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Pentoxifylline for the Treatment of Hemolytic Anemia in a Patient Who Developed Recurrent Gastrointestinal Bleeding While on Continuous-Flow Left Ventricular Assist Device Support

Jennings, Douglas L.*; Williams, Celeste T.; Morgan, Jeffrey A.

doi: 10.1097/MAT.0b013e31829f0eb1
Case Reports

Pentoxifylline is an agent that improves red blood cell deformability (known as a hemorrheologic effect) and reduces blood viscosity. Here, we present a case of a patient with hemolytic anemia after continuous-flow left ventricular assist device (CF-LVAD) implantation that was successfully treated with pentoxifylline. Our case is a 64-year-old African American woman who was implanted with a HeartMate II device on August 6, 2010, as a bridge to transplant for end-stage heart failure. Her postoperative course was complicated by recurrent gastrointestinal bleeding and antiplatelet therapy was discontinued. On October 25, 2011, she was readmitted with anemia and hemoglobin of 6.6 mg/dl and no identifiable source of bleeding. Her lactate dehydrogenase (LDH) was 936 IU/L, indicating severe hemolysis. Due to her evidence of hemolytic anemia and her inability to tolerate antiplatelet therapy due to recurrent bleeding, she was discharged on pentoxifylline 400 mg thrice daily on October 27, 2011, with hemoglobin of 11.2 mg/dl after transfusion. After 60 days of pentoxifylline, her hemoglobin and LDH in clinic were 10.1 mg/dl and 223 IU/L, respectively. The patient was successfully bridged to transplant in June 2012. Additional analysis of pentoxifylline as a therapeutic modality to manage hemolytic anemia after CF-LVAD implantation may be warranted.

From the *Pharmacy Services, Division of Cardiovascular Medicine, and Division of Cardiac Surgery, Henry Ford Hospital, Detroit, Michigan.

Submitted for consideration March 2013; accepted for publication in revised form June 2013.

The results of this work were previously presented at the International Society of Heart and Lung Transplantation, 33rd Annual Meeting and Scientific Sessions, Montreal, California, in April 2013.

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

Reprint Requests: Department of Pharmacy Services, 2799 W. Grand Blvd, Detroit, MI 48201. Email: djennin1@gmail.com

Pentoxifylline improves red blood cell deformability (known as a hemorrheologic effect) and reduces blood viscosity. In this report, we present a case of a patient who developed hemolytic anemia while on continuous-flow left ventricular assist device (CF-LVAD) support and was successfully treated with pentoxifylline.

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Case Report

Our case is a 64-year-old African American woman who underwent implantation of a HeartMate II device (Thoratec Corp., Pleasanton, CA) as a bridge to transplant for end-stage ischemic cardiomyopathy on August 6, 2010. Her postoperative course was complicated by recurrent gastrointestinal bleeding (GIB) secondary to arteriovenous malformations. To reduce her bleeding risk, aspirin was discontinued. However, due to her history of cardioembolic stroke, warfarin therapy with an international normalized ratio goal of 2–3 was continued.

On September 29, 2011, she presented with acute anemia (hemoglobin of 7.2 mg/dl) and signs of another GIB. She was transfused two units of packed red blood cells and discharged with hemoglobin of 9.1 mg/dl. Her lactate dehydrogenase (LDH) was 443 IU/L at that time, and her haptoglobin was undetectable. Three weeks later, she was readmitted with hemoglobin of 6.6 mg/dl without any identifiable source of bleeding. Her LDH was 936 IU/L, and the peripheral smear revealed schistocytes, consistent with severe hemolysis. There were no alternative etiologies for the elevated LDH. The patient’s device settings were normal, and there was no clinical evidence of device thrombosis. A transthoracic echo did not reveal any findings suggestive of device malfunction; the patient’s left ventricular end-diastolic diameter was unchanged from previous reports, and the inflow and outflow velocities were equal at 0.8 m/sec. Given the evidence of hemolytic anemia and her poor candidacy for antiplatelet therapy secondary to recurrent bleeding, she was discharged on pentoxifylline 400 mg thrice daily on October 27, 2011, with hemoglobin of 11.2 mg/dl (after four units of packed red blood cell transfusion). After 60 days of pentoxifylline therapy, her hemoglobin remained stable at 10.1 mg/dl and her LDH was reduced to 223 IU/L.

