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A systematic review on viscoelastic testing in subarachnoid haemorrhage patients
Tjerkstra, M. A., Wolfs, A. E., Verbaan, D., Vandertop, W. P., Horn, J., Müller, M. C. A., Juffermans, N. P.
World Neurosurgery. 2023
Abstract
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.
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The role of point of care thromboelastography (TEG) and thromboelastometry (ROTEM) in management of Primary postpartum haemorrhage: A meta-analysis and systematic review
Khanna P, Sinha C, Singh AK, Kumar A, Sarkar S
Saudi journal of anaesthesia. 2023;17(1):23-32
Abstract
BACKGROUND The utility of instantaneous evaluation of coagulation during primary postpartum haemorrhage (PPH) is paramount in the context of empirical blood product transfusion-related risk of dilutional and consumptive coagulopathy and circulatory overload. METHODS A profound screening of electronic databases till August 15, 2022 was carried out after being enlisted in PROSPERO (CRD42021275514). Randomized control studies, comparative cohort studies, and cross-sectional studies comparing point-of-care viscoelastic test guided blood product transfusion with empirical transfusion in patients with PPH were included. RESULTS We retrieved five studies, with a total of 1914 parturient with PPH. Patients receiving transfusion based upon point of care viscoelastic tests had lesser risk of having emergency hysterectomy (Odds ratio (OR) = 0.55, 95% CI 0.32-0.95, I(2) = 7%), transfusion-associated circulatory overload (TACO) (OR = 0.03, 95% CI 0.00-0.50), reduced transfusion of fresh frozen plasma (OR = 0.07, 95% CI 0.04-0.14, I(2) = 89%), platelets (OR = 0.51, 95% CI 0.28-0.91, I(2) = 89%), packed red blood cell transfusion (OR = 0.70, 95% CI 0.55-0.88, I(2) = 89%), and had better cost-effective treatment [Mean difference (MD) = -357.5, 95% CI - 567.75 to -147.25, I(2) = 93%] than patient received empirical transfusion. However, there was no significant difference in the requirement of ICU admissions (OR = 0.77, 95% CI = 0.46-1.29, I(2) = 82%). No mortality was detected across the studies. CONCLUSIONS Point of care viscoelastic assessment guided transfusion in PPH confederates with reduced morbidity. Nevertheless, more studies on the triggering values for transfusion, long-term survival, and cost-benefit in patients with PPH are warranted to establish its utility.
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Detection of Acute Traumatic Coagulopathy by Viscoelastic Haemostatic Assays Compared to Standard Laboratory Tests: A Systematic Review
Forster, E. K., Hendel, S., Mitra, B.
Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie. 2023;50(4):334-347
Abstract
INTRODUCTION The aim of this systematic review was to investigate whether viscoelastic haemostatic assays (VHAs) offer comparative diagnostic ability of acute traumatic coagulopathy (ATC) compared to the standard laboratory coagulation tests (SLCT). ATC is a complication of major trauma characterized by dysfunctional blood clotting, leading to an increased bleeding risk. Additionally, we aimed to analyse the association of VHA with blood product use and health outcomes. METHODS The search protocol was pre-published and completed on December 2, 2020, assessing manuscripts from 2000 until the present. We searched MEDLINE, Embase, Cochrane Central, BIOSIS, Emcare, CINAHL, and additional online resources and referenced lists. Included were manuscripts that quantitatively reported the detection of ATC using VHAs and SLCTs. A meta-analysis was undertaken including observational studies that reported on patients with injuries to all body regions and results analysed using a random-effects model and reported using pooled odds ratio with 95% confidence intervals (CI). RESULTS There were 14 observational studies and one randomized control trial involving 2,715 participants that satisfied inclusion criteria. We observed significant heterogeneity in the definitions of ATC, study design, setting, and patient population. Among observational studies that reported on patients with injuries to all body regions, VHAs were associated with higher odds of diagnosing ATC compared to SLCT (pooled OR 2.4; 95% CI: 1.4-4.1). There was inadequate evidence to suggest VHAs were associated with reduced blood product usage or lower mortality. CONCLUSION VHAs detected more patients with ATC compared to SLCTs. However, the clinical significance and applicability of this finding remains unknown as translation to management was not adequately reported.
