[Thrombogenicity of the vessel: role of microfibrils and of collagen]. / Thrombogénicité du vaisseau: rôle des mcirofibrilles et du collagène.

Thrombogenicity of the vessel wall: role of the microfibrils and collagen. The study of platelet adhesion to rabbit aortic subendothelium preincubated with highly specific collagenase has revealed that platelets adhere to the microfibrils of the elastic lamina. To certify that an interaction between microfibrils and platelets can occur, microfibrils from two different origins were isolated: placental microfibrils extracted from the villi of human placenta, and aortic microfibrils extracted from adult bovine aorta. Both preparations were histologically homogeneous, and differed in their amino acid composition with an acidic character more pronounced for placental than for aortic microfibrils. Both preparations were able to induce platelet aggregation in plasma, but not after platelet isolation and resuspension in buffer. An interesting feature was the fact that when normal platelets were isolated, washed and resuspended in plasma from severe VWD patients, they were not aggregated by placental or aortic microfibrils. This defect was corrected after perfusion of cryoprecipitate to one patient. Moreover, monoclonal antibody directed against platelet glycoprotein Ib inhibited the aggregation of platelets to microfibrils, not to collagen; this suggested that an axis platelet GPI-FVIII/VWF-microfibrils could represent a pathway for platelet/subendothelium interaction. The adhesion of platelets to collagen seems to involve the staggering of a short amino acid sequence along a collagen fibre. This possibility arises from the requirement for the preservation of the quaternary structure of collagen in the induction of platelet adhesion/aggregation in vitro, and also from the identification and synthesis of a nonapeptide derived from type III collagen, which is also to specifically inhibit the aggregation of platelets by collagen, following its binding to platelet membrane.

Activation of platelets by microfibrils and collagen. A comparative study.

Previous works demonstrated that microfibrils stimulate blood platelets to aggregate. The present study compares the activation of platelets by human placental and bovine aortic microfibrils and by type III collagen. We studied the morphological changes occurring in in platelets during their activation and aggregation, as well as the kinetics of the release reaction and thromboxane B2 formation. As for collagen, the microfibrils-induced platelet aggregation followed a lag phase, during which progressive emission of pseudopodes and centralization of organelles occurred. Aggregation was associated with secretion of beta-thromboglobulin and adenylic adenylic nucleotides, and with formation of thromboxane B2; it was established that the kinetics of secretion and the aggregation curve were parallel. Microfibrils-induced aggregation was also inhibited by ethylenediamine tetraacetic acid, creatine phosphate-creatine phosphokinase, and aspirin, showing that it was calcium-dependent and required a secretion of ADP and formation of endoperoxide and thromboxane. The response to microfibrils was much more rapid than to collagen; placental microfibrils reacted faster than aortic microfibrils. The requirement of plasma in the microfibrils platelets interaction was confirmed: 10 microliters is the minimal amount of plasma necessary for an aggregation of platelets in 400 microliters of buffer. This fact supports the idea of the existence of two different pathways in the interaction between platelet and the subendothelium, depending on the vascular structure (microfibrils or collagen) involved, even though the sequence of events leading to the formation of an aggregate is similar.

Population genetics of the Malmö polymorphism of coagulation factor IX.

The distribution of 1,198 Malmö alleles was examined in 822 men from 16 indigenous populations and 188 women from 7 of the ethnic groups. Subjects were from several European countries, the Mediterranean, East Asia, and the USA (Anglo- and African-Americans). The frequencies of the rarer (Malmö B) allele were approximately equal across Europe, the highest frequencies (0.36) being in the French and Anglo-Americans; no population was observed with clearly the highest frequency. They diminished slightly at moderate distances from Europe (Tunisia, Ethiopia) and greatly at longer distances (East Asia and West Africa). In Orientals, the frequencies ranged from 0.07 (East Indians) to 0.03 (the Chinese) and from 0.0 to 0.15 in African-Americans. Assuming selective neutrality, the data are consistent with the European origin of the 'B' allele when the population was small and outward spread.