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In two patients treated by heparin for thrombosis, thrombocytopenia under 10 000/cumm occured accompanied with bleeding cud recurrent thrombosis. The demonstration in the patients' serum of a factor inducing platelet aggregation and serotonin release in the presence of heparin suggests that the thrombocytopenia could be of immuno-allergic origin. In both cases, the discontinuation of heparin resulted in clinical and biological improvement. The rare cases of heparin-induced thrombocytopenia reported in the literature are discussed.

A monoclonal hybridoma antibody specific for platelet glycoprotein I complex is described. The nature od the antigen was determined by demonstration that it was chymotrypsin sensitive and gave a peak at 150 000 daltons on SDS-PAGE after immunoprecipitation. The expression of the antigen is restricted to platelets and megakaryocytes with at least 1.6 x 10(4) molecules of antigen per platelet. The antibody failed to bind to platelets from patients with Bernard Soulier syndrome, where there is known to be a deficiency of glycoprotein Ib/Is expression. Binding to platelets from patients with Glanzmann's thrombasthenia was normal.

The diagnosis and treatment of apparently idiopathic recurrent thromboembolic disease (RTED) still raise difficult problems. However, recent data suggest that abnormalities of coagulation and fibrinolysis factors are important. Hereditary antithrombin III (AT III) deficiency or abnormal AT III, and hereditary protein C deficiency with autosomal dominant transmission have been associated with severe familiar RTED. More recently, we described a dysfibrinogenemia characterized by abnormal fibrin polymerization and abnormal plasminogen binding to the fibrin clot, responsible for familial RTED. Disorders of fibrinolytic activity in RTED are represented, in 70% of the cases, by reduced release or lack of production by endothelial cells of a vascular plasminogen activator. Hereditary plasminogen deficiency or abnormal plasminogen, although rare, are regularly responsible for RTED.

It is well established that thrombin induces various biological responses in endothelial cells derived from large vessels. However, little is known about the effects of thrombin on the microvasculature. Protein phosphorylation may be one of the mechanisms by which an extracellular stimulus initiates cellular events like proliferation. Therefore, we have compared the effects of either human alpha-thrombin or phorbol esters (TPA) on the proliferation or protein phosphorylation in endothelial cells derived from large vessels (umbilical vein, HUVEC) or microvessels (omental tissue, HOMEC). In HOMEC, thrombin did not stimulate cell proliferation and protein phosphorylation while TPA slightly reduced the cell proliferation and induced the phosphorylation of a 27-kDa protein. In contrast, in HUVEC, thrombin or TPA markedly enhanced the cell proliferation and stimulated the phosphorylation of a 59-kDa protein. These data indicate that (i) endothelial cells from large and small vessels respond differently to thrombin and (ii) there is a complex and as yet unclear relationship between the proliferation and the protein phosphorylation induced by thrombin.

Allogeneic bone marrow transplantation (BMT) successfully corrected type I thrombasthenia in a 4-year-old boy. The donor was his HLA-A, B and D identical 14-year-old brother who was heterozygous for thrombasthenia. A first transplant after conditioning with cyclophosphamide and thoracoabdominal irradiation was rejected, but a second transplant using CCNU, cyclophosphamide, procarbazine and horse antihuman thymocyte globulin in the preparative regimen was successful. Engraftment was proven by studies of platelet membrane antigens, PLA1 and glycoprotein IIb/IIIa complex and by platelet function studies. Haemorrhagic manifestations completely disappeared; platelet membrane markers and clot retraction returned promptly to normal values, and platelet aggregation tests more slowly. Twenty-four months after bone-marrow transplant, the patient was well with mild chronic hepatic graft versus host disease. BMT therefore appears to be a possible treatment for severe inherited platelet disorders.

An IgG antibody isolated from the serum of a patient with the Bernard-Soulier syndrome induced platelet agglutination in the platelet-rich plasma of 50 normal subjects regardless of their ABO, KOa, KOb, HLA, or PlA1 types. This antibody was nonreactive with platelets from three other Bernard-Saulier syndrome patients. Indirect immunoprecipitation tests using this serum (or purified IgG) and soluble membrane antigens labeled with 125I that had been extracted from normal platelets by the nonionic detergent Nonidet P-40 gave a single radioactive peak at 150,000 MW in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These findings strongly suggest that the antigenic determinant reacting with this antibody is absent from platelets of Bernard-Soulier syndrome patients and that the deficient molecule is of 150,000 MW. The role of this molecule in subendothelial adhesion and macromolecular-mediated aggregations is discussed.

We investigated the effect of 1 alpha,25-dihydroxyvitamin D3 (1,25 (OH)2 vit D3) on the 3H-thymidine uptake by Balb/c 3T3 cells and by human skin fibroblasts stimulated by normal human serum or by purified PDGF. We found an inhibitory effect of 1,25 (OH)2 vit D3 on the DNA synthesis of Balb/c 3T3 cells grown in the presence of human serum as well as in the presence of PDGF. At 5% human serum this effect is minimal at 10(-12) M 1,25 (OH)2 vit D3 and is maximal at 10(-9) M. On the DNA synthesis of human fibroblasts stimulated by human serum or by PDGF a modulatory effect of 1,25 (OH)2 vit D3 was shown. On these cells the vitamin had a stimulatory effect between 10(-11) and 10(-9) M and an inhibitory effect at very high concentrations (10(-7) M). Our results suggested that the effect of 1,25 (OH)2 vit D3 on fibroblast DNA synthesis could be mediated by interactions with its specific intracellular receptor. 1,25 (OH)2 vit D3 had no any action on the growth of human fibroblasts stimulated by fibroblast growth factor.