Recombinant human antithrombin III restores heparin responsiveness and decreases activation of coagulation in heparin-resistant patients during cardiopulmonary bypass.

OBJECTIVES: We sought to evaluate the efficacy of recombinant human antithrombin III for restoration of heparin responsiveness in heparin-resistant patients scheduled for cardiac surgery. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study in heparin-resistant patients undergoing elective cardiac surgery. Patients were considered heparin resistant if the activated clotting time was less than 480 seconds after 400 U/kg heparin. Fifty-two heparin-resistant patients were randomized into 2 cohorts. One cohort received a single bolus (75 U/kg) of recombinant human antithrombin III (n = 28), and the other, the placebo group (n = 24), received a normal saline bolus. If the activated clotting time remained less than 480 seconds, this was defined as treatment failure, and 2 units of fresh frozen plasma were transfused. Patients were monitored for adverse events during hospitalization. RESULTS: Six (21%) of the patients in the recombinant human antithrombin III group received fresh frozen plasma transfusions compared with 22 (92%) of the placebo-treated patients ( P < .001). Two units of fresh frozen plasma did not restore heparin responsiveness. There was no increased incidence of adverse events associated with recombinant human antithrombin III administration. Postoperative 24-hour chest tube bleeding was not different in the 2 groups. Surrogate measures of hemostatic activation suggested that there was less activation of the hemostatic system during cardiopulmonary bypass in the recombinant human antithrombin III group. CONCLUSION: Treatment with recombinant human antithrombin III in a dose of 75 U/kg is effective in restoring heparin responsiveness and promoting therapeutic anticoagulation for cardiopulmonary bypass in the majority of heparin-resistant patients. Two units of fresh frozen plasma were insufficient to restore heparin responsiveness. There was no apparent increase in bleeding associated with recombinant human antithrombin III.

Comparison of structured use of routine laboratory tests or near-patient assessment with clinical judgement in the management of bleeding after cardiac surgery.

BACKGROUND: Using algorithms based on point of care coagulation tests can decrease blood loss and blood component transfusion after cardiac surgery. We wished to test the hypothesis that a management algorithm based on near-patient tests would reduce blood loss and blood component use after routine coronary artery surgery with cardiopulmonary bypass when compared with an algorithm based on routine laboratory assays or with clinical judgement. METHODS: Patients (n=102) undergoing elective coronary artery surgery with cardiac bypass were randomized into two groups. In the point of care group, the management algorithm was based on information provided by three devices, the Hepcon, thromboelastography and the PFA-100 platelet function analyser. Management in the laboratory test group depended on rapidly available laboratory clotting tests and transfusion of haemostatic blood components only if specific criteria were met. Blood loss and transfusion was compared between these two groups and with a retrospective case-control group (n=108), in which management of bleeding had been according to the clinician's discretion. RESULTS: All three groups had similar median blood losses. The transfusion of packed red blood cells (PRBCs) and blood components was greater in the clinician discretion group (P<0.05) but there was no difference in the transfusion of PRBCs and blood components between the two algorithm-guided groups. CONCLUSION: Following algorithms based on point of care tests or on structured clinical practice with standard laboratory tests does not decrease blood loss, but reduces the transfusion of PRBCs and blood components after routine cardiac surgery, when compared with clinician discretion. Cardiac surgery services should use transfusion guidelines based on laboratory-guided algorithms, and the possible benefits of point of care testing should be tested against this standard.

Mechanisms and attenuation of hemostatic activation during extracorporeal circulation.

