Ashrani, Aneel A.

Abstract Abstract 2984 Poster Board II-960 In previous studies of venous thromboembolism (VTE) among all residents of Olmsted County, MN, the odds of VTE associated with surgery, medical hospitalization, or active cancer were extremely high (Univariate odds ratio [OR] =14.6; 4.6, and 8.4 respectively). We also showed that nursing home (NH) residency was an independent risk factor for VTE (OR =5.6). From a clinical practice perspective, it is important to identify which NH residents are at risk of VTE. While it might be assumed that, similar to estimates for the population generally, surgery, medical hospitalization, and cancer are associated with increased risk of VTE within the NH population, the answer remains unclear. We took advantage of the previous identification of all Olmsted County, MN residents who met research criteria for incident VTE 1998-2005 (N=1168). We then determined which individuals were resident of a local NH at time of symptom onset, regardless of location of symptom onset (i.e., for purposes of this study, individuals whose VTE occurred in-hospital having been admitted from a NH were considered NH residents). For each such NH VTE case (N=96), we identified 2 same sex Olmsted County residents of similar age and duration-of-medical-history who were resident of a local NH at the time of the case's VTE event (i.e., index date) (N=192). The detailed provider-linked medical records of NH VTE cases and NH non-VTE controls were reviewed for 3 months before index for surgery or medical hospitalization and for 6 months surrounding index for active cancer. Using conditional logistic regression, we tested and estimated the odds ratio associated with each of these potential risk factors. The proportions of NH VTE cases and NH non-VTE controls with surgery (33%, 28%), medical hospitalization (44%, 46%), and active cancer (12%, 9%) were similar. Univariate odds ratios (95% confidence intervals) and p values for surgery, medical hospitalization, and active cancer were 1.5 (0.7-3.1), p=0.30; 1.1 (0.6-2.1), p=0.74; and 1.4 (0.6-3.2), p=0.46 respectively. Compared to the entire Olmsted County population, the odds of VTE associated with surgery, hospitalization, and cancer are surprisingly much lower for NH residents. Additional investigation is needed to characterize the subset of NH residents at increased risk of VTE. Disclosures: No relevant conflicts of interest to declare.

Abstract Background: Venous stasis syndrome (VSS) is a relatively common long-term sequelae of deep vein thrombosis (DVT), although it frequently is noted in individuals with no prior history of DVT. Objective: To evaluate whether: (1) venous stasis syndrome (VSS) is associated with a prior history of DVT; (2a) venous outflow obstruction (VOO) and/or (2b) venous valvular incompetence (VVI) are associated with DVT; and (3) VSS is associated with VVI and/or VOO. Design: Case-control study nested within a population-based inception cohort study. Population: 230 residents of Olmstead County, MN (OCM) with a first lifetime VTE over the 25-year period, 1966 – 1990 (cases), and 135 age, gender and year of incident VTE-matched OCM residents without prior history of VTE (controls). Measurements: Physical examination and patient questionnaire for symptoms or signs of VSS, and strain gauge outflow plethysmography, continuous wave venous Doppler ultrasound, and passive venous drainage and refill testing for VOO and VVI performed between 1996 – 1998. Results: Of the 365 study participants, 43 (12%) had VOO, 136 (37%) had VVI, and 265 (73%) had VSS. In multivariate logistic regression analyses: (1) age at the follow-up visit [OR Δper 10 years: 1.70 (1.41, 2.04)], prior DVT in the affected limb [OR: 4.03 (2.32, 7.01)], and presence of prior varicose veins [OR: 4.36 (1.84, 10.31)] were significantly associated with VSS; (2a) age at the follow-up visit [OR Δper 10 years (95% CI): 1.84 (1.39, 2.44)] and prior DVT in the affected limb [OR: 5.01 (2.61, 9.63)] were significantly associated with VOO; (2b) prior DVT in the affected limb (OR: 3.91 (2.56, 5.97)], presence of prior varicose veins [OR: 2.19 (1.32, 3.63)] and symptoms of VSS prior to incident DVT [OR: 3.42 (1.46, 8.00)] significantly increased the odds for VVI; and (3) VOO (p=0.004) and VVI (p<0.0001) were highly associated with VSS. Having a DVT in the left leg was associated with a greater odds of developing VOO, VVI or VSS in that leg when compared to their association with right leg DVT (OR: 6.69 vs. 3.65; 4.82 vs. 3.09; 4.71 vs. 3.97, respectively). Interestingly, prior DVT in the opposite leg was associated with an increased odds of subsequent VVI [OR: 2.00 (1.28, 3.10) and VSS [OR: 2.20 (1.31, 3.70)], but not VOO, in the test leg. Conclusions: Prior DVT imparts an increased risk for subsequent VSS, likely due to VOO and/or VVI. The odds of VOO or VSS increases with age. Presence of varicose veins increases the odds for VVI and VSS. We speculate that the increased odds of left sided VOO, VVI and VSS in patients with prior DVT may be secondary to May-Thurner syndrome. The increased odds of VVI and VSS in the limb opposite to the one affected by prior DVT could reflect occult DVT in the test limb, inferior vena cava thrombosis, or other mechanisms leading for VVI and VSS.

