Abstract

The activated partial thromboplastin time (APTT) assay is a basic hemostatic assay based on the time it takes for clots to form in plasma samples after the addition of calcium chloride. It is used to screen for various coagulation disorders. Several previous reports have suggested that magnesium (Mg) might contribute to coagulation reactions by binding to specific coagulation proteins. We investigated the effects of Mg on the APTT. In healthy controls, the APTT was significantly prolonged in proportion to the increase in the concentration of magnesium chloride in the range from 2.1 to 16.7 mmol/L. Among eight samples from patients with various disorders that exhibited prolonged APTT, two samples demonstrated shorter APTT when Mg was added, both of which were from patients that were positive for lupus anticoagulant. When we examined 206 clinical APTT samples, we found that Mg shortened the APTT of two samples. These two samples were also from lupus anticoagulant-positive patients (p-value: <0.003). Our findings regarding the unique effects of exogenous Mg on the APTT of lupus anticoagulant-positive patients might shed light on the role of Mg in APTT assays and lead to the development of a novel screening method for lupus anticoagulant.

Highlights

  • The activated partial thromboplastin time (APTT) assay is a basic and widely used hemostatic assay that is based on the time it takes for clots to form in plasma samples

  • Magnesium is capable of binding to the Gla domains of factors IXa and Xa in certain conditions [3, 6], which implies that magnesium ions might affect APTT assays

  • The addition of magnesium prolonged the APTT of normal plasma at all of the examined concentrations, which is in contrast to the shortening effect it has on the prothrombin time, especially at low concentrations, such as those found in physiological conditions

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Summary

Introduction

The activated partial thromboplastin time (APTT) assay is a basic and widely used hemostatic assay that is based on the time it takes for clots to form in plasma samples. The APTT assay is composed of two steps 1) APTT reagents including phospholipids and a contact activator of citrate-anticoagulated plasma are added to the test sample, which is incubated, and 2) the clotting time is measured after the addition of PLOS ONE | DOI:10.1371/journal.pone.0157835. Calcium ions, which are divalent cations, are a crucial component of the coagulation cascade. Magnesium ions, which are divalent cations, are involved in numerous metabolic and biochemical reactions and are found in plasma at concentrations ranging from 0.7 to 1.0 mmol/L [2]. Previous reports have suggested that magnesium might contribute to coagulation reactions by binding to specific coagulation proteins, such as factor IX [3]. The effects of magnesium on the APTT have not been fully elucidated, it has been reported to influence the prothrombin time [4]

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