Oral Anticoagulation after a First Episode of Venous Thromboembolism: How Long? How Strong?

1999 ◽  
Vol 82 (S 01) ◽  
pp. 124-126 ◽  
Author(s):  
H. H. Watzke
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Venous Thrombosis ◽  
Short Duration ◽  
Oral Anticoagulation ◽  
Thrombotic Event ◽  
First Episode ◽  
Optimal Duration ◽  
Optimal Intensity ◽  
Shed Light

SummaryA number of studies have been published in the last years which shed light on the optimal intensity and the optimal duration of oral anticoagulation in patients with venous thrombosis.Based on these studies it is now generally recommended to treat patients with venous thromboembolism at an INR ranging from 2.0 to 3.0. The optimal duration of anticoagulation mainly depends on the nature of the thrombotic event. In patients with a temporary prothrombotic risk factor such as surgery, immobilization or trauma a relatively short duration of oral anticoagulation (3-6 months) is generally recommended. Patients with idiopathic venous thromboembolism require a considerably longer duration of anticoagulation (6 months at least).

High factor VIII and the risk of venous thromboembolism

2003 ◽  
Vol 23 (01) ◽  
pp. 41-44 ◽  
Author(s):  
Paul A. Kyrle
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Venous Thrombosis ◽  
Factor Viii ◽  
Coagulation Factor ◽  
Convincing Evidence ◽  
Important Risk Factor ◽  
First Episode ◽  
Phase Reaction ◽  
Therapeutic Concept

SummaryThere is now convincing evidence that a high level of coagulation factor VIII is an important risk factor for venous thromboembolism. A factor VIII plasma concentration above 1500 IU/l is associated with an almost 5-fold risk for a first episode of venous thrombosis. In thrombosis patients high factor VIII has been shown to persist over time and is not related to an acute phase reaction. High factor VIII is also an important risk factor for recurrence of venous thrombosis. In a prospective cohort study factor VIII levels exceeding the 90th percentile of the patient population confered an almost 7-fold risk of recurrent venous thrombosis. The pathomechanisms leading to venous thrombosis in patients with high factor VIII are still unclear. In many patients, however, a biochemically detectable hypercoagulable state (as represented by elevated levels of the coagulation activation marker prothrombin thrombin fragment F1.2) was demonstrated. The optimal duration of secondary thromboprophylaxis for patients with high factor VIII levels is uncertain. We currently perform an interventional trial comparing conventional to extended anticoagulation. Reduction of factor VIII by administration of a non-selective ß-receptor blocker might be a promising therapeutic concept which is currently under investigation.

Venous Thromboembolism Recurrence after a First Episode of Provoked Venous Thrombosis Due to a Transient Risk Factor. A Systematic Review of the Literature

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3029-3029
Author(s):  
Alfonso Iorio ◽  
Esmeralda Filippucci ◽  
Maura Marcucci ◽  
Clive Kearon ◽  
Gualtiero Palareti
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Recurrence Rate ◽  
Anticoagulant Therapy ◽  
Random Effect ◽  
Random Effect Model ◽  
First Episode ◽  
Risk Of Recurrence ◽  
Effect Model ◽  
Optimal Duration

