Evaluation of a pharmacy managed heparin protocol for extracorporeal membrane oxygenation patients

Introduction: Unfractionated heparin is the preferred anticoagulant in extracorporeal membrane oxygenation (ECMO) patients. However, there is a lack of consensus on its titration and monitoring. The objective of this study was to describe the efficacy and safety of a pharmacy managed heparin protocol utilizing activated partial thromboplastin time (aPTT) in comparison to our standard physician-managed activated clotting time (ACT)-based anticoagulation in ECMO patients. Methods: Patients administered a heparin drip while on ECMO were included in the study. The primary endpoints were the incidence of hemorrhagic and thrombotic complications. Results: A total of 122 adult patients were identified who were on ECMO with heparin anticoagulation; sixty-one patients were managed with each of the physician-managed ACT and pharmacy managed aPTT protocols. No statistically significant difference was observed between the physician ACT and the pharmacy aPTT groups in overall hemorrhagic (69% vs 80%, p=0.145) or thrombotic complications (41% vs 39%, p=0.853). Conclusion: There was a similar rate of thrombotic and bleeding events between the two study groups. A pharmacy managed heparin protocol utilizing aPTT monitoring appears to be a safe and effective method of providing anticoagulation in adult ECMO patients.

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Cost-effectiveness of Argatroban Versus Heparin Anticoagulation in Adult Extracorporeal Membrane Oxygenation Patients

Hospital Pharmacy ◽

10.1177/0018578719890091 ◽

2019 ◽

pp. 001857871989009

Author(s):

Angelina E. Cho ◽

Kathleen Jerguson ◽

Joy Peterson ◽

Deepa V. Patel ◽

Asif A. Saberi

Keyword(s):

Cost Effectiveness ◽

Extracorporeal Membrane Oxygenation ◽

Average Cost ◽

P Value ◽

Bleeding Events ◽

Membrane Oxygenation ◽

Increased Risk ◽

Heparin Anticoagulation ◽

Ischemic Events ◽

Ecmo Therapy

Purpose: The purpose of this study was to evaluate the cost effectiveness of argatroban compared to heparin during extracorporeal membrane oxygenation (ECMO) therapy. Methods: This was a retrospective study of patients who received argatroban or heparin infusions with ECMO therapy at a community hospital between January 1, 2017 and June 30, 2018. Adult patients who received heparin or argatroban for at least 48 hours while on venovenous (VV) or venoarterial (VA) ECMO were included. Patients with temporary mechanical circulatory assist devices were excluded. Each continuous course of anticoagulant exposure that met the inclusion criteria was evaluated. The primary endpoint was the total cost of anticoagulant therapy for heparin versus argatroban, including all administered study drugs, blood or factor products, and associated laboratory tests. Secondary endpoints included safety and efficacy of anticoagulation with each agent during ECMO. Documentation of bleeding events, circuit clotting, and ischemic events were noted. Partial thromboplastin time (PTT) values were evaluated for time to therapeutic range and percentage of therapeutic PTTs. Results: A total of 11 courses of argatroban and 24 courses of heparin anticoagulation were included in the study. The average cost per course of argatroban was less than the average cost per course of heparin ($7,091.98 vs $15,323.49, respectively; P value = 0.15). Furthermore, argatroban was not associated with an increased incidence of bleeding, thrombotic, or ischemic events. Conclusion: Argatroban may be more cost-effective during ECMO therapy in patients with low antithrombin III levels without increased risk of adverse events.

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Anti-Xa versus time-guided anticoagulation strategies in extracorporeal membrane oxygenation: a systematic review and meta-analysis

Perfusion ◽

10.1177/0267659120952982 ◽

2020 ◽

pp. 026765912095298

Author(s):

Ariane Willems ◽

Peter P Roeleveld ◽

Sonia Labarinas ◽

John W Cyrus ◽

Jennifer A Muszynski ◽

...