Abstract BACKGROUND: Complement-mediated thrombotic microangiopathies (TMAs) are a subset of TMAs in which the thrombocytopenia, microangiopathic hemolytic anemia, and end organ damage are caused by mutations in genes encoding the alternative complement pathway. Numerous complement genes have been implicated in complement-mediated TMAs including complement factor H (CFH), CD46 (MCP), complement factor I (CFI), complement component 3 (C3), complement factor B (CFB), factor H related 5 (CFHR5), and thrombomodulin (THBD) among others. Genetic analysis typically yields a mutation in 60% of patients whose TMA is presumed to be mediated by complement dysregulation. However, the description of novel disease-associated variants may increase this proportion. METHODS: A retrospective study of patients with TMAs diagnosed between 2000 and 2014 was performed. TMA diagnosis was made based on thrombocytopenia and evidence of microangiopathic hemolytic anemia. Analysis was performed with Alamut¨ software with additional in silico prediction tools (SIFT, MutationTaster, and Polyphen) for classification of gene variants. Variants of unknown significance (VUS) and likely pathogenic variants were further assessed using several mutation databases, including HGMD, ClinVar, and Factor H database RESULTS: Of patients diagnosed with a TMA, genetic analysis was performed in only a 10% of patients. Of the 29 patients with genetic studies performed, mutations were identified in 18 patients (62%). The majority of the mutations had been described previously in the literature, but four novel variants were identified: three missense and one splice-site. The table below summarizes these variants as well as laboratory findings on presentation. These were two variants of CFH, one variant of CFHR5, and one variant of CFI. In silico modeling of these variants revealed two polymorphisms likely to be pathogenic, one polymorphism likely benign given the lack of predicted splicing changes, and one VUS. Table 1. Protein Mutation Classification Age Sex Hemoglobin (g/dL) Platelets (thousands) Creatinine (mg/dL) CFH c.245-10_245-9dup Likely benign 61 F 11.6 51 6.7 CFH c.476G>A, p.Ser159Asn Likely pathogenic 43 F 9.1 101 9.1 CFHR5 c.1412G>A p.Gly471Glu Likely pathogenic 30 F 9.8 129 4.9 CFI c.1190T>A p.Val397Glu Unknown significance 51 M 9.4 125 6.1 DISCUSSION: With therapy available to target the alternative complement pathway, genetic analysis to identify genetic variants capable of causing complement mediated TMAs is an essential part of the evaluation. This genetic data must be interpreted and correlated with functional analysis and clinical phenotype. The reporting of novel variants in clinical databases, with inclusion of relevant clinical findings, is necessary to accurately classify and verify variants as pathologic mutations or benign polymorphisms. The full understanding of this diverse disease requires a more complete understanding of its genetics. While complement pathway-directed therapies are available, their rational use requires thorough interpretation of laboratory data, including genetic analysis. Disclosures Murray: Mayo Clinic: Patents & Royalties: Patent Application Filed.

