Coagulation factors and the increased risk of stroke in nonvalvular atrial fibrillation.

Abstract

We studied whether hemostatic abnormalities contribute to the increased risk of stroke in patients with nonvalvular atrial fibrillation. Hemostatic function was studied in four agematched groups: 20 patients with nonvalvular atrial fibrillation and a previous ischemic stroke, 20 patients with nonvalvular atrial fibrillation without a previous stroke, 20 stroke patients with sinus rhythm, and 40 healthy controls. Both groups with nonvalvular atrial fibrillation had significantly higher concentrations of von Willebrand factor, factor VM:C, fibrinogen, D-dlmer (a fibrinolytic product), /3-thromboglobulin, and platelet factor 4; a significantly higher fibrinogen/antithrombin ratio; and significantly higher spontaneous amidolytic activity than the healthy controls. Prekallikrein levels were significantly lower in both groups with nonvalvular atrial fibrillation. Stroke patients with sinus rhythm had normal hemostatic function, normal concentrations of platelet-related factors, and a slightly increased concentration of fibrinopeptide A compared with the healthy controls. Both groups with nonvalvular atrial fibrillation differed from the stroke patients with sinus rhythm as they did from the healthy controls. No difference in hemostatic function was seen between the nonvalvular atrial fibrillation patients with and without a previous ischemic stroke. Thus, alterations in hemostatic function may contribute to the increased risk of stroke in patients with nonvalvular atrial fibrillation. (Stroke 1990^1:47-51) N onvalvular atrial fibrillation (NVAF) afflicts 2-4% of 70-year-old people, and its prevalence increases with age. 1 NVAF is an important risk factor for stroke. In the Framingham Study, NVAF was associated with a 5-6 times higher incidence of stroke compared with an age-, sex-, and blood pressure-matched control group without NVAF. 2Left atrial thrombosis causing stroke by arterial embolism has been thought to be the main pathogenetic mechanism in the association between NVAF and stroke. However, the precise mechanism is difficult to determine in individuals with NVAF. As pointed out in recent studies, a considerable proportion of strokes are probably due to atherothrombosis. 3 -4 Generalized atherosclerosis might be the common cause of both NVAF and stroke, thereby explaining the association. If this is true, it can be assumed that there are higher concen-

Anticoagulants for atrial fibrillation: Why is the treatment rate so low?

“…8 The annual incidence of stroke is six times higher in patients with AF than in those with normal sinus rhythm. 1 Atrial fibrillation is associated with an elevation of procoagulant factors in the blood 9 and provides the possibility for thrombi to form in the left atrium when regular effective mechanical contractions are absent. Another related group of patients, who may also be at risk for stroke, are patients with atrial flutter.…”

Angiotensin type 1 receptor blockade prevents endocardial dysfunction of rapidly paced atria in rats

“…1,2 Most strokes in AF patients, one of the major reasons for hospitalisation in this group, 3 are believed to be cardioembolic, caused by embolism of left atrial thrombi. 4 Thrombus formation in the left atrium could result from decrease in blood flow, 5 increase in blood coagulability, 6 and also endocardial dysfunction in the left atrium. 7 Several recent experimental reports including ours have demonstrated that AF per se causes atrial endocardial dysfunction, which is manifested by reduced endothelial nitric oxide synthase (eNOS), increased expression of plasminogen inhibitor-1 (PAI-1) and also decreased expression of tissue factor pathway inhibitor (TFPI) and thrombomodulin (TM) in the left atrial endocardium, leading to local coagulation imbalance on the internal surface of the atrium.…”

Thrombomodulin and Tissue Factor Pathway Inhibitor in Endocardium of Rapidly Paced Rat Atria

“…2 Decreased blood flow with hypercoagulable state in the left atrium has been attributed to the likelihood of clotting formation in the fibrillating atria, as demonstrated in many previous studies. 3,4 In vascular thrombi, however, endothelial dysfunction is also known to play a significant role in addition to the decreased blood flow and hypercoagulability, as shown in the well-known Virchow's triad. Likewise, we could hypothesize that atrial endocardial cells could prevent local thrombus formation under normal conditions and that AF might produce the endocardial dysfunction contributing to the local thrombogenesis, besides the deterioration in the blood flow and coagulability.…”