Efficacy of platelet transfusion in cardiac surgery.

Massive diffuse bleeding is still a problem in cardiovascular surgery. The first line treatment is platelet concentrate transfusion, although there is still insufficient information regarding efficacy, quantity, and timing. The objective of this prospective cohort study was to find out whether the amount of 4 apheresis platelet concentrates could reduce intraoperative bleeding and improve viscoelasticity and aggregometry. 10 patients were enrolled intraoperatively because of life-threatening diffuse bleeding after cardiopulmonary bypass and received 4 apheresis platelet concentrates back-to-back. The units were given every 5 minutes. After every unit, thromboelastometry, performed by ROTEM®, and aggregometry, performed by Multiplate®, were done together with Hematocrit, Hemoglobin, and Platelet Count. Hematocrit and Hemoglobin showed a statistically significant decrease of 14%, whereas Platelet Count showed a statistically significant increase of 205%. MCE-EXTEM increased statistically significant: 46%. There was no statistically significant increase in both ADP and COL results. Even a series of 4 platelet concentrates did not comprehensively improve both essential components of an adequate hemostasis: viscoelasticity and aggregation. Just the transfusion of platelet concentrates alone did not build a sufficient strategy improving hemostasis and reducing bleeding. A positive effect of surgical packing on stopping the bleeding could be seen.

Viscoelastic testing to assess the effects of rapid fibrinogen concentrate administration after cardiopulmonary bypass: insights from the REPLACE study.

Haemorrhage during and following surgery results in increased morbidity and mortality. Low plasma fibrinogen levels have been associated with increased blood loss and transfusion requirements. Fibrinogen supplementation has been shown to reduce bleeding in coagulopathic patients. This post hoc study evaluated fibrinogen repletion and pharmacokinetic data from the REPLACE study. One hundred and fifty-two adult patients undergoing elective aortic surgery requiring cardiopulmonary bypass (CPB) with defined bleeding of 60-250 g at first 5 min bleeding mass were included in the phase III trial. Patients were randomized to receive either fibrinogen concentrate (FCH) or placebo following CPB removal. Plasma fibrinogen levels and viscoelastic testing parameters (ROTEM-based FIBTEM and EXTEM assays) were measured before, during, and after study treatment administration. A mean dose of 6.3 g FCH was administered in the FCH group, with a median infusion duration of 2 min. Immediately following completion of FCH administration, a rapid increase in plasma fibrinogen levels to near baseline (median change from baseline -0.10 g/l) was seen in the FCH group but not in the placebo group (median change from baseline -1.29 g/l). FCH administration also caused an immediate increase in FIBTEM maximum clot firmness (MCF) to 23 mm and improvements in EXTEM coagulation time and clot formation time by the end of infusion. There was a strong correlation between the plasma fibrinogen level and FIBTEM MCF. Treatment with high doses of FCH with a rapid infusion time resulted in immediate recovery to baseline levels of plasma fibrinogen and viscoelastic testing parameters.

Randomized evaluation of fibrinogen versus placebo in complex cardiovascular surgery: post hoc analysis and interpretation of phase III results.

OBJECTIVES: In a multicentre, randomized-controlled, phase III trial in complex cardiovascular surgery (Randomized Evaluation of Fibrinogen vs Placebo in Complex Cardiovascular Surgery: REPLACE), single-dose human fibrinogen concentrate (FCH) was associated with the transfusion of increased allogeneic blood products (ABPs) versus placebo. Post hoc analyses were performed to identify possible reasons for this result. METHODS: We stratified REPLACE results by adherence to the transfusion algorithm, pretreatment fibrinogen level (≤2 g/l vs >2 g/l) and whether patients were among the first 3 treated at their centre. RESULTS: Patients whose treatment was adherent with the transfusion algorithm [FCH, n = 47 (60.3%); placebo, n = 57 (77.0%); P = 0.036] received smaller quantities of ABPs than those with non-adherent treatment (P < 0.001). Among treatment-adherent patients with pretreatment plasma fibrinogen ≤2 g/l, greater reduction in 5-min bleeding mass was seen with FCH versus placebo (median -22.5 g vs -15.5 g; P = 0.071). Considering patients with the above conditions and not among the first 3 treated at their centre (FCH, n = 15; placebo, n = 22), FCH was associated with trends towards reduced transfusion of ABPs (median 2.0 vs 4.0 units; P = 0.573) and greater reduction in 5-min bleeding mass (median -21.0 g vs -9.5 g; P = 0.173). Differences from a preceding single-centre phase II study with positive outcomes included more patients with pretreatment fibrinogen >2 g/l and fewer patients undergoing thoracoabdominal aortic aneurysm repair. CONCLUSIONS: None of the patient stratifications provided a clear explanation for the lack of efficacy seen for FCH in the REPLACE trial versus the positive phase II outcomes. However, together, the 3 factors demonstrated trends favouring FCH. Less familiarity with the protocol and procedures and unavoidable differences in the study populations may explain the differences seen between the phase II study and REPLACE. CLINICAL TRIAL REGISTRATION: NCT01475669 https://clinicaltrials.gov/ct2/show/NCT01475669; EudraCT trial no: 2011-002685-20.

