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ASAIO Journal:
doi: 10.1097/MAT.0000000000000028
Case Series

Left Ventricular Assist Device Pump Thrombosis: Is There a Role for Glycoprotein IIb/IIIa Inhibitors?

Bellumkonda, Lavanya*; Subrahmanyan, Lakshman*; Jacoby, Daniel*; Bonde, Pramod

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From the *Division of Cardiology, Yale School of Medicine, New Haven, Connecticut; and Section of Cardiac Surgery, Yale School of Medicine, New Haven, Connecticut.

Submitted for consideration May 2013; accepted for publication in revised form October 2013.

Disclosure: The authors have no conflicts of interest to report.

Reprint Requests: Lavanya Bellumkonda, MD, Yale School of Medicine, 789 Howard Ave, New Haven, CT 06510. Email Lavanya.bellumkonda@yale.edu.

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Abstract

Left ventricular assist devices (LVADs) fill a critical need by providing circulatory support to patients with end-stage heart failure who are either ineligible for heart transplant or too ill to stably wait for an eventual donor organ. Furthermore, they are critical to the arsenal of the heart failure cardiologist, given the supply/demand mismatch for donor organs. Unfortunately, these devices present their own complications. Despite antiplatelet agents and systemic anticoagulation, a number of patients present with pump thrombosis, a life-threatening event requiring either pump exchange or treatment with systemic thrombolytics. In an effort to avoid these morbid therapies, glycogen IIb/IIIa inhibitors, which have both antiplatelet and thrombolytic properties, have been proposed to treat pump thrombosis. We report here the largest case series using these agents and document a previously unreported high failure rate with this therapy.

Left ventricular assist devices (LVADs) have revolutionized the management of patients with end-stage heart failure by offering a therapy to fill the supply/demand mismatch for cardiac transplant. Modern rotary devices provide excellent intermediate-term survival, although device complications still present a clinical dilemma to the clinicians. Among these, pump thrombosis—if not identified and treated promptly—can be a life-threatening event, requiring immediate medical or surgical intervention. The activated platelet state of the heart failure patient, low flow status, and postsurgical inflammatory state all predispose to pump thrombosis and require continuous antithrombotic and antiplatelet therapy postimplant, most commonly with coumadin and aspirin.1 Despite these therapies, 4% of LVAD patients were reported to develop thrombosis in the destination therapy trial.1

The local environment within the LVAD is thought to predispose to platelet-rich (“white”) thrombi rather than thrombin-rich (“red”) clots, and therapies to treat suspected thrombi have been tailored to this perspective.2 Notably, suspected thrombi are treated both with intensified anticoagulant therapy (heparin) and with additional antiplatelet agents (most commonly the thienopyridine, clopidogrel).3 In addition, fibrinolytics have been given both systemically and intraventricularly, with the significant risk of hemorrhage that these agents entail.4–6

This strategy has the disadvantage of moving directly from a relatively benign regimen of anticoagulant and antiplatelet agents directly to more morbid fibrinolytic therapy. Accordingly, recent reports have focused on intensifying antiplatelet therapy with the addition of glycoprotein IIb/IIIa agents, as an alternative to fibrinolysis. To date, there have been two reports of a total of three patients successfully receiving this therapy.7,8 We report here our experience with four patients treated with the glycoprotein IIb/IIIa agent, eptifibatide, and compare our results with those previously reported.

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Methods

This was a retrospective analysis in which all patients were implanted with HeartMate II (Thoratec Corporation, Pleasanton, CA) device at our institution between 2009 and 2012 (n = 20) who presented with pump thrombosis and were treated with eptifibatide (n = 4). All clinical parameters were extracted from the documented medical chart.

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Results

Patients were 20 to 57 years of age, all were men, and all received a HeartMate II LVAD as a bridge to transplant. All four were maintained on aspirin 81–325 mg daily and coumadin with a target international normalized ratio (INR) of 1.8–3.0. No patient was found to have subtherapeutic INR for more than two sequential clinic visits. Patients 2, 3, and 4 had INR of 1.5, 1.6, and 1.5, respectively, on one occasion, and after adjusting the coumadin dose, the next INR was >2 in all these three patients. Patients presented with various combinations of the classic triad of LVAD thrombosis: increased pump power, elevated lactate dehydrogenase (LDH), and symptoms (hematuria, heart failure, and embolic phenomena; Table 1). Two patients developed thrombi relatively soon after device implantation (1 week and 4 weeks, respectively), while two were thrombus-free for approximately 1 year. We reviewed the chest x-rays of all the patients, and patient 4 had malpositioned inflow cannula with cannula facing the lateral wall as opposed to the mitral inflow. Three of four patients had high power readings and one did not though he did have persistently elevated LDH and hematuria (Figures 1 and 2).

