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Coagulopathy has been associated with clinical scenarios that involve reactive nitrogen species such as peroxynitrite (OONO-). Further, OONO- decreases tissue factor and fibrinogen function in vitro. Thus, we hypothesized that exposure of plasma to the OONO- generated with 3-morpholinosydnonimine (SIN-1), a molecule that produces both nitric oxide and superoxide, would result in a decrease in hemostatic function via diminished coagulation protein activity. Hemostatic function of plasma exposed to SIN-1 (0, 1, 5, and 10 mM for 60 min at 37 degrees C) was assessed with thrombelastography, activated partial thromboplastin time, and prothrombin time in the presence or absence of superoxide dismutase (SOD) or an OONO- scavenger. SIN-1 exposure resulted in a significant (P < 0.05), dose-dependent decrease in plasma hemostatic function and concurrent significant (P < 0.05) decreases in activities of factor VII, factor VIII complex, and factor X. Fibrinogen concentration was not affected by SIN-1. Antithrombin and protein C activity also decreased significantly (P < 0.05). Coincubation with SOD or an OONO- scavenger significantly (P < 0.05) attenuated SIN-1 mediated changes in hemostasis and procoagulant/ anticoagulant activity. We conclude that OONO- may decrease hemostatic function in human plasma by nitration of key procoagulants and that OONO- may play a significant role in hemorrhagic states.

We present the first thrombelastographic descriptions of three patients with δ-storage pool deficiency, a platelet disorder that involves a deficiency of dense granules and moderate bleeding. The patients demonstrated a 49-54% loss of platelet-mediated clot strength over a 1-2-h period after normal thrombus formation. This pattern persisted, with some attenuation of loss of strength following administration of epsilon aminocaproic acid, desmopressin and platelets for tonsillectomy. Assessment of platelet function in patients with platelet granule disorders can be accomplished with thrombelastographic methods in ambulatory and perioperative settings; however, the effects of therapy for this disorder cannot be monitored with thrombelastography without obtaining a blood sample prior to prophylactic hemostatic intervention.

We documented the hemostatic changes associated with placement of a EXCOR Berlin Heart left ventricular assist device in a 15-month-old child before heart transplantation. The development of hypercoagulability was rapid, manifested first by a plasmatic and subsequently platelet-mediated increase in coagulation kinetics and strength that persisted for weeks. The patient had no thrombotic complications for 6 wk before transplant but required extraordinary blood product administration to achieve hemostasis secondary to aggressive, multimodal anticoagulation. In summary, when proscribing anesthetic and surgical management of patients with a Berlin Heart, consideration of hypercoagulable features and anticoagulant therapy must be made to maximize patient safety.

Implications: This case describes the impact of argatroban and off-pump coronary revascularization on hemostasis as assessed by conventional hemostatic measures and Thrombelastography in a patient with heparin-induced thrombocytopenia.

Implications: Hereditary angioedema is a disease associated with acute complement-mediated inflammation and swelling of the airway and other vital organs. This case describes the impact of hereditary angioedema and cardiopulmonary bypass on hemostasis as assessed by thrombelastography.

Purpose: The purpose of this study was to determine if endogenous heparin release would modulate the hemostatic response to hemorrhagic shock in rabbits., Materials and Methods: Anesthetized rabbits (n = 13) underwent hemorrhagic shock (MAP 30-40 mm Hg) for 60 minutes. Blood samples obtained before and 60 minutes after hemorrhagic shock had thrombelasto-graphic variables (R, reaction time [min]; angle, alpha [ degrees ]; and G [dynes/cm(2)]) determined. Hemostatic function was assessed by modified thrombelastography under four conditions: (1) unmodified sample; (2) platelet inhibition with cytochalasin D; (3) heparinase I exposure; and (4) platelet inhibition and heparinase I exposure., Results: Thrombelastographic variable values in samples without platelet inhibition or heparinase exposure did not significantly change after hemorrhage (before hemorrhage: R = 22.01 +/- 0.7 min, alpha 43.6 +/- 1.3 degrees, G 7,089 +/- 379 dyne/cm(2); after hemorrhage: R 22.1 +/- 2.4, alpha 41.6 +/- 3.9, G = 5,662 +/- 564; mean +/- SEM). However, blood samples exposed to heparinase after hemorrhage demonstrated enhanced hemostatic function with thrombelastographic values (R = 13.4 +/- 1.5, alpha 56.0 +/- 3.4, G = 7012 +/- 565) significantly different (P <.05) from samples not exposed to heparinase. Samples with platelet inhibition demonstrated a similar pattern., Conclusion: Hemorrhagic shock significantly increased circulating endogenous heparin activity, attenuating the thrombotic response to hemorrhage in rabbits. Heparin-mediated regulation of hemostasis may serve as a protective mechanism in shock states., (Copyright 2001 by W.B. Saunders Company)

Unlabelled: Perioperative hemorrhage and thrombosis are serious complications associated with major vascular surgery. We hypothesized that thoracic aortic occlusion-reperfusion in rabbits would adversely affect hemostasis as assessed by thromboelastographic variables (reaction time, alpha angle and G [a measure of clot strength]). Isoflurane-anesthetized rabbits underwent either sham operation (n = 10) or 30 min of aortic occlusion followed by 90 min of reperfusion (n = 10). Blood samples (350 microL) were exposed to 10 microL of either 0.9% NaCl or cytochalasin D (a platelet inhibitor, 10 microM final concentration) and analyzed for 1 h by using thromboelastography after 30 min of postpreparation equilibration and at 30 and 90 min of reperfusion. Aortic occlusion-reperfusion resulted in a significant (P: < 0.05) increase in reaction time, decrease in alpha angle, and decrease in G at 30 and 90 min of reperfusion compared with the sham-operated group. The decrease in hemostatic function after aortic occlusion-reperfusion was observed to the same degree in samples with or without platelet inhibition. There were no significant differences in platelet concentration between the sham-operated and aortic occlusion-reperfusion groups. Aortic occlusion-reperfusion decreased hemostatic function in rabbits primarily by decreasing the coagulation factor-dependent, platelet-independent contribution to clotting., Implications: Thoracic aortic occlusion-reperfusion decreased hemostatic function in rabbits primarily by decreasing the coagulation factor-dependent, platelet-independent contribution to clotting. This decrease in hemostatic function may contribute to hemorrhagic complications associated with major vascular surgery.

Purpose: The purpose of this study was to determine if whole blood thrombelastographic variables (reaction time, K, alpha, and maximum amplitude) would be adversely effected by exposure to the nitric oxide (NO) donor, DETANONOate, in vitro or after alveolar instillation in vivo., Materials and Methods: Conscious rabbits (n = 10) had blood sampled from ear arteries anticoagulated with sodium citrate. The blood was then incubated with 0, 1, 5, 10, or 20 mmol/L DETANONOate for 30 minutes. Arterial blood from anesthetized rabbits (n = 4) was obtained and anticoagulated before and 60 minutes after 1 mmol/L DETANONOate (2 mL/kg) was instilled into the right lung. After incubation, all samples were placed in a thrombelastograph and recalcified, with thrombelastographic variables measured for 45 minutes., Results: In vitro, 10 mmol/L DETANONOate significantly (P < .05) increased reaction time, K, and decreased alpha compared with values observed after incubation with 0, 1, and 5 mmol/L DETANONOate. Twenty mmol/L DETANONOate significantly (P < .05) increased reaction time, K, and decreased alpha and maximum amplitude values compared with all other concentrations. In vivo, DETANONOate administration did not significantly affect thrombelastographic variables., Conclusion: DETANONOate significantly decreased hemostatic function in vitro in a dose-dependent fashion but did not significantly affect hemostatic function in vivo.

