Pruthi, Rajiv K.

Abstract Background Hip and knee arthroplasty (THA and TKA), in general, pose a high risk for venous thromboembolism (VTE), and pharmacologic VTE prophylaxis is often strongly recommended. In patients (pt) with hemophilia undergoing THA/TKA, given the underlying bleeding diathesis, the routine use of pharmacologic VTE prophylaxis is controversial. In this study, we report THA/TKA outcomes in pt with hemophilia in our institution. Methods Retrospective chart review of Mayo Comprehensive hemophilia center pt undergoing THA and TKA. Medical records were reviewed for objectively documented VTE for up to 3 months after surgery. Results 42 consecutive pt with hemophilia A (n=38) or B (n=4) underwent 71 operations: THA (n=32) and TKA (n=39) over a period of 39 years. All pt received compression stockings up to 6 weeks after surgery; 6/71 (8.4%) received sequential intermittent compression and 2/71 (2.8%) received postoperative low molecular weight heparin (LMWH). Symptomatic femoral vein DVT occurred in 1/42 pt (2%); (1/71, 1.4% of operations (1.4%)), 10 days after THA for traumatic hip fracture and after the LMWH was discontinued. The patient was subsequently found to be heterozygous for the factor V Leiden gene mutation. For up to 3 months after surgery, there were no additional cases of symptomatic DVT. There was no unexpected bleeding in the 2 patients receiving LMWH. Conclusion In this this study, routine use of compression stockings without the use of pharmacologic prophylaxis resulted in a low rate of symptomatic VTE in patients with hemophilia. This may be similar to the incidence in the general population receiving LMWH (Heit, JA et al Annals of Internal Medicine 2000) A limited sample size precludes definitive recommendations for practice. For appropriate high risk patients, limited use of pharmacologic prophylaxis may still be important. Disclosures: No relevant conflicts of interest to declare.

Background and Purpose: Bolus infusion (BI) of recombinant FVIIa (rFVIIa) is effective for the treatment of bleeding and surgical prophylaxis in congenital hemophilia A or B patients with FVIII or IX inhibitors. In principle, continuous infusion (CI) of rFVIIa could maintain the hemostatic effect at a steady state while avoiding the peaks and troughs of repetitive BI. The purpose of this study was to compare the efficacy and safety of rFVIIa CI with rFVIIa BI in major surgery in hemophilia patients with inhibitors. Methods: A 10-day, open-label, randomized, multicenter trial was conducted in hemophilia A or B patients (age > 5 yr) with inhibitors to FVIII or FIX who underwent elective major surgery. Patients received rFVIIa as an initial bolus dose of 90 μg/kg followed by intermittent i.v. bolus (90 μg/kg) or i.v. continuous (50 μg/kg/hr) infusion. BI was administered every 2 hours during surgery and through Day 5, then every 4 hours for Days 6 to 10. CI was administered at 50 μg/kg/hr through Day 5 and at 25 μg/kg/hr Days 6 to10. A third control group of 10 non-inhibitor hemophilia A or B patients who underwent similar surgery and were treated with FVIII or FIX (based on current standard of care and physician’s choice) was assessed to compare adverse event and coagulation profiles. Safety was assessed throughout the study periods. Efficacy was defined as having no treatment failures during the given time and was evaluated at 48 hours, 5 days, and 10 days postoperatively. Treatment was considered ineffective in patients who received more than 2 additional doses of rFVIIa beyond the protocol-defined doses during a 24 hour period. Patients who received alternative hemostatic therapy following the permitted two additional doses of rFVIIa were considered treatment failures. Results: Twenty-four patients (12 CI arm, 12 BI arm) underwent 9 major types of surgeries. Knee (n=11) and hip (n=3) replacements were the most common surgeries. Recombinant FVIIa efficacy in major surgeries was 92% (11 CI, 11 BI) at 48 hours; 83% (10 CI) and 92% (11 BI) at Day 5; 83% (10 CI) and 75% (9 BI) at Day 10. Sixty-six rescue doses (rFVIIa, 90 μg/kg) were administered in the CI group (54 in one patient), and 7 in 3 patients in the BI group. Adverse events occurred more frequently in the CI treatment group (239; 141 in one patient) compared to the BI group (89 AEs); 64 AEs occurred in the control group. Eight patients (3 CI, 4 BI, 1 control) experienced 10 serious adverse events (SAEs). SAEs occurred most frequently in the BI treatment group (3 CI, 6 BI, 1 control). The types of SAEs were equally distributed among the three groups. There were no serious thromboembolic events reported during the study. Conclusions: This summary of 24 major surgeries indicates that rFVIIa is effective as prophylactic therapy for major surgery in hemophilia A or B patients with inhibitors. The numbers of patients were too small to distinguish efficacy rates between the two groups. The safety profile for patients treated with rFVIIa (BI or CI) was similar to the profile for non-inhibitor patients treated with other factors. Presented on behalf of the NovoSeven in Surgery Study Investigators.

