Transfer of tissue factor from leukocytes to platelets is mediated by CD15 and tissue factor

Abstract

We describe thrombogenic tissue factor (TF) on leukocyte-derived microparticles and their incorporation into spontaneous human thrombi. Polymorphonuclear leukocytes and monocytes transfer TF+particles to platelets, thereby making them capable of triggering and propagating thrombosis. This phenomenon calls into question the original dogma that vessel wall injury and exposure of TF within the vasculature to blood is sufficient for the occurrence of arterial thrombosis. The transfer of TF+ leukocyte-derived particles is dependent on the interaction of CD15 and TF with platelets. Both the inhibition of TF transfer to platelets by antagonizing the interaction CD15 with P-selectin and the direct interaction of TF itself suggest a novel therapeutic approach to prevent thrombosis.

Recombinant FVIIa

“…However, the presence of TF in platelets and leucocytes was suggested already in 1905 by Morawitz [3]. Further support of TF being present in these cells has accumulated over the years [16–21]. A transfer of TF‐containing particles by monocytes and polymorphonuclear leucocytes to platelets, the process being dependent on the interaction of CD15 and P‐selectin, was reported by Rauch and coworkers [20].…”

“…The presence in whole blood of TF‐containing microparticles originating from platelets has been confirmed [29,30]. Under normal conditions the TF found on cell surfaces as well as in microvesicles seems to be encrypted and thus allows the circulation of such TF‐containing particles without inducing generalized coagulation [20,31]. The de‐encryption of TF bound to various membranes seems to require binding of the TF‐containing particles to injured surfaces where haemostasis is required.…”

“…Further support of TF being present in these cells has accumulated over the years [16–21]. A transfer of TF‐containing particles by monocytes and polymorphonuclear leucocytes to platelets, the process being dependent on the interaction of CD15 and P‐selectin, was reported by Rauch and coworkers [20]. Based on the observations of platelet thrombi‐ and leucocyte‐associated TF reported, the concept of blood‐borne active TF was described [19].…”

Evaluation of hemostasis in flowing blood

“…First, the exact contribution of blood‐borne tissue factor remains unclear. Giesen et al [23] showed the presence, on surface‐adherent platelets, of tissue factor in 1‐ to 2‐μm granules, putative microparticles, which co‐localized with granules positive for CD‐15 [24], indicating a leukocyte origin. Therefore, tissue factor of leukocyte and/or even of endothelial or erythrocyte origin may localize with and augment mural platelet adhesion/aggregation.…”

Hemorrhagic complications in bone marrow transplant: possible roles of recombinant activated coagulation factor VII

“…The trigger complex is not located on the platelet surface, but must be transported to the activated platelet surface by a tissue factor‐bearing microparticle. The origin of the tissue factor‐bearing microparticle remains controversial, but monocytes and granulocyte microparticles have been proposed as the source 42 . The initial production of small amounts of activated factor X resulting from this complex is thought to be crucial for the activation and release of coagulation factor VIII from von Willebrand factor, activation of factor V, the activation of factor XI and the further activation of platelets (Figure 3).…”