title: Endogenous or exogenous coagulation factor level and the response to activated protein C.
abstract: BACKGROUND
  The abnormal response to activated protein C could be the mechanism to explain the prothrombotic role of elevated coagulation factor levels.
  
  
  OBJECTIVE
  We evaluated the effect of factor VIII, II, or X (FVIII, FII, or FX) levels on activated protein C resistance technique and its association with the resistant phenotype.
  
  
  METHODS
  The correlation between APCR and FVIII was assessed in 36 samples, after Desmopressin infusion and the correlation between FII or FX and APCR in 15 patients with plasma levels between 100-125 U/dl. Also, the effect of the addition of purified human factors (FII, FX) to a normal plasma pool (final concentration: 100, 120, 140, 180, 220 U/dl) was estimated on the APCR technique.
  
  
  RESULTS
  APCR values correlated with FVIII increase (r(Spearman) = 0.839; p < 0.001); APCR was abnormal (<2.4) in 9/36 samples, showing higher FVIII values in the abnormal group (VIII(abnormalAPCR) = 176.7 +/- 14.2; VIII(normalAPCR) = 103.5 +/- 8.0). APCR did not correlate with endogenous FII (r(Spearman) = 0.423) or FX (r(Spearman) = -0.169). However, the addition of human FII or FX to the normal plasma pool caused a decrease in APCR (r(SpearmanFII) = -0.843; r(SpearmanFX) = -0.958) without reaching abnormal (<2.4) results. FVIII levels may be associated with a resistant phenotype at values >153.0 U/dl, according to the linear regression analysis. Exogenous FII or FX levels greater than 120 U/dl would affect the APCR, without obtaining abnormal results.
  
  
  CONCLUSIONS
  The data do not allow the direct association of the FII or FX increase with a defect in the protein C system in the current conditions.
authors.affiliation: División Hemostasia, Departamento de Hemostasia y Trombosis, Instituto de Investigaciones Hematológicas Mariano R. Castex, Academia Nacional de Medicina, Buenos Aires, Argentina. laugennari@hematologia.anm.edu.ar
authors.forename: Laura C
authors.initials: LC
authors.lastname: Gennari
authors.forename: Alicia N
authors.initials: AN
authors.lastname: Blanco
authors.forename: Maria P
authors.initials: MP
authors.lastname: Domínguez
authors.forename: Silvia H
authors.initials: SH
authors.lastname: Grosso
authors.forename: Maria A
authors.initials: MA
authors.lastname: Lazzari
mesh_terms: D020016:Activated Protein C Resistance / Q000097:blood; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D005169:Factor VIII / Q000378:metabolism* / Q000494:pharmacology*; D005170:Factor X / Q000378:metabolism* / Q000494:pharmacology*; D006490:Hemostatics / Q000494:pharmacology; D006801:Humans; D011486:Protein C / Q000494:pharmacology*; D011516:Prothrombin / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D006490:Hemostatics; D011486:Protein C; D011516:Prothrombin; D005169:Factor VIII; D005170:Factor X; D003894:Deamino Arginine Vasopressin