Abstract BACKGROUND: Non-hereditary hemolytic anemia of unknown etiology after an exhaustive work-up is commonly known as direct antiglobulin test (DAT)-negative hemolytic anemia. Due to its rarity, limited data are available regarding this condition. We performed this retrospective study to determine the frequency, associated medical conditions, treatments used, and clinical outcome of patients with DAT- negative hemolytic anemia. METHODS: We included adult (age >18 years) patients with DAT-negative hemolytic anemia seen at Mayo Clinic from 1997-2015 who met all of the following criteria: a) hemoglobin (Hb)< 12 g/dL; b) presence of hemolysis (reticulocytosis, elevated lactate dehydrogenase, decreased haptoglobin, and/or elevated indirect bilirubin); c) DAT-negative; and d) unknown etiology of hemolytic anemia after extensive work-up appropriate for clinical context. Remission status after appropriate therapy for perceived hemolysis was defined as follows: a) complete remission (CR; Hb ≥12g/dL and normalization of at least one previously abnormal hemolytic marker); b) partial remission (PR; Hb: 10-11.9 g/dL with evidence of ongoing hemolysis); c) no remission (NR; neither CR nor PR). In order to calculate the relative frequency of DAT-negative hemolytic anemia, we also determined the number of DAT-positive hemolytic anemia cases during the same time period using the above criteria for hemolytic anemia. RESULTS: During the 19-year study period, 24 and 484 patients were diagnosed with DAT- negative and DAT-positive hemolytic anemia, respectively, a ratio of 1:20. Among those with DAT-negative hemolytic anemia, the majority were males (67%) and the median age at diagnosis was 70 years (range, 22-87). Six patients (25%) had pre-existing autoimmune conditions including immune thrombocytopenia (n=3), Crohn's disease (n=2), and Grave's disease (n=1). All patients had negative DAT by conventional method with one patient turning positive at 104 days after initial diagnosis. Enhanced DAT technique using 4°C low-ionic strength saline wash was performed in one case and was negative. In general, peripheral blood smear showed polychromasia, occasional spherocytes, and no schistocytes or bite cells. Additional work-ups performed based on clinical context and proportion of patients tested (all results negative or normal) were as follows: hemoglobin electrophoresis (54%), flow cytometry for paroxysmal nocturnal hemoglobinuria (92%), glucose 6-phosphate dehydrogenase level (67%), osmotic fragility test/eosin-5'-maleimide stain for hereditary spherocytosis (54%), other red blood cell enzymes (46%), computed tomographic scan of the body to look for occult malignancy (46%), and bone marrow biopsy (50%). The median hemoglobin at diagnosis was 8.5 g/dL (range, 4.5-11.8). Fourteen patients (58.3%) required blood transfusion during the course of their disease. Sixteen patients (67%) received prednisone as initial therapy with 19% CR and 38% PR response rates. Subsequent therapies included: rituximab (n=6; 40% PR), cyclophosphamide (n=2; 100% NR), mycophenolate mofetil (n=1; 100% NR), intravenous immunoglobulin (n=2; 100% NR), and splenectomy (n=6; 50% CR and 33.3% PR), respectively. The median follow-up for all cases was 32.9 months (range, 2-433). Six patients (25%) developed hematologic malignancies after a median follow-up of 8.7 months (range, 0.7-29.3), which included primary myelofibrosis (n=2), myelodysplastic syndrome (n=1), mantle cell lymphoma (n=1), non-Hodgkin lymphoma-not otherwise specified (n=1), and T-cell large granular lymphocyte leukemia (n=1). At last follow-up, 9 patients (38%) were in CR and 8 (33%) in PR. Relapses occurred in 67% and 0% of patients who received prednisone and splenectomy, respectively. CONCLUSION: At our institution, DAT-negative hemolytic anemia was approximately 20 times less common than DAT-positive hemolytic anemia. Most patients were treated with either immunosuppressive agents with or without splenectomy. Splenectomy was the most effective treatment. At least a quarter of the patients were eventually diagnosed with hematologic malignancies mostly within a year of DAT-negative hemolytic anemia diagnosis. Routine upfront evaluation for hematologic malignancies might be necessary for these patients. Disclosures No relevant conflicts of interest to declare.

