Clinical benefit of eculizumab in patients with no transfusion history in the International Paroxysmal Nocturnal Haemoglobinuria Registry.

Background: Eculizumab reduces intravascular haemolysis and improves disease symptoms in patients with paroxysmal nocturnal haemoglobinuria (PNH).

Aims: To characterise, in a real-world setting, the effect of eculizumab in patients with haemolytic PNH (lactase dehydrogenase (LDH) ≥ 1.5 upper limit of normal) and no history of red blood cell transfusion, including those with high disease activity (HDA).

Pulmonary hypertension and nitric oxide depletion in sickle cell disease.

During the past decade a large body of experimental and clinical studies has focused on the hypothesis that nitric oxide (NO) depletion by plasma hemoglobin in the microcirculation plays a central role in the pathogenesis of many manifestations of sickle cell disease (SCD), particularly pulmonary hypertension. We have carefully examined those studies and believe that the conclusions drawn from them are not adequately supported by the data. We agree that NO depletion may well play a role in the pathophysiology of other hemolytic states such as paroxysmal nocturnal hemoglobinuria, in which plasma hemoglobin concentrations are often at least an order of magnitude greater than in SCD.

Immune-mediated hemolytic anemia.

Hemolytic anemia due to immune function is one of the major causes of acquired hemolytic anemia. In recent years, as more is known about the immune system, these entities have become better understood and their treatment improved. In this section, we will discuss three areas in which this progress has been apparent.

Clinical course and flow cytometric analysis of paroxysmal nocturnal hemoglobinuria in the United States and Japan.

: To determine and directly compare the clinical course of white and Asian patients with paroxysmal nocturnal hemoglobinuria (PNH), data were collected for epidemiologic analysis on 176 patients from Duke University and 209 patients from Japan. White patients were younger with significantly more classical symptoms of PNH including thrombosis, hemoglobinuria, and infection, while Asian patients were older with more marrow aplasia. The mean fraction of CD59-negative polymorphonuclear cells (PMN) at initial analysis was higher among Duke patients than Japanese patients.

Clinical manifestations of paroxysmal nocturnal hemoglobinuria: present state and future problems.

The clinical pathology of paroxysmal nocturnal hemoglobinuria (PNH) involves 3 complications: hemolytic anemia, thrombosis, and hematopoietic deficiency. The first 2 are clearly the result of the cellular defect in PNH, the lack of proteins anchored to the membrane by the glycosylphosphatidylinositol anchor. The hemolytic anemia results in syndromes primarily related to the fact that the hemolysis is extracellular.

The hematopoietic defect in PNH is not due to defective stroma, but is due to defective progenitor cells.

Although paroxysmal nocturnal hemoglobinuria (PNH) is often associated with aplastic anemia (AA), the nature of the pathogenetic link between PNH and AA remains unclear. Moreover, the PIG-A mutation appears to be necessary but not sufficient for the development of PNH, suggesting other factors are involved. The ability of PNH marrow cells to form in vitro hematopoietic colonies and the ability of PNH marrow to generate stroma that could support hematopoiesis of normal or PNH marrow in cross culture were investigated.

New Views of Sickle Cell Disease Pathophysiology and Treatment.

This review addresses several areas of concern in the care of patients with sickle cell disease. In Sections I and II, the fundamental pathogenetic mechanisms of sickle cell disease and their clinical consequences are discussed. Dr.