ALBERT

Beschreibung: Introduction Patients with a history of HIT, who require cardiopulmonary bypass (CPB), have limited anticoagulation options. Unfractionated heparin (UFH) is preferred by surgeons during CPB because of their extensive experience, short half-life of the drug, and the availability of protamine sulfate to reverse its effect. However, heparin re-challenge may be associated with a risk of recurrence of HIT. A number of instances of successful heparin re-exposure during CPB have been reported in HIT patients. However, small sample size of these reports and a lack of systemic review have prevented better understanding of the potential complications. The objective of this study was to determine the safety of heparin re-exposure in HIT patients and various strategies utilized to reduce the recurrence of HIT. Methods Using several search terms, all cases of heparin re-exposure in HIT patients published and indexed in English language in Pubmed by June 2014 were reviewed. The bibliography of each relevant article was searched for additional related reports. The diagnosis of HIT was based on the clinical probability or 4T scoring system and laboratory tests. The exposure to either UFH or low molecular weight heparin (LMWH) in patients with a history of HIT was considered a re-exposure. In two cases, heparin was used multiple times for repeated cardiovascular surgeries after an initial diagnosis of HIT. Each re-exposure was determined as a different instance of re-exposure during analysis. Results A total of 136 patients with a history of HIT had 141 instances of heparin re-exposure. Median age was 56 years (6 weeks -87 yrs) and 67% were males. Regarding the original HIT diagnosis, UFH (98%) and nadroparin (2%) were the causative agents. Thrombotic complications occurred in 23%. The pretest probability score was high in 79% and moderate in 21%. Platelet aggregation studies (66%), enzyme linked immunosorbent assay (ELISA)/enzyme immunoassay (EIA) (20%), serotonin release assay (SRA) (2%), and both SRA and EIA (12%) were performed for diagnosis. Cardiac (76%) and vascular surgeries (11%) were the most common indications for heparin re-exposure. Although 67% were re-exposed to heparin after 3 months of HIT diagnosis, 11%, 8% and 15% were re-exposed within 1 week, between 1 week to 1 month, and 1 month to 3 months of HIT diagnosis respectively. Anti-platelet factor 4/heparin antibodies were positive in 63% before re-exposure. UFH (93%) or LMWH (7%) were the utilized agents during re-exposure. Sixteen patients (11%) underwent plasmapheresis to lower the level of anti-platelet factor 4/heparin antibodies before the re-exposure. Non-heparin anticoagulants such as bivalirudin, fondaparinux, danaparoid, r-hirudin, argatroban, lepirudin, and warfarin were used singly or in combination after the exposure in 63% of patients. With heparin re-exposure, 4.2% had complications, which included recurrence of HIT (2.1%), and bleeding (2.1%). Among the patients with HIT recurrence (n=3), one patient was re-exposed to UFH within a week of HIT diagnosis and shortly after platelet recovery with LMWH (Intensive Care Med. 1991;17(3):185-6.). The other two patients were initially diagnosed with HIT more than 5 years back and tested negative for anti-platelet factor 4/heparin antibody prior to heparin re-exposure. Conclusion A review of the published reports indicates that intra-operative heparin re-exposure in patients with HIT has a small risk of developing thrombocytopenia or recurrence of HIT. The use of pre-exposure plasmapheresis in patients with positive anti-platelet factor 4/heparin antibody and post-exposure non-heparin anticoagulants may have reduced the risk of recurrence of HIT. Given several limitations of such retrospective review, prospective studies are needed to validate these results. Disclosures No relevant conflicts of interest to declare.

