Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also referred to as COVID-19, was declared a pandemic by the World Health Organization in March 2020. The manifestations of COVID-19 are widely variable and range from asymptomatic infection to multi-organ failure and death. Like other viral illnesses, acute myocarditis has been reported to be associated with COVID-19 infection. However, guidelines for the diagnosis of COVID-19 myocarditis have not been established. Methods Using a combination of search terms in the PubMed/Medline, Ovid Medline and the Cochrane Library databases and manual searches on Google Scholar and the bibliographies of articles identified, we reviewed all cases reported in the English language citing myocarditis associated with COVID-19 infection. Results Fourteen records comprising a total of fourteen cases that report myocarditis/myopericarditis secondary to COVID-19 infection were identified. There was a male predominance (58%), with the median age of the cases described being 50.4 years. The majority of patients did not have a previously identified comorbid condition (50%), but of those with a past medical history, hypertension was most prevalent (33%). Electrocardiogram findings were variable, and troponin was elevated in 91% of cases. Echocardiography was performed in 83% of cases reduced function was identified in 60%. Endotracheal intubation was performed in the majority of cases. Glucocorticoids were most commonly used in treatment of myocarditis (58%). Majority of patients survived to discharge (81%) and 85% of those that received steroids survived to discharge. Conclusion Guidelines for diagnosis and management of COVID-19 myocarditis have not been established and our knowledge on management is rapidly changing. The use of glucocorticoids and other agents including IL-6 inhibitors, IVIG and colchicine in COVID-19 myocarditis is debatable. In our review, there appears to be favorable outcomes related to myocarditis treated with steroid therapy. However, until larger scale studies are conducted, treatment approaches have to be made on an individualized case-by-case basis.

A response in writing: A low‐cost bioactive paper device is designed to perform ABO and RhD blood typing tests, and the paper reports the results in writing. This idea was inspired by the vision of the British author, J. K. Rowling, through her novel “Harry Potter and the Chamber of Secrets” in which a piece of paper could be interrogated for information and unambiguous answers were received from the paper in writing.

We developed and validated a new paper-based assay for the detection of human blood type. Our method involves spotting a 3 μL blood sample on a paper surface where grouping antibodies have already been introduced. A thin film chromatograph tank was used to chromatographically elute the blood spot with 0.9% NaCl buffer for 10 min by capillary absorption. Agglutinated red blood cells (RBCs) were fixed on the paper substrate, resulting in a high optical density of the spot, with no visual trace in the buffer wicking path. Conversely, nonagglutinated RBCs could easily be eluted by the buffer and had low optical density of the spot and clearly visible trace of RBCs in the buffer wicking path. Different paper substrates had comparable ability to fix agglutinated blood, while a more porous substrate like Kleenex paper had enhanced ability to elute nonagglutinated blood. Using optimized conditions, a rapid assay for detection of blood groups was developed by spotting blood to antibodies absorbed to paper and eluted with 200 μL of 0.9% NaCl buffer directly by pipetting. RBCs fixation on paper accurately detected blood groups (ABO and RhD) using ascending buffer for 10 min or using a rapid elution step in 100/100 blood samples including 4 weak AB and 4 weak RhD samples. The assay has excellent reproducibility where the same blood group was obtained in 26 samples assessed in 2 different days. Agglutinated blood fixation on porous paper substrate provides a new, simple, and sensitive assay for rapid detection of blood group for point-of-care applications.

