In Vitro Reversal of Heparin Effect with Heparinas

Abstract

This study was designed to evaluate the potential in vitro use of heparinase to eliminate functionally active heparin prior to performing whole blood (WB) prothrombin time (PT) and activated partial thromboplastin time (APTT) assays. A total of 250 U/kg of heparin for cardiopulmonary bypass (CPB) was administered to 30 cardiac surgical patients in three consecutive, divided doses (20, 80, and 150 U/kg) at 15-min intervals. Blood specimens were obtained prior to heparin administration (baseline) and 10 min after each heparin dose. After collection, blood specimens were fractionated into three aliquots of which the first was used for determination of heparin concentration. After gentle mixing, WB PT and APTT measurements were performed for heparinase (Aliquot 2)- and nonheparinase (Aliquot 3)-treated blood. With consecutive heparin doses of 20 and 80 U/kg, WB PT increased from a baseline of 12.3 +/- 0.1 s to 13.3 +/- 0.2 and 18.5 +/- 1.3 s, while WB APTT increased from a baseline of 28.3 +/- 1.1 s to 89.5 +/- 5.4 after the initial heparin dose (20 U/kg). When compared to baseline (no heparin) results, small, progressive increases in heparinase-treated WB PT (0.7 +/- 0.1, 1.5 +/- 0.1, 2.1 +/- 0.1 s) and APTT (2.3 +/- 0.3, 5.7 +/- 0.4, 9.5 +/- 0.5 s) were seen with increasing heparin concentration (0.23, 1.58, and 3.95 U/mL, respectively). Heparinase was highly effective in eliminating the anticoagulant effects of even large amounts of heparin in plasma from cardiac surgical patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Inactivation of Heparin by Cationically Modified Chitosan

“…However, some animal studies revealed its renal toxicity [41]. Some studies indicate that heparinase is highly effective in eliminating the anticoagulant activity of heparin in vitro in plasma from cardiac surgical patients [42]. On the other hand, heparinase used for heparin anticoagulation reversal in patient after aorto-coronary bypass graft surgery has inferior safety profile, compared to protamine [43].…”

The methods for removal of direct oral anticoagulants and heparins to improve the monitoring of hemostasis: a narrative literature review

“…Its heparin-neutralizing abilities rely on the cleavage of alpha-glycosidic linkages at the ATIII binding site and prevent a heparin-AT-thrombin complexation [92,93]. Lots of studies confirmed the reversal of the heparin effect by heparinase at aPTT, PT and TT tests [14,94]. Heparinase restores the thrombin activity, decreases coagulation time and has a minimal effect on platelets [93,95].…”

“…References with asterisk describe the effect of samples from DOAC or heparin treated patients. PT dabigatran [60,81] TT dabigatran [81] dabigatran [60] dRVVT, aPTT-LA dabigatran [60,81] APC-R dabigatran [60,81] FVII, FVIII, FIX and FX assays dabigatran [60,81] Added in concentration of 125 µg/ml [87] to plasma samples from DOAC-treated patients* TGA dabigatran [82]* Andexanet alfa Added in concentration of 100 µg/ml [92], 200 µg/ ml [93,94] to plasma spiked with DOAC ACT betrixaban [87] edoxaban [87] aPTT rivaroxaban [87], edoxaban [87], betrixaban [87] apixaban [87] PT rivaroxaban [87], apixaban [87], edoxaban [87], betrixaban [87] PiCT rivaroxaban [87], apixaban [87], edoxaban [87], betrixaban [87] Anti-FXa assay rivaroxaban [87], apixaban [87], edoxaban [87], betrixaban [87] dRVVT, aPTT-LA rivaroxaban [88] FVIII, FIX assays rivaroxaban [89] CAT rivaroxaban [87], apixaban [87], edoxaban [87], betrixaban [87] Protamine sulfate Added in concentration of 0-200 µg/ml [109,117,118] to normal plasma spiked with heparin...…”