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The Pitfalls of Global Hemostasis Assays in Myeloproliferative Neoplasms and Future Challenges
Tiu A, Chiasakul T, Kessler CM
Seminars in thrombosis and hemostasis. 2023
Abstract
Venous and arterial thromboembolism are major complications of myeloproliferative neoplasms (MPNs), comprising polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Global hemostasis assays, including thrombin generation assay (TGA), rotational thromboelastometry (ROTEM), and thromboelastography (TEG), have been proposed as biomarkers to assess the hypercoagulability and thrombotic risk stratification in MPNs. We performed a systematic literature review on the parameters of TGA, ROTEM, and TEG and their association with thrombotic events and treatment strategies in MPNs. Thirty-two studies (all cross-sectional) were included, which collectively enrolled 1,062 controls and 1,608 MPN patients. Among the 13 studies that reported arterial or venous thrombosis, the overall thrombosis rate was 13.8% with 6 splanchnic thromboses reported. Out of the 27 TGA studies, there was substantial heterogeneity in plasma preparation and trigger reagents employed in laboratory assays. There was a trend toward increased peak height among all MPN cohorts versus controls and higher endogenous thrombin potential (ETP) between ET patients versus controls. There was an overall trend toward lower ETP between PV and PMF patients versus. controls. There were no substantial differences in ETP between JAK2-positive versus JAK2-negative MPNs, prior history versus negative history of thrombotic events, and among different treatment strategies. Of the three ROTEM studies, there was a trend toward higher maximum clot firmness and shorter clot formation times for all MPNs versus controls. The three TEG studies had mixed results. We conclude that the ability of parameters from global hemostasis assays to predict for hypercoagulability events in MPN patients is inconsistent and inconclusive. Further prospective longitudinal studies are needed to validate these biomarker tools so that thrombotic potential could be utilized as a primary endpoint of such studies.
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Evaluation of coagulopathy in cirrhotic patients: A scoping review of the utility of viscoelastic testing
Azer, A., Kong, K., Basta, D., Modica, S. F., Gore, A., Gorman, E., Sutherland, A., Tafesh, Z., Horng, H., Glass, N. E.
American journal of surgery. 2023
Abstract
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.
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Assessment of Hemostatic Profile in Neonates with Intrauterine Growth Restriction: A Systematic Review of Literature
Karapati E, Sokou R, Iliodromiti Z, Tsaousi M, Sulaj A, Tsantes AG, Petropoulou C, Pouliakis A, Tsantes AE, Boutsikou T, et al
Seminars in thrombosis and hemostasis. 2023
Abstract
Intrauterine growth restriction (IUGR) affects nearly 10 to 15% of pregnancies and is responsible for many short- and long-term adverse consequences, including hemostatic derangement. Both thrombotic and hemorrhagic events are described in the perinatal period in these neonates. The aim of this study was to systematically review the literature on the laboratory studies used to evaluate the hemostatic system of the IUGR small for gestational age neonate. We reviewed the current literature via PubMed and Scopus until September 2022. Following our inclusion/exclusion criteria, we finally included 60 studies in our review. Thrombocytopenia, characterized as hyporegenerative and a kinetic upshot of reduced platelet production due to in utero chronic hypoxia, was the main finding of most studies focusing on growth-restricted neonates, in most cases is mild and usually resolves spontaneously with the first 2 weeks of life. In regard to coagulation, growth-restricted newborns present with prolonged standard coagulation tests. Data regarding coagulation factors, fibrinolytic system, and anticoagulant proteins are scarce and conflicting, mainly due to confounding factors. As thromboelastography/rotational thromboelastometry (TEG/ROTEM) provides a more precise evaluation of the in vivo coagulation process compared with standard coagulation tests, its use in transfusion guidance is fundamental. Only one study regarding TEG/ROTEM was retrieved from this population, where no difference in ROTEM parameters compared with appropriate for gestational age neonates was found. Despite the laboratory aberrations, no correlation could be achieved with clinical manifestations of bleeding or thrombosis in the studies included. More studies are needed to assess hemostasis in IUGR neonates and guide targeted therapeutic interventions.
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Comparison of anticoagulation monitoring strategies for adults supported on extracorporeal membrane oxygenation: A systematic review
Sun J, Ma Y, Su W, Miao H, Guo Z, Chen Q, Zhang Y, Ma X, Chen S, Ding R
Heart & lung : the journal of critical care. 2023;61:72-83
Abstract
BACKGROUND Anticoagulation is critical in patients supported on extracorporeal membrane oxygenation (ECMO). The appropriate monitoring strategies for heparin remain unclear. OBJECTIVES This systematic review aimed to compare the accuracy and safety of various monitoring strategies for patients supported on ECMO. METHODS The PubMed and Web of Science databases were searched for articles in March 2023 without restrictions on publication date. Anticoagulation monitoring strategies for adults supported on ECMO were compared across all included studies. The incidence of bleeding, thrombosis, mortality, blood transfusion, correlation between tests and heparin dose, and the discordance between different tests were discussed in the included studies. The risk of bias was assessed using the Newcastle-Ottawa Scale and Cochrane Collaboration's tool. RESULTS Twenty-six studies, including a total of 1,684 patients, met the inclusion criteria. The monitoring of anticoagulation by activated partial thromboplastin time (aPTT) resulted in less blood product transfusion than that by activated clotting time (ACT). Moreover, the monitoring of anticoagulation by anti-factor Xa (Anti-Xa) resulted in a more stable anticoagulation than that by aPTT. Anti-Xa and aPTT correlated with heparin dose better than ACT, and the discordance between different monitoring tests was common. Finally, combined monitoring showed some advantages in reducing mortality and blood product transfusion. CONCLUSION Anti-Xa and aPTT are more suitable for anticoagulation monitoring for patients supported on ECMO than ACT. Thromboelastography and combination strategies are less applied. Most of the studies were retrospective, and their sample sizes were relatively small; thus, more appropriate monitoring strategies and higher quality research are needed.
