Abnormal Protac-induced coagulation inhibition chromogenic assay results are associated with an increased risk of recurrent venous thromboembolism

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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Non-OO blood type influences the risk of recurrent venous thromboembolism

Thrombosis and Haemostasis ◽

10.1160/th13-06-0488 ◽

2013 ◽

Vol 110 (12) ◽

pp. 1172-1179 ◽

Cited By ~ 33

Author(s):

Esteban Gándara ◽

Michael J. Kovacs ◽

Susan R. Kahn ◽

Philip S. Wells ◽

David A. Anderson ◽

...

Keyword(s):

Risk Factor ◽

Venous Thromboembolism ◽

Anticoagulant Therapy ◽

Oral Anticoagulation ◽

Blood Type ◽

Increased Risk ◽

Recurrent Venous Thromboembolism ◽

Abo Blood Type ◽

Recurrent Vte

SummaryThe role of ABO blood type as a risk factor for recurrent venous thromboembolism (VTE) in patients with a first unprovoked VTE who complete oral anticoagulation therapy is unknown. The aim of this study was to determine if non-OO blood type is a risk factor for recurrent VTE in patients with a first unprovoked VTE who completed 5–7 months of anticoagulant therapy. In an ongoing cohort study of patients with unprovoked VTE who discontinued oral anticoagulation after 5–7 months of therapy, six single nucleotide polymorphisms sites were tested to determine ABO blood type using banked DNA. The main outcome was objectively proven recurrent VTE. Mean follow-up for the cohort was 4.19 years (SD 2.16). During 1,553 patient-years of follow-up, 101 events occurred in 380 non-OO patients (6.5 events per 100 patient years; 95% CI 5.3–7.7) compared to 14 events during 560 patient years of follow-up in 129 OO patients (2.5 per 100 patient years; 95% CI 1.2–3.7), the adjusted hazard ratio was 1.98 (1.2–3.8). In conclusion, non-OO blood type is associated with a statistically significant and clinically relevant increased risk of recurrent VTE following discontinuation of anticoagulant therapy for a first episode of unprovoked VTE.

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Prediction of Recurrent Venous Thromboembolism by Endogenous Thrombin Potential and D-Dimer

Clinical Chemistry ◽

10.1373/clinchem.2008.112243 ◽

2008 ◽

Vol 54 (12) ◽

pp. 2042-2048 ◽

Cited By ~ 82

Author(s):

Sabine Eichinger ◽

Gregor Hron ◽

Marietta Kollars ◽

Paul A Kyrle

Keyword(s):

Venous Thromboembolism ◽

Thrombin Generation ◽

Factor V Leiden ◽

Study Endpoint ◽

Factor V ◽

Risk Of Recurrence ◽

Endogenous Thrombin Potential ◽

Increased Risk ◽

Recurrent Venous Thromboembolism ◽

D Dimer

Abstract Background: Increased thrombin generation is associated with an increased risk of recurrent venous thromboembolism. We investigated the relation between endogenous thrombin potential (ETP) and risk of recurrent venous thromboembolism and evaluated whether prediction of recurrence can be improved by a combined analysis of ETP and D-dimer. Methods: We followed 861 patients with first spontaneous venous thromboembolism and determined ETP and D-dimer after discontinuation of anticoagulation. Patients with natural inhibitor deficiency, lupus anticoagulant, or cancer were excluded. The study endpoint was symptomatic recurrent venous thromboembolism. Results: One hundred thirty patients (15.1%) had recurrence. High ETP (≥100%) conferred a 1.6-fold increased risk of recurrence (95% CI 1.1–2.3) after adjustment for age, sex, factor V Leiden, factor II G20210A, and duration of anticoagulation. After adjustment for D-dimer, risk of recurrence remained significantly higher among patients with high ETP [hazard ratio 1.6 (95% CI 1.01–2.4)]. After adjustment for ETP, high D-dimer (≥0.5 mg/L) conferred a 1.8-fold (95% CI 1.1–2.8) increased risk of recurrence. Compared with patients with low ETP and low D-dimer, risk of recurrence was 2.8-fold (95% CI 1.5–5.3) higher among patients with both high ETP and high D-dimer after adjustment for potential confounders. Conclusions: ETP and D-dimer are independent predictors of recurrent venous thromboembolism. Assessing risk of recurrence can be optimized by combining these indicators of thrombin generation.

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Risk of recurrent venous thromboembolism in COPD patients: results from a prospective cohort study

European Respiratory Journal ◽

10.1183/13993003.00094-2017 ◽

2017 ◽

Vol 50 (1) ◽

pp. 1700094 ◽

Cited By ~ 3

Author(s):

Raphael Le Mao ◽

Cécile Tromeur ◽

Amélie Bazire ◽

Maelenn Gouillou ◽

Marie Guegan ◽

...

