Acquired loss of functional von Willebrand factor (VWF) has been termed the acquired von Willebrand syndrome (AVWS). AVWS is a rare adult-onset bleeding diathesis that is clinically similar to congenital von Willebrand disease (VWD), and occurs with a variety of autoimmune, lymphoproliferative, or myeloproliferative disorders. We have identified four patients with AVWS in association with immunoglobulin light chain (AL) amyloidosis. These patients, lacking any pre-existing or family history of abnormal bleeding, developed cutaneous, mucosal, or gastrointestinal bleeding in the course of their disease without deficiency of clotting factor X or other factors; the activated partial thromboplastin time (aPTT) was prolonged in three out of the four cases. Despite normal VWF antigen levels, VWF ristocetin cofactor activity (VWF:RCo) was low. Electrophoresis patterns of high molecular weight (HMW) VWF multimers were abnormal in two of the four cases. Two of the patients were treated with high-dose intravenous melphalan followed by autologous stem cell transplantation (HDM/SCT) and achieved hematologic remission. In these two patients, the bleeding diathesis improved and the coagulation parameters normalized, confirming a causal relationship between the plasma cell dyscrasia and the AVWS. AVWS should be considered in AL amyloidosis patients with hemorrhagic diatheses and normal clotting factor levels.

Background The Impella 5.5® was approved by the FDA for use for mechanical circulatory support up to 14 days in late 2019 at limited centers in the United States. Our single center’s experience with Impella 5.5® can expand the overall understanding for achieving successful patient outcomes as well as provide support for the expansion of its FDA-approved use. Methods This study is an IRB-approved single-center retrospective cohort analysis of hospitalized adult patient characteristics and outcomes in cases where the Impella 5.5® was utilized for mechanical circulatory support. Results A total of 26 implanted Impella 5.5® devices were identified in 24 hospitalized patients at our institution from January 2020 to January 2021. The overall survival rate during index hospitalization was 75%. Eleven Impella 5.5® devices were identified in 10 patients with an average device implantation greater than 14 days. Average device implantation for this subgroup was 27 days with a range of 15–80 days. Survival rate for Impella 5.5® use greater than 14 days was 67%. In the entire cohort and subgroup of device implantation > 14 days, evidence of end organ damage improved with Impella 5.5® use. Complications in our cohort and subgroup of device implantation > 14 days were similar to previously reported complication incidence of axillary inserted LVAD devices. Conclusions Our institution’s experience with the Impella 5.5® has been strongly positive with favorable outcomes and helps to establish the Impella 5.5® as a viable option for mechanical circulatory support beyond 14 days.

Thromboembolic disease is a major complication of malignant disease, and pancreatic cancer ranks among the malignancies associated with the highest rates of thrombosis. Using laser injury in a mouse model of thrombosis, we previously demonstrated that tissue factor-bearing microparticles circulating in normal plasma accumulate in the developing thrombus through an interaction mediated by P-selectin and PSGL-1. Microparticle tissue factor contributes significantly to fibrin propagation within the thrombus. Based upon this observation, we evaluated the hypothesis that elevated numbers of tissue factor-bearing microparticles might be one of the causes of cancer-associated thrombosis. Microparticles are cell-derived vesicular structures under 1000 nm in diameter. Since the light scattering methodology used in commercial flow cytometers cannot determine particle size when the diameter of the particle (200–1000 nm) is the same order of magnitude as the wavelength of the incident light employed (488 nm), we applied a novel instrumentation to determine the size, size distribution, and concentration of tissue factor-bearing microparticles. An NPE Systems Quanta flow cytometer, using impedance to measure particle size, was extensively modified for this microparticle application. Application of 780 nm fluorescent calibration beads yielded a major population from 740 to 820 nm. Application of 520 nm fluorescent beads yielded a major population from 500 to 540 nm. Using a high affinity antibody to tissue factor, tissue factor-bearing microparticles were measured in platelet-poor plasma derived from normal subjects and subjects with surgically unresectable or metastatic pancreatic cancer. Tissue factor bearing microparticles were detected in significantly more subjects with pancreatic cancer (12 of 17, 70%) than healthy individuals in whom tissue factor-bearing microparticles remained below the level of detection in all but a single individual (1 of 11, P=0.005). By comparison, tissue factor-bearing microparticles were not detected in subjects with advanced stage (III or IV) non-small cell lung cancer (N=9). In subjects with advanced pancreatic cancer, the mean concentration of tissue factor bearing microparticles was 444,000 particles/microliter with a mean diameter ranging between 371 nm to 727 nm. The two patients with pancreatic cancer in this study who suffered a recent lower extremity venous thrombosis had high measurable tissue factor-bearing microparticles levels with a mean concentration of 975,000 particles/microliter. These results indicate that tissue factor-bearing microparticles are present in the plasma of many patients with advanced pancreatic cancer and suggest that tissue factor-bearing microparticles may be central to the pathogenesis of cancer-associated thrombosis.

Introduction: Stability of traditional bradycardia pacing leads (TPL) in the right atria and ventricle has been well established. Left ventricle pacing utilizing branches of the coronary sinus (CS) and is also well established with specifically designed leads. Recent data suggests pacing the left atria (LA) may be desired and beneficial to treating patients with HFpEF and intra-atrial conduction delays 1,2,3 These studies utilized TPL screwed into the CS for stability. 1 Adaptations to other left ventricular leads such as prolapsing has also been suggested. 4 We evaluated pacing the LA via TPL implanted into the body of the CS without active fixation or prolapse. Methods: Retrospective chart review of patients implanted with TPL leads to stimulate the LA were included. TPL were placed into the CS without helix extension with Y-connection to the RA lead (Bi-Atrial). Review and examination of digital X-rays were also analyzed to determine system type, lead position, and any system or lead changes over time. Results: N=74 patients were included (47M:27F) aged 79.7(+/-11.8). Implant to last follow-up ranged from 0.12 to 12.4 years (mean 3.16 +/-13.3). TPL-CS placement was divided into the proximal, mid, and distal portions consisting of n=8(10.8%), n=30(40.5%), and n=36(48.6%) respectively. N=14(18.9%) were part of Bi-A/Bi-Ventricular pacing system and the remaining were Bi-A only systems. N=3 (4%) infections and N=3 (4%) dislodgements occurred in all reviewed patients. Conclusions: In our analysis, TPL leads remained stable in the CS body with similar complication rates to TPL in traditional locations in the heart with fixation. As these leads were utilized with additional components, larger prospective studies may better analyze these findings. In addition, utilizing this technique with outcome data may provide further information for treatment of patients with HFpEF and intra-atrial delays.Introduction: Post cardiac transplant outcomes of patients supported with the Heartmate 3 left ventricular assist device (LVAD) have not been previously reported. The purpose of this analysis was to report status at the time of transplant and survival by continuous flow (CF) device type. Hypothesis: Patients supported with a HeartMate 3 LVAD will have a similar post-transplant survival to other contemporary CF-LVADs. Methods: The study cohort included adult patients supported on contemporary, continuous flow (CF) devices in the UNOS registry who underwent cardiac transplant between the years 2014-2018, prior to the 2018 UNOS allocation system change. The analysis was limited to patients who underwent initial LVAD implantation in 2014 and beyond to allow post-transplant comparisons among patients with similar LVAD support times. Multivariable cox regression was performed to assess the association between LVAD type and post-transplant survival. Results: The study cohort consisted of 3,117 patients who underwent cardiac transplant while on LVAD support (Heartmate 2: 1,545, Heartmate 3: 179, HeartWare (HVAD): 1,393). No patients su...