Effect of sublingual immunotherapy on platelet activity in children with allergic rhinitis / Efeito da imunoterapia sublingual sobre a atividade plaquetária em crianças com rinite alérgica

Abstract Introduction: The role of platelet activation in allergic inflammation is receiving increasing attention. Sublingual immunotherapy for allergic rhinitis can modify the immunological process to an allergen, rather than simply treating symptoms. Objective: The aim of this study was to explore the role of platelet activation during sublingual immunotherapy in children with allergic rhinitis. Methods: Forty-two House Dust Mite - sensitized children with allergic rhinitis were enrolled and received House Dust Mite allergen extract for sublingual immunotherapy or placebo. Serum of different time points during treatment was collected and used for detection of Platelet Factor-4 and Beta-Thromboglobulin concentration by Enzyme-Linked Immuno Sorbent Assay. Results: Our data showed decreased expression of Platelet Factor-4 and Beta-Thromboglobulin protein after one year's sublingual immunotherapy. In addition, the decrease of symptom scores and serum Platelet Factor-4 and Beta-Thromboglobulin protein concentrations was positively related. Conclusion: During sublingual immunotherapy, platelet activation was inhibited significantly. Our results might indicate that inhibition of platelet activation within the systemic circulation is an important mechanism during sublingual immunotherapy.

Resumo Introdução: O papel da ativação de plaquetas na inflamação alérgica recebeu atenção crescente. A imunoterapia sublingual para rinite alérgica pode modificar o processo imunológico a um alérgeno, em vez de tratar os sintomas simplesmente. Objetivo: Explorar o papel da ativação plaquetária durante a imunoterapia sublingual em crianças com rinite alérgica. Método: Quarenta e duas crianças com rinite alérgica sensibilizadas por ácaros de poeira domiciliar (APD) foram inscritas e receberam extrato de alérgeno de APD para imunoterapia sublingual ou placebo. O soro de diferentes pontos no tempo durante o tratamento foi recolhido e usado para a detecção de fator 4 plaquetário e concentração de beta-tromboglobulina por ensaio imunoenzimático. Resultados: Nossos dados mostraram diminuição da expressão de fator 4 plaquetário e proteína beta-tromboglobulina após imunoterapia sublingual de um ano. Além disso, a diminuição dos escores de sintomas e o fator 4 plaquetário sérico e concentrações de proteína beta-tromboglobulina foram relacionados de maneira positiva. Conclusão: Durante imunoterapia sublingual, a ativação plaquetária foi inibida significativamente. Os nossos resultados podem indicar que a inibição da ativação de plaquetas dentro da circulação sistêmica é um mecanismo importante durante imunoterapia sublingual.

The Role of Platelets in Malarial Acute Lung Injury and Acute Respiratory Distress Syndrome: A World of Possibilities.

In recent decades our understanding of platelets’ role in immune response has increased. Traditionally platelets were considered as bleeding-stopping and thrombosis-causing cells. In recent years the platelets’ role in malarial innate and adaptive immune responses is being recognized. Platelets play critical role in pathogenesis of malaria infection leading to variety of outcomes. It is being realized that platelets play dual role in case of malaria (i) by preventing early stage exponential growth of parasitemia (ii) promoting exaggerated immune responses later. Platelets role in pathogenesis of severe and cerebral malaria has been widely studied. However their role in malaria related acute lung injury and respiratory distress has gained less attention. Recently the presence of active megakaryocytes and proplatelets have been explained in human lungs. Simultaneously, the platelets role in pathogenesis of acute lung injury and respiratory distress (ALI/ARDS) was also recognized. This gives a hint that there is a possible association of platelets with malaria related respiratory diseases as well. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. In this review we have attempted to establish the importance of role of platelets in malaria related acute lungs injury and malaria acute respiratory distress syndrome and try to explain the underlying mechanism of this process. In ALI/ARDS, including those caused by malaria, platelets participate sequestration to the vascular bundle facilitating the recruitment of immune cells viz. neutrophils. Additionally, they secrete or induce the secretion of chemokines that result into vascular damage.

Plasma markers of thrombin generation, fibrinolysis and activated platelets in sickle cell disease

Thrombotic phenomenon has an important role in the vasooclusive manifestations of sickle cell disease [SCD] that dominate its clinical spectrum. For evaluation of thrombotic activities in SCD patients, the markers of thrombin generation: thrombin anti-thrombin complex [TAT] and prothrombin fragment 1, 2 [F 1, 2], enhanced fibrinolysis markers: plasmin anti- plasmin complex [PAP] and D-dimer and platelet activation markers: platelet factor 4 [PF4] and B - thromboglobulin [BTG] were measured in 35 patients with SCD [25 during steady state and 10 during crisis], compared to 12 normal controls. The measurements were performed by enzyme-linked immunosorbent assays. The thrombotic markers [TAT and F 1, 2], fibrinolytic markers [PAP and D-dimer] and platelet activation markers [PF4 and BTG] were significantly increased in SCD patients during steady state. During vasooclusive crisis, there were marked increase in TAT, D- dimer, BTG and PF4 while there was no significant increase in the levels of PAP and F 1, 2. Also, there was significantly positive correlation among thrombin generation markers, platelet activation markers and fibrinolysis markers in SCD patients during steady state. During episodes there was significant positive correlation among markers of thrombin generation, fibrinolysis and platelet activation except PAP and F 1, 2 markers as compared with asymptomatic intervals. We concluded that, during pain episodes, there was enhanced platelet procoagulant activity, elevated fibrinolytic activity and thrombin generation. These changes may predict the frequency of pain. These findings suggested that increased their levels may increase the risk of thrombosis in these patients and establish a relationship between the laboratory determination of these parameters and clinical pain episodes in patients with SCD. The findings of platelet activation, fibrinolytic activity and thrombin generation in asymptomatic patients indicate ongoing subclinical thrombogeinc activity in patients with SCD

