RGD Reference Report - Low plasma levels of tissue factor pathway inhibitor in patients with congenital factor V deficiency. - Rat Genome Database

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Low plasma levels of tissue factor pathway inhibitor in patients with congenital factor V deficiency.

Authors: Duckers, C  Simioni, P  Spiezia, L  Radu, C  Gavasso, S  Rosing, J  Castoldi, E 
Citation: Duckers C, etal., Blood. 2008 Nov 1;112(9):3615-23. doi: 10.1182/blood-2008-06-162453. Epub 2008 Aug 11.
RGD ID: 11060145
Pubmed: PMID:18695002   (View Abstract at PubMed)
PMCID: PMC2572790   (View Article at PubMed Central)
DOI: DOI:10.1182/blood-2008-06-162453   (Journal Full-text)

Severe factor V (FV) deficiency is associated with mild to severe bleeding diathesis, but many patients with FV levels lower than 1% bleed less than anticipated. We used calibrated automated thrombography to screen patients with severe FV deficiency for protective procoagulant defects. Thrombin generation in FV-deficient plasma was only measurable at high tissue factor concentrations. Upon reconstitution of FV-deficient plasma with purified FV, thrombin generation increased steeply with FV concentration, reaching a plateau at approximately 10% FV. FV-deficient plasma reconstituted with 100% FV generated severalfold more thrombin than normal plasma, especially at low tissue factor concentrations (1.36 pM) or in the presence of activated protein C, suggesting reduced tissue factor pathway inhibitor (TFPI) levels in FV-deficient plasma. Plasma TFPI antigen and activity levels were indeed lower (P < .001) in FV-deficient patients (n = 11; 4.0 +/- 1.0 ng/mL free TFPI) than in controls (n = 20; 11.5 +/- 4.8 ng/mL), while persons with partial FV deficiency had inter-mediate levels (n = 16; 7.9 +/- 2.5 ng/mL). FV immunodepletion experiments in normal plasma and surface plasmon resonance analysis provided evidence for the existence of a FV/TFPI complex, possibly affecting TFPI stability/clearance in vivo. Low TFPI levels decreased the FV requirement for minimal thrombin generation in FV-deficient plasma to less than 1% and might therefore protect FV-deficient patients from severe bleeding.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
factor V deficiency  IEP 11060145protein:decreased expression:plasma:RGD 
factor V deficiency  ISOTFPI (Homo sapiens)11060145; 11060145protein:decreased expression:plasma:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tfpi  (tissue factor pathway inhibitor)

Genes (Mus musculus)
Tfpi  (tissue factor pathway inhibitor)

Genes (Homo sapiens)
TFPI  (tissue factor pathway inhibitor)


Additional Information