Patients undergoing cardiac surgery with cardiopulmonary bypass are at risk for excessive microvascular bleeding, which often leads to transfusion of allogeneic blood and blood components as well as reexploration in a smaller subset of patients. Excessive bleeding after cardiac surgery is generally related to a combination of several alterations in the hemostatic system pertaining to hemodilution, excessive activation of the hemostatic system, and potentially the use of newer, longer-acting antiplatelet or antithrombotic agents. Although several nonpharmacologic strategies have been proposed, this review summarizes the role of pharmacologic interventions as means to attenuate the alterations in the hemostatic system during CPB in an attempt to reduce excessive bleeding, transfusion, and reexploration. Specifically, agents that inhibit platelets, fibrinolysis, factor Xa and thrombin, as well as broad-spectrum agents, have been investigated with respect to their role in reducing consumption of clotting factors and better preservation of platelet function. Prophylactic administration of agents with antifibrinolytic, anticoagulant, and possibly antiinflammatory properties can decrease blood loss and transfusion. Although aprotinin seems to be the most effective blood conservation agent (which is most likely related to its broad-spectrum nature), agents with isolated antifibrinolytic properties may be as effective in low-risk patients. The ability to reduce blood product transfusions and to decrease operative times and reexploration rates favorably affects patient outcomes, availability of blood products, and overall health care costs.

Warfarin therapy does not increase bleeding in patients undergoing heart transplantation.

BACKGROUND: Historically, warfarin has been discontinued or rapidly reversed with fresh frozen plasma in patients awaiting heart transplantation because of concerns regarding excessive bleeding. Because preoperative warfarin may have effects on bleeding after cardiac operations, we reviewed our experience to determine the risks in patients undergoing heart transplantation while maintained on warfarin. METHODS: The records of consecutive adult patients undergoing heart transplantation from January 1996 to December 1998 were reviewed. Preoperative and 24-hour postoperative data were obtained, including patient demographics; hematologic laboratory values; medication use; repeat or primary sternotomy data; allogeneic blood product administration; and chest tube drainage. Multivariate linear and logistic regression analyses were performed using these variables to determine risk factors for bleeding after heart transplantation. RESULTS: Ninety adult patients, mean age 50 years, underwent orthotopic heart transplantation during the 36-month period. No relationships existed between preoperative international normalized ratio (INR, mean = 1.83 +/- 0.1, p = 0.84) or postoperative INR (mean = 2.2 +/- 0.9, p = 0.63) and chest tube drainage (mean = 721 +/- 63 mL). Relationships were observed between total blood product administration and preoperative INR (partial r = 0.30, p = 0.01) and postoperative INR (partial r = -0.37, p = 0.002); however, preoperative INR did not correlate (p = 0.29) when perioperative use of fresh frozen plasma was factored as a covariate. Inverse relationships were evident between postoperative INR and total blood product exposures, as well as transfusions of platelets (partial r = -0.26, p = 0.03), fresh frozen plasma (partial r = -0.28, p = 0.02), and red cells (partial r = -0.25, p = 0.04). CONCLUSIONS: Although we noted no correlations between INR and chest tube output, inverse relationships were observed with transfusion requirements in the first 24 hours after transplantation. Preoperative warfarin may be safely continued in patients awaiting heart transplantation.

Occurrence of myocardial ischemia immediately after coronary revascularization using radial arterial conduits.

OBJECTIVE: To assess the incidence of myocardial ischemia in patients receiving radial arterial and left internal thoracic arterial conduits (RA+LITA) during the postrevascularization period. DESIGN: Nonrandomized observational sequential cohort. SETTING: University hospital. PARTICIPANTS: Thirty adult patients, scheduled for elective coronary artery bypass graft surgery with RA+LITA, compared with 30 patients who received saphenous vein graft and left internal thoracic arterial conduits. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Myocardial ischemic episodes were defined as reversible ST-segment depressions or elevations >or=1 mm and >or=2 mm at J +60 msec and lasting >or=1 minute using 2-channel Holter monitoring. During the post-cardiopulmonary bypass period, a significantly higher number of patients with >or=2 mm ischemic episodes (21.7%; p = 0.015) and higher number of >or=2 mm ischemic episodes per hour (0.19 +/- 0.4 episodes/hr; p = 0.03) were observed in the radial artery group versus the comparison group (0% of patients and 0 episodes/hr). During the postoperative period (24 hours), a significantly longer duration of >or=2 mm ischemic episodes was observed in the radial artery group (24 +/- 33 minutes v 8.4 +/- 21 minutes; p = 0.046). Radial artery graft, preoperative calcium antagonists, and pulmonary arterial mean pressure were independent predictors of the duration and area under the ST-segment curve of >or=2 mm ischemic episodes during the postoperative period. CONCLUSION: There is an association between the use of the radial artery graft and the incidence and severity of >or=2 mm postrevascularization ischemic episodes.

