Preface

Reproductive tract bleeding in women is a naturally occurring event during menstruation and childbirth. In women with menorrhagia, however, congenital bleeding disorders historically have been underdiagnosed. This consensus is intended to allow physicians to better recognize bleeding disorders as a cause of menorrhagia and consequently offer effective disease-specific therapies. © 2009 Mosby, Inc. All rights reserved

Bleeding disorders in adolescents with heavy menstrual bleeding in a multicenter prospective US cohort

Heavy menstrual bleeding is common in adolescents. The frequency and predictors of bleeding disorders in adolescents, especially with anovulatory bleeding, are unknown. Adolescents referred for heavy menstrual bleeding underwent an evaluation of menstrual bleeding patterns, and bleeding disorders determined a priori. The primary outcome was the diagnosis of a bleeding disorder. Two groups were compared: anovulatory and ovulatory bleeding. Multivariable logistic regression analysis of baseline characteristics and predictors was performed. Kaplan Meier curves were constructed for the time from the first bleed to bleeding disorder diagnosis. In 200 adolescents, a bleeding disorder was diagnosed in 33% (n=67): low von Willebrand factor levels in 16%, von Willebrand disease in 11%, and qualitative platelet dysfunction in 4.5%. The prevalence of bleeding disorder was similar between ovulatory and anovulatory groups (31% vs. 36%; P=0.45). Predictors of bleeding disorder included: younger age at first bleed (OR: 0.83; 95%CI: 0.73, 0.96), Hispanic ethnicity (OR: 2.48; 95%CI: 1.13, 5.05), non-presentation to emergency department for heavy bleeding (OR: 0.14; 95%CI: 0.05, 0.38), and International Society on Thrombosis and Haemostasis (ISTH) Bleeding Assessment Tool score ≥4 (OR: 8.27; 95%CI: 2.60, 26.44). Time from onset of the first bleed to diagnosis was two years in the anovulatory, and six years in the ovulatory cohort (log-rank test,

Laboratory misdiagnosis of von Willebrand disease in post- menarchal females: A multi- center study

Increased awareness of von Willebrand Disease (VWD) has led to more frequent diagnostic laboratory testing, which insurers often dictate be performed at a facility with off- site laboratory processing, instead of a coagulation facility with onsite processing. Off- site processing is more prone to preanalytical variables causing falsely low levels of von Willebrand Factor (VWF) due to the additional transport required. Our aim was to determine the percentage of discordance between off- site and onsite specimen processing for VWD in this multicenter, retrospective study. We enrolled females aged 12 to 50- years who had off- site specimen processing for VWF assays, and repeat testing performed at a consulting institution with onsite coagulation phlebotomy and processing. A total of 263 females from 17 institutions were included in the analysis. There were 251 subjects with both off- site and onsite VWF antigen (VWF:Ag) processing with 96 (38%) being low off- site and 56 (22%) low onsite; 223 subjects had VWF ristocetin co- factor (VWF:RCo), 122 (55%) were low off- site and 71 (32%) were low onsite. Similarly, 229 subjects had a Factor VIII (FVIII) assay, and 67 (29%) were low off- site with less than half, 29 (13%) confirmed low with onsite processing. Higher proportions of patients demonstrated low VWF:Ag, VWF:RCo, and/or FVIII with off- site processing compared to onsite (McNemarʼs test P- value <.0005, for all assays). These results emphasize the need to decrease delays from sample procurement to processing for VWF assays. The VWF assays should ideally be collected and processed at the same site under the guidance of a hematologist.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156476/2/ajh25869.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156476/1/ajh25869_am.pd

Phase 1-2a multicenter dose-escalation study of ezatiostat hydrochloride liposomes for injection (Telintra®, TLK199), a novel glutathione analog prodrug in patients with myelodysplastic syndrome

