A systematic review on viscoelastic testing in subarachnoid haemorrhage patients
World Neurosurgery. 2023
OBJECTIVES Bleeding and thromboembolic complications frequently occur following subarachnoid haemorrhage (SAH) and substantially contribute to poor outcome. Viscoelastic testing could be used for detection of coagulopathies following SAH. This review summarizes literature on the utility of viscoelastic testing to detect coagulopathy in SAH patients and explores whether viscoelastic parameters are associated with SAH-related complications and clinical outcome. MATERIALS AND METHODS PUBMED, EMBASE and Google Scholar were systematically searched on August 18(th), 2022. Two authors independently selected studies which performed viscoelastic testing in SAH patients and assessed the quality of studies using the Newcastle Ottawa Scale or a previously published framework for quality assessment. Data was meta-analysed if methodologically possible. RESULTS The search yielded 19 studies (1160 SAH patients). Pooling of data including all relevant studies was not possible for any of the outcome measurements due to methodological differences. Thirteen of 19 studies evaluated the association of coagulation profiles and SAH, of which 11 studies showed a hypercoagulable profile. Rebleeding was associated with platelet dysfunction, deep venous thrombosis was associated with faster clot initiation and both delayed cerebral ischemia and poor outcome were associated with increased clot strength. CONCLUSIONS This explorative review shows that SAH patients frequently have a hypercoagulable profile. TEG- and ROTEM-parameters are associated with rebleeding, delayed cerebral ischemia, deep venous thrombosis and poor clinical outcome after SAH, however more research on the subject is needed. Future studies should focus on determining the optimal time frame and cut-off values for TEG or ROTEM to predict these complications.
Evaluation of coagulopathy in cirrhotic patients: A scoping review of the utility of viscoelastic testing
American journal of surgery. 2023
BACKGROUND Cirrhosis causes significant coagulopathy. Traditional coagulation tests may not accurately measure coagulopathy in well-compensated patients with cirrhosis. Viscoelastic tests are functional tests that may better assess coagulopathy in cirrhotic patients. METHODS We searched PubMed, ScienceDirect, Google Scholar, and grey literature using terms meaning viscoelastic testing and cirrhosis. After reviewing over 500 titles and abstracts, 40 full-text papers met inclusion criteria. RESULTS Twenty-two papers found viscoelastic testing was a better indicator of baseline coagulation than traditional testing in cirrhosis. Nineteen additional papers evaluated the utility of peri-procedural viscoelastic testing and found they led to a reduction in blood product administration without increasing risk of hemorrhage, thrombotic events, or other complications. CONCLUSIONS The usage of viscoelastic testing in patients with cirrhosis allows for better assessment of coagulopathy, resulting in improved outcomes. Educating physicians to optimize care of this high-risk group is necessary to further improve their treatment.
Rotational thromboelastometry guided blood component use in cirrhotic children undergoing invasive procedures: Randomized Controlled Trial
Liver international : official journal of the International Association for the Study of the Liver. 2022
BACKGROUND & AIMS This randomized controlled trial (RCT) was conducted with the aim to evaluate the efficacy and safety of using ROTEM-based transfusion strategy in cirrhotic children undergoing invasive procedures. METHODS This was a open-label, RCT which included (i) children under 18 years of age with liver cirrhosis; (ii) INR between 1.5 and 2.5; and/or (iii) platelet count between 20x10(9) /L to 50x10(9) /L (for procedures other than liver biopsy) and between 40x10(9) /L to 60x10(9) /L (for liver biopsy); and (iv) listed for invasive procedures. Stratified randomization was done for children undergoing liver biopsies. Patients randomized to the ROTEM and conventional groups received blood component transfusion using predefined criteria. RESULTS A total of 423 invasive procedures were screened for inclusion of which 60 were randomized (30 in each group with comparable baseline parameters). The volume of total blood components, fresh frozen plasma (FFP) and platelets transfused was significantly lower in ROTEM as compared to conventional group. Only 46.7% of children in ROTEM group received a blood component compared to 100% in conventional group (p<0.001). The requirement of FFP (ROTEM 43.3%, Conventional: 83.3%, p = 0.001) was significantly lower in the patients receiving ROTEM guided transfusions. There was no difference in procedure related bleed and transfusion related complications between the 2 groups. ROTEM was cost effective (p=0.002) despite the additional cost of the test. CONCLUSION ROTEM-based transfusion strategies result in lower blood component transfusion in cirrhotic children undergoing invasive procedures without an increase in risk of procedure-related bleed. ROTEM-guided transfusion strategy is cost-effective.
