APC cleavage site. The first one is a new factor V mutation associated with APC resistance (factor V Cambridge, G1091 = C mutation, Arg306 = Thr substitution). This mutation was found in a family with a strong history of thrombosis. Our group has independently described another novel mutation (A1090 = G) that results in Arg306 = Gly substitution but it is, however, not associated with APC resis...

Lupus anticoagulants (LA) can cause acquired activated protein C resistance (APC-R), but the clinical significance is unclear. To investigate thrombosis and acquired APC-R in patients with LA, we enrolled all 132 patients undergoing hypercoagulability testing with positive LA results and in whom APC-R (with factor V-deficient plasma) was performed during a 2.5-year period. Among 121 patients wi...

BACKGROUND AND OBJECTIVES The case of a patient with thrombotic manifestations and severe activated protein C resistance due to an anti-factor V antibody has recently been described. Since activated protein C (APC) is also profibrinolytic we wanted to determine whether the presence of antibodies interfering with the anticoagulant activity of APC also inhibits its profibrinolytic effect. DESIG...

Mutations in the adenomatous polyposis coli (Apc) tumor suppressor gene represent the primary genetic defect in colon carcinogenesis. Apc+/- mouse models exhibit pre-invasive small intestinal adenomas. Cell culture models exhibiting Apc defects in the colon and quantifiable cancer risk provide a novel clinically relevant approach. The tumor-derived Apc-/- colonic epithelial cell line 1638N COL-...

The key effector molecule of the natural protein C pathway, activated protein C (aPC), exerts pleiotropic effects on coagulation, fibrinolysis, and inflammation. Coagulation-independent cell signaling by aPC appears to be the predominant mechanism underlying its highly reproducible therapeutic efficacy in most animal models of injury and infection. In this study, using a mouse model of Staphylo...

BACKGROUND Acute traumatic coagulopathy (ATC) has been linked to an increase in activated protein C (aPC) from 40 pM in healthy individuals to 175 pM. aPC exerts its activity primarily through cleavage of active coagulation factor Va (fVa). Platelets reportedly possess fVa which is more resistant to aPC cleavage than plasma fVa; this work examines the hypothesis that normal platelets are suffic...

Activated protein C (APC) inhibits coagulation by cleaving and inactivating procoagulant factor Va (FVa) and factor VIIIa (FVIIIa). FV, in addition to being the precursor of FVa, has anticoagulant properties; functioning in synergy with protein S as a cofactor of APC in the inhibition of the FVIIIa-factor IXa (FIXa) complex. FV:Q506 isolated from an individual homozygous for APC-resistance is l...

Activated protein C (APC) inhibits coagulation by cleaving and inactivating procoagulant factor Va (FVa) and factor VIIIa (FVIIIa). FV, in addition to being the precursor of FVa, has anticoagulant properties; functioning in synergy with protein S as a cofactor of APC in the inhibition of the FVIIIafactor IXa (FIXa) complex. FV:Q506 isolated from an individual homozygous for APC-resistance is le...

Platelet factor 4 (PF4) is an abundant platelet alpha-granule chemokine released following platelet activation. PF4 interacts with thrombomodulin and the gamma-carboxyglutamic acid (Gla) domain of protein C, thereby enhancing activated protein C (APC) generation by the thrombin-thrombomodulin complex. However, the protein C Gla domain not only mediates protein C activation in vivo, but also pla...