Brown et al.

Journal of Otolaryngology - Head and Neck Surgery (2018) 47:48

https://doi.org/10.1186/s40463-018-0295-6

ORIGINAL RESEARCH ARTICLE Open Access

Management of epistaxis in patients with

ventricular assist device: a retrospective
review
Clifford Scott Brown* , Ralph Abi-Hachem and David Woojin Jang

Abstract
Background: Patients with a ventricular assist device (VAD) are at risk for epistaxis due to the need for
anticoagulation. Additionally, these patients develop acquired von Willebrand syndrome (AvWS) due to these
devices. Management is complicated by the risk of thrombosis if anticoagulation is reversed. This study sought to
characterize the clinical features and management of epistaxis in this high-risk population.
Methods: Retrospective review of adults with VAD and epistaxis necessitating inpatient consultation with the
otolaryngology service were included.
Results: 49 patients met inclusion criteria. All patients had a presumed diagnosis of AvWS. An elevated INR (> 2.0)
was present in 18 patients (36.7%). Anticoagulation was held in 14 (28.6%) patients, though active correction was
not necessary. Multiple encounters were required in 16 (32.7%) patients. Spontaneous epistaxis was associated with
multiple encounters (p = 0.02). The use of hemostatic material was associated with a lower likelihood of bleeding
recurrence (p = 0.05), whereas cauterization with silver nitrate alone was associated with a higher likelihood of re-
intervention (p = 0.05). Surgery or embolization was not required urgently for any patient. Endoscopy under general
anesthesia was performed for one patient electively. Mean follow up time was 16.6 months (σ = 6.3). At six months,
18 (36.7%) patients were deceased.
Conclusion: While these patients are at risk for recurrent spontaneous epistaxis, nonsurgical treatment without
active correction of INR or AvWS was largely successful. Placement of hemostatic material, as opposed to cautery
with silver nitrate, should be considered as a first-line treatment in this group. Multidisciplinary collaboration is
critical for successful management.
Keywords: Epistaxis, von Willebrand syndrome, Ventricular assist device, Anticoagulation

Background ligation (ESPAL) and vascular interventional procedures

Epistaxis remains the most frequent otolaryngologic emer- raises the question of when such interventions should be
gency and the second most common reason for referral to pursued [3].
an otolaryngologist [1]. Over the years, many studies have Epistaxis in the setting of coagulopathy is difficult to
sought to develop algorithms for treatment and preven- manage, as patients often require management of sys-
tion. Despite this, management of epistaxis remains a con- temic coagulopathy in addition to intranasal interven-
troversial and evolving topic. For example, there are no tions. Regardless of whether patients are medically
standard guidelines on duration of nasal packing and anticoagulated or suffer from an acquired or hereditary
whether prophylactic antibiotics are necessary [2]. More coagulopathy, they have longer average inpatient hospital
recently, the advent of endoscopic sphenopalatine artery stays and require more invasive measures of local
hemorrhage control when they develop epistaxis [4].
The incidence is high, with 10–17% of patients develop-
* Correspondence: [email protected]
Division of Head and Neck Surgery & Communication Sciences, Department
ing epistaxis during long-term vitamin K antagonist
of Surgery, Duke University Medical Center, DUMC 3805, Durham, NC 27710, therapy [5]. Given that there are 2.83 million quarterly
USA

© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
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Brown et al. Journal of Otolaryngology - Head and Neck Surgery (2018) 47:48 Page 2 of 6

