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Hemophilia therapies have tremendously improved over the last decades with the development of prolonged half-life factor VIII (FVIII) and FIX concentrates, non-factor therapies, such as emicizumab, anti-TFPI antibodies or siRNA antithrombin and gene therapy. All of these new molecules significantly reduced the burden of the disease and improved the quality of life of patients with severe hemophilia. Emicizumab, a non-factor therapy, is currently the only subcutaneous molecule available for prophylactic treatment of severe hemophilia A. Because of the subcutaneous route of delivery and similar efficacy to FVIII replacement therapy, emicizumab has been rapidly adopted by patients and their families. This clinical observation emphasizes the relevance and need for the development of subcutaneous FVIII concentrates. Here, we report evidence-based advantages and interest in the subcutaneous route of administration for the treatment of hemophilia A and review the stages of development of the different subcutaneous FVIII molecules.

The challenge of pregnancy can be significant to the point of being life-threatening in a woman with a bleeding disorder. Additionally there can be a risk to the fetus and the neonate. A hemostatic defect can affect the course of the pregnancy, but the impact is most feared around delivery in the immediate and the extended post partum period, requiring rapid identification and prompt referral to a hematologist for assistance in management. Identifying the type of congenital bleeding disorder and knowing its inheritance pattern is crucial during counseling prior to conception and in preparation for delivery. A comprehensive approach by a specialized and experienced team in a tertiary care center with access to adequate laboratory monitoring and therapies can facilitate the process. The multidisciplinary team should include a hematologist, an obstetrician, a pediatric hematologist, an anesthesiologist, and in select cases a clinical geneticist and a maternal fetal medicine specialist. In this review article, we will detail the diagnostic path and management of pregnancy and delivery in women with some inherited bleeding disorders, in particular those affected by hemophilia A (HA), hemophilia B (HB), and von Willebrand disease (VWD).

Introduction Haemophilia A is a rare bleeding disorder caused by defects in coagulation factor VIII (FVIII). Damoctocog alfa pegol (BAY 94–9027, Jivi, Bayer, Germany) is a site-specifically PEGylated, extended-half-life, recombinant FVIII, approved for use in previously treated patients (PTPs) aged ≥12 years with haemophilia A. However, a real-world evidence regarding routine clinical use of damoctocog alfa pegol is limited. Methods and analysis HEM-POWR is a multinational, multicentre, non-interventional, prospective, postmarketing cohort study evaluating the effectiveness and safety of real-world treatment with damoctocog alfa pegol. Estimated enrolment is ≥200 PTPs with haemophilia A, receiving damoctocog alfa pegol (on-demand, prophylaxis or intermittent prophylaxis (as per local label)), observed for 36 months. Primary outcomes are total bleeding events and annualised bleeding rate; secondary outcomes include long-term safety, joint health, pharmacokinetics, patient-reported outcomes (PROs) from validated questionnaires and perioperative haemostasis. Where applicable, reasons for switching to damoctocog alfa pegol, choice of treatment regimen and dose will also be captured. Exploratory and descriptive statistical analyses will be performed, and will be stratified by parameters including, but not limited to, prophylaxis regimen and haemophilia severity. Patients can record bleeds and consumption in electronic (e) Diaries, ePROs, and can access non-promotional study information (videos explaining study procedures) via an online patient portal. Optionally, patients can enrol in the LIFE-ACTIVE substudy designed to investigate the relationship between activity (measured by the ActiGraph CP Insight watch) and effectiveness parameters collected from HEM-POWR. Ethics and dissemination Study approval was obtained by local independent ethics committees and authorities in participating study centres across Europe, the Americas and Asia. Informed consent from patients or their legal representative is a requirement for participation. The study results will be submitted for publication in a peer-reviewed scientific journal and presented at scientific conferences. Trial registration numbers NCT03932201, EUPAS26416. Protocol version and date V.1.2, 27 September 2019.

