Inadequate warfarin dosing may be worse than no warfarin in regard to stroke severity

Sokomoto et al (1) investigated the relationship between adequacy of warfarin dosing and severity of stroke in patients with atrial fibrillation. Inadequate was defined as INR less than 2.0 ( less than 1.6 for patients older than 70 years.)

They studied 477 patients with atrial fibrillation (AF) and acute ischemic stroke,53 of whom were undertreated. Inadequate or insufficient dose of warfarin was present in 53 patients and the odds ratio for a severe stroke was 2.7. The numbers in the study were fairly small but  other research had demonstrated a similar pattern.

The authors suggested that underlying pathophysiology or pharmacologic explanation related to the vitamin K dependent anticoagulant protein,Protein C. Protein C levels decrease earlier and with lower doses of warfarin than do the other vitamin K dependent clotting proteins. So early on in warfarin therapy there may be a procoagulant effect. This was why  in the not-too-long ago-days physicians would treat thromboembolism with a few days of heparin along with the warfarin. Too little warfarin may be more of a pro than an anticoagulant medication.

So we have still another reason why the newer oral  direct acting anticoagulants are better than warfarin.




1) Sakamoto, Y et al, Insufficient warfarin therapy is associated with higher severity of stroke than non anticoagulation in patients with atrial fibrillation and acute anterior-circulation Stroke

Circulation Journal Official Journal of the Japanese Circulation society. 2017 December.