Comparison of 125I-fibrinogen kinetics and fibrinopeptide A in patients with disseminated neoplasias.
To provide more information on the pathways of fibrinogen catabolism in generalized cancer, the effect of heparin on fibrinopeptide A (fpA) and on 125I-fibrinogen kinetics was studied in 15 patients with disseminated neoplasia. Three patients had evidence of venous thrombosis and in 2 additional patients a low fibrinogen level together with increased amounts of FDP/fdp and a positive ethanol test indicated disseminated intravascular coagulation (DIC). The plasma levels of fpA were grossly elevated (4.6--20, mean 11.4 ng/ml, normal values 1.01 +/- 0.45 ng/ml) in patients with thrombosis or DIC, and normal to grossly elevated (0.4--10.4, mean 6.1 ng/ml) in the other patients. Intravenous heparin bolus lowered the fpA level in 11/11 patients, and continuous heparin treatment led to an impressive suppression or complete normalization of the plasma fpA in 5/6 patients. This finding is thought to reflect heparin suppression of thrombin activity on fibrinogen. In some cases, the fpA fall after heparin bolus was slow and/or incomplete, suggesting fpA generation at sites not easily accessible to heparin or insufficient heparin dosage. The 125I-fibrinogen kinetics were characterized by a significantly shorter half-life (t1/2: 2.5 days), increased catabolic rate constant (j: 0.44 days-1), and increased absolute turnover (68.9 mg fibrinogen/kg/day) as compared to 4 normal subjects (t1/2: 4.2 days; j: 0.26 days-1; turnover 21.7 mg fibrinogen/kg/day). As estimated from the fpA generation rates, intravascular thrombin action on fibrinogen contributed only in minor part to increase the turnover of 125I-fibrinogen. In particular, the turnover was greatly accelerated in heparin-treated patients despite impressive suppression or normalization of the fpA levels in 5/6 cases.
D000328:Adult; D000368:Aged; D004211:Disseminated Intravascular Coagulation / Q000209:etiology; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000378:metabolism*; D005344:Fibrinopeptide A / Q000378:metabolism*; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000097:blood*; D009369:Neoplasms / Q000097:blood* / Q000150:complications / Q000188:drug therapy
D005338:Fibrin Fibrinogen Degradation Products; D007457:Iodine Radioisotopes; D005344:Fibrinopeptide A; D005340:Fibrinogen; D006493:Heparin