Ann Thorac Surg 2012;93:1534-1540. doi:10.1016/j.athoracsur.2012.02.035
© 2012 The Society of Thoracic Surgeons
Original Articles: Adult Cardiac
Incidence and Management of Gastrointestinal Bleeding With Continuous Flow Assist Devices
Ashim Aggarwal, MD, MRCPa,
Rojina Pant, MDa,
Shivani Kumara,
Priya Sharma, BAa,
Colleen Gallagher, BSNa,b,
Antone J. Tatooles, MDb,
Pat S. Pappas, MDb,
Geetha Bhat, MD, PhDa,*
a Center for Heart Transplant and Assist Devices, Oak Lawn, Illinois
b Department of Cardiothoracic Surgery, Advocate Christ Medical Center, Oak Lawn, Illinois
Accepted for publication February 8, 2012.
Abbreviations and Acronyms ACT = activated clotting time; AoV = aortic valve; AS = aortic stenosis; b-FGF = basic fibroblast growth factor; BTT = bridge to transplant; CF-LVADs = continuous flow left ventricular assist devices; CPB = cardiopulmonary bypass; DT = destination therapy; EGF = endothelial growth factor; GI = gastrointestinal; HF = heart failure; IGF = insulinlike growth factor; INR = international normalized ratio; LGI = lower gastrointestinal; LOS = length of stay; PI = pulsatility index; PRBCs = packed red blood cells; UGI = upper gastrointestinal; VAD = ventricular assist device; vWF = von willebrand factor
* Address correspondence to Dr Bhat, Advocate Christ Medical Center, 4400 W 95th St, Oak Lawn, IL, 60453 (Email: geetha.bhat{at}advocatehealth.com).
Presented at the Poster Session of the Forty-seventh Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Jan 31–Feb 2, 2011.
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Abstract
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Background: Continuous flow left ventricular assist devices (CF-LVADs) have emerged as the standard of care for patients in advanced heart failure (HF) requiring long-term mechanical circulatory support. Gastrointestinal (GI) bleeding has been frequently reported within this population.
Methods: A retrospective analysis of 101 patients implanted with the Heart Mate II from January 2005 to August 2011 was performed to identify incidence, etiology, and management of GI bleeding. Univariate and multivariate regression analysis was conducted to identify related risk factors.
Results: A significant incidence of GI bleeding (22.8%) occurred in our predominantly destination therapy (DT) (93%) population. Fifty-seven percent of the patients with bleeding episodes bled from the upper GI (UGI) tract (with 54% bleeding from gastric erosions and 37% from ulcers/angiodysplasias), whereas 35% of patients bled from the lower GI (LGI) tract. Previous history of GI bleeding (odds ratio [OR], 22.7; 95% CI, 2.2–228.6; p = 0.008), elevated international normalized ratio (INR) (OR, 3.9; CI, 1.2–12.9; p = 0.02), and low platelet count (OR, –0.98; CI, 0.98 –0.99; p = 0.001) were independent predictors of GI hemorrhage. Recurrent bleeding was more common in older patients (mean, 70 years; p = 0.01). The majority of bleeders (60%) rebled from the same site. Management strategies included temporarily withholding anticoagulation, decreasing the speed of LVADs, and using octreotide. Octreotide did not impact the amount of packed red blood cells used, rebleeding rates, length of hospital stay, or all-cause mortality. Only 1 patient died as a direct consequence of GI bleeding.
Conclusions: Multiple factors account for GI bleeding in patients on CF-VADs. A previous history of bleeding increases risk significantly and warrants careful monitoring.
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Introduction
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Heart failure (HF) is one of the leading causes of hospitalizations and deaths in the United States. The estimated direct and indirect cost of HF in the United States for 2010 was $39.2 billion [1]. Several different long-term circulatory support mechanical devices for patients with HF have been developed, ranging from total artificial hearts to ventricular assist devices (VADs). Originally introduced as a temporary bridge to recovery, and then as a bridge to transplantation (BTT), VADs have evolved into permanent or destination therapy (DT) for a growing number of patients with refractory HF [2]. Alongside the VAD evolution, patient survival increased to a reported 58% at 2 years [3]. Furthermore, the advent of the newer continuous flow left ventricular assist devices (CF-LVADs) has revolutionized treatment options for patients with end-stage HF because of smaller portable designs with fewer complications [4]. However new sets of management problems have arisen concurrently. One frequently encountered complication is gastrointestinal (GI) bleeding, which in 1 series was observed nearly 4 times more in patients using continuous flow pumps than in those using pulsatile pumps [5]. A recent study by John and colleagues [6] of 130 patients using the HeartMate II LVAD reported an 18% incidence of GI bleeding. Likewise, Uriel and colleagues [7] showed an even higher incidence (30%) of GI bleeding in their population of patients with HF using CF-LVADs. In both studies, the device was predominantly intended for BTT. Comparable GI bleeding (40%) was reported by Stern and associates [8] in 2010 in patients implanted with CF-LVADs as BTT.
