Bleeding and thrombosis in chronic ventricular assist device therapy

Abstract

Purpose of review LVADs have markedly improved the survival for patients with advanced heart failure but are plagued with significant morbidity, including pump thrombosis and bleeding. Better understanding of the platelet, and their role in the balance of bleeding and thrombosis, stands to impact the frequency and treatment of these significant complications. Recent findings In patients with LVADs, there is little consistency linking traditional biomarkers of platelet activation and clinical events. A number of innovative methods of assessing platelet functionality, including shedding of platelet receptors and formation of microparticle complexes as well as measuring mitochondrial membrane potentials, exist and appear to be clinically relevant. Acquired von Willebrand syndrome, while not explaining all bleeding events, is a central feature of mechanical support and offers a target for innovative therapies Summary Although the platelet is only one component of impacting thrombosis and bleeding in patients supported with LVADs, it plays a central role in mediating these two opposing forces. Innovations in both understanding platelet physiology as well as manipulating genomic and receptor interactions for an individual patient will be critical if we are to decrease these serious adverse events in the future.

The impact of shear stress on device‐induced platelet hemostatic dysfunction relevant to thrombosis and bleeding in mechanically assisted circulation

“…Despite the significant progress in MCS clinical use, MCS therapy is not free of undesirable consequences. The significant complications with MCS, such as thrombosis and bleeding, were associated with worsening morbidity and mortality . Almost all contemporary MCS devices employ a rotary blood pump to pump the blood in the circulation.…”

Shear-mediated platelet activation in the free flow: Perspectives on the emerging spectrum of cell mechanobiological mechanisms mediating cardiovascular implant thrombosis

“…The need to examine platelet behavior during and after dynamic, device-related flow conditions was highlighted by the observation of chronic platelet activation and thromboembolic events in mechanical heart valve patients despite antiplatelet therapy (Butchart et al, 2003). These complications still remain a challenge for current VAD recipients (Koliopoulou et al, 2016). Starting in the early 2000s, researchers began examining platelet activation in response to complex non-physiological fluid shear stress waveforms utilizing markers including thrombin and P-selectin (Zhang et al, 2003; Zhang et al, 2002).…”

Device‐induced platelet dysfunction in mechanically assisted circulation increases the risks of thrombosis and bleeding

“…The loss of high molecular weight multimers (HMWM) of VWF (named as acquired von willebrand syndrome) was observed in almost all patients with rotary pump MCS devices and has been suggested to contribute to the increased events of bleeding in these patients . Since platelets play the important role in initiating the normal hemostasis, HMSS‐induced platelet dysfunction may also be an important factor for the hemostatic dysfunction in patients with MCS. Previous studies revealed that high shear stresses can induce platelet activation .…”