visits with anticoagulation use in the United States, the date of LVAD surgery). Furthermore, anticoagulant and
at-risk population is significant [5–7]. antiplatelet medications, as well as vital signs and lab
One patient population that is especially at risk for epi- values at the time of consultation were extracted. Epi-
staxis are those with ventricular assist devices (VAD). Pa- staxis was categorized as spontaneous versus traumatic.
tients with heart failure may receive a VAD as either a Additionally, the bleeding location, interventions per-
bridge to transplantation or as destination therapy. They formed, outpatient follow-up after discharge, and the
often require multiple anti-coagulant and anti-platelet outcomes of each intervention were extracted.
medications, with a goal international normalized ratio
(INR) of 2.5 [8]. While bleeding is a major risk in these pa- Statistical analysis
tients, sub-therapeutic levels can lead to devastating Data were grouped categorically and analyzed with Pear-
thromboembolic consequences, with a reported incidence son’s chi-squared test. Tests of independence assessed
of 2–47% [9]. Therefore, a delicate balance must be main- for correlations between data points. Statistical analyses
tained. To make matters more complex, virtually all of were performed with SPSS 23.0 software (SPSS Inc., Chi-
these patients develop acquired von Willebrand syndrome cago, IL), with P < 0.05 considered significant.
(AvWS) as a result of the device itself. Patients with VAD
are also poor surgical candidates due to their cardiac Results
co-morbidities. All of the above factors create a complex A total of 49 patients met the inclusion criteria, with 37
situation when such a patient develops epistaxis. male and 12 female patients. Median age was 58 years
Patients may develop von Willebrand disease (VWD) (range: 18–85 years). The types of LVAD included 39
from a variety of etiologies, including hereditary and ac- (79%) HeartMate II (HMII), seven HeartWare (14%),
quired origins. Given that VWD the most common heredi- two Centimag (4%), and one VentrAssist (2%). The me-
tary blood-clotting disorder, its incidence is only increased dian time between LVAD placement and consultation
by the multiple medical conditions that contribute to its de- for epistaxis was 46 days (range 2–2886). There were 15
velopment. On the most basic level, a deficiency in either (30%) patients who required consultation within 10 days
the quantity or quality of von Willebrand factor (vWF) re- of placement. Primary reasons for admission included
sults in impaired platelet adhesion, and even in the mildest cardiac symptoms (79.6%), epistaxis (12.2%), and other
subtypes, epistaxis is a frequent symptom. (8.2%). Forty-six patients were seen in an inpatient unit
To our knowledge, this study would be the first to de- and three patients were seen in the emergency room.
scribe patient characteristics and management of epi- Spontaneous non-traumatic bleeds occurred in 37
staxis in this unique and complex patient population. (75.5%) patients. The presence of spontaneous epistaxis
We aimed to determine the efficacy of current treatment was associated with multiple interventions (Chi-square
modalities as well as to identify risk factors for recur- = 5.345, p-value = 0.02). The most common site of bleed-
rence of epistaxis. Based on the findings of Smith et. Al ing was the anterior septum, with 31 (63.2%) patients
[4], we hypothesized that patients with VAD would be bleeding from the unilateral septum, and 10 (20.4%)
more likely to require aggressive measures such as op- from the bilateral anterior septum (Fig. 1). Sixteen
erative intervention. (32.7%) patients required multiple interventions from
the otolaryngology service. Age, gender, and VAD type
Methods did not correlate significantly with spontaneous bleeding
This is a retrospective review of adult patients (age or the need for multiple interventions. Bleed location
greater than 18 years old) with an LVAD who required and the time between LVAD surgery and consultation
inpatient consultation with the otolaryngology service at did not correlate with spontaneous bleeding or need for
Duke University Medical Center for epistaxis between multiple interventions. Mean follow-up time after initial
July 1, 2006 and July 1, 2016. Institutional review board consultation was 16.6 (σ = 6.3) months. 18 (36.7%) pa-
approval was obtained through Duke University. Patients tients died prior to six month follow-up due to various
were identified through the Duke Enterprise Data Uni- causes, none of which were directly attributed to epi-
fied Content Explorer (DEDUCE). All patients with staxis. These findings are summarized in Table 1.
LVAD were initially selected based on CPT code 0048 T Each subject had an average of 1.59 (σ = 1.09) encounters.
or ICD codes V43.21 and Z95.811. From this group, Interventions included use of oxymetazoline spray with ap-
those with a documented diagnosis of epistaxis (ICD plication of direct pressure as an initial measure in all pa-
codes 784.7 or R04.0) and associated otolaryngology in- tients. Cauterization with silver nitrate was performed in 35
patient consultation were selected. (71.4%) patients. The use of cautery alone was associated
Electronic medical records for these patients were then with a need for repeat interventions (Chi-square = 3.998,
reviewed. Demographic information was recorded as p-value 0.05). Dissolvable hemostatic material was used in
well as information related to the LVAD (LVAD type, 23 (46.9%) patients, with Surgicel (Ethicon, NJ, USA) used
Brown et al. Journal of Otolaryngology - Head and Neck Surgery (2018) 47:48 Page 3 of 6

