Does desmopressin acetate prophylaxis reduce blood loss after valvular heart operations? A randomized, double-blind study.

The effectiveness of prophylactic desmopressin acetate in reducing hemorrhage after cardiopulmonary bypass operations is controversial. We conducted a prospective, randomized, placebo-controlled, double-blind trial to determine its effectiveness and safety in such patients. Eighty-three evaluable patients undergoing valvular heart operations were randomized to receive desmopressin (0.3 microgram/kg) (41) or placebo (42) after cardiac bypass. Demographic characteristics were similar in both groups. There was no significant difference in total 24-hour blood loss between groups (desmopressin 1064.8 +/- 647.1 ml versus placebo 844.4 +/- 507.6 ml; p greater than 0.05), or in the requirement for red blood cell, platelet, or fresh frozen plasma transfusion, or for reexploration for control of hemorrhage. Neither was there a difference in the occurrence of thrombotic complications between groups. Analysis of factor VIII activity, von Willebrand factor, or von Willebrand factor multimers failed to show significant correlations with blood loss or differences between groups except for factor VIII activity, which was significantly higher in the desmopressin group 1 hour after operation than in the placebo group. A detailed comparative analysis of similar trials to determine the reasons for different outcomes suggests that desmopressin should not be used routinely as a prophylactic agent to reduce postsurgical hemorrhage, but that it may be beneficial when used in patients who already manifest excessive bleeding postoperatively.     

A comparative study of prostacyclin infusion given before and during cardiopulmonary bypass to assess the first pass effect of the circuit on platelet number and function

Platelet damage during cardiopulmonary bypass (CPB), although proportional to the duration of bypass, may result in significant dysfunction after the initial contact with an extracorporeal circuit, the so-called 'first pass' phenomenon. The platelet sparing effect of prostacyclin (PGI2) infusion was studied in a double-blind randomized trial on male patients undergoing coronary artery bypass grafts to assess the effect of the 'first pass' through the CPB circuit. Prostacyclin infusion was begun before the onset of CPB or during CPB in two groups which were compared to a placebo control group. A standardized anaesthetic, surgical and perfusion technique were used. Preoperatively and during surgery at pre-set intervals, whole blood platelet aggregation was studied using ADP and collagen agonists. Platelet numbers and function measured by ADP aggregation were conserved in the two PGI2 groups. There was no significant difference between the treated groups. We conclude, therefore, that the initial contact of platelets with the CPB circuit, in the absence of PGI2 did not irreversibly affect platelet function. In addition, the hypotensive action of PGI2 was easier to control once on bypass. It may therefore be preferable to delay PGI2 infusion until CPB has been established.     

Platelet activation and aggregation during normothermic cardiopulmonary bypass

OBJECTIVE: The usefulness of heparin-bonded circuits under normothermic cardiopulmonary bypass has not been elucidated. We studied platelet activation and aggregation differences between heparin-bonded and nonheparin-bonded circuits in patients undergoing surgery involving normothermic cardiopulmonary bypass. METHODS: Eight patients underwent coronary artery bypass grafting with non heparin-bonded circuits (controls) and 7 the same with heparin-bonded circuits (heparin group). Heparin bonding was applied to the blood contact surface of our system, including the oxygenator and connecting tubes. Patient body temperature was kept between 36 and 37 degrees C. Beta-thromboglobulin and platelet factor 4 were measured before, during, and after cardiopulmonary bypass, and platelet aggregation was evaluated by laser-light scattering. RESULTS: Changes in beta-thromboglobulin and platelet factor 4 during and after cardiopulmonary bypass were similar in both groups. Small particle formation was the primary aggregate induced during and after cardiopulmonary bypass in both groups, and serial changes in particle formation up to 24 hours after cardiopulmonary bypass were similar in both groups. CONCLUSIONS: Our results indicate that in 2-3 hours of normothermic cardiopulmonary bypass, heparin-bonded circuits are similar to nonheparin-bonded ones in platelet compatibility.     

Blood conservation techniques and platelet function in cardiac surgery.

