Abrupt versus gradual withdrawal of vitamin K antagonist treatment in patients with venous thromboembolic disease: assessment of hypercoagulability and clinical outcome.
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.
de Groot
M R
MR
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. m_medisch_spectrum_twente@hotmail.com
Njo
T L
TL
van Marwijk Kooy
M
M
Büller
H R
HR
D000074:Acenocoumarol / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013923:Thromboembolism / Q000188:drug therapy*; D019851:Thrombophilia / Q000517:prevention & control*; D020246:Venous Thrombosis / Q000188:drug therapy*; D014812:Vitamin K / Q000037:antagonists & inhibitors*
D000925:Anticoagulants; D014812:Vitamin K; D000074:Acenocoumarol