Fig. 1 Bleeding Location: Distribution of bleeding locations by number and percentage. Note that sites are not mutually exclusive

in 7 (14.3%) patients, and Nasopore (Stryker, MI, USA) non-dissolvable packing alone. Conservative, or non-surgi-
used in 17 (34.7%) patients. Hemospore, which contains cal, therapy was successful in all patients. There was a sin-
chitosan lactate, was not utilized. Non-dissolvable packing gle patient who was taken to the operating room for an
was used in 14 (28.6%) patients, with 8 (16.3%) patients elective lysis of synechiae that had resulted from prior inter-
receiving Merocel (Medtronic, MN, USA) and 7 (14.3%) ventions, requiring general anesthesia secondary to the
receiving Rapid Rhino (ArthroCare, TX, USA). The use of amount of scarring and prior failure of bedside attempts.
dissolvable or non-dissolvable hemostatic material was Dissolvable packing was placed in the nose at the conclu-
associated with a lower likelihood of bleeding recurrence sion of the procedure. No patient required urgent operative
(Chi-square = 4.204, p-value = 0.04), however this effect was intervention or angiography with embolization (Fig. 2).
not significant when assessing either dissolvable and All patients had an a priori diagnosis of AvWS as a result
of the LVAD. Thirty-four patients (69.4%) were concurrently
Table 1 Patient and Epistaxis Characteristics on warfarin, but only 18 (36.7%) of these had a therapeutic
Sex: VAD Type: INR (between 2.0 and 3.0) at the time of epistaxis and only
4 (8.2%) had a supratherapeutic INR (greater than 3.0).
Male: 37 (75%) HMII: 39 (79%)
Twenty-one (42.9%) patients were concurrently on heparin
Female: 12 (25%) HeartWare: 7 (14%)
with 12 (24.5%) of these having prolonged partial thrombo-
Total: 49 CentriMag: 2 (4%) plastin time (greater than 40 s). Thirty-three (67.3%) patients
VentrAssist: 1 (2%) were taking aspirin. Anticoagulant and antiplatelet medica-
Reason For Admission: Cause: tions were held in 14 (28.6%) patients because of epistaxis.
Cardiac: 39 (79%) Spontaneous: 37 (75%) Twenty-seven (55.1%) patients had normal platelet numbers
Epistaxis: 6 (12%) Traumatic: 12 (25%)
(greater than 150,000) and 7 (14.3%) patients had platelet
counts less than 100,000. No patient required active correc-
Other: 4 (8%)
tion of anticoagulation with fresh frozen plasma, vitamin K,
Location: Recurrence: or protamine sulfate. There was no association between
Anterior Septum: 41 (84%) < 7 Days: 6 (12%) spontaneous bleeding or need for multiple interventions and
Inferior Turbinate: 9 (18%) 7–30 Days: 6 (12%) the PTT, INR, or platelet count.
Other: 2 (4%) 1–6 Months: 4 (8%)
> 6 Months: 28 (57%)
Discussion
This study is the first to describe epistaxis management
Death < 6 Months: 18 (37%)
in patients with LVAD. Patients with LVAD represent a
Brown et al. Journal of Otolaryngology - Head and Neck Surgery (2018) 47:48 Page 4 of 6

Fig. 2 Summary of Interventions: Distribution of interventions performed by number and percentage. Note that interventions are not
mutually exclusive

