Detection of tissue factor in platelets: why is it so troublesome?

Tissue factor (TF) is the most important trigger for the extrinsic coagulation pathway. TF, earlier denoted as thromboplastin, has always been a mystery since its discovery due to its abundant presence in most human tissues but not blood. The latter has been extensively studied in a vast quest for possible sources of blood-borne TF yielding many conflicting findings and confusing conclusions regarding the presence of TF mRNA, protein or functional procoagulant activity in virtually all blood cells. Platelets, in particular, have been heavily scrutinized by investigators eager to demonstrate expression of TF. However, some investigators including our own groups have not found evidence for TF in platelets. This article discusses notable reports and possible reasons for erroneous detection of platelet TF antigen and activity including artificially hyper-stimulated platelets, suboptimal purity of cell preparations, flaws in study design and/or choice of reagents.