prostaglandin-d2 and Thrombocytopenia

Topics: Animals; Antineoplastic Agents; Blood Coagulation; Blood Platelets; Blood Vessels; Cell Adhesion; Cell Communication; Cells, Cultured; Cricetinae; Cysteine Endopeptidases; Disease Models, Animal; Endopeptidases; Epoprostenol; Humans; Killer Cells, Natural; Lung Neoplasms; Melanoma; Mice; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Transplantation; Neoplasms, Experimental; Platelet Aggregation; Prostaglandin D2; Prostaglandins D; Rabbits; Rats; Thrombocytopenia; Thromboxane-A Synthase

Thrombocytopenia is a critical problem that occurs in many hematologic diseases, as well as after cancer therapy and radiation exposure. Platelet transfusion is the most commonly used therapy but has limitations of alloimmunization, availability, and expense. Thus, the development of safe, small, molecules to enhance platelet production would be advantageous for the treatment of thrombocytopenia. Herein, we report that an important lipid mediator and a peroxisome proliferator-activated receptor gamma (PPARgamma) ligand called 15-deoxy-Delta(12,14) prostaglandin J(2) (15d-PGJ(2)), increases Meg-01 maturation and platelet production. 15d-PGJ(2) also promotes platelet formation from culture-derived mouse and human megakaryocytes and accelerates platelet recovery after in vivo radiation-induced bone marrow injury. Interestingly, the platelet-enhancing effects of 15d-PGJ(2) in Meg-01 cells are independent of PPARgamma, but dependent on reactive oxygen species (ROS) accumulation; treatment with antioxidants such as glutathione ethyl ester (GSH-EE); or N-acetylcysteine (NAC) attenuate 15d-PGJ(2)-induced platelet production. Collectively, these data support the concept that megakaryocyte redox status plays an important role in platelet generation and that small electrophilic molecules may have clinical efficacy for improving platelet numbers in thrombocytopenic patients.

Topics: Acetylcysteine; Animals; Antineoplastic Agents; Antioxidants; Blood Platelets; Bone Marrow; Cell Line; Female; Glutathione; Humans; Male; Megakaryocytes; Mice; Platelet Transfusion; PPAR gamma; Prostaglandin D2; Radiation Injuries, Experimental; Reactive Oxygen Species; Thrombocytopenia

One case of heparin-induced thrombocytopenia is reported. Aggregation was observed in the platelet-rich plasma of this patient in the presence of two commercial standard heparin preparations (from a final concentration of 0.025 IU/ml upwards), of two semi-synthetic heparin analogues (0.1 APTT U/ml) and of three low-molecular weight heparin (LMWH) fractions (0.1 anti-Xa U/ml) but not in the presence of five other LMWH fractions. The patient's isolated platelets no longer aggregated in the The patient's isolated platelets no longer aggregated in the presence of heparin but the phenomenon recurred after addition of the patient's platelet poor plasma (PPP). Furthermore, addition of patient's PPP to control platelets led to heparin-induced aggregation. The phenomenon was associated with thromboxane generation and could be blocked by in vitro addition of aspirin, PGI2, and PGD2 whereas the lag phase was dose-dependently prolonged by adenosine. It is concluded that platelet aggregation may be induced in some patients by standard heparin and by certain LMWH fractions or semi-synthetic analogues, independently of their molecular weight and anticoagulant activity.

Topics: Adenosine; Aged; Aspirin; Epoprostenol; Heparin; Humans; In Vitro Techniques; Male; Molecular Weight; Platelet Aggregation; Prostaglandin D2; Prostaglandins D; Thrombocytopenia