scholarly journals Signs of Hypofibrinolysis in Patients with Unprovoked Idiopathic Venous Thromboembolism

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3556-3556
Author(s):  
Fernanda Dutra Santiago Bassora ◽  
Fernanda Andrade Orsi ◽  
Graziela Silveira Araujo Alves ◽  
Silmara Aparecida De Lima Montalvão ◽  
Kiara Zapponi ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Conflicts Of Interest ◽  
Healthy Controls ◽  
Lysis Time ◽  
Fibrin Plate ◽  
Global Tests ◽  
Fibrinolysis Inhibitor ◽  
History Of ◽  
Pai 1 ◽  
Plasma Activity

Abstract Background: The causes for venous thromboembolism (VTE) remain undetermined in at least 30% of patients with unprovoked VTE. Hypofibrinolysis may be associated to VTE, however the occurrence of hypofibrinolysis in patients with unprovoked, idiopathic, VTE is not well stablished. Aims: To evaluate whether hypofibrinolysis would be associated with unprovoked idiopathic VTE. Methods: Patients with a history of unprovoked VTE without acquired or inherited thrombophilia were included. Global tests of fibrinolysis, such as euglobolin lysis time (ELT) and lysis area on fibrin plate (LAFP), and specific tests of fibrinolysis, such as plasma activity plasminogen, a-2 antiplasmin (a2AP), plasminogen activator inhibitor-1 (PAI-1), and thrombin activatable fibrinolysis inhibitor (TAFI), were performed in patients and healthy controls. We also analyzed the plasma activity of factor (F) XIII. Results: Thirty-one patients and fifty healthy controls were included. ELT results were higher in patients than in controls (median= 295 and IQ= 205-355 minutes vs. median=250 and IQ= 167-295 minutes, respectively, p = 0.006) and LAFP values were lower in patients compared to controls (median=81 and IQ= 56-110 vs. median= 95 and IQ 72-132 respectively, p = 0.0014), suggesting that they were experiencing a hypofibrinolytic state. Plasma activity of plasminogen (median= 131 and IQ= 119-141 vs. median=120 and IQ=111-137, respectively, p = 0.045) and FXIII (median= 103 and IQ 89-127 vs. median= 96 and IQ=80-105, respectively, p = 0.050), were higher in patients than in controls, whereas plasma activity of α-2AP was lower in patients (median= 124 and IQ 114-128 vs. median= 127 and IQ=121-133, p≤0.001). Interestingly, patient's median TAFI activity was lower than in controls (median=16 and IQ 13-18μg/mL vs. median= 19 and IQ= 17-21g/mL, p≤0.001). However, PAI-1 activity did not differ between groups. Conclusions: Hypofibrinolysis may occur in patients with unprovoked idiopathic VTE and may be detected by global tests of fibrinolysis. It is possible that hypofibrinolysis contribute to the pathogenesis of thrombosis in these selected cases. Disclosures No relevant conflicts of interest to declare.

Plasma fibrin clot properties in the G20210A prothrombin mutation carriers following venous thromboembolism: the effect of rivaroxaban

2017 ◽  
Vol 117 (09) ◽  
pp. 1739-1749 ◽  
Author(s):  
Agnieszka Janion-Sadowska ◽  
Joanna Natorska ◽  
Jakub Siudut ◽  
Michal Zabczyk ◽  
Andrzej Stanisz ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Mutation Carriers ◽  
Lysis Time ◽  
Prothrombin Mutation ◽  
Fibrinolysis Inhibitor ◽  
Heterozygous Carriers ◽  
Mutation Group ◽  
Clot Structure

