The Anticoagulant Activity of Lysosomal Cationic Proteins from Polymorphonuclear Leukocytes *

Abstract

Summary. A cationic protein fraction from rabbit polymorphonuclear leukocyte lysosomes has been shown to exert a potent anticoagulant effect on human blood in vitro. The anticoagulant activity is detectable in the whole blood clotting time, the recalcification time of platelet-rich plasma, the prothrombin time, the partial thromboplastin time, and the thromboplastin generation test. The lysosomal cationic proteins do not inhibit any of the known specific procoagulants. They appear to inhibit clotting by blocking the formation of intrinsic thromboplastin possibly by interfering with the role of phospholipids in the reaction involving Factors V and X and calcium.

Coagulant Activity of Leukocytes. TISSUE FACTOR ACTIVITY

“…1). A possible explanation for this slow activation is the presence of inhibitors in the leukocytes (4). When cellular fractions separated by centrifugation were tested, maximal factor X activation was reached much more rapidly consistent with the possibility that an inhibitor was removed during the fractionation procedure.…”

“…Human circulating leukocytes (1) and rabbit peritoneal leukocytes are known to possess anticoagulant activity (4). Anticoagulant activity was also present in F0 and E2 leukocytes being released in the cell-free supernate of E2 leukocytes incubated in citrate saline at 370C (while procoagulant activity was released when leukocytes were incubated in Hanks solution).…”

“…White cells have been shown to contain both procoagulant and anticoagulant activity (1)(2)(3), the anticoagulant activity having been more thoroughly investigated (4). Also, patients with acute leukemia may present with defibrination and thrombosis (5)(6)(7)(8)(9)(10).…”

Role of Granulocytes in the Development of Venous Thrombosis in Patients with Hip Fractures

“…He proposed that this process was due to the release of leukocytebound proteolytic enzymes. Since then, sev eral authors have shown that heterogeneous lysosomal cationic proteins from PMN leu kocytes contain substances exhibiting in vi tro plasminogen activator activity, but also direct fibrinogenolytic and fibrinolytic activ ity [14][15][16][17][18][19], Thus, the possibility of fibrin dissolution via exudative polymorphonu clear neutrophils was raised. But to date, direct in vivo evidence for this phenomenon has not been obtained.…”

On the Influence of Normal and Leukemic Human Leukocytes on Blood Coagulation

“…Although a possible role of leukocytes in blood coagulation was pointed out in the last century (Buchanan 1845), this problem has only recently attracted attention [10]. These studies have demonstrated that leukocytes may be a source of thromboplastic and antiheparin activities [4,5,6,9,13,15,18,24,29], although the relationship between these activities and platelet factors 3 and 4 [14] are still not clear. Thromboplastic activity was also demonstrated in erythrocytes [7,8].…”