Introduction Acquired hemophilia A (AHA) is a severe bleeding disorder due to autoantibodies against factor VIII (FVIII) with high morbidity/mortality from bleeding and complications from immunosuppression. Outcomes could improve with adequate hemostatic prophylaxis in the outpatient setting and reduced immunosuppression. Emicizumab, a FVIII-mimetic bispecific antibody, has revolutionized prophylaxis for congenital hemophilia A, but the role in AHA is unknown with limited data. Methods 87 hematologists at different US hemophilia treatment centers (HTCs) were queried on the use of emicizumab for AHA. Pediatric hematologists were excluded given the negligible incidence of pediatric AHA. 10 respondents had experience with off label emicizumab for AHA and were prompted for de-identified data on AHA cases treated with emicizumab at their HTC. These responses were compiled into a central database at the University of Washington under IRB exemption. Results Of the 87 US HTCs queried, 32 reported experience treating AHA; combined, 358 patients with AHA were treated at the 32 HTCs within the last 5 years. 10 respondents (31%) used off label emicizumab for a total of 40 patients with AHA. HTCs that had not used emicizumab for AHA had seen fewer cases of AHA in the last 5 years (average 8 vs 17 patients). Most HTCs (86%) would consider emicizumab if safety data in AHA was available. Of the 10 respondents who used emicizumab for AHA, 7 submitted deidentified data for a total of 24 cases of AHA treated with emicizumab. The median age of subjects was 73 years (range 34-87), 10 were female. The majority (17) were Caucasian. 15 had conditions often associated with AHA: autoimmune disease (7, with 4 on immunosuppression), cancer (6), and peripartum (2). Additionally, one patient had mild congenital hemophilia A and developed an autoantibody to FVIII. Other comorbidities included metabolic syndrome (11), vascular disease (10), prior venous thrombosis (3, none on anticoagulation), alcoholic pancreatitis (1) and Alzheimer's dementia (1). 3 had no comorbidities. At time of diagnosis, 4 were on antiplatelet therapy and 2 on therapeutic anticoagulation, which were discontinued in all cases. The majority presented with bleeding (92%): 63% was spontaneous with most in soft tissue (67%), followed by hematuria (17%), hemarthrosis (8%), retroperitoneal (8%), gastrointestinal (8%), subdural hematoma (4%). At diagnosis, the median FVIII was Emicizumab was mostly started to improve bleeding prophylaxis and/or facilitate outpatient management (Table A). Dosing varied with most receiving the standard loading regimen used for congenital hemophilia A (Table A). Bleeding resolved in most after starting emicizumab (Table B). One patient had new ecchymoses after the first loading dose, which resolved after further doses. 3 patients had breakthrough bleeding on maintenance emicizumab: two had hematuria that resolved with hemostatic agents and in one case a procedure; another had severe gastrointestinal bleeding 4 months after starting emicizumab that required an endoscopy and hemostatic agents (Table B). The majority (95%) tolerated emicizumab without complications. One patient developed a lower extremity deep vein thrombosis (DVT) while on maintenance emicizumab 3 mg/kg every other week. This patient had no history of DVT, but was on apixaban for atrial fibrillation until AHA diagnosis. Anticoagulation was resumed after the DVT. Emicizumab was held for 4 weeks and restarted at 1.5 mg/Kg every other week with no additional adverse events. At the time of the survey, 4 patients had died, of whom 2 were on emicizumab. No deaths were attributed to emicizumab. Of the living patients, 8 remain on emicizumab with persistent inhibitors, with 6 off immunosuppression (Figure One). Conclusion Emicizumab could improve AHA outcomes by providing outpatient hemostatic prophylaxis with lower intensity immunosuppression. Additional safety and dosing data are needed to clarify the role of emicizumab in AHA. Figure 1 Figure 1. Disclosures Poston: TeraImmune: Consultancy. von Drygalski: Hematherix, Inc: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Super FVa; uniQure: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL Behring: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Biomarin: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Research Funding; Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Parnes: Shire/Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees; Genentech/Hoffman LaRoche: Research Funding; Sigilon: Membership on an entity's Board of Directors or advisory committees; Sunovion: Consultancy; I-mAb: Consultancy; Aspa: Consultancy; UniQure: Membership on an entity's Board of Directors or advisory committees. Walsh: Tremeau: Consultancy; Takeda: Consultancy; Biomarin: Consultancy; Genentech: Consultancy; Novo Nordisk: Consultancy. Kessler: Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Octapharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding. Janbain: Bayer: Membership on an entity's Board of Directors or advisory committees, Other: Steering Committee member; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Biomarin: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Malec: CSL Behring: Consultancy; Genentech: Consultancy; HEMA Biologics: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy, Research Funding; Takeda: Consultancy. Kruse-Jarres: Biomarin: Consultancy; Genentech: Consultancy, Research Funding; Genentech/Roche: Speakers Bureau; CSL Behring: Consultancy; CRISPR: Consultancy; Pfizer: Consultancy. OffLabel Disclosure: Emicizumab is FDA approved for congential hemophilia A and is a bispecific monoclonal antibody that binds coagulation factors IXa and X. We will discuss off label use for acquired hemophilia A.