Major trauma patients at risk of traumatic coagulopathy are commonly treated with early clotting factor replacement to maintain hemostasis and prevent microvascular bleeding. In the United States, trauma transfusions are often dosed by empiric, low-ratio massive transfusion protocols, which pair plasma and platelets in some ratio relative to the red cells, such as the "1:1:1" combination of 1 units of red cells, 1 unit of plasma, and 1 donor's worth of pooled platelets. Empiric transfusion increases the rate of overtransfusion when unnecessary blood products are administered based on a formula and not on at patient's hemostatic profile. Viscoelastic hemostatic assays (VHAs) are point-of-care hemostatic assays that provided detailed information about abnormal clotting pathways. VHAs are used at many centers to better target hemostatic therapies in trauma. This Pro/Con section will address whether VHA guidance should replace empiric fixed ratio protocols in major trauma., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 International Anesthesia Research Society.)

Background: Storage pool deficiency (SPD) is a rare bleeding disorder characterized by reduction in the number of delta granules within platelets, interfering with hemostasis. Current literature lacks well-designed studies from which to draw concrete conclusions regarding pre-procedural management of bleeding complications. Objective: The purpose of this study is to describe bleeding and safety outcomes of SPD patients receiving either pre-procedural platelet transfusions or platelet-sparing regimens. Methods: An exploratory retrospective cohort study was conducted among SPD patients, comparing major bleeding events between those who received platelet transfusion and those who received desmopressin, tranexamic acid, and/or aminocaproic acid within 24 hours prior to procedure. Results: Rates of major bleeding were not found to be higher among patients who received a platelet-sparing regimen [platelet-sparing: 2/25 (8%); platelet transfusion: 2/29 (6.9%); P =.99]. Incidence of non-major bleeding was higher in the platelet transfusion group, but this was not statistically significant [platelet-sparing: 0/25 (0%); platelet transfusion: 3/29 (10.3%); P =.24]. Treatment-related adverse effects were observed following 8 of 54 procedures (14.8%). Conclusion: Use of a platelet-sparing regimen was not associated with a significantly higher incidence of major or non-major bleeding events. Future prospective trials are recommended to compare outcomes between therapies. [ABSTRACT FROM AUTHOR]

Background: Antifibrinolytic medications have been associated with reduced mortality in pediatric hemorrhage but may contribute to adverse events such as acute kidney injury (AKI). Study Design and Methods: We conducted a secondary analysis of the MAssive Transfusion in Children (MATIC), a prospectively collected database of children with life‐threatening hemorrhage (LTH), and evaluated for risk of adverse events with either antifibrinolytic treatment, epsilon aminocaproic acid (EACA) or tranexamic acid (TXA). The primary outcome was AKI and secondary outcomes were acute respiratory distress syndrome (ARDS) and sepsis. Results: Of 448 children included, median (interquartile range) age was 7 (2–15) years, 55% were male, and LTH etiology was 46% trauma, 34% operative, and 20% medical. Three hundred and ninety‐three patients did not receive an antifibrinolytic (88%); 37 (8%) received TXA and 18 (4%) received EACA. Sixty‐seven (17.1%) patients in the no antifibrinolytic group developed AKI, 6 (16.2%) patients in the TXA group, and 9 (50%) patients in the EACA group (p =.002). After adjusting for cardiothoracic surgery, cyanotic heart disease, preexisting renal disease, lowest hemoglobin pre‐LTH, and total weight‐adjusted transfusion volume during the LTH, the EACA group had increased risk of AKI (adjusted odds ratio 3.3 [95% CI: 1.0–10.3]) compared to no antifibrinolytic. TXA was not associated with AKI. Neither antifibrinolytic treatment was associated with ARDS or sepsis. Conclusion: Administration of EACA during LTH may increase the risk of AKI. Additional studies are needed to compare the risk of AKI between EACA and TXA in pediatric patients. [ABSTRACT FROM AUTHOR]

Background: Leukoreduced whole blood (LR-WB) has received renewed attention as alternative to component-based transfusion in trauma. According to the manufacturer's instructions, leukoreduction should be carried out within 8 h after collection. This study assessed impact of (1) WB collection bag, (2) LR filtration, and (3) timing of filtration on in vitro quality.Study Design and Methods: WB collected into different vendor bags was held at room temperature for <8 h or >16 h but <24 h prior to LR. In vitro quality was assessed before and after filtration, and throughout 3 weeks of storage at 4°C. Cell count and hemoglobin levels were determined by hematology analyzer, platelet activation, and responsiveness to ADP by surface expression of P-selectin by flow cytometry, hemolysis by HemoCue, and metabolic parameters by blood gas analyzer. Hemostatic properties were assessed by rotational thromboelastometry. Plasma protein activities and clotting times were determined by automated coagulation analyzer or quantitative immunoblotting.Results: Bag type had no impact on WB in vitro quality. LR by filtration had some impact, but is aligned with data in the literature. The time between donation and filtration resulted in some statistically significant differences in metabolic activity, platelet yield, platelet activation, and factor protein activity initially; however, these differences in in vitro quality attributes decreased throughout 21-day cold storage.Conclusion: WB hold time showed only a minor impact on WB in vitro quality, so it may be possible for blood processing facilities to explore extended hold times prior to filtration in order to provide greater operational flexibility. [ABSTRACT FROM AUTHOR]

Summary: Bleeding is a significant complication of cardiopulmonary bypass (CPB), despite routine anticoagulation monitoring. This is likely to be multifactorial. In this prospective, single‐centre cohort study of 30 patients undergoing CPB surgery, our aim was to characterise the changes in von Willebrand factor (VWF) function, platelet interaction and the global coagulation changes during and after CPB surgery and to determine whether bleeding can be predicted. Samples were taken at six time points before, during and after CPB surgery. We observed a significant rise in VWF antigen (VWF:Ag) throughout surgery, which continued postoperatively. The absolute VWF collagen‐binding assays (VWF:CB) and VWF ristocetin cofactor (VWF:RCo) rose significantly but the VWF:CB/VWF:Ag and VWF:Ag/VWF:RCo fell significantly (P = 0·0015 and P = 0·0143), suggesting loss of large multimers. We detected a non‐significant trend to loss of VWF:RCo after heparinisation and a significant recovery after protamine reversal which could reflect a direct heparin effect. There was a significant increase in the R and K times with a fall in alpha angle and maximum amplitude after heparin administration, using heparinase‐thromboelastography (TEG). The parameters both significantly improved following protamine (P = 0·007 and P = 0·0054). The activated clotting time (ACT) and heparin anti‐Xa level correlated poorly; neither predicted clinically significant bleeding. None of these parameters had a relationship with intraoperative blood loss or requirement for blood product replacement. [ABSTRACT FROM AUTHOR]