Keyword(s):

Systematic Review ◽

Mortality Rate ◽

Extracorporeal Membrane Oxygenation ◽

Observational Studies ◽

Meta Analysis ◽

Lower Mortality ◽

Bleeding Events ◽

Membrane Oxygenation ◽

Significant Difference

The purpose was to compare time-based vs anti-Xa-based anticoagulation strategies in patients on ECMO. We conducted a systematic review and meta-analysis using multiple electronic databases and included studies from inception to July 19, 2019. The proportion of bleeding, thrombosis, and mortality were evaluated. Twenty-six studies (2,086 patients) were included. Bleeding occurred in 34.2% (95%CI 25.1;43.9) of the patients with anti-Xa-based versus 41.6% (95%CI 24.9;59.4) of the patients with time-based anticoagulation strategies. Thrombosis occurred in 32.6% (95%CI 19.1;47.7) of the patients with anti-Xa-based versus 38.4% (95%CI 22.2;56.1) of the patients with time-based anticoagulation strategies. And mortality rate was 35.4% (95%CI 28.9;42.1) of the patients with anti-Xa-based versus 42.9% (95%CI 36.9;48.9) of the patients with time-based anticoagulation strategies. Among the seven studies providing results from both anticoagulation strategies, significantly fewer bleeding events occurred in the anti-Xa-based anticoagulation strategy (adjusted OR 0.49 (95%CI 0.32;0.74), p < 0.001) and a significantly lower mortality rate (adjusted OR 0.61 (95%CI 0.40;0.95), p = 0.03). There was no significant difference in thrombotic events (adjusted OR 0.91 (95%CI 0.56;1.49), p = 0.71). In these seven observational studies, only a small fraction of the patients were adults, and data were insufficient to analyze the effect of the type of ECMO. In this meta-analysis of observational studies of patients on ECMO, an anti-Xa-based anticoagulation strategy, when compared to a time-based strategy, was associated with fewer bleeding events and mortality rate, without an increase in thrombotic events.

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Preoperative and intraoperative argatroban as anticoagulant for bridging a patient with heparin-induced thrombocytopaenia to lung transplantation

European Journal of Cardio-Thoracic Surgery ◽

10.1093/ejcts/ezz294 ◽

2019 ◽

Vol 57 (5) ◽

pp. 1005-1006 ◽

Cited By ~ 1

Author(s):

Dong Kyu Oh ◽

Dong Kwan Kim ◽

Sehoon Choi ◽

Sang-Bum Hong

Keyword(s):

Extracorporeal Membrane Oxygenation ◽

Lung Transplantation ◽

Partial Thromboplastin Time ◽

Activated Partial Thromboplastin Time ◽

Clotting Time ◽

Membrane Oxygenation ◽

Activated Clotting Time ◽

Thrombotic Complications

Abstract A 65-year-old male was bridged to lung transplantation with veno-venous extracorporeal membrane oxygenation (ECMO). After experiencing heparin-induced thrombocytopaenia, heparin was replaced with argatroban. After 24 days, bilateral sequential lung transplantation was performed with argatroban anticoagulation. Intraoperative argatroban doses ranged between 0.4 and 0.6 μg/kg/min, resulting in activated clotting time of 169–216 s and activated partial thromboplastin time of 45–75 s. The patient was weaned from ECMO immediately after lung transplantation, and no bleeding or thrombotic complications were observed. He was discharged home on postoperative day 140.

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Anti-Factor Xa–Based Anticoagulation during Extracorporeal Membrane Oxygenation: Potential Problems and Possible Solutions

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0039-1697950 ◽

2019 ◽

Vol 46 (04) ◽

pp. 419-427 ◽

Cited By ~ 4

Author(s):

Marco Ranucci ◽

Mauro Cotza ◽

Giuseppe Isgrò ◽

Giovanni Carboni ◽

Andrea Ballotta ◽

...

