PMID- 31904611 OWN - NLM STAT- MEDLINE DCOM- 20200603 LR - 20210203 IS - 1473-5733 (Electronic) IS - 0957-5235 (Linking) VI - 31 IP - 1 DP - 2020 Jan TI - Confounding effect of therapeutic protamine and heparin levels on routine and special coagulation testing. PG - 60-64 LID - 10.1097/MBC.0000000000000882 [doi] AB - : 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 mug/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. FAU - Khandelwal, Aditi AU - Khandelwal A AD - Fellow, Transfusion Medicine, Department of Laboratory Medicine and Pathology, University of Toronto and Canadian Blood Services, Toronto. FAU - Phua, Chai W AU - Phua CW AD - Division of Hematology, Department of Medicine, London Health Sciences Centre, London. FAU - Chaudhry, Hina R AU - Chaudhry HR AD - Department of Hematology and Laboratory Medicine, St. Michael's Hospital, Toronto. FAU - Tsui, Hubert AU - Tsui H AD - Hematological Pathology, Department of Laboratory Hematology, Toronto General Hospital, University Health Network, Toronto, Ontario. FAU - Rivard, Georges E AU - Rivard GE AD - Department of Hematology-Oncology, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec. FAU - Teitel, Jerome M AU - Teitel JM AD - Division of Hematology, Department of Medicine, St. Michael's Hospital. FAU - Sholzberg, Michelle AU - Sholzberg M AD - Division of Hematology, Departments of Medicine and Laboratory Medicine & Pathobiology, St. Michael's Hospital, Li Ka Shing Knowledge Institute, University of Toronto, Toronto, Ontario, Canada. LA - eng PT - Journal Article PL - England TA - Blood Coagul Fibrinolysis JT - Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis JID - 9102551 RN - 0 (Anticoagulants) RN - 0 (Protamines) RN - 9005-49-6 (Heparin) SB - IM MH - Anticoagulants/pharmacology/*therapeutic use MH - Blood Coagulation/*drug effects MH - Blood Coagulation Tests/*methods MH - Heparin/pharmacology/*therapeutic use MH - Humans MH - Middle Aged MH - Protamines/pharmacology/*therapeutic use EDAT- 2020/01/07 06:00 MHDA- 2020/06/04 06:00 CRDT- 2020/01/07 06:00 PHST- 2020/01/07 06:00 [pubmed] PHST- 2020/06/04 06:00 [medline] PHST- 2020/01/07 06:00 [entrez] AID - 00001721-202001000-00009 [pii] AID - 10.1097/MBC.0000000000000882 [doi] PST - ppublish SO - Blood Coagul Fibrinolysis. 2020 Jan;31(1):60-64. doi: 10.1097/MBC.0000000000000882.