Emicizumab is a recombinant, humanized, bispecific, monoclonal antibody that bridges activated factor IX and factor X to restore the function of deficient factor VIII. Treatment of bleeding in patients with hemophilia and inhibitors involves the use of bypassing agents (BPA).These molecules are also used for the management of breakthrough bleeds in patients on prophylaxis with emicizumab, with increased concerns about the risks of combining two procoagulant drugs. Using thrombin generation assay, we tailored the dosage of activated prothrombin complex concentrate (APCC) and successfully treated an acute spontaneous arterial bleeding in a patient on prophylaxis with emicizumab 1.5mg.kg-1. Low dosages of APCC 15-25U.kg-1 were sufficient to normalize thrombin generation. The patient safely recovered with no thrombotic complications despite multiple infusions of APCC given during a 3-week period. We also showed that recombinant factor IX concentrates might represent an alternative to BPA in treating breakthrough bleeds in patients receiving prophylaxis with emicizumab.

Coronary artery disease (CAD), including stable ischemic heart disease (SIHD) and acute coronary syndrome (ACS), remains the leading cause of death in the US and one of the primary modalities used in the treatment of CAD is percutaneous coronary intervention (PCI). Despite the potential benefits of PCI in high risk CAD patients, the risk of hemorrhage presents a dilemma in the treatment of patients with hemophilia A and B. In an attempt to provide guidance on the management of SIHD and ACS in patients with hemophilia, we present the case of a patient with moderate hemophilia B and ACS who subsequently underwent PCI followed by a review of the associated literature.

Background Patients with congenital Factor XIII (FXIII) deficiency have impaired fibrin stabilization and are at high risk for surgical bleeding. Data regarding the use of FXIII concentrates before and during surgery are lacking. The objective of this study was to report the use of plasma-derived FXIII concentrate (Corifact in the United States; Fibrogammin P in other countries) in patients with congenital FXIII deficiency undergoing surgical procedures. Study Design and Methods FXIII concentrate at preoperative doses ranging from 25 to 40 U/kg was administered to six patients with congenital FXIII deficiency undergoing major or minor surgeries. Results FXIII concentrate was administered immediately before surgery for five surgical cases; three of these patients achieved excellent hemostasis during and after surgery, while two had intraoperative bleeding. In one surgical case, a regular prophylactic dose of FXIII concentrate was administered to the patient 1 week before minor surgery. FXIII concentrate provided rapid replacement of FXIII activity. In all but one of the patients given a dose of FXIII designed to increase FXIII levels more than 50%, there was satisfactory intraoperative and postoperative hemostasis. One patient undergoing aortic valve replacement on cardiopulmonary bypass (CPB) was the exception. Intraoperative bleeding in this patient was associated with lower-than-expected blood levels of FXIII. Conclusion Preoperative plasma-derived FXIII concentrate allowed for sufficient hemostasis in most patients with FXIII deficiencies. Additional doses were necessary to achieve hemostasis in one patient who underwent a CPB procedure.

