ProC® Global Assay in the Evaluation of Women with History of Severe Preeclampsia or HELLP Syndrome

Abstract

Preeclampsia/HELLP syndrome has been associated with a high incidence of defects in the protein C pathway and increased anticardiolipin-antibodies/lupus anticoagulants. It is also apparent that thrombophilia is responsible for other pregnancy complications, such as recurrent spontaneous abortion, fetal growth restriction, intrauterine fetal death, and abruptio placentae. ProC Global is a new global dotting assay designed to evaluate the abnormalities in the protein C anticoagulant pathway. It is based on the ability of endogenous activated protein C, generated by activation of protein C by Protac, to prolong an activated partial thromboplastin time. A total of 61 patients with a history of severe preeclampsia or HELLP syndrome and 61 normal pregnant women (controls) were evaluated, 15 of whom had factor V Leiden mutation, 12 had protein C/S deficiency, 30 had a repeated lupus anticoagulants, and 27 increased anticardiolipin antibodies (ACA). All carriers of factor V Leiden mutation (N=15) as well as all the patients with low activated protein C (APC) resistance ratio (N=15) had a ProC Global normalized ratio (NR) less than 0.80 (sensitivity 100%). Twenty-four patients positive for the lupus anticoagulants (LA) and 19 patients positive for ACA (>5.0 IgG U/mL) had a ProC Global NR less than 0.8, while six and eight, respectively, had a ProC Global NR greater than 0.8 (sensitivity, 70%-80%). The detection of a reduced protein C/protein S activity (<70%) was low (sensitivity, 33%-44%). In 25 cases with pathologic ProC Global results, a thrombophilic defect (protein S/LA/ACA without APC resistance) was diagnosed in 18 women; but in 7 cases, no known thrombophilic defect was present. ProC Global is a new screening test to identify patients with defects of the protein C system and an activated dotting system in preeclampsia but cannot correctly cover each thrombophilic component.

Reduced protein C Global assay level in infertile women prior to IVF-ET treatment

“…ProC Global assay has already been explored in women with recurrent thrombo-emolism [16,17], thromboemolic phenomena under hormonal therapy [25] repeat pregnancy loss [26] and in women with severe pre-eclampsia and HELLP syndrome [27]. Moreover, it has been recently explored in women throughout pregnancy; following ART [11] or spontaneous conception [11,12].…”

Reduced Protein C Global Assay Levels in Infertile Women with in vitro Fertilization Failure: A Pilot Study

“…Protein C global assay was previously detected in women with recurrent thromboembolism [16,20], in those with recurrent pregnancy loss [21], and also in women with severe preeclampsia and HELLP syndrome [22]. The test was recently evaluated in women with spontaneous conception [18].…”

Identifying Women at High Risk of Venous Thrombosis before Administration of Hormone Therapy

“…In multicenter studies, abnormal ProC Global assay results were found to be associated with first episode of VTE [22,23] and recurrent VTE [24]. Furthermore, abnormal ProC Global assay results were found to be more common (70%) in women with pregnancy loss, pre-eclampsia, and hemolytic anemia, elevated liver enzymes and low platelet count (HELLP) syndrome compared with healthy women without these complications [25,26].…”