https://scholarlypublications.universiteitleiden.nl/access/item%3A3138188/view

A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis.

The roles of protein C and thrombomodulin in the regulation of blood coagulation.

Role of hemostatic gene polymorphisms in venous and arterial thrombotic disease.

When attempting to feed on their hosts, ticks face the problem of host hemostasis (the vertebrate mechanisms that prevent blood loss), inflammation (that can produce itching or pain and thus initiate defensive behavior on their hosts) and adaptive immunity (by way of both cellular and humoral responses). Against these barriers, ticks evolved a complex and sophisticated pharmacological armamentarium, consisting of bioactive lipids and proteins, to assist blood feeding. Recent progress in transcriptome research has uncovered that hard ticks have hundreds of different proteins expressed in their salivary glands, the majority of which have no known function, and include many novel protein families (e.g., their primary structure is unique to ticks). This review will address the vertebrate mechanisms of these barriers as a guide to identify the possible targets of these large numbers of known salivary proteins with unknown function. We additionally provide a supplemental Table that catalogues over 3,500 putative salivary proteins from various tick species, which might assist the scientific community in the process of functional identification of these unique proteins. This supplemental file is accessble fromhttp://exon.niaid.nih.gov/transcriptome/tick_review/Sup-Table-1.xls.gz.

The role of saliva in tick feeding.

Protein S is an antithrombotic plasma protein that serves as a cofactor for another plasma protein, activated protein C. Protein S is required for the expression of the anticoagulant effect of activated protein C, which inhibits blood clotting at the levels of factors V and VIII in the blood-clotting cascade. We postulated that patients deficient in protein S would have inadequate regulatory control of the clotting cascade and would be prone to thrombotic disease in a manner similar to that of patients congenitally deficient in protein C. To determine whether protein S deficiency is associated with recurrent thrombosis, we developed a functional assay for the plasma protein. With this assay, the protein S activity of normal persons ranges from 63 to 160 per cent. Using this test, we have now identified six unrelated persons with severe recurrent venous thrombosis who were deficient in protein S, with levels between 15 and 37 per cent while they were not receiving warfarin therapy. Our data sugges...

Recurrent venous thromboembolism in patients with a partial deficiency of protein S.

Recent studies have demonstrated that protein C deficiency is associated with recurrent familial thrombosis In plasma, activated protein C functions as an anticoagulant This anticoagulant response requires a vitamin K-dependent plasma protein cofactor, referred to as protein S Since the anticoagulant activity of activated protein C is dependent on protein S, we hypothesized that patients lacking functional protein S might have associated thrombotic disease Two related individuals with otherwise normal coagulation tests are described whose plasma is not effectively anticoagulated with activated protein C Addition of purified human protein S to their plasma restores a normal anticoagulant response to activated protein C We have developed a rapid one-stage clotting assay for protein S to quantitate the level of protein S in their plasma Plasma is depleted of protein S by immunoadsorption with immobilized antiprotein S antibodies The resultant plasma responds poorly to activated protein C, but is effectively anticoagulated in a dose-dependent fashion upon addition of purified protein S or small quantities of plasma The affected individuals possess less than 5% protein S activity Using Laurell rockets, protein S antigen was detected in the plasma but was at reduced levels of 13 and 18% in the two individuals When the barium eluate of the patient plasma was chromatographed on quaternary aminoethyl Sephadex, a single peak of protein S antigen devoid of protein S anticoagulant cofactor activity was detected early in the chromatogram In contrast, the barium eluate from normal donors separated into two peaks, one emerging early and also devoid of anticoagulant cofactor, and the second peak with anticoagulant activity emerging later The first peak of protein S antigen, from both the normal donor and the patient, chromatographed in the region of the complement component C4-binding protein-protein S complex These studies suggest that protein S deficiency may result in recurrent thrombotic disease

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M R Cooper

Papers

Familial protein s deficiency is associated with recurrent thrombosis