Keyword(s):

Venous Thromboembolism ◽

Prospective Cohort ◽

Multivariate Analyses ◽

Anticoagulation Therapy ◽

Secondary Outcome ◽

Risk Of Death ◽

Copd Patients ◽

Increased Risk ◽

Recurrent Venous Thromboembolism ◽

Recurrent Vte

We aimed to assess the risk of recurrent venous thromboembolism (VTE) in patients with chronic obstructive pulmonary disease (COPD) following cessation of anticoagulation therapy.In a prospective cohort of 1468 patients with a documented episode of VTE, followed for up to 5 years after cessation of anticoagulation therapy, the diagnosis of COPD was confirmed in 136. The main outcome was recurrent VTE. The secondary outcome was overall mortality. Univariate and multivariate analyses were performed to identify the risk factors of recurrence.Of the 1468 patients included, recurrent VTE was observed in 306 (34 with COPD and 272 without) during a median follow-up period of 36.5 months. The incidence rate of recurrent VTE was 9.1% (95% CI 6.5–12.8) for COPD patients and 7.0% (95% CI 6.2–7.9) for non-COPD patients. COPD was not associated with an increased risk of VTE recurrence on univariate or multivariate analyses (hazard ratio: 1.0 (95% CI 0.7–1.4)). The risk of death, adjusted for demographic and clinical characteristics, showed no increase in COPD patients, as compared to non-COPD patients.In patients with COPD who had an acute episode of VTE, the risk of recurrent VTE was not any higher than that in non-COPD patients.

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Risk of Venous Thromboembolism Is Not Increased by Elevated TAFI Levels.

Blood ◽

10.1182/blood.v108.11.1484.1484 ◽

2006 ◽

Vol 108 (11) ◽

pp. 1484-1484

Author(s):

Nienke Folkeringa ◽

Jan Leendert P. Brouwer ◽

Nic J.G.M Veeger ◽

Jan van der Meer

Keyword(s):

Risk Factor ◽

Venous Thromboembolism ◽

Protein C ◽

Absolute Risk ◽

Large Family ◽

Protein S ◽

High Plasma ◽

Prothrombin G20210a ◽

Chromogenic Assay ◽

Increased Risk

Abstract TAFI (Thrombin-activatable fibrinolysis inhibitor) is a suppressor of fibrinolysis and high plasma levels of TAFI are assumed to induce venous thromboembolism (VTE). A few studies published on this subject identified TAFI as a mild risk factor for VTE. The risk may be increased if high TAFI levels are combined with other trombophilic defects. We performed a retrospective study to asses the absolute risk of VTE associated with elevated levels of TAFI and the contribution of concomitant thrombophilic defects. Subjects were recruited from a previous large family cohort study, which was designed to estimate the risk of VTE in first degree relatives of probands with documented VTE and a hereditary deficiency of antithrombin, protein C or protein S. Probands were excluded from analysis. Blood samples of relatives were tested on deficiencies of antithrombin, protein C and protein S, prothrombin G20210A, factor FV Leiden, hyperhomocysteinemia and increased levels of factor VIII:C, IX:C and XI:C. TAFI activity was additional measured by chromogenic assay on plasma samples stored at minus 80 degrees Celsius. We analysed 350 of 457 relatives, who were tested on TAFI. TAFI levels observed in women were lower than in men (median 97 versus 106 U/dL) and increased with age (median from 95 U/dL at age 15–30 yr to 107 U/dL at age>60 yr). Relatives with TAFI levels above the 90th percentile (>128 U/dL) had the same absolute risk of VTE as relatives with TAFI levels below the 90th percentile. Annual incidences (AI) were 0.74 versus 0.72 % per year: relative risk (RR) 1.0; 95% CI.0.51–2.10 (Table). Concomitant thrombophilic defects were demonstrated in 82% of the relatives. These defects were equally distributed among relatives with TAFI levels of >90th versus <90th percentile. Relatives with TAFI levels above the 90th percentile and concomitance of at least one other thrombophilic defect were not at increased risk of VTE compared to relatives with lower TAFI levels and concomitant thrombophilic defects (RR 0.83; 95% CI 0.41–1.68). Our data do not support that eleveated TAFI levels are a risk factor for VTE. The high absolute risk of VTE among relatives is mainly due to the presence of other thrombophilic defects rather than elevated TAFI levels, as interactions between TAFI and other thrombophilic defects were not demonstrated. VTE (n) Observation years AI (95% CI) RR (95% CI) TAFI > 90th percentile 9 1209 0.74 (0.3–1.4) 1.0 (0.51–2.10) Concomitance 9 1147 0.78 (0.4–14.9) 0.83 (0.41–1.68) No concomitance 0 62 0 TAFI < 90th percentile 53 7364 0.72 (0.5–0.9) Ref Concomitance 53 5724 0.93 (0.7–1.2) Ref No concomitance 0 1426 0

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The Occurrence of Subsequent Malignancy in Patients Presenting with Deep Vein Thrombosis: Results from a Historical Cohort Study

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614211 ◽

1998 ◽

Vol 79 (01) ◽

pp. 19-22 ◽

Cited By ~ 29

Author(s):

Raghu Rajan ◽

Michael Gent ◽

Jack Hirsh ◽

William Geerts ◽

Peter Skingley ◽

...