Spontaneous intracerebral hemorrhage (SICH) is a severe subtype of stroke. Hematoma expansion could occur in the short term after symptom onset in most patients, leading to neurological deterioration and mortality. Therefore, early hemostasis treatment is essential to save patients' lives and improve prognosis. Currently, the hemostatic agents used for intracerebral hemorrhage are mainly antifibrinolytic drugs and recombinant activated factor VII. However, there is no decisive evidence for the clinical benefit of hemostatic drugs in patients with intracerebral hemorrhage. To provide reference for clinical choice of drugs, this article reviews the hematoma expansion mechanism and hemostatic therapy of spontaneous intracerebral hemorrhage. [ABSTRACT FROM AUTHOR]

Background: Viscoelastic testing is a method of hemostatic analysis that provides a real-time, holistic view of ex vivo clotting. It allows for examination of both cellular and plasma protein contributions to clotting including platelet number and function, fibrin(ogen) function, and coagulation factor function. The method assesses physical clot properties during the transition of blood from a liquid to a gel state, either by measurement of clot shear modulus using physical force transduction or by measurement of clot resonance frequency using sonometric interrogation. Results are reported in a live trace, with different trace parameters reflecting different contributors to hemostasis. These reported parameters vary between testing platforms.Results: In the United States, there are several commonly used Food and Drug Administration (FDA)-approved viscoelastic instruments available on the market. Those instruments that use sonometric clot assessment are more recently available and allow for improved portability for use near the patient's bedside. These instruments generally feature different reagent kits that allow more specific interrogation of different hemostatic pathways. Viscoelastic testing can predict the results of traditional plasma-based coagulation assays and has the added benefit of detecting hypercoagulability and severe hyperfibrinolysis. Implementation of viscoelastic testing in many clinical settings is becoming widespread and has proven to be efficacious in reducing blood transfusion rates in many settings. An impact on overall mortality and morbidity has not yet been demonstrated.Conclusion: This article provides a narrative review of the basic principles of viscoelastic testing, including the science and technology behind the method, as well as currently available testing platforms and reagents. [ABSTRACT FROM AUTHOR]

The most prominent event that defines acute coronary syndrome (ACS) is the formation of an intra-arterial thrombus, usually resulting from activation of platelet and fibrinogen at the ruptured plaque. Usually, conventional coagulation tests (CCTs) are used to estimate the hemostatic properties of patients. However, CCTs have significant limitations because they each assess individual aspects of the coagulation cascade, which is a complex multifaceted process. And CCTs are performed with platelet-poor plasma, while the contribution of platelets to clot formation is not measured. In contrast, thromboelastography (TEG) is a test for global hemostasis with whole blood, from the beginning of coagulation through clot formation to the ending with fibrinolysis. The aim of this study was to investigate whether TEG parameters could be surrogate biomarkers of thrombus formation process and diagnosis of ACS. Receiver operating characteristic（ROC）curve was used to evaluate the diagnosis performance of each index. Logistic regression analysis was utilized to define the independent risk factors of ACS. The results showed that the shear elastic modulus parameter (G) was an independent diagnostic indicator for ACS (odds ratio [OR], 2.600; 95% confidence interval [CI], 2.035-3.322). The area under ROC curve of G was 0.866. The optimal cut-off value for the diagnosis of ACS was 10.55 dyne/cm2, while the sensitivity was 66.2% and the specificity was 92.4%. In conclusion, G could be used as an optimal indicator of activation of platelet and fibrinogen, which is eligible to be a useful biomarker for early diagnosis of ACS. [ABSTRACT FROM AUTHOR]

Background: Ehrlichia canis infection in dogs can cause thrombocytopenia and clinical evidence of bleeding. It is unknown why some dogs show signs of bleeding whereas others do not despite clinically relevant thrombocytopenia. Hypothesis/Objectives: Activated platelets, decreased fibrinolysis or both mitigate bleeding tendency. Assess standard hemostatic variables, platelet dynamics, and specialized coagulation testing in dogs experimentally infected with E. canis to evaluate this clinical discrepancy. Animals: Four healthy laboratory beagles. Methods: Dogs were given blood infected with E. canis IV. Platelet indices of activation, platelet aggregometry, antiplatelet antibodies (percent IgG), complete coagulation panel, and thromboelastography (TEG) were measured before inoculation and on weeks 1‐8. Dogs were treated with doxycycline at approximately 5 mg/kg PO q12h between weeks 3 and 4 (day 24). For each variable, 1‐way repeated measures analysis (1‐way ANOVA) with post‐hoc analysis was performed with statistical significance set at P < .05. Results: Dogs had significantly lower platelet counts, evidence of activated platelets, and antiplatelet antibodies during E. canis infection. Dogs also appeared hypercoagulable and hypofibrinolytic using TEG as compared with baseline, changes that persisted for variable amounts of time after doxycycline administration. No overt signs of bleeding were noted during the study. Conclusions and Clinical Importance: Activated platelets and a hypercoagulable, hypofibrinolytic state could explain the lack of a bleeding phenotype in some dogs despite clinically relevant thrombocytopenia. Findings from our pilot study indicate that additional studies are warranted. [ABSTRACT FROM AUTHOR]

Background: Thrombelastography is a useful tool in assessment of hemostasis. Beside the traditional variables, the velocity curve and the variable delta have lately earned attention. The velocity curve provides knowledge about the speed of clot formation including information about thrombin generation. Delta, which only reflects enzymatic coagulation, allows the determination of the origin of hypercoagulability when compared to clot rigidity, a variable that reflects both platelet and enzymatic activity. The aim was to establish preliminary reference intervals for feline thrombelastography including the velocity curve variables and delta obtained after 60 min of storage including the assessment of coefficients of variation. Furthermore, the effect of citrate storage time (30 versus 60 min) on feline thrombelastography will be determined. Results: Prolonged storage times significantly reduced reaction (R) (P = 0.019) and clotting (K) (P = 0.008) times, split point (SP) (P = 0.019) and time to maximum rate of thrombus generation (TMRTG) (P = 0.023) values whereas maximum rate of thrombus generation (MRTG) significantly increased (P = 0.040). Preliminary reference intervals: R (min): 2.7-18.1; K (min): 0. 8-3.9; alpha (°): 27.6-75.2; maximum amplitude (mm): 18.5-62.5; clot rigidity (dyn/cm2): 1.2-8.2; coagulation index: −4.6 - 2.6; SP (min): 2.4-15.4; delta (min): 0.3-3.1; thrombus generation (mm/min): 255.3-751.2; MRTG (mm/min): 4.0-19.3; TMRTG (min): 3.5-22.0; maximum rate of lysis (mm/min): 0.0-4.7 and time to maximum rate of lysis (min): 0.4-55.8. Conclusion: Storage for 60 versus 30 min induces hypercoagulable tracings including the velocity curve, some of which variables (MRTG, TMRTG) might function as sensitive markers for changes in the coagulation activity. Because of the impact of citrate storage time on thrombelastography, reference intervals have to be established using a specific and constant storage time in each laboratory. [ABSTRACT FROM AUTHOR]

