[Systemic effects of thrombolytic therapy].
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Biomedical subjects
Publications and source records attributed to G Gamba.
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In three patients with monoclonal gammopathies: a case of multiple myeloma, a case of monoclonal gammopathy of uncertain significance (MGUS) and a case of monoclonal gammopathy associated with lymphocytic lymphoma, we found the presence of a circulating lupus-like anticoagulant. Coagulative studies showed that the paraproteins: an IgG3k, an IgG1k and an IgMlambda, were responsible for the anticoagulant activity by interacting with the thromboplastin phospholipids. Using isoelectrofocusing we demonstrated that the three monoclonal immunoglobulins had a strong basic charge which may have contributed to determining their interaction with the acidic thromboplastin phospholipids. The binding of various phospholipids to the monoclonal proteins was assessed by the fluorescence quenching method which showed heterogeneous specificity. In order to establish whether the electrical charge is also relevant in cases with polyclonal lupus anticoagulant, the polyclonal immunoglobulins were fractionated according to their charge. The strongest inhibitor activity was found in the most basic immunoglobulins. Monoclonal lupus-like anticoagulants represent useful tools for investigating the heterogeneous world of polyclonal lupus-like anticoagulants.
We studied 113 patients treated with intravenous amikacin to determine the value of determining serial trough and peak amikacin levels in plasma for predicting nephrotoxicity. Thirteen patients (11.5%) developed renal toxicity, with significant increases from 48 to 96 h in both peak and trough amikacin levels (6.7 +/- 4.7 [standard deviation] days before the serum creatinine rose). The nontoxicity group had no change or even showed decrements in amikacin levels in plasma. A higher nephrotoxicity risk was seen in patients with increments greater than 1 microgram/ml between 48 and 96 h, with odds ratios of 16.4 for trough, 8 for peak, and 7.2 for both levels. We suggest that an increment of at least 1 microgram/ml in amikacin levels in plasma from 48 to 96 h may predict the appearance of renal toxicity.
We report the cytochemical and immunologic features of lymphocytes of 31 patients (26 with haemophilia A and 5 with haemophilia B) chronically treated with commercial clotting factor concentrates. 6 patients, asymptomatic for AIDS were anti-HIV positive. In comparison to aged cross-matched male controls, significant increases of absolute number of lymphocytes and of T and B cell subpopulations with significant reduction of the percentages of CD3, CD4, CD2, CD5, sIg, and CD16 cells was found in haemophiliacs. PAS reaction showed a lower grading score in haemophiliacs and the staining for NBE, AP, NABG revealed a significant reduction of the percentage of the lymphocytes with dot-like positivity in the same patients. The percentage number of AP reactive lymphocytes with dot-like positivity was directly related to the percentage of CD3, and CD4 cells. The anti-HIV positive patients presented lower percentages of CD4 and of dot-like reactive lymphocytes.
The relationship among blood lipids, haemostatic and fibrinolytic parameters have been evaluated, during a follow-up study, in 27 non-insulin dependent (type II) diabetic patients. Upon recruitment, and in periodical controls, we observed that plasma triglycerides and VLDL levels correlated inversely, and HDL directly, with the fibrinolytic activity of plasma and euglobulin precipitate. Furthermore triglycerides and VLDL correlated directly with Factor VIII antigen (vWFAg). After 5 years in the study, 12 patients (44%) had macroangiopathic complications, and 9 of these subjects showed persistently high levels of triglycerides (above 2.36 mmol/l). These haemostatic and lipid components, however, do not influence the progression of diabetic retinopathy and nephropathy. The alterations of lipid, haemostatic and fibrinolytic parameters and their possible relationships seem to play an important role in the occurrence of diabetic macroangiopathy.
Platelet aggregation in whole blood (WB) and in platelet rich plasma (PRP) was studied in 18 consecutive patients affected by idiopathic myelofibrosis (IM). On the basis of WB studies, 22% of patients were classified as normo-aggregating and 22% as hypo-aggregating, while 55% had spontaneous platelet aggregation (SPA). SPA was observed also when platelets from patients were stirred in the presence of normal erythrocytes, while it never occurred when normal platelets were stirred in the presence of red cells from patients. PRP studies revealed that 33% and 66% of patients were, respectively, hypo- and normo-aggregating. The most frequent abnormality in PRP was represented by defective or absent aggregation response to epinephrine.