Introduction Hemophilia is an X linked disorder characterized by an increased tendency to spontaneous bleeding resulting from profound compromise of the hemostatic response with delayed development of a clot and the formation of clots that are vulnerable to fibrinolysis. Optimization of clot stability by adding TXA to low concentrations of factor concentrates may be a way to improve prophylaxis in patients with severe hemophilia (sH) without substantially increasing the cost or the burden of more frequent infusions. Aims We proposed to study whether hemostasis is improved with the addition of TXA to low FVIII plasma concentrations (equivalent to trough levels in prophylactic setting). We specifically studied in vitro the clot stability in patients with sHA; and in vivo the hemostatic response to trauma-induced joint bleed and tail clip in FVIII knock-out (KO) mice. Methods After obtaining informed consent, blood samples of 12 adults with sHA were spiked in vitro to achieve final concentrations (FC) of 0-3-10 and 30 IU/dL of FVIII, then studied with and without TXA at FC 0.1mg/ml. Whole blood (WB) was assessed with ROTEM performed after addition of tPA in 6 patients. Thrombin generation (TG) was measured in plasma (PL) of 6 other patients. Clots obtained from TG were examined under electron microscopy (EM) to evaluate the quality of fibrin clot structure. Diameters of randomly selected 100 fibrin fibers were measured in each clot. In animal studies, 13 FVIII KO mice were given FVIII to a plasma concentration of 3 IU/dL to mimic trough FVIII levels in prophylactic setting; 7 were also infused with TXA (FC 0.1mg/ml). 10 minutes after infusion, joint bleeding was induced by knee puncture using a standardized protocol. 2 days post trauma, MRI was done and the joint bleed (surface of hyper signal into the joint) was compared between the groups with and w/o TXA. 10 other FVIII KO mice were infused with 3 IU/dL rFVIII, of which 5 were also infused with TXA (FC 0.1mg/ml). 10 minutes after infusion, the extremity of the tail was cut at 2mm, and then immersed in pre-heated water-filled tube at 37°C. Blood was collected during 10 minutes. After lysis of erythrocytes, the amount of hemoglobin in collected blood was measured using spectrophotometry; means of optical density (OD) were compared between the 2 groups. Results A dose dependent improvement of TG was observed after adding FVIII alone (p=0.024). As expected, the addition of TXA had no effect on TG capcity. Fibrin fiber diameters were significantly decreased with TXA+FVIII compared to FVIII alone (results shown in fig1), suggesting a stronger fibrin network, as thin fibrin fibers are characteristic of a robust fibrin mesh. Surprisingly, ROTEM was fully normalized after addition of TXA only, with no exogenous FVIII. In FVIII KO mice, the addition of TXA to 3 IU/dL rFVIII significantly decreased joint bleeding compared to 3 IU/dL rFVIII alone (p=0.022) (fig2).With the tail clip experiment, the addition of TXA to 3 IU/dLFVIII showed a trend toward improved bleeding when compared to 3 IU/dLFVIII alone; with means of OD±SEM 0,31±0,19 and 0,94±0,45 respectively, but did not reach statistical significance (p=0,15) (fig3). Conclusion Our in vitro and in vivo results suggest a potential benefit of TXA when used in combination with FVIII in prophylactic setting. Disclosures No relevant conflicts of interest to declare.

A 10-year-old boy presents with a history of severe hemophilia A and high-titer inhibitor that had failed high-dose immune tolerance induction (ITI) with a recombinant factor VIII (rFVIII) product and a plasma-derived FVIII product. You are asked by his mother whether he should be tried on ITI with an extended half-life product, in particular, consideration of a rFVIIIFc concentrate.

