Increased serum levels of transforming growth factor beta-1 in patients affected by thrombotic throbocytopenic purpura (TTP):its implication on bone marrow haematopoiesis

Summary. In this study we evaluated the effect of serum collected from seven thrombotic thrombocytopenic purpura (TTP) patients, either in the acute phase of the disease or in clinical remission, on the in vitro growth of bone marrow haematopoietic progenitor cells, obtained from the same TTP patients in clinical remission and from normal donors. The addition to the cultures of autologous sera collected from TTP patients in acute phase of the disease showed a clear-cut dose-dependent inhibition of immature haematopoietic progenitor cells (BFU-E, CFU-meg and 14th day CFU-GM). On the other hand, no inhibitory effects were observed on more mature 7th day CFU-GM. Interestingly, also sera collected from TTP patients in clinical remission still maintained some inhibitory activity on the growth of immature progenitor cells. A similar inhibitory activity was noticed when TTP sera were tested on normal bone marrow haematopoietic progenitor cells. Such inhibitory activity was significantly reduced in blocking experiments by the addition of a polyclonal neutralizing anti-TGF-β1 antibody and the presence of increased levels of both bioactive and latent TGF-β1 in TTP sera was confirmed in a bioassay on CCL64 cells. These data contribute to explain the lack of a clear compensatory haematopoiesis observed in some patients with active TTP and add further evidence to the notion of the existence of a state of latent platelet activation in TTP patients in clinical remission

Monoclonal antibody to human platelet glycoprotein I. II. Effects on human platelet function.

The effect on platelet function of a monoclonal platelet antibody to platelet membrane glycoprotein I was tested. This antibody, AN51, inhibited ristocetin or bovine factor VIII-induced aggregation but did not modify ADP, collagen type I or type III, thrombin or arachidonic acid induced aggregations. Furthermore, the adhesion-aggregation of platelets induced by microfibrils was also inhibited by the antibody. Platelet adhesion to rabbit aorta subendothelium was impaired by the antibody. The persistent adhesion of platelets to collagenase-treated subendothelium was also inhibited. These findings strongly suggested that platelet membrane glycoprotein I could interact with a non-collagenic microfibrillar component of subendothelium. The binding of factor VIII/von Willebrand factor to platelet membrane in the presence of ristocetin was decreased in the binding site for factor VIII/von Willebrand factor to allow platelet adhesion to subendothelium