FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2897067679> ?p ?o ?g. }

• W2897067679 endingPage "e53" @default.
• W2897067679 startingPage "e52" @default.
• W2897067679 abstract "To the Editor: We read with great interest the intriguing study by Walker et al.1 involving 14 adult patients receiving extracorporeal life support (ECLS) who were transitioned to bivalirudin as alternative systemic anticoagulation in the context of heparin-induced thrombocytopenia (HIT), heparin resistance, persistent clotting or bleeding while on heparin. We commend the authors for their work in this important area and share their passion and enthusiasm for caring for ECLS patients. Results Walker et al.1 reported favorable outcomes with 64% surviving to successful ECLS decannulation and 50% surviving to hospital discharge in this high-risk population. The majority of the patients reported by Walker et al.1 received bivalirudin secondary to suspicion for or confirmed HIT and as such additional attention to this indication is warranted. Although uncommon, HIT during ECLS remains a recognized entity with one study reporting its diagnosis in three of nine acute respiratory distress syndrome patients.2 It should be noted that the diagnosis of HIT in patients treated with ECLS is challenged by the multitude of factors that can precipitate a drop in platelet count including sepsis, disseminated intravascular coagulation, activation by artificial surfaces, and various medical disorders thereby necessitating laboratory testing (heparin-platelet factor 4 enzyme-linked immunosorbent assay [ELISA] and confirmatory heparin-induced platelet aggregation or serotonin release assay).3 However, despite negative test results HIT may still be present.4 Reinforcing this clinical challenge, Walker et al.1 reported positive HIT ELISAs in eight of the 11 cases with a suspicion for HIT. Among the remaining three patients with negative HIT ELISAs, two experienced a 50% decrease in platelets without thrombosis and one patient developed thrombotic complications despite therapeutic heparinization. Discussion Given the necessity of systemic anticoagulation during ECLS and the nontrivial reported incidence and complications of HIT, alternative strategies for achieving therapeutic anticoagulation are necessary. Bivalirudin is a semisynthetic bivalent inhibitor of thrombin that produces transient reversal of thrombin with a short half-life of 25 minutes. Although its clearance is largely organ independent (blood proteases), the kidneys provide approximately 20% of its clearance necessitating dose adjustments with moderate renal insufficiency and its molecular properties facilitate clearance with hemodialysis.5 Unlike the heparin–antithrombin III complex, bivalirudin exerts its effect by directly attaching to and inhibiting both free and fibrin-bound thrombin.6 Potential advantages over unfractionated heparin include the inhibition of fibrin (clot)-bound thrombin, a lack of binding to other plasma proteins yielding a more predictable anticoagulant response, no effect on platelet factor 4, and independence of antithrombin as cofactors producing a cleaner and more consistent anticoagulant effect.7 In addition to the importance of renal clearance well outlined by Walker et al.,1 bivalirudin carries other unique risks that are relevant to the ECLS population. Owing to its pharmacological profile, bivalirudin is rapidly cleaved by proteolytic enzymes with a short elimination half-life. In areas of stagnant blood flow where bivalirudin concentrations cannot be maintained by continuous systemic infusion of the drug, thrombus formation may be experienced because of the rapid cleavage of bivalirudin (such as during cardiac surgery with cardiopulmonary bypass, pericardial and pleural spaces, hard-shell cardiotomy reservoir, and stagnant atrial or ventricular blood flow).8 To avoid this condition, at our center in cases of intracardiac stasis bivalirudin is avoided. If ongoing bivalirudin therapy is necessary then maintenance of partial extracorporeal membrane oxygenation (ECMO) support is provided thereby maintaining a minimal degree of intracardiac blood flow. Given the risks associated with reduced circuit flow when employing bivalirudin, a protocol for anticoagulation management during ECLS weaning is essential to avoid thrombus formation during low-flow states. The authors should be applauded for describing well the impact of renal function and renal replacement therapy on bivalirudin dosing during ECLS. However, the approach as described is reactionary rather than anticipatory in that dosing was guided by activated partial thromboplastin time (aPTT) levels that fluctuated in part because of changes in renal clearance (native or through dialysis). Evidence of the limitations of this approach includes the wide variation in initial infusion rate (0.02–0.26 mg/kg/h) and median