Influence of thrombophilia on risk of recurrent venous thromboembolism while on warfarin: results from a randomized trial

Abstract We sought to determine whether thrombophilic defects increase recurrent venous thromboembolism (VTE) during warfarin therapy. Six hundred sixty-one patients with unprovoked VTE who were randomized to extended low-intensity (international normalized ratio [INR], 1.5-1.9) or conventional-intensity (INR, 2.0-3.0) anticoagulant therapy were tested for thrombophilia and followed for a mean of 2.3 years. One or more thrombophilic defects were present in 42% of patients. The overall rate of recurrent VTE was 0.9% per patient-year. Recurrent VTE was not increased in the presence of factor V Leiden (hazard ratio [HR], 0.7; 95% CI, 0.2-2.6); the 20210G>A prothrombin gene mutation (HR, 0); antithrombin deficiency (HR, 0); elevated factor VIII (HR, 0.7; 95% CI, 0.1-5.4); elevated factor XI (HR, 0.7; 95% CI, 0.1-5.0), or elevated homocysteine (HR, 0.7; 95% CI, 0.1-5.3), but showed a trend to an increase with an antiphospholipid antibody (HR, 2.9; 95% CI, 0.8-10.5). Compared with patients with no thrombophilic defects, the rate of recurrence was not increased in the presence of one (HR, 0.7; 95% CI, 0.2-2.3) or more than one (HR, 0.7; 95% CI, 0.2-3.4) defect. We conclude that single or multiple thrombophilic defects are not associated with a higher risk of recurrent VTE during warfarin therapy.

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

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656023 ◽

1997 ◽

Vol 77 (04) ◽

pp. 624-628 ◽

Cited By ~ 139

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.

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Gene-Gene and Gene-Environment Interactions Determine Risk of Thrombosis in Families With Inherited Antithrombin Deficiency

Blood ◽

10.1182/blood.v94.8.2590.420k40_2590_2594 ◽

1999 ◽

Vol 94 (8) ◽

pp. 2590-2594 ◽

Cited By ~ 91

Author(s):

H.H. van Boven ◽

J.P. Vandenbroucke ◽

E. Briët ◽

F.R. Rosendaal

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Venous Thromboembolism ◽

Genetic Risk ◽

Factor V Leiden ◽

Genetic Defects ◽

Factor V ◽

Antithrombin Deficiency ◽

Gene Environment ◽

Genetic And Environmental Factors

To analyze inherited antithrombin deficiency as a risk factor for venous thromboembolism in various conditions with regard to the presence or absence of additional genetic or acquired risk factors, we compared 48 antithrombin-deficient individuals with 44 nondeficient individuals of 14 selected families with inherited antithrombin deficiency. The incidence of venous thromboembolism for antithrombin deficient individuals was 20 times higher than among nondeficient individuals (1.1% v 0.05% per year). At the age of 50 years, greater than 50% of antithrombin-deficient individuals had experienced thrombosis compared with 5% of nondeficient individuals. Additional genetic risk factors, Factor V Leiden and PT20210A, were found in more than half of these selected families. The effect of exposure to 2 genetic defects was a 5-fold increased incidence (4.6% per year; 95% confidence interval [CI], 1.9% to 11.1%). Acquired risk factors were often present, determining the onset of thrombosis. The incidence among those with exposure to antithrombin deficiency and an acquired risk factor was increased 20-fold (20.3% per year; 95% CI, 12.0% to 34.3%). In conclusion, in these thrombophilia families, the genetic and environmental factors interact to bring about venous thrombosis. Inherited antithrombin deficiency proves to be a prominent risk factor for venous thromboembolism. The increased risks among those with exposure to acquired risk factors should be considered and adequate prophylactic anticoagulant therapy in high-risk situations seems indicated in selected families with inherited antithrombin deficiency.

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"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.

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Risk of Pregnancy-Associated Venous Thromboembolism in Women with a History of Prior Thrombosis.

