Abrupt versus gradual withdrawal of vitamin K antagonist treatment in patients with venous thromboembolic disease: assessment of hypercoagulability and clinical outcome.

Abstract

BACKGROUND:

It is yet unclear whether vitamin K antagonist treatment should be stopped abruptly or gradually after an episode of venous thromboembolism. The mode of withdrawal might influence a potential development of a hypercoagulable state, which could influence the risk for recurrent disease.

METHODS:

We prospectively studied 37 consecutive patients in whom acenocoumarol was discontinued either abrupt (18) or gradually (19) (2/3 and 1/3 of the initial dose for one week). Blood sampling was performed at various time points up to 18 days after complete withdrawal and was analysed for INR, prothrombin fragment F1 + 2 and D-dimer. All patients were clinically followed-up for the assessment of the association between hypercoagulability and occurrence of disease such as recurrent venous thromboembolism or malignancy.

RESULTS:

An approximately fourfold increase was observed (median increase from 0.3 to 1.3 nmol/l) in the F1 + 2 levels after both abrupt and gradual withdrawal and in the D-dimer concentrations in the abrupt withdrawal group (0.10 to 0.44 mg/l), while those in whom acenocoumarol was discontinued gradually showed a less pronounced increase of the D-dimer levels (0.11 to 0.29 mg/L) (not significant). During follow-up one recurrent venous thromboembolic event occurred in each group, and a diagnosis of cancer was made four times. All these patients had the highest D-dimer concentrations measured in the entire study group.

CONCLUSIONS:

This study indicates the potential for a hypercoagulable state after acenocoumarol discontinuation, which was not prevented by tapering the acenocoumarol dose. D-dimer, measured 2 to 3 weeks after acenocoumarol withdrawal, might be an important tool to identify patients at risk for recurrent venous thromboembolism and/or for the presence of an underlying malignancy.

• Authors: M R de Groot, T L Njo, M van Marwijk Kooy, H R Büller
• Journal: Clinical laboratory (Clin Lab) Vol. 46 Issue 11-12 Pg. 575-81 ( 2000) ISSN: 1433-6510 [Print] Germany
• PMID: 11109505 (Publication Type: Clinical Trial, Comparative Study, Controlled Clinical Trial, Journal Article)

Chemical References

• Anticoagulants
• Vitamin K
• Acenocoumarol

Topics

• Acenocoumarol (administration & dosage, adverse effects, therapeutic use)
• Adolescent
• Adult
• Aged
• Anticoagulants (administration & dosage, adverse effects, therapeutic use)
• Drug Administration Schedule
• Female
• Humans
• Male
• Middle Aged
• Thromboembolism (drug therapy)
• Thrombophilia (prevention & control)
• Venous Thrombosis (drug therapy)
• Vitamin K (antagonists & inhibitors)