We present our overall experience (incidence, etiology, and management strategies) for GI bleeding in patients with CF-LVADs implanted for DT and BTT at our center.
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Patients and Methods
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A retrospective electronic medical review was performed for 101 patients supported on CF-LVADs from January 2005 to August 2011 for either BTT (n = 7 [6.9%]) or DT (n = 94 [93%]) at Advocate Christ Medical Center. The study was approved by the institutional review board of our hospital and individual patient consent was waived. Patients were considered to have GI bleeding if they had one or more of the following symptoms: guaiac-positive stool, hematemesis, melena, active bleeding or blood within the GI tract at the time of endoscopy or colonoscopy, and transfusion of packed red blood cells. Upper GI (UGI) bleeding and lower GI (LGI) bleeding was defined as bleeding above the ligament of Treitz and bleeding from the GI tract distal to the ligament of Treitz, respectively. Recurrent bleeding was defined as more than one episode of GI bleeding after implantation of a LVAD. The gastroenterologist determined diagnostic and therapeutic interventions related to GI bleeding and identified the source of bleeding. Cessation of a bleeding episode was confirmed by stabilization of hemoglobin values and relevant imaging as indicated. Intraoperative anticoagulation involved intravenous heparin to a target activated clotting time (ACT) greater than 400 seconds while the patient received cardiopulmonary bypass (CPB). Anticoagulation was reversed with protamine sulfate after CBP, and ACT was checked to ensure reversal before transferring patients out of the operating room. Anticoagulant therapy after LVAD implantation included warfarin (target INR between 1.5 and 2) and was started once hemostasis was achieved and chest tubes were removed. Aspirin (81 mg) served as an antiplatelet agent [9]. Intravenous heparin, in transition to warfarin, was only used in patients with a high risk of thromboembolic events such as chronic atrial fibrillation, documented left atrial or left ventricular thrombus, or low LVAD flow. Patient INRs were closely followed in outpatient VAD clinics weekly to biweekly for the first 6 to 8 weeks and monthly thereafter.
Data collection included detailed reviews of CF-LVAD patient demographics. Laboratory data included INR, platelet count, hemoglobin value, albumin level, and creatinine level. Laboratory data were collected on the day the GI bleeding was suspected/diagnosed; for the patients with no GI bleeding, laboratory data were collected at the mean time to bleeding for the group with GI bleeding (128 days after LVAD implantation). We also reviewed the device characteristics and settings, device strategy (BTT versus DT), rotator speed, and pulsatility index (PI) of the LVAD. The echo parameters reviewed were the aortic valve (AoV) opening at a mean duration of 125 days (average time to bleeding in days) after VAD implantation. Reviewed management measures taken for all GI bleeding episodes included number of units of packed red blood cells transfused, use of octreotide (somatostatin analogue), changes in VAD settings, and recurrent GI bleeding and length of stay (LOS) in hospital.
Statistical Analysis
All statistical analyses were performed using SPSS, version 11.5, statistical software (SPSS Inc, Chicago, IL). Continuous variables are expressed as mean and standard deviation and were compared using a Student's t test. Categorical variables are expressed as number of patients and were compared using a 
2 coefficient or Fisher's exact test. The Wilcoxon rank sum test was used to determine differences in nonnormal distribution. A p value less than 0.05 was considered significant. Univariate and multivariate regression analyses were performed to identify risk factors for bleeding. All data is reported as 95% confidence interval (CI). Kaplan-Meier survival curves were first plotted for the entire duration of the follow-up period (up to 70 months) for all patients. A separate curve was then plotted to look at the difference in survival at 12 months, for which all patients with follow-up greater than 12 months were excluded.