Ligand-induced ectodomain shedding of glycoprotein VI (GPVI) is a metalloproteinase-dependent event. We examined whether shear force, in the absence of GPVI ligand, was sufficient to induce shedding of GPVI. Human-citrated platelet-rich plasma or washed platelets were subjected to increasing shear rates in a cone-plate viscometer, and levels of intact and cleaved GPVI were examined by Western blot and ELISA. Pathophysiologic shear rates (3000-10 000 seconds ؊1 ) induced platelet aggregation and metalloproteinase-dependent appearance of soluble GPVI ectodomain, and GPVI platelet remnant. Shedding of GPVI continued after transient exposure to shear. Blockade of ␣ IIb ␤ 3 , GPIb␣, or intracellular signaling inhibited shear-induced platelet aggregation but minimally affected shearinduced shedding of GPVI. Shearinduced GPVI shedding also occurred in platelet-rich plasma or washed platelets isolated from a von Willebrand disease type 3 patient with no detectable VWF, implying that shear-induced activation of platelet metalloproteinases can occur in the absence of GPVI and GPIb␣ ligands. Significantly elevated levels of sGPVI were observed in 10 patients with stable angina pectoris, with well-defined single vessel coronary artery disease and mean intracoronary shear estimates at 2935 seconds ؊1 (peak shear, 19 224 seconds ؊1 ). Loss of GPVI in platelets exposed to shear has potential implications for the stability of a forming thrombus at arterial shear rates. IntroductionPlatelet activation and accumulation at sites of vascular injury play a critical role in thrombus formation. This complex process is mainly initiated by 3 different but overlapping pathways: (1) exposure of subendothelial matrix proteins, including collagen and VWF, which activate the platelet adhesion-signaling receptors glycoprotein VI (GPVI) and GPIb␣ of the GPIb-IX-V complex, respectively; (2) exposure of tissue factor, which activates the coagulation cascade resulting in formation of active thrombin facilitating fibrin deposition as well as enhancing platelet activation; and (3) disturbed blood flow because of narrowing of the vascular lumen, which modulates the adhesive function of platelets and accelerates platelet activation and thrombus growth. 1 Indeed, changes in blood flow rates and hydrodynamic force are now recognized to play a more critical role in thrombus formation, especially at sites of vascular occlusion, as indicated by the ability of elevated (pathologic) shear stress to induce stable platelet aggregate formation without the requirement for platelet activation and adhesion 2 or for soluble agonists. 3 Human platelets normally circulate in a resting state and are exposed to shear rates within a physiologic range (ϳ 20-2000 seconds Ϫ1 ). Platelets may encounter shear rates beyond 10 000 seconds Ϫ1 under pathologic conditions, for example, in a stenosed atherosclerotic artery, and become activated and begin to aggregate. [3][4][5] Shear-dependent platelet activation is initiated by binding of plasma VWF to platelets primarily throu...

Human platelets express FcγRIIa, the low-affinity receptor for the constant fragment (Fc) of immunoglobulin (Ig) G that is also found on neutrophils, monocytes, and macrophages. Engagement of this receptor on platelets by immune complexes triggers intracellular signaling events that lead to platelet activation and aggregation. Importantly these events occur in vivo, particularly in response to pathological immune complexes, and engagement of this receptor on platelets has been causally linked to disease pathology. In this review, we will highlight some of the key features of this receptor in the context of the platelet surface, and examine the functions of platelet FcγRIIa in normal hemostasis and in response to injury and infection. This review will also highlight pathological consequences of engagement of this receptor in platelet-based autoimmune disorders. Finally, we present some new data investigating whether levels of the extracellular ligand-binding region of platelet glycoprotein VI which is rapidly shed upon engagement of platelet FcγRIIa by autoantibodies, can report on the presence of pathological anti-heparin/platelet factor 4 immune complexes and thus identify patients with pathological autoantibodies who are at the greatest risk of developing life-threatening thrombosis in the setting of heparin-induced thrombocytopenia.

