Priapism is associated with sleep hypoxemia in sickle cell disease.

PURPOSE: We assessed penile rigidity during sleep and the relationship of sleep abnormalities with priapism in adults with sickle cell disease. MATERIALS AND METHODS: This was a case-control study of 18 patients with sickle cell disease and a history of priapism during the previous year, and 16 controls with sickle cell disease. Participants underwent overnight polysomnography and RigiScan® Plus recording to detect penile rigidity oscillations. RESULTS: The priapism group (cases) showed a higher apnea-hypopnea index and oxyhemoglobin desaturation parameters than controls. A lower positive correlation between the apnea-hypopnea index and oxyhemoglobin desaturation time was observed in cases than in controls (Spearman coefficient ρ = 0.49, p = 0.05 vs ρ = 0.76, p <0.01), suggesting that desaturation events occurred independently of apnea. Two controls and 14 cases had a total sleep time that was greater than 10% with oxyhemoglobin saturation less than 90% but without CO(2) retention. Penile rigidity events were observed during rapid eye movement sleep and during stage 2 of nonrapid eye movement sleep, particularly in cases. The duration of penile rigidity events concomitant to respiratory events was higher in cases than in controls. Regression analysis revealed that the periodic limb movement and desaturation indexes were associated with priapism after adjusting for rapid eye movement sleep and lung involvement. Finally, oxyhemoglobin saturation less than 90% was associated with priapism after adjusting for lung involvement, hyperhemolysis and the apnea-hypopnea index. CONCLUSIONS: Oxyhemoglobin desaturation during sleep was associated with priapism history. It may underlie the distribution pattern of penile rigidity events during sleep in these patients.

[Paroxysmal nocturnal hemoglobinuria: from physiopathology to treatment]. / Hemoglobinúria paroxística noturna: da fisiopatologia ao tratamento.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder, an acquired chronic hemolytic anemia, often associated with recurrent nocturnal exacerbations, recurrent infections, neutropenia, thrombocytopenia, and episodes of venous thrombosis. Its clinical course is highly variable. It frequently arises in association with bone marrow failure, particularly aplastic anemia and myelodysplastic syndrome. It is also an acquired thrombophilia, presenting with a variety of venous thrombosis, mainly manifested with intra-abdominal thrombosis, here the major cause of mortality. The triad of hemolytic anemia, pancytopenia, and thrombosis makes a truly unique clinical syndrome of PNH, which was reclassified from a purely acquired hemolytic anemia to a hematopoietic stem cell mutation defect of the phosphatidyl inositol glycanclass-A gene. This mutation results in an early block in the synthesis of glycosylphosphatidylinositol (GPI) anchors, responsible for binding membrane functional proteins. Among these proteins are the complement inhibitors, especially CD55 and CD59, that play a key role in protecting blood cells from complement cascade attack. Therefore, in PNH occurs an increased susceptibility of red cells to complement, and consequently, hemolysis. We here review PNH physiopathology, clinical course, and treatment options, especially eculizumab, a humanized monoclonal antibody that blocks the activation of terminal complement at C5 and prevents formation of the terminal complement complex, the first effective drug therapy for PNH.

Hemoglobinúria paroxística noturna: da fisiopatologia ao tratamento / Paroxysmal nocturnal hemoglobinuria: from physiopathology to treatment

Hemoglobinúria paroxística noturna (HPN) é uma anemia hemolítica crônica adquirida rara, de curso clínico extremamente variável. Apresenta-se frequentemente com infecções recorrentes, neutropenia e trombocitopenia, e surge em associação com outras doenças hematológicas, especialmente com síndromes de falência medular, como anemia aplásica e síndrome mielodisplásica. É considerada ainda um tipo de trombofilia adquirida, apresentando-se com tromboses venosas variadas, com especial predileção por trombose de veias hepáticas e intra-abdominais, sua maior causa de mortalidade. A tríade anemia hemolítica, pancitopenia e trombose faz da HPN uma síndrome clínica única, que deixou de ser encarada como simples anemia hemolítica adquirida para ser considerada um defeito mutacional clonal da célula-tronco hematopoética (CTH). A mutação ocorre no gene da fosfaditilinositolglicana classe-A, e resulta no bloqueio precoce da síntese de âncoras de glicosilfosfaditilinositol (GPI), responsáveis por manter aderidas à membrana plasmática dezenas de proteínas com funções específicas. A falência em sintetizar GPI madura gera redução de todas as proteínas de superfície normalmente ancoradas por ela. Dentre elas estão o CD55 e o CD59, que controlam a ativação da cascata do complemento. Assim, na HPN há aumento da susceptibilidade de eritrócitos ao complemento, gerando hemólise. Revisa-se aqui sua fisiopatologia, curso clínico, os tratamentos disponíveis com ênfase para o transplante de células-tronco hematopoéticas alogênicas e para o eculizumab, um anticorpo monoclonal humanizado que bloqueia a ativação do complemento terminal no nível C5 e previne a formação do complexo de ataque à membrana, a primeira droga a demonstrar eficácia no tratamento da HPN.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder, an acquired chronic hemolytic anemia, often associated with recurrent nocturnal exacerbations, recurrent infections, neutropenia, thrombocytopenia, and episodes of venous thrombosis. Its clinical course is highly variable. It frequently arises in association with bone marrow failure, particularly aplastic anemia and myelodysplastic syndrome. It is also an acquired thrombophilia, presenting with a variety of venous thrombosis, mainly manifested with intra-abdominal thrombosis, here the major cause of mortality. The triad of hemolytic anemia, pancytopenia, and thrombosis makes a truly unique clinical syndrome of PNH, which was reclassified from a purely acquired hemolytic anemia to a hematopoietic stem cell mutation defect of the phosphatidyl inositol glycanclass-A gene. This mutation results in an early block in the synthesis of glycosylphosphatidylinositol (GPI) anchors, responsible for binding membrane functional proteins. Among these proteins are the complement inhibitors, especially CD55 and CD59, that play a key role in protecting blood cells from complement cascade attack. Therefore, in PNH occurs an increased susceptibility of red cells to complement, and consequently, hemolysis. We here review PNH physiopathology, clinical course, and treatment options, especially eculizumab, a humanized monoclonal antibody that blocks the activation of terminal complement at C5 and prevents formation of the terminal complement complex, the first effective drug therapy for PNH.