Document Detail

Laboratory diagnosis of hereditary thrombophilia.
MedLine Citation:
PMID:  9763348     Owner:  NLM     Status:  MEDLINE    
Genetic defects of antithrombin (AT) or one of the components of the protein C pathway are associated with hereditary thrombophilia. Laboratory assays are currently available to diagnose and type hereditary thrombophilia due to deficiency or dysfunction of one of the anticoagulant factors antithrombin (AT), protein C (PC) and protein S (PS), and APC resistance without the need of DNA analysis. There are no functional tests for the prothrombin mutant G20210A and thrombomodulin mutations, which can be diagnosed by a PCR-based test or by gene analysis, respectively. Hereditary AT deficiency is classified in a quantitative type I and three functional type II deficiencies affecting the reactive site (RS), heparin binding site (HBS), or pleiomorphic site of the AT protein. All four types of hereditary AT deficiencies can be diagnosed by a heparin cofactor assay and one immune assay in combination with crossed immunoelectrophoresis of the AT protein. The combination of an enzyme-linked immunoadsorbent assay (ELISA) and a functional Protac-APTT-based assay for PC will detect quantitative type I and dysfunctional type II PC deficiencies. There is a significant overlap in PC antigen and functional levels between heterozygotes of PC deficiency and normals leaving a gray zone of uncertainty in differentiating congenital PC deficiency and normal individuals. Accurate diagnosis of hereditary PS deficiency should be a combination of tests aimed to measure free PS activity and antigen and total PS antigen levels. APTT-, Xa-, and RVVT-based APC-resistance tests, when test plasmas are diluted in factor V deficient plasma, have increased in sensitivity and specificity to 100% for the discrimination of normal individuals from heterozygotes and homozygotes for factor V Leiden. The RVVT-based APC-resistance test provides better separation of factor V Leiden and normals in the various clinical settings, lupus anticoagulant in particular. The modified APC-resistance tests also claim a separation between heterozygotes and homozygotes for factor V Leiden in the normal population, asymptomatic subjects, and thrombosis patients. Below a certain cut-off level, a minor overlap of normalized APC ratios between heterozygotes and homozygotes for factor V Leiden of thrombosis patients has been shown in one study, which still points to the need to perform the more time consuming and expensive DNA test to identify heterozygotes from the more clinically significant homozygotes. The prothrombin-based APC-resistance test, which measures thrombin activated factor Va in highly diluted test plasma, appears to be the most sensitive and specific of all APC-resistance tests and separates normal individuals from heterozygotes and heterozygotes from homozygotes for factor V Leiden without the need of confirmation by a DNA test.
J J Michiels; K Hamulyák
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Seminars in thrombosis and hemostasis     Volume:  24     ISSN:  0094-6176     ISO Abbreviation:  Semin. Thromb. Hemost.     Publication Date:  1998  
Date Detail:
Created Date:  1998-12-10     Completed Date:  1998-12-10     Revised Date:  2006-03-07    
Medline Journal Info:
Nlm Unique ID:  0431155     Medline TA:  Semin Thromb Hemost     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  309-20     Citation Subset:  IM    
Hematology, Hemostasis and Thrombosis Scientific Center, Goodheart Institute, Rotterdam, The Netherlands.
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MeSH Terms
Activated Protein C Resistance
Anticoagulants / therapeutic use
Antithrombins / deficiency,  therapeutic use
Heparin / therapeutic use
Laboratory Techniques and Procedures*
Protein C Deficiency / diagnosis
Protein S Deficiency / diagnosis
Thrombophilia / diagnosis*,  drug therapy,  genetics
Reg. No./Substance:
0/Anticoagulants; 0/Antithrombins; 9005-49-6/Heparin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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