The ionized calcium level in blood is known to be falsely decreased when self-prepared liquid heparin anticoagulant is used, due to dilution and binding effects. The effect of liquid heparin on the determination of ionized magnesium is not as well understood. We compared the effect of liquid sodium heparin on the determination of ionized calcium and magnesium in 44 clinical samples using two types of user-prepared heparin syringes which differed in the amount of residual heparin from the BD Preset(TM) reference syringe. With the type 1 syringe, the liquid heparin was expelled once or twice such that some heparin could be left in the dead space at the syringe hub, while the liquid sodium heparin was thoroughly expelled from the type 2 syringe. The ionized magnesium levels obtained with the type 1 syringe were significantly lower than the reference value (by 0.068 mmol/L) (p < 0.0001), while the value obtained with the type 2 syringe differed less from the reference, by only 0.014 mmol/L (p < 0.0001). The heparin binding effect resulted in more negative bias in ionized magnesium (-0.026 +/- 0.032 mmol/L) than in ionized calcium (-0.009 +/- 0.042 mmol/L, p < 0.0001). In conclusion, we recommend using lyophilized, calcium-balanced, heparinized syringes for the determination of ionized magnesium and ionized calcium due to the increased negative bias in ionized magnesium determinations. When user-prepared syringes are used, the thorough evacuation of heparin solution should be strictly prescribed.
Syringes ; Protein Binding ; Magnesium/*chemistry/metabolism ; Ions ; Humans ; Heparin/administration & dosage/*therapeutic use ; Calcium/*metabolism ; Blood Specimen Collection/*methods ; Blood Chemical Analysis/*methods ; Anticoagulants/therapeutic use

To observe the protective effect of heparin-coated circuits (HCC) on the platelet function during cardiopulmonary bypass (CPB), 23 patients with heart valve replacement were studied. The system heparin dose was 3 mg/kg in the control group (n = 15) and heparin-coated circuits in the HCC group (n = 8). Platelet count, alpha-granule membrane protein-140 (GMP-140) concentrations were determined before CPB, at 60 min of CPB, 30 and 60 min after protamine administration, first 12 h after CPB, respectively. At end of CPB the arterial filters in the circuits were observed by electron microscopy. The amount of first 12-h postoperative blood loss was measured. There was significant reduction in platelet loss during and after CPB in the HCC group in contrast to the control group during CPB (P<0.05). During the first 12 h, postoperative blood loss was reduced in the HCC group as compared with that in the control group (218+/-61 ml, vs. 332+/-118 ml, P<0.05). Electron microscopy showed that in the HCC group the filter meshes and their fringes were clear and fragments of floccules were occasionally seen, without adherent cells or only few adherent cells on their surfaces, whereas several cellular and fibrous components were found to adhere to the surfaces of the filter meshes in the control group. This study indicates that heparin-coated circuits might reduce the platelet loss and activation during CPB and improve hemocompatibility of cardiopulmonary bypass equipment.
Adult ; Anticoagulants ; metabolism ; pharmacology ; therapeutic use ; Blood Coagulation ; drug effects ; Blood Platelets ; metabolism ; Cardiopulmonary Bypass ; instrumentation ; Coated Materials, Biocompatible ; therapeutic use ; Extracorporeal Circulation ; Female ; Fibrinolytic Agents ; metabolism ; pharmacology ; therapeutic use ; Heart Valve Prosthesis Implantation ; Heparin ; metabolism ; pharmacology ; therapeutic use ; Humans ; Male ; Middle Aged ; Mitral Valve Insufficiency ; surgery ; P-Selectin ; metabolism ; Platelet Activation ; drug effects

