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Seminars in Thrombosis and Hemostasis Jul 2024This article represents a republication of an article originally published in STH in 2005. This republication is to help celebrate 50 years of publishing for STH. The... (Review)
Review
This article represents a republication of an article originally published in STH in 2005. This republication is to help celebrate 50 years of publishing for STH. The original abstract follows.Platelets are specialized blood cells that play central roles in physiologic and pathologic processes of hemostasis, inflammation, tumor metastasis, wound healing, and host defense. Activation of platelets is crucial for platelet function that includes a complex interplay of adhesion and signaling molecules. This article gives an overview of the activation processes involved in primary and secondary hemostasis, for example, platelet adhesion, platelet secretion, platelet aggregation, microvesicle formation, and clot retraction/stabilization. In addition, activated platelets are predominantly involved in cross-talk to other blood and vascular cells. Stimulated "sticky" platelets enable recruitment of leukocytes at sites of vascular injury under high shear conditions. Platelet-derived microparticles as well as soluble adhesion molecules, sP-selectin and sCD40L, shed from the surface of activated platelets, are capable of activating, in turn, leukocytes and endothelial cells. This article focuses further on the new view of receptor-mediated thrombin generation of human platelets, necessary for the formation of a stable platelet-fibrin clot during secondary hemostasis. Finally, special emphasis is placed on important stimulatory and inhibitory signaling pathways that modulate platelet function.
Topics: Humans; Blood Platelets; Hemostasis; Platelet Activation; Platelet Adhesiveness; Signal Transduction; Platelet Aggregation
PubMed: 38086407
DOI: 10.1055/s-0043-1777305 -
Topics in Companion Animal Medicine 2023Primary hemostatic disorders such as thrombocytopenia and thrombocytopathia are commonly encountered in small animal practice. The key stages of primary hemostasis... (Review)
Review
Primary hemostatic disorders such as thrombocytopenia and thrombocytopathia are commonly encountered in small animal practice. The key stages of primary hemostasis include platelet adhesion, activation, and aggregation. Understanding the interaction between tissues, platelets, and signaling molecules not only helps clinicians comprehend clot formation but also better recognize thrombocytopathias. Although congenital thrombocytopathia is rare, commercially available platelet function tests allow veterinarians to narrow differentials in many clinical settings. Thrombocytopenia can be easily diagnosed in any clinical setting. In this paper, we review the current understanding of primary hemostasis in veterinary medicine, including the clinical presentation and available diagnostics to identify platelet abnormalities.
Topics: Animals; Hemostasis; Thrombocytopenia; Blood Platelets; Platelet Function Tests; Blood Coagulation Tests; Anemia
PubMed: 37673175
DOI: 10.1016/j.tcam.2023.100818 -
Hamostaseologie Feb 2024
Topics: Humans; Sodium Citrate; Blood Platelets
PubMed: 38417800
DOI: 10.1055/s-0044-1782595 -
Platelets Dec 2023Platelets play a critical role in immune response. Coronavirus disease 2019 (COVID-19) patients with a severe course often show pathological coagulation parameters...
Platelets play a critical role in immune response. Coronavirus disease 2019 (COVID-19) patients with a severe course often show pathological coagulation parameters including thrombocytopenia, and at the same time the proportion of immature platelets increases. In this study, the platelet count and the immature platelet fraction (IPF) of hospitalized patients with different oxygenation requirements was investigated daily over a course of 40 days. In addition, the platelet function of COVID-19 patients was analyzed. It was found that the number of platelets in patients with the most severe course (intubation and extracorporeal membrane oxygenation (ECMO)) was significantly lower (111.5 ∙ 10 /mL) than in the other groups (mild (no intubation, no ECMO): 203.5 ∙ 10 /mL, < .0001, moderate (intubation, no ECMO): 208.0 ∙ 10 /mL, < .0001). IPF tended to be elevated (10.9%). Platelet function was reduced. Differentiation by outcome revealed that the deceased patients had a highly significant lower platelet count and higher IPF (97.3 ∙ 10 /mL, < .0001, 12.2%, = .0003).
Topics: Humans; COVID-19; Blood Platelets; Thrombocytopenia; Platelet Count; Blood Coagulation
PubMed: 36883692
DOI: 10.1080/09537104.2023.2184183 -
International Journal of Biological... 2023Abnormal megakaryocyte maturation and platelet production lead to platelet-related diseases and impact the dynamic balance between hemostasis and bleeding. Cellular...
