No abstract

However, the results of the coagulation assay showed some overlap between groups II and III. In addition, the immunoassay appeared to be much less laborious than the coagulation assay. Therefore, the former assay is recommended in any search for similar families.The results of our family investigation confirm the findings of Egeberg (1965) that inherited antithrombin-III deficiency, giving rise to plasma levels between 50 and 600% of normal, causes thrombophilia and that the pattern of inheritance is autosomal dominant.

Concentrations of plasma fibrinopeptide A (FPA) were measured by radioimmunoassay in 50 patients with venous thromboembolism or disseminated intravascular coagulation or both. A consistent discrepancy was observed in values obtained with two anti-FPA antisera. Analysis of extracts from plasma of these patients by high-performance liquid chromatography (HPLC) revealed the presence of a phosphorylated and an unphosphorylated form of the A peptide. Differences in concentrations of FPA measured with the two antisera could be accounted for by their different reactivity with phosphorylated FPA (FPA-P). The differences were abolished by treatment with alkaline phosphatase. A good correlation was observed between the FPA-P content of free A- peptide material and of fibrinogen in plasma as determined by HPLC (r = .88, P less than .001, n = 11). In patients with elevated FPA levels, the mean FPA-P content of fibrinogen was significantly higher (P less than .002, n = 13) than in patients with normal FPA levels (n = 8) and in healthy controls (n = 14). Phosphorus in fibrinogen did not correlate with fibrinogen degradation products or fibrinogen levels and became normal on adequate anticoagulation. Therefore, blood-clotting activation may lead to a high phosphate content of fibrinogen and of free FPA in plasma.

SummaryUrinary fibrinopeptide A immunoreactivity was determined by radioimmunoassay using two anti-fibrinopeptide A sera with a different specificity in patients with venous thromboembolism, disseminated intravascular coagulation and rheumatoid arthritis. Elevated levels were frequently observed with both sera, and intravenous administration of heparin in patients with a thromboembolic disorder resulted in a decline of urinary fibrinopeptide A (FPA) concentrations to normal or nearly normal values. For both sera significant correlations with plasma levels were found although one of the sera reacted significantly better with the material in urine samples from these patients than the other (p <0.0001, n = 73). Analysis of urinary fibrinopeptide A immunoreactivity by high performance liquid chromatography (HPLC) provided evidence that A peptide material present in this body fluid was heterogeneous. In view of the characteristics of the antisera used in this study, data suggest that urinary FPA immunoreactivity consists to a large extent of carboxyterminally degraded FPA. Excretion of circulating FPA immunoreactive material through the kidneys apparently involves dephosphorylation and carboxyterminal breakdown of the A peptide. Since both synthetic and native phosphorylated or unphosphorylated fibrinopeptide A appeared to be stable in urine in vitro, an active role of the kidney in degrading the A peptide is likely.

Hypercoagulability, known to complicate malignant disease, can be detected by the measurement of fibrinopeptide A (FPA). The aim of the present study was to establish the significance of FPA production in. patients (n = 113) with various types of malignancy, without clinical signs of DIC, venous thromboembolism, not receiving cytostatic, anticoagulant or radiotherapy or bedrest. 8 patients presented laboratory abnormalities compatible with DIC; In this group mean FPA was 9.8 ng/ml (normal 1.4±0.9.2SD) and FPA generation In vitro (ΔFPA) was 15 ng/ml/10 min (normal 0.4±0.8, 230). In the remaining 105 patients, mean FPA was 5.2 ng/ml andFPA was 1.8 ng/ml/10 min. Of the 20 patients with both normal FPA and ΔFPA, 13 were clinically in remission, 5 had malignancies without detectable metastases and only 2 showed metastases. In 2 patients FPA was normal but ΔFPA was slIghtLy accelerated. 50 patients had elevated ΔFPA but normal FPA and in 33 cases both FPA and ΔFPA were increased; in these groups the majority of patients had a metastatic malignancy In 22 patients mean FPA before (4.9 ng/ml) and 20 mln after(4.2 ng/ml) receiving heparin (7500 U, i.v.) was not significantly different. These results suggest that apart from DIC tumor cells or the adjacent inflammatory area of tumors may trigger FPA generation, not being affected by heparin. It Is postulated that “heparin resistant” FPA generation Is potentially a sensitive marker of tumor activity.