complex patient population due to the need for continu- as initial management in patients with LVAD who present
ous anticoagulation and the development of AvWS. with epistaxis.
Moreover, these patients have end-stage heart failure Recently, ESPAL has been shown to be associated with a
and are poor candidates for general anesthesia. reduction in cost and length of hospitalization in compari-
In several ways, our results are consistent with the son to non-surgical treatment [14–17]. However, ESPAL
existing literature. The majority (75.5%) of our patients should be considered carefully in patients with LVAD,
had spontaneous, non-traumatic epistaxis. This is con- given the high cardiac risks with general anesthesia and
sistent with the findings by Parajuli [10], who noted that the bleeding risk from the surgery itself. For example,
80–90% of general epistaxis patients had no identifiable HeartMate II (HMII) devices have been associated with a
cause. Also, 83.6% of episodes reported in our study oc- significantly higher incidence of bleeding complications
curred at the anterior nasal septum. This is consistent during surgical procedures [18]. In addition, the risk of
with the distribution seen in the general population, with postoperative infection is substantial in the LVAD popula-
literature reports of 80–90% of bleeds occurring at this tion, as infection can seed the hardware [19]. Patients with
location [1, 11]. Moreover, the presence of spontaneous LVAD who develop an infection have cumulative survival
epistaxis in our patients was associated with multiple in- rates of 66.9% at 2 years compared to 81.3% for patients
terventions (P = 0.02), with 32.7% requiring multiple in- without an infection [20]. Although recent reviews suggest
terventions. Similarly, Anghel et. Al [1] noted that that patients with LVAD can safely undergo non-cardiac
patients with an idiopathic cause had the highest rate of surgery [21], other studies showed that perioperative death
recurrence over two years (26%). As for interventions, occurred in a range of 6.4–16.7% [22]. Given these risks,
local cauterization with silver nitrate was performed in surgery should be considered with caution in this patient
the majority of LVAD patients (71.4%). However, those population.
undergoing cauterization alone without placement of Because of the associated co-morbidities and need for
hemostatic material were likely to require additional in- anticoagulation with LVADs, a multi-disciplinary ap-
terventions at a later date. In their systematic review, proach must be taken in management of epistaxis. In our
Spielmann et al. noted that cautery was typically inef- study, holding anticoagulation was required in some
fective in patients receiving antiplatelet therapy [3]. patients, while it was continued in other instances. Inter-
In our study, the use of hemostatic material, both ab- estingly, only 4 (8.2%) patients in this cohort had a
sorbable and non-absorbable, was associated with a lower supratherapeutic INR, and no association between spon-
likelihood of bleeding recurrence. However, there was no taneous bleeding or multiple interventions with elevated
difference in efficacy amongst the type of material placed. INR was identified. This is consistent with the US-TRACE
This is consistent with existing literature demonstrating (STudy of Reduced Anti-Coagulation/Anti-platelEt ther-
no significant difference in efficacy of various types of apy) study, which found that recurrent bleeding occurred
nasal packing [12, 13]. Moreover, there were no adverse in 52% of cases despite reduced antithrombotic therapy
events related to nasal packing in our study. Based on [23], suggesting alternative contributing factors to
these findings, hemostatic material should be considered hemorrhagic complications.
Brown et al. Journal of Otolaryngology - Head and Neck Surgery (2018) 47:48 Page 5 of 6

Given the lack of association between INR and recurrent normalized ratio; PTT: Partial thromboplastin time; VAD: Ventricular assist
epistaxis, an important contributor may be AvWS, which device; VWD: Von Willebrand disease; VWF: Von Willebrand factor