The relationship between hirudin and activated clotting time: implications for patients with heparin-induced thrombocytopenia undergoing cardiac surgery.

UNLABELLED: Anticoagulation with recombinant hirudin (r-hirudin) (Refludan) has been suggested as an alternative to heparin for patients with heparin-induced thrombocytopenia requiring cardiac surgery. We sought to develop a modified activated coagulation time (ACT) that would allow quantification of the levels of r-hirudin required during cardiopulmonary bypass (CPB). Twenty-one patients scheduled for elective cardiac surgical procedures requiring CPB were enrolled in this IRB-approved study. R-hirudin was added to blood specimens obtained before heparin administration (before CPB) and 30 min after heparin neutralization with protamine (after CPB) to result in concentrations of 0, 2, 4, 6, 7, or 8 microg/mL. Kaolin/ACT and complete blood count measurements were assayed in native specimens (first 10 patients, Phase I) or in specimens mixed with equal volumes of commercial normal plasma (second 11 patients, Phase II). In Phase I, good (r(2) = 0.83) linear relationships between ACT values and r-hirudin concentrations (< or =4 microg/mL) were observed in specimens obtained before CPB. However, ACT values were markedly prolonged (P < 0.0001) by r-hirudin in specimens obtained after CPB, with ACT values generally exceeding the ACT's detection limit (>999 s) at hirudin concentrations >2 microg/mL. In patient specimens mixed with normal plasma (Phase II), ACT/hirudin relationships (i.e., hirudin/ACT slope values obtained with hirudin concentration < or =4 microg/mL) in the post-CPB period (0.022 +/- 0.004 microg. mL(-1). s(-1)) were similar (P = 0.47) to those (0.019 +/- 0.004 microg. mL(-1). s(-1)) obtained in the pre-CPB period. Accordingly, a significant relationship between normal plasma-supplemented ACT values and predilution hirudin concentration was obtained in the post-CPB (hirudin = 0.039ACT - 4.34, r(2) = 0.91) period. Although our data demonstrate that the ACT test cannot be used to monitor hirudin during CPB, the addition of 50% normal plasma to post-CPB hemodiluted blood specimens yields a consistent linear relationship between hirudin concentration and ACT values up to a predilution concentration of 8 microg/mL. Plasma-modified ACT may be useful in monitoring hirudin anticoagulation during CPB. IMPLICATIONS: A modified activated clotting time test system that may be helpful in monitoring hirudin anticoagulation in patients with heparin-induced thrombocytopenia during cardiac surgery with cardiopulmonary bypass is described.

Transfusion medicine : support of patients undergoing cardiac surgery.

There is still no alternative that is as effective or as well tolerated as blood; nevertheless, the search for ways to conserve, and even eliminate blood transfusion, continues. Based on hemoglobin levels, practice guidelines for the use of perioperative transfusion of red blood cells in patients undergoing coronary artery bypass grafting have been formulated by the National Institutes of Health and the American Society of Anesthesiologists. However, it has been argued that more physiologic indicators of adequacy of oxygen delivery should be used to assess the need for blood transfusion. Methods used for conserving blood during surgery include autologous blood donation, acute normovolemic hemodilution and intra- and postoperative blood recovery and reinfusion. The guidelines for the use of autologous blood transfusion are controversial and it does not appear to be cost effective compared with allogeneic blood transfusion in patients undergoing cardiac surgery. Similarly, the cost effectiveness of intra- and postoperative blood recovery and reinfusion need further evaluation. Treatment with recombinant human erythropoietin (rhEPO) remains unapproved in the US for patients undergoing cardiac or vascular surgery, but it is a valuable adjunct in Jehovah's Witness patients, for whom blood is unacceptable. The characterization of darbepoetin alfa, a novel erythropoiesis stimulating protein with a 3-fold greater plasma elimination half-life compared with rhEPO, is an important advance in this field. Darbepoetin alfa appears to be effective in treating the anemia in patients with renal failure or cancer and trials in patients with surgical anemia are planned. Desmopressin has been used to effectively reduce intraoperative blood loss. Topical agents to prevent blood loss, such as fibrin glue and fibrin gel, and agents that alter platelet function, such as aspirin (acetylsalicylic acid) or dipyridamole, need further evaluation in patients undergoing cardiac surgery. Aprotinin has been shown to preserve hemostasis and reduce allogeneic blood exposure to a greater extent than the antifibrinolytic agents tranexamic acid and aminocaproic acid. Controlled clinical trials comparing the costs of these agents with clinical outcomes, along with tolerability profiles in patients at risk for substantial perioperative bleeding are needed.

