Dean  Ferrera, DO, FSCAI; Craig Beavers, PharmD, FAHA BCPS-AQ Cardiology, CACP; and Faisal Latif, MD, FSCAI

Introduction

Percutaneous mechanical circulatory support with the Impella device (Abiomed) remains a critical tool at the hands of many interventional cardiologists. Observational data sets have demonstrated an increased use of Impella over time for both protected percutaneous coronary intervention (PCI) and cardiogenic shock indications since its approval for use in 2008.¹

Bleeding outcomes remain problematic for patients who require mechanical circulatory support devices, particularly in acute myocardial infarction with cardiogenic shock (AMI-CS).² Moreover, AMI-CS patients may have added bleeding and vascular complication risks compared to matched intra-aortic balloon pump control patients.³

In this Tip of the Month, we focus specifically on the anticoagulation management of Impella patients. Pharmacological management of anticoagulation strategies will be discussed to better understand and optimize the safety of the Impella family of devices to minimize bleeding risk while maximizing device function. Although data remains limited, recommendations regarding anticoagulation strategies are available and remain a focus of this clinical tip).⁴ We will not discuss the routine post-PCI anticoagulation strategies or management of vascular complications in general.

Practical Management of Anticoagulation

The Impella percutaneous left ventricular assist device is a microaxial pump that aspirates blood from the left ventricle into the aorta. Traditionally, a heparin-based purge solution is essential to create a positive purge pressure, lubricate bearings, and prevent the ingress of blood into the motor. Intravenous unfractionated heparin (UFH) is used concomitantly with the purge solution to maintain systemic anticoagulation and prevent thrombus formation. 

The following best practice recommendations and schematic are a useful paradigm to maintain essential pump function, prevent thrombogenesis, and avoid over-anticoagulation, which may lead to adverse bleeding events. Further considerations can also be highlighted via this link.

Best Practice Recommendations for Heparin With Impella Use (Adapted From Reference 4)

1. For the standard heparin-based purge solution, it is recommended dextrose 5% in water be utilized as the standard purge solution fluid at this time (based on the manufacturer’s instructions for use).
2. Higher dextrose concentrations with the heparin-based purge solution, up to 40%, may be utilized in the setting of low-pressure alarms, with a preference of dextrose in 20% water in this setting.
3. If a high-pressure alarm is experienced, it is recommended to decrease dextrose to 5% in water concentration if a higher dextrose concentration with the heparin-based purge solution is being used.
4. Saline should not be used in the purge solution, even if combined with a dextrose-containing fluid.
5. Heparin at a concentration of 25 units/mL is recommended as the standard purge solution when Impella support is continued for ongoing continuous cardiac support outside of procedural settings.
6. Heparin-free purge solutions should be considered in patients with laboratory-confirmed or a very high suspicion of heparin-induced thrombocytopenia (HIT) or in patients with a confirmed allergy to pork or heparin.
7. Direct thrombin inhibitors (bivalirudin and argatroban) are not recommended for the use in the purge solution.
8. A sodium bicarbonate-based purge solution (BBPS, 25 mEq per 1,000mL in 5% of dextrose) may be preferred in scenarios when a heparin-based purge solution is not feasible.
9. Dextrose 5% in water without heparin may be considered when Impella devices are utilized for intraprocedural cardiac augmentation when the device is removed at the end of the procedure. If a purge solution containing heparin is not readily available, it is recommended to change to a heparin-containing purge solution as soon as possible following device insertion. 
10. If clinically significant bleeding occurs with the Impella device in place, removing the heparin from the purge solution and potentially changing to BBPS should be considered.
11. An anti-Xa target range of 0.2-0.4 IU/mL or an activated partial thromboplastin time (aPTT) that corresponds to this anti-Xa range based on local institution’s laboratory reagent is recommended.
12. If anticoagulation targets are not achieved from heparin in the purge solution or heparin is absent from the purge solution, intravenous heparin should be supplemented.
13. The amount of intravenous heparin administered should factor in the amount of heparin currently being supplied from a heparin-based purge solution.
14. If clinically significant bleeding or coagulopathy develops, a stepwise approach is suggested:
    1. Discontinue intravenous heparin and maintain heparin in the purge solution.
    2. If bleeding or coagulopathy persists, then remove heparin from the purge solution and substitute with BBPS.
    3. Consider plain dextrose if BBPS is not available.
15. Until further investigation defines an optimal anticoagulation monitoring assay, it is recommended that centers utilize their standard assay for monitoring intravenous anticoagulation for both heparin and nonheparin agents when managing patients on prolonged support. There currently is insufficient data to suggest one assay over another.

Conclusion 

Anticoagulation remains paramount in maintaining normal Impella function. Given the complexity of patient care in the management of cardiogenic shock, a common approach workflow to prevent device related thrombogenesis — while minimizing patient related bleeding events — remains advantageous to the interventional cardiologist.

References

1. Amin AP, Spertus JA, Curtis JP, et al. The Evolving Landscape of Impella Use in the United States Among Patients Undergoing Percutaneous Coronary Intervention With Mechanical Circulatory Support. Circulation 2020 Jan 28;141(4):273-284.
2. Dhruva SS, Ross JS, Mortazavi BJ, et al. Association of Use of Intravascular Microaxial Left Ventricular Assist Device vs Intra-aortic Balloon Pump With In-Hospital Mortality and Major Bleeding Among Patients with Acute Myocardial Infarction Complicated by Cardiogenic Shock. JAMA. 2020 Feb 25;323(8):734-745.
3. Schrage B, Ibrahim K, Loehn T, et al. Impella Support for Acute Myocardial Infarction Complicated by Cardiogenic Shock. 2019 Mar 5;139(10):1249-1258.
4. Beavers CJ, DiDomenico RJ, Dunn SP, et al. Optimizing anticoagulation for patients receiving Impella support. Pharmacotherapy. 2021 Nov;41(11):932-942.