Children with liver cirrhosis undergoing invasive procedures (n= 60).
ROTEM-based transfusion strategy (n= 30).
Conventional coagulation tests-based transfusion strategy (n= 30).
The volume of total blood components, fresh frozen plasma (FFP) and platelets transfused was significantly lower in ROTEM as compared to conventional group. Only 46.7% of children in ROTEM group received a blood component compared to 100% in conventional group. The requirement of FFP (ROTEM: 43.3%, conventional: 83.3%) was significantly lower in the patients receiving ROTEM guided transfusions. There was no difference in procedure related bleed and transfusion related complications between the two groups. ROTEM was cost-effective despite the additional cost of the test.
Viscoelastic Testing Prior to Non-surgical Procedures Reduces Blood Product Use Without Increasing Bleeding Risk in Cirrhosis
Digestive Diseases and Sciences. 2022;67(11):5290-5299
BACKGROUND/AIMS: Thromboelastography (TEG) and Rotational Thromboelastometry (ROTEM) analyze hemostatic function in patients with coagulopathy. We sought to quantify the impact of TEG and ROTEM-guided transfusion algorithms on blood product utilization in patients with cirrhosis undergoing non-surgical procedures. METHODS We performed a systematic review and meta-analysis on the utility of viscoelastic testing prior to non-surgical procedures to determine their impact on pre-procedural blood product use and post-procedural bleeding events. Studies comparing TEG or ROTEM-guided transfusions with standard-of-care (SOC) prior to non-surgical procedures in adult patients with cirrhosis were included. Primary outcomes were fresh frozen plasma (FFP) and platelet transfusion and secondary outcomes of post-procedure bleeding, transfusion-related complications, and mortality; and were reported as standardized mean differences (SMD) and risk ratios (RR). RESULTS Six studies (five randomized controlled trials and one cohort study) involving 367 patients met inclusion criteria. Compared with SOC, TEG/ROTEM-guided transfusions led to an overall decreased number of patients who received FFP transfusions (SMD = -0.93, 95% CI [-1.54, -0.33], p < 0.001) and platelets transfusions (SMD = -1.50, CI [-1.85, -1.15], p < 0.001). Total amount of FFP (SMD-0.86, p < 0.001) and platelet (SMD = -0.99, p < 0.001) transfused in the TEG/ROTEM group were also lower. Decreased pre-procedure transfusion in the TEG/ROTEM group did not result in increased post-procedure bleeding (RR = 0.61, p = 0.09) or in mortality (RR = 0.91, p = 0.93). CONCLUSION In patients with cirrhosis, TEG or ROTEM significantly reduces blood product utilization prior to non-surgical procedures, with no increase in post-procedure bleeding or mortality. TEG and ROTEM utilization can promote high-value care and improve transfusion stewardship in this population.