Postoperative alterations in platelet function induced by cardiopulmonary bypass (CPB) are of importance. The effect on platelet aggregation of three different techniques for reducing blood consumption was studied in 30 patients undergoing elective aortocoronary bypass grafting from the beginning of anesthesia until the 1st postoperative day. The patients were randomly divided into three groups, in which 1) a cell separator was used during and after CPB; 2) a hemofiltration device was used; and 3) high-dose aprotinin was used in order to reduce the need of homologous blood. A fourth group undergoing neurosurgery procedures served as a control. Platelet aggregation induced by adenosine diphosphate (concentration 0.25, 0.50, 1.0, and 2.0 microM), collagen (4 microliters/ml), and epinephrine (25 microM) was determined by the turbidimetric method. Platelet aggregation was not significantly changed in the control group, indicating that the operation itself did not impair platelet function. At the end of the operation (after retransfusion of the salvaged pump blood), the maximum aggregation and maximum gradient of aggregation induced by all three inductors were most reduced (significantly) in the cell-separator patients. On the 1st postoperative day, platelet aggregation in the hemofiltration patients and the patients treated with aprotinin had normalized. Aggregation of patients pretreated with high-dose aprotinin was not different from that of the hemofiltration patients throughout the investigation. Blood loss was significantly highest in the cell-separator group (770 +/- 400 ml on the 1st postoperative day) but was not different between the hemofiltration (390 +/- 230 ml) and the aprotinin-treated patients (260 +/- 160 ml).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of autologous platelet-rich plasma (PRP) in cardiac surgery

Autologous platelet-rich plasma (PRP) was harvested before cardiopulmonary bypass (CPB). After heparin neutralization, it was returned to patients. The purpose of this study was to examine platelet function and the amount of blood loss and blood transfusion after transfusion of PRP. Twenty-eight patients undergoing elective coronary artery bypass grafting and other procedures were divided into three groups: group A; patients undergoing CAGB between May and October 1997 (n = 10), group B; patients undergoing other between May and October 1997 (n = 8), group C; patients undergoing CAGB before May 1997 (n = 10). Blood cell count, platelet aggregation in response to ADP, and platelet adhesion were measured before CPB, just after CPB, after infusion of protamine and PRP, 24 hrs after CPB and 48 hrs after CPB. Blood loss and blood transfusion in group. A and group C were examined after CPB. There was no significant difference in platelet count between group A and group B. There was significant difference in platelet aggregation in group A. There was no significant difference in blood loss after CPB between group A and group C, but there was a significant difference in blood transfusion between group A and group C. These results suggest that PRP was useful to preserve platelet function and to decrease blood loss after CPB in cardiac surgery.     

Platelet activation and aggregation during cardiopulmonary bypass.

Increases in plasma concentrations of platelet granule products such as platelet factor 4 and beta-thromboglobulin during cardiopulmonary bypass suggest that platelets are activated during extracorporeal circulation. Subsequent circulation of these activated platelets may be responsible for the ubiquitous platelet dysfunction associated with cardiopulmonary bypass. Using flow cytometry and a monoclonal antibody directed against an alpha-granule membrane protein, granule membrane protein 140 (GMP-140), which is expressed on the platelet surface membrane after activation, we directly measured the percentage of circulating activated platelets in 41 patients before, during, and after cardiopulmonary bypass. In addition, we compared the GMP-140 expression with platelet aggregation in response to adenosine diphosphate (ADP). Cardiopulmonary bypass produced a significant increase in the percentage of GMP-140-positive platelets persisting in the circulation; the percentage peaked at a mean of 29% (range 10-58%) before separation from extracorporeal circulation. A significant percentage of these activated platelets continued to circulate in the early postoperative period. Simultaneous measurement of platelet aggregation in response to ADP demonstrated an aggregation defect that had a time course distinct from platelet activation and whose magnitude did not correlate with the degree of platelet activation in individual patients. We conclude that cardiopulmonary bypass causes a complex constellation of platelet defects, which include alpha-granule release, prolonged circulation of activated, "spent" platelets, and impaired platelet aggregation.     

