The impact of hematology electronic consultations on the management of iron deficiency.

Objectives: Delays in the evaluation and treatment of iron deficiency can lead to increased disease-related morbidity and mortality. Electronic consultation (e-consult) is a referral modality that allows providers quicker access to recommendations from a specialist based on electronic chart review. While the use of e-consult is expanding in classical hematology, gaps exist in the understanding of patient outcomes related to its use for iron deficiency.

Factor XI Inhibition for the Prevention of Catheter-Associated Thrombosis in Patients With Cancer Undergoing Central Line Placement: A Phase 2 Clinical Trial.

Background: Despite the ubiquitous utilization of central venous catheters in clinical practice, their use commonly provokes thromboembolism. No prophylactic strategy has shown sufficient efficacy to justify routine use. Coagulation factors FXI (factor XI) and FXII (factor XII) represent novel targets for device-associated thrombosis, which may mitigate bleeding risk.

Psychological toxicity in classical hematology.

Although considered "benign," mild blood count abnormalities, genetic factors imparting inconsequential thrombotic risk, and low-risk premalignant blood disorders can have significant psychological and financial impact on our patients. Several studies have demonstrated that patients with noncancerous conditions have increased levels of anxiety with distress similar to those with malignancy. Additionally, referral to a classical hematologist can be a daunting process for many patients due to uncertainties surrounding the reason for referral or misconstrued beliefs in a cancer diagnosis ascribed to the pairing of oncology and hematology in medical practice.

Clinical outcomes of patients referred for asymptomatic neutropenia: A focus on racial disparities in hematology.

Background: Asymptomatic neutropenia is a common hematology referral, though standardized reference ranges and published clinical outcomes are lacking.

Methods: In our retrospective analysis, we evaluated demographics, laboratory, and clinical outcomes of adult patients referred to an academic hematology practice for evaluation of neutropenia from 2010 to 2018. Primary and secondary outcomes included incidence of hematologic disorders and rates of Duffy-null positivity by race, respectively.

Desmopressin as a hemostatic and blood sparing agent in bleeding disorders.

Intranasal, subcutaneous, or intravenous desmopressin can be utilized to release von Willebrand Factor and Factor VIII into circulation, enhance platelet adhesion and shorten bleeding time. Due to these properties, desmopressin can be effective in controlling bleeding in mild hemophilia A, certain subtypes of von Willebrand disease and in acute bleeding from uremia, end stage renal disease, and liver disease. Its use, however, can be complicated by hyponatremia and rarely arterial thrombotic events.

Ibrutinib Inhibits BMX-Dependent Endothelial VCAM-1 Expression and Pro-Atherosclerotic Endothelial Activation and Platelet Adhesion .

Introduction: Inflammatory activation of the vascular endothelium leads to overexpression of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), contributing to the pro-thrombotic state underpinning atherogenesis. While the role of TEC family kinases (TFKs) in mediating inflammatory cell and platelet activation is well defined, the role of TFKs in vascular endothelial activation remains unclear. We investigated the role of TFKs in endothelial cell activation and in a nonhuman primate model of diet-induced atherosclerosis .

Travel-Associated Venous Thromboembolism.

Introduction: Long-distance travel is assumed to be a risk factor for venous thromboembolism (VTE). However, the available data have not clearly demonstrated the strength of this relationship, nor have they shown evidence for the role of thromboprophylaxis.

Methods: We performed a systematic review of the literature.

Platelet reactivity and platelet count in women with iron deficiency treated with intravenous iron.

Background: Iron deficiency anemia (IDA) and heavy menstrual bleeding are prevalent, interrelated issues impacting over 300 million premenopausal women worldwide. IDA is generally associated with increased platelet counts; however, the effects of IDA and its correction on platelet function in premenopausal women remain unknown.

Objectives: We sought to determine how IDA and intravenous iron affect platelet count and platelet function in premenopausal women.

Severe thrombocytopenia in adults undergoing extracorporeal membrane oxygenation is predictive of thrombosis.

Extracorporeal membrane oxygenation (ECMO) provides lifesaving circulatory support and gas exchange, although hematologic complications are frequent. The relationship between ECMO and severe thrombocytopenia (platelet count <50 × 10/L) remains ill-defined. We performed a cohort study of 67 patients who received ECMO between 2016 and 2019, of which 65.

