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The assessment of hemostatic disorders in neonates is crucial, but remains challenging for clinicians. Although the concept of developmental hemostasis is widely accepted among hemostasis specialists globally, it is probably under-recognized by clinicians and laboratory practitioners. In parallel with age-dependent hemostatic status maturation, comprehension of the differences between normal values is crucial for the accurate diagnosis of potential hemorrhagic and thrombotic disorders of the vulnerable neonatal population. This review outlines the basics of developmental hemostasis and the features of the available coagulation testing methods, with a focus on novel tools for evaluating the neonatal hemostatic profile. Common errors, issues, and pitfalls during the assessment of neonatal hemostasis are discussed, along with their impact on patient management. Current knowledge gaps and research areas are addressed. Further studying to improve our understanding of developmental hemostasis and its reflection on everyday clinical practice is warranted., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: Clinicians often order the international normalized ratio (INR) and activated partial thromboplastin time (APTT) to evaluate for the possibility of inherited bleeding disorders despite sensitivities and specificities of 1%-2%. The most accurate tool to evaluate for bleeding disorders is a validated bleeding assessment tool (BAT). Our aim was to reduce coagulation testing by >50% in a large family practice in Ontario, Canada., Methods: We conducted an implementation study from May 2016 to February 2020. Iterative interventions included introduction of a validated BAT into the electronic medical record (EMR); removal of the APTT as a prepopulated selection from the laboratory requisition; and education targeting family medicine teams and laboratory personnel. The primary outcome was the rate of pre- and post-APTT testing. Creatinine testing was the control. Data were analyzed via an interrupted time series analysis using Stata 13., Results: Immediately following education of the laboratory personnel on coagulation testing, the APTT rate level dropped by 1.26 tests per 100 patient visits per month ( p  < 0.001) and was sustained until the end of the study. Meanwhile, the PT/INR and creatinine testing rate levels did not change (rate level = -0.02 per 100 visits per month, p  = 0.79 and 0.49, p  = 0.22 respectively). There was good uptake of the BAT following integration and 18/88 (20%) obtained a referral to hematology after BAT completion., Conclusions: Multidisciplinary, iterative interventions reduced APTT testing and enabled the use of BATs to guide hematology referrals in a large family practice., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Endothelial dysfunction, one of many causes of arterial changes in end-stage kidney disease (kidney failure), is a likely link between early vascular aging and the risk of thrombosis or bleeding in this condition. To evaluate this, we compared links between arterial stiffness and endothelial/coagulation factors in 55 patients receiving hemodialysis therapy and 57 age-/sex-matched control individuals. Arterial stiffness was assessed from carotid-femoral pulse wave velocity, and coagulation status from the endogenous thrombin generating potential. Markers of endothelial dysfunction (von Willebrand factor, tissue factor pathway inhibitor), neutrophil extracellular traps and tissue factor-positive extracellular vesicles were higher in patients with kidney failure. Prothrombin fragments 1 and 2, and D-dimer markers of in vivo coagulation activation were also higher. However, in vitro in the presence of platelets, endogenous thrombin generating potential was lower and its downregulation by activated protein C impaired. Antiplatelet drugs did not affect these parameters. In multiple regression analysis, prothrombin fragments 1 and 2, D-dimer, factor VIII and monocyte-derived tissue factor-positive extracellular vesicles correlated with higher carotid-femoral pulse wave velocity. In patients with kidney failure, in vivo hypercoagulability occurred with reduced thrombin generation in platelet-rich plasma, likely explaining the opposing thrombotic and bleeding tendencies in patients with kidney failure. Importantly, arteriosclerosis is more closely related to a prothrombotic state. Thus, coagulation changes plus arterial stiffness highlight a major therapeutic challenge for anticoagulant and antiplatelet drug use., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Bleeding disorders (BD) are under-recognized in adolescents with heavy menstrual bleeding (HMB)., Objectives: The lack of clinical guidelines and variable symptomatic management of HMB created the imperative to standardize HMB care to identify and manage BD in adolescents., Methods: We convened an international working group (WG), utilized the results of a literature review to define knowledge gaps in HMB care, and used the collective clinical experience of the WG to develop care considerations for adolescents with BD and HMB. We then solicited input on the appropriateness of HMB care considerations from expert stakeholders representing hematology, adolescent medicine, and obstetrics-gynecology. We conducted an expert panel online, using the ExpertLens platform. During a three-round online modified-Delphi process, the expert panel rated the appropriateness of 21 care considerations using a 9-point scale to designate care as appropriate (7-9), uncertain (4-6), or inappropriate (1-3) covering screening for BD, the laboratory work-up, and management of adolescents with BD that present with HMB. We used the RAND/UCLA appropriateness method to determine the existence of consensus among the interdisciplinary panel of experts., Results: Thirty-nine experts participated in the panel. The experts rated fifteen HMB care considerations as appropriate, six as uncertain, and none as inappropriate., Conclusions: The HMB care statements represent the first set of HMB care considerations in adolescents with BD, developed with broad expert input on appropriateness. Although likely to be of interest to a range of clinicians who routinely manage adolescents with HMB, additional research is required in many key areas., (© 2020 International Society on Thrombosis and Haemostasis.)