Combined administration of nitric oxide gas and iloprost during cardiopulmonary bypass reduces platelet dysfunction: a pilot clinical study

BACKGROUND: Thrombocytopenia and platelet dysfunction are major mechanisms of cardiopulmonary bypass-induced postoperative hemorrhage. This study evaluated the effects of low amounts of nitric oxide, iloprost (prostacyclin analog), and their combination administered directly into the oxygenator on platelet function, platelet-leukocyte interactions, and postoperative blood loss in patients undergoing coronary artery bypass grafting. METHODS: Blood samples from 41 patients randomized to the control, nitric oxide (20 ppm), iloprost (2 ng x kg -1 x min -1 ), or nitric oxide plus iloprost groups were collected during cardiopulmonary bypass. Platelets and leukocytes were enumerated. Platelet membrane glycoprotein Ib and glycoprotein IIb/IIIa, P-selectin, platelet-derived microparticles, leukocyte CD11b/CD18 (Mac-1), and platelet-leukocyte aggregate were quantified by means of flow cytometry. Collagen and thrombin receptor-activating peptide-induced platelet aggregation in whole blood was analyzed by means of aggregometry. RESULTS: Both nitric oxide or iloprost attenuated cardiopulmonary bypass-induced thrombocytopenia, reduction of glycoprotein Ib and glycoprotein IIb levels, translocation of P-selectin, microparticle formation, Mac-1 upregulation, and suppression of collagen-induced aggregation. Nitric oxide plus iloprost was significantly more effective in preventing thrombocytopenia, microparticle formation, and P-selectin translocation. Moreover, this treatment preserved thrombin receptor-activating peptide-induced aggregation, which was not rescued by single treatments. Both nitric oxide and nitric oxide plus iloprost attenuated postoperative blood loss. CONCLUSIONS: Nitric oxide plus iloprost reduced the deleterious effects of cardiopulmonary bypass, such as thrombocytopenia, platelet activation, platelet-leukocyte aggregate formation, and suppression of platelet aggregative responses. The reduced postoperative bleeding observed with this treatment suggests that this is a new and clinically feasible therapeutic option for patients subjected to cardiopulmonary bypass.     

Prophylactic treatment with desmopressin does not reduce postoperative bleeding after coronary surgery in patients treated with aspirin before surgery

The synthetic vasopressin analog desmopressin has hemostatic properties and may reduce postoperative bleeding after coronary artery bypass grafting (CABG). A study on the effects of recent aspirin ingestion on platelet function in cardiac surgery showed a greater impairment of platelet function in patients treated with aspirin <2 days before the operation. We evaluated the effects of desmopressin on postoperative bleeding in CABG patients who were treated with aspirin 75 or 160 mg until the day before surgery. The study was a prospective, randomized, double-blinded, placebo-controlled, parallel group trial. One-hundred patients were included and divided into two groups. One group received desmopressin 0.3 micro g/kg and the other received placebo (0.9% NaCl) after the neutralization of heparin with protamine sulfate. Postoperative blood loss was recorded for 16 h. The mean (SD) bleeding was 606 (237) mL in the desmopressin group and 601 (301) mL in the placebo group (P = 0.93), representing no significant difference (95% confidence interval, -107 to 117 mL). We conclude that desmopressin does not reduce postoperative bleeding in CABG patients treated with aspirin until the day before surgery. IMPLICATIONS: Continuation of aspirin until the day before coronary artery bypass grafting may increase postoperative bleeding. The administration of desmopressin to these patients after the neutralization of heparin with protamine sulfate does not reduce postoperative bleeding.     

The effect of prophylactic epsilon-aminocaproic acid on bleeding, transfusions, platelet function, and fibrinolysis during coronary artery bypass grafting.