Albumin is the most abundant plasma protein. Critical illness is often associated with altered, predominately decreased, serum albumin levels. This hypoalbuminaemia is usually corrected by administration of exogenous albumin. This study aimed to track the concentration-dependent influence of albumin on blood coagulation in vitro. Whole blood (WB) samples from 25 volunteers were prepared to contain low (19.3 ± 7.7 g/L), physiological (45.2 ± 7.8 g/L), and high (67.5 ± 18.1 g/L) levels of albumin. Haemostatic profiling was performed using a platelet function analyzer (PFA) 200, impedance aggregometry, a Cone and Platelet analyzer (CPA), calibrated automated thrombogram, and thrombelastometry (TEM). Platelet aggregation-associated ATP release was assessed via HPLC analysis. In the low albumin group, when compared to the physiological albumin group, we found: i) shortened PFA 200-derived closure times indicating increased primary haemostasis; ii) increased impedance aggregometry-derived amplitudes, slopes, ATP release, as well as CPA-derived average size indicating improved platelet aggregation; iii) increased TEM-derived maximum clot firmness and alpha angles indicating enhanced clot formation. TEM measurements indicated impaired clot formation in the high albumin group compared with the physiological albumin group. Thus, albumin exerted significant anticoagulant action. Therefore, low albumin levels, often present in cancer or critically ill patients, might contribute to the frequently occurring venous thromboembolism. [ABSTRACT FROM AUTHOR]

Excessive bleeding following pediatric cardiopulmonary bypass is associated with increased morbidity and mortality, both from the effects of hemorrhage and the therapies employed to achieve hemostasis. Neonates and infants are especially at risk because their coagulation systems are immature, surgeries are often complex, and cardiopulmonary bypass technologies are inappropriately matched to patient size and physiology. Consequently, these young children receive substantial amounts of adult-derived blood products to restore adequate hemostasis. Adult and pediatric data demonstrate associations between blood product transfusions and adverse patient outcomes. Thus, efforts to limit bleeding after pediatric cardiopulmonary bypass and minimize allogeneic blood product exposure are warranted. The off-label use of factor concentrates, such as fibrinogen concentrate, recombinant activated factor VII, and prothrombin complex concentrates, is increasing as these hemostatic agents appear to offer several advantages over conventional blood products. However, recognizing that these agents have the potential for both benefit and harm, well-designed studies are needed to enhance our knowledge and to determine the optimal use of these agents. In this review, our primary objective was to examine the evidence regarding the use of factor concentrates to treat bleeding after pediatric CPB and identify where further research is required. PubMed, MEDLINE/ OVID, The Cochrane Library and the Cochrane Central Register of Controlled Trials ( CENTRAL) were systematically searched to identify existing studies. [ABSTRACT FROM AUTHOR]

Heme has been characterized as potent trigger of inflammation. In hemostasis, although heme has been shown to both induce and inhibit different compartments of hemostasis, its net effect on the hemostatic balance, and the biological relevance of these effects remain to be determined. Herein we evaluated the effect of heme on hemostasis using a global assay able to generate clinically relevant data in several other complex hemostatic diseases. Citrated whole blood samples from healthy participants were stimulated by heme or vehicle and incubated for 4h at 37°C. Rotational thromboelastometry was immediately performed. The participation of tissue factor in coagulation activation was evaluated using inhibitory antibody. Heme was able of inducing ex vivo coagulation activation in whole blood, affecting predominantly parameters associated with the initial phases of clot formation. This activation effect was at least partially dependent on hematopoietic tissue factor, since the effects of heme were partially abrogated by the inhibition of human tissue factor. In conclusion, using a global hemostasis assay, our study confirmed that heme is able to activate coagulation in whole blood, in a tissue factor-dependent way. These findings could explain the disturbance in hemostatic balance observed in conditions associated with the release of heme such as sickle cell disease. [ABSTRACT FROM AUTHOR]

Thrombelastography (TEG)/thromboelastometry (ROTEM) devices measure viscoelastic clot strength as clot amplitude (A). Transformation of clot amplitude into clot elasticity (E with TEG; CE with ROTEM) is sometimes necessary (eg, when calculating platelet component of the clot). With TEG, clot amplitude is commonly transformed into shear modulus (G; expressed in Pa or dyn/cm2) as follows: G = (5000 × A)/(100 – A). Use of the constant “5000” stems from Hartert's 50-year-old calculation of G for a normal blood clot. We question the value of calculating G as follows: (1) It may be questioned whether TEG/ROTEM analysis enable measurement of elasticity because viscosity may also contribute to clot amplitude. (2) It has been suggested that absolute properties of a blood clot cannot be measured with TEG/ROTEM analysis because the strain amplitude applied by the device is uncontrolled and changes during the course of coagulation. (3) A review of the calculation of G using Hartert's methods and some updated assumptions suggests that the value of 5000 is unreliable. (4) Recalculation of G for the ROTEM device yields a different value from that with Hartert TEG, indicating a degree of inaccuracy with the calculations. (5) Shear modulus is simply a multiple of E/CE and, because of the unreliability of G in absolute terms, it provides no additional value versus E/CE. The TEG and ROTEM are valuable coagulation assessment tools that provide an evaluation of the viscoelastic properties of a clot, not through measuring absolute viscoelastic forces but through continuous reading of the clot amplitude relative to an arbitrary, preset scale. [ABSTRACT FROM AUTHOR]

Haemostatic perturbations are commonly seen in extracorporeal membrane oxygenation (ECMO) patients and remain a clinical challenge, contributing significantly to morbidity and mortality. The approach to anticoagulation monitoring and the management of bleeding varies considerably across ECMO centres. Routine laboratory tests have their limitations in terms of turnaround time and specificity of information provided. Newer point-of-care testing (POCT) for coagulation may overcome these issues, as it provides information about the entire coagulation pathway from clot initiation to lysis. It is also possible to obtain qualitative information on platelet function from these tests. Furthermore, the ability to incorporate these results into a goal-directed algorithm to manage bleeding with targeted transfusion strategies appears particularly attractive and cost effective. Further studies are required to evaluate the utility of POCT to optimise bleeding and anticoagulation management in these complex patients. [ABSTRACT FROM AUTHOR]

Several clinical settings are associated with specific coagulopathies that predispose to uncontrolled bleeding. With the growing concern about the need for optimizing transfusion practices and improving treatment of the bleeding patient, a group of 9 Portuguese specialists (Share Network Group) was created to discuss and develop algorithms for the clinical evaluation and control of coagulopathic bleeding in the following perioperative clinical settings: surgery, trauma, and postpartum hemorrhage. The 3 algorithms developed by the group were presented at the VIII National Congress of the Associação Portuguesa de Imuno-hemoterapia in October 2013. They aim to provide a structured approach for clinicians to rapidly diagnose the status of coagulopathy in order to achieve an earlier and more effective bleeding control, reduce transfusion requirements, and improve patient outcomes. The group highlights the importance of communication between different specialties involved in the care of bleeding patients in order to achieve better results. [ABSTRACT FROM AUTHOR]