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Results
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Total Cohort
A total of 101 patients were identified to have HeartMate II LVADs (Thoratec Corp, Pleasanton, CA) implanted at our institution from January of 2005 to August of 2011. Of these, 22.8% (n = 23) had GI bleeding during LVAD support. The majority of these patients received the device under the DT strategy (n = 94 [93%]). Baseline characteristics with the device type and strategy for both the GI bleeders and non-GI bleeders are outlined in Table 1. There was no significant difference noticed for both groups in terms of age, sex, race, LVAD speed, PI, or CPB times. The mean time to bleeding was 128 ± 155 days after VAD implantation. The mean length of hospital stay for the bleeders was 31 ± 37 days. Transthoracic echocardiograms were reviewed to look at AoV opening as a surrogate marker of pulsatility. No significant difference was seen in either group. The 2 groups did not differ in terms of all-cause mortality (21.7% versus 25.6%; p = 0.70) (Fig 1). In univariate analysis, preoperative AST, ALT, previous history of GI bleeding, and platelet count were significant variables. These variables along with the albumin level (variable, with p 
0.2 in the univariate model) and the other clinically important variables (INR, speed, and the PI) were included in the multivariate regression model. The statistically significant variables in this regression model were the history of GI bleeding (OR, 22.7; CI, 2.2–228.6; p = 0.008 [wide CI secondary to small number of patients in the groups being evaluated]); INR (OR, 3.9; CI, 1.2–12.9; p = 0.02), and platelet count (OR, –0.98; CI, 0.98–0.99; p = 0.01). VAD speed and PI were not significant.
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Fig 1. Kaplan-Meier survival curves. (A) Kaplan-Meier estimates of overall mortality at 70 months (entire duration of follow-up) among patients with and without gastrointestinal (GI) bleeding. (B) Kaplan-Meier estimates of overall mortality at 12 months in patients with and without GI bleeding. (GIB = gastrointestinal bleeding.)
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Location of the Bleeding
Of all the patients who experienced GI bleeding, 57% had an UGI tract cause, whereas 35% had a LGI tract cause (Fig 2). The most common source of bleeding was gastric erosions (54%), whereas arteriovenous (AV) malformations and gastric ulcers (each 15%) were secondary. Of the patients with LGI tract bleeding, an equal percentage (37%) bled from cecal/rectal ulcers and from small bowel angiodysplasias. None of the patients had concomitant bleeding from elsewhere (hemorrhagic strokes, hemoptysis, or bleeding requiring surgical reexploration) except 2 patients with epistaxis that were controlled with nasal packing.
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Fig 2. Pie chart showing the source of GI bleeding. (A) Overall distribution of causes. (B) Causes of upper GI bleeding (UGIB). (C) Causes of lower GI bleeding (LGIB). (AVM = arteriovenous malformation.)
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Recurrent Bleeding
Multiple bleeding episodes were seen in 43.5% (n = 10) of the bleeders. Six patients (60%) bled from the same site. Of the total recurrent bleeders, 8 of 10 patients (80%) bled from an UGI tract cause. The predominant cause was gastric angiodysplasia (7 of 8 patients) and 1 patient bled from a bleeding pyloric canal vessel. The 2 patients with a LGI tract cause, bled from a sigmoid ulcer (n = 1) and another bled from a rectal ulcer (n = 1). There was 1 death as a direct result of GI bleeding in a patient with severe gastric angiodysplasia requiring partial gastrectomy after multiple failed attempts at other nonsurgical treatment options (argon plasma coagulation and octreotide treatment).
Patients with multiple bleeding episodes were significantly older than those with single episodes of GI bleeding (70.60 ± 7.45 years versus 60.62 ± 9.54 years; p = 0.01). There was no significant difference between the 2 groups in terms of LOS, INR, platelet counts, speed, PI, or all-cause mortality (Table 2).
Management
The standard treatment protocol used involved withholding all anticoagulation and decreasing the VAD speed (decreased by a mean of 87.90 ± 130.44 rpm in our patients) to reduce flow and generate pulsatility. Antiplatelet administration was also discontinued. Fresh frozen plasma was not given unless the patient had an active GI bleeding episode. Hemolytic workup was not routinely performed unless there was a high suspicion for hemolysis. All patients were given proton pump inhibitors after a GI bleeding episode. The pharmacotherapy used to control bleeding was octreotide [10, 11] in 43.5% (n = 10) of the GI bleeders. Data were analyzed to compare the clinical outcomes with the use of octreotide versus no octreotide. There was no significant difference seen in the LOS, units of packed red blood cells administered, rebleeding episodes, or mortality (Table 3). None of the patients experienced any thrombotic complications as a result of discontinuation or reversal of anticoagulation.