Abstract Background: Venous thromboembolism (VTE) has a tendency to recur after anticoagulation is stopped. The optimal duration of anticoagulation is influenced by the risk of recurrence: indefinite anticoagulation is recommended after a first VTE associated with a persistent and strong risk factor (e.g. cancer), whereas three months of anticoagulation is adequate if VTE was provoked by a transient risk factor (e.g. surgery). The optimal duration of anticoagulation after a first unprovoked VTE is, however, still a matter of debate. An attractive approach is to identify subgroups of patients with unprovoked VTE who have a high risk of recurrence and treat them with prolonged anticoagulation, and subgroups with a lower risk of recurrence and treat them for only three months. A critical issue, therefore, is to determine a cut-off value for risk of recurrence that is low enough to justify stopping anticoagulant therapy at three months (i.e., a rate of recurrence that is acceptable to patients and physicians). We propose that the rate of recurrence after VTE that was provoked by a transient risk factor represents such a value. Aim of the study: To accurately estimate the risk of recurrence in patients with VTE provoked by a transient risk factor who have completed at least three months of anticoagulant therapy. Materials and Methods: Medline, Embase and Cochrane Collaboration Registry of Randomized Trials were searched for any studies reporting the recurrence rate of VTE after a first episode of VTE associated with a transient risk factor (surgery, trauma, plaster, bed rest, pregnancy, puerperium, hormone treatment). The references of retrieved articles were scanned for any additional relevant studies. Studies were included if enrolling patients met the following criteria: a first episode of VTE provoked by a transient risk factor; a course of at least three months of oral anticoagulant therapy; a follow up of 12 or 24 months after treatment discontinuation with assessment of VTE recurrence rate. Recurrence rate, or data that allowed its calculation, needed to be reported. An overall estimate of the recurrence rate was calculated following Laird (Stats Med 1990), having predefined to use a fixed-effect model if no heterogeneity was found among the studies or a random-effect model otherwise. The inverse variance method was used to calculate weights for the studies. Results: The literature search yield 1089 references. After careful scanning of the potentially relevant papers, 15 papers were included in the final analysis. All studies except one were prospective. 12/15 and 11/15 studies reported data about the recurrence rate at 12 and 24 months, respectively. Overall there were 106 events among of 2217 patients at 12 months and 160 events among 2321 patients at 24 months. The pooled recurrence rate was 4.0% (95% C.I. 3.0%–5.2%) at 12 months and 6.7% (95% C.I. 5.2%–8.6%) at 24 months. Conclusion: The cumulative risk of recurrence in patients with VTE provoked by a reversible risk factor is 6.7% (95% C.I. 5.2%–8.6%) two years after anticoagulant withdrawal. We suggest that it acceptable to stop anticoagulant therapy after three months in subgroups of patients with unprovoked VTE who have been shown to have a risk of recurrence that is similar to, or lower than, this rate.

Combined Factor V Leiden (R506Q) and prothrombin G20210A genotyping in young patients presenting with deep venous thrombosis

2006 ◽  
Vol 21 (1) ◽  
pp. 24-27 ◽  
Author(s):  
A Mansilha ◽  
F Araújo ◽  
M Severo ◽  
S M Sampaio ◽  
T Toledo ◽  
...  
Keyword(s):  
Risk Factor ◽  
Young People ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Young Patients ◽  
Factor V Leiden ◽  
First Episode ◽  
Control Group ◽  
Factor V ◽  
Factor V Leiden Mutation

Objective: To evaluate the association between the Factor V Leiden (FV R506Q) and prothrombin gene (FII G20210A) mutations and deep venous thrombosis (DVT) in young people. Methods: Blood samples were drawn from 199 subjects: 100 healthy controls and 99 unselected patients, with an objectively documented first episode of DVT under 40 years old. DNA analysis was performed using the polymerase chain reaction. Results: The mean age in the patient cohort was 27 years (range 16–40) and 68 (68.7%) were women. Patient prevalences were 20.6% and 10.1% for FV R506Q and FII G20210A, respectively. In the control group, carrier frequencies were 2% and 5%, respectively. We found an increased overall relative risk of DVT with statistical significance for FV R506Q carriers (OR: 12.8; 95% CI: 2.9–56.7; P < 0.001), but not for FII G20210A mutation (OR: 2.1; 95% CI: 0.7–6.5; P = 0.19). Conclusions: Our results suggest a possible increase in DVT risk for the young G20210A allele carriers, which can be more expressed in the presence of a circumstantial risk factor. There is extremely strong evidence that the Factor V Leiden mutation is an important risk factor in the development of a first episode of DVT in young people.

Long-term Clinical Follow-up in 265 Patients with Deep Venous Thrombosis Initially Treated with either Unfractionated Heparin or Dalteparin: A Retrospective Analysis

1999 ◽  
Vol 82 (10) ◽  
pp. 1222-1226 ◽  
Author(s):  
W. Åberg ◽  
D. Lockner ◽  
C. Paul ◽  
M. Holmström
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Unfractionated Heparin ◽  
Malignant Disease ◽  
Duration Of Treatment ◽  
Post Thrombotic Syndrome ◽  
Recurrent Vte

