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

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..

Acute Bleeding Catastrophe: A FACTOR to consider

Acute Bleeding Catastrophe: A FACTOR to consider. Harkarandeep Singh, R3-RGH IMRP; Peter Kouides, MD, RRH Hematologist Objectives: Explain approach to an actively bleeding patient with a suspected bleeding disorder Describe and understand Acquired Hemophili

Regulation and importance of factor VIII levels in hemophilia A carriers

PURPOSE OF REVIEW: To summarize the recent literature related to female hemophilia A carriers with respect to prevalence in the population, the impact of baseline factor VIII levels and other influences on bleeding phenotype, and clinical management needs. RECENT FINDINGS: Many female hemophilia A carriers are at risk for abnormal bleeding, yet they are underrecognized by healthcare providers and their bleeding symptoms are underreported. Low FVIII levels are consistently associated with clinically significant bleeding and correlate well with skewed X chromosome inactivation (XCI). Most interestingly, bleeding tendency is also observed in some hemophilia A carriers with normal factor VIII levels and requires further investigation. Well controlled studies investigating peripartum and periprocedural FVIII levels and adequate hemostatic treatment are necessary to inform management guidelines. SUMMARY: Prevalence and bleeding tendency of hemophilia A carriers remain underreported, despite a significant proportion having low FVIII levels. Skewed XCI may explain low FVIII but does not explain the bleeding risk encountered in a larger proportion of hemophilia A carriers with random XCI and borderline/normal FVIII

When age is truly only a number: late diagnosis of von Willebrand disease type 2B in a 61-year-old woman

von Willebrand disease (VWD) type 2B is a rare bleeding disorder, presenting with moderate-to-severe lifelong bleeding. We present the case of a 61-year-old woman who was misdiagnosed as immune thrombocytopenic purpura during her three pregnancies resulting in a delayed diagnosis of VWD type 2B. This genetically confirmed diagnosis resulted in testing and the establishment of the diagnosis in her otherwise asymptomatic adult son as well. VWD may not be diagnosed till beyond mid adulthood in women with thrombocytopenia previously attributed to pregnancy and should be considered as a differential in female patients developing thrombocytopenia less than 100 × 10/μl with an increased bleeding assessment tool score

The Many Faces of HLH: Hemophagocytic Lymphohistiocytosis

Objectives: Pathophysiology When to suspect/ Clinical features of the disease Case presentations Making the diagnosis Salient features of treatmen