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 Impella heart pump include 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.
The Impella device consists of an intravascular microaxial blood pump and cannula through which blood is aspirated from the left ventricle and expelled into the ascending aorta. Due to the potential thrombotic complications during blood movement through the Impella device, adequate anticoagulation is required.
Heparin in the purge is required to keep two important regions of the pump clear of biomaterial: the small radial purge-flow gap between the rotor shaft and the sleeve bearing within the pump motor, and the 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 in the purge solution enhances protection against ingress, adsorption, deposition, and coagulation of blood components. It also improves bearing working life of Impella CP.
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. The dextrose concentration of the purge solution determines the viscosity and flow rate of the purge fluid. Studies suggest that lower dextrose concentrations, such as 5% (D5W), are less viscous and flow quickly through the purge system, thereby increasing the amount of heparin delivered.2,7 On the other hand, higher dextrose concentrations, such as 20% (D20), are more viscous and result in a slower purge flow rate and less heparin infusion. A change from 20% to 5% dextrose results in approximately 30-40% increase in purge flow rates. Thus, it is suggested that higher dextrose concentrations can be used in patients who may have higher ACT or aPTT levels, or are anticipated to have lower anticoagulation needs, such as those with lower BSA.
*D5W with heparin 25 U/mL or 50 U/mL is acceptable.
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 devices 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.3-6 The development of dosing nomograms to achieve target anticoagulation parameters is imperative for optimizing patient safety with heparin.
The Impella devices 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. 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. The Impella heparin calculator is available at https://www.protectedpci.com/heparin-rate-calculator/.
Heparin is the only anticoagulant approved by the FDA for use in the Impella purge solution. If a patient is intolerant to heparin, due to heparin-induced thrombocytopenia (HIT), it is recommended to utilize an anticoagulant free purge solution and continue an alternative systemic anticoagulant. Impella devices have not been tested with DTIs in the purge solution. Hence, the addition of DTIs such as argatroban or bivalirudin to the Impella purge solution is not recommended. Additional medical information on the use of DTIs in the purge, or other alternatives to heparin in the purge, with Impella devices can be requested at https://www.abiomed.us/npi-search/ or by reaching out to medical affairs at Abiomed, email@example.com.
Systemic delivery of an alternative anticoagulant such as direct thrombin inhibitors (DTIs) should be considered when a patient is intolerant to heparin.4 The dosage and details of the use of DTIs for anticoagulation are available for licensed health care practitioners are at https://www.abiomed.us/npi-search/.
- Jaffer IH, Fredenburgh J C, Hirsh J, Weitz JI. Medical device-induced thrombosis: what causes it and how can we prevent it? J Thromb Haemost 2015;13 Suppl 1:S72-81
- Succar L, Sulaica EM, Donahue KR, Wanat MA. Management of Anticoagulation with Impella® Percutaneous Ventricular Assist Devices and Review of New Literature. J Thromb Thrombolysis. 2019;48:284-291.
- Jennings DL, Nemerovski CW, Kalus JS. Effective anticoagulation for a percutaneous ventricular assist device using a heparin-based purge solution. Ann Pharmacother 2013; 47:1364–1367.
- Burzotta F, Trani C, Doshi SN et al. Impella ventricular support in clinical practice: collaborative viewpoint from a European expert user group. Int J Cardiol 2015;201:684–691.
- Jennings DL, Nemerovski CW, Khandelwal A. Extended use of a percutaneous left-ventricular assist device without a heparin-based purge solution. Am J Health Syst Pharm 2010; 67:1825–1828.
- Seyfarth M, Sibbing D, Bauer I et al. A randomized clinical trial to evaluate the safety and efficacy of a percutaneous left ventricular assist device versus intra-aortic balloon pumping for treatment of cardiogenic shock caused by myocardial infarction. J Am Coll Cardiol 2008; 52:1584–1588.
- Dietrich JN, Kazmi H. Bleeding Risks in Patients on Percutaneous Ventricular Assist Devices Receiving Two Different Dextrose Concentrations of Heparinized Purge Solution: A Case Series. J Pharm Pract. 2019;32:464-469.