Abstract Background: JAK2V617F is a recurring mutation in patients with polycythemia vera (PV) (95%) and essential thrombocythemia (ET) (50%), diseases that are frequently complicated by arterial and/or venous thrombosis. JAK2V617F is also frequently identified in patients with splanchnic vein thrombosis, including in those with occult myeloproliferative disorder (MPD). We previously reported a low prevalence of JAK2V617F in thrombosis patients - only 2% of 210 patients with non-splanchnic vein thrombosis (Leukemia, 2007 Aug;21(8):1828–9), and <1% of 136 patients with arterial stroke (J Thromb Haemost. 2007 Aug;5(8):1784–5). Here, we expanded the analysis to 664 thrombosis patients to describe: JAK2V617F prevalence, and clinical course of patients harboring this mutation. Methods: In Phase I, we screened 439 consecutive patients who underwent thrombophilia testing at our institution in early 2005 - patients with splanchnic vein thrombosis or overt MPD were excluded. In Phase II, we identified 228 additional patients considered to be at high risk for harboring JAK2V617F, who were seen at our institution from 2004 to 2006. JAK2V617F screening (assay sensitivity <1%) was performed as described in the aforementioned references. Results: In the initial cohort of 439 patients (median age=56 years; range 17–93 years; 222 female), 136 (31%) presented with stroke, 114 (26%) with deep venous thrombosis (DVT), 95 (22%) with pulmonary embolism (PE), 50 (11%) with DVT and PE, 10 (2%) with central retinal vein occlusion (CRVO), 7 (2%) with cerebral vein thrombosis, and the remaining 27 (6%) with other thromboses. Five patients (MC1-MC5; median age=78 years) were found to harbor JAK2V617F (prevalence=1%) - none had overt clinical features of MPD and all harbored a low level of JAK2V617F in peripheral blood (median=5–2%; range=2.2–7.5%) (Table). One patient (MC2) carried the Prothrombin G20210A mutation In the subsequent cohort, we studied 197 patients (median age=39 years; range=16–84 years) with recurrent DVT and/or PE, and 28 patients (median age=27 years; range=31–49 years) with acute myocardial infarction at a young age (<50 years). One patient (MC6) who presented with recurrent idiopathic DVT was found to harbor JAK2V617F (prevalence <0.5%) (Table) - this patient had no features of underlying MPD and the mutation burden was low (9%). After a median follow up of 27 months (range=4–66 months), none of the 6 patients harboring JAK2V617F has developed overt MPD. Conclusions: In patients with thrombosis, JAK2V617F is infrequently detected in the absence of overt MPD and/or involvement of splanchnic veins. Thus, JAK2V617F screening cannot be recommended as part of the hypercoagulable workup in routine clinical practice in this setting. The risk of developing overt MPD may be quite low for patients harboring a low JAK2V617F burden at the time of thrombosis although longer follow up is needed in this regard. Furthermore, the thrombosis risk may be well controlled with standard warfarin therapy, and the role of myelosuppressive agents (eg. hydroxyurea) is unclear in these patients. Characteristics of patients harboring JAK2V617F Patient Age Sex Thrombosis JAK2V617F allele burden MPD Follow up (months) Status MC1 84 M PE, DVT 5.3% No 66 Alive MC2 82 F PE, cerebral vein 5% No 38 Alive MC3 74 F PE 2.2% No 4 Dead MC4 78 F Central retinal vein 5.2% No 22 Alive MC5 63 M Stroke 7.5% No 30 Alive MC6 69 M Recurrent DVT No No 24 Alive

Abstract Renal vein thrombosis (RVT), although uncommon, is associated with considerable morbidity and mortality. Neither the etiology nor the natural history of RVT has been adequately described in a large case series. Objective: To determine whether incident RVT is associated with an increased likelihood of recurrent local and systemic venous thromboembolic disease. Methods: Cases were identified by reviewing the Diagnostic Index for all patients with RVT at our institution between 1981 and 2000. Results: The study group consisted of 240 patients (34% women) with a mean age 55± 19 years. The diagnosis of RVT was made by CT (35%), Duplex Ultrasound (35%), MRI±gadolinium (10%) and either at surgery or autopsy in the remainder. The underlying etiology was deemed to be malignancy in 65% of cases. Of these, renal cell carcinoma (74%) and Wilms tumor (3%) made up the majority. Nephrotic syndrome primarily membranous glomerulonephritis was the second most common underlying etiology (23%). Of those tested, a definable thrombophilia was found in only 13 cases including lupus anticoagulant/antiphospholipid antibody (n=4); deficiencies of protein C or S, (n=2 each); heparin induced thrombocytopenia (n=2); antithrombin deficiency, dysfibrinogenemia and hyperhomocysteinemia (n=1 each). Eighty-one patients (34%) were treated with warfarin. Over a mean follow up of 3 years, the rate of recurrence of venous thrombosis at any site was 5%. The mortality rate over this time period was 49%. Conclusion: RVT represents a distinct clinical entity relative to venous thromboembolism of the lower extremity. The observed low rate of recurrence may be explained by the high mortality rate owing to a high percentage of renal malignancy. RVT should prompt an evaluation for an underlying renal malignancy.

