Changes in Von Willebrand factor profile predicts clinical outcomes in patients on mechanical circulatory support.

BACKGROUND: The associations between mechanical circulatory support (MCS), acquired von Willebrand syndrome (AvWS), and clinical outcome are incompletely understood. METHODS: In 128 heart failure patients with pulsatile MCS implants (65 total artificial heart or biventricular assist device implants, 63 left ventricular assist device [LVAD] implants) and 76 patients with continuous flow LVAD implants, we analyzed the von Willebrand factor (vWF) profile before (≤24 h) and 17.5 (standard deviation: 5.1) days after device implant. We determined vWF concentrations, vWF activity, and vWF collagen binding capacity and calculated ratios of vWF activity/binding capacity with vWF concentration. The relation of the vWF profile with clinical outcomes such as stroke, gastrointestinal bleeding, and survival was also evaluated. Events were assessed up to 1 year of device implant. RESULTS: All entities of vWF were already significantly elevated preoperatively and remained high after MCS implantation. The ratios of vWF activity/concentration (vWF:RCo/Ag) and collagen binding capacity/concentration (vWF:CBA/Ag) were significantly reduced preoperatively and remained low postoperatively, indicating AvWS. The preoperative alterations in the vWF profile were already present in patients without intra-aortic balloon pump and/or extracorporeal circulatory membrane oxygenation implants. The vWF profile was unrelated to postoperative stroke. However, a higher postoperative ratio of vWF:CBA/Ag was independently associated with increased gastrointestinal bleeding. In addition, a postoperative increase in vWF concentrations and activity were independent predictors of increased 1-year mortality. CONCLUSIONS: Our data indicate that AvWS is present in heart failure patients before device implantation, and is independently associated with clinical outcomes, especially with 1-year mortality.

Acquired von Willebrand Syndrome in a Patient Undergoing Extracorporeal Membrane Oxygenation: A Case Report.

Acquired von Willebrand syndrome (AvWS) is a rare bleeding disorder caused by dysfunction of the von Willebrand factor (vWF), leading to bleeding manifestations. It usually occurs due to an underlying disorder in patients with no family or personal history of bleeding diathesis. The exact mechanism causing this syndrome is not fully understood, but it involves a complex interplay of factors. Specifically, vWF deficiency or reduced activity can occur due to antibodies, adsorption of vWF onto tumor cells, shear stress, or increased proteolysis. We describe a patient with severe, right-sided heart failure secondary to idiopathic pulmonary hypertension. The patient was admitted to the intensive care unit to be placed on a venoarterial extracorporeal membrane oxygenation (VA ECMO) machine while awaiting bilateral lung transplantation. A few hours after initiation of VA ECMO, the patient experienced epistaxis and continuous bleeding from the cannula tips. The laboratory investigations were based on the measurements of vWF antigen (vWF:Ag), vWF ristocetin cofactor activity (vWF:RCo), and multimer analysis. The obtained results revealed a decreased VWF:RCo/VWF:Ag ratio (<0.7) and the loss of high-molecular-weight multimers of vWF, thus confirming the diagnosis of AvWS. This report reviews how to make the clinical diagnosis of AvWS, including a discussion of necessary laboratory results and their pitfalls, and highlights the importance of having a high index of suspicion of AvWS in the ECMO population so that laboratory values are obtained on time to allow for treatment and successful recovery.

Ambient hemolysis and activation of coagulation is different between HeartMate II and HeartWare left ventricular assist devices.

BACKGROUND: Thromboembolic and bleeding events in patients with a left ventricular assist device (LVAD) are still a major cause of complications. Therefore, the balance between anti-coagulant and pro-coagulant factors needs to be tightly controlled. The principle hypothesis of this study is that different pump designs may have an effect on hemolysis and activation of the coagulation system. Referring to this, the HeartMate II (HMII; Thoratec Corp, Pleasanton, CA) and the HeartWare HVAD (HeartWare International Inc, Framingham, MA) were investigated. METHODS: For 20 patients with LVAD support (n = 10 each), plasma coagulation, full blood count, and clinical chemistry parameters were measured. Platelet function was monitored using platelet aggregometry, platelet function analyzer-100 system ( Siemens, Marburg, Germany), vasodilator-stimulated phosphoprotein phosphorylation assay, immature platelet fraction, platelet-derived microparticles, and von Willebrand diagnostic. RESULTS: Acquired von Willebrand syndrome could be detected in all patients. Signs of hemolysis, as measured by lactate dehydrogenase levels (mean, 470 U/liter HMII, 250 U/liter HVAD; p < 0.001), were more pronounced in the HMII patients. In contrast, D-dimer analysis indicated a significantly higher activation of the coagulation system in HVAD patients (mean, 0.94 mg/liter HMII, 2.01 mg/liter HVAD; p < 0.01). The efficacy of anti-platelet therapy using clopidogrel was not sufficient in more than 50% of the patients. CONCLUSIONS: Our results support the finding that all patients with rotary blood pumps suffered from von Willebrand syndrome. In addition, a distinct footprint of effects on hemolysis and the coagulation system can be attributed to different devices. As a consequence, the individual status of the coagulation system needs to be controlled in long-term patients.