BACKGROUND: Antifibrinolytic medications administered before skin incision decrease bleeding after cardiac surgery. Numerous case reports indicate thrombus formation with administration of epsilon-aminocaproic acid (epsilon-ACA). The purpose of this study was to examine the efficacy of epsilon-ACA administered after heparinization but before cardiopulmonary bypass in reducing bleeding and transfusion requirements after primary coronary artery bypass surgery. METHODS: Seventy-four adult patients undergoing primary coronary artery bypass surgery were randomized to receive 125 mg/kg epsilon-ACA followed by an infusion of 12.5 mg x kg(-1) x h(-1) or an equivalent volume of saline. Coagulation studies, thromboelastography, and platelet aggregation tests were performed preoperatively, after bypass, and on the first postoperative day. Mediastinal drainage was recorded during the 24 h after surgery. Homologous blood transfusion triggers were predefined and transfusion amounts were recorded. RESULTS: One patient was excluded for surgical bleeding and five patients were excluded for transfusion against predefined criteria One patient died from a dysrhythmia 2 h postoperatively. Among the remaining 67, the epsilon-ACA group had less mediastinal blood loss during the 24 h after surgery, 529+/-241 ml versus 691+/-286 ml (mean +/- SD), P < 0.05, despite longer cardiopulmonary bypass times and lower platelet counts, P < 0.05. Platelet aggregation was reduced in both groups following cardiopulmonary bypass but did not differ between groups. Homologous blood transfusion was similar between both groups. CONCLUSIONS: Prophylactic administration of epsilon-ACA after heparinization but before cardiopulmonary bypass is of minimal benefit for reducing blood loss postoperatively in patients undergoing primary coronary artery bypass grafting.     

6%羟乙基淀粉130/0.4和6%羟乙基淀粉200/0.5急性高容量血液稀释对全麻患者凝血功能的影响

目的 评价6%羟乙基淀粉130/0.4(6% HES130/0.4)和6%羟乙基淀粉20010.5(6% HES200/0.5)急性高容量血液稀释(AHHD)对全麻患者凝血功能的影响.方法 择期全麻手术患者60例,ASA Ⅰ或Ⅱ级,年龄18～64岁,随机分为3组(n=20):对照组(C组)、6%HES200/0.5组(H组)及6%HES130/0.4组(V组).H组和V组于麻醉诱导前90 min分别静脉输注6% HES200/0.5或6% HES130/0.4,速率20 ml·kg-1·h-1,扩容量20ml/kg;C组仅静脉输注乳酸钠林格氏液6～8 ml·kg-1·h-1.于AHHD前、AHHD后即刻及AHHD后1 h采血,进行下述指标的测定:血小板计数、凝血酶原时间(PT)、血小板最大聚集率和Sonoclot玻璃珠激活全血凝固时间(gbACT)、凝结速率(CR)、血小板功能(PF)和曲线达峰时间.H组和V组同时还测定活化部分凝血活酶时间(APTT)、凝血因子Ⅷ活性(FⅧ:C)、von Willebrand因子(vWF)水平.结果 与AHHD前比较,H组和V组AHHD后PT和APTY均延长,FⅧ:C下降(P＜0.05),但2组AHHD后1 h FⅧ:C高于AHHD后即刻(P＞0.05);H组和V组AHHD后血小板最大聚集率降低,但AHHD后1 h高于AHHD后即刻(P＜0.05).与H组比较,V组AHHD后CR降低(P＜0.05),其他凝血功能指标比较差异无统计学意义(P＞0.05).结论 6%HES130/0.4和6% HES200/0.5(20 ml/kg)AHHD对全麻患者凝血功能的抑制作用较轻;两者对凝血功能的影响无明显差异.     

Perioperative use of tirofiban hydrochloride (Aggrastat) does not increase surgical bleeding after emergency or urgent coronary artery bypass grafting.

