Defective Binding of Thrombin to Platelets in Myeloid Leukaemia

Abstract

Platelets from patients with myeloid leukaemia showed reduced aggregation with collagen or thrombin. These platelets also had a lower capacity to bind thrombin. This lower thrombin binding is due to a decrease in the total quantity of receptors available and not because of a change in the affinity. In the presence of the patients' plasma, the aggregation behaviour of normal platelets induced by thrombin as well as the clotting time of fibrinogen remained unchanged. The results suggest that the platelet dysfunction in myeloid leukaemia is partially due to a membrane defect involving the thrombin receptors which leads to an impaired induction of the initial stimulation.

Multiple platelet defects identified by flow cytometry at diagnosis in acute myeloid leukaemia

“…This indicates the presence, and random heterogeneous distribution, of qualitative platelet aggregation defects. The present results of impaired platelet micro-aggregate formation are in agreement with previous findings of impaired platelet macro-aggregation in AML ( Van der Weyden et al, 1972;Maldonado & Pierre, 1975;Ganguly et al, 1978;Woodcock et al, 1984), while the heterogeneous distribution of platelet micro-aggregate formations may reflect the heterogeneous involvement of the megakaryocytic lineage in AML (Lemez et al, 2000).…”

“…It is conceivable that the considerable bleeding tendency of the patients is a consequence of dysregulated platelet production, resulting in thrombocytopenia as well as qualitative platelet defects (Friedman et al, 1964;. Previous platelet aggregation studies have demonstrated abnormal platelet function in selected groups of patients (Van der Weyden et al, 1972;Maldonado & Pierre, 1975;Ganguly et al, 1978;Woodcock et al, 1984). However, the use of this method in a representative patient population has been hampered by the dependency of platelet aggregation analysis on platelet number.…”

Platelet enzyme abnormalities in leukemias

“…[4][5][6] Platelet functional defects have been demonstrated by several authors in different types of leukemias, including abnormalities of bleeding time, tourniquet test, clot retraction and platelet thromoplastic activity. [14,[19][20][21][22] Metabolic energy is essential for most platelet functions, including aggregation. The process of platelet aggregation and maintenance of discoid shape depends on metabolic energy that can be supplied through glucose metabolism.…”

Reduced Platelet Factor X-Activating Activity

“…The most common defect reported was absence of aggregation in response to epi nephrine often associated with defective clumping by other aggregating agents such as ADP, collagen, thrombin or serotonin (1). Reduced platelet aggregation with thrombin has been recently reported in a group of patients with myeloid leukaemia; it was associated with defective binding of thrombin to platelets, due to a decrease in the total quantity of receptors available on the platelet mem brane (13). Other tests including platelet adhesiveness, bleeding time and platelet factor 3 (PF3) were also occasionally impaired.…”