Modulation of the expression and activity of cyclooxygenases in normal and accelerated erythropoiesis

OBJECTIVE: The present study was aimed at characterizing the expression and activity of cyclooxygenase (COX) isoenzymes in erythropoiesis. METHODS: The expression and activity of cyclooxygenase (COX) and prostaglandin (PG) synthases were investigated in: 1) erythroblasts developed in culture from human CD34(+) hematopoietic progenitors, 2) erythroblasts in bone marrow specimens, and 3) peripheral erythrocytes isolated from healthy donors and from patients with a high regeneration rate of erythrocytes. RESULTS: While COX-1 protein was observed at each stage of erythroblast development, COX-2 protein was induced at later stages through a p38/MAPK-dependent pathway. Both COX isoforms were also observed in mature erythroblasts of the bone marrow. Erythroblasts developed in culture synthesized significantly more PGE(2) than TXB(2) and indomethacin delayed erythroid maturation. COX-1 and COX-2 were also observed in erythrocytes by immunostainings, although COX expression was confined to a fraction of circulating erythrocytes. Peripheral erythrocytes synthesized low but detectable amounts of PGE(2) and TXB(2). Similarly to erythroblast progenitors, PGE(2) was the prevalent prostanoid released by erythrocytes. This biosynthetic capacity was significantly increased in erythrocytes from patients with accelerated erythropoiesis as compared to controls. CONCLUSIONS: Both COX isoforms are present and enzymatically active during human erythropoiesis, although with different kinetics, and COX-derived prostanoids may play a role in erythroid maturation. Furthermore, peripheral erythrocytes retain in part the capacity of expressing COX and synthesizing prostanoids, which may contribute to the hemostatic/thrombotic response to vascular injury in different diseases, including congenital hemolytic disorders

Determinants of hemoglobin concentration in chronic respiratory insufficiency

the abstracts reports the deteminants of hemoglobin level calculated in a group of patients affected by chronic respiratory insufficienc

Common occurrence of anaemia at the end of pregnancy following exposure to zidovudine-free regimens

Although zidovudine-free regimens are increasingly used in pregnancy, their haematological effects in mothers and newborns are incompletely defined

Worsening of the clinical-hematological picture in a patient with a rare PK-LR compound heterozygosis after mitral replacement

We report a case of a patient affected by compound heterozygosis for two PK-LR gene mutations: p.R486W (c.1456C>T) and p.M4031(c.1209G>A). Our patient suffered from an initial moderate hemolytic anemia which subsequently evolved into a severe form after mitral prosthetic valve replacement for valve regurgitation. Thereafter, the clinical features evolved into a worsening of anemia, heart failure and pulmonary hypertension, in the absence of valve dysfunction. This clinical picture improved only after an intensive transfusion regimen. This case highlights aspects concerning the intricate balance between the risks and benefits of a mechanical prosthetic valve implant in PM-deficient patients