SummaryThe primary objective of this retrospective study was to describe the frequency of a post-thrombotic syndrome in 265 patients previously treated for deep venous thrombosis (DVT). The secondary objectives were to document the frequency of recurrent venous thromboembolism (VTE) and mortality, especially from malignant disease. The patients were evaluated 5-14 years after inclusion in three randomized trials comparing continuous intravenous (i. v.) infusion of unfractionated heparin (UFH) (n = 85) with a low molecular weight heparin (LMWH), dalteparin (n = 180). The median post-thrombotic score at follow-up was 2 (range 0-8). In a multiple step-wise regression analysis the post-thrombotic score was significantly higher among patients with initial proximal DVT (p = 0,0001) as compared with those who had distal DVT. A recurrent venous thromboembolic event was diagnosed in 29,4% of the patients treated with dalteparin and in 23,5% of the patients treated with UFH (ns). A secondary risk factor for venous thromboembolism and a longer duration of treatment with oral anticoagulants (OAC) were significantly associated with a lower risk for recurrent VTE, whereas malignant disease diagnosed during follow-up was associated with a higher risk. During follow-up a total of 40,7% of patients had died. No difference in total mortality or mortality from malignant disease was demonstrated between the two drugs. In conclusion, a severe post-thrombotic syndrome occured relatively infrequent. considering the long observation period. Proximal DVT was significantly associated with a more severe post-thrombotic syndrome. After 14 years follow-up, no significant differences were observed in overall mortality, mortality from malignant disease or recurrent VTE between UFH- and dalteparin-treated patients. Malignant disease was a risk factor for recurrent VTE, the presence of a secondary risk factor and a longer duration of treatment with OAC decreased the risk for recurrent VTE.

P3850Impact of sex and risk factors for venous thromboembolism on the clinical course of first acute venous thromboembolism. Insights from the PREFER in VTE

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Giustozzi ◽  
S Barco ◽  
L Valerio ◽  
F A Klok ◽  
M C Vedovati ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Venous Thromboembolism ◽  
Baseline Risk ◽  
Major Surgery ◽  
First Episode ◽  
Risk Of Recurrence ◽  
Recurrent Vte ◽  
The Impact

Abstract Introduction The interaction between sex and specific provoking risk factors for venous thromboembolism (VTE) may influence initial presentation and prognosis. Purpose We investigated the impact of sex on the risk of recurrence across subgroups of patients with first VTE classified according to baseline risk factors. Methods PREFER in VTE was an international, non-interventional registry (2013–2015) including patients with a first episode of acute symptomatic objectively diagnosed VTE. We studied the risk of recurrence in patients classified according to baseline provoking risk factors for VTE consisted of i) major transient (major surgery/trauma, >5 days in bed), ii) minor transient (pregnancy or puerperium, estroprogestinic therapy, prolonged immobilization, current infection or bone fracture/soft tissue trauma); iii) unprovoked events, iv) active cancer-associated VTE. Results A total of 3,455 patients diagnosed with first acute VTE were identified, of whom 1,623 (47%) were women. The percentage of patients with a major transient risk factor was 22.2% among women and 19.7% among men. Minor transient risk factors were present in 21.3% and 12.4%, unprovoked VTE in 51.6% and 61.6%, cancer-associated VTE in 4.9% of women and 6.3% of men, respectively. The proportions of cases treated with Vitamin-K antagonists (VKAs) and direct oral anticoagulants (DOACs) were similar between sexes. Median length of treatment of VKAs was 181.5 and 182.0 days and of DOACs was 113.0 and 155.0 days in women and men, respectively. At 12-months of follow-up, VTE recurrence was reported in 74 (4.8%) women and 80 (4.5%) men. Table 1 shows the sex-specific proportion of recurrences by VTE risk factor categories. Table 1 Major Transient (n=722) Minor transient (n=573) Cancer-associated (n=195) Unprovoked (1965) Women (361) Men (361) OR (95% CI) Women (346) Men (227) OR (95% CI) Women (79) Men (116) OR (95% CI) Women (837) Men (1128) OR (95% CI) One-year follow-up, n (N%)   Recurrent VTE, 21 (6.2) 10 (2.9) 0.46 (0.2; 0.9) 9 (2.7) 12 (5.4) 2.09 (0.9; 5.0) 6 (8.0) 5 (4.5) 0.54 (0.2; 1.9) 38 (4.7) 53 (4.7) 1.03 (0.7; 1.6)   Major bleeding, 6 (1.8) 5 (1.5) 0.83 (0.3; 2.7) 5 (1.5) 1 (0.5) 0.30 (0.1; 2.6) 1 (1.3) 3 (2.7) 2.07 (0.2; 20) 10 (1.2) 15 (1.4) 1.11 (0.6; 2.4)   All-cause death, 37 (10.2) 31 (8.5) 0.82 (0.5; 1.4) 10 (2.9) 14 (6.2) 2.21 (0.9; 5.1) 26 (32.9) 49 (42.2) 1.49 (0.8; 2.7) 33 (3.9) 30 (2.7) 0.66 (0.4; 1.1) Conclusions The proportion of patients with recurrent VTE events after first acute symptomatic VTE provoked by transient risk factors was not negligible during the first year of follow-up during in both women and men. These results may have implications on the decision whether to consider extended anticoagulant therapy in selected patients with provoked events. Acknowledgement/Funding This study was funded by Daiichi Sankyo.