Keyword(s):

Cohort Study ◽

Deep Vein Thrombosis ◽

Venous Thromboembolism ◽

Oral Anticoagulant Therapy ◽

Historical Cohort ◽

Vein Thrombosis ◽

Historical Cohort Study ◽

Increased Risk ◽

Recurrent Venous Thromboembolism ◽

Deep Vein

SummaryBackground: Several studies have reported that patients who present with idiopathic deep vein thrombosis (DVT) have an increased risk of subsequently developing cancer. A clinical trial had previously been conducted examining the optimal duration of oral anticoagulant therapy following initial heparin treatment in patients with proximal DVT.Methods: A historical cohort study was performed on patients enrolled in the duration of anticoagulant trial. Patients known to have cancer at the time of entry into the trial were excluded. The qualifying DVTs were classified as idiopathic (no known associated risk factors) or secondary without knowledge of subsequent recurrent venous thrombosis or cancer. The patients were then followed for the development of cancer.Results: Thirteen (8.6%) of the 152 patients in the idiopathic cohort subsequently developed cancer compared to eight (7.1%) of 112 patients in the secondary cohort, P = 0.86. Two (5.4%) of 37 patients with recurrent venous thromboembolism and 19 (8.4%) of 227 patients without recurrent thromboembolism developed cancer, P = 0.7.Conclusion: Our study did not detect an increased risk of subsequent cancer in patients presenting with idiopathic DVT compared to secondary DVT; nor did we detect an increased incidence of cancer in patients with recurrent venous thromboembolism. Further studies are required prior to pursuing a policy of aggressive screening for cancer in patients with idiopathic venous thromboembolism.

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Elevated albuminuria associated with increased risk of recurrent venous thromboembolism: results of a population-based cohort study

British Journal of Haematology ◽

10.1111/j.1365-2141.2011.09018.x ◽

2012 ◽

Vol 156 (5) ◽

pp. 667-671 ◽

Cited By ~ 11

Author(s):

Inge M. van Schouwenburg ◽

Bakhtawar K. Mahmoodi ◽

Nic J. G. M. Veeger ◽

Hanneke C. Kluin-Nelemans ◽

Ron T. Gansevoort ◽

...

Keyword(s):

Cohort Study ◽

Venous Thromboembolism ◽

Population Based ◽

Increased Risk ◽

Recurrent Venous Thromboembolism

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S1111 Increased Risk of Recurrent Venous Thromboembolism in Inflammatory Bowel Disease

Gastroenterology ◽

10.1016/s0016-5085(09)60860-x ◽

2009 ◽

Vol 136 (5) ◽

pp. A-191

Author(s):

Gottfried Novacek ◽

Ansgar Weltermann ◽

Anna Sobala ◽

Sabine Eichinger ◽

Wolfgang Petritsch ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Venous Thromboembolism ◽

Bowel Disease ◽

Increased Risk ◽

Recurrent Venous Thromboembolism ◽

Inflammatory Bowel

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Risk factors for recurrent venous thromboembolism after unprovoked pulmonary embolism: the PADIS-PE randomised trial

European Respiratory Journal ◽

10.1183/13993003.01202-2017 ◽

2018 ◽

Vol 51 (1) ◽

pp. 1701202 ◽

Cited By ~ 14

Author(s):

Cécile Tromeur ◽

Olivier Sanchez ◽

Emilie Presles ◽

Gilles Pernod ◽

Laurent Bertoletti ◽

...

Keyword(s):

Risk Factors ◽

Pulmonary Embolism ◽

Venous Thromboembolism ◽

Antiphospholipid Antibodies ◽

Randomised Trial ◽

Double Blind ◽

Increased Risk ◽

Recurrent Venous Thromboembolism ◽

Lung Scan ◽

Pulmonary Embolism Diagnosis

We aimed to identify risk factors for recurrent venous thromboembolism (VTE) after unprovoked pulmonary embolism.Analyses were based on the double-blind randomised PADIS-PE trial, which included 371 patients with a first unprovoked pulmonary embolism initially treated during 6 months who were randomised to receive an additional 18 months of warfarin or placebo and followed up for 2 years after study treatment discontinuation. All patients had ventilation/perfusion lung scan at inclusion (i.e. at 6 months of anticoagulation).During a median follow-up of 41 months, recurrent VTE occurred in 67 out of 371 patients (6.8 events per 100 person-years). In main multivariate analysis, the hazard ratio for recurrence was 3.65 (95% CI 1.33–9.99) for age 50–65 years, 4.70 (95% CI 1.78–12.40) for age >65 years, 2.06 (95% CI 1.14–3.72) for patients with pulmonary vascular obstruction index (PVOI) ≥5% at 6 months and 2.38 (95% CI 1.15–4.89) for patients with antiphospholipid antibodies. When considering that PVOI at 6 months would not be available in practice, PVOI ≥40% at pulmonary embolism diagnosis (present in 40% of patients) was also associated with a 2-fold increased risk of recurrence.After a first unprovoked pulmonary embolism, age, PVOI at pulmonary embolism diagnosis or after 6 months of anticoagulation and antiphospholipid antibodies were found to be independent predictors for recurrence.

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