Hematologic Markers Better Predict Left Ventricular Assist Device Thrombosis than Echocardiographic or Pump Parameters

Bartoli, Carlo; Ghotra, Amaninderapal S.; Pachika, Ajay; Birks, Emma J.; McCants, Kelly C.

doi:10.1055/s-0034-1376891

Cited by 24 publications

(12 citation statements)

References 18 publications

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“…97 These findings are relevant because hemolysis often occurs in patients on LVAD support and is associated with thrombotic events. [98][99][100][101] They also raise an important question regarding the potential redox-regulation of VWF reactivity and cleavage by hemoglobin, which is often called a "biological Fenton's reagent" for its strong oxidative activity (from the heme iron). 102 Oxidative stress has indeed been shown to make VWF hyper-reactive, render them resistant to ADAMTS-13, and inhibit ADAMTS-13 activity.…”

Section: Regulation Of Vwf By Physical Forcesmentioning

confidence: 99%

Acquired von Willebrand syndrome associated with left ventricular assist device

Nascimbene

Neelamegham

Frazier

et al. 2016

Blood

187

150

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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.

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Section: Regulation Of Vwf By Physical Forcesmentioning

confidence: 99%

Acquired von Willebrand syndrome associated with left ventricular assist device

Nascimbene

Neelamegham

Frazier

et al. 2016

Blood

187

150

View full text Add to dashboard Cite

show abstract

“…There is mounting evidence that abnormal hemodynamics [5,22,25] contribute to at least low-level (subclinical) hemolysis in all continuous-flow LVAD patients [9][10][11]26]. In nearly every LVAD patient, LDH, a biomarker of hemolysis, is chronically elevated in the range of 250 to 685 U/L [10,11,26,27] (normal <220 U/L).…”

Section: Lvad-associated Hemolysis Is a Constant Source Of Pfhgb In Pmentioning

confidence: 99%

“…Plasma free hemoglobin (pfHgb) inhibits ADAMTS-13 [7,8]. In patients with a continuous-flow LVAD, subclinical hemolysis is a constant source of elevated pfHgb [9][10][11]. Therefore, in LVAD patients, pfHgb from hemolysis may inactivate ADAMTS-13 and cause hemostatically active vWF multimers to accumulate and initiate clot formation.…”

mentioning

confidence: 99%

Clinical and In Vitro Evidence That Subclinical Hemolysis Contributes to LVAD Thrombosis

Bartoli

Zhang

Kang

et al. 2018

The Annals of Thoracic Surgery

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These are the first data to demonstrate mechanistic relationships between subclinical hemolysis and a procoagulant state during continuous-flow LVAD support. Patients with high pfHgb and LDH were more likely to develop LVAD thrombosis. In vitro experiments demonstrated that free hemoglobin inhibited ADAMTS-13, protected vWF from degradation, increased vWF clotting function, and created a procoagulant state. As such, pfHgb may be a clinical target to prevent LVAD thrombosis.

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“…Slope of left ventricular end‐diastolic diameter measurements in ramp testing, in conjunction with serum LDH values, has been shown to provide excellent sensitivity for LVAD thrombosis, but with limitations . Further, some data suggest that serum biomarkers may become elevated earlier than abnormalities appreciated on ramp testing …”

Section: Discussionmentioning

confidence: 99%

Dynamic prediction of left ventricular assist device pump thrombosis based on lactate dehydrogenase trends

et al. 2019

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AimsThe risk of HeartMate II (HMII) left ventricular assist device (LVAD) thrombosis has been reported, and serum lactate dehydrogenase (LDH), a biomarker of haemolysis, increases secondary to LVAD thrombosis. This study evaluated longitudinal measurements of LDH post‐LVAD implantation, hypothesizing that LDH trends could timely predict future LVAD thrombosis.Methods and resultsFrom October 2004 to October 2014, 350 HMIIs were implanted in 323 patients at Cleveland Clinic. Of these, patients on 339 HMIIs had at least one post‐implant LDH value (7996 total measurements). A two‐step joint model combining longitudinal biomarker data and pump thrombosis events was generated to assess the effect of changing LDH on thrombosis risk. Device‐specific LDH trends were first smoothed using multivariate boosted trees, and then used as a time‐varying covariate function in a multiphase hazard model to analyse time to thrombosis. Pre‐implant variables associated with time‐varying LDH values post‐implant using boostmtree were also investigated. Standardized variable importance for each variable was estimated as the difference between model‐based prediction error of LDH when the variable was randomly permuted and prediction error without permuting the values. The larger this difference, the more important a variable is for predicting the trajectory of post‐implant LDH. Thirty‐five HMIIs (10%) had either confirmed (18) or suspected (17) thrombosis, with 15 (43%) occurring within 3 months of implant. LDH was associated with thrombosis occurring both early and late after implant (P < 0.0001 for both hazard phases). The model demonstrated increased probability of HMII thrombosis as LDH trended upward, with steep changes in LDH trajectory paralleling trajectories in probability of pump thrombosis. The most important baseline variables predictive of the longitudinal pattern of LDH were higher bilirubin, higher pre‐implant LDH, and older age. The effect of some pre‐implant variables such as sodium on the post‐implant LDH longitudinal pattern differed across time.ConclusionsLongitudinal trends in surveillance LDH for patients on HMII support are useful for dynamic prediction of pump thrombosis, both early after implant and late. Incorporating upward and downward trends in LDH that dynamically update a model of LVAD thrombosis risk provides a useful tool for clinical management and decisions.

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Hematologic Markers Better Predict Left Ventricular Assist Device Thrombosis than Echocardiographic or Pump Parameters

Abstract: Hematological markers of hemolysis, but not echocardiographic or pump parameters, reliably changed during LVAD thrombosis. Markers of hemolysis are the best early predictors of LVAD thrombosis.

Cited by 24 publications

References 18 publications

Acquired von Willebrand syndrome associated with left ventricular assist device

Acquired von Willebrand syndrome associated with left ventricular assist device

Clinical and In Vitro Evidence That Subclinical Hemolysis Contributes to LVAD Thrombosis

Dynamic prediction of left ventricular assist device pump thrombosis based on lactate dehydrogenase trends

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