Poor anticoagulation quality in the first 3 months after unprovoked venous thromboembolism is a risk factor for long‐term recurrence

Abstract

unprovoked venous thromboembolism is a risk factor for long-term recurrence. J Thromb Haemost 2005; 3: 955-61.Summary. Background and Aim: Several factors are associated with an increased risk of recurrent venous thromboembolism (VTE). The aim of the study was to investigate whether the quality of oral anticoagulation therapy (OAT) is a long-term risk factor for recurrence of VTE after OAT interruption. Methods and results: A total of 297 patients (170 males) with a recent acute unprovoked VTE episode were prospectively monitored during OAT in our anticoagulation clinic and followed up for 21 months after OAT interruption. Recurrent events were recorded in 42 subjects for 493 years of follow-up [14.1% of patients; 8.5% patient-years (pt-y)] after OAT withdrawal. The rate of recurrence was not correlated to OAT duration. Subjects experiencing recurrence after OAT interruption had spent significantly more time at markedly subtherapeutic international normalized ratio (INR) levels (<1.5) and less time within the therapeutic range (2.0-3.0 INR) during OAT. Relative risk (RR) of recurrence was significantly higher [2.77 (95% confidence interval (CI) 1.49-5.18; P ¼ 0.001) and 2.70 (95% CI 1.39-5.25; P ¼ 0.003) at univariate and multivariate analysis, respectively] in those who spent more time (upper quintile) at INR values <1.5, being especially evident in the first 90 days of OAT. RR was significantly higher at univariate [2.05 (95% CI 1.07-3.96; P ¼ 0.031)] but not at multivariate [1.98 (95% CI 0.98-4.0; P ¼ 0.056)] analysis when the entire OAT period was considered. Subjects in the upper quintile of time spent at INR values <1.5 had significantly higher D-dimer values when OAT was stopped and after 3 months. Conclusions: The amount of time that subjects with an acute unprovoked VTE event spend at near-normal INR values (<1.5) during the first 3 months of treatment is associated with higher D-dimer values measured during OAT and after its interruption and is a significant risk factor for late VTE recurrence.

Epidemiology of Subtherapeutic Anticoagulation in the United States

“…Recall that we defined "low INR" as Յ1.5-a level of underanticoagulation clearly associated with patient harm. [22][23][24] Nevertheless, we found that the median time until a next INR test was 8 days, and the median time until a next in-range INR value was 16 days. These values themselves are not alarming, but the 75th percentile for each (14 and 30 days) indicate that for a considerable proportion of patients in our dataset, low INR was addressed without a particular sense of urgency.…”

“…Some studies have demonstrated that low INR is associated with attenuation of the protective effects of anticoagulation therapy, as would be expected. 7,[22][23][24] Although we know that low INR increases the risk of thromboembolism, relatively little is known about the epidemiology of low INR.…”

“…We examined patient-level risk factors for INR Յ1.5, the threshold below which the risk of thromboembolism rises most acutely. 22,23 We report clinician-documented explanations for low INR, recorded at the time the INR result was obtained. We examine predictors of time until the next INR and the next in-range INR.…”

How I treat the antiphospholipid syndrome

“…70 The importance of maintaining good control of the INR within the therapeutic range to prevent thrombotic recurrences and bleeding complications has been demonstrated in the setting of treatment for stroke 71 and VTE. 72 A consensus statement from the Anticoagulation Forum on the delivery of optimized anticoagulant care has identified and made recommendations on the following 9 key areas: (1) qualifications of personnel, (2) supervision, (3) care management and coordination, (4) documentation, (5) patient education, (6) patient selection and assessment, (7) laboratory monitoring, (8) initiation and stabilization of warfarin therapy, and (9) maintenance therapy. 73 It has been noted, though it seems to be very uncommon, that a small proportion of commercial preparations of thromboplastins may be affected by LA from certain patients, prolonging the prothrombin time (PT), leading to an overestimation of the actual degree of anticoagulation when PT-INR is used for monitoring.…”

Diagnosis and Treatment of Lower Extremity Deep Vein Thrombosis: Korean Practice Guidelines

“…When the primary end-points of recurrent VTE and major bleeding were assessed, there were three events among the 103 [133,134]. Poor-quality INR control, as assessed by the percentage of time with INR <1.5, is associated with a long-term higher risk of recurrent VTE after eventual anticoagulant cessation (RR, 2.7; 95% CI, 1.39-5.25; P=0.003) [135]. NOACs, such as dabigatran and rivaroxaban, directly inhibit thrombin or factor Xa, respectively.…”