288Thrombotic events in bleeding patients treated with andexanet alpha: an ANNEXA-4 sub-study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J Beyer-Westendorf ◽  
P Yue ◽  
M Crowther ◽  
J W Eikelboom ◽  
C M Gibson ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Median Time ◽  
Major Bleeding ◽  
Oral Anticoagulation ◽  
Thrombotic Event ◽  
Thrombotic Risk ◽  
Number Of Patients ◽  
Fxa Inhibitor ◽  
Deep Vein ◽  
Deep Vein Thromboses

Abstract Background/Introduction Andexanet alfa (“andexanet”) was developed as a specific reversal agent for patients with major bleeding while using factor Xa (FXa) inhibitors. While thrombotic events (TEs) have been reported in patients receiving andexanet, the scope, nature, and timing of these events have not been fully characterized. Purpose The ANNEXA-4 study was a prospective, single-arm, open-label clinical trial that evaluated the safety and efficacy of andexanet in patients with acute major bleeding. In this secondary analysis, the occurrence of TEs was investigated. Methods Patients presenting with acute major bleeding within 18 hours after their last dose of FXa inhibitor were treated with andexanet. Safety outcomes, including TEs (reviewed by an adjudication committee), were evaluated at 30 days. Results Among 352 patients treated with andexanet, 34 (9.7%) experienced one or more TEs (Table). Strokes and deep vein thromboses were the most frequent TE types. Compared to patients with arterial TEs, patients with venous TEs were more likely to have been originally anticoagulated for venous thromboembolism. Median time to first TE was 10.5 days (Figure); time to event was shorter for arterial TEs than for venous TEs. TEs were nonfatal for most patients. Subgroups by age, bleed type, baseline anti-fXa activity, FXa inhibitor dose, and andexanet dose were not associated with the occurrence of TEs. Of the 34 TE patients, 26 (76.4%) had TEs before restart of any (full or prophylactic) anticoagulation; all first TEs occurred in patients not receiving oral anticoagulation. No TEs occurred after resumption of oral anticoagulation (N=100). Table 1. Thrombotic event characteristics Characteristic Result (n/N [%]) TE type   Strokes 14/352 (4.0%)   Deep vein thromboses 13/352 (3.7%)   Myocardial infarctions 7/352 (2.0%)   Pulmonary embolisms 5/352 (1.4%)   Transient ischemic attacks 1/352 (0.3%) Bleed type   Intracranial 23/227 (10.1%)   Gastrointestinal 7/90 (7.8%)   Other 4/35 (11.4%) Arterial TEs   Anticoagulated for AF 17/22 (77.3%)   Anticoagulated for VTE 6/22 (27.3%) Venous TEs   Anticoagulated for AF 11/18 (61.1%)   Anticoagulated for VTE 8/18 (44.4%)   Median time to first TE 10.5 days   Arterial 6 days   Venous 15 days Outcome   Fatal 7/34 (20.6%)   Nonfatal 27/34 (79.4%) AF = atrial fibrillation; n = number of patients with TEs; N = total number of patients for each characteristic; TE = thrombotic event; VTE = venous thromboembolism. Figure 1. Thrombotic Events Over Time Conclusions In patients with FXa inhibitor-associated acute major bleeding treated with andexanet, TEs occurred a rate not unexpected given the high thrombotic risk of the population. No factors predictive of TEs were identified. Resumption of anticoagulation was associated with fewer TEs. Acknowledgement/Funding Study funded by Portola Pharmaceuticals, Inc.

