Warfarin for Venous Thromboembolism — Walking the Dosing Tightrope

Schafer, Andrew I.

doi:10.1056/nejme030018

Cited by 11 publications

(5 citation statements)

References 13 publications

(6 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, our patients were on treatment for over 3 months, showing that this hypercoagulability is not restricted to initial treatment states. The results are also in accordance with the finding of increased in vivo prothrombin turnover at low-intensity VKA treatment [7], as well as with the observation that low INR values have been shown to be inadequate for the prevention of myocardial infarction [8] whereas they may or may not have an effect in venous thrombosis [9]. This might suggest that the role of TM differs with the underlying pathology.…”

supporting

confidence: 89%

Procoagulant effect of vitamin K antagonists?

Dieri

Cate‐Hoek

Bloemen

et al. 2011

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

supporting

confidence: 89%

Procoagulant effect of vitamin K antagonists?

Dieri

Cate‐Hoek

Bloemen

et al. 2011

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

“…Assuming rhythm control is the active intervention: RRI = Relative Risk Increase, and a negative NNT value amounts to a 'Number Needed to Harm' (NNH); NNT/year values exceeding 1000 (whether positive or negative) imply negligible effects; Secondary composite endpoint = death, disabling stroke, disabling anoxic encephalopathy, major bleeding, or cardiac arrest; Primary composite endpoint = cardiovascular death, heart failure, thromboembolism, bleeding, pacemaker implantation or severe anti-arrhythmic drug adverse effect. a better benefit/safety profile than with previously advocated higher intensity treatment (6,7). Similarly, better evidence is needed to determine the optimal international normalization ratio for patients who receive long-term warfarin for atrial fibrillation.…”

mentioning

confidence: 92%

The Burden of Rate Control in Atrial Fibrillation

Kumana

Cheung

Lauder

2003

J Cardiovasc Pharmacol Ther

View full text Add to dashboard Cite

The editorial on optimizing ventricular rate control in atrial fibrillation in the recent issue of the Journal of Cardiovascular Pharmacology and Therapeutics (1) was especially timely. By drawing attention to the difference between merely slowing ventricular rate as opposed to how this is achieved, it raises an important issue for patients with chronic persistent or recurrent atrial fibrillation. Resolving this dilemma is especially pertinent in the wake of two recently reported randomized clinical trials (2,3) that challenge the utility of rhythm control in representative populations with this condition.From the published results of the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) (2) and the corresponding European trial (3), we have derived number needed to treat (NNT) and other relevant parameters. These two relatively large studies set out to assess the impact of strategies, primarily directed at rhythm control as opposed to rate control of atrial fibrillation in elderly persons. In both trials, the rhythm control groups enjoyed no clinical benefits; all primary and almost all secondary outcomes showed a trend in favor of rate control (Table 1). Any corresponding negative NNT value for the prevention of an adverse event in the rhythm control group may therefore be regarded as a number needed to harm (NNH); the average number of patients treated for a given period of time

show abstract

“…All PA are of some danger in inducing severe hemorrhages (2,13). Fibrin is not only found in the pathologic thrombus, but also circulates as soluble fibrin polymers in the blood and possesses physiologic functions in the prevention of blood loss or the prevention of bleeding in vital organ areas (14,15). If clinical plasmatic thrombolysis is required, it is suggested that the physiologic activators urokinase or t-PA might be preferred.…”

Section: Discussionmentioning

confidence: 99%

In vitro Simulation of Therapeutic Thrombolysis With Microtiter Plate Clot-Lysis Assay

Stief

2006

Clin Appl Thromb Hemost

View full text Add to dashboard Cite

Only limited comparable data are available on the clot lysis power of the clinically used plasminogen activators (PA). Here the PA were used at different clinically relevant concentrations, and the lysis of the microclots was determined. A microclot lysis assay was used to study thrombolysis by urokinase, tissue-PA (t-PA), streptokinase, plasminogen-streptokinase activator complex (PSAC), reteplase, or tenecteplase. The clot turbidity served as a tool to determine clot mass: 100 microL fresh microclots were incubated with 25 microL PA in 6% bovine serum albumin (BSA)-phosphate-buffered saline (PBS) and 100 microL BSA-PBS or pooled normal human plasma; that is, the PA were in the liquid supernatant of a plasma clot and were not entrapped in the clot, an assay system comparable to normal physiology. The turbidity was determined after 0 to 5 hours (37 degrees C) by a microtiter plate reader. The lysable clot turbidity (clot mass) was expressed in percent of 100% lysable clot control. The clot lysis activity is 100% minus the clot mass in percent. The effective doses at 50% (ED(50)) of lysis of fresh clots after 4 hours (37 degrees C) with 6% BSA or pooled normal human plasma in the clot-supernatant were urokinase 128 or 180 IU/mL; t-PA 0.3 or 0.2 microg/mL; streptokinase 215 or 1371 IU/mL; PSAC 60 or 91 U/mL; reteplase 664 or 996 U/mL; tenecteplase 0.2 or 0.2 microg/mL. The presence of a plasma thrombus with plasma supernatant increases the activity of t-PA approximately 20-fold and that of tenecteplase approximately 400-fold after 4 hours (37 degrees C), when compared to urokinase; in contrast, the lytic activity induced by reteplase decreases; i.e., the plasmin generated by reteplase is hampered on its lytic action against a thrombus. When comparing the clot lysability of microclots of 29 different donors, the only correlation (r> 0.6) was that between u-PA and t-PA. The lysability of individual clots by PA can be measured with the present routine-suited technique. It is suggested that different thrombolytic agents or concentrations thereof would have a different clinical outcome in different individuals.

show abstract

Warfarin for Venous Thromboembolism — Walking the Dosing Tightrope

Abstract: The new england journal of medicine n engl j med 348;15 www.nejm.

Cited by 11 publications

References 13 publications

Procoagulant effect of vitamin K antagonists?

Procoagulant effect of vitamin K antagonists?

The Burden of Rate Control in Atrial Fibrillation

In vitro Simulation of Therapeutic Thrombolysis With Microtiter Plate Clot-Lysis Assay

Contact Info

Product

Resources

About