SummaryWe sought to investigate whether the G20210A prothrombin mutation modifies plasma fibrin clot properties in patients after venous thromboembolism (VTE) and how rivaroxaban treatment affects these alterations. We studied 34 prothrombin mutation heterozygous carriers and sex- and age-matched 34 non-carriers, all at least three months since the first VTE episode, before and during treatment with rivaroxaban. Clot permeability (Ks) and clot lysis time (CLT) with or without elimination of thrombin activatable fibrinolysis inhibitor (TAFI) were assessed at baseline, 2–6 hours (h) after and 20–25 h after intake of rivaroxaban (20 mg/day). At baseline, the prothrombin mutation group formed denser clots (Ks −12 %, p=0.0006) and had impaired fibrinolysis (CLT +14 %, p=0.004, and CLT-TAFI +13 %, p=0.03) compared with the no mutation group and were similar to those observed in 15 healthy unrelated prothrombin mutation carriers. The G20210A prothrombin mutation was the independent predictor for Ks and CLT before rivaroxaban intake. At 2–6 h after rivaroxaban intake, clot properties improved in both G20210A carriers and non-carriers (Ks +38 %, and +37 %, CLT −25 % and −25 %, CLT-TAFI −20 % and −24 %, respectively, all p<0.001), but those parameters were worse in the prothrombin mutation group (Ks −12.8 %, CLT +17 %, CLT-TAFI +13 %, all p<0.001). Rivaroxaban concentration correlated with fibrin clot properties. After 20–25 h since rivaroxaban intake most clot properties returned to baseline. Rivaroxaban-related differences in clot structure were confirmed by scanning electron microscopy images. In conclusion, rivaroxaban treatment, though improves fibrin clot properties, cannot abolish more prothrombotic fibrin clot phenotype observed in prothrombin mutation carriers following VTE.

Decreased anticoagulant response to tissue factor pathway inhibitor in patients with venous thromboembolism and otherwise no evidence of hereditary or acquired thrombophilia

2004 ◽  
Vol 91 (01) ◽  
pp. 80-86 ◽  
Author(s):  
Brigitte Piccapietra ◽  
Johanna Boersma ◽  
Joerg Fehr ◽  
Thomas Bombeli
Keyword(s):  
Venous Thromboembolism ◽  
Venous Thrombosis ◽  
Mean Value ◽  
Healthy Controls ◽  
Crude Odds Ratio ◽  
Sensitivity Ratio ◽  
Increased Risk ◽  
History Of ◽  
Anticoagulant Response ◽  
Acquired Thrombophilia

SummaryNo relevant deficiency of TFPI or genetic polymorphisms could thus far consistently be associated with venous thromboembolism. We hypothesized that the substrates of the TFPI protein, including FVII or FX (rather than the protein itself) could induce a hypercoagulable state. We created a novel TF-based clotting assay that evaluated the anticoagulant response to exogenously added recombinant TFPI. The response to TFPI was expressed as the ratio of the clotting time with and without TFPI. By using 118 healthy controls, we established a reference range between 1.31 and 1.93 (mean value ± 2 standard deviations (SD), 1.62 ± 0.31). We then evaluated samples from 120 patients with a history of venous thromboembolism but no evidence of hereditary and acquired thrombophilia. The range of the patients’ ratios was significantly (P < 0.001) lower, falling between 1.2 and 1.78 (mean value ± 2 SD, 1.49 ± 0.29). Of the 120 patients, 39 (32.5%) had a TFPI sensitivity ratio below the 10th percentile of the controls, compared with 11 (9.3%) of the healthy controls. The crude odds ratio for venous thrombosis for subjects with a TFPI sensitivity ratio below the 10th percentile was 13 (95% CI; range, 3.1 to 54.9) compared with those with a ratio above 1.8 (90th percentile). Patients with idiopathic thromboembolism did not have a decreased TFPI sensitivity ratio more often than patients with thrombosis with a circumstantial risk factor. Based on these results, a reduced response to TFPI may lead to an increased risk of venous thrombosis.

