Evaluating thromboprophylaxis in the sickle cell disease population: Navigating the evidence gap.

Sickle cell disease (SCD) arises from beta-globin gene mutations, with global estimates indicating around 500 000 affected neonates in 2021. In the United States, it is considered rare, impacting fewer than 200 000 individuals. The key pathogenic flaw lies in mutant haemoglobin S, prone to polymerization under low oxygen conditions, causing erythrocytes to adopt a sickled shape.

Long-term clinical outcomes and healthcare utilization of sickle cell disease patients with COVID-19: A 2.5-year follow-up study.

Objectives: This study investigated whether patients with sickle cell disease (SCD) had elevated risk of worse long-term clinical outcomes and healthcare utilization 2.5 years post-SARS-CoV-2 infection.

Methods: This study consisted of 178 patients with SCD who tested positive for COVID-19 between February 1, 2020 and January 30, 2022 in a major academic health system in New York City.

Clinical outcomes of COVID-19 in patients with sickle cell disease and sickle cell trait: A critical appraisal of the literature.

Individuals with sickle cell disease (SCD) and sickle cell trait (SCT) have many risk factors that could make them more susceptible to COVID-19 critical illness and death compared to the general population. With a growing body of literature in this field, a comprehensive review is needed. We reviewed 71 COVID-19-related studies conducted in 15 countries and published between January 1, 2020, and October 15, 2021, including a combined total of over 2000 patients with SCD and nearly 2000 patients with SCT.

Children and young adults hospitalized for severe COVID-19 exhibit thrombotic coagulopathy.

We report the clinical and laboratory coagulation characteristics of 27 pediatric and young adult patients (2 months to 21 years) treated for symptomatic COVID-19 at a children's hospital in the Bronx, New York, between March 1 and May 31, 2020. D-Dimer was > 0.5 μg/mL (upper limit of normal) in 25 (93%) patients at admission; 11 (41%) developed peak D-dimer > 5 μg/mL during admission.

Hemolysis inhibits humoral B-cell responses and modulates alloimmunization risk in patients with sickle cell disease.

Red blood cell alloimmunization remains a barrier for safe and effective transfusions in sickle cell disease (SCD), but the associated risk factors remain largely unknown. Intravascular hemolysis, a hallmark of SCD, results in the release of heme with potent immunomodulatory activity, although its effect on SCD humoral response, specifically alloimmunization, remains unclear. Here, we found that cell-free heme suppresses human B-cell plasmablast and plasma cell differentiation by inhibiting the DOCK8/STAT3 signaling pathway, which is critical for B-cell activation, as well as by upregulating heme oxygenase 1 (HO-1) through its enzymatic byproducts, carbon monoxide and biliverdin.

Acute chest syndrome in the setting of SARS-COV-2 infections-A case series at an urban medical center in the Bronx.

New York City has emerged as one of the epicenters of the SARS-COV-2 pandemic, with the Bronx being disproportionately affected. This novel coronavirus has caused significant respiratory manifestations raising the concern for development of acute chest syndrome (ACS) in patients with sickle cell disease (SCD). We report a series of pediatric SCD SARS-COV-2-positive patients admitted with ACS.

Thromboinflammation in COVID-19 acute lung injury.

Since the initial description in 2019, the novel coronavirus SARS-Cov-2 infection (COVID-19) pandemic has swept the globe. The most severe form of the disease presents with fever and shortness of breath, which rapidly deteriorates to respiratory failure and acute lung injury (ALI). COVID-19 also presents with a severe coagulopathy with a high rate of venous thromboembiolism.

Novel Sickle Cell Disease Therapies: Targeting Pathways Downstream of Sickling.

Sickle cell disease is an inherited hemoglobinopathy characterized by hemolytic anemia, frequent painful episodes, poor quality of life, end organ damage and a shortened lifespan. Although the seminal event is the polymerization of the abnormal hemoglobin, the downstream pathophysiology of vaso-occlusion results from heterotypic interactions between the altered, adhesive sickle cell RBCs, neutrophils, endothelium, and platelets. Ischemia reperfusion injury, hemolysis and oxidant damage all contribute to heightened inflammation and activation of the hemostatic system.

Use of Thrombopoietin Receptor Agonists in Childhood Immune Thrombocytopenia.

Most children with immune thrombocytopenia (ITP) will have spontaneous remission regardless of therapy, while about 20% will go on to have chronic ITP. In those children with chronic ITP who need treatment, standard therapies for acute ITP may have adverse effects that complicate their long-term use. Thus, alternative treatment options are needed for children with chronic ITP.

Actin inhibition increases megakaryocyte proplatelet formation through an apoptosis-dependent mechanism.

Background: Megakaryocytes assemble and release platelets through the extension of proplatelet processes, which are cytoplasmic extensions that extrude from the megakaryocyte and form platelets at their tips. Proplatelet formation and platelet release are complex processes that require a combination of structural rearrangements. While the signals that trigger the initiation of proplatelet formation process are not completely understood, it has been shown that inhibition of cytoskeletal signaling in mature megakaryocytes induces proplatelet formation.

Thrombopoietin receptor agonists: a critical review.

Thrombopoietic agents have created a paradigm shift in the management of chronic or poorly responsive immune thrombocytopenia (ITP). There are ample randomized, placebo-controlled trial data, as well as long-term data gathered for more than 5 years; short-term efficacy and safety are well documented and long-term efficacy and safety data are emerging. The purpose of this review will be to focus critically on what we know or do not know at this point about these agents.

Effect of thrombopoietin receptor agonists on the apoptotic profile of platelets in patients with chronic immune thrombocytopenia.

Platelet survival depends upon mediators of apoptosis e.g., Bcl-xL, Bax, and Bak, which are regulated by thrombopoietin (TPO)-mediated AKT signaling.

Ex vivo production of platelets from stem cells.

Stem cell technology holds great promise for transfusion medicine, and generation of platelets from stem cells would be transformative. Platelet transfusions are life saving for millions of people and the clinical demand for platelets continues to increase: there is a real need to increase the supply of platelets. Accordingly, there is great interest in the potential of producing platelets from stem cells for clinical use.

Rho kinase inhibition drives megakaryocyte polyploidization and proplatelet formation through MYC and NFE2 downregulation.

The processes of megakaryocyte polyploidization and demarcation membrane system (DMS) formation are crucial for platelet production, but the mechanisms controlling these processes are not fully determined. Inhibition of Rho kinase (ROCK) signalling leads to increased polyploidization in umbilical cord blood-derived megakaryocytes. To extend these findings we determined the effect of ROCK inhibition on development of the DMS and on proplatelet formation.