Acquired hemophilia A is a rare autoimmune disorder caused by an autoantibody (inhibitor) to factor VIII (FVIII) that interferes with its coagulant function and predisposes to severe, potentially life-threatening hemorrhage. Disease management focuses on controlling bleeding, primarily with the use of bypassing therapy and recombinant porcine FVIII, and permanently eradicating the autoantibody using various immunosuppressants. Treatment challenges include delayed diagnosis, difficulty achieving hemostasis and durable remissions, and complications associated with the use of hemostatic and immunosuppressive therapy in a primarily older patient population.

OBJECTIVES/SPECIFIC AIMS: To explore the racial differences in rotational thromboelastometry findings using whole blood and plasma samples from healthy volunteers. METHODS/STUDY POPULATION: We studied a cohort of patients at Tulane University Hospitals who came into the pre-op clinic to get blood drawn for labs. The cohort included a total of 44 patients who were otherwise healthy adult volunteers with no history of cardiovascular nor thromboembolic events, 30 African Americans and 14 Caucasians. Patients who required lab work for their upcoming surgery were asked to participate in the study by giving a sample of blood collecting in a light blue-top sodium citrate tube. We excluded patients who were currently on any anticoagulation or antiplatelet medications. We also excluded those with current or previous history of cancer, those with known bleeding disorder, and those who were on chronic transfusion protocol, or had received a blood transfusion within the last 21 days. Data collection was carried out after informed consent was obtained; we collected citrated whole-blood (WB) samples. WB samples were processed within 3 hours of phlebotomy. Platelet free plasma, obtained after centrifugation at 2500 cGy of whole blood for 20 minutes, was kept frozen at −70°C. Frozen plasma was thawed at 37°C for 5 minutes before testing. Samples were recalcified with star-tem reagent, and then the in-tem reagent was added. The latter contains an optimized concentration of ellagic acid and partial thromboplastin phospholipid from rabbit brain. Thromboelastometry (ROTEM) parameters including clotting time, clot formation time, alpha angle, maximum clot firmness, and Lysis Index after 30 and 45 minutes were determined. Data was then retrieved from the ROTEM database and put into an Excel sheet to be analyzed. RESULTS/ANTICIPATED RESULTS: Our results showed that the CFT was higher in both the plasma and the WB of Caucasians when compared with African Americans with a difference between means 137.5±233.7 (p=0.56) and 11±7.85 (p=0.168), respectively; while MCF was increased in the WB and plasma of AA with a difference between means of 1.719±1.974 (p=0.38) and 5.37±2.49 (p=0.037), respectively. In other words, the plasma of Caucasians did seem to take longer to reach the maximum firmness (however not statistically significant p>0.05), while the maximum clot firmness was significantly higher in plasma of AA. In summary and compatibly with the previously published data, our results showed significantly increased prothrombotic profile in the plasma of African Americans when compared with Caucasians. DISCUSSION/SIGNIFICANCE OF IMPACT: This reinforces the role of the whole vascular system and the interaction between its different components in the pathophysiology of thromboembolic events. In one case control study, African ethnicity was associated with increased risk of DVT in parallel with significantly increased peak thrombin on thrombin generation when compared with Caucasians. With our preliminary results, we confirm these data using another tool for the assessment of the plasma in addition to comparing WB samples too. More prospective studies, with higher number of subjects evaluating the value of the results in predicting the risk of development of thromboembolic events in different ethnicities, are needed for better understanding of this disease. In addition, thromboelastometry might require adjustment for ethnicity in studies evaluating ethnically diverse populations.