Essentials Ehlers-Danlos Syndrome (EDS) is a rare heterogeneous group of inherited collagen disorders. A cohort of EDS patients was investigated for bleeding tendency and hemostatic abnormalities. EDS is associated with an increased risk of bleeding. EDS patients have platelet function abnormalities, whose severity correlates with bleeding risk. SUMMARY: Background Ehlers-Danlos syndrome (EDS) includes a heterogeneous group of connective tissue disorders affecting skin, bones, vessels, and other organs. Patients with EDS have an increased risk of bleeding, but a comprehensive study of hemostasis in EDS patients is lacking. Objective To investigate the bleeding tendency of a cohort of patients with EDS by using the Bleeding Assessment Tool of the ISTH, the bleeding severity score (BSS). Methods The BSS was defined as abnormal when it was ≥ 4 in men and ≥ 6 in women. Patients with a bleeding tendency were compared with those without in terms of type and number of hemostatic abnormalities. Results Fifty-nine of 141 patients with EDS (41.7%) had an abnormal BSS. Prothrombin time and activated partial thromboplastin time were slightly prolonged in 10 patients (7.1%) because of mild coagulation factor deficiencies, which were not responsible for the bleeding diathesis. von Willebrand factor antigen, ristocetin cofactor, endogenous thrombin potential and platelet count were normal in all patients. At least one platelet function abnormality was found in 53 patients (90%) with an abnormal BSS and in 64 (78%) with a normal BSS (adjusted odds ratio [OR] 2.55, 95% confidence interval [CI] 0.87-7.48). The risk of bleeding progressively increased with the number of platelet function abnormalities, reaching an OR of 5.19 (95% CI 1.32-20.45) when more than three abnormalities were detected. Conclusions Our results show that nearly half of patients with EDS have an abnormal BSS, which, in 90% of cases, appear, at least in part, to be attributable to platelet function abnormalities. Abnormalities of primary hemostasis may contribute to the risk of bleeding in patients with EDS., (© 2018 International Society on Thrombosis and Haemostasis.)

The past few decades have seen major advances in multidisciplinary obstetric care and management of gynecological conditions in women with bleeding disorders. Awareness of the impact of bleeding disorders has improved among the obstetric and gynecological community. Undiagnosed bleeding disorders can be the underlying cause for a significant proportion of women with heavy menstrual bleeding. They may also be the cause or a contributory factor for other gynecological problems, such as dysmenorrhea, intermenstrual bleeding, and endometriosis. Hemostatic assessment should be considered in women referred for menstrual abnormalities if they have a positive bleeding history as quantified by bleeding assessment tools. The reproductive choices and options for prenatal diagnosis are also expanding for families with hemophilia with a drive toward achieving a non-invasive approach. Current non-invasive prenatal diagnostic techniques are limited to identification of fetal gender. Research is ongoing to overcome the specific diagnostic challenges of identifying hemophilia mutations, utilizing free fetal DNA circulating in maternal plasma. The management of obstetric hemorrhage has recently evolved to include a greater focus on the identification of and early treatment for coagulation disorders. Deficiencies in certain hemostatic variables are associated with progression to more severe bleeding; therefore, specific interventions have been proposed to target this. Evidence is still lacking to support such strategy, and future research is required to assess the efficacy and the safety of these hemostatic interventions in women with persistent PPH., (© 2013 International Society on Thrombosis and Haemostasis.)