Pro715 were more prevalent among controls than patients (21.7% versus 14.7%), however, the difference was statistically not significant (p=0.19). The subgroup of carriers of the SELP Pro715 (n=45) had significantly lower sP-selectin levels than non-carriers (31.31+/−7.94 vs. 44.10+/−14.08, p<0.001). In conclusion, our study shows a highly significant association between elevated sP-selectin levels and VTE. Furthermore, sP-selectin levels correlate with genotype status and individuals carrying the SELP Pro715 have lower levels of sP-selectin.

Download Full-text

Factor V Leiden Mutation Increases the Risk of Venous Thromboembolism in Cancer Patients – Results From the Vienna Cancer and Thrombosis Study (CATS).

Blood ◽

10.1182/blood.v120.21.2253.2253 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2253-2253

Author(s):

Ingrid Pabinger ◽

Cihan Ay ◽

Daniela Dunkler ◽

Johannes Thaler ◽

Eva-Maria Reitter ◽

...

Keyword(s):

Venous Thromboembolism ◽

Cancer Patients ◽

Factor V Leiden ◽

Treatment Modalities ◽

Individual Risk ◽

Factor V ◽

Newly Diagnosed ◽

Factor V Leiden Mutation ◽

Increased Risk ◽

The Impact

Abstract Abstract 2253 Background: Patients with cancer are at an increased risk of venous thromboembolism (VTE). The risk varies markedly in different patient populations and improvement of the prediction of VTE would be of advantage for tailoring thrombosis prophylaxis. Factor V Leiden is the most common genetic risk factor for VTE and the impact of factor V Leiden on cancer-associated thrombosis is not yet fully elucidated. Objective: To study the impact of factor V Leiden on the risk of VTE in cancer patients. Patients and Methods: Nine-hundred-eighty-two patients with newly diagnosed cancer (n=745) or progression of disease after complete or partial remission (n=237) were included in the cancer and thrombosis study (CATS), a prospective observational single centre cohort study at the Medical University Vienna. Patients were followed for a maximum period of 2 years. Blood samples were collected at inclusion and factor V Leiden was determined by genotyping. The main outcome measure was symptomatic or lethal objectively confirmed VTE. All VTE events were adjudicated independently. Results: Of the 982 patients (median age 62 years, interquartile range (IQR) 52–68, 537 men, 445 women) factor V-Leiden was found in 72 (7.3%), 70 had a heterozygous and two a homozygous genotype. Ten of 72 (14%) patients with factor V-Leiden developed VTE, whereas this was the case in 69 of 910 (7.6%) patients without factor V-Leiden. Interestingly, both patients with homozygous factor V Leiden developed VTE. In multivariable analysis that included age, sex, different tumour types, newly diagnosed versus recurrence of disease and the treatment modalities (chemotherapy, radiotherapy and surgery) the hazard ratio (HR) for factor V Leiden was 2.04 (95% confidence interval (CI) 1.04–3.97)). In patients with newly diagnosed tumours the HR for factor V Leiden was 3.7 (95% CI 1.2–12.2) after 30 days. In Kaplan Meier analysis the probability for development of VTE after 6 months was 5.7% in those without and 13% in those with factor V Leiden, after one year the corresponding rates were 7.3% and 15%. Conclusions: Factor V Leiden is a genetically determined and thus disease-independent parameter, which is associated with VTE in cancer patients, especially shortly after cancer diagnosis, and could therefore be used for individual risk assignment. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

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

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650613 ◽

1996 ◽

Vol 76 (04) ◽

pp. 510-513 ◽

Cited By ~ 45

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.

Download Full-text

Hypofibrinolysis and the Risk of Recurrent Venous Thromboembolism: A Prospective Cohort Study,

Blood ◽

10.1182/blood.v118.21.3331.3331 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3331-3331

Author(s):

Sabine Eichinger ◽

Ludwig Traby ◽

Georg Heinze ◽

Marietta Kollars ◽

Lisbeth Eischer ◽

...

Keyword(s):