Blood ◽

10.1182/blood.v108.11.1493.1493 ◽

2006 ◽

Vol 108 (11) ◽

pp. 1493-1493 ◽

Cited By ~ 1

Author(s):

Andrea Gerhardt ◽

Rudiger E. Scharf ◽

Rainer B. Zotz

Keyword(s):

Risk Factor ◽

Venous Thromboembolism ◽

Gene Mutation ◽

Factor V Leiden ◽

Prothrombin G20210a ◽

Factor V ◽

Previous Episode ◽

Recurrent Venous Thromboembolism ◽

History Of ◽

Heparin Prophylaxis

Abstract Background: Previous estimates of the rate of recurrent venous thromboembolism (VTE) during pregnancy in women with a history of VTE have vary between 0 and 13%. Therefore, the decision to administer or withhold heparin - especially in the antepartum period - has been discussed controversial. In a recent study by Brill-Edwards et al. (N Engl J Med2000;343:1439–44), no recurrences of VTE occurred in women (n=44) who had a previous episode of thrombosis that was associated with a temporary risk factor and who also had no evidence of thrombophilia. Based on these results, antepartum heparin prophylaxis is not routinely recommended in women without thrombophilia whose previous episode of thrombosis was associated with a temporary risk factor (ACCP guidelines 2004). The objective of our study was to evaluate the risk of recurrent pregnancy-associated thrombosis in women with a history of VTE. Materials and Methods: We retrospectively studied 198 women with at least one pregnancy (275 pregnancies in total) after a one previous episode of VTE. Sixty-three women (81 pregnancies) were excluded from the analysis because of antepartum heparin prophylaxis. Results: In the subgroup of women without heparin prophylaxis (n=135), 15 (7.7%) thromboembolic events occurred antepartum in 194 pregnancies. Further subgroup analysis, stratified for the nature of first VTE, gave the following number of antepartum VTE per number of pregnancies: 2 VTE/19 pregnancies (10.5%) in 14 women (first VTE: immobilization), 4 VTE/33 pregnancies (12.1%) in 24 women (first VTE: surgery), 5 VTE/69 pregnancies (7.2%) in 46 women (first VTE: oral contraception), 2 VTE/58 pregnancies (3.4%) in 40 women (first VTE: pregnancy), 2 VTE/15 pregnancies (13%) in 11 women (first VTE: idiopathic). Nine of the 15 women with VTE (7/13 women with first VTE triggered by temporary risk factor; 2/2 women with first idiopathic VTE) had a heterozygous factor V Leiden G1691A or prothrombin G20210A gene mutation. In the postpartum period, 16 VTE in 194 pregnancies occurred after live birth in the 135 women without heparin prophylaxis. Nine of these 16 women had a heterozygous FVL or prothrombin G20210A gene mutation. In Conclusion, the risk of recurrent antepartum VTE was similar in women with and without factor V Leiden G1691A or the prothrombin G20210A gene mutation and did not differ between women with first VTE triggered by a transient risk factor or an idiopathic first VTE. In addition to recommended postpartum heparin prophylaxis, our data support the need for a routine antepartum prophylaxis in women without thrombophilia whose previous episode of thrombosis was associated with a temporary risk factor.

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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.

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Influence Of Antithrombin Deficiency On Symptomatic Recurrent Venous Thromboembolism (VTE) In Children: A Multicenter Cohort Study

Blood ◽

10.1182/blood.v122.21.3619.3619 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3619-3619

Author(s):

Gili Kenet ◽

Verena Limperger ◽

Neil A Goldenberg ◽

Christine Heller ◽

Susanne Holzhauer ◽

...