Beschreibung: Introduction Current guidelines recommend use of clinical pretest probability scores, d-dimer assay, and imaging studies in the diagnosis of pulmonary embolism (PE). Studies have shown that normal d-dimer levels with low-intermediate probability in Wells score can safely exclude PE in most cases. Usually, d-dimer level of less than 500 µg/L is used to decide that no further imaging studies such as computed tomography pulmonary angiography (CTPA) or ventilation perfusion (V/Q) scan) are required. However, the conventional cutoff of 500 µg/L may not be as specific in all patients as d-dimer levels increase with age. Thus, use of age-adjusted d-dimer cutoff has been advocated which is defined as (age × 10) µg/L in patients 50 years or older. Objective To study if age-adjusted d-dimer is helpful in decreasing imaging studies without missing the diagnosis of PE in suspected cases. Methods We did an observational retrospective study of all consecutive adult patients who presented to the emergency department from January 2014 to December 2016. The patients who were clinically suspected with PE and underwent subsequent workup along with d-dimer assays were included for analysis. The number of imaging studies performed for PE diagnosis were recorded. Results We included 3,197 patients in the study. Median age was 55 years, and 67% were females (Table 1). Total 2,937 (92%) patients had elevated d-dimer levels based on conventional d-dimer cutoff compared to 2,526 (79%) patients based on age-adjusted d-dimer cutoff. The age-adjusted d-dimer cutoff was more specific (21% vs 8%, p-value

Beschreibung: Introduction: Direct oral anticoagulants (DOACs), also known as non-vitamin K oral anticoagulants, include rivaroxaban, dabigatran, apixiban, edoxaban, and betrixaban. Guidelines have recently identified DOACs as the first line treatment in venous thromboembolism and nonvalvular atrial fibrillation. As the use of these anticoagulants has gradually increased in last few years, the reports of bleeding-related adverse drug events with these agents has increased. There are very few data related to diffuse alveolar hemorrhage (DAH) with DOACs, a dreaded complication of any anticoagulant. Objective: To perform a systematic review of all reported cases of DAH secondary to DOAC use. Methods: Using several search terms, we reviewed all cases of DAH associated with DOACs which were published and indexed in English language in PubMed and EMBASE in the last 10 years. The bibliography of each relevant article was searched for additional related reports. Statistical analysis was performed using Statistical Packages for the Social Science (SPSS). Results: A total of 34 cases were included in the study. Mean age was 69±15 years; 68% were male, 32% were female. Rivaroxaban, dabigatran, apixaban, and edoxaban were used in 41%, 35%, 21%, 3% of patients respectively. Atrial fibrillation was the commonest indication for DOAC use, 68%. Hemoptysis was the commonest presenting symptom, 74%. DAH was diagnosed with Computed Tomography (CT), Bronchoalveolar Lavage (BAL), and both in 68%, 56%, and 35% respectively. A total of 18 (53%) cases required mechanical ventilation. There was a total of 7 (21%) deaths, while 20 (59%) survived. Conclusion: Despite reports of lower risk of major bleeding compared to other anticoagulants, DAH is still a possibility with DOAC use. DOACs' absorption and elimination relies largely on P-glycoprotein (P-gp) efflux transporters, coadministration of P-gp inhibitors such as Amiodarone, a common antiarrhythmic used in atrial fibrillation in conjunction with anticoagulation, may result in disturbance of DOAC's concentrations in the blood, increasing the risk of potential side effects. Autoimmune diseases can lead to DAH independently. Owing to the diseased lung tissue in patients with autoimmune disease, the use of DOAC's may enhance the already present risk of DAH. Renal function plays a role in excretion of DOAC's, AKI may cause accumulation of DOAC's in the body leading to major side effects. Newer cases reported the use of idracuzimab; a newly FDA-approved drug for dabigatran reversal. In conclusion; caution should be taken with the increasing use of DOAC's in management of complex care patients requiring anticoagulation, prompt diagnosis and management is key for survival and prevention of complications, and new reversal agents may play a future role in the management of such complications. Table. Table. Disclosures No relevant conflicts of interest to declare.

