| Title | Modification of the ProC Global assay using dilution of patient plasma in factor V-depleted plasma as a screening assay for factor V Leiden mutation. | | Author(s) | Quincampoix JC, Legarff M, Rittling C, Andiva S, Toulon P | | Institution | Laboratoire d'Hématologie, Hôpital Cochin, Paris, France. | | Source | Blood Coagul Fibrinolysis 2001 Oct; 12(7):569-76. | | MeSH | Activated Protein C Resistance
Agkistrodon
Animals
Anticoagulants
Blood Coagulation Disorders
Blood Coagulation Tests
Crotalid Venoms
Factor V
Heterozygote
Homozygote
Humans
Liver Diseases
Mutation
Partial Thromboplastin Time
Protein C
Protein C Deficiency
Protein S Deficiency
Sensitivity and Specificity
Thrombosis
| | Abstract | The activated protein C (APC) resistant-factor V (factor V Leiden) has emerged as the most common inherited risk factor for thrombosis in the Caucasian population. Beside DNA analysis, the laboratory diagnosis is often based on the detection of a poor anticoagulant response to exogenous APC. The ProC Global assay (Dade Behring, Marburg, Germany) is a global clotting assay, which was primarily developed to evaluate the functionality of the protein C anticoagulant pathway. It is based on the ability of endogenous APC, generated by activation of protein C by an extract from Agkistrodon contortrix contortrix venom, to prolong an activated partial thromboplastin time. It was previously found to be highly sensitive for the factor V Leiden mutation and for protein C deficiency, but only moderately sensitivity for protein S deficiency. Here, we evaluated the performance of a modification of the ProC Global assay using a 1 : 5 pre-dilution of patient plasma in factor V-depleted plasma in the screening of the factor V Leiden mutation-related APC resistance. For that purpose, we investigated selected frozen plasma samples from 341 patients with a history of venous thromboembolism. The sensitivity for the factor V Leiden mutation of the modified assay was found to be 100%, as all the carriers of that mutation (five homozygotes and 77 heterozygotes) had a decreased response to the assay, i.e. a normalized ratio below 0.80. Its specificity was also 100% since none of the other tested patients had a decreased response, i.e. isolated protein C (n = 3) or protein S deficiency (n = 50), or without any abnormality of the protein C pathway (n = 143), even those on oral anticoagulant treatment (n = 76). However, it would be preferable that each laboratory defines both its reference range and its cut-off level. Finally, even if larger-scale multicentre studies are needed before definite recommendations could be made, these results suggest that the ProC Global performed using a 1 : 5 pre-dilution of the patient plasma in factor V-depleted plasma could be validly used as a screening assay of the factor V Leiden mutation-related APC resistance in patients with a history of thrombosis. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 11685046 |
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