results from the LVAD itself. LVADs produce continuous

Acknowledgements
blood flow along an axial path using an internal rotor in not applicable.
the blood [24]. This results in the loss of large von Willeb-
rand factor (vWF) multimers via a cleavage mechanism. In Funding
There are no sources of funding for the research conducted in this study.
this situation, AvWS occurs immediately after implantation,
and only resolves after device explantation [25, 26]. Serious Availability of data and materials
bleeding, defined as episodes that result in death, reopera- The datasets used and/or analyzed during the current study are available
tion, hospitalization, or transfusion, occurs in 19–40% of from the corresponding author on reasonable request.
patients with the HMII, making it the most frequent com-
Author’s contributions
plication [27], with the gastrointestinal tract and the nasal CSB performed the study design, literature review, manuscript drafting and
cavity being the most common sites [28]. The proteolytic review, data analysis and interpretation, accountability for all aspects of the
work.
mechanism that reduces VWF multimers also occurs in
RAH performed manuscript review, interpretation of data, accountability for
those with aortic valve stenosis, pancreatitis, liver cirrhosis, all aspects of work.
and leukemia [29]. According to the International Society DWJ oversaw the research project, was instrumental in study design,
manuscript drafting and review, accountability for all aspects of the work. All
on Thrombosis and Haemostasis, AvWS is most frequently
authors read and approved the final manuscript.
associated with lymphoproliferative (48%), cardiovascular
(21%), myeloproliferative (15%), other neoplastic (5%), and Ethics approval and consent to participate
autoimmune disorders (2%) [30]. Importantly, AvWS must This study was approved by the Institutional Review Board at Duke
University (Pro00071269).
be distinguished from von Willebrand disease (VWD), an
inherited disorder, due to different treatment approaches Consent for publication
[31]. Diagnosis favors AvWS when patients have late onset not applicable.
of bleeding, typically after an uneventful surgery, along with
Competing interests
an associated condition and a negative family history of
The authors declare that they have no competing interests.
bleeding. Desmopressin and VWF-containing concentrates
are treatment options in VWD, but are ineffective in LVAD
patients, with removal of the device being the only defini-
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in
tive treatment. Overall, AvWS is a condition that has impli- published maps and institutional affiliations.
cations beyond the LVAD population and should be
Received: 10 April 2018 Accepted: 27 July 2018
recognized by otolaryngologists.
One limitation of this study is its retrospective nature.
Another limitation is that we included only inpatient and References
emergency room consultations, which were mainly seen 1. Anghel AG, Soreanu CC, Dumitru M, Anghel I. Treatment options for severe
epistaxis, the experience of the Coltea ENT clinic. Maedica (Buchar). 2014
by residents of various training levels. Additionally, return Jun;9(2):179–82.
visits to the emergency department that did not involve a 2. Shrestha I, Pokharel M, Dhakal A, et al. Study of microorganism growth
consultation to otolaryngology were not included. How- Patten in nasal pack of patients visiting the department of ENT, head and
neck surgery. Kathmandu Univ Med J (KUMJ). 2015 Oct-Dec;13(52):303–7.
ever, we believe that our findings can be applied to care in 3. Spielmann PM, Barnes ML, White PS. Controversies in the specialist
the outpatient setting. management of adult epistaxis: an evidence-based review. Clin Otolaryngol.
2012 Oct;37(5):382–9. Doi: 10.111/coa.12024.
4. Smith J, Kim D, Dyer C, Siddiq S. Epistaxis in patients taking oral anticoagulant
Conclusion and antiplatelet medication: prospective cohort study. J Laryngol Otol. 2011
Jan;125(1):38–42. https://doi.org/10.1017/S0022215110001921.
Patients with LVAD present a unique challenge in the 5. Rubboli A, Becattini C, Verheugt FWA. Incidence, clinical impact and risk of
management of their epistaxis. Based on our findings, this bleeding during oral anticoagulation therapy. World J Cardiol. 2011 Nov 26;
difficulty stems from a variety of factors, including the 3(11):351–8. https://doi.org/10.4330/wjc.v3.i11.351.
6. Kirley K, Qato DM, Kornfield R, Stafford RS, Alexander GC. National trends in
need for anticoagulant or antiplatelet medication, develop- oral anticoagulant use in the United States, 2007 to 2011.
ment of irreversible AvWS, and high anesthetic risk. From 7. Barnes GD, Lucas E, Alexander GC, Goldberger ZD. National Trends in
the otolaryngologic perspective, use of hemostatic packing Ambulator Oral Anticoagulant Use. Am J Med. 2015 Dec;128(12):1300–5.e2.
doi: https://doi.org/10.1016/j.amjmed.2015.05.044.
should be considered as a first-line intervention. Overall, a 8. Rossi M, Serraina GF, Jiritano F, Renzuli A. What is the optimal
non-surgical multidisciplinary approach was successful in anticoagulation in patients with a left ventricular assist device? Interact
managing this complex patient population. Cardiovasc Thorac Surg. 2012 Oct;15(4):733–40. https://doi.org/10.1093/
icvts/ivs297.
9. Van den Bergh WM, Lanskin-Hartgring AO, Van Duijin AL, Engström AE,
Abbreviations Lahpor JR, Slooter AJC. Thromboembolic stroke in patients with a
AvWS: Acquired von Willebrand syndrome; ESPAL: Endoscopic HeartMate –II left ventricular assist device – the role of anticoagulation.
sphenopalatine artery ligation; HMII: HeartMate II; INR: International J Cardiothorac Surg. 2015;10:128. https://doi.org/10.1186/s13019-015-0333-7.
Brown et al. Journal of Otolaryngology - Head and Neck Surgery (2018) 47:48 Page 6 of 6