Background: Although the association of acquired isolated factor V (FV) deficiency with myeloproliferative neoplasms (MPN) has been described, it has not been well characterized. Objective: To characterize the clinical and laboratory features of patients with MPN and isolated FV deficiency. Methods: After IRB approval, patients with MPN who underwent coagulation profile diagnostic testing from January 1980 to December 2012 were identified via the Mayo Clinic Special Coagulation Laboratory Registry. Medical records of those with MPN and concurrent isolated FV deficiency or those with mild coagulopathy who had at least 20% discordantly lower FV activity were reviewed. Excluded were patients with known inherited bleeding diathesis, clinically significant liver disease, or on concurrent warfarin treatment. Data on patient demographics, clinical features and laboratory data were abstracted. Results: Thirty three patients met our study criteria (median age 67 years; 55% males; median BMI 25 kg/m2). Twenty one (64%) patients had either primary or post-polycythemia vera (PV) or post-essential thrombocythemia (ET) myelofibrosis; five (15%) had PV; three (9%) had unclassified MPN; two (6%) had ET; and one (3%) each had chronic myeloid leukemia and chronic myelomonocytic leukemia. Majority of these patients had splenomegaly (85%), with a median palpable spleen size of 14.3 cm below the left costal margin. Nearly 40% had hepatomegaly (median 4 cm below the right costal margin). Twelve (36%) patients were being treated with hydroxyurea; nine (27%) with aspirin and seven (21%) with an investigational agent. Nearly two-thirds (n=21; 64%) of these individuals had bleeding episodes, nine (43%) of which were provoked either by a surgical intervention or trauma. Majority of the bleeding episodes (n=15; 71%) were clinically significant/major bleed, as defined by the standard International Society of Thrombosis Haemostasis criteria, of whom eight required red cell transfusion support. Most of the bleeding were from muco-cutaneous surfaces (45%), followed by excessive bleeding from surgical site (24%). Median time from MPN diagnosis to bleeding was 5.4 years (range: 0 – 25). Of note, 42% (n=14) of all patients had thrombotic events (5 ischemic stroke/ TIA; 4 peripheral artery disease; 1 myocardial infarction; 1 splenic artery thrombosis; 3 leg DVT; and 3 splanchnic vein thrombosis) prior to their bleeding episode. Median time from MPN diagnosis to thrombosis was 1.4 years (range: 0.1 – 19.7). The median (range) leukocyte and platelet count were 17.8 (3.6 – 212.7) x 1000/ mm3 and 315 (16 – 1284) x 1000/ mm3, respectively. The median (range) PT [reference range: 10.3 – 12.8 sec] and aPTT [reference range: 26 – 36 sec.] were 13.3 sec (10.1 – 18.7) and 38 sec (29 – 66), respectively. The median FV activity [reference range: 70 – 165%] was 44% (range: 18% - 60%). Seven of the 18 individuals (39%) tested for von Willebrand syndrome had ristocetin cofactor activity (RCoA)/von Willebrand antigen (vWF Ag) ratio of <0.7, although their vWF Ag and RCoA were within the normal reference range. Seventeen (52%) patients had platelet aggregation studies; all had at least one aggregation abnormality. Abnormal or absent response to epinephrine was the commonest noted abnormality (n=15), followed by an abnormal response to collagen (n=6). On univariate analysis, there was no significant correlation of FV activity with age, sex, BMI, myelofibrosis, hepatomegaly, splenomegaly, WBC count, platelet count, or use of hydroxyurea or investigational drugs. Further, on univariate analysis, neither the aforementioned covariates, nor aspirin use, WBC count, platelet count, FV activity, abnormal platelet aggregation, RCoA/vWF Ag ratio < 0.7 were predictive of either overall bleeding, provoked bleeding or clinically significant/major bleed. Conclusions: Isolated FV deficiency associated with MPN often co-exists with platelet dysfunction and/or an acquired vWF abnormality, which together may contribute to a clinically significant bleeding diathesis. Our experience did not lead to identification of specific risk factors for MPN-associated isolated FV deficiency. Disclosures No relevant conflicts of interest to declare.

