Tissue factor pathway inhibitor (TFPI) inhibits the extrinsic coagulation system. A major pool of TFPI is associated with the vascular endothelium and can be mobilized into the circulation by heparin. In circulating blood, TFPI is mainly associated with LDL (80%), whereas 10% to 20% is carrier free. In this study, heparin administration caused a 2.2-fold and a 7.5-fold increase in TFPI activity and TFPI antigen, respectively, in 25 patients with phenotypes IIa and IIb hyperbetalipoproteinemia. Because the antigen determination of TFPI almost exclusively measures carrier-free TFPI, more than 90% of the heparin-induced increase in TFPI activity was caused by mobilization of carrier-free TFPI from the vascular endothelium. Therapeutic lowering of total cholesterol (a decrease of 31.1 +/- 11.6%, P < .001) by 40 mg/d lovastatin in 17 patients with hyperbetalipoproteinemia was accompanied by a parallel decrease in TFPI activity (of 27.7 +/- 24.2%, P < .001) because of a reduction in LDL-TFPI complexes. However, drug intervention did not affect carrier-free TFPI or the magnitude of the vascular pool of TFPI that could be mobilized into the circulation by heparin. Moreover, this reduction of LDL-TFPI complexes did not reduce the anticoagulant potency of TFPI in plasma or of the vascular endothelial pool. The results of this study may imply that the anticoagulant potency of TFPI is associated with its carrier-free form in plasma or on the endothelium and that downregulation of LDL affects neither the size nor the anticoagulant potency of the endothelial pool of TFPI.
Altogether 34 cases of sudden infant death were studied postmortem with particular emphasis on the pathological changes in the lungs. Light microscopy, including application of immunohistochemical methods, and transmission electron microscopy were used for the identification of blood platelets and white blood cell types in alveolar capillaries. The main findings were platelet aggregates and a varying number of neutrophil polymorphonuclear granulocytes in the lung capillaries, mixed with a smaller number of lymphocytes. The findings may be interpreted as an early sign of inflammation with capillary thrombosis, resulting in ischaemia, i.e. arrest of flow. In 21% of the cases, inflammatory cells had also expanded focally into alveolar spaces, creating the picture of localized areas of bronchopneumonia. An infant dying suddenly of a traumatic head injury served as a control. Neither platelets nor leucocytes were observed in the alveolar capillaries of this infant. In conclusion, in lungs from cases of sudden infant death syndrome, the alveolar capillaries are obstructed by platelet aggregates and leucocytes, interpreted as signs of an initial stage of lung inflammation with ischaemia.
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