Abciximab and bleeding during coronary surgery: results from the EPILOG and EPISTENT trials. Improve Long-term Outcome with abciximab GP IIb/IIIa blockade. Evaluation of Platelet IIb/IIIa Inhibition in STENTing.

BACKGROUND: Abciximab during percutaneous coronary revascularization reduces ischemic complications, but concern exists regarding increased bleeding risk should emergency coronary surgical procedures be required. METHODS: Outcomes were assessed among 85 patients who required coronary artery bypass grafting operations after coronary intervention in two randomized placebo-controlled trials of abciximab. Comparisons were made between patients in the pooled placebo and abciximab groups. RESULTS: The incidence of coronary surgical procedures was 2.17% and 1.28% among patients randomized to placebo and abciximab, respectively (p = 0.021). Platelet transfusions were administered to 32% and 52% of patients in the placebo and abciximab groups, respectively (p = 0.059). Rates of major blood loss were 79% and 88% in the placebo and abciximab groups, respectively (p = 0.27); transfusions of packed red blood cells or whole blood were administered in 74% and 80% of patients, respectively (p = 0.53). Surgical reexploration for bleeding was required in 3% and 12% of patients, respectively. Death and myocardial infarction tended to occur less frequently among patients who had received abciximab. CONCLUSIONS: Urgent coronary artery bypass grafting operations can be performed without an incremental increase in major hemorrhagic risk among patients on abciximab therapy.

A randomized trial comparing acute normovolemic hemodilution and preoperative autologous blood donation in total hip arthroplasty.

BACKGROUND: The value of acute normovolemic hemodilution (ANH) as compared to preoperative autologous blood donation (PABD) in orthopedic surgery is unknown. Therefore, a prospective, randomized study was conducted to compare these techniques in patients undergoing primary total hip arthroplasty. STUDY DESIGN AND METHODS: ANH patients underwent phlebotomy for up to 3 units, or to a target Hct level of 28 percent after induction of anesthesia. PABD patients were asked to donate up to 3 units before admission. RESULTS: Mean baseline Hct levels were not different in ANH and PABD patients (39. 7 +/- 4.5 vs. 41.8 +/- 3.8%, p = 0.09). No difference was found in allogeneic blood exposure among ANH and PABD cohorts: 4 (17%) of 23 ANH patients received a total of 9 allogeneic blood units, compared to no allogeneic transfusions in the PABD cohort (p = 0.30). Total blood costs associated with ANH were significantly (p<0.05) lower than blood costs associated with PABD ($151 +/- 154 vs. $680 +/- 253, respectively). CONCLUSION: In patients undergoing total hip arthroplasty, ANH is safe, can be considered equivalent to PABD in effectively reducing exposure to allogeneic RBCs, and is less costly than PABD.

Management approaches to platelet-related microvascular bleeding in cardiothoracic surgery.

