Platelet transfusion.

被引量：- 发表：1970

Splenic filtration of red blood cells in physiology, malaria and sickle cell disease.

The human spleen clears the blood from circulating microorganisms and red blood cells (RBCs) displaying alterations. This review analyzes how generic mechanisms by which the spleen senses RBC, such pitting, trapping and erythrophagocytosis, impact the pathogenesis of two major spleen-related diseases, malaria and sickle cell disease (SCD). Scintigraphy, functional histology, comparison of circulating and splenic RBC, ex-vivo perfusion of human spleens and in-silico modeling enable relevant exploration of how the spleen retains and processes RBC in health and disease. Iterative cross-validations between medical observations, in-vitro experiments and in-silico modeling point to mechanical sensing of RBC as a central event in both conditions. Spleen congestion is a common pathogenic process explaining anemia and splenomegaly, the latter carrying a risk of severe complications such as acute splenic sequestration crisis and hypersplenism in SCD. Sickling of hemoglobin S-containing RBC may contribute to these complications without necessarily being the trigger. Ongoing progress in the exploration and understanding of spleen-related complications in malaria and SCD open the way to optimized prognosis evaluation and therapeutic applications.

被引量：- 发表：1970

Prophylactic red cell transfusions for sickle cell disease pregnancy: increased use of therapy could transform outcomes.

Pregnancy for people with sickle cell disease (SCD) is high risk with persistently high rates of severe maternal and fetal mortality and morbidity. Transfusion therapy is the best-studied treatment for SCD in pregnancy; hydroxyurea is not usually used because of teratogenicity concerns. In high-resource settings, red cell transfusions are likely underutilized, while in low-resource settings, they may be altogether unavailable. A randomized controlled trial and meta-analysis, two of the strongest forms of clinical research, show transfusion significantly reduces maternal and fetal death, painful crisis, thrombosis, and acute respiratory failure. Downstream benefits of treatment are less well measured and may include improving maternal anemia, reducing opioid exposure, and avoiding hospitalization, which presents risk for additional complications. Alloimmunization is a particular transfusion risk in SCD. However, many strategies can mitigate this risk. Accordingly, the American Society of Hematology classifies chronic transfusion in pregnancy as low risk. Given the low risk classification, lack of alternative therapies, dismal, stagnant pregnancy outcomes and the potential for profound treatment benefit, wider use of chronic transfusion therapy for SCD pregnancy is likely indicated. This review discusses the benefits and potential risks of prophylactic transfusions for SCD pregnancy. Use of chronic transfusions during pregnancy is indicated to help urgently transform outcomes.

被引量：- 发表：1970

Histon activities in the extracellular environment: regulation and prothrombotic implications.

Thromboembolic complications are a major contributor to global mortality. The relationship between inflammation and coagulation pathways has become an emerging research topic where the role of the innate immune response, and specifically neutrophils in "immunothrombosis" are receiving much attention. This review aims to dissect the intricate interplay between histones (from neutrophils or cellular damage) and the haemostatic pathway, and to explore mechanisms that may counteract the potentially procoagulant effects of those histones that have escaped their nuclear localization. Extracellular histones exert procoagulant effects via endothelial damage, platelet activation, and direct interaction with coagulation proteins. Neutralization of histone activities can be achieved by complexation with physiological molecules, through pharmacological compounds, or via proteolytic degradation. Details of neutralization of extracellular histones are still being studied. Leveraging the understanding of extracellular histone neutralization will pave the way for development of novel pharmacological interventions to treat and prevent complications, including thromboembolism, in patients in whom extracellular histones contribute to their overall clinical status.

被引量：- 发表：1970

A role of platelet C-type lectin-like receptor-2 and its ligand podoplanin in vascular biology.

Platelets are essential for hemostasis and are also vital in lymphatic and lung development and the maintenance of vascular integrity. Platelet activation receptor C-type lectin-like receptor 2 (CLEC-2) and its endogenous ligand podoplanin (PDPN) in lymphatic endothelial cells (LECs) and other cells regulate these processes. This review aims to comprehensively summarize the roles of platelet CLEC-2 and PDPN. This review also focuses on discussing the underlying mechanisms by which platelet CLEC-2 and PDPN mediate blood/lymphatic separation. CLEC-2/PDPN-induced platelet activation in the primary lymph sacs, developmental lymphovenous junctions, neonatal mesentery, and the site of tumor lymphangiogenesis prevents blood/lymphatic vessel misconnection. Further, CLEC-2/PDPN-induced platelet activation is essential for lung development. Mice deficient in CLEC-2 or PDPN show blood-filled lymphatics, lung malformations, and cerebrovascular abnormalities. CLEC-2 deletion in steady-state adult mice did not result in blood/lymphatic vessel mixing. In adulthood, CLEC-2 maintains vascular integrity and that of high endothelial venules in lymph nodes. CLEC-2 deletion in adulthood results in hemorrhage under inflammatory conditions, and hemolymph nodes. The platelet CLEC-2/LEC PDPN interaction prevents blood/lymphatic vessel mixing at active remodeling sites of the blood/lymphatic system, but not in steady-state adult mice. This interaction also regulates vascular integrity when vascular permeability increases before and after birth.

被引量：- 发表：1970