NONVALVULAR ATRIAL-FIBRILLATION - EVIDENCE FOR A PROTHROMBOTIC STATE

Objective: To determine whether patients with nonvalvular atrial fibri llation (NVAF) have prothrombotic changes compared with patients in si nus rhythm. Design: Cross-sectional study. Hemostatic function compare d in NVAF patients without prior embolic event (transient ischemic att ack or embolic stroke) and control subjects without prior thrombotic s troke, and in NVAF patients with prior embolic event and control subje cts with prior thrombotic stroke. Setting: Internal medicine outpatien t group practice and anticoagulation clinic in 2 teaching hospitals. P atients: A total of 75 NVAF patients (50 without and 25 with prior emb olic event) and 42 control patients (31 without and 11 with prior thro mbotic stroke) recruited concurrently over 18 months during 1990-91. O utcome measures: Platelet count, prothrombin time (PT), partial thromb oplastin time (PTT), and plasma levels of hemoglobin, fibrinogen, von Willebrand factor antigen, factor VIII, fibrin D-dimer, antithrombin I II, protein C, protein S, fibrinopeptide A and prothrombin fragment F1 +2. All statistical analyses were performed after adjustments for age and sex. Results: The NVAF patients without a prior embolic event had significantly higher mean hemoglobin and fibrinogen levels (p < 0.001 and p = 0.05, respectively) than the control subjects without prior th rombotic stroke. The 29 NVAF patients not taking warfarin (none had ha d an embolic event) had significantly lower mean protein C and protein S levels (p = 0.012 and p < 0.001, respectively) and a significantly higher fibrinopeptide A level (p = 0.03, after exclusion of outliers) than the control subjects without prior stroke. The NVAF patients with a prior embolic event had alterations in the hemostatic variables sim ilar to those seen in the control patients with a prior thrombotic str oke. The latter had significantly higher fibrinogen, von Willebrand fa ctor antigen and factor VIII levels (p = 0.04, 0.002 and 0.002, respec tively) and significantly lower protein S levels (p = 0.02) than the c ontrol subjects without prior stroke. Conclusions: NVAF patients witho ut a history of an embolic event show evidence of a prothrombotic stat e compared with patients in sinus rhythm who have not had a thrombotic stroke. NVAF patients with a history of an embolic event show evidenc e of a prothrombotic state similar to that of patients in sinus rhythm who have had a thrombotic stroke. Prospective studies are needed to d etermine whether these abnormalities predict higher risk of stroke in individual NVAF patients.