Abstract Background Congenital/hereditary qualitative platelet disorders (CQPD) can be classified by platelet count (eg, normal or decreased) and platelet size as well as by functional defect. Based on mean platelet volume (MPV), congenital thrombocytopenias (CT) are classified as macro-thrombocytopenias (eg, Bernard-Soulier syndrome [BSS], MYH-9 [myosin heavy chain 9, non-muscle]-associated thrombocytopenias, gray platelet syndrome [GPS], etc.); microthrombocytopenias (eg, Wiskott-Aldrich syndrome and variants); and those with normal platelet size. CQPDs with normal platelet count include Glanzmann thrombasthenia (GT), dense granule storage pool disorders (DG-SPD) including Hermansky-Pudlak syndrome (HPS), platelet secretion disorders and many others. Diagnosis has relied on platelet counting and sizing, blood smear light microscopy, platelet aggregation (agg) and platelet function analyzer (PFA-100) studies. Platelet transmission electron microscopy (PTEM) and flow cytometry can provide supplementary information and molecular analysis is also evolving. The objective of this study was to determine the roles of platelet transmission electron microscopy (PTEM) and flow cytometry in the diagnosis of CQPD and CT. Methods In this retrospective cohort study, after IRB approval, the electronic medical record system was queried for patients (pt) with a confirmed CQPD or CT seen at Mayo Clinic between 2000 and 2015. A detailed chart review was undertaken. Results 54 pt (64% female) met our study criteria; median age was 32 years (range 1 day to 81 years). 18/54 (33%) pt had macrothrombocytopenia: BSS 4 (7%); MYH-9 10 (19%); gray platelet syndrome 4 (7%). 36/54 (66%) had normal MPV: Glanzmann thrombasthenia 6 (11%); storage pool disorders including DG-SPD 10 (19%) and HPS 2 (3%), mild alpha granule deficiency 3 (6%) and York platelet syndrome 4 (7%); platelet secretion disorders 4 (7%); ANKRD26 mutation 3 (6%); congenital amegakaryocytic thrombocytopenia 1 (2%); GATA-1 mutation 1 (2%); RUNX-1 mutation 1 (2%); and Jacobsen syndrome 1 (2%). 44 pt (81%) had a positive bleeding history: epistaxis 52%, cutaneous bleeding 57%, gastrointestinal bleeding 21% and menorrhagia 54%; 10 pt (19%) had a negative bleeding history. Results of standard and esoteric platelet testing are summarized in Table 1. Diagnosis in the 10 pt with glycoprotein deficiency (BSS or GT) was established by agg; flow cytometry was confirmatory but not necessary. Of the 23 pt with SPD, 5 had a negative bleeding history; 4 pt had normal agg and PFA-100 and were diagnosed exclusively by PTEM. In this group, the abnormalities on platelet aggregation and PFA were variable and PTEM allowed for a better definition of the specific abnormalities. For MYH-9 patients, PTEM confirmed leukocyte inclusions that had already been identified on light microscopy. PTEM was the only diagnostic modality able to identify the abnormality in York platelet syndrome. In 5/54 (9%) genetic testing was necessary for diagnosis (GATA-1, ANKRD26 and RUNX-1) Conclusion In this cohort, standard platelet assays established the diagnosis in the large majority of CQPD and CT. PTEM was essential for confirmation in DG-SPD, mild alpha granule deficiency and York platelet syndrome and useful in combination with molecular testing to establish a diagnosis in selected cases. Guidance on selection of patients for such specialized testing requires further study. Table 1. Results of standard and esoteric platelet testing for 54 patients with congenital qualitative platelet disorders and/or thrombocytopenia Disorder n (%) Platelet aggregation PFA PTEM Flow cytometry Confirmation by genetics Done Abnormal Done Abnormal Done Abnormal Done Abnormal Glanzmann thrombasthenia 6 (11) 6 6 5 5 1 0 3 3 0 Bernard-Soulier syndrome & variants 4 (7) 4 4 4 4 3 0 4 4 0 MYH-9 related disorders 10 (19) 7 2 8 3 5 5 4 2 5 Dense granule deficiency and HPS 12 (22) 12 8 12 8 12 12 4 0 0 Alpha granule deficiency* 7 (13) 7 4 7 6 7 7 4 4 1 York platelet syndrome 4 (7) 1 0 1 1 4 4 1 1 0 TXA2 or PG synthesis/receptor defect 4 (7) 4 4 4 3 3 0 3 0 0 CATM 1 (2) 0 - 0 - 0 - 0 - 1 ANKRD26 3 (6) 3 3 3 2 3 3 3 3 3 GATA-1 1 (2) 0 - 1 1 1 1 1 1 1 RUNX-1 1 (2) 1 0 1 1 0 - 0 - 1 Jacobsen syndrome 1 (2) 1 0 1 1 1 1 1 0 1 MYH-9: myosin heavy chain 9, non-muscle (MHY-9) associated thrombocytopenia, HPS: Hermansky-Pudlak Syndrome, TXA2: thromboxane A2, PG: prostaglandin CATM: congenital amegakaryocytic thrombocytopenia. * Includes gray platelet syndrome Disclosures Pardanani: Stemline: Research Funding.