<p>Abstract</p> <p>Background</p> <p>Ezatiostat hydrochloride liposomes for injection, a glutathione S-transferase P1-1 inhibitor, was evaluated in myelodysplastic syndrome (MDS). The objectives were to determine the safety, pharmacokinetics, and hematologic improvement (HI) rate. Phase 1-2a testing of ezatiostat for the treatment of MDS was conducted in a multidose-escalation, multicenter study. Phase 1 patients received ezatiostat at 5 dose levels (50, 100, 200, 400 and 600 mg/m²) intravenously (IV) on days 1 to 5 of a 14-day cycle until MDS progression or unacceptable toxicity. In phase 2, ezatiostat was administered on 2 dose schedules: 600 mg/m²IV on days 1 to 5 or days 1 to 3 of a 21-day treatment cycle.</p> <p>Results</p> <p>54 patients with histologically confirmed MDS were enrolled. The most common adverse events were grade 1 or 2, respectively, chills (11%, 9%), back pain (15%, 2%), flushing (19%, 0%), nausea (15%, 0%), bone pain (6%, 6%), fatigue (0%, 13%), extremity pain (7%, 4%), dyspnea (9%, 4%), and diarrhea (7%, 4%) related to acute infusional hypersensitivity reactions. The concentration of the primary active metabolites increased proportionate to ezatiostat dosage. Trilineage responses were observed in 4 of 16 patients (25%) with trilineage cytopenia. Hematologic Improvement-Erythroid (HI-E) was observed in 9 of 38 patients (24%), HI-Neutrophil in 11 of 26 patients (42%) and HI-Platelet in 12 of 24 patients (50%). These responses were accompanied by improvement in clinical symptoms and reductions in transfusion requirements. Improvement in bone marrow maturation and cellularity was also observed.</p> <p>Conclusion</p> <p>Phase 2 studies of ezatiostat hydrochloride liposomes for injection in MDS are supported by the tolerability and HI responses observed. An oral formulation of ezatiostat hydrochloride tablets is also in phase 2 clinical development.</p> <p>Trial Registration</p> <p>Clinicaltrials.gov: NCT00035867</p

A new hemophilia carrier nomenclature to define hemophilia in women and girls: Communication from the SSC of the ISTH

Hemophilia A and B predominantly attracts clinical attention in males due to X-linked inheritance, introducing a bias toward female carriers to be asymptomatic. This common misconception is contradicted by an increasing body of evidence with consistent reporting on an increased bleeding tendency in hemophilia carriers (HCs), including those with normal factor VIII/IX (FVIII/IX) levels. The term HC can hamper diagnosis, clinical care, and research. Therefore, a new nomenclature has been defined based on an open iterative process involving hemophilia experts, patients, and the International Society on Thrombosis and Haemostasis (ISTH) community. The resulting nomenclature accounts for personal bleeding history and baseline plasma FVIII/IX level. It distinguishes five clinically relevant HC categories: women/girls with mild, moderate, or severe hemophilia (FVIII/IX >0.05 and <0.40 IU/ml, 0.01–0.05 IU/ml, and <0.01 IU/ml, respectively), symptomatic and asymptomatic HC (FVIII/IX ≥0.40 IU/ml with and without a bleeding phenotype, respectively). This new nomenclature is aimed at improving diagnosis and management and applying uniform terminologies for clinical research

The Myriad of Hematological Challenges of COVID-19 Infection

Outline Consequences of the thrombo-inflammatory phenotype of COVID-19 infection - the triad of endothelialopathy, hyperinflammation/hypercoagulation and activation of coagulation Scope and prevalence of thrombotic manifestations Thromboprophylaxis for whom: in out-patients, in-patients - floor vs ICU, post-discharge Thromboprophylaxis at what does: low dose, moderate dose, full dose Vaccine-induced thrombocytopenia and thrombosis (VITT) Red cell and white cells issues Platelets: COVID-19 infections related ITP or exacerbation of known ITP, COVID-19 vaccination related ITP or exacerbation of known IT

Update on Inpatient Thrombosis Prevention and Treatment

Update on Inpatient Thrombosis Prevention and Treatment, Peter Kouides, MD Objectives: Understand the limited role of thrombophilic testing in-house Know when to obtain hematology consult post-discharge Identify several equivalent thromboprophylactic agents for hospitalized patients Know which patients shouild receive post-discharge thromboprophylaxis Know when it is save to use DOAC in very obese patient or in ESRD patien

The Myriad of Hematological Challenges of COVID-19 Infection

The Myriad of Hematological Challenges of COVID-19 Infection, Peter A. Kouides M.D. Medical and Research Director, Mary M. Gooley Hemophilia Center; Clinical Professor of Medicine, University of Rochester School of Medicine; Attending Hematologist, Rochester General Hospital. Outline: Consequences of thrombo-inflammatory phenotype of COVID-19 infection... Scope of prevalence of thrombotic manifestations Thromboprophylaxis for whom... Thromboprophylaxis at what dose... Vaccine-induced thrombocytopenia and thrombosis (VITT) Red cell and white cell issues Platelets..

Rare Coagulation Factor Deficiencies (Factors VII, X, V, and II)

Although rare clotting factor deficiencies primarily referred to as rare bleeding disorders (RBD), including factors II, V, VII, and X, make up ∼5% of all inherited bleeding disorders worldwide, each of these clotting factors play a critical role in the coagulation cascade. Incomplete bleeding evaluation or misinterpretation of laboratory studies can result in delayed diagnoses that ultimately affect patient outcomes. Bleeding manifestations can range from mild to severe, but the most common are mucocutaneous bleeding. The ideal treatment in RBD is dedicated single-factor concentrates that can be used for acute bleeding events, surgical management, and prophylaxis