Diet, Lifestyle and Venous Thromboembolism (VTE) in Thai Population.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1414-1414
Author(s):  
Ponlapat Rojnuckarin ◽  
Lantarima Bhoopat ◽  
Narin Hiransuthikul ◽  
Tanin Intragumtornchai
Keyword(s):  
Venous Thromboembolism ◽  
National Health ◽  
Fast Food ◽  
Conflicts Of Interest ◽  
Health Examination ◽  
Thai Population ◽  
P Values ◽  
Spicy Food ◽  
Prevalence Of Obesity ◽  
History Of

Abstract Abstract 1414 Poster Board I-437 Introduction: Previous studies demonstrated that the incidence of venous thromboembolism (VTE) was very low among Thais (Lancet. 1975; 1: 1357-8, Arch Intern Med. 1988; 148: 1349-53). However, recent investigations in Asian countries strongly indicated that VTE is currently much more common, approaching rates in the western countries. Meanwhile, the latest National Health Surveys showed the inadequate vegetable and fruit intakes, as well as an obvious rise in prevalence of obesity in Thai population. Therefore, changing diet and behaviors are suspected to contribute to this marked increase in the VTE incidence. Patients and Methods The case-control study was conducted. Cases were objectively confirmed venous thromboembolism. Patients with underlying cancer, antiphospholipid syndrome and arterial thrombosis were excluded. Controls are age- and sex-matched healthy volunteers. Body mass indices, history of alcohol intake, smoking and exercise were obtained. Food consumptions were interviewed using a food frequency questionnaire modified from the Thailand National Health Examination Survey III previously validated in Thai population. Results: There were 97 cases and 195 controls. The mean age was 54.6 yr, ranging from 17-93 yr, and 70% were female. VTE was significantly associated with low vegetable intakes (below 3.5 standard servings per day) compared with controls (Odd ratio [OR] 2.5, 95% confidence interval [CI] 1.37-4.67), while there was no difference in fruit consumption (p values =0.53). Notably, low fish intakes (below 0.1 serving per day, OR 3.9, 95%CI 1.58-9.71) and having spicy food less than once a week (OR 1.9, 95%CI 1.15-3.18) also increased the risk. The meat, fat, carbohydrate, fast food or alcohol consumptions were similar. In addition, VTE was associated with overweight (OR 2.1, 95%CI 1.21-3.62) and obesity (OR 3.1, 95%CI 1.46-6.74, p values = 0.002 and 0.001, respectively). Furthermore, estrogen uses also increased the risk of VTE (OR 3.7, 95% CI 1.05-13.20, p=0.02), while smoking and lack of exercise did not. Conclusions: Low vegetable, fish and spicy food intakes, as well as obesity and hormonal uses, are the risk factors for VTE in Thai population. Disclosures: No relevant conflicts of interest to declare.

Circulating Microparticles and Risk of Venous Thromboembolism.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3987-3987
Author(s):  
Paolo Bucciarelli ◽  
Emanuele Previtali ◽  
Ida Martinelli ◽  
Andrea Artoni ◽  
Serena M Passamonti ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Venous Thromboembolism ◽  
Body Mass ◽  
Plasma Levels ◽  
Conflicts Of Interest ◽  
Factor V Leiden ◽  
Control Group ◽  
Dependent Manner ◽  
Healthy Controls ◽  
Increased Risk

