Tissue factor pathway inhibitor (TFPI) in patients with lacunar stroke

Endothelial dysfunction is thought to play a role in the development of silent white matter lesions (WMH) in patients with a first ever lacunar stroke. Hassan et al 1 demonstrated that several plasma markers of endothelial function were elevated in lacunar stroke patients compared to controls, but surprisingly some markers (TFPI) were lower in lacunar stroke patients with extensive WML. They concluded that this endothelial dysfunction would contribute to a pro-thrombotic state through activation of the extrinsic coagulation pathway. Earlier, we performed a pilot study in 74 patients with a first ever lacunar infarct to determine to what extent patients with lacunar stroke and concomitant WML have evidence of endothelial cell activation, and whether this would lead to activated coagulation in plasma. Patients underwent a brain MRI. WMH were graded according to the modified Fazekas scale2. vWFag, sTM and TFPI were measured using ELISA or immuno-turbidimetric assay. Chi square analysis was used to relate concentration of plasma markers (divided into tertiles) to severity of leukoaraiosis (divided into a dichotome variable). We found high levels of TFPI to be associated with extended WMH (p=0.026), but sTM and vWF were divided equal between the two groups. We concluded that higher levels of TFPI in lacunar stroke patients with extensive WML could suggest endothelial dysfunction, the lack of difference in plasma levels of vWF and sTM makes this hypothesis unlikely. In the current study, we want to further evaluate the role of TFPI (truncated and full-length) in lacunar stroke patients, by evaluating the release of TFPI by the endothelium after injection of IV heparin.

1. Is the release of TFPI by endothelium after admission of heparin different between lacunar stroke patient and healthy controls?

2. Is the release of TFPI by endothelium after admission of heparin different between lacunar stroke patients with or without concomitant ischemic white matter lesions?

The first sample of blood is drawn several minutes before administration of heparin.

The second and last sample, 15 minutes after administration of heparin.

Single intravenous dose of 7500 IU of heparin, preceded and followed by withdrawal of 30 ml of blood.