Procoagulant Cell Activities in Acute Leukemia

Abstract

Hacmorrhage is the most common haemostatic disorder in patients with acute leukemias¹. Among other factors, including thrombocytopenia, consumption coagulopathy is considered to be an important cause of this complication.

A dramatic derangement of the blood clotting system, which leads to disseminated intravascular coagulation (DIC), is most commonly associated with acute promyelocytic leukemia², but activation of blood coagulation to different extents has been described in all types of acute leukemias³.

Procoagulant activities associated with blast cells are considered to play an important role in inducing the hemostatic system imbalance, leading to clotting complications. Three procoagulants have so far been identified in leukemic cells: 1. Tissue factor (TF), a glycolipoprotein which forms a complex with factor VII (FVII) to activate factor X (FX) and factor IX (FIX), which is a procoagulant of normal and malignant tissues⁴; 2. A membrane factor V receptor, which facilitates the assembly of prothrombinase complex, thereby accelerating its activity up to 100,000 times⁵; 3. Cancer procoagulant (CP), a cysteine proteinase that directly activates FX, independently of the presence of FVII⁶, and has thus far been described only in malignant tissue, but never in the corresponding normal counterparts⁷,⁸. We have conducted a series of studies in order to characterize the procoagulant activity (PCA), particularly CP, of blast cells freshly isolated from leukemic patients' bone marrow. Our data demonstrate that CP can be present in different proportions in the various phenotypes.

More recently we have confirmed the same results in leukemic cell lines stabilized either in vitro or in immunodeficient mice. These studies also add new data to the evidence that CP expression is a property confined to the transformed and not the normal phenotype.