Search

Background: HIT is a life-threatening complication that occurs in a subset of heparin-treated patients. To our knowledge, a large population-based estimate of HIT disease burden, complication rates and economic cost has not been reported previously. Based on small studies, wide variations in the incidence of HIT has been observed in some patient populations. For example, among patients undergoing knee and hip arthroplasties, rates of HIT were reported to be less than 0.5% in some studies, but others, including a recent study suggest a much higher risk (Blood. 2016 25;127(8):1036-43). Similarly, rates of HIT reported in patients undergoing hemodialysis are highly variable, with some reporting an incidence as high as 3.9% (AJKD 1996; 28(1):82-5). To better address these discrepant findings and to benchmark disease burden and complication rates, we performed an analysis of the Nationwide Inpatient Sample (NIS). Methods: The NIS is a large inpatient healthcare database in the US. Unweighted, it contains data from >7 million hospital stays each year and weighted, it estimates >35 million hospitalizations. Full-year HIT data was available for 2009-2013, and this study period was queried to identify patients >18 years of age with a discharge diagnosis of HIT. Survey weighted domain analysis was conducted to estimate the incidence of HIT. HIT rates were also estimated in patients who underwent specific procedures (coronary artery bypass grafting [CABG, a known "high" risk setting for HIT development], hip and knee replacement, and dialysis. Incidence of thrombosis, bleeding, in-hospital mortality, and length and cost of hospitalization were also calculated. Outcomes in HIT patients were compared to those without HIT using ANOVA and Chi-squared test for continuous and categorical variables, respectively. Results: The annual HIT burden averaged ~22,000 annually over the study period with no change over that time frame (Fig 1A, p=0.1). The incidence of HIT was highest in patients undergoing CABG at 0.51%, followed closely by dialysis at 0.43% (Fig 1B). HIT rates were low in knee and hip arthroplasty at 0.02% each, even lower than the 0.07% overall rate of HIT for all patients (Fig 1B). The incidence of thrombosis was high in HIT (Fig 1B) with venous thrombosis being the most common type (17.9%), followed by pulmonary embolism (8.3%) and arterial thrombosis (2.3%) (Fig 1C), consistent with the relative incidence reported in the published literature. Rates of major bleeding in HIT is estimated to be 10-20% with direct thrombin inhibitor therapy. Our analysis yielded much lower major bleeding rates of 2.5% and 0.7% for gastrointestinal and intracranial bleeding, respectively (Fig 1D). In-hospital mortality in HIT was 9.5%, almost five times higher than in patients without HIT (Fig 1E). Notably, the length of hospitalization and cost of care were approximately 3x higher in patients with HIT compared to those without (Fig 1E & 1F). Conclusions: Surprisingly, HIT disease burden was large and unchanged during the study period averaging >20,000 cases annually. A recent study suggests that an "avoid unfractionated heparin" protocol can significantly decrease the incidence of HIT (Blood. 2016; 127(16):1954-9). Large scale interventions of this type may be needed to tackle this common disorder. Our data also suggests that rate of HIT in knee and hip arthroplasty are low, while in patients undergoing dialysis it is more common than generally believed. We found that thrombosis, a serious complication of HIT is a very common finding, but major bleeding rates were low. HIT also resulted in a disproportionate utilization of resources with costs per patient of ~ $150,000. There are important limitations with use of data from the NIS, where missing/miscoded information are concerns. Additionally, the NIS has no information on drug use. For example, HIT incidence in CABG includes all patients who underwent the procedure whether or not heparin exposure occurred (both off- and on-pump). In addition, rates of thrombosis may be overestimates as heparin may have been used to treat thrombosis in some patients and caused HIT with isolated thrombocytopenia. Despite these shortcomings, in addition to disease benchmarking, this information may aid healthcare providers and public health professionals plan and implement broad preventative and therapeutic interventions to tackle this dangerous yet common disease. Figure 1 Figure 1. Disclosures Padmanabhan: Bloodcenter of Wisconsin: Patents & Royalties: A patent application has been filed on a Method of detecting platelet activating antibodies that cause heparin-induced thrombocytopenia/thrombosis; PCT/US14/62591; Fenwal (Fresenius Kabi): Research Funding; Terumo BCT: Consultancy, Honoraria; Mallinckrodt Pharmaceuticals: Consultancy, Honoraria; LEK Consulting: Consultancy, Honoraria; Schlesinger & Associates: Consultancy, Honoraria.

