Biomedical subjects
Publications and source records attributed to P Viero.
Platelet function was assessed in 17 patients with hairy cell leukemia who had undergone splenectomy. Defective PAF-induced aggregation and selective reduction of beta-thromboglobulin were found in platelets from six and eight patients respectively. These defects were not necessarily associated with bleeding complications.
Several investigators have suggested that hairy cells are neoplastic B lymphocytes. These cells, however, also share some biological properties with mononuclear phagocytes. A property of these cells is the capacity to generate procoagulant activity (PCA) in response to a variety of stimuli. In this study we investigated the PCA of peripheral blood hairy cells in 19 consecutive patients with hairy cell leukaemia (HCL). Monocyte-depleted blood mononuclear cells, tested immediately after isolation, expressed little, if any, activity. However, after exposure to endotoxin, a marked increase in PCA was observed (42.1 +/- 8.7 vs 1.3 +/- 0.2 units/5 X 10(1) hairy cells). A significant correlation was found between the number of lymphocytes/hairy cell and the level of endotoxin-induced PCA suggesting that lymphocytes potentiate the procoagulant response of hairy cells. When stimulated with 12-0-tetradecanoyl-phorbol-13-acetate (TPA), patients' cells produced about 2-8 times more PCA than endotoxin-stimulated cells. The PCA induced by endotoxin and TPA was identified as tissue factor. These findings suggest some further relationship between hairy cells and monocytes.
6 patients with a chronic, clinically heterogeneous proliferative disorder of the large granular lymphocytes (LGL) were investigated. In each case the majority of peripheral blood lymphocytes reacted with HNK-1, OKT3 and T11 monoclonal antibodies, whereas morphology and other immunological features varied from case to case. 2 cases were of particular interest. 1 patient had an expansion of HNK-1 stained, large agranular rather than granular lymphocytes; another patient's LGL simultaneously expressed HNK-1, OKT4 and T8 antigens. The heterogeneous features of these abnormally expanded cell populations are similar to those of the normal cell subsets from which they are likely to have originated.
Platelets from 6 out of 10 patients with myeloproliferative disorders showed only a single reversible wave of aggregation when challenged with platelet activating factor (PAF). Preexposure to subthreshold concentrations of adrenaline resulted in a full irreversible response to PAF. Aspirin, however, removed this synergism. In the remaining 4 patients, PAF induced a full response but aspirin abolished the synergism with adrenaline in 2 of them. In platelets from all controls aspirin failed to abolish the synergism between PAF and adrenaline. It is suggested that patients with myeloproliferative disorders lack - to varying degrees - an aspirin-independent mechanism which amplifies the primary response to PAF. Such a mechanism could involve the products of arachidonic acid metabolism catalyzed by lipoxygenase.
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We have investigated 10 patients with T gamma-lymphoproliferative disorders (T gamma LPD) for cell migratory capacity. Large granular lymphocytes (LGLs) expanding in these subjects expressed natural killer cell markers (HNKI, B73.1, AB8.28, N901, OKM1) to a variable extent. The patients' LGLs mediated antibody-dependent cellular cytotoxicity, while appreciable natural killer activity was only measurable in 3 patients. The migratory capacity of T gamma LPD was examined by using nitrocellulose filters. The patients' LGLs migrated into filters and showed responsiveness (in 9 of 10 patients) to activated serum, used as chemoattractant, as normal LGLs do. No clearcut correlation emerged between in vitro migratory capacity and disease aggressiveness or involvement of abdominal organs. These results confirm in T gamma LPD the migratory potential of LGLs and suggest the possibility that acquisition of enhanced locomotor capacity is not a crucial determinant of disease aggressiveness in T gamma LPD.
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Platelets of patients with myeloproliferative disorders (MD) such as polycythaemia vera (PV), chronic myelogenous leukaemia (CML), idiopathic myelofibrosis (IM) and essential thrombocythaemia (ET) have been found to have low 5HT levels measured both by a fluorimetric and a liquid chromatographic assay. Km and Vmax for platelet active uptake of 3H-5HT were not significantly different in controls and patients. Inhibition of 5HT reuptake by imipramine or induction of moderate release by fenfluramine were not sufficient to distinguish the group of MD platelets from controls, although some patients had less of a tendency to retain intraplatelet amine. The low platelet 5HT content found in our patients seems not to be the consequence of disturbed active transport of 5HT across platelet membrane. Although defective storage of this amine within the cell is probable, the results of the present study do not rule out the possibility that platelets from MD patients undergo in vivo activation by endogenous stimuli not inhibited by aspirin. 10 d treatment with aspirin did not result in any significant rise in intraplatelet 5HT concentration.