Abstract Abstract 3987 Poster Board III-923 Background Microparticles (MPs) are circulating, submicroscopic fragments (<1 μm of diameter) of membrane-bound cytoplasm that shed from the surface of an activated or apoptotic cell and play a role in coagulation, inflammation, cell remodelling and proliferation. There is increasing evidence that MPs are involved in thrombosis, but whether or not they are an independent risk factor for venous thromboembolism (VTE) is not established. Aim of the study To investigate the association between high plasma levels of MPs and risk of VTE Patients and Methods In a case-control study, 186 patients with a first episode of VTE (deep venous thrombosis and/or pulmonary embolism) and 418 healthy controls were included. MPs were analyzed by flow cytometry with a gate defined by a 1 μm beads and using APC-Annexin V together with FITC anti-CD41 or FITC anti-CD142 antibodies in order to identify platelet MPs (MP-Plts) and MPs exposing tissue factor (MP-TF), respectively. MPs levels were expressed as number/μL. Results Patients had significantly higher median plasma levels of both MPs-Plts and MPs-TF than controls [1942 vs 1519 (p<0.0001) and 579 vs 454 (p<0.0001)]. Higher median levels of MP-Plts and MP-TF were found in 41 patients who underwent blood sampling within 6 months from VTE than in those sampled later [2114 vs 1694 (p=0.086) and 652 vs 543 (p=0.120)]. Sex, age, body mass index and factor VIII plasma levels had no influence on MPs levels, as well as the use of oral contraceptives (this latter evaluated only in controls). In the whole study population, carriership of thrombophilia (antithrombin, protein C or protein S deficiency, factor V Leiden, prothrombin G20210A, antiphospholipid antibodies, hyperhomocysteinemia or combined abnormalities) had higher levels of MP-Plts and MP-TF than non-carriers [1907 vs 1565 (p=0.002) and 532 vs 468 (p=0.011)]. The odds ratio (OR) for VTE, adjusted for sex, age, body mass index and thrombophilia was 2.5-fold higher in individuals with MPs plasma levels >95th percentile of the control group (3633/μL for MPs-Plts and 1113/μL for MPs-TF) than in those with MPs levels ≤95th percentile [for MPs-Plts: OR=2.59 (95%CI 1.23 – 5.45); for MPs-TF: OR=2.38 (1.15 – 4.92)]. The risk increased in a dose-dependent manner for both MPs-Plts and MPs-TF, particularly above the 75th percentile of the distribution in controls. The exclusion of patients whose MPs levels were measured within 6 months from VTE (in order to avoid the possible effect of the acute phase on MPs measurements), did not change the results [adjusted OR: 2.63 (1.18 – 5.89) for MPs-Plts and 2.36 (1.10 – 5.19) for MPs-TF]. The Table shows the relative risks of VTE associated with the presence or absence of high MPs levels and thrombophilia. Individuals with MPs >95th percentile or thrombophilia alone had a 2 to 3-fold increased risk of VTE, whereas those with both MPs-Plts >95th percentile and thrombophilia had a 9-fold increased risk of VTE. This synergistic effect was confirmed also for MPs-TF and remained after the exclusion of patients whose blood sample was collected within 6 months from VTE [OR 7.72 (1.68-35.4) for MP-Plts and 8.14 (2.08-31.8) for MP-TF]. Conclusions Plasma levels of MPs are significantly higher in patients with VTE than in healthy controls. MPs levels >95th percentile are associated with a 2.5-fold increased risk of VTE. There is a synergistic interaction between high levels of MPs and thrombophilia on VTE risk. Disclosures: No relevant conflicts of interest to declare.

Application of Thrombomodulin-Thrombin Generation to Diverse Abnormalities of the Protein C System

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 31-32
Author(s):  
Marilyn J Manco-Johnson ◽  
Linda Jacobson ◽  
Dianne Thornhill ◽  
Christine Baird ◽  
Beth Boulden Warren
Keyword(s):  
Family History ◽  
Lupus Anticoagulant ◽  
Protein C ◽  
Thrombin Generation ◽  
Conflicts Of Interest ◽  
Positive Family History ◽  
Factor V Leiden ◽  
Healthy Controls ◽  
Blood Draw ◽  
History Of

