Management of intracranial surgery for refractory epilepsy in severe factor VII deficiency: choosing the optimal dosing regimen

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106864/1/hae12397.pd

Tissue Plasminogen Activator (Rtpa) Induced Fibrinolysis ‐ Standardization Of Method On Thrombelastography

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106093/1/jth00259.pd

Recommendations for the assessment of non‐extremity venous thromboembolism outcomes: communication from the SSC of the ISTH

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110812/1/jth12809.pd

Emergency department visits in children with hemophilia

Background The pediatric emergency department (ED) management of bleeding and other complications of hemophilia constitutes an increasingly important component of hemophilia therapy. This retrospective study examined the overall ED use by children with hemophilia in a single center, with a particular aim to investigate visits related to injury or bleeding, and those related to blood stream infection in patients with a central venous catheter (CVC). Methods Electronic medical records of patients with hemophilia presenting to Children's Hospital of Michigan ED were reviewed. Different categories of ED visits over a 5‐year period (January 2006–December 2010) were examined. Results There were 536 ED visits from 84 male patients (median age 4 years, range 0–21) with hemophilia over the 5‐year period. The reasons for ED visits were: injury or bleeding (61.2%); suspected CVC‐related infection (11.8%); causes unrelated to hemophilia (19.2%); and routine clotting factor infusion (7.8%). Eighteen visits from six patients were secondary to injury or bleeding in a patient not yet diagnosed with hemophilia. An intracranial hemorrhage was detected in five visits. Overall, 5.4% of all visits represented distinct episodes of bloodstream infection. Conclusion The pediatric ED is an indispensable component of the overall hemophilia care, because: (1) patients with potentially lethal problems such as ICH or CVC‐related infection may present to the ED for their initial management; (2) previously undiagnosed patients with hemophilia may also present to the ED for their first bleeding episodes, initiating the diagnostic investigations; (3) the ED provides after‐hours treatment service for many episodes of injury or bleeding, and also for clotting factor infusion. Pediatr Blood Cancer 2013; 60: 1188–1191. © 2012 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98369/1/24401_ftp.pd

Influence Of Nanopolymers With Different End‐Functionalities On Platelets And Coagulation. An Ex‐Vivo Study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106058/1/jth03252.pd

Recommendations for future research in relation to pediatric pulmonary embolism: communication from the SSC of the ISTH

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142464/1/jth13902_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142464/2/jth13902.pd

ETV6 germline mutations cause HDAC3/NCOR2 mislocalization and upregulation of interferon response genes

ETV6 is an ETS family transcription factor that plays a key role in hematopoiesis and megakaryocyte development. Our group and others have identified germline mutations in ETV6 resulting in autosomal dominant thrombocytopenia and predisposition to malignancy; however, molecular mechanisms defining the role of ETV6 in megakaryocyte development have not been well established. Using a combination of molecular, biochemical, and sequencing approaches in patient-derived PBMCs, we demonstrate abnormal cytoplasmic localization of ETV6 and the HDAC3/NCOR2 repressor complex that led to overexpression of HDAC3-regulated interferon response genes. This transcriptional dysregulation was also reflected in patient-derived platelet transcripts and drove aberrant proplatelet formation in megakaryocytes. Our results suggest that aberrant transcription may predispose patients with ETV6 mutations to bone marrow inflammation, dysplasia, and megakaryocyte dysfunction

Clinical practice: The bleeding child. Part II: Disorders of secondary hemostasis and fibrinolysis

Bleeding complications in children may be caused by disorders of secondary hemostasis or fibrinolysis. Characteristic features in medical history and physical examination, especially of hemophilia, are palpable deep hematomas, bleeding in joints and muscles, and recurrent bleedings. A detailed medical and family history combined with a thorough physical examination is essential to distinguish abnormal from normal bleeding and to decide whether it is necessary to perform diagnostic laboratory evaluation. Initial laboratory tests include prothrombin time and activated partial thromboplastin time. Knowledge of the classical coagulation cascade with its intrinsic, extrinsic, and common pathways, is useful to identify potential defects in the coagulation in order to decide which additional coagulation tests should be performed

Continuous infusion of recombinant activated factor VII: a review of data in congenital hemophilia with inhibitors and congenital factor VII deficiency

Madhvi Rajpurkar,1 David L Cooper2 1Division of Hematology/Oncology, Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Children’s Hospital of Michigan, Detroit, MI, USA; 2Clinical, Medical and Regulatory Affairs, Novo Nordisk Inc., Plainsboro, NJ, USA Introduction: Continuous infusion (CI) of clotting factors as a replacement therapy for perioperative hemostatic protection has been performed for many years, including with factors VIII and IX and recombinant activated factor VII (rFVIIa). This approach provides steady factor levels without requiring frequent administration of bolus doses. Aim: To review safety, efficacy, and dosing data regarding CI of rFVIIa for hemostatic management of patients with congenital hemophilia with inhibitors (CHwI) or congenital factor VII deficiency (C7D). Materials and methods: A literature review identified instances of CI of rFVIIa in patients with CHwI or C7D undergoing surgery or experiencing bleeding episodes. Data regarding safety, efficacy, and dosing were extracted. Results: The safety and efficacy of 50 mcg/kg/h CI of rFVIIa following a 90 mcg/kg bolus injection, vs a standard bolus injection regimen, was reported for 24 patients with CHwI undergoing elective surgery in an open-label, randomized, Phase III trial. Efficacy was similar between CI and bolus injection groups at all postoperative time points assessed. Additionally, a postmarketing surveillance study reported effective (80%) and partially effective (20%) CI of rFVIIa in a Japanese cohort of ten patients with CHwI who underwent 15 surgical procedures. Finally, the safety and dosing of rFVIIa CI in 193 and 26 patients with CHwI and C7D, respectively, were reported in 11 prospective studies, 10 retrospective studies, and 30 case reports. No unexpected safety findings were reported. Conclusion: rFVIIa CI has been performed safely and effectively in patients with CHwI and C7D undergoing surgery and during bleeding episodes in patients with CHwI. Keywords: rFVIIa, continuous infusion, surgery, bleedin