Unfractionated Heparin Protocol During Percutaneous Left Ventricular Mechanical Circulatory (Impella) Support

The Impella is one of several left ventricular assist devices (LVADs) used in a variety of clinical conditions in which arterial circulation is compromised due to diminished cardiac output. ¹ The Impella system operates on the principle of an Archimedes screw pump. It continuously draws blood from the left ventricle via an inlet port, transports it through the aortic valve, and expels it into the ascending aorta via an outlet port. The Impella requires a specific purge pressure range (300-1100 mm Hg) for optimal pump flow and a specific systemic activated clotting time (ACT) anticoagulation range (160-180 seconds) for sustained function. Despite a critical anticoagulation requirement, the 2015 SCAI/ACC/HFSA/STS Clinical Expert Consensus Statement on the use of LVADs remains silent on methodology recommendations to achieve the mandatory anticoagulation intensity. ¹ In this brief report, we describe our use of an unfractionated heparin (UFH) protocol that we find easy to use, safe, and effective at the MemorialCare Heart & Vascular Institute, Long Beach Memorial, California.

To evaluate whether our systemic UFH protocol for Impella is safe and effective in maintaining the required target intensity of anticoagulation, we conducted a quality improvement (QI) analysis. As a QI evaluation of an existing standard of care protocol, informed consent was not required. When the purge pressure solution containing UFH was inadequate in maintaining the ACT within the required target goal range, a second source of UFH was initiated as an intravenous (IV) infusion. Patients who did not require a second source of IV UFH infusion were excluded from this analysis. Therapy was monitored at bedside using point-of-care ACT, and the IV UFH was initiated and titrated as outlined in the systemic heparin protocol (Table 1). Patient demographics, type of Impella, duration of LVAD support, and utilization of second systemic IV UFH infusion were noted, and all ACT values during dual UFH infusion (intra-arterial and IV) were collected and analyzed.

Table 1.

Systemic IV Heparin Protocol for Use in Conjunction With Impella.

Target ACT 160-180 seconds
Diagnostic Testing/Labs
Activated clotting time (ACT)	Obtain ACT hourly until in the range of 160-180 seconds and then every 6 hours
Activated clotting time (ACT)	Every 6 hours and every 4 hours after each dosage change
INR	Every morning
CBC without differential	Every 12 hours (0600 and 1800)
Heparin Dose
Initial Heparin Dosage—For ACT <130, begin infusion at 200 U/h. For ACT 130-159, begin infusion at 100 U/h. No bolus at any time
IV heparin infusion rates are rounded to nearest 50 U/h
Heparin Titration
ACT (seconds)	Systemic Heparin Infusion
<130	Increase rate by 200 U/h
131-159	Increase rate by 100 U/h
160-180	Same rate
181-200	Reduce rate by 50 U/h
201-230	Hold ×30 minutes and reduce rate by 100 U/h
231-260	Hold heparin, ACT hourly until <200 seconds, then reduce rate by 150 U/h
261-300	Hold heparin, ACT hourly until <200 seconds, then reduce rate by 200 U/h
301-350	Hold heparin, ACT hourly until <200 seconds, then reduce rate by 50%.
>350	Hold heparin and call the physician for new orders
Treatment/Interventions
Adequate anticoagulation is required at all times unless specified by the physician
Use activated clotting time (ACT) for monitoring anticoagulation with heparin
Blood samples for ACT, APTT, and INR analysis should be drawn from the venous sheath to avoid cross contamination with heparin present in the arterial line. If blood samples are drawn from the arterial line, the line should be cleared of other potential source of heparin (draw a waste sample before drawing the sample for testing).

Abbreviations: ACT, activated clotting time; IV, intravenous.

If the ACT >180 seconds with the heparinized purge solution alone, reduce the heparin concentration in the purge solution from 50 to 25 U/mL.