Abstract Introduction: The prevalence of venous thrombosis and pulmonary embolism (VTE) increases with age. Definitive VTE diagnosis or exclusion relies on imaging modalities, which are found to be negative in a high proportion of tested patients. Algorithms based on pretest clinical probability (low and intermediate) in conjunction with negative d-dimer test results have reliably excluded VTE sparing the need for additional imaging studies. Currently, the cutoff for a negative d-dimer is based on reference ranges regardless of age of the donor population. Since baseline d-dimer increases with aging, an age-adjusted d-dimer (AADD) cutoff for patients older than 50 years (age*10 ng/mL FEU) has been shown to improve specificity of diagnosis while still maintaining a high sensitivity (>97%) of detecting VTE/PE (Righini, et al. JAMA, 2014). Due to FDA restrictions, clinical laboratories cannot implement and report such AADD cutoffs. Major hurdles include: AADD cutoffs are assay-dependent, and there is a lack of feasible strategy for laboratories to verify the AADD cutoffs. We hypothesize that an adequate study of age-distribution of baseline d-dimer levels of healthy donors can assist the verification of AADD cutoffs and ultimately ensure patient safety in the VTE patient population. Objective: Establish an age dependent reference range for patients 50 years or older with the HemosIL HS 500 D-dimer reagent on the ACL TOP 700 (Instrumentation Laboratory, Bedford MA, USA); and compare this range with the manufacturer provided and literature recommended AADD cutoffs. Methods: D-dimer assay was performed on plasma samples from normal adult donors per the manufacturers' instructions. D-Dimer age, gender distribution and association were analyzed using non-parametric Wilcoxon rank sum, Kolmogorov-Smirnov tests, and quantile regression methods to estimate the 95th percentile to establish a reference range. Results: We studied 241 healthy donors, ranging from 21-91 years of age. Statistically significant differences between males and females (100 [42%] male) were detected (p-value <0.001; p-value =0.0009). Using CLSI guidelines, these statistical differences (median d-dimer for men = 200, while median d-dimer for women = 300) are not considered clinically significant, since only 6% of women would be outside an overall reference range (CLSI guideline states to partition if over 8% for either group would be outside the overall reference range). Using the quantile regression method, a significant association between d-dimer and age was found at the median (P<0.0001). We then established a reference range (95th percentile) for donors younger than age 50 at 635 ng/mL FEU for both men and women and AADD reference range for patients 50 and older (635 + (age - 50)*10 ng/mL) (Figure 1). This reference range was verified with our sample set, with only 6.2% of donors higher than the established reference limit. If we used the non-AADD cutoff provided by the manufacturer for donors younger than 50 (500 ng/mL FEU) and the literature recommended AADD cutoffs for older donors (age*10 ng/mL FEU), 13.3% of our normal donors were above the limits, resulting in not validating this literature reference range per CLSI guidelines in EP28-A3c. These data imply that if both manufacturer and literature recommended AADD cutoffs were adopted, HemosIL HS 500 D-dimer assay should have sufficient sensitivity and negative predictive value, although with slightly lower specificity than those reported by Righini, et al. for detecting VTE/PE. Conclusion: Our study verifies the association between d-dimer level and age and for the first time, to our knowledge, determined AADD normal range for the HemosIL HS 500 D-dimer assay. The manufacturer and literature recommended AADD cutoffs should provide sufficient sensitivity and negative predictive value for VTE/PE exclusion. Figure 1 Age distribution of D-Dimer values (n=241). Figure 1. Age distribution of D-Dimer values (n=241). Disclosures No relevant conflicts of interest to declare.