Thromboelastography-Guided Therapy Enhances Patient Blood Management in Cirrhotic Patients: A Meta-analysis Based on Randomized Controlled Trials
Seminars in thrombosis and hemostasis. 2022
Patients with cirrhosis often have abnormal hemostasis, with increased risk of hemorrhage and thrombosis. Thromboelastography provides a rapid assessment of the coagulation status and can guide product transfusions in adult patients with cirrhosis. This study aimed to determine whether the use of thromboelastography in adult patients with cirrhosis decreases blood product use and impacts adverse events or mortality compared with standard practice. A registered (PROSPERO CRD42020192458) systematic review and meta-analysis was conducted for randomized controlled trials (RCTs) comparing thromboelastography-guided hemostatic management versus standard practice (control). Co-primary outcomes were the number of transfused platelet units and fresh frozen plasma (FFP) units. Secondary outcomes were mortality, adverse events, utilization of individual blood products, blood loss or excessive bleeding events, hospital/intensive care unit stay, and liver transplant/intervention outcomes. The search identified 260 articles, with five RCTs included in the meta-analysis. Platelet use was five times lower with thromboelastography versus the control, with a relative risk of 0.17 (95% confidence interval [CI]: [0.03-0.90]; p = 0.04), but FFP use did not differ significantly. Thromboelastography was associated with less blood product (p < 0.001), FFP + platelets (p < 0.001), and cryoprecipitate (p < 0.001) use. No differences were reported in bleeding rates or longer term mortality between groups, with the thromboelastography group having lower mortality at 7 days versus the control (relative risk [95% CI] = 0.52 [0.30-0.91]; p = 0.02). Thromboelastography-guided therapy in patients with cirrhosis enhances patient blood management by reducing use of blood products without increasing complications.
Patients with cirrhosis (5 studies, n= 302).
Thromboelastography-guided haemostatic management.
Standard coagulation testing (standard practice).
Platelet use was five times lower with thromboelastography vs. standard practice, with a relative risk of 0.17 (95% confidence interval [CI]: [0.03-0.90]), but fresh frozen plasma (FFP) use did not differ significantly. Thromboelastography was associated with less blood product, FFP + platelets, and cryoprecipitate use. No differences were reported in bleeding rates or longer-term mortality between groups, with the thromboelastography group having lower mortality at 7 days vs. standard practice (relative risk [95% CI] = 0.52 [0.30-0.91]).
Viscoelastic Testing in the Clinical Management of Subarachnoid Hemorrhage and Intracerebral Hemorrhage
Seminars in thrombosis and hemostasis. 2022
Subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH) are both debilitating and life-threatening incidents calling for immediate action and treatment. This review focuses on the applicability of viscoelastic testing (rotational thromboelastometry or thromboelastography [TEG]) in the management of SAH and ICH. A systematic literature search was performed in PubMed and EMBASE. Studies including patients with SAH or ICH, in which viscoelastic testing was performed, were identified. In total, 24 studies were included for analysis, and further subdivided into studies on SAH patients investigated prior to stenting or coiling (n = 12), ICH patients (n = 8) and studies testing patients undergoing stenting or coiling, or ischemic stroke patients undergoing thrombolysis or thrombectomy and developing ICH as a complication (n = 5). SAH patients had increased clot firmness, and this was associated with a higher degree of early brain injury and higher Hunt-Hess score. SAH patients with delayed cerebral ischemia had higher clot firmness than patients not developing delayed cerebral ischemia. ICH patients showed accelerated clot formation and increased clot firmness in comparison to healthy controls. Patients with hematoma expansion had longer clot initiation and lower platelet aggregation than patients with no hematoma expansion. During stent procedures for SAH, adjustment of antiplatelet therapy according to TEG platelet mapping did not change prevalence of major bleeding, thromboembolic events, or functional outcome. Viscoelastic testing prior to thrombolysis showed conflicting results in predicting ICH as complication. In conclusion, viscoelastic testing suggests hypercoagulation following SAH and ICH. Further investigation of the predictive value of increased clot firmness in SAH seems relevant. In ICH, the prediction of hematoma expansion and ICH as a complication to thrombolysis might be clinically relevant.