Abnormal megakaryocyte maturation and platelet production lead to platelet-related diseases and impact the dynamic balance between hemostasis and bleeding. Cellular repressor of E1A-stimulated gene 1 (CREG1) is a glycoprotein that promotes tissue differentiation. However, its role in megakaryocytes remains unclear. In this study, we found that CREG1 protein is expressed in platelets and megakaryocytes and was decreased in the platelets of patients with thrombocytopenia. A cytosine arabinoside-induced thrombocytopenia mouse model was established, and the mRNA and protein expression levels of CREG1 were found to be reduced in megakaryocytes. We established megakaryocyte/platelet conditional knockout () and transgenic mice (tg-). Compared to mice, mice exhibited thrombocytopenia, which was mainly caused by inefficient bone marrow (BM) thrombocytopoiesis, but not by apoptosis of circulating platelets. Cultured -megakaryocytes exhibited impairment of the actin cytoskeleton, with less filamentous actin, significantly fewer proplatelets, and lower ploidy. CREG1 directly interacts with MEK1/2 and promotes MEK1/2 phosphorylation. Thus, our study uncovered the role of CREG1 in the regulation of megakaryocyte maturation and thrombopoiesis, and it provides a possible theoretical basis for the prevention and treatment of thrombocytopenia.
Topics: Animals; Mice; Blood Platelets; Bone Marrow; Megakaryocytes; Mice, Transgenic; Thrombocytopenia; Thrombopoiesis; Humans
PubMed: 37496998
DOI: 10.7150/ijbs.78660 -
Journal of Thrombosis and Haemostasis :... Dec 2023Upon vessel injury, platelets adhere to exposed matrix constituents via specific membrane receptors, including the von Willebrand factor receptor glycoprotein...
BACKGROUND
Upon vessel injury, platelets adhere to exposed matrix constituents via specific membrane receptors, including the von Willebrand factor receptor glycoprotein (GP)Ib-IX-V complex and integrins β1 and β3. In platelets, the Fes/CIP4-homology Bin-Amphiphysin-Rvs protein PACSIN2 associates with the cytoskeletal and scaffolding protein filamin A (FlnA), linking GPIbα and integrins to the cytoskeleton.
OBJECTIVES
Here we investigated the role of PACSIN2 in platelet function.
METHODS
Platelet parameters were evaluated in mice lacking PACSIN2 and platelet integrin β1.
RESULTS
Pacsin2 mice displayed mild thrombocytopenia, prolonged bleeding time, and delayed thrombus formation in a ferric chloride-mediated carotid artery injury model, which was normalized by injection of control platelets. Pacsin2 platelets formed unstable thrombi that embolized abruptly in a laser-induced cremaster muscle injury model. Pacsin2 platelets had hyperactive integrin β1, as evidenced by increased spreading onto surfaces coated with the collagen receptor α2β1-specific peptide GFOGER and increased binding of the antibody 9EG7 directed against active integrin β1. By contrast, Pacsin2 platelets had normal integrin αIIbβ3 function and expressed P-selectin normally following stimulation through the collagen receptor GPVI or with thrombin. Deletion of platelet integrin β1 in Pacsin2 mice normalized platelet count, hemostasis, and thrombus formation. A PACSIN2 peptide mimicking the FlnA-binding site mediated the pull-down of a FlnA rod 2 construct by integrin β7, a model for integrin β-subunits.
CONCLUSIONS
Pacsin2 mice displayed severe thrombus formation defects due to hyperactive platelet integrin β1. The data suggest that PACSIN2 binding to FlnA negatively regulates platelet integrin β1 hemostatic function.
Topics: Animals; Mice; Blood Platelets; Hemostasis; Hemostatics; Integrin beta1; Peptides; Platelet Activation; Platelet Adhesiveness; Platelet Glycoprotein GPIIb-IIIa Complex; Platelet Membrane Glycoproteins; Receptors, Collagen; Thrombosis
PubMed: 37678551
DOI: 10.1016/j.jtha.2023.08.026 -
Platelets Dec 2023Extracellular vesicles (EVs) contain the characteristics of their cell of origin and mediate cell-to-cell communication. Platelet-derived extracellular vesicles (PEVs)... (Review)
Review
Extracellular vesicles (EVs) contain the characteristics of their cell of origin and mediate cell-to-cell communication. Platelet-derived extracellular vesicles (PEVs) not only have procoagulant activity but also contain platelet-derived inflammatory factors (CD40L and mtDNA) that mediate inflammatory responses. Studies have shown that platelets are activated during storage to produce large amounts of PEVs, which may have implications for platelet transfusion therapy. Compared to platelets, PEVs have a longer storage time and greater procoagulant activity, making them an ideal alternative to platelets. This review describes the reasons and mechanisms by which PEVs may have a role in blood transfusion therapy.