This study evaluated shedding of the platelet collagen receptor, glycoprotein VI (GPVI) in human plasma. Collagen or other ligands induce metalloproteinasemediated GPVI ectodomain shedding, generating approximately 55-kDa soluble GPVI (sGPVI) and approximately 10-kDa platelet-associated fragments. In the absence of GPVI ligands, coagulation of platelet-rich plasma from healthy persons induced GPVI shedding, independent of added tissue factor, but inhibitable by metalloproteinase inhibitor, GM6001. Factor Xa (FXa) common to intrinsic and tissue factor-mediated coagulation pathways was critical for sGPVI release because (1) shedding was strongly blocked by the FXa-selective inhibitor rivaroxaban but not FIIa (thrombin) inhibitors dabigatran or hirudin; (2) Russell viper venom that directly activates FX generated sGPVI, with complete inhibition by enoxaparin (inhibits FXa and FIIa) but not hirudin; (3) impaired GPVI shedding during coagulation of washed platelets resuspended in FX-depleted plasma was restored by adding purified FX; and (4) purified FXa induced GM6001-inhibitable GPVI shedding from washed platelets. In 29 patients with disseminated intravascular coagulation, mean plasma sGPVI was 53.9 ng/mL (95% confidence interval, 39.9-72.8 ng/mL) compared with 12.5 ng/mL (95% confidence interval, 9.0-17.3 ng/mL) in thrombocytopenic controls (n ‫؍‬ 36, P < .0001), and 14.6 ng/mL (95% confidence interval, 7.9-27.1 ng/mL) in healthy subjects (n ‫؍‬ 25, P ‫؍‬ .002). In conclusion, coagulation-induced GPVI shedding via FXa down-regulates GPVI under procoagulant conditions. FXa inhibitors have an unexpected role in preventing GPVI down-regulation. (Blood. 2011;117(14):3912-3920) IntroductionIn atherothrombotic disease, thrombus formation at arterial shear rates involves initial platelet adhesion and activation at sites of vascular injury/collagen exposure, and activation of coagulation that generates active thrombin and stabilizes the thrombus by fibrin. 1 Bidirectional regulation of platelet function and coagulation is important in both the pathology of atherothrombotic diseases, such as heart attack or acute ischemic stroke, and in the clinical use of antiplatelet or anticoagulant drugs. [2][3][4][5] The platelet collagen receptor, glycoprotein (GP)VI, is a promising target of antithrombotic therapy because it is not only critical for initiating platelet activation and thrombus formation at arterial shear rates but also promotes thrombus growth and stability because of effects on coagulation. [6][7][8][9] In experimental models, depletion of platelet GPVI results in decreased responsiveness to collagen, impaired procoagulant activity and thrombin generation ex vivo and in vivo, and protection from tissue factor (TF)-induced thromboembolism. 9-11 GPVI agonists also increase phosphatidylserine exposure and microparticle formation, whereas stimulation of platelets with a GPVI ligand (convulxin) and thrombin increase active factor X (FXa) and thrombin, regulated by a subpopulation of platelets with increased binding of c...

COVID-19 (coronavirus disease 2019) vaccines induce immunity through different mechanisms. The aim of this study is to compare the titers of specific antibodies in subjects vaccinated with either the Pfizer-BioNTech COVID-19 vaccine or the Sinopharm vaccine. This prospective observational cohort included Jordanian adults vaccinated with two doses, 21 days apart, of either of the two aforementioned vaccines. Titers were collected 6 weeks after the administration of the second dose. Overall, 288 participants were included, of which 141 were administered the Pfizer-BioNTech vaccine, while 147 were administered the Sinopharm vaccine. Remarkably, 140 (99.3%) of the Pfizer-BioNTech vaccine recipients had positive IgG titers, while 126 (85.7%) of Sinopharm recipients had positive IgG (p < 0.001). The mean titer for IgG among Pfizer-BioNTech recipients was 515.5 ± 1143.5 BAU/mL, compared to 170.0 ± 230.0 BAU/mL among Sinopharm subjects (p < 0.001). Multivariable regression analysis showed that the Pfizer-BioNTech vaccine positively correlated with positive IgG titers (OR: 25.25; 95% CI: 3.25–196.15; p = 0.002), compared with a negative effect of cardiovascular diseases (OR: 0.33; 95% CI: 0.11–0.99; p = 0.48) on IgG titers. In conclusion, fully vaccinated recipients of the Pfizer-BioNTech vaccine had superior quantitative efficiency compared to Sinopharm recipients. A booster dose is supported for Sinopharm recipients, or those with chronic immunosuppressive diseases.

Background and Purpose-Ischemic stroke induced by thrombosis may be triggered by atherosclerotic plaque rupture and collagen-induced platelet activation. Collagen induces glycoprotein VI shedding. Methods-We measured plasma-soluble glycoprotein VI (sGPVI) by enzyme-linked immunosorbent assay in 159 patients with acute (Ͻ7-day) ischemic stroke and age/sex-matched community-based control subjects. Results-sGPVI was elevated in stroke compared with controls (Pϭ0.0168). ORs were higher in Quartile 4 for stroke cases (Pϭ0.0121), and sGPVI was significantly elevated in stroke associated with large artery disease across Quartiles 2 to 4 and small artery disease in Quartile 4. sGPVI decreased 3 to 6 months after antiplatelet treatment, consistent with elevated sGPVI due to platelet activation during the thrombotic event. sGPVI correlated with P-selectin (Pϭ0.0007) and was higher in individuals with the GPVIa haplotype (Pϭ0.024). Conclusion-Glycoprotein VI shedding is implicated in the pathology of acute ischemic stroke. (Stroke. 2011;42: 498-500.)