Hemostasis and Fibrinolysis following Aneurysmal Subarachnoid Hemorrhage: A Systematic Review on Additional Knowledge from Dynamic Assays and Potential Treatment Targets
Seminars in thrombosis and hemostasis. 2021
Mortality after aneurysmal subarachnoid hemorrhage (aSAH) is augmented by rebleeding and delayed cerebral ischemia (DCI). A range of assays evaluating the dynamic process of blood coagulation, from activation of clotting factors to fibrinolysis, has emerged and a comprehensive review of hemostasis and fibrinolysis following aSAH may reveal targets of treatment. We conducted a systematic review of existing literature assessing coagulation and fibrinolysis following aSAH, but prior to treatment. PubMed, Embase, and Web of Science were searched on November 18, 2020, without time boundaries. In total, 45 original studies were eventually incorporated into this systematic review, divided into studies presenting data only from conventional or quantitative assays (n = 22) and studies employing dynamic assays (n = 23). Data from conventional or quantitative assays indicated increased platelet activation, whereas dynamic assays detected platelet dysfunction possibly related to an increased risk of rebleeding. Secondary hemostasis was activated in conventional, quantitative, and dynamic assays and this was related to poor neurological outcome and mortality. Studies systematically investigating fibrinolysis were sparse. Measurements from conventional or quantitative assays, as well as dynamic fibrinolysis assays, revealed conflicting results with normal or increased lysis and changes were not associated with outcome. In conclusion, dynamic assays were able to detect reduced platelet function, not revealed by conventional or quantitative assays. Activation of secondary hemostasis was found in both dynamic and nondynamic assays, while changes in fibrinolysis were not convincingly demonstrable in either dynamic or conventional or quantitative assays. Hence, from a mechanistic point of view, desmopressin to prevent rebleeding and heparin to prevent DCI may hold potential as therapeutic options. As changes in fibrinolysis were not convincingly demonstrated and not related to outcome, the use of tranexamic acid prior to aneurysm closure is not supported by this review.
Clinical utility of viscoelastic testing in chronic liver disease: A systematic review
World Journal of Hepatology. 2020;12(11):1115-1127
BACKGROUND Conventional coagulation tests are widely used in chronic liver disease to assess haemostasis and to guide blood product transfusion. This is despite the fact that conventional tests do not reliably separate those with a clinically significant coagulopathy from those who do not. Viscoelastic testing such as thromboelastography (TEG) correlate with bleeding risk and are more accurate in identifying those who will benefit from blood product transfusion. Despite this, viscoelastic tests have not been widely used in patients with chronic liver disease outside the transplant setting. AIM: To assess the utility of Viscoelastic Testing guided transfusion in chronic liver disease patients presenting with bleeding or who require an invasive procedure. METHODS PubMed and Google Scholar searches were performed using the key words "thromboelastography", "TEG" or "viscoelastic" and "liver transplantation", "cirrhosis" or "liver disease" and "transfusion", "haemostasis", "blood management" or "haemorrhage". A full text review was undertaken and data was extracted from randomised control trials that evaluated the outcomes of viscoelastic test guided transfusion in those with liver disease. The study subjects, inclusion and exclusion criteria, methods, outcomes and length of follow up were examined. Data was extracted by two independent individuals using a standardized collection form. The risk of bias was assessed in the included studies. RESULTS A total of five randomised control trials included in the analysis examined the use of TEG guided blood product transfusion in cirrhosis prior to invasive procedures (n = 118), non-variceal haemorrhage (n = 96), variceal haemorrhage (n = 60) and liver transplantation (n = 28). TEG guided transfusion was effective in all five studies with a statistically significant reduction in overall blood product transfusion compared to standard of care. Four of the five studies reported a significant reduction in transfusion of fresh frozen plasma and platelets. Two studies showed a significant reduction in cryoprecipitate transfusion. No increased risk of bleeding was reported in the three trials where TEG was used perioperatively or prior to an invasive procedure. Two trials in the setting of cirrhotic variceal and non-variceal bleeding showed no difference in control of initial bleeding. In those with variceal bleeding, there was a statistically significant reduction in rate of re-bleeding at 42 d in the TEG arm 10% (vs 26.7% in the standard of care arm P = 0.012). Mortality data reported at various time points for all five trials from 6 wk up to 3 years was not statistically different between each arm. One trial in the setting of non-variceal bleeding demonstrated a significant reduction in adverse transfusion events in the TEG arm 30.6% (vs 74.5% in the control arm P < 0.01). In this study there was no significant difference in total hospital stay although length of stay in intensive care unit was reduced by an average of 2 d in the TEG arm (P = 0.012). CONCLUSION Viscoelastic testing has been shown to reduce blood product usage in chronic liver disease without compromising safety and may enable guidelines to be developed to ensure patients with liver disease are optimally managed.