Abstract Abstract 2279 Surgery for patients with von Willebrand disease (VWD) is increasingly common, however there is a paucity of data on hemostatic outcomes for VWD patients undergoing joint replacement surgery when compared to patients without bleeding disorders. The aim of this study was to evaluate hemostatic prophylaxis and outcomes in VWD patients who underwent hip or knee joint replacement, with comparison to matched case control patients. Methods: We retrospectively reviewed medical records of VWD patients who underwent total hip (THA) or total knee (TKA) arthroplasty between February 1993 and January 2011 at Mayo Clinic Rochester. Outcomes for each VWD patient were compared with two case controls matched for age, gender, surgeon and surgery. For VWD patients the hemostatic prophylaxis regimen during and following surgical procedures was evaluated including results of serial monitoring of plasma levels of VWF:RCo, VWF:Ag and FVIII:C. We compared VWD and control cases for bleeding complications (major and minor), transfusion requirements, DVT (deep vein thrombosis) prophylaxis and occurrence, duration of hospitalization, and other complications. Results: Twelve VWD patients (7 female) underwent 12 TKA and 7 THA surgeries; the median age was 62 (range 42–76) years. Seven had Type 1 VWD, one had Type 3 and four had Types 2A, 2B or 2M VWD. The 19 surgical episodes were matched to 38 control surgeries. Indications for arthroplasties were mainly degenerative joint disease in both subject groups. The median BMI was 30 (range 21–45) in the VWD patients and 31.9 (20–53) in controls. Three patients with mild Type 1 VWD received during 5 surgeries only one preoperative dose of DDAVP (desmopressin 0.3μg/kg body weight). Infusions of VWF/FVIII concentrates (Humate-P or occasionally Koate-DVI) were prescribed for twelve procedures, with median preoperative dose 52 IU/kg (range 19–71). Postoperative maintenance doses were infused once or twice daily usually for up to 7 days (more than 7 days only for one Type 3 and one Type 2A VWD patient), with median ranges 22 to 38 IU/kg, and highest dose 90 IU/kg and lowest dose 11 IU/kg (typically when treatment was administrated twice daily). These substantial ranges may be explained by dose adjustments based on monitoring postoperative plasma levels of VWF:RCo and FVIII:C. The median number of infusions per procedure was 5.5 (range 1–13). One hour after the preoperative dose the median of all factors was more than 110 IU/dL, specifically VWF:RCo 154 UI/dL (range 72–277), VWF:Ag 178 IU/dL (range 101–307), and FVIII:C 114 IU/dL (range 64–290). The lowest factor levels measured during daily postoperative follow-up are represented in Figure 1. Assessment of red blood cell transfusion requirements showed no difference between baseline and D1 blood hemoglobin levels for VWD and control groups (decline of 3.0 g/dL). During follow-up, hemoglobin levels and total blood losses were also not different between both groups. However, the number of patients transfused was twice as high for the VWD group (63% vs 32% for controls, respectively), and the mean number of RBC units transfused was higher in VWD patients than in controls (1.5 vs. 0.6 units, respectively). DVT prophylaxis (low molecular weight heparin (LMWH) injections or warfarin), was administrated to 58% of VWD patients vs. 97% of controls. No postoperative thrombotic events were identified in either group. Finally, the median duration of hospitalization for VWD patients and controls was not different: 5 days (range 3–13) and 5 days (range 3–7) respectively. Conclusions: Few data are available in published literature analyzing treatment regimens and hemostatic outcomes for patients with VWD undergoing THA or TKA, a relatively common treatment for advanced degenerative joint disease. This is the first large retrospective study which reports the effectiveness of prophylactic regimens specifically in joint replacement for patients with VWD. Our results support that, as recommended in the 2008 NHLBI/NIH treatment guidelines, monitoring of plasma VWF and FVIII levels at least once daily allows for efficient and relatively low dose maintenance administration. Further, our study helps identify an adequate duration of treatment for these major surgeries, without substantively increased blood loss for VWD patients compared with controls. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 4201 Background: Hereditary AT deficiency is classified as type 1 (quantitative) or type 2 (qualitative). Type 2 deficiency can be further subdivided into type 2a (reactive center loop [RCL]), type 2b (heparin binding domain), and type 2c (pleiotropic) based on functional and molecular AT analysis. Patients with heterozygous type 2b AT deficiency are thought to be at a lower risk for venous thromboembolism (VTE). Objectives: 1) To estimate the frequency of type 2 hereditary AT deficiency. 2) To utilize molecular analysis to accurately sub type patients with type 2 defects. 3) To correlate thrombotic and obstetric complications with AT deficiency sub types. Methods: Apparently unrelated Mayo Clinic AT-deficient patients (n=20) were categorized as type 1 or 2 based on plasma AT activity and antigen, or by molecular analysis for previously reported type 2a-c mutations. Demographic and clinical characteristics were abstracted from patient medical records. The SERPINC1 putative promoter region, all exons (n=7) and splice junctions, and the 3′UTR were PCR amplified from leukocyte genomic DNA, and sequenced with nested forward and reverse primers. For patients without identifiable mutations, multiplex ligand-dependent probe amplification (MLPA) was performed. Results: Out of 20 probands tested 7 (35%) had type 2 AT deficiency. The mean patient age at diagnosis was 36 years (range 18–65) and 5 (69%) were women. There were 2 patients with type 2a, 4 with type 2b (including 1 with a homozygous defect), and 1 with type 2c AT deficiency. The mean plasma AT (range) activity/antigen for these patients were 50% (37-67%)/93% (78-103%) [AT activity & antigen normal range=80-130%]. 6 patients had a previously described mutation, whereas 1 had a novel mutation [S380R] affecting the RCL (Table1). All patients with type 2a and type 2c AT deficiency had unprovoked VTE occurring at a young age. All 3 patients with heterozygous type 2b AT deficiency had no VTE or obstetric complications. One patient with a homozygous type 2b defect (AT Vienna) presented with an unprovoked DVT at age 15. One family with AT Toyama (type 2b AT deficiency) had 5 asymptomatic adult family members with the mutation. Background: Molecular testing is important for an accurate subtyping of patients with type 2 AT deficiency. Type 2 defects have a diverse clinical spectrum. Patients with heterozygous type 2b AT deficiency have a low rate of VTE and obstetric complications. Homozygous type 2b AT deficiency can be compatible with adult life. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 3660 Background: Evidence based guidelines for management of acute coronary syndrome (ACS) in patients (pt) with congenital hemophilia A & B (HA/HB) and von Willebrand disease (VWD) are lacking and confined to case reports and expert opinion (Schutgens et al, 2009). Aims: To review the management of ACS in patients with HA/HB and VWD followed at the Mayo Comprehensive Hemophilia Center. Methods: All pt with HA/HB and VWD who presented with symptoms of ACS to our institution between 2000 and 2010 were retrospectively identified using the hemophilia center database. Medical notes were reviewed, focusing on types of intervention and bleeding complications. Results: Ten pt, HA = 3 and VWD=7, experienced 13 ACS or suspected ACS events. Median age at time of event was 74 years (45 – 80 years), with M:F = 7:3. All 13 events presented with chest pain. 6/13 events presented to the emergency department (ED), 4/13 events presented to a Mayo outpatient clinic, 2/13 events occurred in hospitalized pt and 1 event was a direct referral from a non-Mayo outpatient clinic to our Cardiology in-patient service. ED pt received 325 mg aspirin (HD-ASA) in 5/6 events and intravenous unfractionated heparin (UFH) in 4/6 events, per ACS management guidelines. One ED pt did not receive either ASA or UFH due to atrio-venous malformation (AVM)-related gastrointestinal (GI) bleed (Hg 6 g/dL). Of the inpatients, one received HD-ASA while the other was already on daily low-dose aspirin (LD-ASA); neither received UFH. The pt admitted directly to the Cardiology in-patient service received HD-ASA but not UFH. Of the outpatients, one was started on LD-ASA while another was already on LD-ASA; none received UFH as they were considered low-risk for ACS but warranted further diagnostic evaluation. Coronary angiography (CA) via a right femoral arterial approach was performed in 12/13 events; of which 5 received prophylactic factor concentrate prior to CA. One pt (no prior prophylaxis) experienced minor bleeding at the puncture site, requiring factor concentrate