BACKGROUND: The platelet glycoprotein IIb/IIIa inhibitor tirofiban hydrochloride improves outcome in patients with acute coronary syndrome. Nevertheless, a considerable number of patients require emergency or urgent coronary artery bypass grafting and may be at increased risk of postoperative bleeding after treatment with this molecule. The aim of this study is to evaluate the incidence of bleeding complications among patients undergoing bypass grafting after treatment with tirofiban. METHODS: We investigated the influence of the molecule on postoperative bleeding after cardiac surgery, comparing 2 groups of patients undergoing emergency or urgent coronary artery bypass grafting: group A (n = 20) received tirofiban, and group B (n = 68) received conventional therapy with intravenous heparin up until the operation. A total of 88 patients underwent coronary artery bypass surgery within 2 hours of ceasing the hemodynamic study. Clinical outcome, chest tube outputs, bleeding complications, transfusion requirements, platelet and hemoglobin counts, and clinical complications were examined. RESULTS: Bleeding differences were noted between the 2 groups at 8, 16, and 24 hours postoperatively. The incidence of blood, platelet, and fresh frozen plasma transfusions was higher in the control group. Postoperative thrombocytopenia was preserved in group A (199.5 +/- 70.4 vs 150.6 +/- 33.4 10(3)/mL, P <.01). No significant differences were noted between the 2 groups in the incidence of perioperative myocardial infarction, but significant differences were noted in enzyme levels, length of stay in the intensive care unit, and length of stay in the hospital. No deaths were observed. Hospital morbidity was increased in group B because of factors that were not apparently linked with tirofiban infusion. CONCLUSIONS: Patients may safely undergo coronary artery bypass surgery after treatment with tirofiban hydrochloride. This molecule, administered in the immediate preoperative period, has no adverse clinical effects and does not seem to negatively influence the incidence of perioperative myocardial infarction. Although extracorporeal circulation can modify platelet numbers and function, our ongoing data could show significant reduction in the loss of platelets induced by cardiopulmonary bypass, minor postoperative bleeding, and a minor transfusion requirement in general.     

Effects of nafamostat mesilate and minimal-dose aprotinin on blood-foreign surface interactions in cardiopulmonary bypass

BACKGROUND: The pharmacological inhibition of blood-foreign surface interactions is an attractive strategy for reducing the morbidity associated with cardiopulmonary bypass. We compared the inhibitory effects of nafamostat mesilate (a broad-spectrum synthetic protease inhibitor) and minimal-dose aprotinin on blood-surface interactions in clinical cardiopulmonary bypass. METHODS: Eighteen patients undergoing coronary surgery were divided into three groups: (1) the control group (heparin, 4 mg/kg; n = 6), (2) the nafamostat mesilate group (heparin plus nafamostat, 0.2 mg/kg bolus followed by 2.0 mg/kg/h during cardiopulmonary bypass; n = 6), and (3) the aprotinin group (heparin plus aprotinin, 2.0 x 10(4) KIU/kg; n = 6). Platelet count, platelet aggregation, beta-thromboglobulin, prothrombin fragment F1.2, thrombin-antithrombin complex, plasminogen activator inhibitor-1, alpha2-plasmin inhibitor-plasmin complex, D-dimer, neutrophil elastase, and interleukin-6 were measured before, during, and after bypass. Bleeding times and blood loss were recorded. RESULTS: There were no significant differences between groups in platelet count, beta-thromboglobulin, plasminogen activator inhibitor-1, interleukin-6, bleeding times, or blood loss. Platelet aggregation was better preserved at 12 hours after surgery in the nafamostat and aprotinin groups than in the control group. Prothrombin fragment F1.2, thrombin-antithrombin complex and neutrophil elastase levels were significantly reduced by aprotinin, but not by nafamostat as compared with the control group. The alpha2-plasmin inhibitor-plasmin complex and D-dimer were significantly lower with either of the drugs. Aprotinin showed better control of D-dimer than did nafamostat. CONCLUSIONS: Nafamostat mesilate fails to reduce thrombin formation and neutrophil elastase release, whereas minimal-dose aprotinin inhibits both. Neither nafamostat nor aprotinin inhibits platelet activation. Nafamostat reduces fibrinolysis during cardiopulmonary bypass, although its effect is not as potent as aprotinin.     

Efficacy of FK633, an ultra-short acting glycoprotein IIb/IIIa antagonist on platelet preservation during and after cardiopulmonary bypass.

