Analysis of the activated partial thromboplastin time test using mathematical modeling

Thromb Res. 2001 Feb 15;101(4):299-310. doi: 10.1016/s0049-3848(00)00405-9.

Abstract

Activated partial thromboplastin time (APTT) is a laboratory test for the diagnosis of blood coagulation disorders. The test consists of two stages: The first one is the preincubation of a plasma sample with negatively charged materials (kaolin, ellagic acid etc.) to activate factors XII and XI; the second stage begins after the addition of calcium ions that triggers a chain of calcium-dependent enzymatic reactions resulting in fibrinogen clotting. Mathematical modeling was used for the analysis of the APTT test. The process of coagulation was described by a set of coupled differential equations that were solved by the numerical method. It was found that as little as 2.3 x 10(-9) microM of factor XIIa (1/10000 of its plasma concentration) is enough to cause the complete activation of factor XII and prekallikrein (PK) during the first 20 s of the preincubation phase. By the end of this phase, kallikrein (K) is completely inhibited, residual activity of factor XIIa is 54%, and factor XI is activated by 26%. Once a clot is formed, factor II is activated by 4%, factor X by 5%, factor IX by 90%, and factor XI by 39%. Calculated clotting time using protein concentrations found in the blood of healthy people was 40.5 s. The most pronounced prolongation of APTT is caused by a decrease in factor X concentration.

MeSH terms

  • Blood Coagulation Disorders / blood
  • Blood Coagulation Disorders / diagnosis
  • Blood Coagulation Factors / metabolism
  • Factor XIIa / metabolism
  • Humans
  • Kinetics
  • Models, Biological*
  • Models, Theoretical
  • Partial Thromboplastin Time*

Substances

  • Blood Coagulation Factors
  • Factor XIIa