Abstract Background: While Factor V Leiden is associated with an increased risk of thrombosis, the magnitude of that risk among homozygous carriers is uncertain. Methods: In a cross-sectional study of Mayo Clinic patients referred to the Special Coagulation Laboratory for a thrombophilia profile (n=379) over the 18-year period, 1996-2013, the prevalence of venous and arterial thrombosis was estimated for patients found to be Factor V Leiden carriers based on leukocyte genomic DNA genotyping. T tests and chi-square tests were used for continuous and categorical variables, respectively. Results: Among homozygous (n=111) and heterozygous (n=268) carriers, the mean age at testing (50.3 and 50.5 years, respectively; p=0.9) and the proportion of females (50% and 54%, respectively; p=0.5) did not differ significantly. Of 29 asymptomatic carriers at the time of testing, 14 were homozygotes. Of the remaining 350 carriers, the mean age at first venous or arterial thrombosis (42 vs 43.8 years; p=0.5) among homozygous and heterozygous carriers, respectively, did not differ significantly. Thirty-five (33%) and 83 (31%) homozygous and heterozygous carriers, respectively, had at least one recurrent venous or arterial thrombosis (p=0.72). The prevalence of deep venous thrombosis (DVT) was 61% and 46% in homozygous and heterozygous carriers, respectively (p=0.008); the prevalence of pulmonary embolism was 18% and 20%, respectively (p=0.69). The prevalence of arterial thrombosis (mainly stroke and/or TIA) was higher in heterozygous (23%) compared to homozygous carriers (8%). Conclusion: In the largest sample of homozygous Factor V Leiden carriers reported to date, thrombosis penetrance and phenotype did not appear to differ among homozygous vs. heterozygous carriers with the exception of a higher prevalence of DVT among homozygous carriers. These data should be interpreted with caution due to the potential for referral bias. Disclosures No relevant conflicts of interest to declare.

