Depressed fibrinolysis in patients with acute leukaemia.

The fibrinolytic system was studied in 46 patients with acute leukaemia at diagnosis. Untreated patients (with the sole exception of the M3 subgroup) showed an inhibition of fibrinolytic activity, measured by the euglobulin lysis time and area. This inhibition was accompanied by reduced t-PA antigen and t-PA inhibitor activity. No correlation was found between the above-mentioned fibrinolytic parameters and the biochemical haematological values considered, nor with clinical and/or laboratory features of DIC, fever, liver failure. The decrease in immunological plasminogen and functional alpha 2-antiplasmin, showed a significant correlation with the presence of clinical and/or laboratory signs of DIC, as diagnosed on the basis of concomitant increase in fibrin monomers, plasmatic fibrinopeptide A and serum FDP.

Procoagulant cellular activity (PCA) in the classification of acute leukemia.

The procoagulant cellular activity (PCA) of leukemic cells was evaluated, before and after endotoxin stimulation, in 38 patients with acute leukemia at presentation subdivided according to the FAB classification. In the M4 and M5 subgroups the stimulated leukemic cells showed a significant increase in the production of PCA compared with freshly isolated cells. No evident PCA was documented in M1 and M2 AML as well as in the majority of acute lymphoid leukemias tested, both before and after endotoxin stimulation. The myeloid and lymphoid leukemic cells appear to behave similarly to normal leucocytes, within which only monocyte/macrophages are capable of producing PCA following endotoxin stimulation. These findings suggest that in human leukemic cells the endotoxin-induced production of PCA may be considered a indicator of monocyte/macrophage differentiation and thus represent a valuable diagnostic tool in the classification of acute leukemias.

Human myeloid precursor cells do not possess or produce procoagulant activity (PCA).

The procoagulant cellular activity (PCA) of human myeloid precursor cells was evaluated after fractionation of normal bone marrow cells over a discontinuous albumin density gradient. No PCA was documented in any of the six freshly isolated fractions (F1-F6); significant amounts of PCA were instead produced, after a 4-h endotoxin preincubation, in fractions F1 and F2, which, unlike the other fractions, contained up to 5% monocyte-macrophages. After removal of the latter by plastic adherence, the PCA was abolished. This study shows that PCA can be produced only by monocyte-macrophages upon endotoxin activation, while myeloid precursor cells, at all stages of differentiation, are incapable of PCA. The PCA demonstrated in some human acute myeloid leukemias, other than that of the monoblastic subgroup, appears therefore to be related to the neoplastic transformation rather than to a maturation arrest or to a toxemic stimulation.

Procoagulant cellular activity and disseminated intravascular coagulation in acute non-lymphoid leukaemia.

The procoagulant cellular activity (PCA) of intact and lysed leukaemic cells was evaluated at diagnosis in 23 patients with acute non-lymphoid leukaemia (ANLL). The leukaemic cells of all 13 patients having DIC feature (excess of fibrin monomers, serum FDP and plasma fibrino-peptide A) showed a significant (P less than 0.0001) increase of PCA, while a pattern similar to that of normal granulocytes and lymphomonocytes was observed in the remaining 10 patients without evidence of DIC. When the patients were subdivided according to the FAB cytological classification, features of DIC and increased PCA were demonstrated in 3/3 M3 patients, 5/6 M5 patients and only in 5/14 remaining patients. These findings indicate that in ANLL patients: (1) the increased PCA of leukaemic cells is closely related to the occurrence of DIC; (2) the increased PCA seems related to the differentiation line and maturation level of the leukaemic cells.