Elevated Prothrombin and Activated Protein C Resistance in Patients with Thoracic Aortic Atheroma

Abstract

Patients with protruding aortic atheroma containing mobile emboli are at risk for peripheral emboli and stroke. This risk may possibly be reduced by anticoagulation, but whether or not such patients have an increased prevalence of thrombotic risk factors has not been previ ously determined. Twenty-two patients were studied (11 with protruding thoracic aortic atheromas and superimposed mobile thrombi on transesophageal echocardiography were compared to 11 age-matched controls). The authors evaluated activated protein C resistance (APC-R) by measuring the prolongation of the partial thromboplastin time (PTT) in response to activated protein C (APC). Concentrations of fibrinogen, antithrombin III (AT III), factor II, factor V, and D-dimer were also determined in all patients. There was significant resistance to APC (a smaller prolongation in PTT) in patients with atheromas and thrombi. They also had signifi cantly higher concentrations of factor II. Factor V and fibrinogen were higher, and AT III lower, in patients than in controls; however, these latter differences did not reach statistical signifi cance. Patients with aortic atheroma and mobile thrombi may have an increased prevalence of thrombotic risk factors. There is significantly increased resistance to activated protein C in patients with protruding atheroma and mobile thrombi in their thoracic aorta. There was also a trend toward elevated fibrinogen, homocysteine, and apo (a) concentrations as well as lower antithrombin III concentrations in these patients.

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References

Tunick PA , Rosenzweig BP , Katz ES , et al: High risk for vascular events in patients with protruding aortic atheromas: A prospective study. J Am Coll Cardiol 23:1085-1090, 1994.

Amarenco P. , Cohen A. , Tzourio C. , et al: Atherosclerotic disease of the aortic arch and the risk of ischemic stroke. N Engl J Med 331:1474-1479, 1994 .

Tunick PA , Kronzon I. : The improved yield of transesophageal echocardiography over transthoracic echocardiography in patients with neurologic events is largely due to detection of aortic protruding atheromas. Echocardiography 9:491-495, 1992.

Amarenco P. : The French study of aortic plaques in stroke group atherosclerotic disease of the aortic arch as a risk factor for recurrent ischemic stroke . N Engl J Med 334:1216-1221, 1996 .

Montgomery DH , Ververis JJ , McGorisk G. , et al: Natural history of severe atheromatous disease of the thoracic aorta: A transesophageal echocardiographic study. J Am Coll Cardiol 27:95-101, 1996.

Tunick PA , Lackner H. , Katz ES , et al: Multiple emboli from a large aortic arch thrombus in a patient with thrombotic diathesis. Am Heart J 124:239-241, 1992.

Blackshear JL , Jahangir A. , Oldenburg WA , et al: Digital embolization from plaque-related thrombus in the thoracic aorta: Identification with transesophageal echocardiography and resolution with warfarin therapy. Mayo Clin Proc 68:268-272, 1993.

Vaduganathan P. , Ewton A. , Nagueh SF , et al: Pathologic correlates of aortic plaques, thrombi and mobile "aortic debris" imaged in vivo with transesophageal echocardiography . J Am Coll Cardiol 30:357-363, 1997.

Schafer AI : Hypercoagulable states: Molecular genetics to clinical practice. Lancet 344:1739-1742, 1994.

10.

Nachman R. , Silverstein R. : Hypercoagulable states. Ann Intern Med 199:819-827, 1993.

11.

Bertina RM , Koeleman Bpc , Koster T. , et al: Mutation in blood coagulation factor V is associated with resistance to activated protein C. Nature 369:64-67, 1994.

12.

Price DT , Ridker PM : Factor V Leiden mutation and the risks for thromboembolic disease: A clinical perspective. Ann Intern Med 27:895-903, 1997.

13.

Rodgers GM : Activated protein C resistance and inherited thrombosis. Am J Clin Pathol 103:261-262, 1995.

14.