Background: APL is a distinct but rare subtype of acute myeloid leukemia. Once very lethal, the discovery of all-trans retinoic acid (ATRA) as treatment has resulted in high rates of cure. Despite this, early mortality rates remain as high as 10% in clinical trials and may be even higher in general practice, where there may not be significant experience with this uncommon malignancy. Prompt recognition of APL and access to ATRA are critical to preventing early death, which is typically due to hemorrhage-related complications stemming from disseminated intravascular coagulation. We hypothesized that patients treated at teaching hospitals would have lower rates of early mortality as compared to non-teaching hospitals. Methods: We queried the Nationwide Inpatient Sample (NIS) from year 2008-2013 to identify patients >18 years of age with a discharge diagnosis of APL based on ICD-9 CM code of 205.00. A survey weighted domain analysis was conducted to describe the relationship between hospital teaching status and clinical outcomes among adult patients. Teaching hospitals have an AMA-approved residency program or have membership in the Council of Teaching Hospitals. Patient characteristics and clinical outcomes (in-hospital mortality, 7-day in-hospital mortality, disseminated intravascular coagulation (DIC), bleeding, stroke, cardiac dysrhythmia, acute myocardial infarction (AMI), pulmonary embolism (PE), deep vein thrombosis (DVT), and length of stay) were compared across hospital teaching status using ANOVA for continuous variables and Chi-squared tests for categorical variables. Multiple logistic regression was used to compare binary outcomes by hospital teaching status adjusting for patient characteristics. Results: The baseline characteristics of the patients are described in Table 1. Patients at non-teaching hospitals were older (mean age 68 yrs. vs. 60.3 yrs., p Conclusion: Our analysis from the large NIS database showed that the early in-hospital mortality in patients with APL was significantly higher in patients treated at non-teaching hospitals as compared to teaching hospitals. Patients treated at teaching hospitals had better outcomes despite higher rates of DIC, ICH, and PE. The overall rate of death during initial hospitalization was higher than what is typically reported in clinical trials but there was no difference between the two hospital settings. The lower rate of early hospital mortality in teaching hospitals may be attributable to early recognition and initiation of ATRA therapy due to clinician experience. Thus, efforts should be made to increase awareness of APL in the non-teaching hospital setting so that prompt treatment and appropriate referral can be considered if needed. Disclosures Michaelis: Pfizer: Equity Ownership; Cellgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte Corporation: Consultancy, Honoraria. Hamadani:Janssen: Consultancy; Celgene: Honoraria, Research Funding; Takeda Pharmaceuticals: Research Funding. Fenske:Millennium/Takeda: Research Funding; Seatle Genetics: Honoraria; Celgene: Honoraria; Pharmacyclics: Honoraria.