Association between spontaneous echocardiographic contrast in descending aorta and platelet factor 4 and D-dimer in patients with non-rheumatic atrial fibrillation

The aim of this study was to determine the relationship between spontaneous echocardiographic contrast in the descending thoracic aorta and plasma levels of platelet factor 4 [PF4] and D-dimer as hemostatic markers in patients with nonrheumatic atrial fibrillation. This study included 60 patients [mean age, 58 +/- 3 years; 34 males] with non-rheumatic chronic atrial fibrillation who underwent transesoph…geal echocardiography Plasma levels of PF4 as. a measure of platelet activation and D-dimer as an index of thrombogenesis were determined on the day of TEE. 27 patients who had aortic spontaneous echocardiographic contrast [Ao-SEC] were older [61 years vs 57 years; p<0.05 than 33 patients without AoSEC. D-dimer levels were significantly higher in patients with AoSEC than in those without AoSEC, whereas PF4 was not different between the two groups. Although the prevalence of prior cerebral embolism did not differ between the two groups [22% in patients with AoSEC vs 18% in patients without AoSEC], the prevalence of peripheral arterial embolism was r in patients with AoSEC than in those without AoSEC [11% vs 0%; p<0.05]. The LA appendage peak flow velocity was significantly lower in patients with AoSEC than in those without AoSEC. The grade of LASEC and the prevalence of LA thrombi were higher in patients with AoSEC than those without. Although aortic dimensions did not differ between the two groups aortic atherosclerotic grade was greater in patients SEC than in those without AoSEC. Multivariate analysis revealed that mitral regurgitation, LASEC, and aortic atherosclerosis emerged as independent predictors of AoSEC. Search for AoSEC in addition to LA appendage dysfunction with TEE could provide valuable information on prothrombotic state in patients with nonrheumatic AF. Patients with nonrheumatic AF complicated with AoSEC could have enhanced thrombogenesis; therefore, intensive anticoagulation with oral warfarin may be recommended for these patients

Cognitive function in patients with non valvular atrial fibrillation: correlation to markers of thrombogenesis

There is increasing evidence that non valvular atrial fibrillation NVAF is associated with an increased risk of asymptomatic or silent cerebral infarctions. An important question is whether these infarction are truly asymptomatic and whether anti-thrombotic treatment could be beneficial in those patients. In this study we examined components of cognitive function [Event Related Potentials "ERP[s]" P300 and Wechsler Adult Intelligence Scale "WAIS"] and markers of thrombogenesis [fibrinogen, fibrinopeptide A "FPA". platelet aggregation, platelet factor 4 "PF-4" and beta-thromboglobulin "beta T.G"] in 20 neurologically asymptomatic NVAF patients comparing them to a well matched group in sinus rhythm. In addition, parameters of cognitive function components were correlated to those of thrombogenesis in the group of AF patients. NVAF patients had significantly prolonged latency and significantly reduced amplitude of P300 component of ERPs in AF Vs sinus rhythm group respectively and significantly reduced verbal intelligence quotient [VIQ] component of [WAIS] Vs sinus rhythm group P< 0.006. In addition, NVAF patients had significantly elevated levels of fibrinogen [p< 0.01], FPA [p<0.001], significant platelet aggregation is response to 2 ug/ml collagen [p< 0.001] and 1 ug/ml collagen [P< 0.001] and significantly elevated levels of PF-4 [P< 0.01] and beta T. G [P< 0.001] compared to the group in sinus rhythm respectively. In the NVAF group, there was positive association between P300 latency of ERPs components and each of FPA and PF-4 with high P< 0.1 and marginal P= 0.05 significance respectively and significant inverse correlation between all parameters of WAIS components and those of thrombogenesis except for the relation of performance intelligence quotient [PIQ] to each of FPA and beta T.G levels. These results may aid in identifying those patients at high risk of developing dementia and may help decision making when anti thrombotic therapy is being considered in NVAF patients. We recommend cognitive

Released platelet and granule contents: implication of thrombospondin in haemorrhagic diathesis in hepatosplenic schistosomiasis

This work was carried out on 75 subjects, 60 patients suffering from hepatosplenic schistosomiasis in different stages of the disease; in addition to 15 nonbilharzial normal controls. Thrombospondin and other platelet alpha granule contents including firbronectin, platelet factor 4, Beta-thromboglobulin, alpha 2-antiplasmin, plasminogen activator inhibitor, C1 inactivator, histidine rich glycoprotein, fibrinogen and plasminogen were studied. They were estimated in all groups in a trial to clarify the impact of thrombospondin and other alpha-granule contents on the alteration or haemostasis and haematemesis in hepatosplenic schistosomiasis. Specific investigations for platelets were estimated including bleeding time, platelet count and platelet aggregation. The data obtained revealed significant progressive decrease of the platelet alpha-granule contents studied [except thrombospondin] with the advancement of the disease especially in advanced fibrotic and haematemesis groups. Thrombospondin [TSP] showed significant progressive increase parallel to the progress of the disease. This may be explained by its longer life span and by its extraplatelet sources mainly the vascular endothelium. The data confirm that high level of TSP may serve as a templet whereupon the cofactors for the initiation or enhancement of fibrinolysis occur. These data confirm that the platelets play an important role in haemorrhagic diathesis in late stages of hepatosplenic schistosomiasis; this is through thrombocytopenia, decrease platelet function and its alpha-granule contents including antiproteases in addition to the important role played by TSP