BACKGROUND: Warfarin is a widely used oral anticoagulant with broad within- and between-individual dose requirements. Warfarin concentrations can be monitored by assessing its pharmacologic effects on International Normalized Ratio (INR). However, this approach has not been applied in the routine clinical management of patients receiving warfarin therapy. We performed a plasma warfarin assay using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) to determine if such an assay can be utilized in routine clinical practice. METHODS: We included a total of 105 patients with atrial fibrillation, and who were receiving warfarin for more than 1 yr. The plasma concentrations of total warfarin and 7-hydroxywarfarin were determined by HPLC-MS/MS (Waters, UK). We assessed the association between warfarin dose, concentration, and INR as well as the effects of these factors on warfarin concentrations. RESULTS: The mean maintenance dose of warfarin in 105 patients was 4.1+/-1.3 mg/day (range, 1.7-8.0 mg/day) and their mean plasma warfarin concentration was 1.3+/-0.5 mg/L. We defined a concentration range of 0.6-2.6 mg/L (corresponding to the 2.5th to 97.5th percentile range of the Plasma warfarin levels in the 74 patients showing INR within target range) as the therapeutic range for warfarin. The correlation of warfarin dose with warfarin concentration (r2=0.259, P<0.001) was higher than that with INR (r2=0.029, P=0.072). CONCLUSIONS: There was a significant correlation between warfarin dose and plasma warfarin concentrations in Korean patients with atrial fibrillation. Hence, plasma warfarin monitoring can help determine dose adjustments and improve our understanding of individual patient response to warfarin treatment.
Adult ; Aged ; Aged, 80 and over ; Anticoagulants/*blood/therapeutic use ; Asian Continental Ancestry Group ; Atrial Fibrillation/drug therapy ; Chromatography, High Pressure Liquid ; Female ; Humans ; Male ; Middle Aged ; Republic of Korea ; Tandem Mass Spectrometry ; Warfarin/analogs & derivatives/*blood/metabolism/therapeutic use

To investigate the effects of complex danshen solution and heparin on the changes of blood coagulation factors in rats with hemorrhagic shock, and to explore the therapy of coagulopathy by compound danshen solution, the rat model of hemorrhagic shock was set up, 40 SD rats were randomized into four groups: sham operation, shock, compound danshen solution and heparin groups, each group was composed of 10 SD rats. Plasma SFMC, TM, ATIII, D-D, t-PA, PAI levels and APTT were detected, incidences of bleeding complications between heparin and danshen group were compared. The results showed that plasma SFMC, D-D levels in shock group were higher but ATIII level in shock group was lower than that in sham operation group, compound danshen solution group and heparin group (P < 0.001), TM levels obviously increased in shock group and heparin group (P < 0.001). There was no significant difference between compound danshen solution and sham-operation groups. Plasma t-PA, D-D levels obviously increased after shock for 2 hours, PAI level reached the peak after shock for 4 hours, but t-PA decreased. After shock for 6 hours, plasma PAI descended, t-PA continually drop in, but PAI and D-D remained in higher levels. Plasma D-D level in heparin group was lower than that in shock group, t-PA level was higher than that in shock group, but there was no significant difference between in heparin and shock groups. Plasma t-PA, PAI and D-D levels in compound danshen solution group were lower than that in shock group. APTT of danshen group was lower than that of shock group and heparin group. Bleeding incidences was 30% in heparin group and 0% in danshen group, respectively. It is concluded that compound danshen solution may used to treat hypercoagulation and hyperfibrinolysis. In comparsion with heparin, danshen posses-ses advantages of safety with less bleeding complication and needs not tight monitor.
Animals ; Anticoagulants ; therapeutic use ; Blood Coagulation ; drug effects ; Blood Coagulation Factors ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Fibrin Fibrinogen Degradation Products ; metabolism ; Heparin ; therapeutic use ; Male ; Partial Thromboplastin Time ; Phytotherapy ; Plasminogen Activator Inhibitor 1 ; blood ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Salvia miltiorrhiza ; chemistry ; Shock, Hemorrhagic ; blood ; drug therapy ; Thromboplastin ; metabolism ; Tissue Plasminogen Activator ; blood

A 73-yr-old Korean man with permanent atrial fibrillation visited outpatient clinic with severely increased International Normalized Ratio (INR) values after taking a usual starting dosage of warfarin to prevent thromboembolism. We found out later from his blood tests that he had hyperthyroidism at the time of treatment initiation. His genetic analysis showed CYP2C9*1/*3 and VKORC1+1173TT genotypes. We suspect that both hyperthyroidism and genetic variant would have contributed to his extremely increased INR at the beginning of warfarin therapy. From this case, we learned that pharmacogenetic and thyroid function test might be useful when deciding the starting dosage of warfarin in patients with atrial fibrillation.
Aged ; Anticoagulants/blood/metabolism/therapeutic use ; Aspirin/therapeutic use ; Atrial Fibrillation/*diagnosis ; Chromatography, High Pressure Liquid ; Cytochrome P-450 CYP2C9/*genetics ; Genotype ; Humans ; Male ; Polymorphism, Single Nucleotide ; Tandem Mass Spectrometry ; Thromboembolism/prevention & control ; Thyrotoxicosis/*diagnosis ; Vitamin K Epoxide Reductases/genetics ; Warfarin/*blood/metabolism/therapeutic use