Sixteen patients received an Impella 2.5, 5.0, or CP during the study period. Six patients were excluded: 1 patient had a lower ACT target goal of 141 to 160 seconds and the other 5 patients did not require the second source of UFH infusion intravenously. The remaining 10 patients received UFH intra-arterially via the purge pressure solution plus intravenously via the heparin protocol simultaneously and were included in the analysis. The average duration of Impella use was 3.80 (±1.54) days. The patients’ age ranged from 50 to 78 years, 6 (60%) were male, and majority were overweight or obese with body mass index (BMI) ≥25 kg/m². During dual UFH administration, a total of 101 ACT values were measured: 28 (28%) were <160 seconds (median: 154, range: 111-159), 55 (55%) were within the target range of 160 to 180 seconds (median: 166, range: 160-179), 18 (17%) were >180 seconds (median: 185, range: 181-215), and 73 (73%) were in the effective range with ACT >160 seconds. The median and range of ACT for each distinct type of Impella pump were similar. Additionally, the median and range of ACT as a function of BMI were comparable as well. The main results of the analysis are summarized in Table 2. Of the 101 ACT values assessed, 39 were measured in presence of a purge pressure dextrose concentration of 20% (D20) and the remaining 62 in presence of a dextrose concentration of 5% (D5). The median of the ACT values in presence of D20 and D5 purge pressure solutions was 164 and 166 seconds, respectively.

Table 2.

Distribution of ACT Values During IV Heparin Administration.^a

Category	Value
Total # of patients	10
Total # of ACT values	101
ACT <160	154 (111-159)
ACT 160-180	166 (160-179)
ACT >180	185 (181-215)
By category
ACT <160	28 (28%)
ACT 160-180	55 (55%)
ACT >180	18 (17%)
Body mass index	166 (111-215)
<25 (n = 3)	160 (146-191)
25-30 (n = 2)	163 (111-190)
>30 (n = 5)	169 (142-215)
All Impella (n = 10)	166 (97-300)
Impella 2.5 (n = 4)	166 (111-300)
Impella 5.0 (n = 2)	165 (97-181)
Impella CP (n = 4)	166 (142-215)

Abbreviations: ACT, activated clotting time in seconds; IV, intravenous.

^a Unless otherwise indicated, numbers represent median (range) for continuous variables and number (%) for categorical data.

Study patients were relatively young, had a comparable sex distribution, and majority were overweight or obese. Since UFH remains in the vascular system and does not distribute into muscle or fat tissue, dosing UFH in overweight or obese patients presents a unique challenge during therapy. ² Although a small number of patients were studied, the cumulative number of ACT values measured were deemed adequate for our analysis. For ACT values below or above the target range, the median ACT values were within 10 seconds of the target values. Additionally, the majority of the ACT measurements were within the effective range. The specific type of Impella blood flow used and patient BMI had no appreciable influence on the results of the measured ACT. The latter was unexpected and may be due to the design of the protocol with frequent ACT measurements and dose titrations. There were no systemic thrombotic complications due to inadequate ACT in any of the 10 patients analyzed. Similarly, there were no Impella pump failures due to inadequate ACT. Although the total amount of heparin required to achieve optimal ACT is multifactorial in any clinical setting, in our patients, its antithrombotic effect did not appear to change appreciably in the presence of D20 compared to D5. This observation may suggest that viscosity of the purge pressure solution, as a function of dextrose concentration, did not have a measurable effect on maintaining the optimal ACT goal while using the secondary IV heparin protocol.

A recent comprehensive pharmacologic review by Allender, et al offers an UFH protocol for the Impella device using anti-Xa monitoring. ³ The anti-Xa assay is not routinely available in the majority of medical facilities and it is more expensive than the point-of-care ACT. Additionally, a small pilot study of an anti-Xa inhibitor protocol resulted in high incidence of major bleed despite tightly controlled anti-Xa monitoring to guide therapy. ⁴ Use of argatroban, a direct thrombin inhibitor, has also been described in isolated case reports and would be an essential substitute to UFH in those with suspected or definitive heparin-induced thrombocytopenia. ^5,6

As the result of this analysis, we have increased the frequency of ACT measurements under our protocol from every 6 hours to every 4 hours around the clock, while maintaining the same initial dose and titration doses outlined in the IV UFH protocol. This change is expected to more rapidly shift the number of subtherapeutic and supratherapeutic ACT values to within the target range, without exposing the patients to the potential risks associated with excessively elevated ACT values. Our systemic IV UFH protocol provides a unique approach to ensuring patients with an Impella LVAD achieve and maintain the therapeutic ACT goal. Our report includes a limited number of participants, and further validation of this protocol is warranted.