The improved quality of postoperative analgesia after intrathecal morphine does not result in improved recovery and quality of life in the first 6 months after orthopedic surgery: a randomized controlled pilot study.

OBJECTIVE: In orthopedic surgery, it is well known that the use of intrathecal morphine (ITM) leads to an improved quality of postoperative analgesia. Little is known how this improved analgesia affects the long-term course after surgery. STUDY DESIGN: A randomized, double-blind trial. SETTING: Academic medical center. SUBJECTS: Forty-nine patients undergoing total hip or knee replacement surgery in spinal anesthesia. METHODS: Patients were randomly assigned to receive either 0.1 mg (n=16) or 0.2 mg (n=16) morphine sulfate intrathecally or physiological saline (n=17) added to 3 mL 0.5% isobaric bupivacaine for spinal anesthesia. As a function of the quality of the short-term postoperative analgesia, the effect on recovery and quality of life was evaluated at various time points up to 26 weeks after surgery. RESULTS: In both ITM groups, the additionally required postoperative systemic morphine dose was significantly reduced compared with the placebo group (P=0.004). One week after operation, patients with ITM reported significantly less pain at rest (P=0.01) compared to the placebo group. At discharge, in comparison with the 0.1 mg ITM and placebo group, the 0.2 mg ITM group showed a higher degree of impairment regarding pain, stiffness, and physical function of the respective joint (P=0.02). Over the further follow-up period of 6 months after surgery, recovery and the quality of life did not differ significantly between the three study groups (P>0.2). CONCLUSION: Morphine (0.1 mg) as adjunct to 0.5% bupivacaine for spinal anesthesia is effective to produce a pronounced postoperative analgesia with a beneficial analgesic effect up to 1 week after surgery. With this study design, the different quality of postoperative analgesia had no effect on quality of life and recovery in patients over the 6-month follow-up period. In the medium term, ITM may induce hyperalgesic effects.

Deep Neuromuscular Blockade Improves Laparoscopic Surgical Conditions: A Randomized, Controlled Study.

INTRODUCTION: Sustained deep neuromuscular blockade (NMB) during laparoscopic surgery may facilitate optimal surgical conditions. This exploratory study assessed whether deep NMB improves surgical conditions and, in doing so, allows use of lower insufflation pressures during laparoscopic cholecystectomy. We further assessed whether use of low insufflation pressure improves patient pain scores after surgery. METHODS: This randomized, controlled, blinded study (NCT01728584) compared use of deep (1-2 post-tetanic-counts) or moderate (train-of-four ratio 10%) NMB, and lower (8 mmHg) or higher (12 mmHg; 'standard') insufflation pressure in a 2 × 2 factorial design. Primary endpoint was surgeon's overall satisfaction with surgical conditions, rated at end of surgery using an 11-point numerical scale. Post-operative pain scores were also evaluated. Data were analyzed using analysis of covariance. RESULTS: Of 127 randomized patients, 120 had evaluable data for the primary endpoint. Surgeon's score of overall satisfaction with surgical conditions was significantly higher with deep versus moderate NMB indicated by a least-square mean difference of 1.1 points (95% confidence interval 0.1-2.0; P = 0.026). Furthermore, strong evidence of an effect was observed for standard versus low pressure: least-square mean difference of 3.0 points (95% confidence interval 2.1-4.0; P < 0.001). No significant difference was observed in average pain scores within 24 h post-surgery for low versus standard pressure [0.17 (95% confidence interval -0.67 to +0.33); P = 0.494]. CONCLUSIONS: Although associated with significantly improved surgical conditions, deep NMB alone was insufficient to promote use of low insufflation pressure during laparoscopic cholecystectomy. Furthermore, low insufflation pressure did not result in reduced pain, compared with standard pressure. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01728584. FUNDING: Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Intrathecal dexmedetomidine as adjuvant to ropivacaine in hysteroscopic surgery: a prospective, randomized control study.