On January 3, 2012, she was readmitted with another GIB and hemoglobin 6.6 mg/dl. However, her LDH remained low at 219 IU/L, which suggested that her hemolysis remained suppressed. The patient continued on successful device support until her heart transplant on June 11, 2012. There was no visual evidence of device thrombosis upon explantation.

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Discussion

Although CF-LVADs have yielded improved outcomes, such as increased survival and fewer postoperative adverse events, they can also induce hemolysis of red blood cells due to sheer stress from high rotor speed, artificial device surfaces, and mechanical bearings.1,2 Although antiplatelet and anticoagulant therapies are used to minimize device-related hemolysis, they can increase the risk of bleeding. This can be problematic as these patients are predisposed to bleeding, particularly GIB, by nature of their device support.3

The patient in our case represented a challenging clinical scenario. The patient’s primary cause of anemia was recurrent GIB, which made her a poor candidate for anticoagulation. However, withdrawal of anticoagulation would have substantially increased her risk for a cardioembolic stroke. Her case was further complicated by a secondary hemolytic anemia, and administering antiplatelet agents to reduce hemolysis would have likely exacerbated her recurrent GIB. Given the high prevalence of GIB during CF-LVAD support, clinicians caring for these patients are likely faced with similar dilemmas when trying to balance the risks and benefits of anticoagulation and antiplatelet therapy. The ideal pharmacologic agent for these patients would reduce mechanical destruction of erythrocytes that results from device support without significantly increasing the risk of bleeding.

Pentoxifylline increases in erythrocyte flexibility and reduces whole blood viscosity.4 Although the exact mechanism remains unknown, it appears to facilitate the ability of erythrocytes to maintain their integrity, apparently by modulating the phosphorylation/dephosphorylation reactions of membrane proteins that are involved in maintaining erythrocyte shape and deformability. Furthermore, pentoxifylline reduces plasma fibrinogen concentration and increases fibrinolytic activity, subsequently resulting in decreased erythrocyte aggregation and plasma viscosity, which contribute to an overall reduction in viscosity of whole blood. However, pentoxifylline does not appear to inhibit platelet deposition on the blood vessel wall and does not affect primary hemostasis or prolong bleeding time; therefore, use has not been reported to cause appreciable bleeding in patients receiving therapeutic doses of the drug for intermittent claudication.5

This case suggests that these unique pharmacodynamics properties of pentoxifylline may reduce mechanical destruction of red blood cells and ameliorate hemolytic anemia in patients with CF-LVAD support who experience recurrent GIB. As this drug lacks appreciable antiplatelet or anticoagulant properties, there is no anticipated increased risk of bleeding with its use. Pentoxifylline, therefore, may be a prudent alternative therapy for managing hemolytic anemia in patients on CF-LVAD support who also have a history of GIB.

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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. Stepanenko A, Krabatsch T, Hennig E, et al. Retrospective hemolysis comparison between patients with centrifugal biventricular assist and left ventricular assist devices. ASAIO J. 2011;57:382–387
3. Morgan JA, Paone G, Nemeh HW, et al. Gastrointestinal bleeding with the HeartMate II left ventricular assist device. J Heart Lung Transplant. 2012;31:715–718
4. Gorbatschova FE, Turaschwili GA, Kvassov VT, et al. The circulatory and clinical effects of pentoxifylline. Pharmatherapeutica. 1978;2:100–107
5. Aviado DM, Dettelbach HR. Pharmacology of pentoxifylline, a hemorheologic agent for the treatment of intermittent claudication. Angiology. 1984;35:407–417

pentoxifylline; hemolytic anemia; ventricular assist device

Copyright © 2013 by the American Society for Artificial Internal Organs