Background: Increased thrombin generation is an interesting candidate as a potential indicator of hypercoagulability and thrombosis risk. Increased thrombin generation using the calibrated automated thrombogram (CAT) has been reported in antithrombin deficiency but the CAT does not reflect protein C deficiency without the addition of thrombomodulin (TM). TM activates protein C (PC) in the CAT and reduces thrombin generation. Objective: The objective of this study was to determine the capacity of the TM-augmented CAT to detect defects in various protein C system components; the lupus anticoagulant was also investigated as a cause of decreased protein C activation. Methods: The CAT-TM was performed with reagents and methods per the manufacturer's instructions using 5 pM tissue factor and TM (Stago). Other assays included: PC (chromogenic), free protein S (PS, LIA), activated protein C resistance (aPTT-based clotting assay), factor V Leiden (FVL PCR) and lupus anticoagulant (LA, dRVVT and Staclot LA, Stago). Platelet poor plasma samples were obtained from the biobank of a consented prospective inceptional cohort study of thrombosis and thrombophilia or a positive family history of either (ThromboPICS #05-0339); samples from healthy controls with no personal or family history of thrombosis or thrombophilia were collected on a consented protocol (#09-0816). Samples from participants on therapeutic inhibitors of factor Xa or thrombin were treated with appropriate neutralizers; no sample was tested on warfarin. Clinical data included gender, age (&lt; 18 versus ≥ 18 years), history of thrombosis, timing of sample from most recent thrombosis (acute &lt; 14 days; subacute 14-90 days; or chronic &gt; 90 days) and use of anticoagulants at the time of the blood draw. Tests for violations of normality were negative. Therefore, results of cohorts versus controls were compared with independent sample t-test and subgroup analyses relative to control used One-Way ANOVA. Post-hoc comparisons of each subgroup to the controls were collected for multiple comparisons using the Bonferroni correction. Results: Ninety-nine cases and 45 normal controls were studied. Overall half of the cases had a history of thrombosis and 66% of those with thrombosis were on no anticoagulation at the time of testing. Table 1 displays results of the CAT-TM in the 2 control and 6 study groups. Control adults and children showed a mean 50% thrombin reduction in thrombin generation with CAT-TM; overall, persons with protein C system defects showed approximately 25% reduction, with the least reduction of thrombin generation in the cohort of PC deficiency at 19%. Sensitivity of the CAT-TM was 100% for PC deficiency, 81% for LA positivity, 80% for PS deficiency and 72% for FVL positivity with no difference in degree of thrombin reduction between hetero- and homozygous FVL. In addition, we identified 14 individuals with CAT-TM results similar to protein C system defects but with confirmed normal PC, PS, FVL and LA tests. Although 9 of these unknowns had a personal (7) or family (2) history of thrombosis, five came from the healthy controls. The false positive results in 3 adult and 2 pediatric controls conferred a CAT-TM test specificity of 89%. Furthermore, analyses showed no differences in CAT-TM results related to gender, age group, history of thrombosis, age of clot at blood draw (acute, subacute or chronic) or use of anticoagulation at the time of blood draw. Conclusions: The CAT-TM is a useful screening test for defects in the protein C system, including LA, although this test could not discriminate between heterozygous and homozygous FVL. The etiology of positive CAT-TM in normal individuals or individuals with a personal or family history of thrombosis without identified PC system defects is currently unknown and under ongoing investigation. Disclosures No relevant conflicts of interest to declare.

Over-Expression of PAI-1 and TAFI Predict Stroke: Two Faces of Ame Coin

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5249-5249
Author(s):  
Giorgio Corinaldesi
Keyword(s):  
Conflicts Of Interest ◽  
Early Stage ◽  
Serine Proteinase ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Over Expression ◽  
Control Subjects ◽  
Fibrinolysis Inhibitor ◽  
Healthy Control ◽  
Pai 1

