Background: Activated partial thromboplastin time (APTT) reagents consist of phospholipids and activators such as ellagic acid and colloidal silica. However, anticoagulant effects of silica have also been reported (Margolis. Aust J Exp 1961).

Aims: To assess in vitro effects of colloidal silica on clotting of plasma with or without various coagulation abnormalities.

Methods: APTT reagents were prepared with three concentrations (low: 0.025 %; intermediate: 0.05 %; high: 0.1 %) of colloidal silica. Plasma with or without various coagulation factor deficiencies, heparization with unfractionated heparin (0.3IU/ml), lupus anticoagulant (LA) positivity, or high fibrinogen concentration (800mg/dL) were subjected to APTT measurements using the automated analyzer STACIA (LSI Medience).

Results: In normal plasma, APTT at the low and intermediate concentrations of colloidal silica was similar while being prolonged at the high concentration, unexpectedly revealing anticoagulant effects. Similar observations were obtained from plasma with Factor II deficiency, heparization, LA positivity, or high fibrinogen concentration. Especially, Factor II deficiency and heparization enhanced APTT prolongation. When comparing APTT at the low and intermediate concentrations, APTT was shortened at the intermediate concentration in each coagulation factor deficiency except Factor II deficiency. Comparison of APTT measurements at the intermediate and high concentrations revealed differences in colloidal silica effects among various coagulation factor deficiencies. In the deficiency of Factor VII, VIII, or IX, APTT was prolonged at the high concentration, exhibiting anticoagulant effects. In the deficiency of Factor V, XI, or XII, APTT at the high concentration was roughly equivalent to that at the intermediate concentration, exhibiting neither procoagulant nor anticoagulant effects. In the deficiency of Factor X, APTT was shortened at the high concentration, exhibiting procoagulant effects.

Conclusion(s): It remains to be elucidated how coagulation factor deficiencies and heparization are relevant to colloidal silica effects. Basic aspects of colloidal silica impacting the intrinsic coagulation pathway should be addressed.

Table 1. Dose-dependent effects of colloidal silica on APTT measurements in various plasma samples

For each sample, the APTT measurement at the intermediate concentration -0.05 %- of colloidal silica was used as 100 % to indicate the relative changes at the low and high concentrations -0.025 % and 0.1 %, respectively-. Decreased percentages show accelerated coagulation while increased percentages show decelerated coagulation. UHF, unfractionated heparin; LA, lupus anticoagulant.

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