Patients undergoing cardiac surgery with cardiopulmonary bypass are at increased risk for microvascular bleeding that requires perioperative transfusion of blood components. Platelet-related defects have been shown to be the most important hemostatic abnormality in this setting. The exact association between preoperative use of potent platelet inhibitors and either bleeding or transfusion in patients undergoing cardiac surgical procedures is currently being defined. Laboratory evaluation of platelets and coagulation factors can facilitate the optimal administration of pharmacologic and transfusion-based therapy. However, their turnaround time makes laboratory-based methods impractical for concurrent management of surgical patients, which has led many investigators to study the role of point-of-care coagulation tests in this setting. Use of point-of-care tests of hemostatic function can optimize the management of excessive bleeding and reduce transfusion. Accordingly, point-of-care tests that assess platelet function may also identify patients at risk for acquired, platelet-related bleeding. The ability to reduce the unnecessary use of blood products and to decrease operative time or reexploration rates has important consequences for blood inventory, blood costs, and overall health care costs.

The effect of epsilon-aminocaproic acid on HemoSTATUS and kaolin-activated clotting time measurements.

UNLABELLED: New point-of-care assays have been used to identify patients with heparin resistance (i.e. heparin dose response test; Medtronic Blood Management, Parker, CO) and who have platelet dysfunction (i.e. HemoSTATUS; Medtronic Blood Management). We examined the effect of epsilon-aminocaproic acid on results from these two point-of-care tests in patients undergoing cardiac surgery. Twenty patients scheduled for elective cardiac surgical procedures were enrolled in this prospective study. HemoSTATUS clot ratio (% maximal) values in Channels (Ch) 3-6 (Ch 3: 26 +/- 25, Ch 4: 66 +/- 23, Ch 5: 84 +/- 20, Ch 6: 106 +/- 18) obtained after the IV administration of epsilon-aminocaproic acid were similar to values obtained before the administration of this agent (Ch 3: 26 +/- 20, Ch 4: 69 +/- 23, Ch 5: 86 +/- 19, Ch 6: 109 +/- 14). Slope values (86 +/- 23 s x U(-1) x mL(-1)) and projected heparin concentrations (4 +/- 1 U/mL) obtained before the administration of epsilon-aminocaproic acid were similar to slope values (88 +/- 21 s x U(-1) x mL(-1)) and projected heparin concentrations (4 +/- 1 U/mL) values obtained after administration of this agent. Our data indicate that HemoSTATUS clot ratio values and heparin dose response values are not significantly affected after IV dosing of epsilon-aminocaproic acid. IMPLICATIONS: Values from two activated coagulation time-based test systems used to identify significant heparin resistance or platelet dysfunction after cardiopulmonary bypass were not significantly affected by epsilon-aminocaproic acid administered IV.

Clinical evaluation of a new, point-of-care hemocytometer.

OBJECTIVE: This study was designed to compare results obtained with a new point-of-care hemocytometer with those of two established (point-of-care and laboratory-based) instruments. DESIGN: To compare CBC values between established laboratory-based and point-of-care instruments, measurements were performed on routinely obtained blood specimens for CBC analysis in our institutional laboratory (phase I) and on specimens from cardiac surgical patients before initiation of cardiopulmonary bypass and after discontinuation of cardiopulmonary bypass in phase II. SETTING: Surgical and hospitalized patients at a tertiary care center. PATIENTS: Measurements were obtained by using blood specimens obtained from 141 hospitalized patients from different services (phase I) or from a consecutive series of 204 patients undergoing cardiac operations (phase II). MEASUREMENTS AND MAIN RESULTS: Hemoglobin (HGB), platelet count (PLT), red blood cell count, and white blood cell count (WBC) were measured with two on-site and one laboratory-based instruments. Hematocrit (HCT) was calculated by using measured variables. Linear regression demonstrated good correlations between Ichor and T540 HGB (r2 = .95), HCT (r2 = .95), PLT (r2 = .94), and WBC (r2 = .95) results (n = 408); similarly, good correlations were observed with Coulter STKS HGB (r2 = .92), HCT (r2 = .91), and PLT (r2 = .94) results (n = 141). The relationship between Ichor and Coulter STKS WBC (r2 = .27) was poor; however, when two Ichor-derived outlier values (>50) were excluded, the relationship was very good (r2 = .99). Bias analysis (mean +/- SD) demonstrated similar results between Ichor and T540 HGB (0.003+/-0.5), HCT (-0.21+/-1.5), WBC (0.79+/-1.3), and PLT values (-9.2+/-16.6) as well as STKS HGB (-0.08+/-0.7), HCT (-0.69+/-2.3), WBC (-0.62+/-5.8), and PLT values (-10.2+/-21.4). CONCLUSIONS: The Ichor hemocytometer provides accurate hematologic results that can facilitate rapid quantitative assessment of CBC variables and thus may be clinically useful, especially in critically ill patients.

