Device‐induced platelet dysfunction in patients after left ventricular assist device implantation

Klaeske, Kristin; Dieterlen, Maja‐Theresa; Eifert, Sandra; Scholz, Ute; Garbade, Jens; Jawad, Khalil; Sieg, Franz; Borger, Michael A.; Meyer, Anna

doi:10.1111/jth.15279

Cited by 19 publications

(22 citation statements)

References 35 publications

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“…Heart failure is a risk factor for stroke in patients with atrial fibrillation (39) and therefore one could expect a similar mechanism in our series. Another explanation may be an altered expression of platelet receptors P-selectin, GPIbα and PECAM-1 in context of oxidative stress linked to a high bleeding risk as recently described by Klaeske et al (35). Furthermore, most of our patients were on any anti-platelet medication or anti-coagulated with LMWH or oral anticoagulation.…”

Section: Discussionmentioning

confidence: 81%

“…The etiologies of postoperative bleeding are multifactorial and include thrombocytopenia and activation of fibrinolytic systems. In particular, the recognition of postoperative platelet dysfunction as an important risk factor for bleeding (32) has prompted extensive research in the field of LVAD-induced platelet dysfunction in recent years (33)(34)(35). This research discovered the importance of both acquired von Willebrand syndrome (AvWS) (33,34) and platelet receptor alterations (35) after LVAD implantation.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, the recognition of postoperative platelet dysfunction as an important risk factor for bleeding (32) has prompted extensive research in the field of LVAD-induced platelet dysfunction in recent years (33)(34)(35). This research discovered the importance of both acquired von Willebrand syndrome (AvWS) (33,34) and platelet receptor alterations (35) after LVAD implantation. Furthermore, in cases of clinical deterioration the LVAD implantation cannot be delayed and a sustained impact of anti-platelet medication or of anticoagulants taken before LVAD implantation that enhances the bleeding risk is highly probable.…”

Section: Discussionmentioning

confidence: 99%

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A Prospective Observational Study on Multiplate®-, ROTEM®- and Thrombin Generation Examinations Before and Early After Implantation of a Left Ventricular Assist Device (LVAD)

et al. 2022

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BackgroundHeart failure patients are frequently on coagulation-active medications before LVAD implantation and perioperative bleeding is a frequent complication after left ventricular assist device (LVAD) implantation. The role of point-of-care coagulation tests in assessing bleeding risk for LVAD implantation and the early postoperative time course of these tests is not well established.MethodsWe prospectively enrolled 25 patients with terminal heart failure undergoing LVAD implantation. Study related TRAP-, ASPI- and ADP- tests of Multiplate® platelet aggregometry, ROTEM® rotational thromboelastometry (INTEM, EXTEM, FIBTEM), thrombin generation assay and conventional laboratory studies were measured at 11 predefined time-points during the first 21 postoperative days. We examined if preoperative TRAP-, ASPI-, ADP- and ROTEM values are correlated with estimated total blood loss (primary outcome parameter) during the first 21 days after LVAD implantation and compared the baseline values of these measurements between patients with a bleeding event to those without. We performed Spearman's correlation and non-parametric tests for paired and non-paired comparisons.Results7 out of 25 (28%) patients experienced a bleeding event of which 4 required surgical revision. Of the preoperatively performed measurements the TRAP test [Spearman's Rho (ρ) = −0.5, p = 0.01], INTEM CFT (ρ = 0.72, p < 0.001), INTEM alpha (−0.7, p < 0.001), EXTEM MCF (ρ = −0.63; p < 0.001), EXTEM alpha (ρ = −0.67; p < 0.001), FIBTEM MCF (ρ = −0.41; p = 0.042), Fibrinogen (Clauss) (ρ = −0.5; p = 0.011), Anti-thrombin activity (ρ = −0.49; p = 0.013) and platelet count (ρ = −0.42; p = 0.034) were significantly correlated to total blood loss. Patients undergoing a surgical bleeding revision had significantly reduced values in TRAP—[31.5 IQR (17.25–43.5U) vs. 69 IQR (52.5–87U); p = 0.004], ASPI—[16.5 IQR (5.5–35.7U) vs. 39 IQR (24.5–62.5U); p = 0.038], ADP—[30 IQR (22–69U) vs. 12.5 IQR (8.7–21.5U); p = 0.01], EXTEM MCF—[63 IQR (57.7–63.7) vs. 67 IQR (65–75.5); p = 0.019] and EXTEM alpha [74 IQR (68.75–74) vs. 79 IQR (78–80.5); p = 0.002] values before LVAD implantation.ConclusionMultiplate® and ROTEM® measurements before LVAD implantation may identify LVAD candidates with platelet dysfunction and alterations of the primary hemostasis and could guide anesthetists and intensive care practitioners in bleeding risk stratification and in the perioperative clinical management.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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A Prospective Observational Study on Multiplate®-, ROTEM®- and Thrombin Generation Examinations Before and Early After Implantation of a Left Ventricular Assist Device (LVAD)

et al. 2022

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“…Additionally, studies have shown that this form of treatment leads to changes of the following platelet receptors: GPIbα, P-selectin, and PECAM-1. Furthermore, elevated oxidative stress may lead to the exacerbation of nonsurgical bleeding in these patients [23].…”

