Acquired von Willebrand factor deficiency caused by LVAD is ADAMTS-13 and platelet dependent

Jilma‐Stohlawetz, Petra; Quehenberger, Peter; Schima, Heinrich; Stoiber, Martin; Knöbl, Paul; Steinlechner, Barbara; Felli, Alessia; Jilma, Bernd

doi:10.1016/j.thromres.2015.11.002

Cited by 44 publications

(35 citation statements)

References 36 publications

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“…High shear stress, which presumably unfolds the central A2 domain of ultra large plasmatic vWF, restores the sensitivity of vWF to ADAMTS13 [ 21 ]. Pump-induced shear stress in LVAD patients might therefore enhance HMWM-vWF breakdown into smaller units, leading to lower vWF activity [ 22 ]. Elevated HMWM-vWF cleavage consumes ADAMTS13 during its action on vWF [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

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Effects of HeartWare ventricular assist device on the von Willebrand factor: results of an academic Belgian center

Esmaeilzadeh

Wauters

Wijns

et al. 2016

BMC Cardiovasc Disord

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BackgroundLeft Ventricular Assist Device (LVAD) is a promising therapy for patients with advanced heart failure (HF), but bleeding complications remain an important issue. Previous series show that acquired von Willebrand syndrome was present in up to 100 % of first generation LVAD recipients. We report the effects of new generation LVADs on vW factor (vWF) metabolism and activity in our center.MethodsFifteen LVAD recipients (HeartWare®, Framingham, MA, USA) were compared to 12 HF patients, matched for age and body mass index. vWF antigen and activity, as well as D-dimers, were measured on hemostasis analyzers. A vWF LVAD-induced alteration was evocated when the [vWF activity]/[vWF antigen] ratio was <0.6. ADAMTS13 and high molecular weight multimers of vWF were also assessed.ResultsLVAD recipients had similar levels of endothelial vWF production than the HF subjects (137 ± 14.5 vs. 147 ± 11.7 %; respectively, p = 0.611) but a decreased vWF activity (90 ± 11 vs. 132.6 ± 13 %; respectively, p = 0.017). [vWF activity]/[vWF antigen] ratio was 0.65 ± 0.02 in the LVAD recipients and 0.92 ± 0.06 in the subjects with HF (p = 0.001). ADAMTS13 activity was 80.3 ± 4.7 % in LVAD recipients and 96.2 ± 3.5 % in the HF patients (p = 0.016). LVAD patients disclosed markedly elevated D-dimers (3217.7 ± 735 vs. 680.6 ± 223.2 ng/mL FEU in the HF patients, p = 0.006). The LVAD patients experienced one major hemorrhagic event and one systemic thrombotic event during the median follow-up of 345 days.ConclusionsLVAD recipients achieved a new hemostatic equilibrium characterized by infrequent major hemorrhagic and thrombotic events, despite a mildly impaired vWF function and a markedly enhanced thrombin formation.Trial registrationISRCTN39517567Electronic supplementary materialThe online version of this article (doi:10.1186/s12872-016-0334-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

“…Pump-induced shear stress in LVAD patients might therefore enhance HMWM-vWF breakdown into smaller units, leading to lower vWF activity [ 22 ]. Elevated HMWM-vWF cleavage consumes ADAMTS13 during its action on vWF [ 22 ]. As a result, both vWF activity and ADAMTS13 levels decrease [ 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of HeartWare ventricular assist device on the von Willebrand factor: results of an academic Belgian center

Esmaeilzadeh

Wauters

Wijns

et al. 2016

BMC Cardiovasc Disord

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“…In addition to native and prosthetic valve disease, high shear stress is also encountered with LVADs. There have been numerous studies to suggest that VWF is a player in the established association between LVAD and bleeding . Van Belle et al performed VWF analysis in patients with the HeartMate‐II LVAD (Thoratec Corporation) .…”