The contact activation inhibitor AB023 in heparin-free hemodialysis: results of a randomized phase 2 clinical trial.

End-stage renal disease (ESRD) patients on chronic hemodialysis have repeated blood exposure to artificial surfaces that can trigger clot formation within the hemodialysis circuit. Dialyzer clotting can lead to anemia despite erythropoietin and iron supplementation. Unfractionated heparin prevents clotting during hemodialysis, but it is not tolerated by all patients.

Thrombosis and Bleeding in Extracorporeal Membrane Oxygenation (ECMO) Without Anticoagulation: A Systematic Review.

Extracorporeal membrane oxygenation (ECMO) causes both thrombosis and bleeding. Major society guidelines recommend continuous, systemic anticoagulation to prevent thrombosis of the ECMO circuit, though this may be undesirable in those with active, or high risk of, bleeding. We aimed to systematically review thrombosis and bleeding outcomes in published cases of adults treated with ECMO without continuous systemic anticoagulation.

Factor XII plays a pathogenic role in organ failure and death in baboons challenged with Staphylococcus aureus.

Activation of coagulation factor (F) XI promotes multiorgan failure in rodent models of sepsis and in a baboon model of lethal systemic inflammation induced by infusion of heat-inactivated Staphylococcus aureus. Here we used the anticoagulant FXII-neutralizing antibody 5C12 to verify the mechanistic role of FXII in this baboon model. Compared with untreated control animals, repeated 5C12 administration before and at 8 and 24 hours after bacterial challenge prevented the dramatic increase in circulating complexes of contact system enzymes FXIIa, FXIa, and kallikrein with antithrombin or C1 inhibitor, and prevented cleavage and consumption of high-molecular-weight kininogen.

Heparin Resistance Is Common in Patients Undergoing Extracorporeal Membrane Oxygenation but Is Not Associated with Worse Clinical Outcomes.

Extracorporeal membrane oxygenation (ECMO) protocols generally require systemic anticoagulation with heparin to prevent circuit thrombosis. The prevalence, risk factors, and outcomes of heparin resistance in this setting are ill-defined. To better understand the prevalence and clinical consequences of heparin resistance in this population, we conducted a retrospective analysis of all patients treated with ECMO at a single academic medical center between 2016 and 2019.

The efficacy and safety of thrombopoietin receptor agonists in patients with chronic liver disease undergoing elective procedures: a systematic review and meta-analysis.

Thrombopoietin receptor agonists (TPO-RAs) can mitigate preprocedural thrombocytopenia in patients with chronic liver disease (CLD) however their effects on procedural outcomes is unclear. In this meta-analysis, we aimed to better define the efficacy, thrombotic risk and bleeding mitigation associated with the use of preoperative TPO-RAs in patients with CLD. We performed a systematic review and meta-analysis of randomized placebo-controlled clinical trials to assess the use of preprocedural TPO-RAs in patients with CLD, searching MEDLINE, EMBASE and the Cochrane library database.

Anticoagulation strategies in extracorporeal circulatory devices in adult populations.

Extracorporeal circulatory devices such as hemodialysis and extracorporeal membrane oxygenation can be lifesaving; however, they are also prone to pathologic events including device failure, venous and arterial thrombosis, hemorrhage, and an accelerated risk for atherosclerotic disease due to interactions between blood components and device surfaces of varying biocompatibility. While extracorporeal devices may be used acutely for limited periods of time (eg, extracorporeal membrane oxygenation, continuous venovenous hemofiltration, therapeutic apheresis), some patients require chronic use of these technologies (eg, intermittent hemodialysis and left ventricular assist devices). Given the substantial thrombotic risks associated with extracorporeal devices, multiple antiplatelet and anticoagulation strategies-including unfractionated heparin, low-molecular-weight heparin, citrate, direct thrombin inhibitors, and direct oral anticoagulants, have been used to mitigate the thrombotic milieu within the patient and device.

A multicenter study evaluating the effectiveness and safety of single-dose low molecular weight iron dextran vs single-dose ferumoxytol for the treatment of iron deficiency.

There are multiple intravenous (IV) iron formulations available, of which several may be administered as single-dose infusions such as low-molecular weight iron dextran (LMWID), ferumoxytol, ferric carboxymaltose, and ferric derisomaltose. However, administration of ferumoxytol as a single-dose infusion is off-label as it is approved as a two-dose series. Previous studies of ferumoxytol alone support the effectiveness and safety of the single-dose regimen, but there is a paucity of data directly comparing single-dose ferumoxytol to other single-dose IV iron formulations.