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Comment
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Use of CF-LVADs as a treatment for end-stage HF has increased substantially in the past decade. Despite a decade of experience with newer devices, GI bleeding (compared to the first-generation pulsatile LVADs) is increasing. Whether it is secondary to the need for anticoagulation or linked to continuous flow effects and low pulsatility, von Willebrand syndrome, and development of bleeding diathesis is unclear.
Several studies have shown an increased incidence of GI bleeding in patients with CF-LVADs [5, 6, 8, 12]. Letsou and colleagues [13] in 2005 first described a GI bleeding incidence of 14% in patients with HF on a Jarvik 2000 (Jarvik Heart, Inc, New York, NY). All 3 patients had GI bleeding secondary to AV malformations. Stern and colleagues [8] compared GI bleeding rates among recipients of 20 HeartMate II (Thoratec Corp), 9 HeartMate XVE (Thoractec Corp), and 4 VentrAssist (VentraCor Ltd, Brisbane, Australia) devices. Patients with HeartMate II devices had a 40% incidence of GI bleeding, whereas no GI bleeding was reported in the other groups [8]. Demirozu and colleagues [14] in 2011 reported a 19% incidence of GI bleeding in patients with the HeartMate II device. A similar incidence (18%) was reported by John and colleagues [6] in 130 patients with HeartMate II devices (majority for BTT). At our center, the incidence of GI bleeding in patients with CF-LVADs was 22.8%, which is in accordance with the expected range of 15% to 50% observed in previous studies [12].
In our study, a history of GI bleeding (before LVAD implantation) was associated with a significantly increased risk of GI bleeding after implantation. However the number of such patients was small. Thus the majority of patients who bled, lacked a previous history of GI bleeding. Patients with previous GI bleeding need to be carefully evaluated preceding VAD implantation because of their elevated risk profile.
Most patients bled from the UGI tract. Gastric erosion was the primary cause, whereas AV malformation and gastric ulcers were secondary. For LGI bleeding, ulcers (colonic/cecal/rectal) and AV malformations were equally responsible. Recurrent bleeding was seen in 43.5% of GI bleeders, and 60% of recurrent bleeders had same-site bleeding. A single death resulted as a direct consequence of GI bleeding from severe gastric angiodysplasia.
Patients with CF-LVADs have states physiologically similar to aortic stenosis (AS) because of the narrow pulse pressure. GI bleeding in patients with AS, first described by Heyde in 1958, resulted in a nomenclature of Heyde's syndrome [15]. Several mechanisms have since been proposed for the relationship between AS and GI bleeding, which may also hold true for CF devices. Boley and associates [16] suggested that increased intraluminal pressure with muscular contraction may result in dilatated mucosal veins that favor development of AV communication, which may bleed when exposed to trauma/stress. Alternatively, a neurovascular cause proposed by Cappell and Lebwohl [17] indicates that increased sympathetic tone results in smooth muscle relaxation and development of angiodysplasia. Another mechanism proposes that lowered pulse pressure, as in AS, leads to intestinal hypoperfusion and resulting hypoxia, leading to vascular dilatation and angiodysplasia. AoV opening in patients with CF-LVADs can be prevented by removing virtually all preload in the left ventricule. A review of transthoracic echocardiograms of all patients found that in 52% of the GI bleeders, the AoV did not open with LV systole. As a standard treatment protocol in the management of GI bleeding, the pump speed was decreased under echocardiographic guidance to allow AoV opening in an effort to try and restore normal pulse pressure and phasic flow.
Another important mechanism of GI bleeding in these patients is acquired von Willebrand disease. This association in AS patients was originally described by Warkentin [18] in 1992. Uriel and colleagues [7] provided vital contributions to the understanding of potential cause-and-effect relationships between continuous flow physiology and GI bleeding, which is the development of von Willebrand syndrome as evidenced by the depletion of high-molecular-weight von Willebrand factor multimeres in 31 patients with HeartMate II devices. Eighteen of these patients experienced GI bleeding. Klovaite and associates [19] tested the putative impact of the LVAD on vWF-dependent platelet aggregation in 16 patients with HeartMate II LVADs. The study demonstrated that 11 of the16 patients had impaired ristocetin-induced platelet aggregation, whereas 9 of the 10 patients with severely impaired ristocetin-induced platelet aggregation had histories of minor or major bleeding. vWF is a protein expressed by the vascular endothelium and megakaryocytes that polymerizes to multimeres and binds to exposed collagen of denuded vessels. Platelets adhere to vWF through receptors, which induces their activation, adhesion, and aggregation. The integrity of vascular endothelium, as evidenced by border protein expressions such as vWF, is partially dependant on the stretch and distention created by the pulsatile flow. CF- LVADs, like AS, create a high shear stress environment of blood flow that results in destruction of large multimeres. This plays an important homeostatic role in areas of high shear stress, such as GI AV malformations [19–21]. The lack of measured vWF levels in our patients poses an important limitation.
