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.

Trombocitopenia inducida por heparina: Nuevas opciones terapéuticas / Heparin-induced thrombocytopenia. New therapeutical options

La trombocitopenia inducida por heparina (TIH) es una reacción adversa inmunológica mediada por la formación de anticuerpos contra el complejo heparina-factor plaquetario 4 (FP4), caracterizada por la presencia de trombocitopenia y la asociación paradojal de trombosis arterial o venosa. Es una complicación poco frecuente pero grave del uso de cualquier tipo de heparina. En tratados con procedimientos cardiovasculares como intervención coronaria percutánea y cirugía de revascularización cardiaca, la prevalencia de anticuerpos es significativamente mayor que en otros escenarios clínicos. El reconocimiento de las características clínicas y de laboratorio permite la suspensión inmediata de la heparina y la instauración de tratamiento anticoagulante alternativo, para evitar la progresión y formación de nuevos trombos y sus complicaciones. En la presente revisión se resumen las diferentes alternativas terapéuticas para la TIH, en particular los anticoagulantes orales directos (DOACS) como el dabigatran, rivaroxaban y apixaban que pueden proporcionar una nueva opción para el tratamiento de TIH.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse reaction due to antibodies to a multimolecular complex of heparin and platelet factor 4 (PF4) characterized by moderate thrombocytopenia and paradoxical arterial or venous thrombosis. It is a relatively infrequent complication related to the administration of any type of heparin. In patients undergoing percutaneous coronary revascularization or coronary artery by-pass graft the prevalence of HIT is higher than in other clinical settings. Recognizing clinical and laboratory features of HIT allow immediate discontinuation of heparin and the use of alternative anticoagulants to avoid serious thrombotic complications. In this review, we summarize different therapeutic options for the treatment of HIT with special emphasis on direct oral anticoagulants (DOACS) such as dabigatran, rivaroxaban and apixaban. DOACS might represent a therapeutic alternative for HIT treatment.

Tratamiento exitoso con fondaparinux en trombocitopenia inducida por heparina y trombosis / Successful treatment with fondaparinux in heparin-induced thrombocytopenia and thrombosis

La trombocitopenia inducida por heparina (TIH) es una reacción adversa inmunológica caracterizada por trombocitopenia y la asociación paradojal de trombosis arterial o venosa. Es causada por la formación de anticuerpos IgG contra el complejo multimolecular de heparina-factor plaquetario 4 (FP4). Fondaparinux es un inhibidor selectivo del factor Xa que tiene escasa afinidad por el FP4 y posee un menor potencial para inducir una respuesta inmunológica, haciendo del mismo un agente potencialmente útil en el tratamiento de la TIH. Se presenta el caso de una mujer de 73 años con TIH asociada a fenómenos trombóticos arteriales y venosos, que recibió exitosamente fondaparinux, con normalización del recuento plaquetario y sin progresión trombótica.

Heparin induced thrombocytopenia (HIT) is an immune-mediated adverse reaction characterized by thrombocytopenia and paradoxical arterial or venous thrombosis, due to the formation IgG antibodies directed to a multimolecular complex of heparin-platelet factor 4 (PF4). Fondaparinux is a selective factor Xa inhibitor with little affinity for PF4 and thus less likely to induce an immune response, making fondaparinux a potentially useful drug for the treatment of HIT. Herein we report the case of a 73 years old woman with HIT associated with arterial and venous thrombosis that was successfully treated with fondaparinux, with normalization of the platelet countand without progression of thrombosis.

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.

The Incidence, Causes, and Prognostic Significance of New-Onset Thrombocytopenia in Intensive Care Units: A Prospective Cohort Study in a Korean Hospital

This study was designed to investigate the incidence, causes, and outcomes of new-onset thrombocytopenia (NOT) in Korean intensive care units (ICUs). A prospective cohort study was conducted in medical ICUs of Samsung Medical Center between August 2010 and February 2011. All newly admitted patients were included if they stayed in the ICU for more than 48 hr and did not have thrombocytopenia upon admission. A total of 186 patients were included. NOT developed in 37.1%. Most common cause of NOT was sepsis with disseminated intravascular coagulation (66.7%), followed by drug-induced thrombocytopenia (18.8%), and heparin-induced thrombocytopenia (2.9%). IgG-specific antibody to platelet factor 4/heparin was positive in 2.4% among patients treated with heparin, and thrombosis occurred in two patients. Twenty eight-day mortality was higher in patients that developed NOT compared to those that did not develop NOT (39.1% vs 12%, P < 0.001). NOT increased the odds ratio of 28-day mortality and was an independent risk factor for mortality (OR 3.52; 95% CI 1.32-9.38; P = 0.012). In conclusion, NOT is common and is an independent risk factor for mortality in Korean ICU patients. Therefore, clinicians should make every effort to correct the causes of NOT.

