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In 124 patients with various types of malignancy, fpA and delta fpA were measured. In 35 of these patients the effect of heparin injection on fpA and delta fpA was studied. All patients were ambulant without clinical signs of venous thromboembolism or DIC and had not received cytostatic, anticoagulant, or radiotherapy recently. In about 75% of these patients, fpA was elevated, whereas in the blood of one third of the patients, both elevated fpA levels and accelerated delta fpA were detected. Eight of the 45 patients with accelerated delta fpA (and elevated fpA) presented laboratory signs of low-grade DIC. In the patients taken at random for heparin administration, delta fpA normalized upon heparin injection, whereas in the majority of patients, irrespective of the fpA-generation rate, fpA levels were not affected by "adequate" heparinization. These results indicate that (1) about 30% of the (selected) patients admitted to our cancer clinic present with evidence of intravascular thrombin activity and (2) in 70% of these patients fpA is generated, at least in part, at a site not accessible to heparin. In addition 95% of patients with active metastatic disease showed an elevated fpA, whereas 90% of cancer patients in remission and 80% of patients without metastasis had a normal fpA, indicating that fpA can potentially be used to estimate the spread and the activity of the malignant process.

Urinary 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 less than 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.

A Dutch family (family A) with inherited antithrombin-III deficiency and an increased incidence of venous thrombosis was investigated. Antithrombin-III levels were measured by means of a coagulation assay in plasma and by single radial immunodiffusion in plasma and serum.THREE GROUPS COULD BE DISTINGUISHED: group I comprised the relations-in-law of family A, group II the members of family A with a plasma antithrombin-III level higher than 90% of normal, when determined by the immunoassay, and group III the members of family A with an antithrombin-III level of less than 60%. To group III belonged all eight adults with an abnormal tendency to thrombosis, and furthermore nine children, all having a parent with abnormally low antithrombin-III levels. Mean plasma and serum antithrombin-III levels were significantly decreased in group III. 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 60% of normal, causes thrombophilia and that the pattern of inheritance is autosomal dominant.