Macrophage Migration Inhibitory Factor Promotes Thromboinflammation and Predicts Fast Progression of Aortic Stenosis.

Background: Aortic stenosis (AS) is driven by progressive inflammatory and fibrocalcific processes regulated by circulating inflammatory and valve resident endothelial and interstitial cells. The impact of platelets, platelet-derived mediators, and platelet-monocyte interactions on the acceleration of local valvular inflammation and mineralization is presently unknown.

Methods: We prospectively enrolled 475 consecutive patients with severe symptomatic AS undergoing aortic valve replacement.

Extracorporeal membrane oxygenation aggravates platelet glycoprotein V shedding and δ-granule deficiency in COVID-19-associated acute respiratory distress syndrome.

Background: Extracorporeal membrane oxygenation (ECMO) is a lifesaving therapy in patients with acute respiratory distress syndrome (ARDS). Hemostatic complications are frequently observed in patients on ECMO and limit the success of this therapy. Platelets are key mediators of hemostasis enabling activation, aggregation, and thrombus formation by coming in contact with exposed matrix proteins via their surface receptors such as glycoprotein (GP) VI or GPIb/V/IX.

Thrombocytopenia Absent Radius (TAR)-Syndrome: From Current Genetics to Patient Self-Empowerment.

Thrombocytopenia absent radius (TAR) syndrome is a rare form of hereditary thrombocytopenia associated with a bilateral radial aplasia. TAR syndrome is genetically defined by the combination of a microdeletion on chromosome 1 which includes the gene , and a single nucleotide polymorphism (SNP) in the second allele. While most patients with TAR syndrome harbor a SNP in either the 5' UTR region or in intron 1 of , further SNPs associated with TAR syndrome are still being identified.

State-of-the-Art Targeted High-Throughput Sequencing for Detecting Inherited Platelet Disorders.

Inherited platelet disorders (IPDs) are a heterogeneous group of rare entities caused by molecular divergence in genes relevant for platelet formation and function. A rational diagnostic approach is necessary to counsel and treat patients with IPDs. With the introduction of high-throughput sequencing at the beginning of this millennium, a more accurate diagnosis of IPDs has become available.

Loss of zinc transporters ZIP1 and ZIP3 augments platelet reactivity in response to thrombin and accelerates thrombus formation .

Zinc (Zn) is considered as important mediator of immune cell function, thrombosis and haemostasis. However, our understanding of the transport mechanisms that regulate Zn homeostasis in platelets is limited. Zn transporters, ZIPs and ZnTs, are widely expressed in eukaryotic cells.

Isolation, In Vitro Differentiation, and Culture of Murine Megakaryocytes From Fetal Liver and Adult Bone Marrow.

Megakaryocytes (MKs) are the source of circulating platelets and are readily recognized by their large size and distinctive morphology. Their poor representation in hematopoietic tissues often requires enrichment or considerable ex vivo expansion to generate cells for biochemical and cell biological studies. These experimental protocols describe the enrichment of primary MKs directly from the murine bone marrow as well as in vitro differentiation of fetal liver- or bone marrow-derived hematopoietic stem cells into MKs.

Ontogenesis of functional platelet subpopulations from preterm and term neonates to adulthood: The PLINIUS study.

Erythrocytes undergo a well-defined switch from fetal to postnatal circulation, which is mainly reflected by the stage-specific expression of hemoglobin chains. Perinatal alterations in thrombopoiesis are poorly understood. We assessed the ontogenesis of platelet phenotype and function from early prematurity to adulthood.

Rapid isolation of mature murine primary megakaryocytes by size exclusion via filtration.

Megakaryocytes (MKs), the largest and rarest cells of the hematopoietic system, differentiate by increasing their size, DNA and cytoplasmic contents during maturation in order to release high numbers of blood platelets into the circulation. The gold-standard to study these complex cells is the isolation of primary MKs from the native bone marrow (BM). This is typically achieved by using fluorescence- or magnetic-activated cell sorting.

Uncoupling of platelet granule release and integrin activation suggests GPIIb/IIIa as a therapeutic target in COVID-19.

Thromboembolic events are frequent and life-threating complications of COVID-19 but are also observed in patients with sepsis. Disseminated thrombosis can occur despite anticoagulation, suggesting that platelets play a direct but incompletely understood role. Several studies demonstrated altered platelet function in COVID-19 with some controversial findings, while underlying disease-specific mechanisms remain ill defined.

Impaired microtubule dynamics contribute to microthrombocytopenia in RhoB-deficient mice.

Megakaryocytes are large cells in the bone marrow that give rise to blood platelets. Platelet biogenesis involves megakaryocyte maturation, the localization of the mature cells in close proximity to bone marrow sinusoids, and the formation of protrusions, which are elongated and shed within the circulation. Rho GTPases play important roles in platelet biogenesis and function.

G6b-B regulates an essential step in megakaryocyte maturation.

G6b-B is a megakaryocyte lineage-specific immunoreceptor tyrosine-based inhibition motif-containing receptor, essential for platelet homeostasis. Mice with a genomic deletion of the entire Mpig6b locus develop severe macrothrombocytopenia and myelofibrosis, which is reflected in humans with null mutations in MPIG6B. The current model proposes that megakaryocytes lacking G6b-B develop normally, whereas proplatelet release is hampered, but the underlying molecular mechanism remains unclear.

CXCL12-Abundant Reticular (CAR) Cells Direct Megakaryocyte Protrusions across the Bone Marrow Sinusoid Wall.

Megakaryocytes (MKs) release platelets into the lumen of bone marrow (BM) sinusoids while remaining to reside within the BM. The morphogenetic events of this complex process are still not fully understood. We combined confocal laser scanning microscopy with transmission and serial block-face scanning electron microscopy followed by 3D-reconstruction on mouse BM tissue sections.