Plasmin-α2-antiplasmin Complex in Patients with Atrial Fibrillation

William M. Feinberg; Elizabeth Macy; Elaine S. Cornell; Sarah D. Nightingale; Lesly A. Pearce; Russell P. Tracy; Edwin G. Bovill; for the Stroke Prevention in Atrial Fibrillation Investigators

doi:10.1055/s-0037-1614636

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1999; 82(01): 100-103
DOI: 10.1055/s-0037-1614636

Rapid Communication

Schattauer GmbH

Plasmin-α₂-antiplasmin Complex in Patients with Atrial Fibrillation

Authors

William M. Feinberg

¹From the Department of Neurology, The University of Arizona, Tucson, Arizona
Elizabeth Macy

²From the Laboratory for Clinical Biochemistry Research, Department of Pathology, University of Vermont, Burlington, Vermont
Elaine S. Cornell

²From the Laboratory for Clinical Biochemistry Research, Department of Pathology, University of Vermont, Burlington, Vermont
Sarah D. Nightingale

²From the Laboratory for Clinical Biochemistry Research, Department of Pathology, University of Vermont, Burlington, Vermont
Lesly A. Pearce

³From the Statistical Consultant, Minot, North Dakota, USA
Russell P. Tracy

²From the Laboratory for Clinical Biochemistry Research, Department of Pathology, University of Vermont, Burlington, Vermont
Edwin G. Bovill

²From the Laboratory for Clinical Biochemistry Research, Department of Pathology, University of Vermont, Burlington, Vermont

for the Stroke Prevention in Atrial Fibrillation Investigators

Abstract

Summary

Plasmin-α₂-antiplasmin complex (PAP) is an index of recent fibrinolytic activity. We examined PAP levels in patients with atrial fibrillation (AF) to determine whether these levels are correlated with clinical characteristics associated with stroke risk. We obtained blood for measurement of PAP in a non-random sample of 586 patients with AF on entering the Stroke Prevention in Atrial Fibrillation III Study. PAP levels were measured with an ELISA assay. PAP values were transformed with a natural logarithm (PAP_ln) prior to all analyses. Older age, female gender, recent congestive heart failure, decreasing fractional shortening, recent onset of AF, and coronary artery disease were each univariately associated with higher levels of PAP (all p <0.05, two-sample t-test, simple linear regression). Older age, recent congestive heart failure, decreasing fractional shortening, and recent onset of AF were independently associated with higher PAP levels by multivariate analysis (linear regression). Among patients receiving warfarin, PAP levels were not correlated with INR levels (linear regression, p = 0.60). Patients classified as high-risk for thromboembolism by our risk stratification criteria (systolic blood pressure >160 mm Hg, prior thromboembolism, recent congestive heart failure, poor left ventricular function, and women over age 75) had higher PAP levels than low-risk patients (antilog mean PAP_ln 5.6 vs 4.9, p <0.001, two-sample t-test). PAP levels in patients with AF are associated with clinical characteristics predictive of thromboembolism. Elevated PAP levels are particularly associated with poor left ventricular function and are not affected by anticoagulation. PAP levels may be a marker of stroke risk in patients with AF.

Presented in part at the American Heart Association 22nd annual Joint Conference on Stroke and the Cerebral Circulation, Anaheim, CA, February, 1997.

