scholarly journals Acquired von Willebrand syndrome associated with left ventricular assist device

Blood ◽  
2016 ◽  
Vol 127 (25) ◽  
pp. 3133-3141 ◽  
Author(s):  
Angelo Nascimbene ◽  
Sriram Neelamegham ◽  
O. H. Frazier ◽  
Joel L. Moake ◽  
Jing-fei Dong
Keyword(s):  
Left Ventricular ◽  
Ventricular Assist Devices ◽  
Left Ventricular Assist Devices ◽  
Ventricular Assist ◽  
Acquired Von Willebrand Syndrome ◽  
Left Ventricular Assist ◽  
End Stage ◽  
Von Willebrand ◽  
Internal Rotor ◽  
Willebrand Factor

Abstract Left ventricular assist devices (LVAD) provide cardiac support for patients with end-stage heart disease as either bridge or destination therapy, and have significantly improved the survival of these patients. Whereas earlier models were designed to mimic the human heart by producing a pulsatile flow in parallel with the patient’s heart, newer devices, which are smaller and more durable, provide continuous blood flow along an axial path using an internal rotor in the blood. However, device-related hemostatic complications remain common and have negatively affected patients’ recovery and quality of life. In most patients, the von Willebrand factor (VWF) rapidly loses large multimers and binds poorly to platelets and subendothelial collagen upon LVAD implantation, leading to the term acquired von Willebrand syndrome (AVWS). These changes in VWF structure and adhesive activity recover quickly upon LVAD explantation and are not observed in patients with heart transplant. The VWF defects are believed to be caused by excessive cleavage of large VWF multimers by the metalloprotease ADAMTS-13 in an LVAD-driven circulation. However, evidence that this mechanism could be the primary cause for the loss of large VWF multimers and LVAD-associated bleeding remains circumstantial. This review discusses changes in VWF reactivity found in patients on LVAD support. It specifically focuses on impacts of LVAD-related mechanical stress on VWF structural stability and adhesive reactivity in exploring multiple causes of AVWS and LVAD-associated hemostatic complications.

Patients With End Stage Congestive Heart Failure Have Decreased High Molecular Weight Von Willebrand Factor Multimers and Higher Plasma Levels Of Total TGF-β1: Implantation Of a Left Ventricular Assist Devices (LVAD) Exacerbates Both Abnormalities

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1057-1057 ◽  
Author(s):  
Jasimuddin Ahamed ◽  
Juan Monteagudo ◽  
Mona Kinkhabwala ◽  
Mayte Suarez-Farinas ◽  
Arthur Reshad Garan ◽  
...  
Keyword(s):  
Left Ventricular ◽  
Ventricular Assist Devices ◽  
Healthy Controls ◽  
Left Ventricular Assist Devices ◽  
Ventricular Assist ◽  
Left Ventricular Assist ◽  
Before And After ◽  
End Stage ◽  
Von Willebrand ◽  
Tgf Β1

Abstract Left ventricular assist devices (LVADs) have improved survival of patients with end stage congestive heart failure (HF), but patients are at high risk of both hemorrhage and thrombosis. Acquired von Willebrand (vW) disease is observed in most patients after continuous flow LVAD insertion, presumably due to shear-dependent vW factor (vWf) cleavage, which may contribute to hemorrhage, but there are no validated thrombosis biomarkers. Since shear can also activate platelets, and platelets contain high concentration of transforming growth factor β1 (TGF-β1), we analyzed plasma TGF-β1 levels in patients before and after LVAD implantation and correlated the data with the loss of high molecular weight (HMW) vWf multimers. Blood samples were collected from 14 HF patients enrolled either as a destination therapy (n=2) or as a bridge to transplantation (n=12) at the Columbia University before and after LVAD implantation. Plasma was prepared by centrifuging blood at 12,000 rpm for 5 min at 4°C within 5 min of blood drawing. Total TGF-β1 levels were measured after acidification of samples using a 2-antibody ELISA (R&D Systems). The platelet α-granule proteins thrombospondin 1 (TSP-1) and platelet factor 4 (PF4) were detected by immunoblotting. vWf multimers were analyzed by electrophoresis of plasma after running in 1.2% discontinuous agarose gel followed by in-gel immunoreactivity band quantification using the LI-COR imaging system. HMW-vWf multimers were defined as the percentage of total vWf antigen contributed by multimers above the 11th identifiable band, starting from the cathodal position. Plasma total TGF-ß1 levels were higher in HF patients before LVAD implantation than in 16 healthy controls (3.76 ± 1.55 vs. 1.0 ± 0.60 ng/ml; p <0.001). After LVAD insertion, the levels in HF patients increased further to 5.20 ± 2.30 ng/ml (p=0.014). Plasma TGF-ß1 levels in HF patients before and after LVAD implantation were positively correlated with TSP-1 levels (r=0.86; p<0.0001), but PF4 was not detectable, suggesting in vivo release of TGF-β1 from platelets. A reduced percentage of HMW-vWf multimers was observed in HF patients before LVAD insertion compared to healthy controls (18.0 ± 10.0 vs. 29.5 ± 2.5 %; p=0.018), and the percentage was further reduced after LVAD implantation (11.0 ± 9.0 %; p=0.027). There was a weak negative correlation between the percentage of HMW-vWf multimers and TGF-ß1 after LVAD implantation (r= - 0.40; p=0.05). We conclude that HF itself, even before LVAD insertion, is associated with both loss of HMW-vWf multimers and elevation of plasma TGF-ß1 levels and both abnormalities are exacerbated by LVAD implantation. Disclosures: No relevant conflicts of interest to declare.