Beschreibung: Introduction: Immune thrombocytopenia (ITP) is an autoimmune phenomenon causing increased destruction and insufficient platelet production. ITP can be a healthcare burden due to prolonged treatment (medical and sometimes surgical = splenectomy) required to prevent the relapse and frequent hospitalizations for management of complications such as epistaxis, gastrointestinal bleeding (GIB) or intracranial hemorrhage (ICH). In addition, septicemia and coagulation disorders can occur related to therapy. In this study we analyzed demographics among inpatient admissions with ITP and the variation of length of stay (LOS) and mortality with different complications. Methods: We performed a retrospective cohort analysis of the National Inpatient Sample 2014 Database (HCUP-NIS). Patients were included in the study if they had a primary or secondary diagnosis of ITP and age 〉18 years. We performed descriptive statistics to characterize the cohort in terms of personal demographic factors (age, race, sex, insurance type, community level income level), hospital characteristics (size, region, teaching status, and urban or rural location). The cohort was classified on based on splenectomy status using procedure diagnosis code. The cohort was further analyzed for complications such as coagulation disorders, GIB, ICH, septicemia and epistaxis using their principal diagnosis. Furthermore, we also looked at the variation in LOS and mortality among them. Univariate and multivariate regression analysis were performed to determine statistical significance. All analyses applied the HCUP-NIS weights. Results: There were 11,535 patients in the cohort. Most were white (64.4%), females (57.95%), and aged 〈 60 years (55.6%). A significant proportion were covered by Medicare (41.33%). Most care was delivered in large hospitals (55.17%), that were disproportionately urban (94.4%) or teaching (70.61%) institutions. The greatest segment of patients were in the South Atlantic region (20.8%). Epistaxis occurred in 15.3% of patients, GIB in 3.12%, ICH in 0.41%, and septicemia in 0.99%. The mean LOS was 4.73 days (95% CI 4.49 to 4.97). Mean LOS was highest in patients with septicemia (12.3 days), followed by GIB (8.98 days) and ICH (7.99 days), and epistaxis and coagulation disorders (6 days each). LOS was significantly shorter in patients who had undergone splenectomy (AMD -10.67 95% CI-18.32 to -3.03), and longer with septicemia (AMD 9.06 95% CI 1.84 to 16.27). Compared to Medicare, other insurances statuses had shower LOS: uninsured (AMD -6.60 95% CI -10.76 to -1.39), Medicaid (AMD -3.57 95% CI -7.07 to -0.086), and private (AMD -2.67 95% CI -5.39 to 0.037). Risk of death was much higher with GIB (OR 227 95% CI 7.63 to 6757.48, p=0.002) and ICH (OR 100.88 95% CI 10.27 to 990.91, p

Beschreibung: Introduction Increased risk of venous thromboembolism (VTE) has been noted among cancer patients as compared to non-cancer. VTE identified as leading cause of death among those with cancer. Cancer associated thrombosis caused increased hospitalizations, increased inpatient/outpatient medical and prescription claims, and increased total health care costs per patient. Our objective was to study demographic, clinical and laboratory risk factors for venous thromboembolism (VTE) among hospitalized cancer patients and built a predictive model for VTE risk. Methods Ours was a retrospective cohort study focused on patients with VTE and cancer from January 2013 - September 2015. Univariate and multivariate logistic regression analysis using stepwise approach was performed. A final predictive model was derived using receiver-operating characteristics (ROC) curves and concordance indices (c-statistics). Results N=3948 cancer inpatients were identified which was split into a derivation cohort and a validation cohort, each with 1957. Mean age 65.9±13.8 years; 52.6% were male; 85.6% Caucasian, 7% African Americans; 15.5% were obese; common comorbidities were hypertension (46%), pulmonary disease (34.5%), diabetes (22.9%), renal disease (20.9%) and congestive heart failure (10.4%). Overall, there was 152 (3.9%) events of VTE with 77 (3.9%) in derivation and 75 (3.8%) in validation cohort. On univariate analysis, comorbidities such as infection and renal diseases, laboratory findings such as low hemoglobin and low albumin was associated with high VTE risk. The derivation set had a c-statistic or AUC of 0.668 while the validation set had an AUC of 0.65. Conclusions Infection, renal disease (comorbidity) and low albumin levels were associated with a higher risk of VTE. Digestive and respiratory cancers were associated with higher VTE risk. We identified three clinical and laboratory variable that was associated with increased risk of VTE in addition to the cancer group. Future research could use this analysis as a basis for forming a risk score that could be used by clinicians to identify those cancer patients at risk for VTE. Disclosures No relevant conflicts of interest to declare.