Extended Therapy for Primary and Secondary Prevention of Venous Thromboembolism

2010 ◽  
Vol 23 (4) ◽  
pp. 313-323 ◽  
Author(s):  
Susan E. Conway ◽  
Todd R. Marcy
Keyword(s):  
Health Care ◽  
Venous Thromboembolism ◽  
Secondary Prevention ◽  
Practice Guidelines ◽  
Anticoagulation Therapy ◽  
Patient Specific ◽  
First Episode ◽  
Care Providers ◽  
Primary And Secondary Prevention ◽  
Optimal Duration

Clinical practice guidelines currently suggest extended anticoagulation therapy for primary and secondary prevention of venous thromboembolism (VTE). The optimal duration of anticoagulation has been an active area of clinical investigation for patients undergoing orthopedic surgeries and those diagnosed with a first episode of unprovoked VTE. Practice guidelines, VTE incidence, clinical predictors/mediators, and clinical trial evidence is reviewed to help pharmacists and other health care providers make an informed, patient-specific decision on the optimal duration of anticoagulation therapy. Extended anticoagulation up to 5 weeks following orthopedic surgery for primary VTE prevention and indefinitely following a first episode of unprovoked VTE for secondary VTE prevention should be considered only if the risk of bleeding is not high and the cost and burden of anticoagulation is acceptable to the patient. The optimal duration of anticoagulation therapy for primary or secondary prevention of VTE should include the health care provider and patient making a decision based on evaluation of individual benefits, risks, and preferences.

Comparison of 1 month with 3 months of anticoagulation for a first episode of venous thromboembolism associated with a transient risk factor

2004 ◽  
Vol 2 (5) ◽  
pp. 743-749 ◽  
Author(s):  
C. Kearon ◽  
J. S. Ginsberg ◽  
D. R. Anderson ◽  
M. J. Kovacs ◽  
P. Wells ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
First Episode

Prospective Evaluation of plasma Levels of FVIII in Patients with venous Thromboembolism,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3348-3348
Author(s):  
Luis Fernando Bittar ◽  
Bruna Mazetto Fonseca ◽  
Silmara Lima Montalvão ◽  
Fernanda Loureiro de Andrade Orsi ◽  
Erich V de Paula ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Plasma Levels ◽  
Conflicts Of Interest ◽  
Coagulation Factor ◽  
Geographic Area ◽  
First Episode ◽  
Control Group ◽  
Post Thrombotic Syndrome

Abstract Abstract 3348 Introduction: Venous thromboembolism (VTE) is a multifactorial disease, and increased levels of coagulation factor VIII (FVIII) has been demonstrated as risk factor for first and recurrent episodes of VTE. Some authors reported that these high levels of FVIII were still persistent after 4 years of the episode, but median follow-up in these studies are relatively short. The aim of the study was investigate if after a long-term follow-up of 4–15 years (median of 10 years), patients with high levels of FVIII after anticoagulant treatment still showed this alteration. Design and Methods: Previously, we selected 174 adult patients with a first episode of acute VTE between January 1990 and September 2004. One hundred seventy four healthy adult individuals selected from blood donors were chosen as controls, from the same geographic area of origin. Of this group of VTE patients, 68 patients with plasma FVIII: C levels above the 90th percentile were selected. FVIII levels (FVIII:C) were measured by a one-stage clotting assay with FVIII-deficient plasma in duplicate in an automated coagulometer. Levels were measured twice, in 2004 and then in 2011. C-reactive protein (CRP) levels were determined in the same samples by a nephelometric method to evaluate the influence of inflammation on FVIII levels. For individuals with CRP values higher than 1mg/dL, an additional blood sample was analyzed. High FVIII levels were only considered for further analysis when in the presence of normal CRP levels. The presence of post-thrombotic syndrome (PTS) was evaluated and classified clinically by the Clinical-Etiologic-Anatomic-Pathophysiologic (CEAP) classification System. Results: 68 patients with VTE and high levels of FVIII (19M:49F) with a median age of 47 years (range 20–70) were included in the study. The control group consisted of 59 subjects (42M:17F) with a median age of 35 years (range 21–56 years). VTE was spontaneous in 26 (38.2%) patients and secondary to an acquired risk factor in 61.8%. In the 1st evaluation, in 2004, patients with VTE had higher plasma levels of FVIII:C (median 235.8 IU/dL vs. 127.0 IU/dL; p<0.001) compared to controls. In 2011, seven years after the first evaluation and after a median follow-up of 10 years after the first VTE episode, this difference was still present (median 144.6 IU/dL vs. 96.4 IU/dL; p<0.001). Patients with severe PTS (167 IU/dL) showed higher plasma levels of FVIII when compared with patients without PTS (median 141.4 IU/dL), mild PTS patients (median 142.8 IU/dL), and moderate PTS patients (median 143.2); p=0.04. Conclusions: Our results show that even after a median of 10 years of VTE, patients still have increased levels of FVIII. Moreover, there seems to be a relationship between severe post-thrombotic syndrome and increased plasma levels of FVIII. Disclosures: No relevant conflicts of interest to declare.

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