Confounding effect of therapeutic protamine and heparin levels on routine and special coagulation testing

Abstract

The management of a patient with hemophilia undergoing cardiovascular surgery relies on accurate coagulation test results. Both unfractionated heparin (UFH) and protamine sulfate used during cardiac surgery can interfere with factor and inhibitor assays. Here we describe the effects of UFH and protamine sulfate on routine coagulation, factor activity, and inhibitor assays. Pooled normal plasma (PNP) with UFH, PNP with protamine sulfate, PNP with both protamine sulfate and UFH were tested for the activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), UFH anti-Xa, one-stage factor VIII (FVIII) activity, one-stage factor IX (FIX) activity, and Bethesda inhibitor assays for FVIII and FIX. UFH had a dose-dependent effect with TT, aPTT, and PT. On Bethesda inhibitor testing, FIX inhibition was detected at 1 U/ml UFH and 3 U/ml UFH for FVIII. Increasing protamine sulfate concentration in PNP prolonged the PT and aPTT in a dose-dependent manner, decreased FVIII and FIX activity and did not affect TT or UFH anti-Xa. At protamine sulfate doses of at least 200 μg/ml there was weak FVIII and FIX inhibition detected. At lower ratios of protamine sulfate to UFH (0.6 : 1–0.8 : 1), the aPTT decreased, suggesting reversal of UFH. However, at protamine sulfate to UFH ratios of 1.0 : 1 and higher, aPTT prolongation was observed. Inhibition of FVIII and FIX was detected at low ratios of protamine sulfate to UFH (below 0.4 : 1) and disappeared at higher ratios. UFH and protamine sulfate, alone or in combination, impact factor activity and inhibitor testing for both FVIII and FIX. Hence, factor activity and inhibitor assay results should be interpreted with caution when UFH or protamine sulfate are present.

Interaction of a Phospholipid and a Coagulating Protein: Potential Candidate for Bioelectronic Applications

“… 23 , 24 On the other hand, PS is a strongly cationic polypeptide derived from herring fish. 25 PS is widely used in gene therapy to enhance lipid-mediated gene transfection, 26 cardiac surgery, 27 nanopharmaceuticals, 28 and vaccination. 29 It also has antibacterial activity against Gram-positive and Gram-negative bacteria.…”

“…DOPC is a zwitterionic phospholipid with unsaturated fatty acid. , On the other hand, PS is a strongly cationic polypeptide derived from herring fish . PS is widely used in gene therapy to enhance lipid-mediated gene transfection, cardiac surgery, nanopharmaceuticals, and vaccination . It also has antibacterial activity against Gram-positive and Gram-negative bacteria. , Due to the cationic nature induced by −NH 3 + groups in PS, it can interact electrostatically with anionic and zwitterionic molecules.…”