fibrinopeptide-a and Heart-Failure

Abnormalities of baseline hemostatic variables have been related to a hypercoagulable state in patients with chronic heart failure (CHF). Given that physical exercise leads to an activation of coagulation physiologically, this study addressed the question of whether the exercise-induced hemostatic activation is enhanced in patients with CHF. Ten patients with dilated cardiomyopathy (ejection fraction < 40%) and 10 healthy individuals (matched for sex, age and body mass index) were subjected to a maximal exercise test on a bicycle ergometer. Healthy subjects performed a second exercise test at a submaximal intensity level, in which oxygen consumption (VO2) was adjusted to the peak oxygen consumption (VO2peak) of the corresponding patient. Exercise testing had only marginal effects on markers of thrombin formation in patients and healthy individuals alike. In patients with CHF, exercise-induced changes in fibrinopeptide A, an index of fibrin formation, paralleled those observed in controls after submaximal exercise whereas most pronounced changes occurred in healthy subjects after maximal exercise. Plasmin-antiplasmin complexes increased almost three-fold with maximal exercise in both groups, thus indicating a marked formation of plasmin. Maximal physical exercise does not induce an exaggerated formation of thrombin and fibrin in CHF patients. The fibrinolytic response to exercise in terms of plasmin formation is not compromised in patients with dilated cardiomyopathy.

Topics: Adult; Cardiomyopathy, Dilated; Case-Control Studies; Exercise; Exercise Test; Exercise Tolerance; Fibrinolysin; Fibrinopeptide A; Heart Failure; Humans; Male; Middle Aged; Peptide Fragments; Protein Precursors; Prothrombin; Thrombin; Thrombophilia

Thromboembolism is an important complication of heart failure. To test the hypothesis that heart failure may be associated with hemostatic dysfunction, we studied hemostatic function in 21 patients with stable chronic heart failure and related these measures to the severity of heart failure as assessed by clinical evaluation, neuroendocrine activation, radionuclide ventriculography, and cardiopulmonary exercise testing. Plasma and blood viscosity were elevated; all patients showed evidence of platelet activation, and many had elevated plasma concentrations of fibrinopeptide A, D-dimer, and von Willebrand factor. The plasma concentrations of these variables were poorly interrelated and related poorly to the severity of heart failure. Plasma concentrations of angiotensin II and endothelin were correlated, and the latter was also correlated with the plasma concentration of von Willebrand factor. Patients with chronic heart failure have hemostatic abnormalities that may predispose them to thromboembolic events and may be in part due to neuroendocrine activation.

Topics: Adult; Aged; Angiotensin II; Blood Coagulation; Blood Viscosity; Chronic Disease; Endothelins; Exercise Test; Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Heart Failure; Humans; Male; Middle Aged; Neurosecretory Systems; Platelet Activation; Radionuclide Ventriculography; Thromboembolism; von Willebrand Factor

The hemostatic alterations in two adult patients who were supported by left ventricular assist devices (LVADs) because of postcardiotomy heart failure were evaluated. In both patients, fibrinopeptide A and thrombin-antithrombin III complex increased markedly during the first several days, and thereafter decreased moderately but remained above normal over the entire procedure. Furthermore, fibrinopeptide B beta 15-42 and alpha 2 plasmin inhibitor-plasmin complex were also markedly increased over the entire course of LVAD treatment. These data show that the LVAD system strongly activates both the coagulation and the fibrinolytic system, even when thromboembolic or bleeding complications are not clinically evident. Furthermore, the decrease in physiological coagulation inhibitors, especially protein C, indicates that these factors are activated and consumed during LVAD treatment. Because protein C is important in regulating the coagulation cascade during LVAD treatment, exhaustion of this system might result in thromboembolic complications during LVAD treatment.

Topics: Aged; Antithrombin III; Female; Fibrinopeptide A; Fibrinopeptide B; Heart Failure; Heart-Assist Devices; Hemostasis; Humans; Male; Middle Aged; Peptide Hydrolases; Postoperative Complications; Protein C

The prompt reduction of elevated fibrinopeptide A (FPA) levels (normal less than 1.3 pmole/ml) by heparin therapy in patients with thromboembolism suggests that measuring the FPA level may provide a good index of disease activity and be a useful method of monitoring therapy. Sepsis or malignancy may elevate FPA levels and coexist with thromboembolism. FPA levels were surveyed in 51 patients with thromboembolism (including 15 with concurrent sepsis or malignancy) during heparin treatment in an attempt to distinguish the effects of coexistent disease and the progression of thromboembolism. The anticoagulant effect of heparin was within the therapeutic range for 81% of the study period. In patients with thromboembolism alone and marked resolution of emboli on repeat lung scan, the mean daily FPA levels were lower than the values in patients with minimal resolution (p less than 0.005). In patients with marked resolution of pulmonary embolism or venous thrombosis and a concurrent disorder, the mean FPA level remained elevated compared to normal values in patients with thromboembolism alone. These results suggest that FPA levels monitored during heparin therapy of thromboembolism may be useful as an index of disease activity except in the presence of coexisting sepsis or malignancy.

Topics: Adenocarcinoma; Adult; Aged; Anticoagulants; Carcinoma, Squamous Cell; Female; Fibrinogen; Fibrinopeptide A; Heart Failure; Heparin; Humans; Leukemia, Lymphoid; Lupus Erythematosus, Systemic; Male; Middle Aged; Polycythemia Vera; Pulmonary Embolism; Sepsis; Thromboembolism