BACKGROUND: To compare the effects and side effects of intrathecal ropivacaine supplemented with dexmedetomidine and fentanyl in hysteroscopic surgery under spinal anesthesia. METHODS: Female patients (n = 108) undergoing operative hysteroscopic procedures under spinal anesthesia were randomly allocated to the following groups for subarachnoid drug delivery: R (n = 36) received 7.5 mg ropivacaine; RD (n = 36) received 7.5 mg ropivacaine plus 5 µg dexmedetomidine; RF (n = 36) received 7.5 mg ropivacaine plus 15 µg fentanyl. The onset and regression time of sensory and motor blockade, together with the postoperative analgesia and side effects were recorded. RESULTS: There was no significant difference as to sensory and motor onset time between groups. RD had significantly longer sensory and motor blockade time than RF and R. The mean time of sensory regression to the S1 segment was 191.25 ± 40.24 minutes in RD, 149.86 ± 37.46 minutes in RF, and 139.44 ± 38.97 minutes in R (RD vs. R and RD vs. RF, p < 0.001). The regression time of motor blockade to Bromage score 0 was 146.31 ± 40.72 minutes in RD, 80.28 ± 41.18 minutes in RF, and 84.94 ± 26.11 minutes in R (RD vs. R and RD vs. RF, p < 0.001). RD produced similar analgesia effect with RF, (2 hour visual analog scale (VAS) was 0.00 ± 0.00 and 0.31 ± 0.79, respectively) better than the R group (1.35 ± 1.65, p < 0.005). No pruritus occurred in the RD group, while the rate was 36.1% in the RF group. However, the RD group produced milder postsurgical hypotension (RD vs. R and RD vs. RF, p < 0.05). CONCLUSION: Intrathecal dexmedetomidine (5 µg) produced prolonged motor and sensory blockade and less pruritus compared with fentanyl (15 µg) in hysteroscopic surgery.

Randomized, double-blinded, placebo-controlled trial of fibrinogen concentrate supplementation after complex cardiac surgery.

BACKGROUND: Postoperative bleeding after heart operations is still a common finding, leading to allogeneic blood products transfusion. Fibrinogen and coagulation factors deficiency are possible determinants of bleeding. The experimental hypothesis of this study is that a first-line fibrinogen supplementation avoids the need for fresh frozen plasma (FFP) and reduces the need for any kind of transfusions. METHODS AND RESULTS: This was a single-center, prospective, randomized, placebo-controlled, double-blinded study. One-hundred sixteen patients undergoing heart surgery with an expected cardiopulmonary bypass duration >90 minutes were admitted to the study. Patients in the treatment arm received fibrinogen concentrate after protamine administration; patients in the control arm received saline solution. In case of ongoing bleeding, patients in the treatment arm could receive prothrombin complex concentrates (PCCs) and those in the control arm saline solution. The primary endpoint was avoidance of any allogeneic blood product. Patients in the treatment arm had a significantly lower rate of any allogeneic blood products transfusion (odds ratio, 0.40; 95% confidence interval, 0.19 to 0.84, P=0.015). The total amount of packed red cells and FFP units transfused was significantly lower in the treatment arm. Postoperative bleeding was significantly (P=0.042) less in the treatment arm (median, 300 mL; interquartile range, 200 to 400 mL) than in the control arm (median, 355 mL; interquartile range, 250 to 600 mL). CONCLUSIONS: Fibrinogen concentrate limits postoperative bleeding after complex heart surgery, leading to a significant reduction in allogeneic blood products transfusions. No safety issues were raised. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01471730.

Fibrinogen concentrate as first-line therapy in aortic surgery reduces transfusion requirements in patients with platelet counts over or under 100×10(9)/L.