OBJECTIVE: Temporary pharmacologic inhibition of platelet function during and after cardiopulmonary bypass (CPB) (platelet anesthesia) is an attractive strategy for preserving platelets during CPB. We examined the efficacy of FK633, an ultra-short acting glycoprotein IIb/IIIa antagonist. METHODS: The study was carried out in six mongrel dogs that received an intravenous bolus of 0.1 mg/kg of FK633 at the time of administration of heparin (group F), and six control dogs (group C). All animals underwent 60 min of normothermic CPB followed by a 2-h observation period. Blood samples for platelet count, platelet aggregation to adenosine diphosphate and parameters concerning the coagulation system were obtained at eight time points. Hemodynamics, bleeding time, and postoperative blood loss were assessed serially. Scanning electron micrograph of the oxygenator's membrane was investigated. RESULTS: FK633 significantly protected platelet number (group F, 59+/-10% versus group C, 38+/-15% of the pre-CPB value; P < 0.01), and inhibited platelet aggregation to adenosine diphosphate (group F, 13+/-12% versus group C, 35+/-9% of the pre-CPB value; P < 0.01) during CPB. Postoperative blood loss did not significantly differ between the two groups, but there was a tendency of less bleeding in group F (group F, 73+/-23 ml versus group C, 111+/-44 ml; P = 0.09). In group F, scanning electron micrograph of the oxygenator's membrane showed that its surface was free from platelets. There were no significant differences between the groups in hemodynamics. CONCLUSIONS: An ultra-short acting glycoprotein IIb/IIIa antagonist, FK633, is effective in preventing both platelet aggregation and thrombocytopenia during CPB, and may be effective for minimizing postoperative bleeding.     

小剂量抑肽酶结合自体输血对体外循环围术期凝血和纤溶功能的影响

目的：观察小剂量抑肽酶加自体输血对体外循环围术期凝血和纤溶功能的影响。方法：２０例体外循环心脏直视手术病人，分为抑肽酶＋自体输血组（Ａ组）和对照组（Ｃ组），连续监测围术期凝血及纤溶功能的变化。结果：Ａ组病人在术中及术后ＰＡｇＴ、ＰＬＧ、α２－ＡＰ等均显著高于Ｃ组，（Ｐ＜０．０５或０．０１），而Ｄ－Ｄ却显著低于Ｃ组（Ｐ＜０．０１）。Ａ组病人术后出血量和输血量均显著少于Ｃ组（Ｐ＜０．０１）。结论：小剂量抑肽酶＋自体输血能显著减轻体外循环引起的凝血功能紊乱，预防和减轻继发纤溶亢进，从而显著减少了术后出血和输血量。     

Pharmacological effect of nitroprusside on platelet aggregation

Adequate platelet function and numbers are critical for postcardiopulmonary bypass patients. Endogenous and pharmacological sources of nitric oxide (NO) are known inhibitors of platelet aggregation. Sodium nitroprusside (SNP), used clinically to control blood pressure, is an inorganic source of NO. Our long-term goal is to determine if SNP infusion in the venous return line of the cardiopulmonary bypass system would preserve platelet numbers and function without affecting systemic vascular resistance. Our first requirement to accomplish this goal was to develop an assay that would detect the SNP effect on platelet aggregation. We, therefore, tested the hypothesis that clinical concentrations of SNP would inhibit platelet aggregation. We quantified platelet aggregation with the Medtronic Hepcon HMS whole blood aggregometer. Normal heparinized human blood was treated with 0.625 to 12.5 nM platelet activating factor (PAF), 0.25 to 5.0 microM epinephrine, or 0.20 to 10 microM adenosine 5'-diphosphate (ADP) to stimulate platelet aggregation. SNP was added at 10(-5) M to determine its affect on PAF, epinephrine, and ADP stimulated platelet aggregation. The results demonstrated that PAF-stimulated platelet aggregation was significantly inhibited with SNP (10(-5) M) to 82% (p < .05) of control and epinephrine and ADP mediated aggregation were not significantly affected. In conclusion, at clinically relevant concentrations SNP inhibits platelet aggregation by PAF but not with ADP or epinephrine.     

