Hemoglobinúria paroxística no urna e eventos trombóticos: uma revisão integrativa

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare haematopoietic disorder that can affect the erythrocytes, platelets and leukocytes and consists of a deficiency of glycosylphosphatidylinositol (GPI), an important phosphoglyceride present in cell membranes. It can be classified into three subtypes: classic PNH, associated with bone marrow aplasia and subclinical PNH, which may present variations in the degree of cellular involvement, symptoms and prognosis. The GPI is responsible for anchoring numerous proteins involved in the most diverse cellular mechanisms and when absent, it makes cells more susceptible to destruction, mediated mainly by the complement system. Therefore, the patient may develop anemia, leukopenia, thrombocytopenia and hemoglobinuria, in addition to serious complications, including embolisms and thrombotic events. In this sense, thrombosis is the most dangerous consequence of the disease, and can lead to death in most untreated cases. Hence, the present study aimed to analyze the relationship between PNH and thrombosis, through the existing bibliography on the subject, consisting, therefore, of an integrative review of the literature. Based on the selected articles, relevant aspects about thrombosis in the disease were discussed, contemplating the manifestations and possible clinical correlations, pathophysiology, laboratory findings, available treatments, and possible outcomes. The studies analyzed highlighted the strong involvement of platelet activation, leukocyte mediation, hemolysis products and complement system regulation in the development of thrombi. Furthermore, there was divergence regarding the relationship between the proportion of affected cells (PNH clone size) and the progression of the disease. Most articles associated the presence of larger clones with increased thrombotic risk, while only one demonstrated no expressive association. However, regarding management, all articles attest to the efficacy of eculizumab in controlling the disorder, especially when associated with the use of anticoagulants to contain thrombosis. Finally, it was possible to conclude that agility in diagnosis is essential to protect patients from the risks involved and increase survival. Thus, more detailed studies are necessary to expand knowledge about the mechanisms of the disorder and improve diagnostic and treatment methods.