BACKGROUND: Administration of fibrinogen concentrate, targeting improved maximum clot firmness (MCF) of the thromboelastometric fibrin-based clot quality test (FIBTEM) is effective as first-line haemostatic therapy in aortic surgery. We performed a post-hoc analysis of data from a randomised, placebo-controlled trial of fibrinogen concentrate, to investigate whether fibrinogen concentrate reduced transfusion requirements for patients with platelet counts over or under 100×10(9)/L. MATERIAL AND METHODS: Aortic surgery patients with coagulopathic bleeding after cardiopulmonary bypass were randomised to receive either fibrinogen concentrate (n=29) or placebo (n=32). Platelet count was measured upon removal of the aortic clamp, and coagulation and haematology parameters were measured peri-operatively. Transfusion of allogeneic blood components was recorded and compared between groups. RESULTS: After cardiopulmonary bypass, haemostatic and coagulation parameters worsened in all groups; plasma fibrinogen level (determined by the Clauss method) decreased by 43-58%, platelet count by 53-64%, FIBTEM maximum clot firmness (MCF) by 38-49%, FIBTEM maximum clot elasticity (MCE) by 43-54%, extrinsically activated test (EXTEM) MCF by 11-22%, EXTEM MCE by 25-41% and the platelet component of the clot by 23-39%. Treatment with fibrinogen concentrate (mean dose 7-9 g in the 4 groups) significantly reduced post-operative allogeneic blood component transfusion requirements when compared to placebo both for patients with a platelet count≥100×10(9)/L and for patients with a platelet count<100×10(9)/L. DISCUSSION: FIBTEM-guided administration of fibrinogen concentrate reduced transfusion requirements when used as a first-line haemostatic therapy during aortic surgery in patients with platelet counts over or under 100×10(9)/L.

Effect of reversal of neuromuscular blockade with sugammadex versus usual care on bleeding risk in a randomized study of surgical patients.

BACKGROUND: Previous studies show a prolongation of activated partial thromboplastin time and prothrombin time in healthy volunteers after treatment with sugammadex. The authors investigated the effect of sugammadex on postsurgical bleeding and coagulation variables. METHODS: This randomized, double-blind trial enrolled patients receiving thromboprophylaxis and undergoing hip or knee joint replacement or hip fracture surgery. Patients received sugammadex 4 mg/kg or usual care (neostigmine or spontaneous recovery) for reversal of rocuronium- or vecuronium-induced neuromuscular blockade. The Cochran-Mantel-Haenszel method, stratified by thromboprophylaxis and renal status, was used to estimate relative risk and 95% confidence interval (CI) of bleeding events with sugammadex versus usual care. Safety was further evaluated by prespecified endpoints and adverse event reporting. RESULTS: Of 1,198 patients randomized, 1,184 were treated (sugammadex n = 596, usual care n = 588). Bleeding events within 24 h (classified by an independent, blinded Adjudication Committee) were reported in 17 (2.9%) sugammadex and 24 (4.1%) usual care patients (relative risk [95% CI], 0.70 [0.38 to 1.29]). Compared with usual care, increases of 5.5% in activated partial thromboplastin time (P < 0.001) and 3.0% in prothrombin time (P < 0.001) from baseline with sugammadex occurred 10 min after administration and resolved within 60 min. There were no significant differences between sugammadex and usual care for other blood loss measures (transfusion, 24-h drain volume, drop in hemoglobin, and anemia), or risk of venous thromboembolism, and no cases of anaphylaxis. CONCLUSION: Sugammadex produced limited, transient (<1 h) increases in activated partial thromboplastin time and prothrombin time but was not associated with increased risk of bleeding versus usual care.

Management of hemorrhage in cardiothoracic surgery.

Bleeding is an important issue in cardiothoracic surgery, and about 20% of all blood products are transfused in this clinical setting worldwide. Transfusion practices, however, are highly variable among different hospitals and more than 25% of allogeneic blood transfusions have been considered inappropriate. Furthermore, both bleeding and allogeneic blood transfusion are associated with increased morbidity, mortality, and hospital costs. In the past decades, several attempts have been made to find a universal hemostatic agent to ensure hemostasis during and after cardiothoracic surgery. Most drugs studied in this context have either failed to reduce bleeding and transfusion requirements or were associated with severe adverse events, such as acute renal failure or thrombotic/thromboembolic events and, in some cases, increased mortality. Therefore, an individualized goal-directed hemostatic therapy ("theranostic" approach) seems to be more appropriate to stop bleeding in this complex clinical setting. The use of point-of-care (POC) transfusion and coagulation management algorithms guided by viscoelastic tests such as thromboelastometry/thromboelastography in combination with POC platelet function tests such as whole blood impedance aggregometry, and based on first-line therapy with fibrinogen and prothrombin complex concentrate have been associated with reduced allogeneic blood transfusion requirements, reduced incidence of thrombotic/thromboembolic and transfusion-related adverse events, and improved outcomes in cardiac surgery. This article reviews the current literature dealing with the management of hemorrhage in cardiothoracic surgery based on POC diagnostics and with specific coagulation factor concentrates and its impact on transfusion requirements and patients' outcomes.