Higher levels of fibrinogen, a critical element in hemostasis, are associated with increased postoperative survival rates, especially for patients with massive operative blood loss. Fibrinogen deficiency after surgical management of intracranial tumors may result in postoperative intracranial bleeding and severely worsen patient outcomes. However, no previous studies have systematically identified factors associated with postoperative fibrinogen deficiency. In this study, we retrospectively analyzed data from patients who underwent surgical removal of intracranial tumors in Beijing Tiantan Hospital date from 1/1/2013to12/31/2013. The present study found that patients with postoperative fibrinogen deficiency experienced more operative blood loss and a higher rate of postoperative intracranial hematoma, and they were given more blood transfusions, more plasma transfusions, and were administered larger doses of hemocoagulase compared with patients without postoperative fibrinogen deficiency. Likewise, patients with postoperative fibrinogen deficiency had poorer extended Glasgow Outcome Scale (GOSe), longer hospital stays, and greater hospital expenses than patients without postoperative fibrinogen deficiency. Further, we assessed a comprehensive set of risk factors associated with postoperative fibrinogen deficiency via multiple linear regression. We found that body mass index (BMI), the occurrence of postoperative intracranial hematoma, and administration of hemocoagulasewere positively associated with preoperative-to-postoperative plasma fibrinogen consumption; presenting with a malignant tumor was negatively associated with fibrinogen consumption. Contrary to what might be expected, intraoperative blood loss, the need for blood transfusion, and the need for plasma transfusion were not associated with plasma fibrinogen consumption. Considering our findings together, we concluded that postoperative fibrinogen deficiency is closely associated with postoperative bleeding and poor outcomes and merits careful attention. Practitioners should monitor plasma fibrinogen levels in patients with risk factors for postoperative fibrinogen deficiency. In addition, postoperative fibrinogen deficiency should be remediated as soon as possible to reduce postoperative bleeding, especially when postoperative bleeding is confirmed. [ABSTRACT FROM AUTHOR]

Objective Evaluation of hemostasis using thromboelastometry in dogs with leishmaniasis before and after treatment. Design Longitudinal observational study. Setting University veterinary teaching hospital. Animals Eighty-four adult, client-owned dogs. Measurements and Main Results Whole blood samples for the coagulation profile were collected from symptomatic dogs with leishmaniasis (group S), asymptomatic dogs with leishmaniasis after treatment (group T), and a control group of healthy dogs (group H). Hemostasis was evaluated by means of standard coagulation profile (prothrombin time, activated partial thromboplastin time, and fibrinogen) and by thromboelastometry (ROTEM). Prothrombin time and activated partial thromboplastin time were within the upper reference range in all 3 groups. Comparison of the ROTEM variables between the 3 groups showed statistically significant differences between group S versus groups T and H, but remaining within the reference ranges. Statistically significant differences in hematocrit and fibrinogen concentrations were noted between groups (group S vs. H: hematocrit P = 0.001, fibrinogen P = 0.002; Group S vs. T: hematocrit P = 0.001, fibrinogen P = 0.001). These variations have interfered with some parameters of the ROTEM profile. Conclusions This study showed normal standard coagulation profiles in all 3 groups evaluated. The ROTEM results did not fall outside of the maximum values of the reference ranges. [ABSTRACT FROM AUTHOR]

Background An immature coagulation system coupled with the hypothermia and hemodilution associated with cardiopulmonary bypass ( CPB) in infants makes the activated clotting time ( ACT) an ineffective monitor for anticoagulation in this population. The Medtronic HMS Plus Hemostasis Management System ( HMS; Medtronic, Inc., Minneapolis, MN, USA) is shown to decrease thrombin generation and blood product requirements. Aim We conducted a quality improvement initiative to test our hypothesis that the use of HMS results in reduced incidence of subtherapeutic ACT values, blood product usage, and operating room time for infants undergoing cardiac surgery. Methods Fifty consecutive patients weighing <10 kg having cardiac surgery requiring CPB had anticoagulation managed by the HMS. Data were compared to that of 50 consecutive patients weighing <10 kg having cardiac surgery who had their anticoagulation monitored by the ACT alone. Comparisons between categorical variables were performed with chi-square tests. Comparisons between continuous variables were performed with the Wilcoxon rank-sum test. Statistical significance was defined as two-tailed P value < 0.05. Results The HMS group had a 61% decrease in incidence of ACT values <480 s and elimination of ACT values < 400 s at any time on bypass. The HMS group received fewer blood products and spent fewer minutes in the operating room after protamine administration, translating to fewer donor exposures and a savings of $403 in transfusion costs and $440 in operating room time costs. Conclusion Our findings highlight the benefits of individualized heparinization for pediatric patients undergoing CPB with a monitored heparinization system. [ABSTRACT FROM AUTHOR]

Haemostasis is a complex process affected by many factors including both cellular and plasma components. It is a multistep process starting with platelet adhesion to damaged endothelium and ending in clot fibrinolysis. There are several methods available to study different aspects of haemostasis including adhesion, aggregation, coagulation and fibrinolysis. This review describes the different methods, what aspects of haemostasis they measure and their limitations. Methods discussed include methods to study adhesion (e.g. PFA-100, cone and platelet(let) analyzer and perfusion chambers) and aggregation (e.g. Multiplate, VerifyNow and Plateletworks). Furthermore the principles behind viscoelastic haemostatic assays are presented as well as methods that can analyse aspects of haemostasis in plasma or platelet-rich-plasma samples (thrombin generation, overall haemostasis potential and Thrombodynamics Analyzer). [ABSTRACT FROM AUTHOR]

Fibrinogen plays a critical role in achieving and maintaining hemostasis and is fundamental to effective clot formation. There is increasing awareness of the important role of fibrinogen as a key target for the treatment and prevention of acquired bleeding. Fibrinogen is the first coagulation factor to fall to critically low levels (<1.0 g/L) during major hemorrhage (normal plasma fibrinogen levels range from 2.0 to 4.5 g/L), and current guidelines recommend maintaining the plasma fibrinogen level above 1.5 g/L. Fibrinogen supplementation can be achieved using plasma or cryoprecipitate; however, there are a number of safety concerns associated with these allogeneic blood products and there is a lack of high-quality evidence to support their use. Additionally, there is sometimes a long delay associated with the preparation of frozen products for infusion. Fibrinogen concentrate provides a promising alternative to allogeneic blood products and has a number of advantages: it allows a standardized dose of fibrinogen to be rapidly administered in a small volume, has a very good safety profile, and is virally inactivated as standard. Administration of fibrinogen concentrate, often guided by point-of-care viscoelastic testing to allow individualized dosing, has been successfully used as hemostatic therapy in a range of clinical settings, including cardiovascular surgery, postpartum hemorrhage, and trauma. Results show that fibrinogen concentrate is associated with a reduction or even total avoidance of allogeneic blood product transfusion. Fibrinogen concentrate represents an important option for the treatment of coagulopathic bleeding; further studies are needed to determine precise dosing strategies and thresholds for fibrinogen supplementation. [ABSTRACT FROM AUTHOR]

