Platelet and Erythrocyte Extravasation across Inflamed Corneal Venules Depend on CD18, Neutrophils, and Mast Cell Degranulation.

Platelet extravasation during inflammation is under-appreciated. In wild-type (WT) mice, a central corneal epithelial abrasion initiates neutrophil (PMN) and platelet extravasation from peripheral limbal venules. The same injury in mice expressing low levels of the ß2-integrin, CD18 (CD18hypo mice) shows reduced platelet extravasation with PMN extravasation apparently unaffected. To better define the role of CD18 on platelet extravasation, we focused on two relevant cell types expressing CD18: PMNs and mast cells. Following corneal abrasion in WT mice, we observed not only extravasated PMNs and platelets but also extravasated erythrocytes (RBCs). Ultrastructural observations of engorged limbal venules showed platelets and RBCs passing through endothelial pores. In contrast, injured CD18hypo mice showed significantly less venule engorgement and markedly reduced platelet and RBC extravasation; mast cell degranulation was also reduced compared to WT mice. Corneal abrasion in mast cell-deficient (KitW-sh/W-sh) mice showed less venule engorgement, delayed PMN extravasation, reduced platelet and RBC extravasation and delayed wound healing compared to WT mice. Finally, antibody-induced depletion of circulating PMNs prior to corneal abrasion reduced mast cell degranulation, venule engorgement, and extravasation of PMNs, platelets, and RBCs. In summary, in the injured cornea, platelet and RBC extravasation depends on CD18, PMNs, and mast cell degranulation.

Chronic Ulcers and Malnutrition in an African Patient.

An 11-year-old girl with a congenitally malformed left hand, sickle cell trait, asthma, and history of appendicitis was transferred from Zambia for evaluation and treatment of widespread suppurative and ulcerative skin lesions that typically appeared after trauma to her skin. The ulcers first presented 3 years earlier but had markedly worsened in the 9 months before transfer, spreading circumferentially on her extremities and abdomen at the site of an appendectomy. They were painful and did not resolve with multiple courses of intravenous antibiotics and close management by a pediatric infectious disease specialist working for a nongovernmental organization (NGO) in her home country. Per NGO records, she had previously been  average weight-for-age. On presentation after international transfer, she was severely malnourished, with lesions covering âˆ¼35% of her body. In initial workup, leukocytosis of 21 × 103 cells per µL (79% neutrophils), hemoglobin of 6.1 g/dL, and mean corpuscular volume of 66 fL were found. Iron studies revealed an iron level of 18 µg/dL, ferritin level of 55 ng/mL, total iron binding capacity of 222 µg/dL, and transferrin saturation of 8%. Inflammatory markers were elevated, C-reactive protein was 20.1 mg/dL, and the erythrocyte sedimentation rate was 131 mm/h. A chest computed tomography scan revealed bilateral pulmonary nodules, the largest in her left upper lobe measuring 2.4 × 2.0 × 1.9 cm. Our panel of experts reviews the evaluation and treatment of this patient with extensive suppurative and ulcerative skin lesions and the factors considered in offering charity care to international patients.

Microvascular thrombosis: experimental and clinical implications.

A significant amount of clinical and research interest in thrombosis is focused on large vessels (eg, stroke, myocardial infarction, deep venous thrombosis, etc.); however, thrombosis is often present in the microcirculation in a variety of significant human diseases, such as disseminated intravascular coagulation, thrombotic microangiopathy, sickle cell disease, and others. Further, microvascular thrombosis has recently been demonstrated in patients with COVID-19, and has been proposed to mediate the pathogenesis of organ injury in this disease. In many of these conditions, microvascular thrombosis is accompanied by inflammation, an association referred to as thromboinflammation. In this review, we discuss endogenous regulatory mechanisms that prevent thrombosis in the microcirculation, experimental approaches to induce microvascular thrombi, and clinical conditions associated with microvascular thrombosis. A greater understanding of the links between inflammation and thrombosis in the microcirculation is anticipated to provide optimal therapeutic targets for patients with diseases accompanied by microvascular thrombosis.