Fibrinogen concentrate reduces intraoperative bleeding when used as first-line hemostatic therapy during major aortic replacement surgery: results from a randomized, placebo-controlled trial.

OBJECTIVES: We assessed whether fibrinogen concentrate as targeted first-line hemostatic therapy was more effective than placebo or a standardized transfusion algorithm in controlling coagulopathic bleeding in patients undergoing major aortic surgery. METHODS: In this single-center, prospective, double-blind study, adults undergoing elective thoracic or thoracoabdominal aortic replacement surgery involving cardiopulmonary bypass were randomized to intraoperative fibrinogen concentrate (n = 29) or placebo (n = 32). Study medication was given if patients had clinically relevant coagulopathic bleeding, measured by 5-minute bleeding mass, after cardiopulmonary bypass removal, protamine administration, and surgical hemostasis. Fibrinogen concentrate dosing was individualized using the thromboelastometric FIBTEM test. If bleeding continued, a standardized transfusion algorithm was followed. In the placebo group, all 32 patients received 1 transfusion cycle of fresh-frozen plasma/platelets, and 30 patients required a second transfusion cycle; none of these patients received any other procoagulant therapy. Change in bleeding rate after treatment was compared using t tests. RESULTS: Mean change in bleeding rate after fibrinogen concentrate was -48.3 g/5 min, compared with 0.4 g/5 min after placebo (P < .001), -16.1 g/5 min after 1 transfusion cycle (fresh-frozen plasma or platelets; P = .003), and -28.0 g/5 min after 2 transfusion cycles (fresh-frozen plasma and platelets; P = .11). Reductions in bleeding rate were greater for patients with higher bleeding rates before treatment, especially with fibrinogen concentrate. CONCLUSIONS: FIBTEM-guided intraoperative hemostatic therapy with fibrinogen concentrate is more effective than placebo in controlling coagulopathic bleeding during major aortic replacement surgery. Fibrinogen concentrate is also more effective than 1 cycle of fresh-frozen plasma/platelets and is more rapid than--and at least as effective as--2 cycles of fresh-frozen plasma/platelets.

Effects of fibrinogen concentrate as first-line therapy during major aortic replacement surgery: a randomized, placebo-controlled trial.

BACKGROUND: Fibrinogen is suggested to play an important role in managing major bleeding. However, clinical evidence regarding the effect of fibrinogen concentrate (derived from human plasma) on transfusion is limited. The authors assessed whether fibrinogen concentrate can reduce blood transfusion when given as intraoperative, targeted, first-line hemostatic therapy in bleeding patients undergoing aortic replacement surgery. METHODS: In this single-center, prospective, placebo-controlled, double-blind study, patients aged 18 yr or older undergoing elective thoracic or thoracoabdominal aortic replacement surgery involving cardiopulmonary bypass were randomized to fibrinogen concentrate or placebo, administered intraoperatively. Study medication was given if patients had clinically relevant coagulopathic bleeding immediately after removal from cardiopulmonary bypass and completion of surgical hemostasis. Dosing was individualized using the fibrin-based thromboelastometry test. If bleeding continued, a standardized transfusion protocol was followed. RESULTS: Twenty-nine patients in the fibrinogen concentrate group and 32 patients in the placebo group were eligible for the efficacy analysis. During the first 24 h after the administration of study medication, patients in the fibrinogen concentrate group received fewer allogeneic blood components than did patients in the placebo group (median, 2 vs. 13 U; P < 0.001; primary endpoint). Total avoidance of transfusion was achieved in 13 (45%) of 29 patients in the fibrinogen concentrate group, whereas 32 (100%) of 32 patients in the placebo group received transfusion (P < 0.001). There was no observed safety concern with using fibrinogen concentrate during aortic surgery. CONCLUSIONS: Hemostatic therapy with fibrinogen concentrate in patients undergoing aortic surgery significantly reduced the transfusion of allogeneic blood products. Larger multicenter studies are necessary to confirm the role of fibrinogen concentrate in the management of perioperative bleeding in patients with life-threatening coagulopathy.

Effect of haematocrit on fibrin-based clot firmness in the FIBTEM test.