Anticoagulation monitoring during cardiac surgery: a review of current and emerging techniques.

The literature does not consistently support the importance of anticoagulation monitoring techniques during CPB. This is best reflected by studies that have evaluated the impact of the ACT method on blood loss and transfusion outcomes. Inconsistent findings from studies that evaluated the impact of ACT monitoring may be related to either suboptimal study design (i.e., retrospective, unblinded, nonrandomized) or possibly the diagnostic inprecision of the ACT method used in these studies. There are a small number of well-controlled studies, some of which suggest that bleeding and transfusion outcomes can be improved by refining heparin monitoring techniques, either by sustaining better anticoagulation during CPB or by optimizing protamine doses (i.e., when empiric protocols result in excessive protamine doses). More well-controlled studies are needed to better define the importance of anticoagulation management during CPB.

Anticoagulation and anticoagulation reversal with cardiac surgery involving cardiopulmonary bypass: an update.

Accelerated thrombin generation is central to the development of hemostatic abnormalities during cardiopulmonary bypass (CPB) that are associated with both thromboembolic complications and serious, abnormal bleeding. Thrombin not only converts fibrinogen to fibrin, but also activates platelets and coagulation factors V, VIII, and XI and causes release of von Willebrand factor from vascular endothelium. Thrombin can also downregulate the hemostatic system by inducing formation of platelet inhibitory agents, such as nitric oxide and prostacyclin, and release of tissue plasminogen activator, facilitating activation of protein C, and releasing tissue factor pathway inhibitor. Excessive thrombin activity may also result in substantial consumption of platelets, fibrinogen, and labile coagulation factors and abnormal bleeding. Elevated tissue plasminogen activator levels secondary to activation of the contact system and surgery catalyze the formation of plasmin, which also consumes or internalizes platelet glycoprotein receptors and coagulation factors V, VIII, and fibrinogen. Heparin can reduce the generation of and mediate neutralization of excessive and CPB-associated thrombin activity. Heparin anticoagulation is commonly monitored with the activated clotting time (ACT). However, the ACT may be prolonged by factors other than heparin during CPB, such as hemodilution and hypothermia, and therefore may not accurately reflect the extent of anticoagulation by heparin. Aprotinin, a nonspecific serine protease inhibitor used with CPB, can also prolong celite-based ACT values, rendering it less reliable for monitoring heparin anticoagulation. Therefore, several alternative anticoagulation strategies have been recommended when aprotinin is used, such as a higher celite ACT trigger (>750 seconds), monitoring of whole blood heparin concentrations (eg, >2.7 U/mL), or administration of heparin based on a CPB duration-dependent, fixed-dose regimen. Administration of heparin doses higher than those generally recommended, as guided by predetermined, patient-specific whole blood heparin concentration measurements during bypass, can reduce excessive thrombin-mediated consumption of platelets and coagulation factors as well as post-CPB blood loss and blood component transfusions. New modalities of improving suppression of excess thrombin generation during CPB include use of heparin-bonded CPB circuits, heparin cofactor II or related analogs, supplemental antithrombin III, direct thrombin inhibitors (eg, hirudin, argatroban), and inhibitors of the contact and tissue factor pathways. The safety and efficacy of these approaches remains to be established by additional, appropriately powered, prospective studies.

A randomized trial of acute normovolemic hemodilution compared to preoperative autologous blood donation in total knee arthroplasty.