Background It is well established that hematocrit ( Hct) influences whole blood thromboelastography ( TEG) tracings. Previous studies showed hypercoagulable TEG tracings in anemic patients despite clinical expectations that anemia often prolongs bleeding. TEG is a viscoelastic assessment of clot kinetics, and Hct is the main determinant of whole blood viscosity. TEG changes in anemia may be an in vitro artifact due to Hct effect on blood viscosity rather than true in vivo changes in hemostasis. The effect of changes in whole blood viscosity on TEG independent of Hct is not well understood. Study Design and Methods Twenty-one blood samples from seven dogs were manipulated to produce one of three Hct conditions (45, 20, and 10%). Each was tested in two situations: viscosity adjusted to normal by adding alginate ( ALG) or dilution with equal volume of saline ( SAL). Both samples were analyzed with TEG simultaneously. Results Twenty percent Hct plus ALG and 10% Hct plus ALG were significantly more viscous than their SAL counterparts (p = 0.0156). Ten percent Hct plus SAL, 20% Hct plus SAL, and 45% Hct plus SAL all had different viscosities (p = 0.006). Twenty percent Hct plus SAL and 10% Hct plus SAL had significantly shorter K and higher angle, MA, and G compared to their ALG counterparts as well as 45% Hct plus SAL (p < 0.05). Conclusions ALG samples with low Hct, normal viscosity showed hypocoagulable tracings, whereas SAL samples with low Hct, low viscosity showed hypercoagulable tracings. TEG variables are influenced by whole blood viscosity altered with ALG, independently of Hct. [ABSTRACT FROM AUTHOR]

The article presents a study on the capacity of biocompatible coatings to attenuate the effects of cardiopulmonary bypass. It notes that biocompatible circuits (BCC) are designed to decrease blood activation to the artificial cardiopulmonary bypass (CPB) surface. The study concludes that BCC, though not harmful, are ineffective in preserving tromboelastography (TEG).

Background In the pathogenesis of sepsis, inflammation-induced changes in coagulation play a pivotal role. Methods In total, 90 patients (30 patients with septic shock, 30 surgical patients following major abdominal surgery and 30 healthy volunteers) were enrolled. Blood samples from patients with septic shock were collected at the time of sepsis diagnosis as well as 24 h, 4 days, 7 days, 14 days and 28 days later. Samples from surgical patients with a post-surgical inflammatory response were collected three times (before surgery, immediately after surgery and 24 h after surgery) and once from healthy volunteers. Thromboelastometry ( ROTEM®), as well as whole blood impedance aggregometry ( Multiplate®) were performed. Additionally, plasma concentrations of interleukin-6 and tumour necrosis factor-alpha were measured using enzyme-linked immunosorbent assay kits. Results Thromboelastometry lysis index was shown to be a reliable biomarker for septic shock. Furthermore, in septic patients with overt disseminated intravascular coagulation, thromboelastometry revealed signs indicating a hypocoagulable status, whereas patients without overt disseminated intravascular coagulation were found to be hypercoagulable. Platelet aggregation capability, as assessed by whole blood impedance aggregometry, was significantly reduced in septic patients with overt disseminated intravascular coagulation, whereas it was comparable with healthy volunteers and in septic patients without overt disseminated intravascular coagulation. Conclusion Viscoelastic and aggregometric point-of-care testing was shown to be potentially useful for bedside diagnosis of sepsis. Moreover, viscoelastic and aggregometric point-of-care testing was able to determine the phase of septic coagulopathy (hypercoagulability vs. hypocoagulability) and therefore identified patients at high risk for overt disseminated intravascular coagulation. [ABSTRACT FROM AUTHOR]

Purpose: Hydroxyethyl starch solutions (HES) are plasma volume expanders which affect hemostasis. Newer HES 130/0.4 is said to be safer. Reevaluation of published evidence is necessary after the recent retraction of studies. Methods: Systematic review of studies assessing HES 130/0.4 effects on hemostasis by thrombelastography (TEG, ROTEM) or Sonoclot (SCR) in comparison with crystalloid or albumin control fluids was performed. Only studies which provided statistical comparisons between study fluids were analyzed. Studies were divided into in vitro or in vivo hemodilution studies. We assessed study quality, HES effects which differed significantly from controls, values outside normal range, degree of hemodilution, and cumulative HES dose. Results: Seventeen in vitro and seven in vivo hemodilution studies were analyzed. Four studies reported quality control measures. Nineteen studies (all 15 ROTEM studies, 3 of 5 in vitro TEG, and 1 of 2 SCR studies) showed a significant hypocoagulatory effect of HES 130/0.4 on clot formation, while clotting time was not uniformly affected. Three in vivo TEG studies with low HES doses or cancer patients found mixed or nonsignificant results. In studies which provided normal ranges ( n = 9), more values were outside normal ranges in the HES than in the control groups (87/122 vs. 58/122, p < 0.001). Dose effects were apparent in the in vitro studies, which investigated higher dilutions up to 80%. In vivo studies were fewer and did not investigate doses >40 ml/kg. Conclusions: HES 130/0.4 administration results in a weaker and smaller clot. Until results from well-designed clinical trials are available, safer fluids should be chosen for patients with impaired coagulation. [ABSTRACT FROM AUTHOR]

The article presents a study which aimed to determine the effects of cytochalasin D and abciximab on hemostatic parameters in canine citrated whole blood. The study found no evidence that the addition of abciximab to canine citrated whole blood would affect the thromboelastography (TEG) tracing. However, abciximab was found to inhibit platelet aggregation under shear stress.

Background: Hydroxyethyl starches (HES) could differ with regard to the origin, and the influence on the coagulation of the raw material is unknown. This study compared the effects of a new potato-derived HES with a maize-derived HES and two crystalloid solutions. Methods: Whole blood from 10 healthy individuals was diluted by 20% and 40% using either non-balanced potato-derived HES 130/0.42/6 : 1, non-balanced maize-derived HES 130/0.4/9 : 1, isotonic saline or Ringer's lactate solution. Samples were analysed by thromboelastometry ROTEM®: Coagulation was initiated by acid ellagic [intrinsic thromboelastometry (INTEM)] or tissue factor (extrinsic thromboelastometry) with and without cytochalasin to determine the functional component of fibrinogen [cytochalasin-d-modified thromboelastometry (FIBTEM)]. Platelet count and fibrinogen activity were measured. Results: No effect of raw material was found as no difference was detected among the HES solutions. Whatever the solution, progressive haemodilution impaired haemostasis in a dose-dependant manner: For INTEM, the clot formation time was increased up to 308% and the maximum clot firmness (MCF) was decreased down to 49%. As dilution increased, initiation of coagulation was also impaired. Thromboelastometric alterations were more severe with HES than with crystalloids, especially regarding fibrin polymerization explorations: MCF of FIBTEM was considerably reduced from 12[10-14] to 2[2-3] mm ( P<0.05). Fibrinogen activity and platelet count were reduced by dilution in a dose-dependant manner and decreased similarly in all groups. Conclusion: Maize- and potato-derived HES have similar effects on coagulation. Both the starch preparations tested lead to more severe haemostatic defects than crystalloids, and impairment of fibrin polymerization appears to be a leading determinant of this coagulopathy. [ABSTRACT FROM AUTHOR]