Section: Vwf and Lvadmentioning

confidence: 99%

“…There have been numerous studies to suggest that VWF is a player in the established association between LVAD and bleeding. 15,48,49 Van Belle et al performed VWF analysis in patients with the HeartMate-II LVAD (Thoratec Corporation). 17 The study found a significant reduction in HMWM as well as VWF:CB/ VWF:Ag ratio shortly after initiating the pump.…”

Section: Vwf and Lvadmentioning

confidence: 99%

Von Willebrand factor revisited

Yasar

Abdullah

Fay

et al. 2017

J Interven Cardiology

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Degenerative aortic valve stenosis is the most common valvular heart disease seen in developed countries. Since the implementation of transcatheter aortic valve replacement, there has been a surge of efforts to improve procedural technique as well as reduce mortality. Until recently, the mainstay method of assessment of valve implantation as well as paravalvular regurgitation has relied heavily on imaging techniques including transesophageal echocardiography and aortic root angiography. There has been a lot of scientific inquiry to identify biomarkers in the management of patients with aortic stenosis. von Willebrand factor activity and high molecular weight multimer level assessment has emerged as an excellent biomarker with intraoperative, point of care potential. These implications can both supplement imaging modalities as well as potentially serve as a more accurate assessment TAVR complications.

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“…Recently, an in vitro model of VAD circulation confirmed the depletion of large VWF multimers is dependent on both ADAMTS13 and platelets. 42 The diagnosis of AVWS is based on decreased VWF activity to antigen ratio and diminished or total absence of large multimer bands on VWF multimeric structure assay. However, VWF antigen and activity in these patients can be normal or even increased.…”

Section: Acquired Von Willebrand Syndromementioning

confidence: 99%

Management of Hemostasis for Pediatric Patients on Ventricular-Assist Devices

Adachi

Kostousov

Hensch

et al. 2017

Semin Thromb Hemost

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Ventricular-assist devices (VADs) have seen increased utilization in the pediatric population. Formerly, this therapeutic modality was limited to only the pulsatile VAD, EXCOR (Berlin Heart GmbH). However, the continuous flow VAD devices, HeartMate II (Abbott Inc.) and HeartWare (Medtronic Inc.), are now increasingly used in this population. Postoperatively, VAD patients are acutely anticoagulated using unfractionated heparin, often beginning 24 to 48 hours after VAD placement. Once the patient is stabilized and ready to transition to a lower acuity or outpatient setting, low-molecular-weight heparin or warfarin therapy may be instituted. Also, because of the risk for thrombotic and thromboembolic complications, antiplatelet strategies are employed using medications such as aspirin, clopidogrel, or dipyridamole. Platelet-rich plasma or whole blood platelet aggregation studies, platelet function analyzer-100 (Siemens), VerifyNow (Accriva Diagnostics), or thromboelastography platelet mapping (Haemonetics) may be used to help monitor antiplatelet effects, though the interpretation of the strength of the antiplatelet effect remains difficult. Care must be taken to monitor the hematologic complications of VAD, including acquired von Willebrand syndrome, which increases the risk for bleeding, and intravascular hemolysis, which increases the risk of thrombosis. Appropriate device placement and anticoagulation management are imperative to help avoid neurological dysfunction and ischemic stroke, the most devastating potential complications of VAD therapy. As our experience grows, we continue to gain an increased understanding of the management of anticoagulation, need for antiplatelet medication, and appropriate monitoring for these critical patients.

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Acquired von Willebrand factor deficiency caused by LVAD is ADAMTS-13 and platelet dependent

Abstract: An in vitro model for LVAD associated aVWD demonstrated that ADAMTS-13 and platelets contribute to the depletion of HMWM of VWF.

Cited by 44 publications

References 36 publications

Effects of HeartWare ventricular assist device on the von Willebrand factor: results of an academic Belgian center

Effects of HeartWare ventricular assist device on the von Willebrand factor: results of an academic Belgian center

Von Willebrand factor revisited

Management of Hemostasis for Pediatric Patients on Ventricular-Assist Devices

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