Fourteen patients with idiopathic thrombocytopenic purpura (ITP) refractory to steroids and/or splenectomy were treated with danazol (200 mg 3 times a day) for 2 months. The following responses were achieved: excellent (platelet count greater than 100 X 10(9)/l) in 5 patients; good (greater than 50 X 10(9)/l, but less than 100 X 10(9)/l) in 2 patients, and poor in (no increase of platelet count) 7 patients. In three cases remission lasted more than 7 months. Danazol was well tolerated and in most patients better suited than steroids for long-term intake.
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A patient with concurrent multiple myeloma and B-cell chronic lymphocytic leukemia (CLL) is presented. Immunologic studies showed an identity between the myeloma protein and surface immunoglobulin of CLL cells.
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A case of childhood chronic neutropenia due to myelokathexis is reported. This extremely rare condition (the fourth case in the literature) has been diagnosed from the characteristic bone marrow abnormalities in the neutrophils.
80% of patients with chronic autoimmune thrombocytopenic purpura (ATP) may reach normalization of platelet count after steroids or splenectomy. In some of these cases a bleeding tendency may still persist and this has been attributed to abnormalities of platelet function resulting from the effect of platelet-bound antibodies. We have studied 49 ATP patients in order to assess the frequency and the pattern of this immune thrombopathia, and the correlation with the levels of platelet associated IgG (PAIgG). Only 3 patients (6%) had prolonged bleeding time and persistence of mucocutaneous haemorrhages, whereas 36% presented an altered platelet aggregation pattern. Platelet serotonin content, platelet and plasma beta-thromboglobulin concentration, and malondialdehyde generation after thrombin stimulus were found also altered, but the findings were not clearly correlated with the concentration of PAIgG.
Procoagulant activity of peripheral blood mononuclear leucocytes was studied in 24 consecutive patients with Hodgkin's disease. Mononuclear cells, tested immediately after isolation, expressed very low activity which was, however, somewhat higher than that of cells from a matched control group (P = 0.063). Procoagulant activity generated by patients' mononuclear cells following stimulation with bacterial endotoxin was significantly higher than that produced by control cells (P less than 0.01). There was no apparent relation between procoagulant activity and pathological staging. The increased capacity of mononuclear phagocytes to produce procoagulant activity might help explain activation of blood coagulation and subsequent fibrin deposition in patients with Hodgkin's disease.
A series of 101 consecutive patients with chronic myeloproliferative disorders including polycythaemia vera, chronic myelogenous leukaemia, idiopathic myelofibrosis and essential thrombocythaemia have been studied. The aim was to establish the incidence of thrombotic and haemorrhagic complications and the possible role played by platelet number and function. The total incidence of haemostatic complications was 21% and the platelet functional tests investigated (platelet aggregation, generation of malondialdehyde, endogenous serotonin, beta-thromboglobulin and platelet coagulant activity) were of little help for predicting these clinical complications.
Chronic lymphocytic leukaemia (CLL) is associated with a low incidence of thrombotic complications, or disseminated intravascular coagulation (DIC), or both, despite the frequent occurrence of severe infections. We have investigated the capacity of blood mononuclear cells to produce procoagulant activity when stimulated with bacterial endotoxin in 16 patients with untreated chronic lymphocytic leukaemia (CLL). Procoagulant activity generated by patients' cells after prolonged incubation with endotoxin was significantly lower than that produced by cells from a matched control group (p less than 0.001). The defect could not be attributed to an inhibitory effect of leukaemic lymphocytes. It is suggested that in CLL the monocyte has an intrinsic functional abnormality of the procoagulant response to endotoxin and possibly to other stimuli. These findings help explain why CLL patients do not develop thrombotic complications despite the high incidence of severe infectious diseases.
14 patients with myeloproliferative diseases (MD) showed low 5-hydroxytryptamine (5-HT) platelet content and high beta-thromboglobulin (beta-TG) plasma levels. This pattern could support the view that MD platelets undergo "in vivo" degranulation. A single dose of aspirin was unable to induce modifications of platelet 5-HT and plasma beta-TG, whereas 6 out of 14 patients treated over 7 days period with the drug showed a decrease but not normalization in their beta-TG levels. No modification of platelet 5-HT was obtained suggesting that the cause of dense bodies deficiency may lie in the production of abnormal platelets and not be related to "in vivo" degranulation.