Management strategies for GI bleeding in patients with CF-LVADs consisted of temporarily discontinuing anticoagulation until bleeding ceased in addition to reducing VAD speed. The goal INR for patients with CF-LVADs was 1.5 to 2 [9]. Interestingly, none of our patients had any thromboembolic events on either the lower level of anticoagulation or with its temporary discontinuation. This could be secondary to the sintered titanium blood contacting the surface of the HeartMate II device, which provides enough thromboresistance [20]. Use of octreotide, a synthetic somatostatin analogue, is routine at many centers for pharmacologic management of GI bleeding in patients with VADs and was used in 56.5% (n = 13) of our patients with GI bleeding. It acts by inhibiting gastric acid and other gut hormones, as well as constricting splanchnic and portal circulation. It also inhibits growth factors such as endothelial growth factor, basic fibroblast growth factor, and insulin-like growth factor-1 and is responsible for suppression of angiogenesis [11]. Octreotide was administered either as a continuous infusion or subcutaneous injection. No adverse effect was encountered. Clinical outcomes with and without octreotide were recorded. Octreotide did not impact the LOS, requirement for packed red blood cell transfusion, rebleeding, or mortality (Table 3). Mixed experience and results occurred regarding the use of octreotide in patients with angiodysplasias. Nardone and associates [10] used subcutaneous injections for 6 months in 17 patients with UGI and LGI angiodysplasias. Bleeding stopped in 10 patients, 4 needed cyclic retreatment, and 3 patients failed to respond. Barbara and colleagues [22] reported that the use of octreotide in patients with antral angiodysplasia was not helpful in controlling bleeding episodes.
Preventive steps need to be taken in patients with LVADs to minimize morbidity and mortality from GI bleeding. A few strategies would be to (1) maintain LVAD pump speed at the lowest possible safe range (while ensuring adequate unloading of the left ventricle) under echocardiographic guidance, decrease flow, and gain relative pulsatility; (2) maintain INR at the low end of the recommended range (1.5–2) in patients at high risk of GI bleeding; (3) close out patient monitoring (more frequent than usual out patient monitoring) of the INR, hemoglobin, and platelets; and (4) keeping a low threshold for diagnostic endoscopic evaluation in patients suspected of having GI bleeding.
Multiple limitations were encountered in our study. It is a single-center study, and data collection may be flawed because of the study's retrospective nature. The wide CI set in the regression model was secondary to the small number of events (history of GI bleeding before VAD implantation). We also did not test for the high-molecular-weight vWF in our patients to determine its role in GI bleeding as indicated in several recent studies. Improved prospective studies with randomized designs are needed to look at the impact of the following variables on GI bleeding: high versus low INR, high versus low VAD speeds, and outcomes with octreotide use.
In summary, CF-LVAD-supported patients have a significant risk of GI bleeding. Past history of GI bleeding (before LVAD implantation) is an important predictive risk factor for future bleeding episodes. Cause of bleeding, although unclear, is multifactorial. Older individuals have a tendency to bleed multiple times. Most patients with multiple bleeding episodes rebleed from the same site. Elevated INR (significant in the multivariate model despite being nonsignificant in the univariate model) and low platelet count increase the bleeding risk. Octreotide does not appear to affect clinical outcomes. A better understanding is needed for the pathophysiologic basis and mechanisms underlying GI bleeding in patients with mechanical VADs.
