The ability of the thromboelastogram (TEG® R-time difference between kaolin and heparinase) as a point of care test to predict residual heparin activity after in vitro protamine titration
| dc.contributor.advisor | Levin, Andrew I. | en_ZA |
| dc.contributor.author | Joseph, Lauren Ann | en_ZA |
| dc.contributor.other | Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Anaesthesiology and Critical Care. | en_ZA |
| dc.date.accessioned | 2017-11-21T15:55:27Z | |
| dc.date.accessioned | 2017-12-11T10:36:54Z | |
| dc.date.available | 2019-05-21T03:00:08Z | |
| dc.date.issued | 2017-12 | |
| dc.description | Thesis (MMed)--Stellenbosch University, 2017. | en_ZA |
| dc.description.abstract | ENGLISH ABSTRACT: Background: Differentiation between surgical bleeding and coagulopathy is critical as re-exploration is associated with increases in mortality and morbidity. Adequate reversal of heparin with protamine at the end of cardiopulmonary bypass (CPB) is critical to prevent postoperative bleeding. Meticulous dosing of protamine is required as excessive dosages has deleterious side effects on clotting. Traditional methods make use of an activated clotting time (ACT) for evaluation of adequate heparin reversal. However, recent use of other point of care (POC) tests, the thromboelastogram (TEG®) has started challenging the utility and exclusive use of ACT to evaluate effective reversal. Differences between thromboelastographic Rkaolin and R-heparinase times is an indicator of residual heparin. However, the exact relationship between these parameters and the exact amount of residual heparin is unknown. The rationale for this study was to accurately determine the relationship between the magnitude of the R-kaolin and R-heparinase time difference and blood heparin concentrations. Aims: This study was performed to define the in-vitro relationship between the difference between the thromboelastographic R-kaolin and R-heparinase time difference (TEG® Delta-kh R-time) and plasma heparin concentrations. The primary outcome was to determined the relationship between the TEG® Delta-kh R-time difference and heparin concentrations. The secondary outcome was to determine the concentration of heparin at or below which R-kaolin times become measureable. Methods: This was a single centre, prospective, randomized laboratory study. Following institutional ethics approval and informed consent, sixty-two samples were taken during CPB from 20 patients meeting inclusion criteria. Samples were randomized to one of three groups which would dictate the protamine dose. The three groups were based on a protamine to heparin ratio (expressed as milligram protamine per milligram heparin administered to the patient) approximating 0.25, 0.5, and 0.75 mg/mg respectively. Each sample of blood was then administered a dose of protamine. The TEG® analysis entailed measuring the R-kaolin and R-heparinase time and noting the difference. Thereafter, each blood sample was sent for heparin concentration determination using an anti-Xa activity assay. Results: No relationship between the measurable R-kaolin time and heparin concentration could be demonstrated (p=0.80), as well as no relationship between measurable TEG® Delta-kh R- time difference and heparin activity (p=0.42). However, we did identify a high probability to be able to predict a measurable R-kaolin time (negative predictive value 90%, 95% CI 74% to 98%) when heparin concentration is less than 1.24IU/ml. Conclusions: We were unable to predict heparin concentration using TEG® in this study. It is likely that this was related to methodological problems. The protamine dose was a complex calculation and there is uncertainty with regard to the actual amounts used. There were also multiple laboratory technicians, with a possible loss of standardization. However, R-kaolin time will likely be measurable at heparin concentrations below 1.24 IU/ml, and not measurable above that value. This observation is immensely valuable for clinicians and researchers. Future studies should take this into account and attempt to determine the relationship between TEG® Delta-kh R- time differences and heparin activity only when heparin concentration are less than 1.24IU/ml. | en_ZA |
