Use of left ventricular assist devices (LVADs) for management of advanced heart failure is becoming increasingly common; however, device associated thrombosis remains an important cause of mortality in this patient population. We hypothesize that inflammation in LVAD implanted patients dysregulates the protein C pathway, creating a hypercoagulable state leading to thrombosis. Plasma samples from 22 patients implanted with the Thoratec HeartMate II LVAD were analyzed by commercial ELISAs. Retrospective sample selection included those collected 1-3 months prior to and within 1 month after a thrombotic or bleeding event. Unrelated to warfarin dosing, total protein S and free protein S ( p = 0.033) levels were 20% lower in patients with LVAD-thrombosis than in patients with LVAD-bleeding. Levels of protein C, soluble endothelial cell protein C receptor, and soluble thrombomodulin were similar in both groups before and after the event. Compared to normal, C-reactive protein levels were 25-fold elevated in LVAD-thrombosis patients but only 9-fold elevated in LVAD-bleeding patients. This study suggests that protein S, influenced by the inflammatory state, is a gatekeeper for the function of protein C in patients with LVAD-associated thrombosis.

The Los Angeles urban heat island has been recently described as a large, coastal, urban archipelago. Rather than one symmetric UHI, the sprawling metropolitan region can be thought to have several heat islands of differing sizes and magnitudes. Both of these parameters are dynamic, changing over time. The current study focuses on this dynamic nature, showing diurnal, seasonal and spatial aspects to the Los Angeles heat islands. Rather than finding one value for the surface air heat islands, we present the evolving magnitudes based on observational data not models. We also show the significance of the city's changing land use as a primary cause for the growing heat islands. Using downtown Los Angeles weather data (DTLA), the downtown heat island is defined by the difference between a suburban residential site, an open space site near suburbs and DTLA. Hourly temperature differences are presented for all months and seasons. Another comparison of the downtown heat island is made using the coastal airport (LAX) data. The influences of coastal sea breezes, complex topography, and a climatic rapid warming away from the coast will also be discussed as it hinders evaluating the urbanization inputs. From the two inland sites, there are definite heat island characteristics when compared to the downtown location. DTLA shows continued warming over the 2000-2010 period of nearly 7 o C/century for Tmin and 10 o C/century for Tmax, which is pretty frightening. The inland sites warm much less during the day and showed a slight cooling for Tmin over the decade. Land use change in the urban Los Angeles County and impervious surface percentages are also calculated for the 1970-2010 period.

e13615 Background: Transplant Survivorship Clinic at our institution serves to improve outcomes and overall health of allogeneic transplant survivors. The COVID19 pandemic allowed for growth of telemedicine in our program. We examine the patterns of use of telehealth and hypothesize that the use of telemedicine allowed continued access to care compared to the era prior to availability. We compared our transplant survivorship clinic data from July- December 2020, when telehealth was well established and compared to July-December 2019. Methods: All patients seen by the survivorship team for end of treatment visits, graft versus host disease assessments and survivorship visits annually between July-December 2019 and July-December 2020 were included. Their zip codes were used to get direct distance to survivorship clinic, average drive time, driving distance and average household income as in zip-codes.com database. Results: Total number of office visits in July-Dec 2019 was 163 visits (0% via telehealth) and in July-Dec 2020 was 228 (66.2% via telehealth). All encounters (telehealth and office visits) were lower in July and August 2020 compared to July and August 2019 but higher in months of September -December 2020 compared to 2019. Comparing all encounters during 7/2019-12/2019 to 7/2020-12/2020, there was no statistically significant difference in median age (58yr vs 60 yr), gender (males: 58% vs 59%), race (non-white: 11% vs 8.7%), median years from transplant (4yr vs 3 yrs), median income of patient neighborhood ($63,735 vs $60,465) and average drive time to center from zip code (40 min vs 51min). Comparison of patients who chose telehealth vs. office visit is summarized in table. While there was no statistically significant difference in age when comparing all encounters in 2019 and 2020, those who chose telehealth were younger (55yrs vs 60yrs, p=0.003). Conclusions: There were higher patient encounters in the 2020 period compared to 2019. Most of these 2020 encounters were via were telehealth, demonstrating the role of telehealth in increasing access. Younger patients appeared to choose telehealth, but telehealth served patients up to the age of 77 yrs. Utilization of telehealth appeared to be irrespective of demographics such as gender, neighborhood income and driving distance to the center. Comparison of telehealth vs office visit for July-December 2019 and 2020.[Table: see text]

