The multiple levels of endothelial cell-coagulation factor interactions

P. P. Nawroth, D. Handley, David Stern

Research output: Contribution to journalReview article

21 Citations (Scopus)

Abstract

The data presented in this review clearly indicate that endothelial cells can provide a focal point for the interaction of mechanisms inhibiting and promoting the activation of coagulation. These mechanisms are highly integrated. Synthesis and expression of factor V may be important in assembly of the prothrombinase complex as well as protein C activation. Promotion of low levels of thrombin formation by endothelium, following minimal pertubation, may be essential for priming the protein C pathway. The activated protein C thus formed can interact with protein S on the endothelial cell surface resulting in the functional anticoagulant complex. This complex can block activation of coagulation by inactivating the cofactors, factors Va and VIIIa. In contrast, when pertubation of the endothelium is more severe, interleukin 1 synthesis and release occurs. Interleukin 1 not only induces the initiation of coagulation, through induction of tissue factor, but abolishes effective function of the protein C pathway on the endothelial cell surface. In addition, thrombin generation can lead to the activation of platelets and with anti-coagulant cell surface heparin-like molecules. In this situation, the amount of thrombin formed exceeds the need for priming anticoagulant mechanisms, such as the protein C pathway, and can tip the balance of haemostatic activities towards clot formation. Multiple mechanisms augmenting the procoagulant response initiated by the endothelial cell procoagulation pathway can then be set into motion. Thrombin interacting with platelets activates them, causing release of factor V and thus augmentating prothrombin activation. Thrombin itself, fibrin degradation products, and clot formation can lead to interruption of the continuity of endothelium. Exposure of the subendothelium further augments thrombus formation. The model provides a simple endothelial-cell-dependent mechanism for initiation of coagulation at the site of an injured or pathological vessel. On the quiescent endothelial cell surface, procoagulant reactions are balanced by anticoagulant mechanisms. In contrast, on the surface of perturbed endothelial cells procoagulant mechanisms would predominate, resulting in promotion of clot formation.

Original languageEnglish (US)
Pages (from-to)293-321
Number of pages29
JournalClinics in Haematology
Volume15
Issue number2
StatePublished - Dec 1 1986

Fingerprint

Blood Coagulation Factors
Endothelial Cells
Protein C
Thrombin
Anticoagulants
Endothelium
Factor V
Interleukin-1
Factor VIIIa
Factor Va
Fibrin Fibrinogen Degradation Products
Coagulants
Protein S
Platelet Activation
Thromboplastin
Prothrombin
Hemostatics
Heparin
Thrombosis
Blood Platelets

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology

Cite this

The multiple levels of endothelial cell-coagulation factor interactions. / Nawroth, P. P.; Handley, D.; Stern, David.

In: Clinics in Haematology, Vol. 15, No. 2, 01.12.1986, p. 293-321.

Research output: Contribution to journalReview article

Nawroth, P. P. ; Handley, D. ; Stern, David. / The multiple levels of endothelial cell-coagulation factor interactions. In: Clinics in Haematology. 1986 ; Vol. 15, No. 2. pp. 293-321.
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