Rosendaal FR , Siscovick DS , Schwartz SM , et al: Factor V Leiden (resistance to activated protein C) increases the risk of myocardial infarction in young women. Blood 89:2817-2821, 1997 .

15.

Foley PW , Irvine CD , Standen GR , et al: Activated protein C resistance, factor V Leiden and peripheral vascular disease. Cardiovasc Surg 2:157-160, 1997.

16.

Kronzon I. , Tunick PA : Atheromatous disease of the thoracic aorta: Pathologic and clinical implications . Ann Intern Med 126:629-637, 1997.

17.

Dressler FA , Craig WR , Catello R. , et al: Mobile atheroma and systemic emboli: Efficacy of anticoagulation and influence of plaque morphology on recurrent stroke. J Am Coll Cardiol 31:134-138, 1998.

18.

Ferrari E. , Vidal R. , Chevallier T. , et al: Atherosclerosis of the thoracic aorta and aortic debris as a marker of poor prognosis: Benefit of oral anticoagulants. J Am Coll Cardiol 33:1317-1322, 1999 .

19.

The Stroke Prevention in Atrial Fibrillation Investigators Committee on Echocardiography : Transesophageal echocardiography correlates with thromboembolism in high-risk patients with nonvalvular atrial fibrillation. Ann Intern Med 128:639-647, 1998.

20.

Rosenberg RD , Aird WC : Vascular-bed-specific hemostasis and hypercoagulable states. N Engl J Med 340:1555-1564, 1999 .

21.

Thomas DP , Roberts HR : Hypercoagulability in venous and arterial thrombosis. Ann Intern Med 126:638-644, 1997.

22.

Kiechl S. , Muigg A. , Santer P. , et al: Poor response to activated protein C as a prominent risk predictor of advanced atherosclerosis and arterial disease. Circulation 99:5,614-619, 1999.

23.

Sampram ES , Lindblad B. , Dahlback B. : Activated protein C resistance in patients with peripheral vascular disease . J Vasc Surg 28:624-629, 1998.

24.

Kluft C. , Meijer P. , Gram J. , et al: Acquired activated protein C resistance. Lancet 353:1882, 1999.

25.

Ernst E. , Resch KL : Fibrinogen as a cardiovascular risk factor: A meta analysis and review of the literature. Ann Intern Med 118:956-963, 1993.

26.

Guba SC , Fink LM , Fonseca V. : Hyperhomocysteinemia: An emerging and important factor for thromboembolic and cardiovascular disease. Am J Clin Pathol 106:709-722, 1996.

27.

Konecky N. , Malinow MR , Tunick PA , et al: Correlation between plasma homocysteine and aortic atherosclerosis . Am Heart J 133:534-540, 1997.

28.

Hajjar KA , Garish D. , Breslow JL , et al: Lipoprotein (a) modulation of endothelial surface fibrinogen and its potential role in atherosclerosis. Nature 339:303-305, 1989.

29.

Jurgens G. , Taddei-Peters WC , Költringer P. , et al: Lipoprotein (a) concentration and apolipoprotein (a) phenotype correlate with severity and presence of ischemic cerebrovascular disease. Stroke 26 :1841-1848, 1995.

30.

DeStefano V. , Finazzi G. , Mannucci PM : Inherited thrombophilia: Pathogenesis, clinical syndromes and management. Blood 87:3531-3544, 1996.

31.

van de Loo J. : Circulating factors of the homeostatic system as indicators of increased or reduced coronary risk. Br J Haematol 91:777, 1995.

32.

Ens GE : Atherosclerotic disease and hemostasis. Clin Hemostasis Rev 2:1, 1997.

33.

Croft SA , Daly ME , Steeds RP , et al: The prothrombin allele 20210A and its association with myocardial infarction. Thromb Haemost 81:861-864, 1999.

34.

Souto JC , Mateo J. , Soria JM , et al: Homozygotes for prothrombin gene 20210 A allele in a thrombophilic family without clinical manifestations of venous thromboembolism. Haematologica 84:627-632, 1999.