Viscoelastic point-of-care testing to assist with the diagnosis, management and monitoring of haemostasis: a systematic review and cost-effectiveness analysis

Abstract

BackgroundPatients with substantive bleeding usually require transfusion and/or (re-)operation. Red blood cell (RBC) transfusion is independently associated with a greater risk of infection, morbidity, increased hospital stay and mortality. ROTEM (ROTEM®Delta, TEM International GmbH, Munich, Germany;www.rotem.de), TEG (TEG®5000 analyser, Haemonetics Corporation, Niles, IL, USA;www.haemonetics.com) and Sonoclot (Sonoclot®coagulation and platelet function analyser, Sienco Inc., Arvada, CO) are point-of-care viscoelastic (VE) devices that use thromboelastometry to test for haemostasis in whole blood. They have a number of proposed advantages over standard laboratory tests (SLTs): they provide a result much quicker, are able to identify what part of the clotting process is disrupted, and provide information on clot formation over time and fibrinolysis.ObjectivesThis assessment aimed to assess the clinical effectiveness and cost-effectiveness of VE devices to assist with the diagnosis, management and monitoring of haemostasis disorders during and after cardiac surgery, trauma-induced coagulopathy and post-partum haemorrhage (PPH).MethodsSixteen databases were searched to December 2013: MEDLINE (OvidSP), MEDLINE In-Process and Other Non-Indexed Citations and Daily Update (OvidSP), EMBASE (OvidSP), BIOSIS Previews (Web of Knowledge), Science Citation Index (SCI) (Web of Science), Conference Proceedings Citation Index (CPCI-S) (Web of Science), Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA) database, Latin American and Caribbean Health Sciences Literature (LILACS), International Network of Agencies for Health Technology Assessment (INAHTA), National Institute for Health Research (NIHR) HTA programme, Aggressive Research Intelligence Facility (ARIF), Medion, and the International Prospective Register of Systematic Reviews (PROSPERO). Randomised controlled trials (RCTs) were assessed for quality using the Cochrane Risk of Bias tool. Prediction studies were assessed using QUADAS-2. For RCTs, summary relative risks (RRs) were estimated using random-effects models. Continuous data were summarised narratively. For prediction studies, the odds ratio (OR) was selected as the primary effect estimate. The health-economic analysis considered the costs and quality-adjusted life-years of ROTEM, TEG and Sonoclot compared with SLTs in cardiac surgery and trauma patients. A decision tree was used to take into account short-term complications and longer-term side effects from transfusion. The model assumed a 1-year time horizon.ResultsThirty-one studies (39 publications) were included in the clinical effectiveness review. Eleven RCTs (n = 1089) assessed VE devices in patients undergoing cardiac surgery; six assessed thromboelastography (TEG) and five assessed ROTEM. There was a significant reduction in RBC transfusion [RR 0.88, 95% confidence interval (CI) 0.80 to 0.96; six studies], platelet transfusion (RR 0.72, 95% CI 0.58 to 0.89; six studies) and fresh frozen plasma to transfusion (RR 0.47, 95% CI 0.35 to 0.65; five studies) in VE testing groups compared with control. There were no significant differences between groups in terms of other blood products transfused. Continuous data on blood product use supported these findings. Clinical outcomes did not differ significantly between groups. There were no apparent differences between ROTEM or TEG; none of the RCTs evaluated Sonoclot. There were no data on the clinical effectiveness of VE devices in trauma patients or women with PPH. VE testing was cost-saving and more effective than SLTs. For the cardiac surgery model, the cost-saving was £43 for ROTEM, £79 for TEG and £132 for Sonoclot. For the trauma population, the cost-savings owing to VE testing were more substantial, amounting to per-patient savings of £688 for ROTEM compared with SLTs, £721 for TEG, and £818 for Sonoclot. This finding was entirely dependent on material costs, which are slightly higher for ROTEM. VE testing remained cost-saving following various scenario analyses.ConclusionsVE testing is cost-saving and more effective than SLTs, in both patients undergoing cardiac surgery and trauma patients. However, there were no data on the clinical effectiveness of Sonoclot or of VE devices in trauma patients.Study registrationThis study is registered as PROSPERO CRD42013005623.FundingThe NIHR Health Technology Assessment programme.

Routine use of viscoelastic blood tests for diagnosis and treatment of coagulopathic bleeding in cardiac surgery: updated systematic review and meta-analysis

“…The trial by Karkouti and colleagues 7 also failed to demonstrate any difference in overall complication rates; although again the exact complications and their frequencies were not specified. Overall, the results of this trial mirrored the findings of the 2016 Cochrane review; 33 notably, that the use of viscoelastic testing reduced transfusion, but had no benefit with respect to objective clinically important end points. This is at odds with the findings of the systematic review conducted by Whiting and colleagues, 33 who concluded that viscoelastic testing was likely to be cost-effective.…”

“…Overall, the results of this trial mirrored the findings of the 2016 Cochrane review; 33 notably, that the use of viscoelastic testing reduced transfusion, but had no benefit with respect to objective clinically important end points. This is at odds with the findings of the systematic review conducted by Whiting and colleagues, 33 who concluded that viscoelastic testing was likely to be cost-effective. Their analysis directly informed current National Health Service NICE Guidelines, which recommend routine use of viscoelastic testing in cardiac surgery.…”

“…33 Using assumptions based on historical data showing strong associations between RBC transfusion and adverse clinical outcomes, 35 they estimated that this reduction in RBC transfusion would be cost-effective. 33 However, cause and effect between RBC transfusion and adverse outcome has been questioned by recent studies, 36 including the Transfusion Indicating Threshold Reduction 2 (TITRE2) trial, where reductions in RBC transfusion attributable to application of a restrictive transfusion threshold increased mortality. 37 Combined with the uncertain effects of bias on subjective transfusion decisions, these results question the accuracy of existing NICE guidance.…”

Impact of Early Thromboelastography-Directed Therapy in Trauma Resuscitation

“…In trauma patients with TIC, evidence exists that viscoelastic tests supersede CCTs in delineating the process of the clotting cascade and therefore are useful in guiding blood products transfusion [7]. Recent guidelines on the management of TIC encourages a treatment strategy focused on goal directed resuscitation with more restriction in the use of intravenous fluids during initial resuscitation [10].…”

Neurosurgical applications of viscoelastic hemostatic assays

“…65 Evidence also supports the cost-effectiveness of VHAs compared with CCTs. 66 Device-specific limitations may influence the preference of one VHA platform over the other. While the standard ROTEM device is automated and capable of analyzing 4 samples simultaneously, the TEG device is limited to 2 samples at a time.…”