A new chromogenic assay (HemosIL ThromboPath) is sensitive to major prothrombotic risk factors affecting the protein C pathway. Results of a multicenter study

Toulon, Pierre; Smirnov, Mikhail D.; Triscott, Mark; Safa, Omid; Biguzzi, Eugenia; Bouziane, Kader; Tripodi, Armando

doi:10.1016/j.thromres.2008.11.017

Cited by 29 publications

(44 citation statements)

References 38 publications

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“…[8][9][10][18][19][20] Third, PICI% levels observed for patients with cirrhosis were equivalent to those observed for patients with the factor V Leiden mutation (Fig. 3), a condition associated with an impaired protein C pathway, 22 reduced PICI%, 12 and an increased risk of VTE. 23 Fourth, PICI% were significantly (negatively) correlated with the levels of factor VIII, significantly (positively) correlated with the levels of protein C, and significantly (negatively) correlated with the ratio of factor VIII-to-protein C, which can be taken as an index of the procoagulant versus anticoagulant imbalance (Table 3).…”

Section: Discussionmentioning

confidence: 57%

“…Recently, an assay meant to explore the anticoagulant protein C pathway was made available. 12 It is based on the ability of endogenous activated protein C, generated after activation of protein C by Protac, to reduce the tissue factor-induced thrombin generation. Results for this test are conveniently expressed as PICI% (i.e., Protac-induced coagulation inhibition), and low PICI% values can be taken as an index of hypercoagulability.…”

Section: Discussionmentioning

confidence: 99%

“…21 In a multicenter evaluation, the PICI% Thrombopath proved effective in detecting hypercoagulability secondary to congenital as well as acquired defects of the protein C anticoagulant pathway such as protein C, protein S, and the gain-offunction factor V Leiden mutation. 12 Interestingly, the method was also found to be sensitive to increased plasma levels of factor VIII. 12 We hypothesized that the above characteristics could make it suitable to investigate the procoagulant versus anticoagulant imbalance that occurs in cirrhosis because of the partial deficiency of protein C combined with the relative increase of factor VIII.…”

Section: Discussionmentioning

confidence: 99%

“…12 Interestingly, the method was also found to be sensitive to increased plasma levels of factor VIII. 12 We hypothesized that the above characteristics could make it suitable to investigate the procoagulant versus anticoagulant imbalance that occurs in cirrhosis because of the partial deficiency of protein C combined with the relative increase of factor VIII.…”

Section: Discussionmentioning

confidence: 99%

“…This is a commercially available chromogenic assay (HemosIL Thrombopath; Instrumentation Laboratory, Orangeburg, NY) designed to globally evaluate the functionality of the protein C anticoagulant system. 12 It is based on the ability of endogenous activated protein C generated after activation of protein C by a snake venom extract (Protac) to reduce the tissue factor-induced thrombin generation. The amount of thrombin is evaluated by recording changes in optical density (OD) at 405 nm in the presence (A) or absence (B) of Protac after adding a thrombin-specific chromogenic substrate.…”

Section: Measurementsmentioning

confidence: 99%

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Detection of the imbalance of procoagulant versus anticoagulant factors in cirrhosis by a simple laboratory method

et al. 2010

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Patients with cirrhosis possess an imbalance in procoagulant versus anticoagulant activity due to increased factor VIII and decreased protein C. This imbalance can be detected by thrombin-generation assays performed in the presence/absence of thrombomodulin (predicate assay) that are not readily available in clinical laboratories. We sought to assess this hypercoagulability with a simpler thrombin-generation assay performed in the presence/ absence of Protac, a snake venom that activates protein C in a manner similar to thrombomodulin (new assay). We analyzed blood from 105 patients with cirrhosis and 105 healthy subjects (controls). Results for the predicate-assay or the new-assay were expressed as ratio (with:without thrombomodulin) or as Protac-induced coagulation inhibition (PICI%). By definition, high ratios or low PICI% translate into hypercoagulability. The median(range) PICI% was lower in patients (74% [31%-97%]) than controls (93% [72%-99%]; P < 0.001), indicating that patients with cirrhosis are resistant to the action of Protac. This resistance resulted in greater plasma hypercoagulability in patients who were Child class C than those who were A or B. The hypercoagulability of Child C cirrhosis (63% [31%-92%]) was similar to that observed for patients with factor V Leiden (69% [15%-80%]; P 5 0.59). The PICI% values were correlated with the levels of protein C (rho 5 0.728, P < 0.001) or factor VIII (rho 5 20.517, P < 0.001). Finally, the PICI% values were correlated with the predicate assay (rho 5 20.580, P < 0.001). Conclusion: The hypercoagulability of plasma from patients with cirrhosis can be detected with the new assay, which compares favorably with the other markers of hypercoagulability (i.e., high factor VIII and low protein C) and with the predicate-assay based on thrombin-generation with/without thrombomodulin. Advantages of the new assay over the predicate assay are easy performance and standardized results. Prospective trials are needed to ascertain whether it is useful to predict thrombosis in patients with cirrhosis. (HEPATOLOGY 2010;52:249-255)

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