Molecular Subunits and Transamidase Activity of Factor XIII During Disseminated Intravascular Coagulation in Acute Leukaemia

Summary

The "in vivo" thrombin generation which occurs during disseminated intravascular coagulation (DIC) leads to complex coagulation abnormalities. The subunit A of fibrin stabilizing factor (Factor XIII) is a sensitive target for thrombin whilst the subunit S, is not. The two subunits seem to be insensitive to plasmin.

A typical DIC picture has been found in 15 out of 200 cases of acute leukaemia; the subunits and the transamidase activity (TA) of the enzyme were severely reduced. The biologically active component, subunit A, and its TA were found to be much more reduced (P < 0.001) in patients with DIC than in those with AML without typical laboratory DIC pattern ("controls"). The levels of subunit A were correlated only with fibrinogenaemia. No difference in subunit S levels was found between normal healthy subjects and "controls". On the other hand this subunit was significantly reduced in DIC patients.

It is assumed that thrombin affects the zymogen Factor XIII leading to the activation product A₂S which could be cleared from the circulation. An alternative explanation of the decrease of subunit S, insensitive to thrombin, could be sought in a defect of its synthesis which seems to be related to that of subunit A, as it has been shown in congenital Factor XIII deficiency.

Haemorrhagic complications are common and often fatal in patients with acute leukaemia. Platelet transfusion therapy has reduced the risk of haemorrhage but there are cases, not responsive to platelets, in whom the haemostatic mechanism is altered, generally by disseminated intravascular coagulation (DIC) (1). This syndrome results from an exaggerated response to cell damage with release of thromboplastic substances which activate "in vivo" the coagulation system. Thus, the "in vivo" thrombin generation leads to a consumption pattern including reduced levels of platelets, fibrinogen, factor V, VIII and XIII; positive paracoagulation tests; prolonged thrombin time and increased fibrin degradation products (FDP). However, patients with haemorrhages, presumably due to DIC, do not always show all of the above laboratory features (2, 3). Moreover, conclusive and extensive clinical studies of the biological expression of the syndrome are missing especially in acute leukaemia. Consequently, the diagnostic criteria for DIC are not yet well established and the diagnostic or prognostic role of a single coagulation factor is not definitively known. Concerning Factor XIII in acute

Keywords

Acute leukaemia - DIC-Factor XIII

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