Keyword(s):

Multivariate Analysis ◽

Venous Thromboembolism ◽

Pediatric Patients ◽

Cox Regression ◽

Conflicts Of Interest ◽

Antithrombin Deficiency ◽

Increased Risk ◽

Recurrent Venous Thromboembolism ◽

At Deficiency ◽

Recurrent Vte

Abstract Objective To determine the importance of antithrombin [AT] deficiency as risk factor or predictor for fatal/non-fatal recurrent venous thromboembolism (VTE) in children. Methods In the present cohort of 874 consecutively enrolled pediatric patients with VTE aged newborn to <18 years the rate of VTE recurrence and the time to recurrence in relation to AT-deficiency [confirmed by underlying gene mutations; type 1 deficiency n=17; type 2 deficiency n=3], age and sex was determined. Twenty of 874 patients [2.4%] suffered from AT-deficiency. From the same cohort 150 VTE children carrying the heterozygous F5 G1691A mutation [F5: 17.7%] served as controls. Patients were prospectively followed for a median of 84 months. Data were pooled across participating sites to increase power and to enhance the generalisability of the data. Incidence rates were given as events per 1000 person-years. Results Of the 170 children enrolled 26 [AT n=9; F5 n=17] had recurrent VTE at a median of 15 months [95%CI: 12-36] following VTE onset: two of nine [AT] and two of 17 [F5] children suffered recurrent VTE while on anticoagulation with warfarin. The overall incidence rate of recurrence was 61.5 in patients with AT-deficiency compared to 23.5 for pediatric F5 carriers [p=0.02]. The recurrent-free survival probability is shown in the figure [logrank p-value: p=0.001]. When comparing AT patients and F5 children multivariate analysis [Cox regression] adjusted for age, sex and duration of anticoagulation treatment showed that AT deficiency [HR/95%CI: 4.1/1.8-9.4] significantly influenced the hazard for recurrent VTE. Conclusions Based on multivariate analysis, the presence of AT deficiency was associated with an increased risk of VTE recurrence. AT-deficiency in pediatric patients should be identified at VTE onset and the possible influence of intensified treatment protocols on recurrence should be studied in future prospective international studies. Condensed abstract To determine the relative importance of antithrombin deficiency or factor V (FV) mutations as risk factors for fatal/non-fatal recurrence in pediatric thromboembolism (VTE). Antithrombin deficiency influenced the hazard for recurrent VTE. Disclosures: No relevant conflicts of interest to declare.

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The incidence of recurrent venous thromboembolism in carriers of factor V Leiden is related to concomitant thrombophilic disorders

British Journal of Haematology ◽

10.1046/j.0007-1048.2001.03303.x ◽

2002 ◽

Vol 116 (3) ◽

pp. 625-631 ◽

Cited By ~ 32

Author(s):

Johan R. Meinardi ◽

Saskia Middeldorp ◽

Pieter J. De Kam ◽

Maria M. W. Koopman ◽

Elisabeth C. M. Van Pampus ◽

...

Keyword(s):

Venous Thromboembolism ◽

Factor V Leiden ◽

Factor V ◽

Recurrent Venous Thromboembolism

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One- Week Prophylaxis with Enoxaparin after Hospital Discharge Is Effective in Preventing Venous Thromboembolism in Living Liver Donors- Single Institution Retrospective Analysis

Blood ◽

10.1182/blood-2019-124169 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2442-2442

Author(s):

Leila Khaddour ◽

Zaid Al Saheli ◽

Yaser Alkhatib ◽

Marwan Abouljoud ◽

Philip Kuriakose

Keyword(s):