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Rotational ThromboElastometry-guided blood component administration versus standard of care in patients with Cirrhosis and coagulopathy undergoing Invasive ProcEdures (RECIPE): study protocol for a randomised controlled trial
Janko, N., Majeed, A., Kemp, W., Hogan, C., Nandurkar, H., Roberts, S. K.
Trials. 2023;24(1):516
Abstract
BACKGROUND Patients with cirrhosis often undergo invasive procedures both for management of complications of their advanced liver disease, including treatment for hepatocellular carcinoma, as well as underlying comorbidities. Despite a current understanding that most patients with cirrhosis are in a rebalanced haemostatic state (despite abnormalities in conventional coagulation tests, namely INR and platelet count), patients with cirrhosis are still often given prophylactic blood components based on these conventional parameters, in an effort to reduce procedure-related bleeding. Viscoelastic tests such as Rotational Thromboelastometry (ROTEM) provide a global measurement of haemostasis and have been shown to predict bleeding risk more accurately than conventional coagulation tests, and better guide blood product transfusion in a number of surgical and trauma-related settings. The aim of this study is to assess the utility of a ROTEM-based algorithm to guide prophylactic blood component delivery in patients with cirrhosis undergoing invasive procedures. We hypothesise that ROTEM-based decision-making will lead to a reduction in pre-procedural blood component usage, particularly fresh frozen plasma (FFP), compared with standard of care, whilst maintaining optimal clinical outcomes. METHODS This is a multi-centre randomised controlled trial comparing ROTEM-guided prophylactic blood component administration to standard of care in patients with cirrhosis and coagulopathy undergoing invasive procedures. The primary efficacy outcome of the trial is the proportion of procedures requiring prophylactic transfusion, with the primary safety outcome being procedure-related bleeding complications. Secondary outcomes include the amount of blood products (FFP, platelets, cryoprecipitate) transfused, transfusion-related side effects, procedure-related complications other than bleeding, hospital length of stay and survival. DISCUSSION We anticipate that this project will lead to improved prognostication of patients with cirrhosis, in terms of their peri-procedural bleeding risk. We hope to show that a significant proportion of cirrhotic patients, deemed coagulopathic on the basis of standard coagulation tests such as INR and platelet count, are actually in a haemostatic balance and thus do not require prophylactic blood product, leading to decreased and more efficient blood component use. TRIAL REGISTRATION RECIPE has been prospectively registered with the Australia and New Zealand Clinical Trials Registry on the 30th April 2019 ( ACTRN12619000644167 ).
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What is the optimal management of thromboprophylaxis after liver transplantation regarding prevention of bleeding, hepatic artery or portal vein thrombosis? A systematic review of the literature and expert panel recommendations
Kirchner VA, O'Farrell B, Imber C, McCormack L, Northup PG, Song GW, Spiro M, Raptis DA, Durand F
Clinical transplantation. 2022;:e14629
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Abstract
BACKGROUND A key tenet of clinical management of patients post liver transplantation (LT) is the prevention of thrombotic and bleeding complications. This systematic review investigated the optimal management of thromboprophylaxis after LT regarding portal vein thrombosis (PVT) or hepatic artery thrombosis (HAT) and prevention of bleeding. METHODS Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Seven databases were used to conduct extensive literature searches focusing on the use of anticoagulation in LT and its impact on the following outcomes: PVT, HAT, and bleeding. (CRD42021244288) RESULTS Of the 2,478 articles/abstracts screened, 16 studies were included in the final review. All articles were critically appraised by a panel of independent reviewers. There was wide variation regarding the anticoagulation protocols used. Thromboprophylaxis with therapeutic doses of heparin/Vitamin K antagonist combination did not decrease the risk of de novo or the recurrence of PVT but was associated with an increased risk of bleeding in some studies. Only the use of aspirin resulted in a small but significant decrease in the incidence of HAT post-LT, yet it did not increase the risk of bleeding. CONCLUSIONS Based on existing data and expert opinion, thromboprophylaxis at therapeutic or prophylactic dose is not recommended for prevention of de novo PVT following LT in patients not at high risk. Aspirin should be considered as the standard of care following LT to prevent HAT. Thromboprophylaxis should be strongly considered in recipients at risk of HAT and PVT following LT. This article is protected by copyright. All rights reserved.
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Rotational thromboelastometry guided blood component use in cirrhotic children undergoing invasive procedures: Randomized Controlled Trial
Maria A, Lal BB, Khanna R, Sood V, Mukund A, Bajpai M, Alam S
Liver international : official journal of the International Association for the Study of the Liver. 2022
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Editor's Choice
Abstract
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.
PICO Summary
Population
Children with liver cirrhosis undergoing invasive procedures (n= 60).
Intervention
ROTEM-based transfusion strategy (n= 30).
Comparison
Conventional coagulation tests-based transfusion strategy (n= 30).
Outcome
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.