Ponatinib coronary microangiopathy: novel bedside diagnostic approach and management with N-acetylcysteine.

Ponatinib produces a coronary microangiopathy that mimics myocardial infarction and can be detected rapidly by contrast echocardiography. N-acetylcysteine therapy can potentially resolve ischemic complications caused by ponatinib-related microangiopathy.

Design of a Microfluidic Bleeding Chip to Evaluate Antithrombotic Agents for Use in COVID-19 Patients.

Introduction: Interventions that could prevent thrombosis, clinical decompensation, and respiratory compromise in patients with novel coronavirus disease (COVID-19) are key to decrease mortality rate. Studies show that profound cytokine release and excessive activation of blood coagulation appear to be key drivers of COVID-19 associated mortality. Since limited methods exist for assessing the effects of anticoagulants on hemostasis, the development of novel therapies to safely prevent thrombosis in COVID-19 patients relies on preclinical animal models and early phase human trials.

Evaluation of the Antihemostatic and Antithrombotic Effects of Lowering Coagulation Factor VII Levels in a Non-human Primate.

Introduction: Tissue factor (TF) and factor (F) VII, components of the extrinsic pathway of blood coagulation, are essential for hemostatic plug formation in response to injury; less clear are their roles in propagating thrombosis, as observational data in humans with congenital FVII deficiency suggests persistent thrombotic and bleeding risk even at significantly decreased FVII levels. We aimed to define the contribution of FVII to thrombus formation and hemostasis using a non-human primate model.

Methods: We treated baboons with a FVII antisense oligonucleotide (ASO) and measured platelet and fibrin deposition inside and distal to collagen- or TF-coated vascular grafts.

When to consider targeted therapies in thrombotic microangiopathies in the modern era: walking the tightrope between cost, safety, and efficacy.

Thrombotic Microangiopathy (TMA) is a heterogeneous collection of syndromes that encompasses TTP, HUS, and other processes characterized by thrombocytopenia, microangiopathic hemolytic anemia, and, if untreated, organ failure and death. Novel therapies have recently been approved for the management of certain thrombotic microangiopathies, including caplacizumab for immune-mediated TTP, and eculizumab for atypical HUS. These options have complicated the standard workflow, which includes initiation of plasma exchange until ADAMTS13 testing can be resulted.

Diagnosis and management of hereditary haemochromatosis.

Hereditary haemochromatosis, one of the most common genetic disorders in the United States, can produce systemic iron deposition leading to end-organ failure and death if untreated. The diagnosis of this condition can be challenging as elevated serum ferritin may be seen in a variety of conditions, including acute and chronic liver disease, a range of systemic inflammatory states, and both primary and secondary iron overload syndromes. Appropriate and timely diagnosis of haemochromatosis is paramount as simple interventions, such as phlebotomy, can prevent or reverse organ damage from iron overload.

The many roles of tranexamic acid: An overview of the clinical indications for TXA in medical and surgical patients.

Clinically significant bleeding can occur as a consequence of surgery, trauma, obstetric complications, anticoagulation, and a wide variety of disorders of hemostasis. As the causes of bleeding are diverse and not always immediately apparent, the availability of a safe, effective, and non-specific hemostatic agent is vital in a wide range of clinical settings, with antifibrinolytic agents often utilized for this purpose. Tranexamic acid (TXA) is one of the most commonly used and widely researched antifibrinolytic agents; its role in postpartum hemorrhage, menorrhagia, trauma-associated hemorrhage, and surgical bleeding has been well defined.

The role of iron repletion in adult iron deficiency anemia and other diseases.

Iron deficiency anemia (IDA) is the most prevalent and treatable form of anemia worldwide. The clinical management of patients with IDA requires a comprehensive understanding of the many etiologies that can lead to iron deficiency including pregnancy, blood loss, renal disease, heavy menstrual bleeding, inflammatory bowel disease, bariatric surgery, or extremely rare genetic disorders. The treatment landscape for many causes of IDA is currently shifting toward more abundant use of intravenous (IV) iron due to its effectiveness and improved formulations that decrease the likelihood of adverse effects.