Abstract Abstract 4930 Background: Autoimmune disorders have been observed in pts with myeloid neoplasms but their frequency and impact on the natural history of the myeloid neoplasms remains to be defined. Aim: To describe the frequency and prognostic impact of autoimmunity in pts with CMML. Methods: After IRB approval, a retrospective chart review of all pts diagnosed with CMML at Mayo Clinic between 1994 – 2011. Autoimmunity (AI) was defined as positive serologic tests (Anti-nuclear antibodies (ANA), rheumatoid factor (RF), anti –cyclic citrullinate peptide (CCP), and antineutrophil cytoplasmic antibodies (ANCA)), diagnosis of connective tissue disease (Rheumatoid arthritis, RA), vasculitis, or auto-immune thrombocytopenia (ITP). Survival estimates were calculated using Kaplan-Meier estimates and Cox regression model for multivariate analysis for via JMP software v. 9. Results: During the study period, 288 pts with CMML were evaluated at Mayo Clinic, 35% (n=100) were female. Median age at diagnosis was 71yr (20–95). Median hemoglobin was 11 g/dL(6–16), median white blood cell (WBC) 12 x109/L (1–302), and median platelet count 86 x109/L (1–1110). Median peripheral blood (PB) and bone marrow (BM) blasts were 0 and 5 respectively, while median PB and BM monocytes were 20% and 8% respectively. Eight-nine percent of pts had CMML1, while 10% had CMML2 and only 2 pts had CMML transforming into acute myeloid leukemia (-t). Karyotype analysis performed in demonstrated normal (diploid) karyotype in 180 (63%) pts and complex karyotype in 31 pts (11%). JAK2 mutation analysis was performed in 76 pts, 13% (10/76) of which were positive for JAK2V617F mutation. Autoimmunity was found in 46 (16%) of 288 pts. When tested, positive ANA, RF, CCP, and ANCA were found in 28/89 (31%), 8/61 (13%), 1/20 (5%), and 7/25 (28%), respectively. However, RA was reported positive in 6/288 (2%), and vasculitis was reported in only 4 pts. Median overall survival of the 288 patients was 496 days. Pts with evidence of autoimmunity had a median survival of 400 days compared to 527 days to the rest of the group (p 0. 73). On multivariate analysis, autoimmunity was not an independent risk factor for survival (p 0. 15), but age, platelets, WBC and body mass index (BMI) were independent factors. Conclusion: Autoimmunity is a frequent finding in pts with CMML. When tested, autoimmune antibodies were very frequent up to 31% of pts with CMML, but this did not confer into higher frequency of autoimmune diseases. Presence of positive autoimmune antibodies did not affect overall survival adversely. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 2256 Background: The incidence of venous thromboembolism (VTE) may be increasing due to the obesity epidemic. Objective: To estimate the incidence of VTE and describe trends in incidence adjusted for the population's increase in BMI. Methods: Using the resources of the Rochester Epidemiology Project, we identified all Olmsted County, MN residents with an incident deep vein thrombosis (DVT) or pulmonary embolism (PE) over the 13-year period, 1988–2000 (n=1,400). Age and BMI at VTE diagnosis and gender were collected for all cases. Age was categorized into 10 year intervals. Using a model for the population distribution of BMI derived from several (n=6) non-VTE Olmsted County cohorts (n=8,011 individuals), we calculated the probability of falling into each of five BMI categories (<18.5, 18.5–24, 25–29, 30–34, 35+) for each age, gender and calendar year. In Olmsted County in the median age group, the prevalence of BMI >30 kg/m2increased from approximately 15% in 1980 to 36% in 2000. We applied these probabilities to the decennial census data for 1980, 1990, 2000 using linearly interpolated census values for intra-census years to obtain Olmsted County age/sex/calendar year/BMI category denominators. Generalized linear modeling assuming a Poisson error structure, and using a log link function, and a log (population) offset was used to assess the relationship of crude incidence rates to gender, year of diagnosis, age and BMI. Results: The overall average age- and sex-adjusted annual VTE incidence was 120 per 100,000 person-years (DVT: 66 per 100,000; PE: 54 per 100,000), with higher age-adjusted rates among men than women (129 versus 113 per 100,000, respectively). VTE incidence rates increased exponentially with age for both genders, ranging from 3 to 1,079 per 100,000 for age groups 0–19 to 90–110 years. Age and sex-adjusted VTE incidence increased by increasing BMI category (88, 112, 106, 150, and 195 per 100,000 person-years, respectively, by increasing BMI category). Unadjusted for BMI, VTE incidence was unchanged from 1988 through 2000 (p=0.70). After adjusting for age, gender and calendar year, VTE incidence increased with increasing BMI (p<0.0001). The calendar year incidence slope estimate decreased numerically from 3% per decade to minus 4% per decade after adjusting for increasing BMI, remaining nonsignificant (p=0.57). Conclusions: VTE remains a major national health problem, especially among the obese. Despite the dramatically increasing population BMI, and the significant association of BMI category with VTE incidence, the overall incidence of VTE remained unchanged over the timeframe, 1988–2000. Disclosures: No relevant conflicts of interest to declare.