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References
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- Writing Group MembersLloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, et al. Heart disease and stroke statistics—2010 update: a report from the American Heart Association Circulation 2010;121:e46-e215.[Free Full Text]
- Rose EA, Gelijns AC, Moskowitz AJ, et al. Long-term use of a left ventricular assist device for end-stage heart failure N Engl J Med 2001;345:1435-1443.[Medline]
- Pereira NL, Chen D, Kushwaha SS, Park SJ. Discontinuation of antithrombotic therapy for a year or more in patients with continuous-flow left ventricular assist devices Interact Cardiovasc Thorac Surg 2010;11:503-505.[Abstract/Free Full Text]
- Slaughter MS, Rogers JG, Milano CA, et al. Advanced heart failure treated with continuous-flow left ventricular assist device N Engl J Med 2009;361:2241-2251.[Medline]
- Crow S, John R, Boyle A, et al. Gastrointestinal bleeding rates in recipients of nonpulsatile and pulsatile left ventricular assist devices J Thorac Cardiovasc Surg 2009;137:208-215.[Abstract/Free Full Text]
- John R, Kamdar F, Eckman P, et al. Lessons learned from experience with over 100 consecutive HeartMate II left ventricular assist devices Ann Thorac Surg 2011;92:1593-1599discussion 1599–600.[Abstract/Free Full Text]
- Uriel N, Pak SW, Jorde UP, et al. Acquired von Willebrand syndrome after continuous-flow mechanical device support contributes to a high prevalence of bleeding during long-term support and at the time of transplantation J Am Coll Cardiol 2010;56:1207-1213.[Medline]
- Stern DR, Kazam J, Edwards P, et al. Increased incidence of gastrointestinal bleeding following implantation of the HeartMate II LVAD J Card Surg 2010;25:352-356.[Medline]
- Slaughter MS, Pagani FD, Rogers JG, et al. Clinical management of continuous-flow left ventricular assist devices in advanced heart failure J Heart Lung Transplant 2010;29(4 suppl):S1-S39.[Medline]
- Nardone G, Rocco A, Balzano T, Budillon G. The efficacy of octreotide therapy in chronic bleeding due to vascular abnormalities of the gastrointestinal tract Aliment Pharmacol Ther 1999;13:1429-1436.[Medline]
- Blich M, Fruchter O, Edelstein S, Edoute Y. Somatostatin therapy ameliorates chronic and refractory gastrointestinal bleeding caused by diffuse angiodysplasia in a patient on anticoagulation therapy Scand J Gastroenterol 2003;38:801-803.[Medline]
- Slaughter MS. Hematologic effects of continuous flow left ventricular assist devices J Cardiovasc Transl Res 2010;3:618-624.[Medline]
- Letsou GV, Shah N, Gregoric ID, Myers TJ, Delgado R, Frazier OH. Gastrointestinal bleeding from arteriovenous malformations in patients supported by the Jarvik 2000 axial-flow left ventricular assist device J Heart Lung Transplant 2005;24:105-109.[Medline]
- Demirozu ZT, Radovancevic R, Hochman LF, et al. Arteriovenous malformation and gastrointestinal bleeding in patients with the HeartMate II left ventricular assist device J Heart Lung Transplant 2011;30:849-853.[Medline]
- Islam S, Cevik C, Islam E, Attaya H, Nugent K. Heyde's syndrome: a critical review of the literature J Heart Valve Dis 2011;20:366-375.[Medline]
- Boley SJ, Sammartano R, Adams A, DiBiase A, Kleinhaus S, Sprayregen S. On the nature and etiology of vascular ectasias of the colon. Degenerative lesions of aging. Gastroenterology 1977;72(4 Pt 1):650-660.[Medline]
- Cappell MS, Lebwohl O. Cessation of recurrent bleeding from gastrointestinal angiodysplasias after aortic valve replacement Ann Intern Med 1986;105:54-57.[Medline]
- Warkentin TE, Moore JC, Morgan DG. Aortic stenosis and bleeding gastrointestinal angiodysplasia: is acquired von Willebrand's disease the link? Lancet 1992;340:35-37.[Medline]
- Klovaite J, Gustafsson F, Mortensen SA, Sander K, Nielsen LB. Severely impaired von Willebrand factor-dependent platelet aggregation in patients with a continuous-flow left ventricular assist device (HeartMate II) J Am Coll Cardiol 2009;53:2162-2167.[Medline]
- John R, Lee S. The biological basis of thrombosis and bleeding in patients with ventricular assist devices J Cardiovasc Transl Res 2009;2:63-70.[Medline]
- Malehsa D, Meyer AL, Bara C, Struber M. Acquired von Willebrand syndrome after exchange of the HeartMate XVE to the HeartMate II ventricular assist device Eur J Cardiothorac Surg 2009;35:1091-1093.[Abstract/Free Full Text]
- Barbara G, De Giorgio R, Salvioli B, Stanghellini V, Corinaldesi R. Unsuccessful octreotide treatment of the watermelon stomach J Clin Gastroenterol 1998;26:345-346.[Medline]
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Abstract
Introduction