Abstract 5249 TAFI (thrombin-activated fibrinolysis inhibitor) and PAI-1 play important roles in fibrinolysis, as they both reduce plasmin generation; PAI-1 a 50 KDa glycoprotein is a serine-proteinase inhibitor; TAFI is a 55 KDa plasma zymogen that is activated by either plasmin/thrombin or thrombin/thrombomodulin complex into an active carboxypeptidase, in particular, it is a basic zinc dependent metallo-carboxipeptidase specific for C-terminal lysine and arginine residue inhibiting degradation of the fibrin clot. We investigated the influence of PAI-1 and TAFI levels on stroke by determining their plasmatic antigen concentration by an electro-immunoassay. We found that PAI-1 levels are increased during the early stage of stroke and that it may also predict clot lysis resistance in patients treated with trombolysis (38.8 ng/ml +/− 14.6, p <0.0001) compared with control subjects (16.2 ng/ml +/−6.8, p <0.0001); TAFI levels were significantly higher in patient with stroke (184.8 nmol/l +/− 62.6 nmol/l), than in healthy control subjects (102.4 nmol/l +/− 36.4 nmol/l, p <0.0001). We have observed that a combination of both PAI-1 higher than 24.6 mg/ml (OR: 12.8. CI: 1.16 to 134.2), and TAFI higher than >180 nmol/l (OR.12.9 CI 1.42 to 116.6), had a sensibility of 92.2%, and a specificity of 98.4% in predicting stroke. The analysis of these results showed that TAFI antigen levels higher than 180nmo/L combined with PAI-1 levels higher than 24 mg/ml are a strong risk factor for clot lysis, stroke (for the evolution, severity, and outcome) and showed a potentially attractive target for fibrinolytic therapies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Fibrinolysis in pregnancy: a study of plasminogen activator inhibitors

Blood ◽  
1987 ◽  
Vol 69 (2) ◽  
pp. 460-466 ◽  
Author(s):  
EK Kruithof ◽  
C Tran-Thang ◽  
A Gudinchet ◽  
J Hauert ◽  
G Nicoloso ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Fibrinolytic System ◽  
Tissue Type ◽  
Single Chain ◽  
Type Plasminogen Activator ◽  
Fibrin Plate ◽  
Pai 1 ◽  
In Pregnancy ◽  
Plasma Activity

During pregnancy the plasma concentration of two different inhibitors of plasminogen activators (PAIs) increases. The only one found in the plasma of nonpregnant women (PAI1) is immunologically related to a PAI of endothelial cells; its plasma activity, as deduced from the inhibition of single-chain tissue-type plasminogen activator (t-PA), increased from 3.4 +/- 2.3 U/mL (mean +/- 95% confidence limits) in the plasma of nonpregnant women to 29 +/- 7 U/mL at term, and its antigen level, measured by a radioimmunoassay, increased from 54 +/- 17 ng/mL to 144 +/- 25 ng/mL. In pregnancy plasma a second PAI (PAI 2) related to a PAI found in placenta extracts was observed. Its level, quantified with a radioimmunoassay, increased from below the detection limit (approximately 10 ng/mL) in normal plasma to 260 ng/mL at term. One hour after delivery, PAI 1 activities and antigen decreased sharply, but the PAI 2 antigen levels remained constant. Three days later, the PAI 1 antigen levels had fallen to normal levels, but the PAI 2 antigen levels were still at least eightfold above the nonpregnant values. During pregnancy, the t-PA and prourokinase (u-PA) antigen concentrations increased 50% and 200%, respectively, whereas the plasminogen and alpha 2-antiplasmin levels remained constant. Despite the large variations in the levels of PAs and PAIs, the overall fibrinolytic activity as measured in diluted plasma by a radioiodinated fibrin plate assay did not change significantly. Just after delivery, a great increase in the t-PA antigen levels was observed. Three to five days after delivery most parameters of the fibrinolytic system were normal again. Our results demonstrate that during pregnancy and in the puerperium profound alterations of the fibrinolytic system occur that are characterized by increases in PAs and their inhibitors, but these alterations do not affect the overall fibrinolytic activity.