Venous Thromboembolism ◽

Factor V Leiden ◽

Antiphospholipid Antibody ◽

Factor V ◽

Right Hepatectomy ◽

At Iii ◽

Thrombophilia Screening ◽

Liver Donation ◽

Living Liver Donors ◽

Liver Donors

Background: Living donor liver transplant (LDLT) has expanded organ availability to patients with advanced liver failure. While this procedure decreased morbidity and mortality in recipients, it could pose a risk to the donors. Deep vein thrombosis and pulmonary embolism are known postoperative complications associated with morbidity and mortality in living liver donors. At our institution thrombophilia screening starts during donor selection process with antiphospholipid antibody panel and screening coagulation tests for all candidates. This is followed by hematology evaluation to determine the need for inherited thrombophilia screening and accordingly, hypercoagulability risk. Additionally, the institution strategy for venous thromboembolism (VTE) prevention in liver donors involves prophylactic subcutaneous heparin within 24 hours of the surgery and maintained until discharge followed by enoxaparin for 7 days after discharge. We conducted this retrospective analysis to evaluate the efficacy of these measures in reducing the rate of VTE in this population. Methods: Retrospective electronic medical chart review to analyze data on living liver donors in our institution between January 2000 and February 2019. Inclusion criteria: all adult living liver donors who underwent partial right hepatectomy and followed for at least 6 weeks after surgery. The primary endpoint is the rate of VTE within 6 weeks of liver donation in patients who received post-discharge enoxaparin for one week in comparison to donors who did not receive enoxaparin. Secondary endpoints: re-admission rate and bleeding events. All continuous data was presented using means, medians and standard deviation, while categorical data were presented using counts and percentages. Results: At our institution 112 liver donors underwent right hepatectomy. Baseline characteristics (Table-1): The average age was 34 years, 58% were females and 86% were white. 10% of donors reported family history of DVT/PE. 90% of donors were screened for antiphospholipid antibody syndrome, with one case with positive titers. 34% of donors were screened for protein C (PC), Protein S (PS) and Antithrombin deficiency (AT-III). There were no cases of PC or AT-III deficiency, but one case of mild PS deficiency was identified. 38% cases were screened for factor V Leiden and prothrombin mutations, with 3 donors carrying heterozygous factor V Leiden mutation and one with heterozygous prothrombin mutation. All donors received prophylactic heparin during their stay in the hospital. A total of 15 donors had coagulation factors checked before and after the surgery. Post operatively, there was significant transient deficiency in PC, PS and AT-III, as well as significant increase in factor VIII level. This imbalance peaked within one week of surgery, with PC mean activity of 48%, PS mean activity of 48%, AT-III mean activity of 53% and FVIII of 290%. Factor activities started to recover by third week of surgery and returned to baseline within 8 weeks (figure 1). A total of 100 patients received one week of prophylaxis with Enoxaparin after being discharged from the hospital (Table-2). There was no VTE incidents in this group. 14/100 were readmitted to the hospital within 6 weeks of initial hospital admission; none due to bleeding. A total of 12 patients did not receive any pharmacological preventive measures upon discharge; due to in-hospital bleeding in 3 cases, prior to starting this strategy in 4 cases, unknown reason in 5 cases. VTE events and subsequent readmissions occurred in 2/12 (16.7%) (figure 2). Odds ratio could not be performed due to the very small number of patients in the comparison group (Table-2). Conclusion: Partial hepatectomy for liver donation is associated with significant remote hypercoagulable state due to the sudden loss in liver volume and concomitant transient deficiency of PC, PS and AT-III as well as increasing Factor VIII activity. This thrombophilia peaks within one week after the surgery and starts to recover by the third week. Clinicians should consider performing baseline thrombophilia screening and subsequently exclude potential donors with preexisting hypercoagulable state. Extending pharmacological VTE prevention with enoxaparin for 7 days after hospital discharge has been successful in reducing the VTE risk without increasing risk of bleeding or readmission rate in our patient population. Disclosures Kuriakose: Alexion: Consultancy, Honoraria, Speakers Bureau; Bayer: Consultancy.

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Prothrombin Fragment F1+2 Is not Predictive for Recurrent Venous Thromboembolism

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656062 ◽

1997 ◽

Vol 77 (05) ◽

pp. 0829-0833 ◽

Cited By ~ 19

Author(s):

P A Kyrle ◽

S Eichinger ◽

I Pabinger ◽

A Stümpflen ◽

M Hirschl ◽

...