The value of acute normovolemic hemodilution (ANH) compared to preoperative autologous blood donation (PAD) in elective surgery is controversial. We therefore conducted a prospective, randomized study to compare these techniques in patients undergoing total knee arthroplasty. ANH patients underwent up to 4 units phlebotomy or to a target hematocrit level of 28% after induction of anesthesia. PAD patients were asked to donate 1 (unilateral) or 2 (bilateral, revisions) units before admission. Mean baseline hematocrit levels were not different between ANH and PAD patients (40.6+/-4.1 vs. 38. 4+/-3.4, p = 0.09). Eight (73%) of 11 patients undergoing bilateral revision procedures received a total of 22 allogeneic blood units, whereas only 3 (14%) of 21 patients undergoing primary, unilateral procedures received a total of 3 allogeneic units (p = 0.002). We found no differences in allogeneic blood transfusions between ANH and PAD cohorts for all (n = 32) patients (1.0+/-1.2 vs. 0.6+/-1.4, p = 0.45), for unilateral knee (n = 21) replacement (0.25+/-0.46 vs. 0.08+/-0.28, p = 0.29), or for bilateral/revision (n = 11) procedures (1.9+/-1.3 vs. 2.5+/-1.9, p = 0.53). We conclude that each technique is equally effective in reducing allogeneic blood exposure. Patients undergoing revision or bilateral knee arthroplasties require adjunctive therapy to autologous blood procurement to further reduce allogeneic blood exposure.

Adverse events in platelet apheresis donors: A multivariate analysis in a hospital-based program.

OBJECTIVES: This study was designed to review the incidence of adverse events during nearly 20,000 apheresis procedures over a 4-year period in a hospital-based program. METHODS: Data were obtained from a review of: (1) apheresis adverse event forms (2) hospital or emergency room medical records (3) the databank for donor and procedure-related variables. Adverse events during or after the apheresis procedures were analyzed according to the following categories: (1) complications related to citrate toxicity; (2) hypotensive or vasovagal episodes; (3) complications or symptoms consistent with coronary ischemia; (4) complications related to percutaneous needle insertion, and (5) miscellaneous procedure-related events or nonspecific symptoms. Serious adverse events were categorized as persistent or severe hemodynamic changes as well as other events that required further medical evaluation. RESULTS: Of 19,736 apheresis procedures, 159 (0.81%) were associated with adverse events. In 2,376 first-time donations, 26 (1.09%) developed adverse events compared to 133 (0.77%) of 17,360 repeat procedures (p = 0.10). Seventy (0.35%) of 159 donation-related adverse events involved hemodynamic or citrate-related complications and 73 (0.37%) involved venipuncture-related complications, of which 2 required subsequent neurologic consultation. The remaining 23 (0. 12%) adverse events involved procedure-related, nonspecific complications. Forty-seven (0.24%) of the 19,736 apheresis procedures were associated with serious adverse events (SAEs). Seven of these serious adverse events required admission to an emergency department, and 2 required hospitalization for further evaluation. Multivariate analysis revealed that apheresis machine model, donor gender and weight, the concomitant harvesting of plasma, the frequency of donation, and citrate-related symptoms (e.g. paresthesias) were independently associated with severe hypotensive reactions. CONCLUSIONS: Apheresis procedures have a 150-fold higher incidence of SAEs requiring hospitalization compared to whole blood donation. Identification of donors at risk for complications can facilitate modification of the apheresis procedure in order to reduce the likelihood of adverse events. Although our study did not demonstrate a cause-effect relationship between platelet donation and the development of acute coronary syndromes, underlying cardiovascular disease was detected in 2 donors during or after the apheresis who were otherwise asymptomatic.

Use of point-of-care test in identification of patients who can benefit from desmopressin during cardiac surgery: a randomised controlled trial.