Tranexamic acid reduces bleeding and the need for blood transfusion in primary myocardial revascularization

BACKGROUND: The objective of this study was to study the effect of low-dose tranexamic acid (TA) on postoperative bleeding and coagulation variables after coronary artery bypass grafting operation. METHODS: Fifty patients undergoing primary coronary artery bypass grafting were randomly assigned to receive either placebo (0.9% NaCl; n = 25) or 10 mg/kg TA followed by infusion of 1 mg/kg per hour during the operation (n = 25). Data measured included blood loss, transfusion, reoperation, fibrinogen level, fibrinogen split products, platelet size, and platelet function. Measurements were made after induction of anesthesia, after heparin administration, during patient warming, after skin closure, and 24 hours after operation. RESULTS: Patients in the TA study group weighed less. Other demographic characteristics were similar between groups. Postoperative bleeding was less in the TA group (194 +/- 135 mL versus 488 +/- 238 mL, p < 0.001), whereas blood requirement was higher in the control group (1.68 +/- 1 versus 0.52 +/- 0.9 U of packed cells per patient, p < 0.001). The percent of patients exposed to blood products was significantly less in the TA group (36% versus 100%, p < 0.001). Fibrinogen split products were lower in the TA group during bypass (p < 0.001). Fibrinogen levels fell in both groups during cardiopulmonary bypass. Platelet number and function were reduced equally in both groups by cardiopulmonary bypass. Other test results were not different between groups. CONCLUSIONS: The use of low-dose TA during coronary artery bypass grafting significantly reduced the coagulopathy-induced postoperative bleeding and allogeneic blood products requirement. The low levels of fibrinogen split products during bypass in the study group reflect the inhibiting effect of TA in fibrinolysis. Tranexamic acid had no effect on platelet function during cardiopulmonary bypass.     

The effect of desmopressin acetate (DDAVP) on postoperative blood loss after cardiac operations in children

We investigated the effect of an intraoperative desmopressin acetate infusion on blood loss after cardiac operation in 60 children, by using a prospective, randomized, double-blind trial. Thirty patients received a desmopressin dose of 0.3 microgram/kg intravenously over 15 minutes at the conclusion of cardiac bypass, and 30 received a saline placebo. The two groups were comparable with respect to age, sex, cardiac lesion, presence of cyanosis, and prevalence of Down's syndrome. Results showed no significant difference in postoperative blood loss between the two groups (30.5 +/- 37.9 ml/kg in the placebo group versus 40.0 +/- 33.1 ml/kg in the desmopressin group). Postoperative bleeding time, total urine output, postinfusion hemodynamics, and postoperative coagulation studies did not differ significantly between the two groups. We conclude that postbypass desmopressin infusion does not reduce blood loss in children undergoing cardiac operations.     

Effect of tranexamic acid on blood loss reduction after cardiopulmonary bypass

OBJECTIVE: We evaluated the effect of tranexamic acid on blood loss in patients undergoing elective cardiopulmonary bypass for coronary artery bypass surgery. METHODS: We randomly assigned 7 of 14 patients to a group receiving 50 mg/kg tranexamic acid before skin incision and after the start of cardiopulmonary bypass and the other 7 as controls. RESULTS: Intraoperative and postoperative blood loss was significantly (p = 0.025) reduced in the tranexamic acid group. A similar decrease in platelet count was observed during cardiopulmonary bypass in both groups. Antithrombin III was significantly (p = 0.013) decreased in both groups during cardiopulmonary bypass. Antithrombin III and thrombin-antithrombin III complexes were significantly (p = 0.001) increased after protamine administration. A significant (p = 0.010) decrease in alpha 2-plasmin inhibitor was noted at 5 and 60 minutes after the start of cardiopulmonary bypass in the tranexamic acid group. alpha 2-plasmin inhibitor-plasmin complexes were significantly (p = 0.001) increased after the start of cardiopulmonary bypass in both groups and were significantly (p = 0.012) decreased after protamine administration. alpha 2-plasmin inhibitor-plasmin complexes in the tranexamic acid group were significantly (p = 0.030) lower than in controls 60 minutes after the start of cardiopulmonary bypass, just prior to the end of cardiopulmonary bypass, and after protamine administration. CONCLUSIONS: These findings showed that tranexamic acid administration effectively prevented perioperative blood loss without thromboembolic complications and that tranexamic acid during cardiopulmonary bypass coordinates the anticoagulative effect of heparin and the antifibrinolytic effect of tranexamic acid.     