Introduction: Mechanical circulatory support using an implanted ventricular assist device (VAD) is an important means of enhancing or maintaining the quality of life for heart failure patients awaiting heart transplant (bridge to transplant), during the recovery of their own heart (bridge to recovery) or for long-term destination therapy (no transplant). The non-physiologic continuous blood flow of a VAD (CF-VAD) exposes blood and vasculature to abnormal shear stress and leads to a variety of hemostatic derangements that likely contribute to the development of bleeding complications, neurologic dysfunction and venous thromboembolism in these patients. Additionally, the implanted CF-VAD likely stimulates the body's natural innate immune response to a foreign object. We hypothesize that the continuous activation of platelets due to the non-physiologic blood flow and the foreign nature of the CF-VAD combine to stimulate an immune response. Previous studies have suggested thatanti-PF4/heparin antibodies [as targeted in a diagnosis of heparin-induced thrombocytopenia (HIT)] can develop in the absence of heparin. It is believed that these antibodies are not related to heparin per se but rather are generated as a physiological response by platelets, in their capacity to generate an innate immune response, reacting to non-self substances. This study evaluated the time course of anti-PF4/heparin titers in patients supported by CF-VADs. Methods: Blood samples were collected from 13 randomly selected patients prior to implantation of a HeartMate II CF-VAD and at routine clinic visits following implantation. Median follow-up was 183 days (range: 32-352 days). Anti-PF4/heparin antibody titers were determined by the PF4 Enhanced X-45 Assay (Immucor GTI Diagnostics, Waukesha, WI). Patients were treated with heparin at the time of implant; long-term anticoagulation was maintained with warfarin (INR 1.5-2.0) and low-dose aspirin. Results: Following CF-VAD implantation, there was an acute increase in median platelet count from 169,000 to 420,000/µl. With increasing time post-implant, the median platelet count returned to pre-implant levels; no patients became thrombocytopenic. Pre-implant, 6 of 13 patients had 'positive' anti-PF4/heparin titers (OD >0.4 using the HIT criteria); the median OD for all patients was 0.433. There was a progressive increase in median titer with increasing time post-implant. At 1 month the median OD was 0.54. By 2 months all patients had an OD >0.4 with a median value of 0.82 (>0.750 is high clinical thrombosis risk using the HIT criteria). The median OD continued to rise through 8 months post-implant. At 5 months and later OD values >1.5 were common. OD values >1.5 were present in some patients as early as 1 month post-implant. Discussion: The mechanism(s) associated with CF-VAD pump thrombosis and other adverse events remains unclear. The above data shows that long-term implant of a CF-VAD leads to the development of anti-PF4/heparin antibodies. Such a response may result from shear-induced platelet activation and subsequent release of PF4. This response is similar to a previous report in which patients who underwent total knee or hip arthroplasty and subsequently received dynamic mechanical thromboprophylaxis demonstrated an anti-PF4/heparin immune response even in the absence of heparin (Bito et al, Blood 2016). CF-VAD-related infection may also contribute to the generation of anti-PF4/heparin antibodies as PF4 bound to bacteria has previously been shown to induce antibody formation (Krauel et al, Blood 2011). Data from our lab has shown that patients with implanted CF-VADs are frequently in heightened states of inflammation (ASH 2016 abstract) with excessive levels of C-reactive protein in patients who develop pump thrombosis. CRP has been shown to activate platelets and accelerate thrombogenesis (Xu et al, BMC Immunology 2015). Thus, it is plausible that the development of anti-PF4/heparin antibodies may be an indicator of an early activation mechanism of adverse events in CF-VAD implanted patients through the cross-talk between the hemostatic and immune systems. Larger studies are required to determine whether the presence of such antibodies confers any risk to LVAD patients. The presence of anti-PF4/heparin antibodies may be of particular concern for LVAD patients undergoing a subsequent surgery for pump replacement or heart transplant. Disclosures No relevant conflicts of interest to declare.

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