Section: Bleeding During Lvad Therapymentioning

confidence: 99%

Hemostasis Disturbances in Continuous-Flow Left Ventricular Assist Device (CF-LVAD) Patients—Rationale and Study Design

Kuczaj

Hudzik

Kaczmarski

et al. 2022

JCM

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Left ventricular assist devices are a treatment option for end-stage heart failure patients. Despite advancing technologies, bleeding and thromboembolic events strongly decrease the survival and the quality of life of these patients. Little is known about prognostic factors determining these adverse events in this group of patients. Therefore, we plan to investigate 90 consecutive left ventricular assist device (LVAD) patients and study in vitro fibrin clot properties (clot lysis time, clot permeability, fibrin ultrastructure using a scanning electron microscope) and the calibrated automated thrombogram in addition to the von Willebrand factor antigen, fibrinogen, D-dimer, prothrombin time/international normalized ratio (PT/INR), and activated partial thromboplastin time (APTT) to identify prognostic factors of adverse outcomes during the course of therapy. We plan to assess the hemostasis system at four different time points, i.e., before LVAD implantation, 3–4 months after LVAD implantation, 6–12 months after LVAD implantation, and at the end of the study (at 5 years or at the time of the adverse event). Adverse outcomes were defined as bleeding events (bleeding in general or in the following subtypes: severe bleeding, fatal bleeding, gastrointestinal bleeding, intracranial bleeding), thromboembolic events (stroke or transient ischemic attack, pump thrombosis, including thrombosis within the pump or its inflow or outflow conduits, arterial peripheral thromboembolism), and death.

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“…Elevated oxidative stress biomarkers, platelet receptor shedding of glycoprotein (GP) Ibα, GPVI and an activation of GPIIb/IIIa were reported in patients with post-implant bleeding complications [ 6 , 9 , 10 , 11 , 12 , 13 , 14 ]. Therefore, the loss of functional surface receptors results in a defective platelet function and may contribute to an increased bleeding risk in LVAD patients.…”

Section: Introductionmentioning

confidence: 99%

Decreased Platelet Specific Receptor Expression of P-Selectin and GPIIb/IIIa Predict Future Non-Surgical Bleeding in Patients after Left Ventricular Assist Device Implantation

Klaeske

Meyer

Saeed

et al. 2022

IJMS

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Non-surgical bleeding (NSB) is one of the major clinical complications in patients under continuous-flow left ventricular assist device (LVAD) support. The increased shear stress leads to an altered platelet receptor composition. Whether these changes increase the risk for NSB is unclear. Thus, we compared the platelet receptor composition of patients with (bleeder group, n = 18) and without NSB (non-bleeder group, n = 18) prior to LVAD implantation. Blood samples were obtained prior to LVAD implantation and after bleeding complications in the post-implant period. Platelet receptor expression of GPIbα, GPIIb/IIIa, P-selectin and CD63 as well as intra-platelet oxidative stress levels were quantified by flow cytometry. Bleeders and non-bleeders were comparable regarding clinical characteristics, von Willebrand factor diagnostics and the aggregation capacity before and after LVAD implantation (p > 0.05). LVAD patients in the bleeder group suffered from gastrointestinal bleeding (33%; n = 6), epistaxis (22%; n = 4), hematuria or hematoma (17%; n = 3, respectively) and cerebral bleeding (11%; n = 2). Prior to LVAD implantation, a restricted surface expression of the platelet receptors P-selectin and GPIIb/IIIa was observed in the bleeder group (P-selectin: 7.2 ± 2.6%; GPIIb/IIIa: 26,900 ± 13,608 U) compared to non-bleeders (P-selectin: 12.4 ± 8.1%, p = 0.02; GPIIb/IIIa: 36,259 ± 9914 U; p = 0.02). We hypothesized that the reduced platelet receptor expression of P-selectin and GPIIb/IIIa prior to LVAD implantation may be linked to LVAD-related NSB.

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Device‐induced platelet dysfunction in patients after left ventricular assist device implantation

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 19 publications

References 35 publications

A Prospective Observational Study on Multiplate®-, ROTEM®- and Thrombin Generation Examinations Before and Early After Implantation of a Left Ventricular Assist Device (LVAD)

A Prospective Observational Study on Multiplate®-, ROTEM®- and Thrombin Generation Examinations Before and Early After Implantation of a Left Ventricular Assist Device (LVAD)

Hemostasis Disturbances in Continuous-Flow Left Ventricular Assist Device (CF-LVAD) Patients—Rationale and Study Design

Decreased Platelet Specific Receptor Expression of P-Selectin and GPIIb/IIIa Predict Future Non-Surgical Bleeding in Patients after Left Ventricular Assist Device Implantation

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