The Incidence, Causes, and Prognostic Significance of New-Onset Thrombocytopenia in Intensive Care Units: A Prospective Cohort Study in a Korean Hospital

This study was designed to investigate the incidence, causes, and outcomes of new-onset thrombocytopenia (NOT) in Korean intensive care units (ICUs). A prospective cohort study was conducted in medical ICUs of Samsung Medical Center between August 2010 and February 2011. All newly admitted patients were included if they stayed in the ICU for more than 48 hr and did not have thrombocytopenia upon admission. A total of 186 patients were included. NOT developed in 37.1%. Most common cause of NOT was sepsis with disseminated intravascular coagulation (66.7%), followed by drug-induced thrombocytopenia (18.8%), and heparin-induced thrombocytopenia (2.9%). IgG-specific antibody to platelet factor 4/heparin was positive in 2.4% among patients treated with heparin, and thrombosis occurred in two patients. Twenty eight-day mortality was higher in patients that developed NOT compared to those that did not develop NOT (39.1% vs 12%, P < 0.001). NOT increased the odds ratio of 28-day mortality and was an independent risk factor for mortality (OR 3.52; 95% CI 1.32-9.38; P = 0.012). In conclusion, NOT is common and is an independent risk factor for mortality in Korean ICU patients. Therefore, clinicians should make every effort to correct the causes of NOT.

Utility of ELISA Optical Density Values and Clinical Scores for the Diagnosis of and Thrombosis Prediction in Heparin-induced Thrombocytopenia / 대한진단검사의학회지

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction caused by antibodies to the heparin/platelet factor 4 (PF4) complex, resulting in thrombocytopenia and prothrombotic state. HIT diagnosis is challenging and depends on clinical presentation and laboratory tests. We investigated the usefulness of clinical scores and heparin/PF4 ELISA optical density (OD) as a diagnostic marker and thrombosis predictor in HIT. METHODS: We analyzed 92 patients with suspected HIT. The heparin/PF4 antibody was measured using a commercial ELISA kit (GTI, USA). For each patient, the 4 T's score and Chong's score were calculated. RESULTS: Of the 92 patients, 28 were anti-heparin/PF4-seropositive. The 4 T's score and Chong's score showed good correlation (r=0.874). The 4 T's score and OD values showed good performance for diagnosis of the definite and unlikely HIT groups; however, OD levels showed better sensitivity (93.8%) than the 4 T's score used alone (62.5%). Of the 92 patients, 26 developed thrombosis. The OD values were significantly higher in patients with thrombosis than in those without thrombosis (0.52 vs. 0.22, P0.4) had an increased risk of thrombosis (adjusted odds ratio 9.44 [3.35-26.6], P<0.001) and a shorter 250-day thrombosis-free survival (32.1% vs. 54.7%, P=0.012). CONCLUSIONS: ELISA OD values in combination with clinical scoring can improve the diagnosis of and thrombosis prediction in HIT. More attention should be paid to the use of clinical scores and OD values as thrombosis predictors in HIT.

Anti-Heparin-Platelet Factor 4 Antibody is a Risk Factor for Vascular Access Obstruction in Patients Undergoing Hemodialysis

Since heparin is an anticoagulant commonly used in hemodialysis and the patients on hemodialysis are repeatedly exposed to heparin, heparin may be the cause of the development of heparin-dependent antibodies and thrombotic complications in patients on hemodialysis. The purpose of this study was to determine the prevalence and the clinical significance of the antibodies against heparin-platelet factor 4 complexes as determined by enzyme immunoassay in patients on maintenance hemodialysis. The prevalence of anti-heparin-platelet factor 4 antibodies was higher in hemodialysis patients than in normal subjects (8.8 vs 0.0%, p<0.05). The number of past episodes of vascular access obstruction per year was significantly higher in the anti-heparin-platelet factor 4 antibody positive group than antibody negative group. Anti-heparin-platelet factor 4 antibody positive patients experienced more frequent vascular access obstructions than control subjects. In conclusion, anti-heparin-platelet factor 4 antibody might be a risk factor for vascular access obstructions in patients with end-stage renal disease on maintenance hemodialysis.