Thromboelastography versus standard coagulation testing in the assessment and reversal of coagulopathy among cirrhotics: a systematic review and meta-analysis
European journal of gastroenterology & hepatology. 2020;32(3):291-302
The utility of thromboelastography/thromboelastometry currently has unvalidated clinical benefit in the assessment and reversal of coagulopathy among cirrhotic patients as compared to standard coagulation testing. A novel systematic review and meta-analysis was conducted in order to assess pooled outcome data among patients receiving thromboelastography/thromboelastometry as compared to standard coagulation testing. As compared to standard coagulation testing, there was a significant reduction in the number of patients requiring pRBC, platelet, and fresh frozen plasma transfusions among thromboelastography/thromboelastometry group with pooled OR 0.53 (95% CI 0.32-0.85; P = 0.009), 0.29 (95% CI 0.12-0.74; P = 0.009), and 0.19 (95% CI 0.12-0.31; P < 0.00001), respectively. Similarly, there was a significant reduction in number of pRBC, platelet, and fresh frozen plasma units transfused in the thromboelastography/thromboelastometry group with pooled MD -1.53 (95% CI -2.86 to -0.21; P = 0.02), -0.57 (95% CI -1.06 to -0.09; P = 0.02), and -2.71 (95% CI -4.34 to -1.07; P = 0.001), respectively. There were significantly decreased total bleeding events with pooled OR 0.54 (95% CI 0.31-0.94; P = 0.03) and amount of intraoperative bleeding during liver transplantation with pooled MD -1.46 (95% CI -2.49 to -0.44; P = 0.005) in the thromboelastography/thromboelastometry group. Overall, there was no significant difference in mortality between groups with pooled OR 0.91 (95% CI 0.63-1.30; P = 0.60). As compared to standard coagulation testing, a thromboelastography/thromboelastometry-guided approach to the assessment and reversal of cirrhotic coagulopathy improves overall number of patients exposed to blood product transfusions, quantity of transfusions, and bleeding events.
The use of viscoelastic haemostatic assays in non-cardiac surgical settings: a systematic review and meta-analysis
Blood Transfusion = Trasfusione Del Sangue. 2018;:1-3.
Thrombelastography (TEG) and rotational thromboelastometry (ROTEM) are viscoelastic haemostatic assays (VHA) which exploit the elastic properties of clotting blood. The aim of this systematic review and meta-analysis was to evaluate the usefulness of these tests in bleeding patients outside the cardiac surgical setting. MATERIALS AND METHODS We searched the Cochrane Library, MEDLINE, EMBASE and SCOPUS. We also searched clinical trial registries for ongoing and unpublished studies, and checked reference lists to identify additional studies. RESULTS We found 4 randomised controlled trials (RCTs) that met our inclusion criteria with a total of 229 participants. The sample size was small (from 28 to 111 patients) and the follow-up periods very heterogenous (from 4 weeks to 3 years). Pooled data from the 3 trials reporting on mortality (199 participants) do not show any effect of the use of TEG on mortality as compared to standard monitoring (based on the average treatment effect from a fixed-effects model): Risk Ratio (RR) 0.71; 95% Confidence Interval (CI): 0.43 to 1.16. Likewise, the use of VHA does not reduce the need for red blood cells (mean difference -0.64; 95% CI: -1.51 to 0.23), platelet concentrates (mean difference -1.12; 95% CI: -3.25 to 1.02), and fresh frozen plasma (mean difference -0.91; 95% CI: -2.02 to 0.19) transfusion. The evidence on mortality and other outcomes was uncertain (very low-certainty evidence, down-graded due to risk of biases, imprecision, and inconsistency). CONCLUSIONS Overall, the certainty of the evidence provided by the trials was too low for us to be certain of the benefits and harms of viscoelastic haemostatic assay in non-cardiac surgical settings. More, larger, and better-designed RCTs should be carried out in this area.