Acquired Von Willebrand Factor Deficiency Caused By Left Ventricular Assist Devices Is Adamts-13 Dependent

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3602-3602
Author(s):  
Petra Jilma-Stohlawetz ◽  
Schima Heinrich ◽  
Martin Stoiber ◽  
Peter Quehenberger ◽  
Sabine Schranz ◽  
...  
Keyword(s):  
Left Ventricular ◽  
Ventricular Assist Devices ◽  
High Shear ◽  
Left Ventricular Assist Devices ◽  
Ventricular Assist ◽  
Assist Devices ◽  
Left Ventricular Assist ◽  
Extracorporeal Circuits ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Background The high shear rates are induced by artificial heart valves or left ventricular assist devices cause acquired von Willebrand factor syndrome (aVWS). We hypothesised that an ex vivo model could be established to study whether mechanical shear alone causes aVWS or whether this process depends also on the VWF cleavage protein ADAMTS-13. Methods Healthy volunteers and two patients with congenital ADAMTS-13 deficiency donated blood. In vitro extracorporeal circuits were established using medically approved left ventricular assist devices (Heartware®) and silicone tubings with blood inlets and outlets. The pump speed and circulating blood volume were adjusted to correspond to in vivo use in humans. Anticoagulated blood circulated for 1-4 hours in the extracorporeal circuits. VWF multimers were quantified by sodium dodecyl sulphate-agarose discontinuous gel (1.2%) electrophoresis followed by Western-Blotting and consequent quantification with a luminescence image analyzer and a commercially available software, VWF antigen was measured by an STA assay and ristocetin co-factor activity (VWF:RCo) was quantified by turbidometry using a commercial kit (BC von Willebrand reagent; Dade Behring/Siemens, Marburg, Germany). Platelet function was measured by multiple electrode aggregometry in whole blood. Results The high shear stress in the extracorporeal circulation rapidly decreased VWF:RCo and thereby the VWF:RCo/VWF:Ag ratio by 47% (p<0.01) to pathologically low values. Concomitantly, high molecular weight multimers (HMWM) decreased, resembling the pathophysiological events that occur when an LVAD is implanted into humans. Up to 14-15 mers were visible on the gels at baseline, which were reduced by a maximum of 6-7 mers, corresponding to an average 68% lower densitometry signal of HMWM (p<0.01). This was accompanied by a 3-fold reduction in ristocetin induced aggregation (p<0.01). In contrast, the two patients with congenital thrombocytopenic purpura and virtually complete deficiency of ADAMTS-13 activity had only a minimal or no decrease in multimers (p<0.05 vs. healthy controls). Conclusion A model for LVAD associated aVWS was established, which demonstrated that ADAMTS-13 activity is essential for the depletion of HMWM of VWF that occurs in VAD-associated aVWS. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Bleeding in critical care associated with left ventricular assist devices: pathophysiology, symptoms, and management

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 88-96
Author(s):  
F. W. G. Leebeek ◽  
R. Muslem
Keyword(s):  
Critical Care ◽  
Left Ventricular ◽  
Ventricular Assist Devices ◽  
Bleeding Complications ◽  
Left Ventricular Assist Devices ◽  
Ventricular Assist ◽  
Assist Devices ◽  
Left Ventricular Assist ◽  
End Stage ◽  
Von Willebrand

Abstract Chronic heart failure (HF) is a growing health problem, and it is associated with high morbidity and mortality. Left ventricular assist devices (LVADs) are nowadays an important treatment option for patients with end-stage HF not only as a bridging tool to heart transplantation but also, as a permanent therapy for end-stage HF (destination therapy). The use of LVAD is associated with a high risk for bleeding complications and thromboembolic events, including pump thrombosis and ischemic stroke. Bleeding is the most frequent complication, occurring in 30% to 60% of patients, both early and late after LVAD implantation. Although the design of LVADs has improved over time, bleeding complications are still the most common complication and occur very frequently. The introduction of an LVAD results in an altered hemostatic balance as a consequence of blood-pump interactions, changes in hemodynamics, acquired coagulation abnormalities, and the strict need for long-term anticoagulant treatment with oral anticoagulants and antiplatelet therapy. LVAD patients may experience an acquired coagulopathy, including platelet dysfunction and impaired von Willebrand factor activity, resulting in acquired von Willebrand syndrome. In this educational manuscript, the epidemiology, etiology, and pathophysiology of bleeding in patients with LVAD will be discussed. Because hematologist are frequently consulted in cases of bleeding problems in these individuals in a critical care setting, the observed type of bleeding complications and management strategies to treat bleeding are also reviewed.

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