Hirudin versus citrate as an anticoagulant for ROTEM platelet whole blood impedance aggregometry in thrombocytopenic patients.

Citrate is widely used as an anticoagulant for platelet function tests (PFTs). Due to an intrinsic inhibitory effect of citrate on platelet function, hirudin is used as an alternative. However, studies comparing the effect of these anticoagulants on rotational thromboelastometry (ROTEM) platelet whole blood impedance aggregometry in thrombocytopenic patients are scant. Cross-sectional study was done in 105 patients who entered the critical phase of Dengue hemorrhagic fever with plasma leakage and severe thrombocytopenia (<100 × 109/L). Samples were collected on two consecutive days and considered as a combined data set for analysis, out of which 200 have been included in the data analysis. Platelet count was used from routine full blood count. ROTEM platelet used TRAPTEM assay, which was performed with 3.2% sodium citrate and 525 ATU/ml hirudin anticoagulated blood. Means of all the TRAPTEM parameters were significantly higher in hirudin, compared to citrate samples (p < .05). Significantly higher overall platelet aggregation was observed in hirudinized samples with a significant mean difference (p < .05) compared to citrate in each quartile of platelet count. Higher platelet aggregation was observed with hirudin compared to citrate in ROTEM platelet whole blood impedance aggregometry in thrombocytopenic patients elaborating the importance of using hirudin anticoagulation in PFTs, particularly in patients with severe thrombocytopenia.

Citrate is the most commonly used anticoagulant for coagulation studies including rotational thromboelastometry (ROTEM).Hirudin is an alternative option to be used as an anticoagulant for PFTs because of the inhibitory effect of citrate on platelet function.One study (Nissen et al. (2020)) reported higher precision and platelet aggregation with hirudinized blood of healthy individuals, over citrate using ROTEM platelet.However, none of the studies were performed in patients in actual clinical context.We evaluated the potential benefit of using hirudin anticoagulated blood over citrate in thrombocytopenic patients due to Dengue hemorrhagic fever using ROTEM platelet.We observed higher platelet aggregation with hirudin compared to citrate suggesting the importance of using hirudin anticoagulation in PFTs, particularly in patients with severe thrombocytopenia.

Rotational thromboelastometry in critical phase of dengue infection: Association with bleeding.

Background: The critical phase of dengue carries a high risk of bleeding. Associations of coagulation test parameters and the risk of bleeding in the critical phase is unclear. This study examines the association of rotational thromboelastometry (ROTEM delta and ROTEM platelet) with bleeding risk of patients with dengue in the critical phase. Methods: A total of 105 patients with confirmed dengue in the critical phase were recruited, with two subsequent prospective time point analyses of ROTEM parameters and platelet count within 24 and 48 hours from the onset of the critical phase. Conventional coagulation tests were performed only at the initial time point. Results: Twenty of 105 patients developed bleeding after onset of the critical phase. Within the first 24 hours of critical-phase onset, platelet count, coagulation tests, and ROTEM delta were unable to differentiate patients with bleeding manifestations from those without (P < .05). Area under the curve of thrombin receptor activating peptide-6 assay of ROTEM platelet (TRAPTEM) discriminated patients with bleeding manifestations from those without, at a cutoff value of <12.5 Ω*min at a sensitivity and specificity of 73.7%, and 60.2%. In patients who developed bleeding, the maximum lysis of extrinsic pathway of ROTEM was significantly lower in patients with severe bleeding compared to those with mild to moderate bleeding. (4.3 ± 3.4% vs 9.4 ± 7.5%; P = .01). Conclusion: An association with bleeding manifestations and TRAPTEM suggest a potential role for defective platelet aggregation in the pathogenesis of bleeding in the critical phase of dengue.

Bleeding risk stratification in coronary artery surgery: the should-not-bleed score.

