FAQ: Anticoagulation

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 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.

2. Why is systemic anticoagulation needed with Impella heart pumps?

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. 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, are addressed in a separate question.

3. Why are additional additives in the purge needed?

Additional additives, like heparin, in the purge are required to keep two important regions of the pump clear of debris:  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 These additives in the purge solution enhance protection against ingress, adsorption, deposition, and coagulation of blood components. It also improves bearing working life of Impella CP®.

4. What is the recommended heparin concentration in the purge solution with Impella heart pumps?

The recommended purge solution with Impella heart pumps is 25 U/ml* of unfractionated heparin with 5% glucose in water (G5). It is important to note that saline solution should not be used in the purge solution as this may impact motor durability. The glucose concentration of the purge solution determines the viscosity and flow rate of the purge fluid. Studies suggest that lower glucose concentrations, such as 5% (G5), are less viscous and flow quickly through the purge system, thereby increasing the amount of heparin delivered.² On the other hand, higher glucose concentrations, such as 20% (G20), are more viscous and result in a slower purge flow rate and less heparin infusion. A change from 20% to 5% glucose results in approximately 30-40% increase in purge flow rates. Thus, it is suggested that higher glucose 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.

*G5 with heparin 25 U/mL or 50 U/mL is acceptable.

5. What is the recommended bicarb concentration in the purge solution with Impella heart pumps?

The background to the effectiveness of sodium bicarbonate is that it changes the pH of the otherwise slightly acidic purge solution. Sodium bicarbonate increases the pH of G5% to a range of 8.1-8.4 and increases the electrostatic repulsion of the proteins. This results in a more stable environment in the purge solution, reducing the risk of blood protein denaturation. The recommended dosage for the purge solution is 25mmol sodium bicarbonate in 1L G5%. Systemic anticoagulation is still recommended and levels should be monitored regularly in all patients.

6. 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 mmHg) 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 heart pumps have built-in pressure sensors, through which the device automatically sets and adjusts the purge flow anywhere between 2 and 30 ml/h to maintain the adequate purge pressure range. If Heparin is administered with the purge, 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.

7. Are there alternatives to heparin while using Impella heart pumps?

As previously mentioned, Bicarb (see 5) is an approved alternative to Heparin in the Purge solution. Otherwise, Heparin is the only anticoagulant approved by the FDA for use in the Impella purge solution. If a patient is intolerant to heparin, e.g. due to heparin-induced thrombocytopenia (HIT), it is recommended to utilize an anticoagulant free purge solution with Bicarb as an additive and continue an alternative systemic anticoagulant.  Impella heart pumps have not been tested with DTIs in the purge solution, and recent data suggests they 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 recommended.⁸  Additional medical information on alternatives to heparin in the purge, with Impella heart pumps can be requested here or by reaching out to medical affairs at Abiomed, [email protected].

Systemic delivery of an alternative anticoagulant such as direct thrombin inhibitors (DTIs) should be considered when a patient is intolerant to heparin.⁴