Does tranexamic acid reduce desmopressin-induced hyperfibrinolysis?

OBJECTIVE: Desmopressin releases tissue-type plasminogen activator, which augments cardiopulmonary bypass--associated hyperfibrinolysis, causing excessive bleeding. Combined use of desmopressin with prior administration of the antifibrinolytic drug tranexamic acid may decrease fibrinolytic activity and might improve postoperative hemostasis. METHODS: This prospective randomized study was carried out with 100 patients undergoing coronary artery bypass operations between April 1999 and November 2000 in Gülhane Military Medical Academy. Patients were divided into 2 groups. Desmopressin (0.3 microg/kg) was administrated just after cardiopulmonary bypass and after protamine infusion in group 1 (n = 50). Both desmopressin and tranexamic acid (before the skin incision at a loading dose of 10 mg/kg over 30 minutes and followed by 12 hours of 1 mg.kg(-1).h(-1)) were administrated in group 2 (n = 50). RESULTS: Significantly less drainage was noted in group 2 (1010 +/- 49.9 mL vs 623 +/- 41.3 mL, P =.0001). Packed red blood cells were transfused at 2.1 +/- 0.5 units per patient in group 1 versus 0.9 +/- 0.3 units in group 2 (P =.0001). Fresh frozen plasma was transfused at 1.84 +/- 0.17 units per patient in group 1 versus 0.76 +/- 0.14 units in group 2 (P =.0001). Only 24% of patients in group 2 required donor blood or blood products compared with 74% of those in the isolated desmopressin group (group 1, P =.00001). Group 1 and group 2 findings were as follows: postoperative fibrinogen, 113 +/- 56.3 mg/dL versus 167 +/- 45.8 mg/dL (P =.0001); fibrin split product, 21.2 +/- 2.3 ng/mL versus 13.5 +/- 3.4 ng/mL (P =.0001); and postoperative hemoglobin level, 7.6 plus minus 1.2 g/dL versus 9.1 plus minus 1.2 g/dL (P =.0001). CONCLUSION: Tranexamic acid administration significantly reduces desmopressin and bypass-induced hyperfibrinolysis. Combined use of tranexamic acid and desmopressin decreases both postoperative blood loss and transfusion requirement.     

Platelet protection by aprotinin in cardiopulmonary bypass: electron microscopic study.

To evaluate the functional integrity of platelets in patients administered the proteinase inhibitor aprotinin during cardiopulmonary bypass, 20 patients undergoing a complicated and prolonged open heart operation were studied. They were randomized to receive either a high dose of aprotinin (total dose, 6 to 7 x 10(6) KIU) before and during cardiopulmonary bypass (10 patients) or a placebo (10 patients). Blood samples were collected preoperatively, at the termination of bypass, and 90 minutes thereafter to assess platelet count and aggregation on extracellular matrix, which was studied by scanning electron microscopy. On a scale of 1 to 4, mean preoperative platelet aggregation grades were similar in both groups (3.5 +/- 0.5). Postoperatively, at the termination of cardiopulmonary bypass and 90 minutes thereafter, all 10 patients treated with aprotinin revealed normal, unchanged platelet aggregation (grade, 3.5 +/- 0.5), whereas all placebo-treated patients showed severely disturbed aggregation (grade, 1.4 +/- 0.5) (p less than 0.001). The platelet count was similar in both groups before and after operation (preoperatively, 182 +/- 75 x 10(9)/L and 146 +/- 30 x 10(9)/L, and postoperatively, 87 +/- 13 x 10(9)/L and 80 +/- 27 x 10(9)/L for the aprotinin and placebo groups, respectively). Total 24-hour postoperative bleeding and blood requirement were significantly lower in the aprotinin group (371 +/- 84 mL and 2 +/- 0.7 units, respectively) compared with the placebo group (608 +/- 28 mL and 3.4 +/- 1.3 units, respectively) (p less than 0.01). These results demonstrate that improved postoperative hemostasis is directly related to the complete preservation of platelet function achieved by the protective properties of aprotinin.