Keywords

Atrial fibrillation - plasmin - hemostatic markers

Full Text

References

References
1 Wolf P, Abbott R, Kannel W. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991; 22: 983-8.
2 Atrial Fibrillation Investigators Risk factors for stroke and efficacy of anti-thrombotic therapy in atrial fibrillation: analysis of pooled data from five randomized controlled trials. Archives of Internal Medicine 1994; 154: 1449-57.
3 Stroke Prevention in Atrial Fibrillation Investigators Predictors of thromboembolism in atrial fibrillation. I: clinical features of patients at risk. Annals of Internal Medicine 1992; 116: 1-5.
4 Cheseboro J, Fuster V, Halperin J. Atrial fibrillation - risk marker for stroke (editorial). New England Journal of Medicine 1990; 323: 1556-8.
5 Hart R, Halperin J. Atrial fibrillation and stroke: Revisiting the dilemmas. Strok 1994; 25: 1337-41.
6 Feinberg W, Bruck D, Pearce L. Intravascular coagulation in patients with atrial fibrillation[abstract]. Neurology 1991; 41 (Suppl. 01) 298
7 Gustafsson C, Blombäck M, Britton M, Hamsten A, Svensson J. Coagulation factors and the increased risk of stroke in nonvalvular atrial fibrillation. Stroke 1990; 21: 47-51.
8 Kumagai K, Fukunami M, Ohmori M, Kitabatake A, Kamada T, Hoki N. Increased intravascular clotting in patients with chronic atrial fibrillation. Journal of the American College of Cardiology 1990; 16: 377-80.
9 Collen D, Wiman B. Turnover of antiplasmin, the fast-acting plasmin inhibitor of plasma. Blood 1979; 53: 313-24.
10 Holvoet P, de Boer A, Verstreken M, Collen D. An enzyme-linked immunosorbent assay (ELISA) for the measurement of plasmin-α₂-antiplasmin complex in human plasma – application to the detection of in vivo activation of the fibrinolytic system. Thromb and Haemost 1986; 56: 124-7.
11 Wiman B, Haegerstrand-Björkman M. Plasmin/α₂-antiplasmin complex in plasma – a global fibrinolytic assay (abstract). Thromb and Haemost 1993; 69 (06) 1091
12 Nagayama M, Shinohara Y, Nagayama T. Detection of prothrombotic state in ischemic stroke by monitoring plasma molecular markers. Journal of Stroke and Cerebrovascular Diseases 1994; 4: 250-4.
13 Takano K, Yamaguchi T, Uchida K. Markers of a hypercoagulable state following acute ischemic stroke. Stroke 1992; 23: 194-8.
14 Montes R, Páramo J, Anglès-Cano E, Rocha E. Development and clinical application of a new ELISA assay to determine plasmin-α₂-antiplasmin complexes in plasma. British Journal of Haematology 1996; 92: 979-85.
15 Pelzer H, Pilgrim A, Schwarz A, Merte D, Keuper H, Hock H. Determination of 2- antiplasmin-plasmin complex in human plasma with an enzyme-linked immunosorbent assay. Fibrinolysis 1993; 7: 69-74.
16 Stroke Prevention in Atrial Fibrillation Investigators The Stroke Prevention in Atrial Fibrillation III Study: Rationale, design, and patient features. Journal of Stroke and Cerebrovascular Diseases 1997; 6: 341-53.
17 Stroke Prevention in Atrial Fibrillation Investigators Risk factors for thromboembolism during aspirin therapy in patients with atrial fibrillation: The Stroke Prevention in Atrial Fibrillation Study. Journal of Stroke and Cerebrovascular Diseases 1995; 5: 147-57.
18 Stroke Prevention in Atrial Fibrillation Investigators Adjusted-dose war-farin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial. Lancet 1996; 348: 833-8.
19 Margaglione M, Di Minno G, Grandone E, Vecchione G, Celentano E, Cap-pucci G, Grilli M, Simone P, Panico S, Mancini M. Abnormally high circulation levels of tissue plasminogen activator and plasminogen activator inhibitor-1 in patients with a history of ischemic stroke. Arteriosclerosis and Thrombosis 1994; 14 (11) 1741-5.
20 Lindgren A, Lindoff C, Norrving B, Åstedt B, Johansson B. Tissue plasminogen activator and plasminogen activator inhibitor-1 in stroke patients. Stroke 1996; 27: 1066-71.
21 de Bono D. Significance of raised plasma concentrations of tissue-type plasminogen activator and plasminogen activator inhibitor in patients at risk from ischaemic heart disease. British Heart Journal 1994; 71: 504-7.
22 Cushman M, Psaty B, Macy E, Bovill E, Cornell E, Kuller L, Tracy R. Correlates of thrombin markers in an elderly cohort free of clinical cardiovascular disease. Arteriosclerosis Thrombosis and Vascular Biology 1996; 16: 1163-9.
23 Feinberg W, Cornell E, Nightingale S, Pearce L, Tracy R, Hart R, Bovill E. Relationship between prothrombin activation fragment F1.2 and international normalized ratio (INR) in patients with atrial fibrillation. Stroke 1997; 28: 1101-6.
24 Yamamoto K, Ikeda U, Furuhashi K, Irodawa M, Nakayama T, Shimada K. The coagulation system is activated in idiopathic cardiomyopathy. Journal of the American College of Cardiology 1995; 25: 1634-40.
25 Levin I R, Harpel PC, Weil D, Chang TS, Rifkin DB. Aspirin inhibits vascular plasminogen activator activity. Journal Clinical Investigation 1984; 74: 571-80.