British journal of haematology
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A survey of 870 different adult blood samples (primarily from patients with non-haematological disorders) found that 269 (31%) had increased proportions (> 25%) and/or absolute numbers (> 1.0 x 10(9)/l) of morphologically-defined large granular lymphocytes (LGL), and/or phenotypically-defined NK-associated (NKa) cells. Of these, 112 were re-analysed at least 6 months after initial presentation and were classified as 'persistent' (92/112) or 'transient' (20/112) according to whether or not the original abnormality was still present. Lymphocyte counts in most patients with persistent abnormalities were within normal limits (18/92) or slightly increased (68/92), with only six having a lymphocytosis exceeding 10.0 x 10(9)/l. ⋯ Persistent neutropenia (n = 15) also appeared to be associated with primary abnormalities of CD8+NKa+ cells (12/15), with 10 of these additionally showing rearranged TCR genes. In contrast, persistently increased CD8dim+NKa+ and CD8-NKa+ components did not appear to phenotypically differ from their corresponding 'counterparts' in normal bloods or in patients with transient LGL/NKa+ abnormalities. This survey has therefore established that persistent LGL/NKa+ abnormalities are considerably more common than suggested in published work, that a high proportion of patients with expanded CD8+NKa+ components, with quite diverse clinical histories, show evidence of clonal lymphoid populations, and that the clonal nature of such disorders appears to be associated with abnormal NKa phenotypic patterns.
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We have recently described the in vitro mechanism of action of anticardiolipin (aCL) and lupus anticoagulant (LA) antibodies in patients with the antiphospholipid syndrome. LA antibodies inhibit coagulation reactions in plasma because they appear to recognize the complex of lipid-bound (human) prothrombin, whereas aCL antibodies require beta 2-glycoprotein I (beta 2-GPI) for binding to anionic phospholipids. aCL antibodies can be divided into two subgroups, according to their behaviour in lipid-dependent coagulation reactions: aCL-type A enhances the anti-coagulant effect of beta 2-GPI, whereas aCL-type B does not. In the present study we investigated the effect of purified aCL-type A and B and of LA antibodies on the procoagulant activity of both Ca-ionophore activated platelets and platelet-derived microvesicles, using an assay system with highly purified bovine coagulation factors Xa, Va, and prothrombin from human and bovine origin. ⋯ LA antibodies were able to inhibit in a dose-dependent way the procoagulant activity of activated platelets and platelet-derived microvesicles. With two LA preparations this inhibition was only apparent when human prothrombin was used as substrate, while a third preparation exhibited its inhibitory effect both in the presence of human and bovine prothrombin. The data indicate that, in the presence of their respective cofactors beta 2-GPI and prothrombin, aCL and LA antibodies interact with the membrane of activated platelets and platelet-derived microvesicles in a very similar way as previously observed for their interaction with anionic phospholipid surfaces.