replacement post-CA. Another patient continued to receive prophylactic factor concentrate for 4 days post-CA. Major bleeding or bleeding requiring red blood cell (RBC) transfusion did not occur. Following CA, in 2/12 events, pt underwent bare metal stent (BMS) placement and glycoprotein 2b/3a inhibitor infusion, with no bleeding complications. In 4/12 events, pt proceeded to coronary artery bypass grafting (CABG) and received prophylactic factor concentrate; of which one required multiple post-operative RBC transfusions due to ongoing AVM-related GI bleed. The remaining 6 events were managed medically. The 1 pt who did not undergo CA experienced a post-total knee replacement ACS and was medically managed. On discharge, in 5/13 events, pt were started on daily ASA (HD-ASA, n=2; LD-ASA, n=3). 2 of these received a month of clopidogrel, in addition to LD-ASA, due to BMS placement and were not placed on prophylactic factor concentrate for the duration of dual anti-platelet agent therapy; there were no bleeding complications. Daily ASA was continued in 4/13 events (HD-ASA, n=1; LD-ASA, n=3), with 1 patient receiving both LD-ASA and a month of warfarin for DVT prophylaxis post-orthopedic surgery. In the remaining 4 events, pt were dismissed without ASA, due to bleeding complications (n=2) or the perceived risk of bleeding outweighed the benefit (n=2). During long term follow-up, 1 patient had to stop HD-ASA after 2 years due to GI bleed, while another patient stopped LD-ASA due to episodic epistaxis requiring nasal packing. Conclusion: In this small series of patients, outcomes of management of ACS did not result in significant acute bleeding complications. In addition, long-term treatment with anti-platelet agents appears to be safe and should be strongly considered for all patients with coronary artery disease. Disclosures: No relevant conflicts of interest to declare.

Abstract Background Acquired Factor VIII inhibitor or autoimmune hemophilia A (AHA), has an estimated incidence of up to 1.5 cases per million/year and may result in severe hemorrhagic complications and death. Approximately 50% of cases have an underlying condition such as malignancies, autoimmune disorders and post-partum state. AHA should be suspected in any patient presenting with unexplained bleeding and an inhibited aPTT. Management consists of maintaining hemostasis and elimination of the inhibitor, however management is not standardized. We present 62 cases of AHA managed at Mayo Clinic Rochester, over the course of 36 years. We also analyzed whether aPTT at presentation correlated with the strength of inhibition measured by Bethesda Titer. Methods After IRB approval, medical records of patients with AHA were reviewed and all clinical data collected. Cumulative incidence of death was estimated by Kaplan-Meier analysis. Spearman correlation was used to calculate relation of APTT to Bethesda titer. Results Between 1976 and 2012, we identified 62 patients (male: 35), with a median age at diagnosis of AHA 69 years (mean 64, range 20-86). Clinical presentation consisted of extensive ecchymoses (n=40, 64%) in majority of cases. 29/62 (47%) patients had at least 1 identifiable predisposing condition with 12/62 (19%) patients with an underlying malignancy and 16/62 (26%) with underlying autoimmune conditions. Median Bethesda titer was 29 (range 1 to 1178). Bethesda titer was not related to the number or duration of hospitalizations. Most (69%) patients had at least one hospitalization and 12 (19%) had more than one hospitalization for bleeding complication. Inpatient therapy for bleeding consisted most commonly of FEIBA in 21 pts (34%) and rFVIIa in 6 pts (10%). Prednisone was the most common immunosuppressant used in 54 (87%) patients while Rituximab was used in 11 (18%) patients. Of 32 patients with available follow up labs most (69%) achieved remission. There was no difference in remission rates between patients treated or not treated with Rituximab (p=0.1735). Conclusion Acquired Hemophilia A is a rare condition with very heterogenous presentation. It affects mostly older male patients who present with ecchymoses and elevated APTT. The degree of APTT prolongation at the time of diagnosis does not correlate with the strength of the Bethesda titer and should not guide choice of therapy in a patient presenting with an acute bleed. Rituximab use in the 11 patients treated at Mayo did not seem to influence remission rates or survival. Disclosures: No relevant conflicts of interest to declare.