Marburg I polymorphism of factor VII–activating protease is associated with idiopathic venous thromboembolism

Blood ◽  
2005 ◽  
Vol 105 (4) ◽  
pp. 1549-1551 ◽  
Author(s):  
Berthold Hoppe ◽  
Farzaneh Tolou ◽  
Hartmut Radtke ◽  
Holger Kiesewetter ◽  
Thomas Dörner ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Odds Ratio ◽  
Independent Risk Factor ◽  
Case Control Study ◽  
Case Control ◽  
Factor Vii ◽  
Healthy Controls ◽  
History Of ◽  
Control Study

AbstractThe factor VII–activating protease (FSAP) variant Marburg I is known to attenuate the profibrinolytic system in vitro and was recently shown to be a significant predictor for the evolution and progression of carotid stenosis. The objective of this case-control study was to assess FSAP Marburg I's role in the occurrence of venous thromboembolism (VTE). The frequency of FSAP Marburg I was significantly increased in patients with a history of VTE (17 of 213 patients, 8.0%, P = .014) or idiopathic VTE (12 of 103 patients, 11.7%, P = .002) compared to healthy controls (5 of 213 controls, 2.3%). Logistic regression analysis confirmed FSAP Marburg I to be an independent risk factor for VTE (odds ratio, 3.5; 95% confidence interval [CI], 1.2-10.0) and idiopathic VTE (odds ratio, 6.2; 95% CI, 2.0-18.9).

Family History of Venous Thromboembolism (VTE) and the Risk of VTE Recurrence in Patients with a First Unprovoked VTE: A Multicenter Prospective Cohort Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2299-2299
Author(s):  
Karine Gauthier ◽  
Elham Sabri ◽  
Susan R. Kahn ◽  
Philip S Wells ◽  
David Anderson ◽  
...  
Keyword(s):  
Cohort Study ◽  
Venous Thromboembolism ◽  
Family History ◽  
Conflicts Of Interest ◽  
Anticoagulation Therapy ◽  
Degree Relative ◽  
National Cohort ◽  
History Of ◽  
Recurrent Vte ◽  
Second Degree

Abstract Abstract 2299 Introduction: The duration of anticoagulation after unprovoked venous thromboembolism (VTE) has been characterized as the most important unanswered question in clinical thrombosis management. This has led to research to identify predictors of recurrent VTE to identify high-risk patients who might warrant indefinite anticoagulation. Many clinicians assume that a family history of VTE is a predictor of recurrent VTE. This study aims to assess the value of family history as a predictor for recurrent VTE. Methods: Prospective multi-center multi-national cohort study recruited patients with a first objectively proven unprovoked VTE who completed 5 to 7 months of anticoagulation therapy. A detailed family history of VTE was completed for every subject. The information recorded included the number of affected relatives, whether they were first or second degree relatives and if the VTE was unprovoked or secondary. Patients were then followed for recurrent VTE. Results: 664 subjects were enrolled between October 2001 and March 2006, 649 subjects were followed for a mean duration of 3.8 years (3.6–3.98 95% C.I.). The mean age of subjects in this cohort was 53 years (min-max 18–95) and 49% of subjects were females. A family history of VTE in at least 1 first-degree relative was recorded for 112 (17.3%) subjects. A total of 142 (21.9%) suspected VTE events were adjudicated as recurrences. The recurrence rate was 5.94% (4.89–7.15 95% C.I.) per patient-year for patients without any family history of VTE, and it was 4.82% (3.02–7.30 95% C.I.) per patient-year in patients with a family history of VTE in at least 1 first-degree relative. In secondary analyses, neither a family history of unprovoked VTE, multiple unprovoked VTE, in first-degree nor second-degree relatives was a predictor of recurrent VTE. A multivariate analysis was performed to adjust for known risk factors for VTE recurrence, but the adjusted hazard ratios were again not significantly different. Conclusion: A family history of VTE is not a predictor for recurrent VTE, and therefore should not be used to segregate unprovoked VTE patients in high- and low-risk categories. Disclosures: No relevant conflicts of interest to declare.

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