time to target aPTT (0.4–13.7 hours) that Walker et al.1 reported. In addition, the median maintenance infusion rates of bivalirudin for all patients regardless of their renal function and for those patients who received CRRT were reported in the study. However, drawing conclusions from the data and applying the maintenance dosing in clinical practice is limited because of the small sample size (n = 14) and the limited number of patients within each creatinine clearance ranges. In contrast, our center developed an algorithmic-based approach that determines initial starting dose and dose adjustments based on estimated creatinine clearance. It is possible that this approach may accelerate the time to therapeutic anticoagulation while minimizing the number of titration steps necessary to achieve therapeutic dose particularly during rapidly changing effective renal function. This approach may also be easily adopted and applied by other ECMO centers. We would like to congratulate the authors for their shrewd observation that in some patients, there is limited aPTT response at times despite notable increases in the bivalirudin infusion rates. It is in line with our center’s experience. The plausible explanations behind this phenomenon are likely twofold in addition to what might be attributed to intra- and interpatient variability. First of all, it is a known conundrum that all parenteral direct thrombin inhibitors (DTI) experience flattening of the dose response curve with a loss of linearity of DTI concentration and aPTT values at high dose ranges.9 This is an inherent limitation of using aPTT to monitor DTIs. Second, the less well-known phenomenon of the so-called apparent DTI resistance has started to gain recognition and understanding among the medical professionals with the increased widespread use of DTIs.10,11 Apparent DTI resistance refers to the presence of elevated factor VIII levels that interfere with the laboratory aPTT assays, which makes the aPTT value artificially low and seemingly disproportionate to the degree of the increase in DTI doses. Elevated factor VIII levels are widely prevalent in the critically ill patient population as one of the acute phase reactants.12 This is similar to what has been recognized and described in cases of elevated factor VIII levels contributing to apparent heparin resistance (an inadequate aPTT response in vitro despite appropriate in vivo antithrombotic efficacy of heparin as measured by anti-Xa levels).13 This phenomenon has significant clinical implications in terms of its recognition and management. At our center, if this phenomenon is suspected in setting of a confirmed elevated factor VIII level, alternate laboratory tests including thrombin time and activated clotting time have been pursued as an adjunct to monitor bivalirudin effect (Ecarin clotting time is not readily available). In addition to the dose capping as alluded to by Walker et al.1, the most important measure is to use clinical indicators including ECMO circuit patency and potential thrombotic and bleeding complications as our ultimate guidance for anticoagulation titration rather than solely relying on the number of aPTT values. Conclusions Although the available evidence for the use of bivalirudin as first line for systemic anticoagulation (i.e., not as salvage therapy because of refractory hemorrhage, thrombosis, HIT, or heparin resistance) remains limited, bivalirudin has been demonstrated to have potential advantages in post cardiotomy ECMO patients including a substantial reduction in aPTT variability, a reduction in blood loss, a decrease in allogeneic blood product transfusions, and a reduction in total patient cost versus heparin-based anticoagulation.14,15 The largest case series to date describing the use of bivalirudin in pediatric patients on ECMO found it viable as a potential option in patients who develop heparin resistance, heparin-induced thrombocytopenia, or significant thrombosis while on heparin.16 Although we concede that it is premature to recommend bivalirudin as first line during ECLS, based on the available published evidence it is time that larger well-conceived retrospective, or ideally randomized prospective, studies be undertaken to clarify the indication and role of bivalirudin in ECLS. Furthermore, a better understanding of the optimal dosing, monitoring, and the unique considerations of bivalirudin in ECLS patients is crucial given the relatively high rates of thrombotic and hemorrhagic complications in this complex patient population. Troy G. SeelhammerJohn K. BohmanDevon O. AgangaDepartment of Anesthesiology and Perioperative MedicineMayo Clinic College of MedicineRochester, Minnesota[email protected] Simon MaltaisDepartment of Cardiovascular SurgeryMayo Clinic College of MedicineRochester, Minnesota Yanjun ZhaoDepartment of PharmacyMayo ClinicRochester, Minnesota" @default.