BACKGROUND: An estimated 20% of allogeneic blood transfusions in the United States are associated with cardiac surgery. It is estimated that 11% of red cell resources were used for transfusion support of patients undergoing coronary artery bypass grafting (CABG) with a documented wide variability in transfusion rate (7.8 to 92.8%). To address the issue of unnecessary transfusions within the CABG population, we developed a model to predict which patients are at low risk of bleeding for whom transfusion treatment might be considered unnecessary. Herein we present our "SHOULD-NOT-BLEED-SCORE" application developed for the Windows® software platform which is based on our previous research. METHODS: This study is aimed to develop a user-friendly application that stratifies patients with respect to bleeding risk. The statistical model we used in our previous research was focused on detection of CABG patients at low risk of bleeding. The rationale behind such an approach was to identify a CABG patient subgroup at low risk of bleeding. By identifying patients at low risk of bleeding we can define a subgroup of patients for whom transfusion treatment might be considered unnecessary. We developed a Windows platform application based on risk modelling which we previously calculated for 1426 patients undergoing elective CABG from January 2010 to January 2018. RESULTS: The SHOULD-NOT-BLEED-SCORE risk score is developed for the Windows software platform. A mathematical model that is based on multivariate analysis was used for app development. The variables that entered the scoring system were: Age; Body Mass Index; Chronic Renal Failure; Preoperative Clopidogrel Exposure; Preoperative Red Blood Cells Count; Preoperative Fibrinogen Level; Preoperative Multiplate ASPI test area under the curve (AUC) units. The SHOULD-NOT-BLEED-SCORE identifies/predicts patients without a risk for excessive bleeding with strong discriminatory performance (Receiver Operating Curve (ROC) analysis AUC 72.3%, p < 0.001). CONCLUSION: The SHOULD-NOT-BLEED risk scoring application may be useful in the preoperative risk screening process. The clinical and economic burden associated with unnecessary transfusions may be adequately addressed by a preoperative scoring system detecting patients at low risk of bleeding for whom transfusion treatment might be considered unnecessary.

Association among Clopidogrel Cessation, Platelet Function, and Bleeding in Coronary Bypass Surgery: An Observational Trial.

OBJECTIVES: This study sought to determine (1) the association between the length of preoperative clopidogrel discontinuation, blood loss, and transfusion requirements and (2) whether preoperative platelet function testing predicts excessive postoperative bleeding in patients undergoing coronary artery bypass grafting (CABG) surgery. METHODS: In this retrospective analysis, patients undergoing CABG were divided into three groups with regard to the period between preoperative clopidogrel cessation and surgery: group 1 (n = 94, ≤3 days), group 2 (n = 100, 4-5 days), and group 3 (n = 83, 6-7 days), respectively. Impedance aggregometry (Multiplate) with arachidonic acid (ASPI) test assay (used for platelets stimulation) and adenosine diphosphate (ADP) test (used for platelets stimulation) was performed before the surgery. Primary outcome was 24 hours chest tube output (CTO) and transfusion requirements (red blood cell concentrate [RBCC], platelet concentrate [PC], fibrinogen concentrate [FC], and fresh-frozen plasma [FFP]) were considered as secondary outcomes. RESULTS: CTO during 24 hours was significantly higher in group 1 as compared with groups 2 and 3, respectively (p = 0.003). Considering secondary outcomes, RBCC (p = 0.043), PC (p = 0.001), FC (p = 0.003), and FFP (p = 0.010) were more frequently transfused in group 1 as compared with groups 2 and 3, respectively. Multiple electrode aggregometry ASPI and ADP tests were significantly correlated with the 24-hour CTO (ASPI test-rho = -0.258, p < 0.001; ADP test-rho = -0.164, p = 0.007). A significant correlation was observed between clopidogrel-free interval and 24-hour CTO (rho = -0.200, p < 0.001). Receiver-operating characteristics (ROC) curve analysis revealed cutoff values to delineate bleeding tendency (ASPI test ≤ 25 area under the aggregation curve [AUC], ADP test ≤63 AUC, and clopidogrel-free interval ≤3 days). CONCLUSION: Excessive postoperative bleeding occurred less frequently if the period between clopidogrel discontinuation and surgery was longer than 3 days, as compared with shorter waiting time. Inadequate recovery of the platelets function following clopidogrel cessation in preoperative period was associated with increased bleeding risk. Platelet function testing was found to be a useful tool for postoperative bleeding management in our hands.

Cost Analysis of Transfusion Therapy in Coronary Artery Surgery.