BACKGROUND: Platelet dysfunction is a major cause of excessive microvascular bleeding after cardiac surgery. A new point-of-care test (hemoSTATUS) can identify patients at risk of excessive bleeding. We aimed to find out whether patients who can benefit from desmopressin during cardiac surgery can be identified by this test. METHODS: We enrolled 203 patients scheduled for elective cardiac surgery in a prospective, double-blind, placebo-controlled trial. Patients with abnormal hemoSTATUS clot-ratio results (<60% of maximum in channel 5) after discontinuation of cardiopulmonary bypass were randomly assigned desmopressin (n=50) or placebo (n=51). Patients with normal clot ratios were included in an untreated control group (n=72). FINDINGS: Intraoperative platelet counts and clot ratios were significantly higher in the untreated control group than in the study-drug groups. In intensive care, clot ratios in patients who received desmopressin were similar to those in the untreated control group, despite significantly lower platelet counts, but were lower in the placebo group than in the other two groups (p=0.0001). Compared with the placebo group, patients who received desmopressin had less blood loss in 24 h (mean 624 [SD 209] vs 1028 mL [682] p=0.0004) and required less transfusion of red blood cells (1.1 [022] vs 2.2 U [0.32] p=0.009), platelets (0.1 [0.04] vs 1.9 U [4.5] p=0.0001), and fresh-frozen plasma (0.1 [0.07] vs 0.75 U [0.21] p=0.0008), and had less total blood-donor exposures (1.56 [0.31] vs 5.2 [0.8] p=0.0001). Placebo patients also had substantially higher blood loss and transfusion requirements than untreated control patients. INTERPRETATION: Patients identified with hemoSTATUS as being at increased risk of excessive bleeding after cardiac surgery can benefit from administration of desmopressin. Further studies are, however, needed to confirm these findings as well as to identify the mechanism of action and safety of desmopressin in the clinical setting.

Effects of nicardipine and nitroglycerin on perioperative myocardial ischemia in patients undergoing coronary artery bypass surgery.

Perioperative myocardial ischemic episodes are predictive of adverse cardiac outcomes after coronary artery bypass surgery. We compared the efficacy of continuous infusions of nicardipine (group NIC) and nitroglycerin (group NTG) in reducing the frequency and severity of myocardial ischemic episodes. Patients received either a nicardipine infusion, 0.7 to 1.4 microg/kg/min (n = 30), nitroglycerin infusion, 0.5 to 1 microg/kg/min (n = 30), or neither medication (group C; n = 17) after aortic occlusion clamp release and for 24 hours postoperatively. Myocardial ischemic episodes were considered as ST segment depressions or elevations of 1 mm or greater from baseline, each at J + 60 milliseconds and lasting 1 minute or greater, using a two-channel Holter monitor. Only nicardipine significantly decreased the duration (3.2 +/- 1.2 min/h) and the area under the ST time curve (AUC; 5.7 +/- 15.7 AUC/h) of 1-mm or greater myocardial ischemic episodes compared with group C (17.2 +/- 5.6 min/h and 30.1 +/- 49 AUC/h, respectively) during the intraoperative postbypass period. A trend toward lower frequency, duration, and area under the ST time curve of myocardial ischemic episodes was observed in group NIC compared with group NTG. Cardiac indices and mixed venous oxygen saturations were significantly greater, whereas systemic pressures were less in group NIC compared with group NTG for the same period. These results suggest that nicardipine, but not nitroglycerin, decreased the duration and area under the ST time curve of myocardial ischemic episodes shortly after coronary revascularization. Larger studies are required to verify the efficacy of nicardipine in reducing the severity of myocardial ischemia during cardiac surgery.

Optimal management of bleeding and transfusion in patients undergoing cardiac surgery.

Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) are at increased risk for excessive perioperative blood loss requiring transfusion of blood products. Point-of-care evaluation of platelets, coagulation factors, and fibrinogen can enable physicians to rapidly assess bleeding abnormalities, facilitate the optimal administration of pharmacological and transfusion-based therapy, and also identify patients with surgical bleeding. The ability to reduce the unnecessary use of blood products in this setting has important implications for emerging issues in blood inventory and blood costs. The ability to decrease surgical time, along with exploration rates, has important consequences for health care costs in an increasingly managed health care environment.