BACKGROUND: Point-of-care thromboelastometry (ROTEM(®)) can be used to assess coagulation in whole blood. In the ROTEM(®) FIBTEM test, cytochalasin D eliminates the contribution of platelets to the whole blood clot; hence, only the remaining elements, including fibrinogen/fibrin, red blood cells and factor XIII, contribute to clot strength. We investigated the relationships between FIBTEM maximum clot firmness (MCF), whole blood fibrinogen concentration and plasma fibrinogen concentration to determine the impact of haematocrit on these parameters during cardiac surgery. MATERIALS AND METHODS: The relationships between FIBTEM MCF and both whole blood fibrinogen concentration and plasma fibrinogen concentration (Clauss assay) were evaluated pre-operatively and after cardiopulmonary bypass/protamine administration in haematocrit-based subgroups. RESULTS: The study included 157 patients. The correlation coefficient rho between FIBTEM MCF and plasma fibrinogen concentration was 0.68 at baseline and 0.70 after protamine, while that between FIBTEM MCF and whole blood fibrinogen concentration was 0.74 at baseline and 0.72 after protamine (all P <0.001). In subgroup analyses based on haematocrit levels, pre-operative FIBTEM MCF and whole blood fibrinogen concentration were both significantly higher (P <0.05) for the lowest haematocrit subgroup, but plasma fibrinogen concentration was similar in all groups. After protamine, no significant differences were observed between the lowest haematocrit group and the other groups for any of the three parameters. CONCLUSIONS: The effect of haematocrit on blood clotting is not reflected by plasma fibrinogen concentration, in contrast to FIBTEM MCF which incorporates the contribution of haematocrit to whole blood clot firmness. This effect does, however, appear to be negligible in haemodiluted patients.

Haemostatic therapy in coronary artery bypass graft patients with decreased platelet function: comparison of fibrinogen concentrate with allogeneic blood products.

BACKGROUND: Patients undergoing coronary artery bypass grafting (CABG) are at risk of postoperative bleeding because of decreased platelet function and cardiopulmonary bypass (CPB)-induced haemostatic impairment. Fibrinogen concentration decreases by 34-42% of the preoperative level by the end of CPB. An inverse relationship between perioperative plasma fibrinogen levels and postoperative bleeding has been reported in CABG patients. Administration of fibrinogen concentrate after weaning from CPB in patients with diffuse microvascular bleeding may help promote haemostasis. We compared patient outcomes following fibrinogen concentrate administration or transfusion of allogeneics in CABG patients with decreased platelet function. METHODS: Thirty-eight patients with decreased preoperative platelet function in Multiplate aggregometry were included. Patients with bleeding after CPB received either fibrinogen concentrate (guided by the measurement of fibrin clot quality using the FIBTEM thromboelastometric test) or allogeneics. RESULTS: Twenty-nine of 38 patients received haemostatic therapy (bleeding + fibrinogen group, n = 10; bleeding + allogeneics group, n = 19). Total transfusion (median (interquartile range)) was significantly lower in the bleeding + fibrinogen group (0 (0, 3.8) units), compared with the bleeding + allogeneics group (6 (5, 8) units, p = 0.0073). Bolus administration of fibrinogen concentrate increased FIBTEM maximum clot firmness from 10.5 (9.3, 11) mm after CPB to 20.5 (20, 21.8) mm at the end of surgery. Postoperative outcomes were similar in both groups. No treatment-related complications were observed after fibrinogen concentrate. CONCLUSIONS: In CABG patients with bleeding after CPB, FIBTEM-guided administration of fibrinogen concentrate resulted in overall decreased transfusion, compared with haemostatic therapy with allogeneics. Fibrinogen concentrate administration increased the fibrin clot quality and helped achieve haemostasis.

Platelet function following trauma. A multiple electrode aggregometry study.

Platelets play a central role in coagulation. Currently, information on platelet function following trauma is limited. We performed a retrospective analysis of patients admitted to the emergency room (ER) at the AUVA Trauma Centre, Salzburg, after sustaining traumatic injury. Immediately after admission to the ER, blood was drawn for blood cell counts, standard coagulation tests, and platelet function testing. Platelet function was assessed by multiplate electrode aggregometry (MEA) using adenosine diphosphate (ADPtest), collagen (COLtest) and thrombin receptor activating peptide-6 (TRAPtest) as activators. The thromboelastometric platelet component, measuring the contribution of platelets to the elasticity of the whole-blood clot, was assessed using the ROTEM device. The study included 163 patients, 79.7% were male, and the median age was 43 years. The median injury severity score was 18. Twenty patients (12.3%) died. Median platelet count was significantly lower among non-survivors than survivors (181,000/µl vs. 212,000/µl; p=0.01). Although platelet function defects were relatively minor, significant differences between survivors and non-survivors were observed in the ADPtest (94 vs. 79 U; p=0.0019), TRAPtest (136 vs. 115 U; p<0.0001), and platelet component (134 vs.103 MCEEXTEM - MCEFIBTEM; p=0.0012). Aggregometry values below the normal range for ADPtest and TRAPtest were significantly more frequent in non-survivors than in survivors (p=0.0017 and p=0.0002, respectively). Minor decreases in platelet function upon admission to the ER were a sign of coagulopathy accompanying increased mortality in patients with trauma. Further studies are warranted to confirm these results and investigate the role of platelet function in trauma haemostatic management.