Beschreibung: Introduction MMF is an immunosuppressive drug frequently used for graft-versus-host disease (GVHD) prophylaxis and management. MMF-induced colitis is a known complication, however, details regarding its clinical manifestations, treatment options, and outcomes are less clear. Differentiating MMF-induced colitis from gut GVHD on the basis of histology may be difficult, hence deeper clinical understanding of MMF-induced colitis can be valuable. The aim of this systematic review was to analyze the reported cases of MMF-induced colitis to provide summative data. Methods Inclusion criteria included prospective or retrospective clinical studies and case series, reported in English language, providing data on clinical manifestations, treatment options, and outcomes of colitis induced by MMF or its derivatives (such as mycophenolic acid, and enteric coated mycophenolate sodium). Cases were included irrespective of the indication of MMF. Using various search terms, all cases indexed in PubMed, EMBASE, Cochrane and Scopus from inception to July 2016 were reviewed. The bibliography of each relevant article was searched for additional reports. Non-human studies and colitis attributed to other etiologies such as infection, GVHD or inflammatory bowel disease were among the 138 articles that were excluded. Results Forty-four articles with a total of 544 patients and 560 episodes of suspected or confirmed MMF-induced colitis were included. The median age was 41 years (range 5-70), and 30% were females. The latency between the use of MMF and onset of colitis was 990 days (range 3- 5760). Watery diarrhea as frequent as every 20 minutes in one case and large volume at times, was the presenting symptom in 92% of cases. Other less common presentations included bloody diarrhea, abdominal pain, and steatorrhea. MMF was discontinued or dose reduced in 65%, switched to enteric coated mycophenolate mofetil sodium in 14% and continued in 21% of cases. Ninety-eight percent of cases managed with discontinuation or dose reduction of MMF responded to the treatment. About 93% of cases who switched from MMF to enteric coated mycophenolate mofetil sodium responded. Among the patients who continued MMF, diarrhea was persistent in 17% while it resolved spontaneously in 83% (Figure 1). The median time to response to either change to enteric coated mycophenolate sodium or discontinuation of treatment was 20 days (range 1-45). Complications developed in 3.5% (n=19) of cases including graft rejection in solid-organ transplant (n=11) after discontinuation or dose reduction of MMF, acute dehydration (n=6), toxic colitis (n=1), and severe weight loss of 〉60 pounds (n=1). Conclusion MMF-induced colitis generally presents with watery diarrhea but rarely blood may be noted in stool. The latency period can be as long as months to years, hence a long latency period does not exclude the possibility. A vast majority of patients respond to cessation of MMF or dose reduction within a few weeks, however, cessation of MMF may result in graft rejection. In cases where continuation of immunosuppressive therapy is considered important to prevent graft rejection, alternate management option for management of MMF-induced colitis could include switching to a different drug formulation. Figure 1 Management and outcomes of MMF-induced colitis Figure 1. Management and outcomes of MMF-induced colitis Disclosures No relevant conflicts of interest to declare.