Background: Plasmablastic lymphoma (PBL) is an aggressive subtype of non-Hodgkin's lymphoma (NHL). While classically associated with the human immunodeficiency virus (HIV), cases of PBL in immunocompetent patients have been increasingly described. PBL shares common morphological and immunohistochemical features with diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM). Due to the rarity of PBL, there is no current consensual standard therapy available. As a result, PBL treatment is mirrored after aggressive NHL regimens. One of the newly emerged therapeutic options for PBL is bortezomib, which is a proteasome inhibitor and a cornerstone in MM therapy. In recently published cases, bortezomib has shown promising results in PBL. Case Report: In this report, we describe a patient with HIV-negative PBL who dramatically responded to bortezomib after failing several other lines of therapy. We also review 4 other, similar cases reported in the literature. Results and Conclusion: We conclude that bortezomib resulted in rapid and dramatical responses regardless of the line of therapy. Although most of these responses were not sustained, bortezomib represents a new therapeutic option for PBL that should be further explored in larger clinical trials.

Racial differences in the incidence of arterial and venous thrombotic events are well established in literature, with a higher incidence noted in African Americans compared to Caucasians. Several studies have tried to explain this difference, by looking separately at chemical biomarkers, socioeconomic and clinical risk factors. Yet the exact reason behind this disparity remains unclear. At least one study of thrombin generation suggested that African ethnicity was associated with increased peak thrombin generation when compared to Caucasians. Rotational thromboelastometry is a visco-elastic methodology that offers a global assessment of hemostasis using either whole blood or plasma. We explored the racial differences in rotational thromboelastometry findings using plasma samples from healthy volunteers. We studied a cohort of 9 otherwise healthy adult volunteers with no history of cardiovascular nor thromboembolic events, 5 African Americans and 4 Caucasians. After informed consent, we collected citrated whole blood samples and processed them within 3 hours of phlebotomy. Platelet free plasma, obtained after centrifugation of whole blood for 20 minutes, was kept frozen at -70°C, and then thawed at 37°C for 5 minutes prior to testing. Samples were re-calcified with star-tem® reagent, and then the in-tem® reagent was added. The latter contains an optimized concentration of ellagic acid and partial thromboplastin phospholipid from rabbit brain. Thromboelastometry parameters including Clot Formation Time, Alpha Angle, and Maximum Clot Firmness were determined. We then compared the data between the two study populations using parametric unpaired Student’s t-test. Our results showed that the Clot Formation Time was higher in the plasma of Caucasians when compared to African Americans with a difference between means of 40.1 ± 4.4 seconds (p Despite the limited number of participants, the striking observed differences in the thromboelastometry parameters suggest that global assays may offer benefit in assessing thrombotic risks in disparate patient populations, as they incorporate multiple components of the hemostatic system. Higher numbers of subjects and assessment of both whole blood and plasma are indicated. We are currently in the process of expanding our cohort to confirm these preliminary results. Disclosures No relevant conflicts of interest to declare.

Background Vaso-occlusive phenomena and hemolysis are the clinical hallmarks of sickle cell disease (SCD). In addition, pain crisis was identified as the initial clinical manifestation in 61.9% of sickle cell patients who died shortly after hospital admission from thromboembolism and micro vascular thrombi. Knowing that the vaso-occlusive events may be related to activation of the hemostatic system, and that thromboelastometry (TEM) assesses the functionality of this system from a global standpoint, it will be challenging to characterize the findings in patients with SCD as a way to differentiate their clinical phenotype upon presentation, and to predict the impact of these manifestations on their prognosis, mortality and morbidity. Objective To characterize the findings of TEM in patients with SCD during periods of steady state and acute illness, to compare these results with those of healthy controls and sickle cell trait (SCT), to compare the findings in whole blood (WB) to plasma (PL) for each category, in a way to analyze the findings in plasma and their applicability in clinical practice as well as to delineate the contribution of the cellular component in whole blood samples. Design In a cross-sectional study, we obtained TEM and other hemostatic data on 24 adult patients with SCD (16 in steady state and 8 in acute illness); and 13 race and age matched healthy controls (6 with sickle cell trait (SCT) and 7 with no trait). We specifically studied coagulation time (CT) as a function of coagulation factors; clot firmness time (CFT) and alpha angle(α) assessing platelet and fibrinogen function; and maximum clot firmness (MCF) evaluating the mechanical clot quality (plt, fibrinogen and factorXIII) and finally thrombodynamic potential index (TPI) as a function of patient’s global coagulation. Results Overall, patients with SCD had higher TPI in WB (p=0.23;=0.25) and lower TPI in PL (p Conclusion Whole blood of SCD patients seems to be hypercoagulable in comparison to WB of controls and SCT. While the plasma of SCD patients was significantly hypocoagulable when compared to PL of healthy controls. Overall, TEG profiles of WB were different than PL. This was more obvious in SCD patients reinforcing the contribution of the cellular component to the pathophysiology of this disease and the possible compensatory hypocoagulable status of the plasma in these patients. Further study of larger and more homogeneous patient groups, is required to adequately assess the clinical utility of TEM in patients with sickle cell disease. Disclosures: Kruse-Jarres: Baxter Healthcare: Consultancy; Bayer HealthCare: Consultancy; Biogen IDEC: Consultancy; Grifols: Consultancy; Kedrion: Consultancy; Novo Nordisk: Consultancy.