Topics: Humans; Blood Platelets; Platelet Transfusion; Extracellular Vesicles; Blood Transfusion
PubMed: 37578045
DOI: 10.1080/09537104.2023.2242708 -
International Immunopharmacology Jul 2023Dimethyl fumarate (DMF) is a methyl ester of fumaric acid and has been approved for treating multiple sclerosis (MS) and psoriasis due to anti-inflammatory effect. There...
BACKGROUND
Dimethyl fumarate (DMF) is a methyl ester of fumaric acid and has been approved for treating multiple sclerosis (MS) and psoriasis due to anti-inflammatory effect. There is a close association between platelets and the pathogenesis of MS. Whether DMF affects platelet function remains unclear. Our study intends to evaluate DMF's effect on platelet function.
METHODS
Washed human platelets were treated with different concentrations of DMF (0, 50, 100 and 200 μM) at 37 °C for 1 h followed by analysis of platelet aggregation, granules release, receptors expression, spreading and clot retraction. In addition, mice received intraperitoneal injection of DMF (15 mg/kg) to assess tail bleeding time, arterial and venous thrombosis.
RESULTS
DMF significantly inhibited platelet aggregation and the release of dense/alpha granules in response to collagen-related peptide (CRP) or thrombin stimulation dose-dependently without altering the expression of platelet receptors α, GPIbα, and GPVI. In addition, DMF-treated platelets presented significantly reduced spreading on collagen or fibrinogen and thrombin-mediated clot retraction along with the decreased phosphorylation of c-Src and PLCγ2. Moreover, administration of DMF into mice significantly prolonged the tail bleeding time and impaired arterial and venous thrombus formation. Furthermore, DMF reduced the generation of intracellular reactive oxygen species and calcium mobilization, and inhibited NF-κB activation and the phosphorylation of ERK1/2, p38 and AKT.
CONCLUSION
DMF inhibits platelet function and arterial/venous thrombus formation. Considering the presence of thrombotic events in MS, our study indicates that DMF treatment for patients with MS might obtain both anti-inflammatory and anti-thrombotic benefits.
Topics: Humans; Mice; Animals; Platelet Activation; Fibrinolytic Agents; Dimethyl Fumarate; Thrombin; Platelet Aggregation; Blood Platelets; Thrombosis
PubMed: 37245302
DOI: 10.1016/j.intimp.2023.110381 -
Biomaterials Science Aug 2023Platelet-derived extracellular vesicles (PEVs) are a subset of EVs that are released from platelets, which are small nuclear cell fragments that play a critical role in... (Review)
Review
Platelet-derived extracellular vesicles (PEVs) are a subset of EVs that are released from platelets, which are small nuclear cell fragments that play a critical role in hemostasis and thrombosis. PEVs have been shown to have important roles in a variety of physiological and pathological processes, including inflammation, angiogenesis, and cancer. Recently, researchers, including our group have utilized PEVs as drug delivery platforms as PEVs could target inflammatory sites both passively and actively. This review summarizes the biological function of PEVs, introduces recent applications of PEVs in targeted drug delivery, and provides an outlook for the further development of utilizing PEVs for drug delivery.
Topics: Humans; Blood Platelets; Extracellular Vesicles; Drug Delivery Systems; Hemostasis; Thrombosis
PubMed: 37489841
DOI: 10.1039/d3bm00893b -
Cell Reports Methods Jul 2023A characteristic clinical complication in cancer patients is the frequent incidence of thrombotic events. Numerous studies have shown hyperactive/activated platelets to...
A characteristic clinical complication in cancer patients is the frequent incidence of thrombotic events. Numerous studies have shown hyperactive/activated platelets to be a critical earlier trigger for cancer-associated thrombus formation. However, there currently is no viable approach to monitor specific changes in tumor-associated platelet activity. Here, we describe a chromatograph-like microfluidic device that is highly sensitive to the activity status of peripheral circulating platelets in both tumor-bearing mice and clinical cancer patients. Our results show a strongly positive correlation between platelet activation status and tumor progression. Six-month follow-up data from advanced cancer patients reveal positive links between platelet activity level and thrombus occurrence rate, with a high predictive capacity of thrombotic events (AUC = 0.842). Our findings suggest that circulating platelet activity status determined by this microfluidic device exhibits sensitive, predictive potential for thrombotic events in cancer patients for directing well-timed antithrombosis treatment.
Topics: Mice; Animals; Blood Platelets; Platelet Activation; Thrombosis; Neoplasms
PubMed: 37533637
DOI: 10.1016/j.crmeth.2023.100513