Beschreibung: Introduction Polypharmacy, commonly defined as taking ≥5 prescribed medications, is a major issue in adults, especially those ≥60 years of age. Drug-drug interactions can significantly increase toxicities while undergoing chemotherapy, and may affect OS in AML. Polypharmacy can also increase treatment costs. We aimed to evaluate the effects of polypharmacy on OS in AML. Methods We included adult AML patients diagnosed from 2000-2016 at University of Nebraska Medical Center. Based on the number of prescribed medications at the time of AML diagnosis, patients were divided into 2 groups: patients with (≥5 medications) versus without polypharmacy (

Beschreibung: Introduction: Hospital volume and provider experience affects survival among patients with hematologic malignancies (Giri et al Blood 3359-60). Whether hospital volume affects outcomes of autologous hematopoietic cell transplant (autoSCT) among patients with multiple myeloma (MM) remains unclear. Methods: We utilized the Nationwide Inpatient Sample (NIS) database to identify all adults 〉18 years diagnosed with MM who underwent autoSCT in 2009-2011. NIS is the largest all-payer inpatient database in the US that captures about 20% of all US hospitalizations. Hospitals were divided into quartiles, based on the annual number of autoSCT performed, and classified into high volume (above 75th percentile) and low volume centers (below 25th percentile). In-hospital outcomes including inpatient mortality, infection, mechanical ventilation, and costs of hospitalization were compared between the two groups. All p-values were 2 sided, and the level of significance was chosen at 0.05. Statistical analysis was done using STATA 13.0 (StataCorp, College Station, TX). Results: A total of 2,750 autoSCTs were reported among patients with MM during the study period. The characteristics of study population included mean age of 58.7 ± 8.7 years, 56% males (n=1547) and 72% whites (n=1822). No significant difference existed in in-hospital mortality rate (0.86% vs. 1.59%; p=0.183) between high volume (≥178 autoSCTs per year) versus low volume centers (≤56 autoSCTs per year). The rate of fungal infection (5.32% vs. 4.94%; p=0.75), herpes simplex virus infection (1.58% vs. 1.59%; p=0.98), and the need for mechanical ventilation (1.87% vs. 1.27%) was similar between the high volume and low volume centers. Higher rates of stomatitis (57% vs. 46%; p

Beschreibung: Introduction: Venetoclax (VEN) in combination with a hypomethylating agents (HMA) is associated with a high rate of composite remission (complete remission [CR] and complete remission with incomplete recovery [CRi]) among older and unfit patients with untreated AML. However, data regarding the activity of VEN-HMA in those patients with favorable-risk AML is limited, particularly in those with core-binding factor (CBF) alterations. Although more frequent among younger patients, favorable-risk alterations are also observed among older patients, often unfit for intensive regimens. Even among the subset of older patients (〉60 years) with favorable-risk AML eligible for intensive regimens, long-term outcomes are poorer in comparison to younger patients. Methods: We retrospectively analyzed outcomes of 46 patients with favorable-risk AML who underwent therapy with VEN-HMA between 2016-2020 at 4 academic cancer centers in US. Favorable-risk AML was defined by the presence of either CBF [t(8;21) and inv(16) or t(16;16)], NPM1 mutation in the absence of FLT-3 ITD mutations; or bi-allelic CEBPA mutations. Results: Forty-six patients with favorable risk AML were treated with HMA-VEN, including 26 (57%) with newly diagnosed (ND) and 20 (43%) with relapsed/refractory (R/R) AML (Table1). Ten (22%) patients had CBF, 21 (46%) had NPM1 mutations (NPM1m), and 13 (28%) had bi-allelic CEBPA mutations (CEBPAm). The median age was 70 years, and 54% were females. Patients with R/R AML were younger than ND patients (56 vs. 72 yrs, p=0.003). Twenty (44%) patients had secondary or therapy-related AML, including half of ND patients. The median lines of prior therapy were 2(1-4) in patients with R/R AML, including 6 (30%) who had failed prior allogeneic HCT. Eleven (24%) patients had received HMA prior to HMA-VEN therapy, including 1 patient in the ND cohort for prior MDS. Eleven (24%) patients received azacitidine in combination with VEN, while the rest (76%) of patients received decitabine, including 14 patients who received 10-day decitabine during the first cycle. The CR/CRi rate among the whole cohort was 80%, including 52% CR and 28% CRi. There was no statistically significant difference in CR/CRi rate between ND and R/R patients (88% vs. 70%, P =0.15). However, patients with history of prior HMA exposure had lower response rate compared to HMA-naïve patients (55% vs. 88%, p= 0.025). No difference in response was observed based on the favorable genetic alteration subgroups (80% in CBF vs. 86% in NPM1m vs. 77% in CEBPAm, p=0.44). Furthermore, no difference in response was observed according to patient age (p= 0.83), AML types (de novo vs. secondary; p= 0.47), prior transplant (p=1.00), or the type and schedule of HMA (P=0.66). Among the responders who had MRD assessment done (n= 26), 22 (85%) achieved MRD negativity by multicolor flow cytometry. Post response, 13 (35%) patients underwent allogeneic transplant consolidation. The median overall survival (OS) for the whole cohort was 18 months (12.5-NA). Median leukemia-free survival (LFS) was 13.2 months (7-20.2) for all responders, 11.2 months (1.7-NA) for ND responders, and 14.0 months (1-NA) for RR responders (p=0.986). The 30- and 60-day mortality for the whole cohort was 0% and 9%, respectively. Conclusion: In patients with favorable-risk AML, VEN-HMA combination is associated with a highly promising CR/CRi rate, with durable responses. The majority of responders achieved MRD negativity. Patients with prior use of HMA had lower response rate with VEN-HMA, nonetheless, over half of these patients responded despite most being treated in the R/R setting. Disclosures Pullarkat: Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genetech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie, Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Dova: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Stein:Stemline: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau. Marcucci:Abbvie: Speakers Bureau; Merck: Other: Research Support (Investigation Initiated Clinical Trial); Novartis: Speakers Bureau; Pfizer: Other: Research Support (Investigation Initiated Clinical Trial); Takeda: Other: Research Support (Investigation Initiated Clinical Trial); Iaso Bio: Membership on an entity's Board of Directors or advisory committees. Yaghmour:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Alexion: Consultancy, Speakers Bureau. Bhatt:Omeros: Consultancy; Agios: Consultancy; Rigel: Consultancy; Tolero: Research Funding; Pfizer: Research Funding; Abbvie: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Partnership for health analytic research: Consultancy; Takeda: Consultancy; Jazz: Research Funding; National Marrow Donor Program: Research Funding; Oncoceutics: Other. Fathi:Takeda: Consultancy, Research Funding; Jazz: Consultancy; Forty Seven: Consultancy; Daiichi Sankyo: Consultancy; Amphivena: Consultancy; Blueprint: Consultancy; Kura Oncology: Consultancy; Boston Biomedical: Consultancy; Astellas: Consultancy; Trovagene: Consultancy; Novartis: Consultancy; PTC Therapeutics: Consultancy; Agios: Consultancy, Research Funding; BMS/Celgene: Consultancy, Research Funding; Kite: Consultancy; Pfizer: Consultancy; Trillium: Consultancy; Amgen: Consultancy; Seattle Genetics: Consultancy, Research Funding; Abbvie: Consultancy; Newlink Genetics: Consultancy.

Beschreibung: Introduction Acute promyelocytic leukemia (APL), considered a medical emergency, requires prompt treatment at the first suspicion of the diagnosis. Treatment is initiated even before cytogenetic or molecular confirmation of diagnosis because of high early mortality with APL, mostly due to hemorrhage and disseminated intravascular coagulation. Once a cancer with dismal prognosis, APL is now considered a highly curable cancer with the introduction of all-trans retinoic acid and arsenic trioxide. In fact, recent clinical trials in APL report excellent outcomes with 〉90% OS at 3-years with