Antibodies to thromboplastin in systemic lupus erythematosus: isotype distribution and clinical significance in a series of 92 patients.

We determined the prevalence and relationship with clinical manifestations of antibodies to thromboplastin (aTP) in 92 patients with systemic lupus erythematosus (SLE). Thirty-two (35%) patients had aTP: 13 (14%) were positive for IgG aTP, 13 (14%) for IgM aTP, and 6 (7%) for both. Patients with aTP had an increased incidence of thrombosis (p = 0.01), thrombocytopenia (p < 0.001), hemolytic anemia (p < 0.001), and fetal losses (p = 0.03). When the IgG and IgM aTP isotypes were analysed separately, the IgG aTP were found to be associated with thrombosis (p < 0.001), thrombocytopenia (p < 0.001), and fetal losses (p = 0.02). The IgM aTP were associated with hemolytic anemia (p < 0.001). A correlation was found between the titers of aTP and those of anticardiolipin antibodies, in both IgG (p < 0.01, r = 0.6) and IgM (p < 0.01, r = 0.64) isotypes, and between the titers of IgG aTP and the diluted Russell's viper venom time used to detect the lupus anticoagulant (p < 0.001, r = 0.42). This test is a reliable, reproducible and sensitive assay for the detection of antiphospholipid antibodies, specially in those patients under anticoagulant therapy.

Comparative study of spleen pathology in drug abusers with thrombocytopenia related to human immunodeficiency virus infection and in patients with idiopathic thrombocytopenic purpura. A morphometric, immunohistochemical, and ultrastructural study.

A morphometric and immunohistochemical study was performed to assess the spleen's alterations in patients with autoimmune thrombocytopenia and in drug abusers with thrombocytopenia (DAT) related to human immunodeficiency virus (HIV) infection. A total of 34 patients were included in the study: 20 DAT patients and 14 with idiopathic thrombocytopenic purpura (ITP). Twenty HIV-negative splenectomy patients without thrombocytopenia were included as controls. Spleen weight in DAT patients (323.25 +/- 149.96 g, mean + standard deviation) was significantly increased compared with the ITP (164.28 +/- 29.79 g, P < 0.0001) and control (175.50 +/- 49.14 g, P < 0.0001) groups. The mean diameter of lymphoid follicles in the spleens of DAT patients (446.83 +/- 99.16 microns, was significantly higher than in those of the control patients (370.87 +/- 55.30 microns, P = 0.019). In control patients' spleens, the number of platelets in Billroth's cords was significantly higher (59.54 +/- 32.72/10(4) microns 2) than in those of the DAT (2.13 +/- 1.42/10(4) microns 2, P < 0.0001) and ITP (P < 0.0001) patients. The number of macrophages and ceroid histiocytes per 10(4) microns 2 of red pulp was significantly increased in both DAT (5.14 +/- 1.90) and ITP (7.48 +/- 4.38) patients compared with the control patients (3.66 +/- 1.10, P < 0.0001) and P = 0.06, respectively), and in ITP patients compared with DAT patients (P = 0.0136). The number of granulopoietic precursors per 10(4) microns 2 of red pulp was higher in the spleens of DAT (1.41 +2- 1.46, P < 0.0001) and ITP (0.92 +/- 0.75, P < 0.0001) patients compared with those of the control group. Transmission electron microscopy studies demonstrated platelet phagocytosis by macrophages of Billroth's cords and presence of myeloid metaplasia in spleens of DAT and ITP patients. Immunohistochemical studies showed a depletion of CD4+ lymphocytes in the T zone of splenic white pulp and an increased number of CD8+ lymphocytes in red pulp of DAT patients' spleens compared with those of ITP and control patients. There were no significant alterations in dendritic reticular cell network in the DAT group compared with the ITP and control groups.

Antiphospholipid antibodies in unselected patients with repeated abortion.