Background: Lympho-proliferative disorders are among the most common neoplasms affecting the ocular adnexa. OALD represents 1% of all lymphomas and 10-15% of extra nodal presentations. The outcomes of local radiation therapy (RT) in MALT vs. non-MALT histology are not known. Herein we present outcomes of local therapy in MALT vs. non-MALT OALD treated at a specialized lymphoma program. Methods: The analysis included 112 consecutive patients (pts) with OALD diagnosed at our institution between 1975- 2014. Patient characteristics, treatment modality and the response to treatment were retrospectively collected. Histology was reviewed by an expert hematopathologist. The primary objective of the study was to assess the failure free survival (FFS) in pts with marginal zone lymphoma of mucosa associated lymphoid tissue (MALT) of ocular adnexa (OA) and non-MALT OA lymphomas treated with local radiation therapy. Complete remission was defined as absence of any disease by imaging. Local failure was defined as any failure within the OA; extra-orbital failure was either regional (within the radiation field) or distant (for cases with limited stage disease at presentation). FFS was defined as time from treatment to any failure (local, regional and distant) and overall survival (OS) as time from treatment to last follow up or death from any cause. FFS and OS were estimated using the Kaplan-Meier methods. Results: Baseline characteristics are shown in Table 1. Of 112, 71(57.7%) of the pts had ocular MALT, and 41(33.3%) had non-MALT (23 follicular, 8 diffuse large cell B cell lymphomas, 3 mantle cell, 6 small lymphocytic lymphoma and 1 T cell lymphoma). Unilateral eye involvement (83.9%) with mass/swelling (55.3%) was the most common presentation. Staging was performed with CT scan and bone marrow biopsy in select cases (n=63, 51%). PET scan was utilized in 33 (29.4%) pts. but was able to upstage in only 5 cases. For ocular MALT, 62(87.3%) received involved field radiation therapy (IFRT), 9(12.6%) chemotherapy. For non-MALT, 34(82.9%) had IFRT, 7(17%) chemotherapy. Among those who received IFRT, 55(75%) in MALT and 21(52%) in non-MALT had limited stage disease (I/II). Among OALD pts treated with only IFRT, 91.7% in ocular MALT and 90.9% in non-MALT achieved complete remission. Resolution of symptoms occurred in 83.3% and 93.3% of ocular MALT and non-MALT respectively. Failure rates of IFRT in ocular MALT vs. non-MALT were as follows: local (7% vs. 12.1%), regional (9.8% vs. 7.3%), and distant (5.6% vs 2.4%). Median follow-up was 3(1-22) years in each group. Median time to failure was 14 years for ocular MALT and 9 years for non-MALT. 3 year and 5 year failure-free survival was 88% and 81% for ocular MALT and 78% and 71% for non-MALT respectively (log rank p=0.26 for FFS) (Fig 1). Conclusions: Both the MALT and non-MALT OALD pts achieved excellent disease control with IFRT with no significant difference in local, regional and distant failure rates. 3 year and 5-year failure free survival were comparable between the two groups. PET scan resulted in upstaging in 5% of pts but did not alter treatment selection, indicating that PET had minimal utility in initial staging of OALD. Table 1. Baseline characteristics TOTAL, N=112 MALT71(63.3%) NON-MALT41(36.6%) Age (median),years 64 (22-84) 66(25-87) Sex, M 25 (35.2%) 16(39%) Race, Caucasian 63 (88%) 34(83%) Symptoms at presentation - Mass/Swelling - Visual changes - Other 35 (49.2%) 11 (15.4%) 2 (2.8%) 27(66%) 11(27%) 1(2.4%) Site of origin - Orbital - Conjunctival - Lacrimal gland - Eyelid - Other 31 (43.6%) 26 (36.6%) 10 (14%) 1 (1.4%) 4 (5.6%) 14(34.1%) 14(34.1%) 10(24.3%) 3(7.3%) 0 Unilateral Involvement 60 (86%) 34(83%) Stage at presentation - I - II - III - IV - Unknown 60 (85%) 0 1 (1.4%) 8 (11.2%) 2(2.8%) 24(59%) 4(9.7%) 2(4.8%) 7(17%) 4(9.7%) Figure 1. Failure free surivival MALT(marginal zone) vs. non-MALT(other) with IFRT Figure 1. Failure free surivival MALT(marginal zone) vs. non-MALT(other) with IFRT Disclosures Hari: BMS: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Spectrum: Consultancy. Fenske:Millennium/Takeda: Research Funding; Seattle Genetics: Honoraria; Pharmacyclics: Honoraria; Celgene: Honoraria.