Current recommendations for resuscitation of the critically injured patient are limited by a lack of point-of-care (POC) assessment of coagulation status. Accordingly, the potential exists for indiscriminant blood component administration. Furthermore, although thromboembolic events have been described shortly after injury, the time sequence of post-injury coagulation changes is unknown. Our current understanding of hemostasis has shifted from a classic view, in which coagulation was considered a chain of catalytic enzyme reactions, to the cell-based model (CBM), representing the interplay between the cellular and plasma components of clot formation. Thromboelastography (TEG), a time-sensitive dynamic assay of the viscoelastic properties of blood, closely parallels the CBM, permitting timely, goal-directed restoration of hemostasis via POC monitoring of coagulation status. TEG-based therapy allows for goal-directed blood product administration in trauma, with potential avoidance of the complications resulting from overzealous component administration, as well as the ability to monitor post-injury coagulation status and thromboprophylaxis. This overview addresses coagulation status and thromboprophylaxis management in the trauma patient and the emerging role of POC TEG. [ABSTRACT FROM AUTHOR]

Coagulation management requires the balancing of different components that contribute to clot formation. These components include the interactions between platelets, procoagulant, anticoagulant, and fibrinolytic factors. The cause of bleeding or thrombotic events is often multifactorial; however, the tests clinicians most frequently use to assess hemostasis do not reflect the complexity of the coagulation system. The paucity of global measurements of hemostasis has resulted in either an empirical or a one-size-fits-all approach to treatment. In contrast, thromboelastography is a test that monitors the different phases of clot formation and lysis, providing the clinician with a tool for making informed therapeutic decisions. This review provides an overview of thromboelastography in the management of hypocoagulable and hypercoagulable conditions. [ABSTRACT FROM AUTHOR]

There is a potential for significant paradigm shift in the assessment of haemostasis from the conventional plasma recalcification times, such as prothrombin time (PT) and activated partial thromboplastin time (APTT), which correspond to artificially created compartments of haemostasis to tests that assess the entire process in a more physiological and holistic manner. These include the thrombin generation test, thromboelastogram and the clot wave form analysis. While these tests have been described many years ago, there is renewed interest in their use with modified technology for assessing normal haemostasis and its disorders. Although early data suggest that they can provide much greater information regarding the overall haemostasis process and its disorders, many challenges remain. Some of them are possible only on instruments that are proprietary technology, expensive and are not widely available. Furthermore, these tests need to be standardized with regard to their reagents, methodology and interpretation, and finally, much more data need to be collected regarding clinical correlations with the parameters measured. [ABSTRACT FROM AUTHOR]

The article discusses the strengths and limitations of point-of-care techniques for the detection of antiplatelet drug effects. Global assessments of haemostasis are not specific for platelet function and are insensitive to cyclooxygenase. The most widely used technique was the laboratory turbidometric platelet aggregometry. Thrombelastography provides a real time assessment of the clot's viscoelastic properties as it forms ex vivo. The functions of Clot Signature Analyzer and Platelet Activated Clotting Test are also described.

Most often, thrombelastographic analyses are carried out using citrated blood and re-calcification. However, calcium chelation may affect dynamics of tissue-factor-initiated thrombin generation. The present study investigates the effect of sample anticoagulant on the response of a colloid induced dilutional coagulopathy model to recombinant activated factor VII (rFVIIa) as measured by thrombelastography. Thrombelastographic evaluation of whole blood coagulation activated with minute amounts of tissue factor in a model of in vitro haemodilution with hydroxyethyl starch (HES) 130/0.4 in a prospective laboratory study. Whole blood coagulation was evaluated before and after 30% dilution with HES 130/0.4, and following in vitro addition of rFVIIa to whole blood collected into tubes containing citrate, corn trypsin inhibitor (CTI), and no stabilizers. Haemodilution with HES 130/0.4 induces a coagulopathy characterised by a reduced maximum rate of clot formation and a pronounced reduction in the final clot firmness. With all test mediums investigated, rFVIIa significantly shortened clot initiation phase. In cases of native whole blood and CTI-stabilised whole blood, rFVIIa shortens the clotting time but also demonstrated an acceleration of the maximum velocity of clot formation. When citrate is used as anticoagulants in thrombelastographic clotting assays, these may artificially mask the haemostatic effect of rFVIIa in colloid haemodilution. The effect in vitro of rFVIIa in citrated blood samples may underestimate the haemostatic potential of rFVIIa. [ABSTRACT FROM AUTHOR]

BACKGROUND: The increasing demand for platelet (PLT) transfusions has focused attention on appropriate use. Coated PLTs are a subpopulation of highly procoagulant PLTs formed by simultaneous stimulation by the agonist's collagen and thrombin hypothesized to drive clot formation at the site of vascular injury. Prolonged storage of PLTs may reduce their ability to support optimal hemostasis upon transfusion. STUDY DESIGN AND METHODS: PLT concentrates (PCs) stored for 1, 4, 6, and 8 days were costimulated with thrombin and the collagen glycoprotein VI (GPVI) receptor agonist convulxin, and their ability to form coated PLTs was determined by flow cytometry. Further, a plasma-based thrombin generation assay and thrombelastography were used to evaluate the aged PCs' capacity to support thrombin generation and clot formation, respectively. The stored PCs were additionally tested by standard quality control methods. RESULTS: PLT quality as measured by standard analyses was acceptable according to current practice. The hemostatic potential, however, was impaired with increasing storage time. The formation of coated PLTs decreased significantly from approximately 85 to 55 percent with increasing storage time (p < 0.05). The velocity of clot formation was significantly increased from Day 4 (p < 0.05). The velocity of thrombin generation and resistance against fibrinolysis were significantly reduced on Day 8 compared to Day 1 of storage (p < 0.05). CONCLUSION: Data in the present study suggest that storage significantly reduced the stored PLTs' ability to respond to conditions expected to exist at the site of vascular injury and that storage-induced reduction in PLT activation sensitivity correlated with a loss of hemostatic potential. [ABSTRACT FROM AUTHOR]