Venous Thromboembolism ◽

Conflicts Of Interest ◽

Factor V Leiden ◽

Cox Proportional Hazards Model ◽

Fibrinolytic System ◽

Tissue Type ◽

Clot Lysis ◽

Clotting Factors ◽

Increased Risk ◽

Recurrent Vte

Abstract Abstract 3331 Hypercoagulability reflected by enhanced activity of clotting factors or a natural inhibitor deficiency is a risk factor of venous thromboembolism (VTE). Whether defects in the fibrinolytic system confer an increased risk of VTE is unclear. We assessed the relationship between fibrinolytic system activity (reflected by clot lysis time [CLT]) and the risk of recurrent VTE. We followed 704 patients (378 women; mean age 48 years) with a first unprovoked VTE for an average of 46 months after anticoagulation withdrawal. Patients with a natural coagulation inhibitor deficiency, lupus anticoagulant, cancer, female hormone use, homozygosity or double heterozygosity for factor V Leiden or prothrombin mutation, or requirement for indefinite anticoagulation were excluded. The fibrinolytic potential was assessed using a plasma based clot-lysis assay according to Lisman et al. (1). A tissue factor-induced clot was lysed by adding tissue-type plasminogen activator and the optical density was measured at 405 nm in an absorbance microplate reader every 30 seconds in order to get a clot-lysis turbidity profile. Study end point was symptomatic recurrent VTE. 135 (19%) patients had recurrent VTE. Recurrence was unprovoked in 117 patients and was more frequent in men (97/326, 29.8%) than in women (38/378, 10.1%). When CLT was entered as continuous variable in a Cox proportional hazards model, hazard ratio (HR) for recurrence was 1.13 (95% CI 1.02–1.25; p=0.02) for each 10 minutes prolongation. The HR for recurrence was 1.11 (95% CI 1.11–1.24; p=0.046) after adjustment for age and 1.08 (95% CI 0.98–1.20; p=0.13) after additional adjustment for sex. After 5 years, the likelihood of recurrence was 23.8% (95% CI 19.3%-28.3%) in patients with a CLT longer than 63.5 minutes (25th percentile) as compared with 14.1% (95% CI 7.4%-20.8%; p=0.04) among those with a shorter CLT. Men and women differed with regard to CLT (76.1±16.2 vs. 71.5±13.6 sec, p<0.001). After adjustment for age, the HR was 1.04 (95% CI 0.92–1.18; p=0.54) among men and 1.14 (95% CI 0.93–1.14; p=0.22) among women. Hypofibrinolysis confers an increased risk of recurrent VTE. The effect was more pronounced in women than in men. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Third Generation Oral Contraceptives and Heritable Thrombophilia as Risk Factors of Non-fatal Venous Thromboembolism

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614213 ◽

1998 ◽

Vol 79 (01) ◽

pp. 28-31 ◽

Cited By ~ 30

Author(s):

Birthe Søgaard Andersen ◽

Jørn Olsen ◽

Gunnar Lauge Nielsen ◽

Flemming Hald Steffensen ◽

Henrik Toft Sørensen ◽

...

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Oral Contraceptives ◽

Factor V Leiden ◽

Factor V ◽

Third Generation ◽

Confounding By Indication ◽

Antithrombin Deficiency ◽

Factor V Leiden Mutation ◽

Increased Risk

SummaryThird generation oral contraceptives (OCs) are apparently stronger risk factors for venous thromboembolism (VTE) than other OCs, however, the increased risk may be due to confounding by indication related to differences in prescription behaviour.We estimated the risk of VTE associated with use of OCs with and without the presence of Factor V Leiden mutation, protein C-, protein S- or antithrombin deficiency.Sixty-seven cases with VTE were compared with 134 controls. The risk of VTE in the presence of thrombophilia was of the same magnitude for third generation OC users as for users of other OCs; OR: 52.5 (95% CI: 3.7-738.1) and OR: 63.3 (95% CI: 6.2-648.4), respectively.It is unlikely that confounding by indication entirely explains the risk of VTE associated with third generation OCs since the combined effect exceeds what could be explained if this source of error was the only determinant of the association.

Download Full-text

An abnormal ProC Global test result is associated with an increased risk of venous thromboembolism independent of test sensitivity for protein C pathway abnormalities

Thrombosis and Haemostasis ◽

10.1160/th05-06-0418 ◽

2007 ◽

Vol 98 (07) ◽

pp. 228-233 ◽

Cited By ~ 3

Author(s):

Patricia Perez ◽

Jocelyn Rapp ◽

Raphaël Adda ◽

Pierre Toulon

Keyword(s):

Venous Thromboembolism ◽

Protein C ◽

Critical Role ◽

Factor V Leiden ◽

Global Test ◽

Factor V Leiden Mutation ◽

Increased Risk ◽

Significant Difference ◽

Assay Result ◽

Test Result

SummaryThe ProC® Global assay is a clotting assay primarily developed to globally evaluate the functionality of the protein C (PC) pathway. It was shown to lack both sensitivity and specificity for PC pathway abnormalities, i.e. factor V Leiden mutation, PC and PS deficiency. The hypothesis that an abnormal test result could be associated with venous thromboembolism (VTE) was evaluated in a case-control study. The proportion of reduced response was significantly higher in cases than in controls [n=71/139 (51.1%) vs. n=28/147 (19.0%); p<0.0001] and the same applied after exclusion of those subjects with any PC pathway abnormality [n=53/119 (44.5%) vs. n=25/143 (17.5%); p<0.0001]. An abnormal ProC® Global assay result was significantly associated with thrombosis both in the whole population (odds ratio [OR]=4.44, 95% confidence interval [CI]=2.61–7.53) and in those subjects without any PC pathway abnormality (OR=3.70, 95%CI=2.16–6.66). The ProC® Global assay result was significantly lower in cases with idiopathic VTE than in those with secondary VTE (p<0.0001). No significant difference was observed when cases were classified according to the presence or absence of recurrent episodes. Moreover, a reduced response was found to be associated with VTE both in subjects with normal or elevated factor VIII (FVIII) level. In vitro, FVIII was found to play a critical role in the ProC® Global assay result as suggested by the significant trend toward decreasing response with increasing FVIII levels. In conclusion, our results suggest that an abnormal ProC® Global assay result is associated with an increased risk of VTE independently of its sensitivity for PC pathway abnormalities.

Download Full-text

Predicting the risk of recurrent venous thromboembolism

Hämostaseologie ◽

10.5482/hamo-13-03-0018 ◽

2013 ◽

Vol 33 (03) ◽

pp. 201-209 ◽

Cited By ~ 12

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.

Download Full-text