BACKGROUND: In patients undergoing coronary artery bypass grafting (CABG), wide variability in transfusion rate (7.8% to 92.8%) raises the question of the amount of unnecessary transfusions. The aim of the study was (1) to identify CABG patients at low risk of bleeding to whom transfusion treatment should be avoided and (2) to calculate the amount of possible cost savings that would be achieved by avoiding transfusion in low bleeding risk patients. METHODS: This retrospective observational study enrolled patients undergoing isolated elective CABG from January 2010 to January 2018. Patients were divided with respect to the presence of excessive bleeding and transfusion costs were compared between the two groups. Predictors for postoperative excessive bleeding were defined and multivariable logistic regression analysis and risk modeling were performed. The use of a model to predict patients at low risk of bleeding allowed for the estimation of transfusion cost savings assuming the patients who were found to be at low risk of bleeding should not be transfused. RESULTS: A total of 1,426 patients were enrolled in the analysis. Of those, 28.3% had excessive postoperative bleeding. The multivariate logistic regression analysis model was developed to identify/predict patients without excessive bleeding (receiver operating characteristic curve analysis, area under the curve 72.3%, p < 0.001). When applied to the existing database, the use of the developed model identifying patients at low risk of bleeding may result in a 39.1% reduction of transfusions. Specifically, cost savings would be 48.2% for packed red blood cells, 38.9% for fresh frozen plasma, 10.9% for platelets concentrate, and 17.9% for fibrinogen concentrate. CONCLUSION: The clinical and economic burdens associated with unnecessary transfusions are significant. Avoiding transfusion in CABG patients found to be at low risk of bleeding may result in significant reduction of transfusion rate and transfusion-associated costs.

Coagulation pattern in critical liver dysfunction.

PURPOSE OF REVIEW: This article reviews the current literature dealing with pathophysiology, diagnostics, bleeding management, and thromboprophylaxis in patients with acute and chronic liver dysfunction. RECENT FINDINGS: Routine coagulation tests such as prothrombin time and International Normalized Ratio (INR) are not able to define whether a patient with critical liver dysfunction is hypocoagulable or hypercoagulable and are not able to predict the risk of bleeding in patients with liver dysfunction. Therefore, prophylactic transfusion of fresh frozen plasma and platelets in order to correct laboratory values is not appropriate. Notably, patients with liver dysfunction and increased INR are not 'autoanticoagulated'. In contrast, thrombin generation assays in the presence and absence of thrombomodulin or Protac, a snake venom that activates protein C in a manner similar to thrombomodulin, as well as viscoelastic tests (thrombelastography/thromboelastometry) indicate that patients with liver dysfunction are rather hypercoagulable with the inherent risk of thrombosis. SUMMARY: Coagulopathy in patients with critical liver dysfunction is complex and can quickly decompensate to bleeding as well as to thrombosis. Both are associated with worse outcome. Hemostatic interventions should only be performed in case of clinically relevant bleeding and thromboprophylaxis should strongly be considered.

High brain-natriuretic peptide level predicts cirrhotic cardiomyopathy in liver transplant patients.

Cirrhotic cardiomyopathy may appear following liver transplantation. Brain-natriuretic peptide (BNP) values exceeding 391 pg/ml or 567 pg/ml may partially reflect ventricular stress because of cardiac dysfunction or indicate cirrhotic cardiomyopathy, respectively. The aim of the study was to assess cardiac dysfunction in liver transplant patients and its correlation with BNP as a biomarker. From 1/2008 to 7/2009, 157 adult liver transplant recipients with proven cirrhosis were recruited for the study. BNP and liver enzymes were recorded upon admission, on the first postoperative day (POD) and 1 week after transplantation. Patients with ischemic heart attacks were excluded from the study. We identified two groups of patients. Group 1 was characterized by a BNP <391 pg/ml and Group 2 by a BNP >391 pg/ml. Group 2 had a significantly higher model of end-stage liver disease score than Group 1 (median 30, range 10-40 versus median 22, range 10-40, respectively; P = 0.003), required significantly more dialysis treatments and had a significantly higher mortality rate. Postoperative echocardiography in patients with a BNP >391 pg/ml indicated diastolic dysfunction in all of the patients and systolic dysfunction in 10 of the patients. Increased serum-BNP was associated with an overall higher mortality rate.

Hemostatic and hemorrhagic problems in neurosurgical patients.

BACKGROUND: Abnormalities of the hemostasis can lead to hemorrhage, and on the other hand to thrombosis. Intracranial neoplasms, complex surgical procedures, and head injury have a specific impact on coagulation and fibrinolysis. Moreover, the number of neurosurgical patients on medication (which interferes with platelet function and/or the coagulation systems) has increased over the past years. METHOD: The objective of this review is to recall common hemostatic disorders in neurosurgical patients on the basis of the "new concept of hemostasis". Therefore the pertinent literature was searched to provide a structured and up to date manuscript about hemostasis in Neurosurgery. FINDINGS: According to recent scientific publications abnormalities of the coagulation system are discussed. Pathophysiological background and the rational for specific (cost)-effective perioperative hemostatic therapy is provided. CONCLUSIONS: Perturbations of hemostasis can be multifactorial and maybe encountered in the daily practice of neurosurgery. Early diagnosis and specific treatment is the prerequisite for successful treatment and good patients outcome.