Keyword(s):

Extracorporeal Membrane Oxygenation ◽

Reaction Times ◽

Factor Xa ◽

Real Effects ◽

Membrane Oxygenation ◽

Chromogenic Assay ◽

Relative Contribution ◽

Activated Clotting Time ◽

Thrombotic Complications

AbstractChoices for monitoring of unfractionated heparin (UFH) anticoagulation in extracorporeal membrane oxygenation (ECMO) patients include activated clotting time, activated partial thromboplastin time, reaction times of viscoelastic tests, and anti-factor Xa activity (between 0.3 and 0.7 IU/mL). Recent studies propose the anti-factor Xa to be the gold standard for monitoring UFH anticoagulation in ECMO. However, many extraneous factors combined question the utility of anti-factor Xa as the sole method of monitoring of UFH effects in ECMO. Anti-factor Xa is a chromogenic assay, which may be biased by the frequently elevated values of bilirubin and free hemoglobin in ECMO patients. The test may alternatively underestimate UFH effects in cases of low antithrombin values. More importantly, the anti-factor Xa assay is a plasma-based test which does not take into account the role of platelets and fibrinogen in forming a stable clot. Thrombocytopenia and platelet dysfunction are common features in ECMO patients, and underestimating their role may lead to over-anticoagulation, should only anti-factor Xa guiding be used to adjust the UFH dose. Conversely, fibrinogen is an acute phase protein, and some patients may experience high levels of fibrinogen during the ECMO course. In this case, an UFH monitoring based on anti-factor Xa is insensitive to this condition, although it may potentially be associated with thrombotic complications. Finally, the generally suggested range of 0.3 to 0.7 IU/mL is a somewhat arbitrary estimate, based on the desired range for treating and preventing thrombotic events in non-ECMO patients. In conclusion, anti-factor Xa may offer useful information on the real effects of UFH only when combined with a whole blood test capable of assessing the relative contribution of platelets and fibrinogen to clot formation.

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Antithrombin Supplementation during Extracorporeal Membrane Oxygenation: Study Protocol for a Pilot Randomized Clinical Trial

10.21203/rs.2.62/v1 ◽

2018 ◽

Author(s):

Mauro Panigada ◽

Elena Spinelli ◽

Alberto Cucino ◽

Elisa Cipriani ◽

Giovanna Panarello ◽

...

Keyword(s):

Extracorporeal Membrane Oxygenation ◽

Pilot Trial ◽

Study Groups ◽

Control Group ◽

Membrane Oxygenation ◽

Transfusion Requirements ◽

Hemorrhagic Events ◽

Secondary Endpoints ◽

Thrombotic Complications ◽

The Impact

Abstract Background: Normal levels of plasma antithrombin (AT) activity might decrease heparin requirements to achieve anticoagulation target during treatment with extracorporeal membrane oxygenation (ECMO), possibly reducing the risk of bleeding. Acquired AT deficiency during ECMO is common, but formal recommendation on target, timing, and rate of AT supplementation is lacking. Thus, we conceived a pilot trial to evaluate the feasibility and safety of prolonged AT supplementation in patients requiring veno-venous ECMO for respiratory failure. Methods: GATRA is a phase 3, prospective, randomized, single blinded multicenter controlled two-arm trial. Patients undergoing veno-venous ECMO will be randomized to either receive AT supplementation to maintain a functional AT level between 80%-120% (AT supplementation group) or not (control group) for the entire ECMO course. In both study groups anticoagulation will be provided with unfractionated heparin following a standardized protocol. The primary endpoint will be the dose of heparin required to maintain ratio of activated partial thromboplastin time between 1.5-2. Secondary endpoints will be the adequacy of anticoagulation and the incidence of hemorrhagic and thrombotic complications. Discussion: GATRA is a pilot trial that will test the efficacy of a protocol of AT supplementation in decreasing the heparin dose and improving anticoagulation adequacy during ECMO. If positive, it might provide the basis for a future larger trial aimed at verifying the impact of AT supplementation on a composite outcome endpoint including hemorrhagic events, transfusion requirements and mortality. Trial registration: ClinicalTrials.gov, NCT03208270. Registered on 5 July 2017.

