Rao Saleem

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.

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

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 &mgr;g/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 (r2 = 0.83) linear relationships between ACT values and r-hirudin concentrations (≤4 &mgr;g/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 &mgr;g/mL. In patient specimens mixed with normal plasma (Phase II), ACT/hirudin relationships (i.e., hirudin/ACT slope values obtained with hirudin concentration ≤4 &mgr;g/mL) in the post-CPB period (0.022 ± 0.004 &mgr;g · mL−1 · s−1) were similar (P = 0.47) to those (0.019 ± 0.004 &mgr;g · 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, r2 = 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 &mgr;g/mL. Plasma-modified ACT may be useful in monitoring hirudin anticoagulation during CPB.

Monitoring Hirudin Anticoagulation in Two Patients Undergoing Cardiac Surgery with a Plasma-modified Act Method

HEPARIN-INDUCED thrombocytopenia (HIT) is an immunologically-mediated reaction to unfractionated heparin that can result in life-threatening thrombotic complications. When patients with a history of HIT present for cardiac surgery, anticoagulation for cardiopulmonary bypass (CPB) can be challenging. Recombinant hirudin (r-hirudin) has been reported as a feasible alternative for anticoagulation. 1-8 R-hirudin is a potent direct thrombin inhibitor that works independently of antithrombin-III, offers a rapid onset of anticoagulation, and has a relatively short half-life (60-90 min) in patients with normal renal function. 9 The ability to rapidly and reliably monitor intraoperative levels of r-hirudin anticoagulation, however, has been problematic. The levels of r-hirudin recommended for anticoagulation during CPB (3.5-4.5 μg/ml) 10 exceed those that can be effectively monitored with either the partial thromboplastin time or activated clotting time. 11 The authors described a plasma-modified kaolin-activated clotting time (PM-ACT) assay as a new point-of-care monitoring tool for r-hirudin anticoagulation has been previously described. 12 This assay, accomplished by mixing patient whole blood samples with an equal volume of citrated commercial normal plasma, extends the ACT monitoring range by correcting for hemodilution of coagulation factors and diluting r-hirudin plasma concentrations. The authors present two cases where the PM-ACT was used to monitor r-hirudin anticoagulation during cardiac surgery, and describe the potential for significant perioperative bleeding complications.

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.

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

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 · U−1 · 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 · U−1 · 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.