We have studied, prospectively, the incidence of several antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-phosphatidylserine, anti-phosphatidic acid, anti-phosphatidylinositol and anti-thromboplastin antibodies) in 65 consecutive patients with two or more (range 2-8, mean 3.1) abortions. Lupus anticoagulant activity was detected in seven (10.7%) patients and all of them exhibited other antiphospholipid antibodies. Of the previous pregnancies in these seven women, 88% had ended in spontaneous abortion. Four of them achieved pregnancy after low-dose aspirin therapy was started, and carried successfully to term. It is concluded that antiphospholipid antibodies, namely lupus anticoagulant, should be routinely screened in the recurrent spontaneous aborter.

Anticardiolipin antibodies in patients with autoimmune diseases: isotype distribution and clinical associations.

A prospective study of IgG and IgM isotypes of anticardiolipin antibodies (aCL) was performed in a series of 167 patients with various autoimmune diseases, including rheumatic and nonrheumatic disorders, and in a group of 100 healthy blood donors. The IgG aCL serum was regarded as positive if a binding index (BI) greater than 2.85 (3.77 SD) was detected and a BI greater than 4.07 (3.90 SD) was defined as positive for IgM aCL. Forty patients (24%) were found to be positive for IgG and/or IgM aCL. IgG aCL were detected in 23% of patients with systemic lupus erythematosus (SLE), in 9% with idiopathic thrombocytopenic purpura, in 7% with progressive systemic sclerosis, and in 6% with dermatomyositis-polymyositis. IgM aCL were present in 43% patients with primary biliary cirrhosis, in 33% with rheumatoid arthritis, in 22% with SLE, and in 8% with giant-cell arteritis. IgG aCL were found to have a significant association with thrombosis and thrombocytopenia, and IgM and aCL with haemolytic anaemia and neutropenia, in SLE but not in the other autoimmune diseases. The identification of these differences in the aCL isotype associations, depending on the autoimmune disorder, may improve the clinical usefulness of these tests.

Kinetics of platelets, megakaryocytes and their precursors: what to measure?

A sequential exploration of the kinetics of platelets, megakaryocytes, and their progenitors is devised, wherein abnormalities at one level of differentiation are the subject of further analysis at the preceding level. Platelet kinetics yield estimates of mean platelet life span, fraction of platelet mass in circulation and daily production, making it possible to recognize the disorders of hyperdestruction, hypersequestration, hypoproduction, and hyperproduction. Theoretical considerations and regression analysis of a variety of computer-simulated survival tests show that sufficient information is contained in the first four days of the disappearance curve of population labeled platelets to provide an estimate of mean life span with an error of 9%--15%. Identifying the type of destruction disorder depends on developing tests and parameters which will make it possible to integrate into a coherent model such indices as the rate of senescence, the rates of reversible and irreversible aggregation, and the rates of adhesion to and phagocytosis by the reticuloendothelial system. Foremost among the existing models is the multiple-hit theory, although its validity rests on the unproved assumption that platelets keep a permanent memory of their injuries. Identifying the type of production disorder is the purpose of megakaryocyte kinetics. The daily production of megakaryocytes could be derived from the daily platelet production and the number of platelets released per megakaryocyte; determining megakaryocyte number would also yield the mean megakaryocyte maturation time. All these parameters could be obtained by combining a simple radioiron dilution method with cytochemical identification of megakaryocytes and with advanced, automated morphometric techniques. Abnormalities of megakaryocyte number and size can be further analyzed by studying the kinetics of thrombocytic precursors in tissue culture, i.e., by recording the distribution of precursor doublings and megakaryocyte ploidy histograms. The application of these techniques to cultures of bone marrow suggest that endomitosis may be initiated by any megakaryocyte precursor and that the kinetics of this process influence the number and final ploidy level of megakaryocytes.

Platelet formation in Mediterranean macrothrombocytosis.

Platelet size distribution and survival parameters were studied in control subjects and ten subjects presenting Mediterranean macrothrombocytosis. The comparison showed that the latter group maintains a normal platelet circulating mass (thrombocytocrit) by combining normal platelet survival, increased splenic pooling and production of a reduced number of greatly enlarged cells. In addition to offering new insight into the megakaryocytic mechanisms that determine platelet size, the study of Mediterranean macrothrombocytosis indicates that platelet size distributions and survival parameters should be integrated in order to provide a meaningful picture of human platelet kinetics.