• W2897067679 created "2018-10-26" @default.
• W2897067679 creator A5007480558 @default.
• W2897067679 creator A5019025747 @default.
• W2897067679 creator A5021856520 @default.
• W2897067679 creator A5070582129 @default.
• W2897067679 creator A5091641477 @default.
• W2897067679 date "2019-07-01" @default.
• W2897067679 modified "2023-09-28" @default.
• W2897067679 title "Bivalirudin and ECLS: Commentary and Considerations" @default.
• W2897067679 cites W1482291463 @default.
• W2897067679 cites W1534764765 @default.
• W2897067679 cites W1579223497 @default.
• W2897067679 cites W1884856356 @default.
• W2897067679 cites W1986420206 @default.
• W2897067679 cites W1986902970 @default.
• W2897067679 cites W2008894053 @default.
• W2897067679 cites W2026410273 @default.
• W2897067679 cites W2057934428 @default.
• W2897067679 cites W2083163901 @default.
• W2897067679 cites W2100034967 @default.
• W2897067679 cites W2102807089 @default.
• W2897067679 cites W2125743489 @default.
• W2897067679 doi "https://doi.org/10.1097/mat.0000000000000891" @default.
• W2897067679 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30299300" @default.
• W2897067679 hasPublicationYear "2019" @default.
• W2897067679 type Work @default.
• W2897067679 sameAs 2897067679 @default.
• W2897067679 citedByCount "5" @default.
• W2897067679 countsByYear W28970676792019 @default.
• W2897067679 countsByYear W28970676792021 @default.
• W2897067679 countsByYear W28970676792022 @default.
• W2897067679 crossrefType "journal-article" @default.
• W2897067679 hasAuthorship W2897067679A5007480558 @default.
• W2897067679 hasAuthorship W2897067679A5019025747 @default.
• W2897067679 hasAuthorship W2897067679A5021856520 @default.
• W2897067679 hasAuthorship W2897067679A5070582129 @default.
• W2897067679 hasAuthorship W2897067679A5091641477 @default.
• W2897067679 hasConcept C164705383 @default.
• W2897067679 hasConcept C177713679 @default.
• W2897067679 hasConcept C2777565915 @default.
• W2897067679 hasConcept C2780400711 @default.
• W2897067679 hasConcept C500558357 @default.
• W2897067679 hasConcept C71924100 @default.
• W2897067679 hasConceptScore W2897067679C164705383 @default.
• W2897067679 hasConceptScore W2897067679C177713679 @default.
• W2897067679 hasConceptScore W2897067679C2777565915 @default.
• W2897067679 hasConceptScore W2897067679C2780400711 @default.
• W2897067679 hasConceptScore W2897067679C500558357 @default.
• W2897067679 hasConceptScore W2897067679C71924100 @default.
• W2897067679 hasIssue "5" @default.
• W2897067679 hasLocation W28970676791 @default.
• W2897067679 hasLocation W28970676792 @default.
• W2897067679 hasOpenAccess W2897067679 @default.
• W2897067679 hasPrimaryLocation W28970676791 @default.
• W2897067679 hasRelatedWork W1970371692 @default.
• W2897067679 hasRelatedWork W201942647 @default.
• W2897067679 hasRelatedWork W2025630420 @default.
• W2897067679 hasRelatedWork W2053426227 @default.
• W2897067679 hasRelatedWork W2075335231 @default.
• W2897067679 hasRelatedWork W2128100443 @default.
• W2897067679 hasRelatedWork W2289214695 @default.
• W2897067679 hasRelatedWork W2948807893 @default.
• W2897067679 hasRelatedWork W3135394311 @default.
• W2897067679 hasRelatedWork W2778153218 @default.
• W2897067679 hasVolume "65" @default.
• W2897067679 isParatext "false" @default.
• W2897067679 isRetracted "false" @default.
• W2897067679 magId "2897067679" @default.
• W2897067679 workType "article" @default.