A comparison of fibrinogen measurement methods with fibrin clot elasticity assessed by thromboelastometry, before and after administration of fibrinogen concentrate in cardiac surgery patients.

BACKGROUND: Fibrinogen concentrate administration can be guided by measuring fibrinogen concentration or quality of the fibrin-based clot. This study compared different fibrinogen concentration measurement methods with maximum clot firmness (MCF) of the fibrin clot, assessed by thromboelastometry (FIBTEM), in 33 cardiovascular surgery patients receiving fibrinogen concentrate for hemostatic therapy. STUDY DESIGN AND METHODS: Blood samples were collected after cardiopulmonary bypass (CPB) and after fibrinogen concentrate administration. FIBTEM MCF was measured using a rotational thromboelastometry device (ROTEM, Tem International). Fibrinogen concentration was measured using photo-optical (CA-7000, Siemens Healthcare Diagnostics), mechanical (KC-10 steel ball, Schnitger and Gross hook, Amelung GmbH), and electromechanical (STA-R, Diagnostica Stago) coagulometers. Assessments included agreement between fibrinogen concentration measurements and correlations between fibrinogen concentration and FIBTEM MCF. RESULTS: After CPB, correlations were significant (p < 0.001) between FIBTEM MCF and fibrinogen concentration determined by steel ball (r = 0.71), hook (r = 0.73), STA-R (r = 0.81), and CA-7000 (r = 0.82) coagulometers. After fibrinogen concentrate administration, agreement between fibrinogen measurement methods was severely impaired, and correlations with FIBTEM MCF were 0.39 (steel ball), 0.33 (hook), 0.59 (STA-R), and 0.33 (CA-7000). CONCLUSION: Agreement between fibrinogen concentration measurement methods decreased considerably after fibrinogen concentrate administration. All methods correlated acceptably with FIBTEM MCF at the end of CPB, but not after hemostatic therapy. Further investigation is needed to explain these findings.

Fibrin formation is more impaired than thrombin generation and platelets immediately following cardiac surgery.

INTRODUCTION: Cardiac surgery performed on cardio-pulmonary bypass (CPB) may be complicated by coagulopathy and bleeding. This prospective observational study investigated the CPB-induced changes in thrombin generation, fibrin formation, and in the platelet component of the whole blood clot elasticity. The effects of haemostatic therapy with fresh frozen plasma (FFP) and platelet concentrate on these parameters were also evaluated. MATERIALS AND METHODS: In 90 cardiac surgery patients, thrombin generation was measured using the calibrated automated thrombogram, fibrin formation was assessed as the maximum clot elasticity of the fibrin-based clot in the thromboelastometry FIBTEM test (MCE(FIBTEM)), and the platelet component was defined as the difference in maximum elasticity between the whole blood clot obtained through extrinsic activation and the fibrin-based clot (MCE(EXTEM)-MCE(FIBTEM)). Blood samples were collected before surgery, immediately after CPB, and after administration of FFP or FFP and platelet concentrate. RESULTS: Following CPB, the endogenous thrombin potential decreased to 93%, from median 1485 (interquartile range 1207, 1777) to 1382 (1190, 1533) nM*min (P>0.05), MCE(FIBTEM) decreased to 62%, from 21 (19, 29) to 14 (12, 19) (P<0.001), and the platelet component to 73%, from 139 (119, 174) to 101 (87, 121) (P<0.001). Administration of 11 (10, 13) ml per kg of bodyweight (ml/kgbw) FFP (40 patients), or of 13 (10, 18) ml/kgbw FFP and 7 (5, 9) ml/kgbw platelet concentrate (18 patients) brought no statistically significant changes in these parameters. CONCLUSIONS: Fibrin formation is more impaired than thrombin generation and the platelet component of the whole blood clot immediately after cardiopulmonary bypass.

Fibrinogen concentrate in the treatment of severe bleeding after aortic aneurysm graft surgery.

