Analysis of the Activated Partial Thromboplastin Time Test Using Mathematical Modeling

• Published in: Thrombosis research Vol. 101; no. 4; pp. 299 - 310
• Main Authors: Kogan, Alexander E., Kardakov, Denis V., Khanin, Mikhail A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 15-02-2001
• Subjects: APTT test; Blood Coagulation Disorders - blood; Blood Coagulation Disorders - diagnosis; Blood Coagulation Factors - metabolism; Contact activation; Factor XIIa - metabolism; Humans; Kinetics; Mathematical modeling; Models, Biological; Models, Theoretical; Partial Thromboplastin Time; TFPI, tissue factor pathway inhibitor; K, kallikrein; C1-Inh, C1-inhibitor; AT-III, antithrombin III; α 2M, α 2-macroglobulin; PK, prekallikrein; Contact activation; α 2AP, α 2-antiplasmin; HMWK, high molecular weight kininogen; APTT test; Mathematical modeling; α 1-AT, α 1-antitrypsin (α 1-proteinase inhibitor); PAI-1, plasminogen activator inhibitor type 1; APTT, activated partial thromboplastin time
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/S0049-3848(00)00405-9

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 2.3×10
−9 μM of factor XIIa (1/10
000 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.