Unexpected Abrupt Increase in Left Ventricular Assist Device Thrombosis

Rame, J. Eduardo; Atluri, Pavan; Acker, Michael A.

doi:10.1056/nejmc1402425

Cited by 16 publications

(10 citation statements)

References 9 publications

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“…In terms of secular trends in anticoagulation management, the rate of pump thrombosis has been increasing over time, and anticoagulation and antiplatelet regimens have varied over time. 7, 8, 22 Although we did not quantify von-Willebrand factor or platelet function, other LVAD studies have found that acquired von-Willebrand s contributes to GI bleeding. 23 Furthermore, screening for thrombosis has intensified, potentially resulting in more frequent detection of suspected pump thrombosis.…”

Section: Discussionmentioning

confidence: 94%

Relationship Between Anticoagulation Intensity and Thrombotic or Bleeding Outcomes Among Outpatients With Continuous-Flow Left Ventricular Assist Devices

Nassif

LaRue

Raymer

et al. 2016

Circ: Heart Failure

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Background We evaluated thrombotic and bleeding outcomes in patients with continuous flow left ventricular assist devices (CF-LVADs), stratified by anticoagulation intensity. Previous studies of outpatients with CF-LVADs have suggested that target international normalized ratio (INR) values less than 2.5 (range 2-3) may be used. However, recent studies reported an increase in pump thrombosis among CF-LVADs, especially within the first 6 months of implant. Methods and Results We retrospectively reviewed 249 outpatients at our center who received a CF-LVAD between 1/2005 and 8/2013. Using Poisson models we analyzed their 10,927 INRs to determine INR-specific rates of thrombotic (ischemic stroke and suspected pump thrombosis) and hemorrhagic (gastrointestinal bleeding and hemorrhagic stroke) events occurring outside of the hospital. In multivariate analyses, we adjusted for age, sex, atrial fibrillation, coronary disease, and LVAD type as time-dependent Cox proportional hazard models. During a mean follow-up of 17.6 ± 13.6 months, thrombotic events occurred in 46 outpatients. The highest event rate (0.40 thrombotic events per patient-year) was in the INR range of < 1.5, but INR values of 1.5-1.99 also had high rates (0.16 thrombotic events per patient-year). INR was inversely associated with thrombotic events (HR 0.40, 95% 0.22-0.72; P = 0.002). The optimal INR based on weighted mortality of thrombotic and bleeding events was 2.6. Conclusions INR is inversely related to thrombotic events occurring outside of the hospital among patients supported with CF-LVADs. INR values less than 2.0 increase the rate of thrombotic events occurring outside of the hospital among patients supported with CF-LVADs.

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Section: Discussionmentioning

confidence: 94%

Relationship Between Anticoagulation Intensity and Thrombotic or Bleeding Outcomes Among Outpatients With Continuous-Flow Left Ventricular Assist Devices

Nassif

LaRue

Raymer

et al. 2016

Circ: Heart Failure

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“…Recent results show that increasing lactate dehydrogenase (LDH) levels can be monitored as a possible predictor of pump thrombosis in VAD patients (4). Developing a greater understanding of other hemocompatibility parameters such as changes in vWF, platelet, or leukocyte activation, may provide even more sensitive or early prediction of adverse reactions in clinical trials of blood pumps.…”

Section: Discussionmentioning

confidence: 99%

“…This has stimulated interest in even smaller devices aimed at improving quality of life and minimizing potentially life-threatening complications. Pump thrombosis and systemic thromboembolism persist as the major limitation of this technology and has proven difficult to predict from in vivo testing in sheep or calves (4). Nonetheless, extensive preclinical testing is mandatory prior to clinical application of any new LVAD (5).…”

mentioning

confidence: 99%

The CentriMag Centrifugal Blood Pump as a Benchmark for In Vitro Testing of Hemocompatibility in Implantable Ventricular Assist Devices