Abstract 4632 Background: FXIII is an essential component of normal hemostasis. Congenital deficiency of FXIII activity is a rare autosomal recessive bleeding disorder with an estimated incidence of one in 3–5 million. A fibrin-stabilizing FXIII concentrate that provides both A and B subunits of FXIII was FDA approved last year for routine prophylactic treatment of congenital FXIII deficiency. There are few data available on replacement of FXIII concentrate in patients with congenital deficiency undergoing surgery and there is no published information on managing FXIII deficient patients undergoing cardiopulmonary bypass (CPB) surgery. It is known that FXIII levels decrease in normal individuals who are placed on the cardiopulmonary bypass pump. Patients/Methods: A 52 year old man with congenital FXIII deficiency (baseline level 20%) underwent an aortic valve replacement. On the day of surgery, immediately prior to intubation, he was given a dose of FXIII concentrate (42 U/kg) which had previously been shown to correct his FXIII level to 100%. Early in surgery, the patient became hypotensive and did not respond to vasopressors, so the chest was opened urgently, internal CPR was performed and the patient was placed on cardiopulmonary bypass. He experienced heavy, poorly controlled bleeding intraoperatively. Factor XIII levels were checked intraoperatively at 3 hrs and 7 hrs post administration of the pre-op FXIII dose, and were 40% and 43% respectively. These levels were considerably lower than expected based on FXIII pharmacokinetic studies done 2 weeks prior to surgery. He received an additional dose of FXIII concentrate (42 U/kg) 8 hours after the original pre-op dose. During surgery he also received 9 units of PRBCs, 3 units of platelets, 7 units of FFP and a single dose of rFVIIa (90 mcg/kg) during the period of excessive bleeding, with ultimate control of bleeding; the patient was transferred to the surgical ICU 6 hours after the surgery was started. He recovered uneventfully and his post-operative FXIII levels were consistent with the published FXIII concentrate half-life of 6–8 days. Discussion: Studies have shown that plasma levels of FXIII decrease by 10–33% in a general population of patients undergoing CPB surgery which is presumed to be due to FXIII consumption during extracorporeal circulation. This raises concerns for effective replacement of FXIII in cases of congenital FXIII deficiency. In the case presented, FXIII levels were approximately 60% lower than anticipated based on pre-surgical pharmacokinetic testing of exogenous FXIII concentrate, and likely resulted in significant clinical bleeding intraoperatively. Further information is needed on surgical management, especially in cases involving extracorporeal circulation; collection of such cases in a registry may be helpful to improve our understanding on how to care for these patients. For now, we recommend using an increased dose of FXIII prior to such surgeries as the 100% correction dose determined in a preoperative challenge test was not enough to restore this patient's FXIII levels during surgery and prevent intraoperative bleeding. Disclosures: Off Label Use: FXIII CONCENTRATE IN SURGERY. Leissinger:CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.