J.F. Stoltz

Hemorheological and hemostatic parameters in children with nephrotic syndrome undergoing steroid therapy.

Disturbances in hemostatic and hemorheological parameters have been investigated in a group of 29 children with nephrotic syndrome: 23 children classified as steroid-sensitive and 6 as steroid-resistant. Studies were performed before prednisone treatment and 3 weeks later, after initiation of steroid therapy. Before treatment, the alterations in hemostatic system involved moderate thrombocytosis with spontaneous aggregation in 19 patients. High levels of fibrinogen, factor VIII, Willebrand factor, protein C, protein S and alpha 2-macroglobulin (alpha 2M) were observed. Factor XII and alpha 1-antitrypsin (alpha 1AT) were lower than normal. Antithrombin III (ATIII) level was normal in the majority of patients. A plasma and blood hyperviscosity syndrome was also observed as well as an increase in erythrocyte aggregation. During treatment, an improvement in the hemostatic parameters was observed in the patients who responded to prednisone. The expected increase in factor VIII (frequently described in the literature) was not observed, while there was a significant increase in protein C. In the steroid-resistant patients, the only significant changes observed were decreased fibrinogen and increased protein C. The hemorheological parameters showed a tendency towards normality regardless of whether or not the treatment provided remission of NS. The relationship between hemorheological and hemostatic factors changes are discussed.

Beta-thromboglobulin levels in diabetes mellitus : Influence of degenerative lesions and glycemic regulation using an artificial pancreas

Plasma beta-Thromboglobulin levels (beta-TG) were measured by radioimmunoassay in two groups of diabetic patients: first group of 152 diabetics classified according to their vascular complications and anti-diabetic therapy, a second group of 21 poorly controlled insulin-dependent diabetics before and after 24 and 48 hours of strict blood glucose control using an artificial pancreas. beta-TG levels were on average higher in diabetic patients than in 47 healthy subjects. There was no difference between beta-TG levels in non-insulin-dependent patients with one or two microangiopathic lesions were not different from patients without complications. Only diabetics with severe degenerative lesions reveal plasma beta-TG levels significantly increased. Blood Glucose control during 48 hours is accompanied by a significant reduction of beta-TG levels, although the values remained higher than those of the control group. These results suggest that platelet hyperfunction shown in diabetes by beta-TG can precede the appearance of clinically detectable lesions, but the influence of lesions on platelet behaviour is still obscure. It appears however that strict metabolic control of diabetes could have some part in platelet hyperactivity.

Experimental investigation of the rheological activation of blood platelets.

In order to define various aspects of platelet rheological activation, samples of whole blood and platelet-rich plasma (PRP) from the same donors were subjected for 5 min to shear rates increasing from 10 to 10000 sec-1 (shear stresses from 10(-2) to 30 Pa approximatively) in a Couette type viscometer. The following parameters were measured: erythrocyte hemolysis; lactic dehydrogenase activity; plasma B-Thromboglobulin (B-TG); adenine nucleotides, and platelet photometric aggregation. The experimental results reveal that: In whole blood, hemolysis only reached at maximum 2% of the total hemolysis. Plasma LDH activity increased regularly beyond 500 sec-1, in close correlation with B-TG plasma concentration. In contrast, ADP and ATP levels remained stable up to 1000 sec-1 then increased slowly. In PRP, the LDH, ADP and ATP levels remain practically stable up to shear rates around 5000 sec-1. In contrast, B-TG appeared to be released in plasma at shear rate values of 3000 sec-1 and its progression is only correlated with the other parameters, when the platelet lysis occurred. Finally, a rapid and complete inhibition of platelet aggregation to ADP was observed from 5000 sec-1.

Evaluation of a biochemical method for measuring platelet life-span.

Acetylsalicylic Acid (Aspirin) inhibits the formation of Malonaldehyde, a degradation product of the proaggregating Prostaglandins, during the life-span platelets in the circulating blood. After ingestion of 1.5 g of aspirin, there is a blockage of the formation of Malonaldehyde, followed by a progressive return to normal values, after an average of 8 days, in a healthy person. This fact is applied to the determination of half-life, found to be 3.7 +/- 1.3 days; a value in accord with those found by the isotopic method using 51Cr. The reproductibility of this method indicates a clinical application.

Blood Viscosity and Platelet Functions During Cerebrovascular Accidents

Cerebrovascular accident (CVA) is one of the most frequent causes of death, and its mechanisms are not completely understood. The role of platelets in the thromboembolic pathogenesis has often been pointed out, and particularly their interaction with the vascular endothelium when it is damaged by atheroma. Consequently platelet hyperactivity has been proposed in vivo and in vitro [5, 7, 14, 21]. Nevertheless, other risk factors may be involved, such as arterial hypertension, diabetes mellitus, and cardiovascular diseases [6, 12].

Hemorheology and Platelet Activation: Theoretical and Experimental Aspects

Rheological and biophysical processes of aggregation or platelet adhesion can be diagramatically divided in 3 more or less simultaneous phases (1): a) Transport of cells towards the vascular wall or towards other cells. b) Activation phase: cell activation is achieved by aggregating agents released by platelets or other blood-cells (mainly erythrocytes). This primarily biochemical phase may also be related to flow and rheological parameters (rheological activation). c) Adhesion, aggregation phase and platelet deposits: from a kinetic point of view, there is no doubt that the slowest process determines the overall rate of the whole process.