A.M. Mamusa

Fibrinogen and fibrinolytic activity in hyperthyroidism before and after antithyroid treatment

Plasma concentration of fibrinogen and Bβ 15–42, a specific product of fibrinogen metabolism induced by plasmin, were measured in a group of patients with untreated hyperthyroidism and in controls. Significantly increased plasma levels of both parameters were observed in hyperthyroid patients. The restoration of euthyroidism either by antithyroid drug or by radioiodine caused a significant decrease of fibrinogen and Bβ15–42. These data indicate that hyperthyroidism is another clinical condition associated with increased concentration of fibrinogen and Bβ 15–42.

α2antiplasmin and disseminated intravascular coagulation in liver cirrhosis

Subnormal concentrations of alpha 2 Antiplasmin (alpha 2 AP) in liver cirrhosis may be due to an impaired hepatic synthesis and/or to a fibrinolysis activation in disseminated intravascular coagulation (DIC). In order to clarify this problem, in 26 cirrhotic patients (15 compensated and 11 decompensated) alpha 2 AP plasma activity and plasma Fibrinopeptide A (FPA) were measured. Serum albumin, p-Cholinesterase (p-CHE), Fibrinogen and Fibrinogen Degradation Products (FDP) were also carried out. Our data show that alpha 2 AP and FPA were equally abnormal in compensated and decompensated cirrhosis. The significant negative correlation obtained between alpha 2 AP and FPA as well as the lack of correlation between alpha 2 AP and albumin, alpha 2 AP and p-CHE in both groups suggests that, in our patients, alpha 2 AP decrease may be due to a fibrinolysis activation induced by a DIC which appears chronic since Fibrinogen and FDP were normal. These findings are in agreement with the results obtained in the four subgroups a posteriori selected on the basis of FPA levels: alpha 2 AP in subgroups with high FPA was significantly different from controls while it did not differ in subgroups with normal FPA.

Thrombin Activity and Oral Anticoagulant Therapy: A Preliminary Study

The aim of this work was to investigate whether the thrombin activity is related to the degree of anticoagulation induced by oral anticoagulants. Moreover, we tried to detect an optimal anticoagulation range at which the lowest possible thrombin activity can be reached. We investigated 28 patients (19 women and 9 men, mean age 54 +/- 9 years). Anticoagulation had been induced by acenocoumarol for at least 1 year before the beginning of this study. The degree of anticoagulation was monitored by the thrombotest coagulation method. The therapeutic range was 5-13%. The thrombin activity was measured by means of the fibrinopeptide A radioimmunological assay. In 15, 7, and 6 of the patients, thrombotest and fibrinopeptide A were carried out twice, once, and three times, respectively. Our results show first of all a significant positive relationship between thrombotest and fibrinopeptide A (p less than 0.001). Once this result was obtained, we tried to improve our identification of the behaviour of the thrombin activity in relation to the degree of anticoagulation assessed by thrombotest. For this purpose we employed a third-degree polynomial regression analysis which showed a better fit of the data. Since the curve became steeper from about 10% thrombotest levels, we divided the FPA values on the basis of thrombotest ranges. FPA values for the 14- to 25% thrombotest range were significantly different from those in the thrombotest range of 4-10%. Moreover, FPA levels in the 11 to 13% thrombotest range were significantly different from those in the thrombotest range of 4-10%. Our results suggest that a significant decrease in thrombin activity may be achieved only with a deep anticoagulation.

Fibrinopeptide A and Bβ 15–42 in Liver Cirrhosis

In order to detect even minimal fibrinolysis activation in liver cirrhosis, we measured fibrinopeptide Bβ 15–42 (Bβ 15–42), an indicator of plasmin activity in vivo and α2-antiplasmin (α2-AP) in a group of cirrhotic patients. The second goal of this study was to investigate whether an increased fibrinolytic activity is related to a chronic disseminated intravascular coagulation. For this purpose we concomitantly measured fibrinopeptide A (FPA), marker of thrombin activity in vivo. Results show significantly higher levels of Bβ 15–42 in cirrhotic patients than in control (p 2-AP was lower in patients with high FPA levels than in patients with normal FPA (p 2-AP only in patients with high FPA (p 2-AP when all patients were considered. These findings confirm that in liver cirrhosis fibrinolysis activation may occur. The primary pathogenetic role of DIC may be important in this respect. However the lack of correlation between FPA and Bβ 15–42 suggests that other pathogenetic factors may be involved in determining fibrinolysis activation.

Subclinical activation of fibrinolysis in atherosclerotic disease detected by Bβ 15–42 assay

SummaryPlasma Bβ 15–42 and fibrinopeptide A (FPA) concentrations, which are respectively indicators of plasmin and thrombinin vivo activity, were measured in 46 patients with ischemic arterial disease without signs of acute thrombosis. In the group as a whole, an increase in both Bβ 15–42 and FPA was found. When the patients were divided in two groups on the basis of their reversible (transitory ischemic attacks and unstable angina) or irreversible (stroke and myocardial infarction) ischemic episodes, the levels of Bβ 15–42 were significantly elevated only in the former group when compared to controls (p<0.01). In the latter group we found significantly increased levels of FPA with respect to both controls (p<0.01) and patients with reversible and transient ischemic episodes (p<0.05). Moreover, the Bβ 15–42/FPA ratio was significantly lower in patients with irreversible ischemic episodes than in controls (p<0.01) and patients with transient ischemic episodes (p<0.01), while no difference was found between the latter group and controls, although FPA and Bβ 15–42 were significantly higher. These results suggest that in patients with transient and reversible ischemic episodes fibrinolytic activity is able to counterbalance an increased thrombin activity, while this does not appear to occur in patients with irreversible ischemic episodes.

Evidence for a Relationship between High Fibrinogen Levels and Decreased Thrombin Activity in vivo in Elderly Subjects

In order to investigate whether high fibrinogen levels were associated with elevated thrombin activity, we measured fibrinogen and fibrinopeptide A in 37 elderly healthy subjects ranging from 60 to 93 years. Fibrinogen levels (519.1 +/- 127.0 mg/dl) and fibrinopeptide A (5.9, 0.9-18.1 ng/ml) were significantly higher than in younger controls. A highly significant negative linear correlation was found between fibrinogen and fibrinopeptide A in the elderly subjects (p less than 0.01). However, a polynomial regression showed that this negative relationship was present at the fibrinogen levels ranging between 420 and 700 mg/dl. Our results suggest that high fibrinogen levels in elderly subjects do not necessarily mean that their thrombin activity is concomitantly increased.

Relationship between Elevated Fibrinopeptide A Levels and Alpha-2-Antiplasmin

In order to investigate whether alpha 2-antiplasmin (alpha 2-AP) levels may be related to thrombin activity, we measured alpha 2-AP and fibrinopeptide A (FPA) in 51 patients with clinical conditions frequently associated with increased thrombin activity. The diagnoses were: atherosclerotic disease, chronic inflammatory disease and hematological neoplastic disease. A significant negative correlation was found between alpha 2-AP and FPA (p less than 0.01). When patients were divided into three subgroups on the basis of their FPA levels, a significant reduction in alpha 2-AP was found in patients with the highest FPA concentration (greater than 9 ng/ml). Accordingly, a significant negative relationship between alpha 2-AP and FPA was found only in this subgroup (p less than 0.01). Our data suggest that the partial consumption of alpha 2-AP in patients with elevated FPA levels may reflect a subclinical fibrinolysis activation secondary to increased thrombin activity.