Table 1
Table 1
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Figure 1
Figure 1
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Figure 2
Figure 2
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Once pump thrombus was suspected, all four patients were started on a heparin infusion with partial thromboplastin time targeted to 60–80 seconds, in addition to aspirin 325 mg daily. Given ongoing elevated LDH levels (patients 2–4), persistent hematuria (patient 1), or continued signs of left-sided failure (patient 4) after 12 hours of heparin therapy, all four patients were started on eptifibatide infusion at 1 μg/kg/min after a bolus of 180 μg/kg for 2 to 4 days. Only one patient probably responded to this therapy. His hematuria cleared within 12 hours of eptifibatide infusion, his LDH rapidly recovered to baseline levels, and ultimately he was successfully transplanted. Patient 2 had persistently elevated LDH and elevated device power, had presented with a massive cerebrovascular accident, and after extensive discussions with his family, care was withdrawn. Patients three and four ultimately had successful LVAD exchange for persistently elevated LVAD power and continued heart failure symptoms (patient 4).

After LVAD removal, rotor thrombosis was confirmed in patient 3 (as shown in Figure 3) and patient 4. No thrombus was found in the LVAD explanted from patient 1.

Figure 3
Figure 3
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Discussion

This study represents the largest case series to date of LVAD patients treated with glycoprotein IIb/IIIa agents for suspected device thrombosis and documents for the first time failure of this therapy for patients with pathologically confirmed events. Clinical response to eptifibatide was observed in only one patient. Absence of pump power elevations in this case may be indicative of lack of rotor involvement or early presentation. The remainder of patients failed to have a clinically measurable response to therapy. Furthermore, in this group, clinicopathological correlation confirmed rotor thrombosis in two of three cases supporting the hypothesis that rotor involvement signified by increased pump power is an indicator of poor response to ramped antiplatelet therapy. Unfortunately, thromboelastography or a reliable assay for platelet aggregometry was not available to us. This would have been a helpful tool to monitor platelet response to therapy. While evaluating a patient for suspected pump thrombosis, one should also consider mechanical causes such as malpositioned inflow cannula as a cause of hemolysis and also a contributor to pump thrombosis. This can be easily evaluated with a chest x-ray or a computed tomography scan of the chest.

This report suggests that the role for eptifibatide treatment of pump thrombosis may be limited, and, in contrast to a prior report, documents a high failure rate for this therapy, requiring either more aggressive medical therapy (fibrinolysis) or device exchange (as instituted in our experience). In our cohort, response was observed when thrombus appears acute and was not associated with elevated pump power. These agents are associated with increased risk of major bleeding complications, including spontaneous retroperitoneal bleeding, gastrointestinal and genitourinary bleeding along with the risk of thrombocytopenia. Given the variable experience with this agent and the additional glycogen IIb/IIIa agent, tirofiban, larger case series will be needed to clearly define the clinical settings in which these agents may be optimal therapy for pump thrombosis.

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References

1. Slaughter MS, Rogers JG, Milano CA, et al.HeartMate II Investigators. Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med. 2009;361:2241–2251

2. Ledford ID, Labedi M, Kfoury AG, et al. 235 Thrombus within the HeartMate II left ventricular assist device (LVAD): Are all clots created equal? J Heart Lung Transplant. 2012;31:2

3. Studer MA, Kennedy CE, Dreyer WJ, et al. An alternative treatment strategy for pump thrombus in the DeBakey VAD Child: Use of clopidogrel as a thrombolytic agent. J Heart Lung Transplant. 2006;25:857–861

4. Rothenburger M, Wilhelm MJ, Hammel D, et al. Treatment of thrombus formation associated with the MicroMed DeBakey VAD using recombinant tissue plasminogen activator. Circulation. 2002;106(12 suppl 1):I189–I192

5. Hayes H, Dembo L, Larbalestier R, O’Driscoll G. Successful treatment of ventricular assist device associated ventricular thrombus with systemic tenecteplase. Heart Lung Circ. 2008;17:253–255

6. Kamouh A, John R, Eckman P. Successful treatment of early thrombosis of HeartWare left ventricular assist device with intraventricular thrombolytics. Ann Thorac Surg. 2012;94:281–283

7. Thomas MD, Wood C, Lovett M, Dembo L, O’Driscoll G. Successful treatment of rotary pump thrombus with the glycoprotein IIb/IIIa inhibitor tirofiban. J Heart Lung Transplant. 2008;27:925–927

8. Al-Quthami AH, Jumean M, Kociol R, et al. Eptifibatide for the treatment of HeartMate II left ventricular assist device thrombosis. Circ Heart Fail. 2012;5:e68–e70

left ventricular assist device; thrombus; eptifibatide

Copyright © 2014 by the American Society for Artificial Internal Organs

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