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Antithrombin Supplementation during Extracorporeal Membrane Oxygenation: Study Protocol for a Pilot Randomized Clinical Trial

10.21203/rs.2.62/v2 ◽

2019 ◽

Author(s):

Mauro Panigada ◽

Elena Spinelli ◽

Alberto Cucino ◽

Elisa Cipriani ◽

Stefano De Falco ◽

...

Keyword(s):

Extracorporeal Membrane Oxygenation ◽

Pilot Trial ◽

Study Groups ◽

Control Group ◽

Membrane Oxygenation ◽

Transfusion Requirements ◽

Hemorrhagic Events ◽

Secondary Endpoints ◽

Thrombotic Complications ◽

The Impact

Abstract Background: Normal levels of plasma antithrombin (AT) activity might decrease heparin requirements to achieve an adequate level of anticoagulation during treatment with extracorporeal membrane oxygenation (ECMO). Acquired AT deficiency during ECMO is common, but formal recommendation on target, timing, and rate of AT supplementation is lacking. Thus, we conceived a pilot trial to evaluate the feasibility and safety of prolonged AT supplementation in patients requiring veno-venous ECMO for respiratory failure. Methods: GATRA is a phase 3, prospective, randomized, single blinded multicenter controlled two-arm trial. Patients undergoing veno-venous ECMO will be randomized to either receive AT supplementation to maintain a functional AT level between 80%-120% (AT supplementation group) or not (control group) for the entire ECMO course. In both study groups anticoagulation will be provided with unfractionated heparin following a standardized protocol. The primary endpoint will be the dose of heparin required to maintain ratio of activated partial thromboplastin time between 1.5-2. Secondary endpoints will be the adequacy of anticoagulation and the incidence of hemorrhagic and thrombotic complications. Discussion: GATRA is a pilot trial that will test the efficacy of a protocol of AT supplementation in decreasing the heparin dose and improving anticoagulation adequacy during ECMO. If positive, it might provide the basis for a future larger trial aimed at verifying the impact of AT supplementation on a composite outcome endpoint including hemorrhagic events, transfusion requirements and mortality. Trial registration ClinicalTrials.gov, NCT03208270. Registered on 5 July 2017.

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Anticoagulation after VA-ECMO decannulation, providing new insights

European Heart Journal Acute Cardiovascular Care ◽

10.1093/ehjacc/zuab020.168 ◽

2021 ◽

Vol 10 (Supplement_1) ◽

Author(s):

A Maestro-Benedicto ◽

A Duran-Cambra ◽

M Vila-Perales ◽

J Sans-Rosello ◽

J Carreras-Mora ◽

...

Keyword(s):

