Pathologic von Willebrand factor degradation with a left ventricular assist device occurs via two distinct mechanisms: Mechanical demolition and enzymatic cleavage

Bartoli, Carlo; Restle, David; Zhang, David M.; Acker, Michael A.; Atluri, Pavan

doi:10.1016/j.jtcvs.2014.09.031

Cited by 96 publications

(111 citation statements)

References 35 publications

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“…41 Manipulating the natural regulation of vWF proteolysis by ADAMTS-13 represents a potential therapeutic option for nonsurgical LVAD bleeding. Direct inhibition of vWF degradation could also be achieved with monoclonal antibodies targeting the vWF D4 domain.…”

Section: Therapeutic Considerationsmentioning

confidence: 99%

Bleeding and thrombosis in chronic ventricular assist device therapy

Koliopoulou

McKellar

Rondina

et al. 2016

Current Opinion in Cardiology

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Purpose of review LVADs have markedly improved the survival for patients with advanced heart failure but are plagued with significant morbidity, including pump thrombosis and bleeding. Better understanding of the platelet, and their role in the balance of bleeding and thrombosis, stands to impact the frequency and treatment of these significant complications. Recent findings In patients with LVADs, there is little consistency linking traditional biomarkers of platelet activation and clinical events. A number of innovative methods of assessing platelet functionality, including shedding of platelet receptors and formation of microparticle complexes as well as measuring mitochondrial membrane potentials, exist and appear to be clinically relevant. Acquired von Willebrand syndrome, while not explaining all bleeding events, is a central feature of mechanical support and offers a target for innovative therapies Summary Although the platelet is only one component of impacting thrombosis and bleeding in patients supported with LVADs, it plays a central role in mediating these two opposing forces. Innovations in both understanding platelet physiology as well as manipulating genomic and receptor interactions for an individual patient will be critical if we are to decrease these serious adverse events in the future.

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Section: Therapeutic Considerationsmentioning

confidence: 99%

Bleeding and thrombosis in chronic ventricular assist device therapy

Koliopoulou

McKellar

Rondina

et al. 2016

Current Opinion in Cardiology

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“…33 Affected individuals have a decrease of high molecular weight VWF multimers as a result of increased shear stress and subsequent mechanical demolition and easier proteolysis by ADAMTS13. 34 Usually that does not result in abnormal VWF:Ag, VWF:RCo, or VWF:CB levels but the VWF:RCo/Ag and VWF:CB/Ag ratio is often reduced. The question is whether these changes in multimers result in phenotypic bleeding.…”

Section: Acquired Von Willebrand Syndrome (Avws)mentioning

confidence: 99%

Acquired bleeding disorders in the elderly

Kruse‐Jarres

2015

Hematology

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The hemostatic balance changes with advancing age which may be due to factors such as platelet activation, increase of certain clotting factor proteins, slowing of the fibrinolytic system, and modification of the endothelium and blood flow. Generally, this predisposes the elderly to thrombosis rather than bleeding. It often necessitates antiplatelet or anticoagulation therapy, which can cause significant bleeding problems in an aging population. Additionally, changing renal function, modification in immune regulation, and a multitude of other disease processes, can give rise to acquired bleeding disorders. Bleeding can prove difficult to treat in a dynamic environment and in a population that may have underlying thrombotic risk factors.This article discusses some specific challenges of acquired bleeding arising in the elderly. The use of anticoagulation and nonsteroidal anti-inflammatory medications is prevalent in the treatment of the elderly and predisposes them to increased bleeding risk as their physiology changes. When prescribing and monitoring these therapies, it is exceedingly important to weigh thrombotic versus bleeding risks. There are additional rare acquired bleeding disorders that predominantly affect the elderly. One of them is acquired hemophilia, which is an autoimmune disorder arising from antibodies against factor VIII. The treatment challenge rests in the use of hemostatic agents in a population that is already at increased risk for thrombotic complications. Another rare disorder of intensifying interest, acquired von Willebrand syndrome, has a multitude of etiologic mechanisms. Understanding the underlying pathophysiology is essential in making a treatment decision for this disorder. Learning Objectives• To recognize that coagulation changes with age and that it may predispose elderly patients on antithrombotic therapies to bleeding • To recognize the underlying thrombotic risk and comorbidities complicating the treatment of acquired hemophilia A • To understand the various pathophysiologic mechanisms leading to Acquired Von Willebrand Syndrome and assign appropriate treatment according to that mechanism Acquired bleeding disorders in the aging population are of concern because they are not readily diagnosed. In a study, community physicians from various specialties were presented with a hypothetical older adult woman complaining of recurrent epistaxis. Although most practitioners ordered complete blood counts and activated partial thromboplastin time (aPTT) as part of their work-up, less than one-half of nonhematologists repeated a significantly prolonged aPTT and Ͻ45% consulted a hematologist. Of those, emergency medicine physicians were least likely to consult hematology. 1

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“…6,[10][11][12] In addition, further delineation of mechanisms of avWD development has occurred. 13 Yet, there is scant literature regarding pulsatile VADs and the development of avWD. [14][15][16] The Berlin EXCOR has been in use in our institution since April 2008.…”

Section: Introductionmentioning

confidence: 99%