Abstract Background Based on data from the CDC, over the next 20 years, approximately 12,500 patients (pt) with bleeding disorders will require a screening colonoscopy. For a 75 kg adult receiving an average factor dose of 35 units/kg, this translates into utilization of approximately 30 million units over this time period which will vary with pt weight and disease severity. In the absence of evidence based guidelines, current practice is to provide prophylactic clotting factor concentrates to all such pt. Herein we report our institutional experience. Materials and Methods Retrospective chart review of Mayo Comprehensive Hemophilia Treatment Center pt undergoing colonoscopies. Eligible pt had congenital von Willebrand disease (VWD), hemophilia A (HA) and B (HB). Data collected included pt demographics, factor concentrate and antifibrinolytic agent use, biopsy and polypectomy procedures, and bleeding complications (up to 1 month). Results From 1993-2013, 69 pt underwent 130 colonoscopies, 40/69 (58%) were males. Median (range) age at the time of the procedure was 60 years (3 to 87). The distribution of diagnoses were as follows: HA mild n=13, moderate n=5, severe n=5 and severe with inhibitor n=1; symptomatic carrier of HA n=2; HB mild n=6, severe n=1; VWD types 1: n=23, 2A: n=5, 2B: n=5, 2M: n=2; 3: n=3. 40/69 (58%) pt had one colonoscopy, the remainder 2 to 8 colonoscopies. The procedures were performed as outpatient in 119 (92%) and as inpatient in 11 (8%). Colonoscopy indications included: GI bleeding (49/130, 38%); screening (32/130, 25%); history of polyps (24/130, 18%); iron deficiency anemia (7/130, 6%); Crohn’s disease (5/130, 4%); diarrhea (4/130, 3%); colon cancer followup (3/130, 2%); abnormal imaging (3/130, 2%); family history of colon cancer, diverticulitis, and ulcerative colitis (combined 3/130, 2%). Of the 130 procedures, 25/130 (19%) received no factor or antifibrinolytic treatment, 58/130 (45%) received pre-procedure prophylactic factor only, 1/130 (1%) received post-procedure factor only, 29/130 (22%) received both, 3/130 (2%) received pre-factor and an antifibrinolytic, 3/130 (2%) received post-factor and an antifibrinolytic, 11/130 (8%) received pre and post-procedure factor and an antifibrinolytic. None received an antifibrinolytic alone. Biopsy was performed in only 56/130 (43%) of colonoscopies. Types of biopsies: polyp 37/56 (66%), mucosal 11/56 (20%), mucosal & polyp 5/56 (9%), lesion 1/56 (2%), lesion & polyp 2/56 (4%). Of the pt receiving a biopsy, 39/56 (70%) received pre-procedure factor and 25/56 (45%) received post-procedure factor. The pt most likely to be biopsied were those with an indication of history of polyps 15/56 (27%), GI bleed 13/56 (23%), screening 10/56 (18%), and Crohn’s disease/colon cancer follow up/ diarrhea/iron deficiency anemia each 3/56 (5%). Of the total number of procedures, 39/130 (30%) underwent a polypectomy. Of these, 26/39 (67%) received pre-procedure factor and 17/39 (44%) received post-procedure factor. The average number of polypectomies per patient was 2.3 and the average number of polyps removed per procedure was 3.2. Hemorrhagic complications were noted in 26/130 procedures (13/26 procedural only, 4/26 post-procedure only, 9/26 both), of which 8/26 (31%) were major (requiring hospitalization or RBC transfusion) and 18/26 (69%) were minor (requiring factor or observation). Of all the bleeding complications observed, 15/26 (58%) received factor alone (3/15 major bleeds, 12/15 minor bleeds), 3/26 (11%) received nothing (3/3 minor bleeds), and 8/26 (31%) received a combination of factor concentrate and an antifibrinolytic (5/8 major bleeds, 3/8 minor bleeds). There were 14/56 (25%) pt who underwent a biopsy or polypectomy without receiving any pre/post factor or antifibrinolytic. In 3/14 (21%), there was a minor bleeding complication and in 0/14 (0%), there was a major bleeding complication. No pt experienced colonic perforation. Conclusion In this study, most pt did not receive a biopsy or polypectomy. A risk stratification approach could be taken when deciding on factor concentrate infusions. For low risk pt, factor could be withheld but with post-procedure infusion provided for those undergoing biopsy or polypectomy. For high risk pt, current practices are reasonable. Based on the results presented here and the potential magnitude of impact, this topic deserves further study in a prospective fashion. Disclosures: No relevant conflicts of interest to declare.