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We studied the mechanisms of platelet activation by sublines exhibiting different metastatic potential of two murine experimental tumors: sublines M4 and M9 of the benzopyrene-induced mFS6 sarcoma and sublines B77-AA6 and B77-3T3 of RSV-transformed BALB/c 3T3 fibroblasts. The neoplastic cells of both models induced platelet aggregation, secretion and prostaglandin biosynthesis. In the first model but not in the second, all these processes correlated with the in vivo malignancy of cells. Pretreatment of B77-AA6 and B77-3T3 cells with apyrase significantly decreased platelet aggregation, while pretreatment of M4 cells was ineffective. However, pretreatment with trypsin or neuraminidase was effective in reducing platelet aggregation induced by M4 cells, but not that induced by any of the others; furthermore, phospholipase A2 reduced the platelet response by all sublines. Finally, platelet-activating activity was also found in the pellets obtained following centrifugation of culture media. These results suggest that platelets are stimulated by cancer cells through different mechanisms; platelet activation by a sialo-lipo-protein complex of the cellular membrane was found to be characteristic of the model in which the platelet-aggregating activity of neoplastic cells correlated with their in vivo metastatic behavior.
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The case is reported of a 78 year old female admitted to our Department with symptoms compatible with intestinal obstruction and melena. Upper gastrointestinal x-ray examination and endoscopy did not lead to a precise diagnosis. On the contrary, double contrast x-ray examination revealed the presence of a probably benign gastric tumour with gastroduodenal intussusception. Cholestasis was also present, as suggested by elevated serum conjugated bilirubin levels and by intravenous cholangiography. These findings were confirmed during surgical operation; a partial gastrectomy with gastroentero anastomosis was performed; histologic examination showed that the tumour was a gastric leiomyoma. All the symptoms disappeared quickly and the patient is still in good health after 2 years.
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The effect of Dimethylformamide on platelet function and on clotting system has been studied on eight workers exposed to the product, widely used in industry as a solvent of acrylic resins. A significant reduction of the number of the platelets and a drawing out of PTT and PT has been noticed. Such informations has been explained as chronical peripheral use or as modification of phospholipid components induced by DMF instead of synthesis defect, as no significant variation of the fibrinogen and of AT III values, proteins synthetized by liver, has been observed. The platelet aggregation has pointed out, in vivo, a reduction of ADP aggregation in the exposed subjects; in vitro, increasing quantities have determined an increasing reduction of the primary ADP and adrenaline aggregation.
In a previous study we found a correlation between metastatic potential and platelet aggregating activity in sublines of a benzopyrene-induced murine fibrosarcoma ( mFS6 ); the purpose of the present work was to elucidate the role of thromboxane biosynthesis by platelets and/or by neoplastic cells in the activation of platelets in this system. The cells of the more malignant subline induced higher aggregation and TxB2 production than those of the non metastasizing one. The supernatants of aggregating cell suspensions contained very few TxB2; furthermore, preincubation of platelets with ASA or Apyrase resulted in inhibition of aggregation and TxB2 production, while preincubation of the cells was ineffective; these results suggest the platelet origin of the measured TxB2 and indicate that platelet-derived ADP plays an important role in their activation, while the production of ADP by the cells does not seem to be relevant in this model. The involvement of platelet prostaglandin biosynthesis pathway in neoplastic cell induced platelet activation could play an important role in the development of platelet-dependent tumour metastasis.
The case of a young man with the plasma cell type of Castleman's disease is described. Beyond the well known systemic manifestations the coagulation tests showed a decrease in the activity of factors V, VIII and X due to the presence of lupus-like circulating anticoagulants. After surgical excision of the mediastinal mass both hematochemical pathological data and the coagulation defect disappeared. It is suggested that the lupus-like anticoagulant was secreted by the tumor.