| dc.description.abstract | AFRIKAANSE OPSOMMING: Agtergrond Onderskeiding tussen chirurgiese bloeding en koagulopatie is krities belangrik, want hereksplorasie is geassosieer met ‘n toename in mortaliteit en morbiditeit. Die voldoende omkeuring van heparien met protamien aan die einde van Kardiolpulmonêre omleiding (KPO) is krities om postoperatiewe bloeding te voorkom. Noukeurige dosering van Protamien word benodig aangesien oormatige dosering nadelige newe-effekte op stolling. Geaktiveerde Sollingstyd (ACT) word gebruik om voldoende omkeuring van Heparien te evalueer. Onlangse gebruik van Point-of-Care toets, Tromboelastogram (TEG®), het egter die eksklusiewe gebruik van ACT uit te daag. ‘n Verskil tussen Tromboelastografiek R-kaolin en R-heparienase tyd is aanduidend van oorblywende heparien. Die presiese verhouding tussen hierdie twee parameters is nie bekend nie. Die rasionaal was om akkuraat die verhouding tussen die hoeveelheid van die verskil tussen die R-kaolin en R-heparienase tyd en bloed Heparien konsentrasies te bepaal. Doel: Hierdie studie was uitgevoer om die in-vitro verhouding te definieer tussen die verskil van Tromboelastografiek R-kaolin en R-heparienase tyd (TEG® Delta-kh R-tyd) en plasma heparien konsentrasies. Die primêre uitkoms was vasgestel as die verhouding tussen die TEG® Delta-kh R-tydsverskil en heparienaktiwiteits-konsentrasies. Die sekondere uitkoms was om die heparien konsentrasies te bepaal waaronder die Rkaolin tyd meetbaar raak. Metodiek: Hierdie was ‘n enkel sentrum, prospektiewe gerandomiseerde laboratorium studie. Na institusionele etiese goedkeuring en ingeligte toestemming, is 62 monsters geneem tydends KPO van 20 pasiente wat die insluitings kriteria vervul het. Die monsters was gerandomiseer tot een van drie groepe wat die Protamien titreringsdosering sal dikteer. Die drie groepe was gebaseer op ‘n Protamien tot Heparien verhouding (uitgedruk as milligram protamien per milligram heparien toegedien aan die pasient) wat 0.25, 0.5, en 0.75mg/mg onderskeidelik benader. ‘n Dosis Protamien was toegedien tot elke monster. Die TEG® analise het behels om die R-koalin en R-heparienase tyd te meet en die verskil daarvan aan te dui. Daarna is elke bloed monster gestuur vir die bepaling van die Heparien konsentrasie met die gebruik van ‘n anti-Xa aktiwiteitstoets. Resultate: Geen verwantskap tussen die R-kaolin tyd en Heparien konsentrasie kon getoon word nie. (P=0.80). Daar was ook geen verwantskap getoon tussen meetbare TEG® Deltakh R- tyd en Heparien aktiwiteit nie. (P=0.42). Ons het wel ‘n hoë waarskynlikheid geidentifiseer om die meetbare R-kaolin tyd (negatiewe voospellings waarde 90%, 95% CI 74% tot 98%) te voorspel wanneer Heparien konsentrasie minder is as 1.24IU/ml. Gevolgtrekking: Ons was nie in staat om Heparien konsentrasie te voorspel, in die studie, met die gebruik van TEG® nie. Dit is moontlik dat dit toegeskryf kan word aan metodieke tekortkominge. Die Protamien titreringsdosering was ‘n kompleks berekening en daar is onsekerheid oor die werklike hoeveelhede wat gebruik was. Daar was ook veelvuldige laboratorium tegnikuste, ten spyte van opleiding, het ‘n moontlike verlies van standaardisering plaasgevind. R-kaolin tyd sal egter waarskynlik meetbaar wees by ‘n Heparien konsentrasie onder 1.24IU/ml en nie meetbaar by konsentrasies onder daardie waarde nie. Die observasie is van waarde vir klinikuste en navorsers. Toekomstige studies moet dit in oorweging bring en probeer om die verwantskap tussen TEG® Delta-kh R- tydsverskil en Heparien aktiwiteit te bepaal. | af_ZA |
| dc.description.version | Masters | en_ZA |
| dc.embargo.terms | 2019-05-21 | |
| dc.format.extent | 76 pages | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/10019.1/102650 | |
| dc.language.iso | en_ZA | en_ZA |
| dc.publisher | Stellenbosch : Stellenbosch University | en_ZA |
| dc.rights.holder | Stellenbosch University | en_ZA |
| dc.subject | Thromboelastogram | en_ZA |
| dc.subject | Heparin reversal -- Measurement | en_ZA |
| dc.subject | Cardiopulmonary bypass | en_ZA |
| dc.subject | Blood -- Coagulation | en_ZA |
| dc.subject | Hemorrhage -- Prevention | en_ZA |
| dc.subject | Protamine | en_ZA |
| dc.subject | UCTD | |
| dc.title | The ability of the thromboelastogram (TEG® R-time difference between kaolin and heparinase) as a point of care test to predict residual heparin activity after in vitro protamine titration | en_ZA |
| dc.type | Thesis | en_ZA |