Keyword(s):

Venous Thromboembolism ◽

Venous Thrombosis ◽

Protein C ◽

Oral Anticoagulants ◽

Factor V Leiden ◽

Factor V ◽

Recurrent Thrombosis ◽

Prothrombin Fragment ◽

Recurrent Venous Thromboembolism ◽

History Of

SummaryIt would be important to estimate in advance the risk of recurrent thrombosis. Deficiencies of antithrombin, protein C or protein S, or resistance to activated protein C are associated with a biochemically detectable prethrombotic state. It is thus far unknown whether in patients with a history of thromboembolism but without a defined clotting abnormality a heightened coagulation activation is detectable.We investigated the value of prothrombin fragment Fl+2 (FI+2) as a predictor of recurrent venous thromboembolism. Furthermore, we compared the Fl+2 levels of thrombosis patients without a defined clotting defect to those of Factor V Leiden patients with a history of venous thrombosis and to those of healthy controls. 180 patients without a defined clotting abnormality and 73 patients with Factor V Leiden were prospectively followed after discontinuation of oral anticoagulants for venous thrombosis and Fl+2 was measured at regular intervals.Recurrent venous thromboembolism occurred in 23 (9%) of the 253 patients. Before or at several time points after oral anticoagulants, no significant difference in Fl+2 levels was found in patients with and without recurrent thrombosis. Fl+2 levels at 3 weeks and prior to recurrence were not significantly different in both patient groups. Over a one-year observation period, Fl+2 levels of both patients with and without Factor V Leiden were higher than those of the controls. No difference in Fl+2 was seen between patients with and without Factor V Leiden.We conclude that monitoring of Fl+2 is not suitable for identification of individuals at risk of recurrent venous thrombosis. Permanent hemostatic system activation is detectable both in patients with a defined abnormality of the clotting system and in patients in whom a particular defect has not (yet) been identified.

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Co-inheritance of the 20210A Allele of the Prothrombin Gene Increases the Risk of Thrombosis in Subjects with Familial Thrombophilia

Thrombosis and Haemostasis ◽

10.1055/s-0038-1665427 ◽

1997 ◽

Vol 78 (06) ◽

pp. 1426-1429 ◽

Cited By ~ 114

Author(s):

M Makris ◽

F E Preston ◽

N J Beauchamp ◽

P C Cooper ◽

M E Daly ◽

...

Keyword(s):

Venous Thromboembolism ◽

Protein C ◽

Factor V Leiden ◽

Protein S ◽

Factor V ◽

Protein C Deficiency ◽

Antithrombin Deficiency ◽

Control Subjects ◽

Increased Risk ◽

Venous Thromboembolic

SummaryThe presence of the 20210A allele of the prothrombin (PT) gene has recently been shown to be a risk factor for venous thromboembolism. This is probably mediated through increased plasma prothrombin levels. The aim of this study was to compare the prevalence of the prothrombin 20210A allele in control subjects and in subjects with recognised thrombophilia and to establish whether the additional inheritance of the PT 20210A allele is associated with an increased risk of venous thromboembolism. 101 subjects with a history of venous thromboembolism and diagnosed as having either factor V Leiden (R506Q) or heritable deficiencies of protein C, protein S or antithrombin were studied. The prevalence of the PT 20210A allele in this group was compared with the results obtained for 150 control subjects. In addition, the relationships were examined between genetic status and the number of documented thromboembolic episodes, and between plasma prothrombin levels and possession of the PT 20210A allele. 8 (7.9%) of the 101 patients were also heterozygous for the PT 20210A allele. This compares with 0.7% in the control subjects (p = 0.005). After exclusion of patients on warfarin, the mean plasma prothrombin of 113 subjects without 20210A was 1.09 U/ml, as compared with 1.32 U/ml in 8 with the allele (p = 0.0002). Among the 101 patients with either factor V Leiden, protein S deficiency, protein C deficiency or antithrombin deficiency, the age adjusted mean (SD) number of venous thromboembolic episodes at diagnosis was 3.7 (1.5) in those with the PT 20210A allele, as compared with 1.9 (1.1) in those without (p = 0.0001). We have demonstrated that the prevalence of the PT 20210A allele is significantly greater in subjects with venous thrombosis and characterised heritable thrombophilia than in normal control subjects and that the additional inheritance of PT 20210A is associated with an increased risk of venous thromboembolism. We have also confirmed that plasma prothrombin levels are significantly greater in subjects possessing the PT 20210A compared with those who do not.

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