Aortic aneurysm graft surgery involving cardiopulmonary bypass is often associated with substantial coagulopathic perioperative bleeding, requiring hemostatic intervention with allogeneic blood products, such as fresh frozen plasma, platelet concentrate, and red blood cells. We conducted a pilot study to determine the effects of fibrinogen concentrate in patients with microvascular bleeding during aortic valve surgery with ascending aorta replacement. Dosing of fibrinogen concentrate was individualized based on thromboelastometry. First-line therapy with fibrinogen concentrate reduced the need for allogeneic blood product support, including transfusions of fresh frozen plasma, platelet concentrate, and red blood cells. Similar results were seen in a second cohort study conducted in patients undergoing thoraco-abdominal aortic aneurysm surgery: patients who received fibrinogen concentrate required significantly less allogeneic blood product support following surgery. These results prompted the initiation of a randomized placebo-controlled trial in patients undergoing thoraco-abdominal aortic aneurysm surgery, aortic valve surgery with ascending aorta replacement, or aortic arch surgery. Results are expected to be published soon. Larger, multicenter studies are needed to determine the exact role of fibrinogen concentrate in the management of perioperative bleeding following cardiac surgery and cardiopulmonary bypass.

Platelet concentrates transfusion in cardiac surgery in relation to preoperative point-of-care assessment of platelet adhesion and aggregation.

Platelet dysfunction is an important cause of bleeding early after cardiac surgery. Whole-blood multiple electrode aggregometry (MEA), investigating the adhesion and aggregation of activated platelets onto metal electrodes, has shown correlations with platelet concentrates transfusion in this setting. Platelet activity in vivo is dependent on shear stress, an aspect that cannot be investigated with MEA, but with the cone and plate(let) analyzer (CPA) Impact-R that measures the interaction of platelets and von Willebrand factor (vWF) in whole blood under shear. We hypothesized that preoperative CPA may show better correlation with platelet concentrates transfusion post-cardiac surgery than MEA, since it is dependent on both platelet activity and platelet interaction with vWF multimers. Blood was obtained preoperatively from 30 patients undergoing aorto-coronary bypass (ACB) and 20 patients with aortic valve (AV) surgery. MEA was performed in hirudin-anticoagulated blood. The Impact-R analyses were performed in blood anticoagulated with hirudin, heparin or the standard anticoagulant citrate. For the light microscopy images obtained, the parameter surface coverage (SC) was calculated. Preoperative Impact-R results were abnormally decreased in AV patients and significantly lower than in ACB patients. For the Impact-R analysis performed in citrated blood, no correlation with platelet concentrates transfusion was observed. In contrast, MEA was comparable between the groups and correlated significantly with intraoperative platelet concentrates transfusion in both groups (rho between -0.47 and -0.62, p < 0.05). Multiple electrode aggregometry appeared more useful and easier to apply than CPA for preoperatively identifying patients with platelet concentrates transfusion in cardiac surgery.

Comparative assessment of coagulation changes induced by two different types of heart-lung machine.

The cardiopulmonary bypass (CPB) used in heart surgery has a deleterious effect on hemostasis. The aim of our study was to assess by means of standard laboratory and point-of-care methods changes induced by CPB in coagulation parameters, particularly in platelet function, and to determine whether these changes differ depending on the type of heart-lung machine (HLM) used: minimal extracorporeal circulation system (MECC) and standard HLM. The study enrolled 88 patients scheduled for coronary artery bypass surgery performed on pump. Forty-four interventions were performed with MECC and 44 with standard HLM. Blood was sampled preoperatively, after 30 min on CPB, after weaning from CPB, and 24 h postoperatively. Coagulation and platelet function were assessed using multiple electrode aggregometry (MEA), rotation thromboelastometry, as well as standard laboratory tests. Rotation thromboelastometry and standard laboratory reflected significantly impaired hemostasis after weaning from CPB but no significant differences between the two groups at different time points. Aggregation decreased significantly in both groups as early as 30 min after the institution of CPB (P < 0.05, Mann-Whitney U-test) and recovered within the first 24 h postoperatively, without reaching the preoperative level. Intraoperatively, aggregometry values reflected a significantly more severe reduction of platelet function in standard HLM group than in the MECC group (P < 0.01, ProcMixed test). Our findings suggest that MEA and thromboelastometry reflect impairment of coagulation in cardiac surgery performed on different types of HLM and that platelet function is less affected by MECC than by standard HLM.