10. Parajuli R. Evaluation of etiology and treatment methods for epistaxis: a

review at a tertiary Care Hospital in Central Nepal. Int J Otolaryngol. 2015;
https://doi.org/10.1155/2015/283854.
11. Rudmik L, Smith TL. Management of intractable spontaneous epistaxis. Am J
Rhinol Allergy. 2012 Jan-Feb;26(1):55–60. https://doi.org/10.2500/ajra.2012.26.3696.
12. Badran K, Malik TH, Belloso A, Timms MS. Randomized controlled trial
comparing Merocel and RapidRhino packing in the management of
anterior epistaxis. Clin Otolaryngol. 2005 Aug;30(4):333–7.
13. Wang J, Cai C, Wang S. Merocel versus Nasopore for nasal packing: a meta-
analysis of randomized controlled trials. PLoS One. 2014 Apr 7;9(4):e93959.
https://doi.org/10.1371/journal.pone.0093959.
14. Moshaver A, Harris JR, Liu R, Diamond C, Seikaly H. Early operative
intervention vs. conventional treatment in epistaxis: randomized prospective
trial. J Otolaryngol. 2004 Jun;33(3):185–8.
15. Zou Y, Deng YQ, Xia CW, Kong YG, Xu Y, Tao ZZ, Chen SM. Comparison of
outcomes between endoscopic surgery and conventional nasal packing for
epistaxis fornix of the inferior nasal meatus. Pak J Med Sci. 2015 Nov-Dec;
31(6):1361–5. Doi: https://doi.org/10.12669/pjms.316.8340.
16. Rudmik L, Leung R. Cost-effectiveness analysis of endoscopic
sphenopalatine artery ligation vs arterial embolization for intractable
epistaxis. JAMA Otolaryngol Head Neck Surg. 2014;140(9):802–8. https://doi.
org/10.1001/jamaoto.2014.1450.
17. Liu J, Zhong G, Wang Y. A retrospective analysis of 163 cases with
intractable epistaxis managed by nasal endoscopic surgery. Lin Chung Er Bi
Yan Hou Tou Jing Wai Ke Za Zhi. 2013 Jun;27(11):590–2. Chinese.
18. Topkara VK, Kondareddy S, Malik F, Wang IW, Mann DL, Ewald GA, Moazami N.
Infectious complications in patients with left ventricular assist device: etiology
and outcomes in the continuous-flow era. Ann Thorac Surg. 2010;90:1270–7.
19. Kaplan JA. Ventricular Assist Devices, Cardiac Transplants, and Implanted
Electrical Devices in Noncardiac Surgery. Chapter 45. Section 7. Kaplan’s
Cardiac Anesthesia: For Cardiac and Noncardiac Surgery. Seventh Edition. 2017.
20. Uriel N, 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 Oct 5;56(15):1207–13. https://doi.org/10.1016/j.jacc.2010.05.016.
21. Nelson EW, et al. Management of LVAD patients for noncardiac surgery: a
single-institution study. J Cardiothorac Vasc Anesth. 2015 Aug;29(4):898–900.
https://doi.org/10.1053/j/jvca.2015.01.017.
22. Davis J, Sanford D, Schilling J, Hardi A, Colditz G. Systematic review of
outcomes after noncardiac surgery in patients with implanted left
ventricular assist devices. ASAIO J. 2015 Nov-Dec;61(6):648–51. https://doi.
org/10.1097/MAT.0000000000000278.
23. Katz JN, Adamson RM, John R, et al. TRACE study. Safety of reduced anti-
thrombotic strategies in HeartMate II patients: a one-year analysis of the US-
TRACE study. J Heart Lung Transplant. 2015;34(12):1542–8.
24. Nascimbene A, Neelamegham S, Frazier OH, Moake JL, Dong JF. Acquired von
Willebrand syndrome associated with left ventricular assist device. Blood. 2016
Jun 23;127(25):3133–41. https://doi.org/10.1182/blood-2015-10-636480.
25. Goda M, et al. Time course of acquire von Willebrand disease associated
with two types of continuous-flow left ventricular assist devices: HeartMate
II and CicuLite synergy pocket micro-pump. J Heart Lung Transplant. 2013
May;32(5):539–45. https://doi.org/10.1016/j.healun.2013.02.006.
26. Steinlechner B, et al. Platelet dysfunction in outpatients with left ventricular
assist devices. Ann Thorac Surg. 2009 Jan;87(1):131–7. https://doi.org/10.
1016/j.athoracsur.2008.10.027.
27. Starling RC, Naka Y, Boyle AJ, et al. Results of the post-U.S. Food and Drug
Administration-approval study with a continuous flow left ventricular assist
device as a bridge to heart transplantation: a prospective study using the
INTERMACS (interagency registry for mechanically assisted circulatory
support). J Am Coll Cardiol. 2011;57(19):1890–8.
28. Suarez J, Patel CB, Felker GM, Becker R, Hernandez AF, Rogers JG.
Mechanisms of bleeding and approach to patients with axial-flow left
ventricular assist devices. Circ Heart Fail. 2011;4(6):779–84.
29. Federici AB, Berkowitz SD, Lattuada A, Mannucci PM. Degradation of von
Willebrand factor in patients with acquired clinical conditions in which
there is heightened proteolysis. Blood. 1993;81(3):720–5.
30. Federici AB, Rand JH, Bucciarelli P, et al. Acquired von Willebrand syndrome:
data from an international registry. Thromb Haemost. 2000;84(2):345–9.
31. Tiede A, Rand JH, Federici AB, et al. How I treat the acquired von Willebrand
syndrome. Blood 2011 117:6777–6785; doi: https://doi.org/10.1182/blood-
2010-11-297580.