Extracorporeal Membrane Oxygenation ◽

Cardiogenic Shock ◽

Anticoagulation Therapy ◽

Thromboembolic Events ◽

Bleeding Events ◽

Membrane Oxygenation ◽

Funding Sources ◽

Va Ecmo ◽

A Prospective Study

Abstract Funding Acknowledgements Type of funding sources: None. INTRODUCTION Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is an essential tool for the management of refractory cardiogenic shock. Little is known about the incidence of thromboembolic events after V-A ECMO decannulation, although some studies report a high incidence of cannula-related venous thrombosis after venovenous extracorporeal membrane oxygenation (VV-ECMO). Due to this fact, in our institution anticoagulation therapy is systematically prescribed for at least 3 months after VA-ECMO per protocol. AIM The main objective of this study was to explore the feasibility of 3-month anticoagulation therapy after VA-ECMO decannulation. METHODS We performed a prospective study that included 27 consecutive patients who were successfully treated with VA-ECMO in a medical ICU between 2016 and 2019 and were prescribed 3-month anticoagulation therapy per protocol after decannulation. Exclusion criteria was dying on ECMO or while on the ICU. Data analysis included demographics, mean days on ECMO, 3-month survival, and thromboembolic and bleeding events (excluding immediate post-decannulation bleeding, since anticoagulation was prescribed 24h after). RESULTS Our cohort consisted mainly of men (N = 21, 78%), with a mean age of 60 ± 11 years and a mean time on VA-ECMO of 8 ± 3 days, who primarily suffered from post-cardiotomy cardiogenic shock (N = 9, 34%) or acute myocardial infarction (N = 6, 23%). 5 patients (18%) received a heart transplant. Regarding anticoagulation, 15 patients (60%) had other indications apart from the protocol, like incidental thrombus diagnosis (N = 7, 26%) or valve surgery (N = 5, 18%). Anticoagulation therapy was not feasible in 1 patient (4%) with severe thrombopenia. No patients had severe or life-threatening bleeding events in the follow-up, although 8 patients (30%) had bleeding events, mainly gastrointestinal bleeding (N = 4, 15%), requiring withdrawal of anticoagulation in 1 patient. The incidence of thromboembolic events was 7%; two patients with low-risk pulmonary embolisms. During the 3-month follow-up survival rate was 95%. CONCLUSIONS This is the only study to date addressing the strategy of 3-month anticoagulation therapy after VAECMO, showing it is feasible and safe and may be helpful in reducing or ameliorate thromboembolic complications in the follow-up, although it is not exempt of complications. Abstract Figure. Kaplan-Meier survival analysis

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Veno-arterial extracorporeal membrane oxygenation with concomitant Impella versus concomitant intra-aortic-balloon-pump for cardiogenic shock

Perfusion ◽

10.1177/02676591211033947 ◽

2021 ◽

pp. 026765912110339

Author(s):

Shek-yin Au ◽

Ka-man Fong ◽

Chun-Fung Sunny Tsang ◽

Ka-Chun Alan Chan ◽

Chi Yuen Wong ◽

...

Keyword(s):

Extracorporeal Membrane Oxygenation ◽

Mechanical Circulatory Support ◽

Primary Outcome ◽

Left Ventricular ◽

Circulatory Support ◽

Queen Elizabeth Hospital ◽

Intra Aortic Balloon Pump ◽

Membrane Oxygenation ◽

Significant Difference ◽

Va Ecmo

Introduction: The intra-aortic balloon pump (IABP) and Impella are left ventricular unloading devices with peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) in place and later serve as bridging therapy when VA-ECMO is terminated. We aimed to determine the potential differences in clinical outcomes and rate of complications between the two combinations of mechanical circulatory support. Methods: This was a retrospective, single institutional cohort study conducted in the intensive care unit (ICU) of Queen Elizabeth Hospital, Hong Kong. Inclusion criteria included all patients aged ⩾18 years, who had VA-ECMO support, and who had left ventricular unloading by either IABP or Impella between January 1, 2018 and October 31, 2020. Patients <18 years old, with central VA-ECMO, who did not require left ventricular unloading, or who underwent surgical venting procedures were excluded. The primary outcome was ECMO duration. Secondary outcomes included length of stay (LOS) in the ICU, hospital LOS, mortality, and complication rate. Results: Fifty-two patients with ECMO + IABP and 14 patients with ECMO + Impella were recruited. No statistically significant difference was observed in terms of ECMO duration (2.5 vs 4.6 days, p = 0.147), ICU LOS (7.7 vs 10.8 days, p = 0.367), and hospital LOS (14.8 vs 16.5 days, p = 0.556) between the two groups. No statistically significant difference was observed in the ECMO, ICU, and hospital mortalities between the two groups. Specific complications related to the ECMO and Impella combination were also noted. Conclusions: Impella was not shown to offer a statistically significant clinical benefit compared with IABP in conjunction with ECMO. Clinicians should be aware of the specific complications of using Impella.

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