Albumin is often cited in textbooks as the gold standard for fluid replacement in paediatrics, but in practice artificial colloids are more frequently used. Although one concern with the use of artificial colloids is their intrinsic action on haemostasis, the available data in children are inconclusive for 6% hydroxyethyl starch 130/0.4 (HES) and no data exist for gelatine solution with respect to coagulation. A total of 42 children (3–15 kg) undergoing surgery and needing colloid replacement were randomly assigned to receive 15 ml.kg−1 of either albumin 5%, 4% modified gelatine solution or 6% hydroxyethyl starch 130/0.4 solution. Standard coagulation tests and modified thrombelastography (ROTEM) were performed. After colloid administration, routine coagulation test results changed significantly and comparably in all groups, although activated partial thromboplastin time values increased more with gelatine and HES. Coagulation time was unchanged in the children who received albumin or gelatine but other activated modified thrombelastography values were significantly impaired in all groups. After gelatine and after albumin the median clot firmness decreased significantly but remained within the normal range. Following HES, coagulation time increased significantly, and clot formation time, α angle, clot firmness, and fibrinogen/fibrin polymerisation were significantly more impaired than for albumin or gelatine, reaching median values below the normal range. From a haemostatic point of view it might be preferable to use gelatine solution as an alternative to albumin; HES showed the greatest effects on the overall coagulation process. [ABSTRACT FROM AUTHOR]

Background: Platelet activation is a critical step in primary hemostasis and clot formation. We tested a hypothesis that platelet stimulating effects of vasoactive agents or platelet agonists could be shown using thrombelastography (TEG®) as faster onset or increased clot strength. We further examined if TEG® could be modified to evaluate activated platelets as a reversal of anticoagulation in the presence of partial thrombin inhibition. Methods: Blood samples were obtained from 126 non-cardiac surgical patients. Effects of vasoactive agents on TEG® and aggregometry were examined using epinephrine, norepinephrine, vasopressin, desmopressin acetate, milrinone and olprinone (Experiment I). Platelet agonists (epinephrine, ADP and collagen) were separately tested on TEG® (Experiment II). Effects of platelet agonists (ADP and collagen) on TEG® under anticoagulation in the absence or presence of abciximab were studied (Experiment III). We also tested antiplatelet effects of milrinone and olprinone in the presence of anticoagulants on TEG® (Experiment IV). Results: Neither vasoactive agents nor platelet agonists affected TEG® or aggregometry results except for milrinone and olprinone on aggregometry (Experiment I, II). Platelet agonists facilitated clotting in the presence of anticoagulants (Experiment III). Abciximab-treated platelets still exhibited procoagulant effects in the presence of heparin, while not in the presence of argatroban (Experiment III). Platelet inhibition on the modified TEG® was more extensive with milrinone than olprinone, and it was dose dependent (Experiment IV). Conclusion: Modified TEG® using heparin or argatroban might delineate the procoagulant effects of platelets by adding platelet specific agonist. [ABSTRACT FROM AUTHOR]

Background: Hydroxyethyl starch (HES) administration has resulted in decreased hemostasis and fibrinogen (FI)-thrombin-(FIIa)-Factor XIII (FXIII) interactions. I proposed to determine the hemostatic effect of hemodilution with PentaLyte® (6% HES, mean molecular weight 220 kDa) and Voluven® (6% HES, 130 kDa). Methods: Rabbits were intravenously administered 20 ml/kg PentaLyte® or Voluven® ( n = 8 per fluid) over 10 min. Plasma was obtained prior to, 1 min and 1 h after hemodilution. Thrombelastography was performed, with clot initiation (R, sec), clot propagation (α, degrees), and clot strength (shear elastic modulus, G, dynes/cm2) determined over 20 min. Celite-activated samples had either no additions or addition of FI, FIIa or activated FXIII (FXIIIa) to restore protein content to pre-diluted values. Results and conclusions: While there were no significant differences between the groups, R significantly decreased 1 h after hemodilution compared with values observed before and 1 min after hemodilution, whereas α and G significantly decreased 1 min after hemodilution and then significantly, but only partially, increased 1 h after hemodilution compared with pre-dilution values. Addition of FI, FIIa and FXIIIa significantly decreased R in both groups. α and G 1 min after hemodilution were significantly enhanced by FI, FIIa, FXIIIa in both groups; however, 1 h after hemodilution, rabbits administered PentaLyte® had α and G enhanced only by FI and FXIIIa addition, whereas animals administered Voluven® had α and G significantly enhanced by FI addition. PentaLyte® and Voluven® hemodilution initially diminishes FIIa-FI and FXIIIa-fibrin, but within an hour primarily inhibit FXIIIa-fibrin interactions in the rabbit. [ABSTRACT FROM AUTHOR]

Background: Bacterial infections have been proposed as a trigger for portal hypertensive bleeding in cirrhotic patients. Endogenous low molecular weight heparinoids have been previously detected in vitro by heparinase-modified thromboelastography, but it is not known what type of heparinoids they are. The aim of this study was to assay anti-Xa concentrations to detect heparin activity in infected cirrhotics in vivo. Methods: We evaluated 30 cirrhotic patients (15 with bacterial infection, 15 not infected) and 9 non-cirrhotic patients with bacterial infection. The anti-Xa assay was performed at the start of infection in all patients and after resolution of infection in 8 cirrhotics (5 to 10 days after starting antibiotics); thromboelastography (native and heparinase I-modified TEG) was performed in a subgroup of 11 cirrhotic patients with infection, 8 cirrhotics without infection and 8 non-cirrhotics with infection. Results: Anti-Xa activity was detected in 9 of the 15 infected cirrhotics (60%) and only in 1 of 15 non-infected cirrhotics (6.7%) ( P < 0.01). In the infected cirrhotic patients, a heparinase effect was shown in the heparinase I-modified TEG: k time ( P < 0.01), α-angle ( P < 0.01) and r time ( P = 0.05), with no effect in the non-infected cirrhotics. Four of 9 (44%) infected non-cirrhotics were positive with the anti-Xa assay. Conclusion: In cirrhotic patients, bacterial infections modify haemostasis by producing endogenous heparin-like substances which can inhibit the activated clotting factor X (factor Xa). In infected non-cirrhotics, anti-Xa activity can also be found. [ABSTRACT FROM AUTHOR]

The adhesion of blood clots to wounds is necessary to seal injured vasculature and achieve hemostasis. However, it has not been specifically tested if adhesive failure of clots is a major contributor to rebleeding and what mechanisms prevent clot delamination. Here, we quantified the contribution of adhesive and cohesive failure to rebleeding in a rat model of femoral artery injury, and identified mechanisms that contribute to the adhesive strength of bulk clots in a lap-shear test in vitro. In the rat bleeding model, the frequency of clot failures correlated positively with blood loss (R = 0.81, p = 0.014) and negatively with survival time (R = − 0.89, p = 0.0030), with adhesive failures accounting for 51 ± 14% of rebleeds. In vitro, adhesion depended on fibrinogen and coagulation factor XIII (FXIII), and supraphysiological FXIII improved adhesive strength. Furthermore, when exogenous FXIII was topically applied into the wound pocket of rats, eleven adhesive failures occurred between eight rats, compared to seventeen adhesive failures between eight untreated rats, whereas the number of cohesive failures remained the same at sixteen in both groups. In conclusion, rebleeding from both adhesive and cohesive failure of clots decreases survival from hemorrhage in vivo. Both endogenous and exogenous FXIII improves the adhesive strength of clots. [ABSTRACT FROM AUTHOR]