Activation of factor IX by erythrocyte membranes causes intrinsic coagulation

Abstract

As an extension of our earlier work, procoagulant activity of erythrocyte [red blood cell (RBC)] membrane was examined using biochemical and rheological techniques. Western blot analysis of coagulation factors incubated with erythrocytes (RBCs) showed that only factor IX (FIX) was activated by RBC membranes in the presence of calcium ions. A fluorogenic assay suggested that activated FIX is capable of activating factor X. A preliminary crude extraction of the substance from RBC membranes suggested that a FIX-activating enzyme may be located on the RBC membrane. The initiation of FIX activation by RBCs was enhanced by an elevation in hematocrit. Moreover, the rate of FIX activation by RBCs from normal pregnant women and diabetic patients was much faster than that from normal subjects. In addition, glucose treatment of normal RBCs resulted in the increase in procoagulant activity. It is suggested that FIX activation by RBC membranes may serve as a triggering mechanism for blood coagulation, although further study will be required to clarify the putative FIX activating enzyme on the RBC membrane and to permit more extensive physiological experiments to be performed.

Important Regulatory Role of Activated Platelet-Derived Procoagulant Activity in the Propagation of Thrombi Formed Under Arterial Blood Flow Conditions

“…Nevertheless, some investigators have demonstrated the initiation of the coagulation cascade by phospholipids and Factor XI on erythrocytes, even in the absence of tissue factor, 49 which may be relevant to our present results. In any case, further investigations are required to elucidate the correct mechanism of the initiation of the activation of the coagulation cascade on the surface of the platelet thrombi under blood flow conditions.…”

“…Regulatory role of platelet-derived procoagulant activity on the continuous activation of platelet and thrombus growth. Platelets, once they interact with subendothelial matrix such as collagen or von Willebrand factor (VWF), 48,49 activated to release ADP-containing dense granules. Next, the released ADP stimulates ADP receptors (P2Y1 and P2Y12).…”

Rheological study on coagulation of blood with special reference to the triggering mechanism of venous thrombus formation

“…To determine which factor (i.e., F-IX or F-X) was activated by RBCs, Western blot analysis of F-IX and F-X incubated with washed normal human RBCs was performed [12]. A band corresponding to activated F-IX (F-IXa) appeared (Fig.…”

“…However, clinical evidence to support the view that markedly reduced venous flow directly induces the initiation of thrombus formation at an intact vessel wall remains contradictory [9,10]. In our previous papers [11][12][13][14], it was shown that the coagulation reaction initiated through a direct activation of F-IX by an enzyme on RBC membranes serves as a triggering mechanism for pathogenesis of venous thrombosis.…”

Acute pulmonary thromboembolism occurring during treatment with tolvaptan in a patient with autosomal-dominant polycystic kidney disease

“…Dehydration increases the hematocrit and blood viscosity both of which could induce thrombotic tendency [4]. Moreover, elevated hematocrit levels are reported to promote activation of factor IX (an intrinsic factor for coagulation cascade) by erythroelastase IX (factor IX-activating enzyme) in erythrocytes, which could further enhance the coagulation pathway [5,6]. In addition, patients with reduced renal function are more likely to develop pulmonary thromboembolism than those with normal kidney function [7].…”