Fibrinogen survival and fibrinopeptide A in acute leukemia.
BACKGROUND. Hypofibrinogenemia and increased fibrin(ogen) degradation products in acute leukemia have been attributed to intravascular thrombin generation triggered by leukemic cells. However, the strict relationship between fibrinogen catabolism and turnover of fibrinopeptide A (FPA), which is a sensitive and specific marker of thrombin activity, has not been evaluated in acute leukemia (AL) with or without disseminated intravascular coagulation (DIC) to see whether mechanisms other than thrombin activity could be responsible for fibrinogen consumption. We report here the 125I-fibrinogen kinetics and FPA measurements in 19 patients with AL, 6 of them with DIC. METHODS AND RESULTS. Radiolabelled fibrinogen kinetics were studied in all the patients concomitantly with the start of chemotherapy. Fibrinopeptide A was measured by a radioimmunoassay at time of diagnosis and during chemotherapy. The kinetics of disappearance of radiolabelled fibrinogen where biphasic, with a rapid phase in the first 1-3 days of chemotherapy and a subsequent slow phase associated with the reduction or disappearance of blast cells. Patients with DIC had a significantly shorter half-life and turnover than patients without DIC. The latter group had significant shortening of these parameters in comparison to normal subjects. The thrombin-dependent catabolic rate of fibrinogen, calculated from the mean level of FPA during the first phase of disappearance curve and by assuming 2 moles of FPA generated per mole of fibrinogen, was similar in patients without DIC and in normal subjects, whereas patients with DIC had a significantly higher catabolic rate, even though the increase was not sufficient to account for all the turnover of fibrinogen. No relationship was observed between fibrinogen turnover and FPA turnover.
Department of Hematology, San Bortolo Hospital, Vicenza, Italy.
G
G
Castaman
E
E
Galloni
A V
AV
Dri
F
F
Rodeghiero
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000347:Afibrinogenemia / Q000209:etiology; D000368:Aged; D020152:Antithrombin III Deficiency; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000209:etiology; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D005344:Fibrinopeptide A / Q000032:analysis*; D006207:Half-Life; D006801:Humans; D007938:Leukemia / Q000097:blood* / Q000150:complications; D008297:Male; D008875:Middle Aged; D013917:Thrombin / Q000378:metabolism
D005344:Fibrinopeptide A; D005340:Fibrinogen; D013917:Thrombin