et al. 2014

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Implantable ventricular assist devices (VADs) have proven efficient in advanced heart failure patients as a bridge-to-transplant or destination therapy. However, VAD usage often leads to infection, bleeding, and thrombosis, side effects attributable to the damage to blood cells and plasma proteins. Measuring hemolysis alone does not provide sufficient information to understand total blood damage, and research exploring the impact of currently available pumps on a wider range of blood cell types and plasma proteins such as von Willebrand factor (vWF) is required to further our understanding of safer pump design. The extracorporeal CentriMag (Thoratec Corporation, Pleasanton, CA, USA) has a hemolysis profile within published standards of normalized index of hemolysis levels of less than 0.01 g/100 L at 100 mm Hg but the effect on leukocytes, vWF multimers, and platelets is unknown. Here, the CentriMag was tested using bovine blood (n = 15) under constant hemodynamic conditions in comparison with a static control for total blood cell counts, hemolysis, leukocyte death, vWF multimers, microparticles, platelet activation, and apoptosis. The CentriMag decreased the levels of healthy leukocytes (P < 0.006), induced leukocyte microparticles (P < 10−5), and the level of high molecular weight of vWF multimers was significantly reduced in the CentriMag (P < 10−5) all compared with the static treatment after 6 h in vitro testing. Despite the leukocyte damage, microparticle formation, and cleavage of vWF multimers, these results show that the CentriMag is a hemocompatible pump which could be used as a standard in blood damage assays to inform the design of new implantable blood pumps.

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“…However, MCS therapy with currently available LVADs remains suboptimal and is often associated with serious complications . The United States Food and Drug Administration (US FDA) approved LVAD, HeartMate II (HMII) (Abbott, Pleasanton, CA, USA), uses a pair of ball‐and‐cup bearings to support its impeller; the predominant location of thrombosis observed in explanted HMII devices . Another FDA approved LVAD, HVAD (HeartWare, Miami Lakes, FL, USA), uses hydrodynamic bearing technology, which might contribute to the increased thrombotic and hemolytic risks, due to high shear stress in the small gap .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of in vitro hemolysis and platelet activation of a newly developed maglev LVAD and two clinically used LVADs with human blood

et al. 2019

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In vitro hemolysis testing remains one of the most important performance measures to judge the hemocompatibility of a left ventricular assist device (LVAD). Clinically relevant operating conditions and appropriate testing blood are essential to infer in vitro data for potential clinical use. This in vitro study was carried out to evaluate and compare the hemolytic performance of a newly developed magnetically levitated (maglev) LVAD (CH‐VAD) with two clinically used LVADs (HVAD and HeartMate II (HMII)) using fresh human blood. A small volume (~300 mL) in vitro circulating flow loop was constructed with a LVAD generated flow of 4.5 L/min at the nominal or reported clinical operating speed for each LVAD. The blood was circulated in the loop for 4 hours with samples drawn at baseline and hourly. Plasma‐free hemoglobin (PFH) concentrations in the hourly blood samples were determined with spectrophotometry. Normalized index of hemolysis (NIH) was calculated to compare the hemolytic performance of the CH‐VAD and the two reference LVADs. Platelet activation was measured with flow cytometry. The experimental test for each device was repeated at least 7 times. The data from this study showed that all the three LVADs generated very low hemolysis (NIH <0.01 g/100 L). The CH‐VAD was found to have a significantly lower NIH value (0.00135 ± 0.00032 g/100 L) compared to the HVAD (0.00525 ± 0.00183 g/100 L) and the HMII (0.00583 ± 0.00182 g/100 L). No statistically significant difference in device‐generated hemolysis was found between the HVAD and the HMII. The level of platelet activation induced by the CH‐VAD is significantly lower than those by the HVAD and the HMII. The data suggest that the shear‐induced hemolysis and platelet activation of the CH‐VAD are acceptable relative to the two LVADs currently in clinical use.

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Unexpected Abrupt Increase in Left Ventricular Assist Device Thrombosis

Cited by 16 publications

References 9 publications

Relationship Between Anticoagulation Intensity and Thrombotic or Bleeding Outcomes Among Outpatients With Continuous-Flow Left Ventricular Assist Devices

Relationship Between Anticoagulation Intensity and Thrombotic or Bleeding Outcomes Among Outpatients With Continuous-Flow Left Ventricular Assist Devices

The CentriMag Centrifugal Blood Pump as a Benchmark for In Vitro Testing of Hemocompatibility in Implantable Ventricular Assist Devices

Evaluation of in vitro hemolysis and platelet activation of a newly developed maglev LVAD and two clinically used LVADs with human blood

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