1. What causes thrombus formation among blood-contacting medical devices and what can be done to prevent thrombosis?
Thrombus formation is a common cause of failure among blood-contacting medical devices.1 Blood is composed of cells and plasma. Plasma contains distinct proteins, and rapid adsorption of these plasma proteins onto non-biologic surfaces is thought to be the initiating event in thrombus formation. Protein adsorption on non-biologic surfaces promotes adhesion and activation of platelets, leukocytes and the coagulation cascade leading to thrombus formation.
Efforts to prevent thrombus formation among blood-contacting medical devices such as the Impella® heart pump include systemic administration of anticoagulant medications such as heparin and direct thrombin inhibitors.
Virchow’s triad dictates that three factors are critically important in the development of thrombosis: stasis, activation of coagulation, and endothelial injury, or foreign material surfaces, in the case of devices. Specifically for the Impella, the surface area allowing for thrombus formation is smaller compared to other devices, such as durable LVADs, and the fluid flow profile of the Impella is optimized to avoid any regions allowing for stagnation with low wall shear stress that might initiate thrombosis. Thrombus deposition may occur on the catheter and in the larger gap of the purge system, described in a later question.
2. Why is systemic anticoagulation needed with Impella heart pumps?
The Impella heart pump consists of an intravascular microaxial blood pump and cannula through which blood is aspirated from the left ventricle and expelled into the ascending aorta. Systemic anticoagulation refers to the use of medications such as heparin systemically in order to prevent or decrease the risk of thrombus formation along the length of the catheter or on the body of the device. Reasoning for additional additives in the purge fluid, such as heparin or sodium bicarbonate, are addressed in a separate question.
3. Why are additional additives in the purge needed?
Additional additives, like heparin or sodium bicarbonate, are required in the purge to keep two important regions of the pump clear of biomaterial deposits: the small radial purge-flow gap between the rotor shaft and the sleeve bearing within the pump motor, and the larger axial gap between the sleeve bearing and the back-side of the impeller. As blood flows into the Impella catheter, a purge solution runs in the opposite direction to the blood to create a pressure barrier that prevents blood from entering the Impella motor.2 Heparin and Bicarbonate in the purge solution enhances protection against ingress, adsorption, deposition, and coagulation of blood components by stabilizing serum blood proteins through raising the pH in the micro-environment of the purge and conferring a negative charge to repel the like charge of surface proteins. It also improves bearing working life of Impella CP®. We postulate that the smaller radial purge-flow gap is protected by the purge solution while the larger axial gap has a dual protection from both the purge solution and systemic anticoagulation the patient is receiving3.
4. What is the recommended heparin concentration in the purge solution with Impella heart pumps?
The recommended purge solution with Impella devices is 25 U/mL* of unfractionated heparin with 5% dextrose in water (D5W). It is important to note that saline solution should not be used in the purge solution as this may impact motor durability.
*D5W with heparin 25 U/mL or 50 U/mL is acceptable.
5. How is anticoagulation with Impella heart pumps achieved?
During device insertion, administration of a heparin bolus to target an activated clotting time (ACT) of 250 seconds or longer is required. If the patient has exposure to glycoprotein IIb/IIIa inhibitors, the recommended ACT is 200 seconds or longer. The Impella heart pumps require a specific purge pressure range (300-1100 mm Hg) for optimal pump flow and a specific systemic ACT anticoagulation range (160-180 seconds) for optimal and sustained function. Studies report aPTT targets ranging between 55 and 80 seconds with optimal outcomes or anti-Xa ranges of 0.3-0.5.4-7 The development of dosing nomograms to achieve target anticoagulation parameters is imperative for optimizing patient safety with heparin.
The Impella heart pumps have built-in pressure sensors, through which the device automatically sets and adjusts the purge flow anywhere between 2 and 30 mL/hr to maintain the adequate purge pressure range. In some patients, such as those with a low body surface area (BSA), the target anticoagulation range may be achieved via heparin in the Impella purge solution alone, if heparin is the purge solution utilized. In most patients, concurrent systemic (non-purge) heparin is used to achieve target anticoagulation. Regardless, one must account for both heparin in the purge (which is ultimately delivered systemically) and additional systemic heparin when calculating total heparin exposure and dosing for the patient. This is paramount to patient safety in order to avoid over-anticoagulating the patient. The total dose of heparin while being administered both systemically and through the purge solution is calculated by adding the rate of heparin in the Impella purge solution and the systemic heparin infusion.
6. Are there alternatives to heparin while using Impella heart pumps?
If a patient is intolerant to heparin, due to heparin-induced thrombocytopenia (HIT) or bleeding, it is recommended to utilize sodium bicarbonate 25 mEq/1L D5W and continue an alternative systemic anticoagulant. Recent data suggests that DTIs may be suboptimal as an additive in the purge. Hence, the addition of DTIs such as argatroban or bivalirudin to the Impella purge solution is not recommended9. Additional medical information on sodium bicarbonate can be viewed here and additional questions can be sent to medical affairs at Abiomed at [email protected].
Systemic delivery of an alternative anticoagulant such as direct thrombin inhibitors (DTIs) should be considered when a patient is intolerant to heparin.5
Heparin-Free Purge Solution
Sodium bicarbonate purge solution for Impella® heart pumps received FDA PMA approval in April 2022, as an alternative to heparin, for patients who are intolerant to heparin or in whom heparin is contraindicated (e.g. due to heparin-induced thrombocytopenia or bleeding).
- Jaffer, J.H., et al. (2015). J Thromb Haemost, 13 Suppl 1, S72-S81.
- Succar, L., et al. (2019). J Thromb Thrombolysis, 48(2), 284-291.
- Moretz J.D., et al. (2022). Ann Pharmacother.
- Jennings, D.L., et al. (2013). Ann Pharmacother, 47(10), 1364-1367.
- Burzotta, F., et al. (2015). Int J Cardiol, 201, 684-691.
- Jennings, D.L., et al. (2010). Am J Health Syst Pharm, 67(21), 1825-1828.
- Seyfarth, M., et al. (2008). J Am Coll Cardiol, 52(19), 1584-1588.
- Dietrich, J.N., et al. (2019). J Pharm Pract, 32(4), 464-469.
- Hohlfelder, B., et al. (2021). Int J Artif Organs, 44(5), 367-370.