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Biomedical subjects

M L Randi

Publications and source records attributed to M L Randi.

At least 19 recordsLinked to original sources

Labeling of platelet surface glycoproteins with biotin derivatives.

We describe a non-radioactive method for the labeling of platelet surface proteins, consisting of platelet protein biotinylation by means of N-hydroxysuccinimido-biotin (NHS-B) and biotin-hydrazide (H-B); NHS-B labels proteins amino residues while H-B binds to periodate-modified sialoglycoproteins. Washed platelets were biotinylated and protein bands were detected after SDS-electrophoresis and western-blot using avidin-peroxidase and luminol as substrate to enhance the signal which was then detected by X-ray film. Biotin-labeled platelet proteins were also immunoprecipitated with monoclonal antibodies against glycoproteins Ib and the IIb-IIIa complex. The use of periodate induced biotinylation is the method of choice for labeling platelet surface glycoproteins while NHS-B also labels internal proteins. The sensitivity of this new procedure is similar to that obtained with radiolabeling techniques; biotinylation does not interfere with the antigenic properties of Ib and IIb-IIIa glycoproteins.

Antibodies, Monoclonal

Incidence of thrombocytosis in lymphomas.

Reactive thrombocytosis due to malignancies and in particular those related to lymphomas have not yet been extensively evaluated. We report data on thrombocytosis recognized in 18 out of 101 patients with lymphomas diagnosed in our department over the last 3 years. All showed high platelet counts at the time of diagnosis. The incidence of thrombocytosis seems to be more frequent in males (21.2%) than in females (14.8%) and a slightly higher frequency was found in Hodgkin's disease (21.4%) than in non Hodgkin's lymphomas (16.4%). The incidence of thrombocytosis in lymphomas seems to be similar to that seen in other malignancies and because of this we conclude that a high platelet count cannot be used to distinguish malignancies.

Bone Marrow

Indobufen versus dipyridamole plus aspirin in the treatment of patients with peripheral atherosclerotic disease.

Twenty-seven patients with peripheral atherosclerotic disease were randomized into two therapy regimens consisting of indobufen (Indo) (400 mg/day) and dipyridamole (Dip) (225 mg/day) plus acetylsalicylic acid (ASA) (1 g/day), respectively. Maximal walking distance (MWD) and ankle-arm systolic pressure ratios were measured before and after three and six months of therapy; bleeding time, beta-thromboglobulin (beta-TG), platelet factor 4 (PF4) and serum thromboxane B2 (TXB2) were also assessed. The two treatment groups showed a significant and progressive increase in pain-free walking distance at both three and six months of therapy, but patients taking indobufen showed a greater improvement. On the contrary, the pressure doppler ratio at rest was statistically improved only in the ASA plus Dip group. Basal beta-TG and PF4 levels were normal and no changes occurred during the study in either group, while in all patients bleeding times showed a significant increase above basal values and serum TBX2 decreased.

Aged

Effect of human recombinant erythropoietin on bleeding time, platelet number and function in children with end-stage renal disease maintained by haemodialysis.

We studied platelet number and function in nine anaemic children with end-stage renal disease during a clinical trial with recombinant human erythropoietin (rHu-EPO). All the children showed a correction in both haematocrit and haemoglobin levels which was followed by a significant reduction in bleeding time. We also observed a significant increase in platelet count after both 6 and 12 weeks of therapy; at the same time mean platelet volume decreased and a normal platelet mass was maintained. The mean baseline platelet aggregation response to ADP was normal, but was decreased to collagen (P less than 0.05 vs normal control). Platelet production of thromboxane B2 in serum was also lower than normal controls. After correction of anaemia with rHu-EPO, platelet aggregation improved in patients with a decreased baseline response, and mean levels of thromboxane B2 became normal. In conclusion, the treatment with rHu-EPO improved haemostatic balance not only by correcting anaemia, but also by increasing platelet count and function.

Adolescent

Use of a radioimmunoassay for 5-hydroxytryptamine (5-HT) in thrombocytosis.

A decrease in intra-platelet 5-hydroxytryptamine (5-HT) may be a possible marker for primary thrombocytosis and there are several different methods for the measurement of platelet 5-HT content (e.g. fluorimetry, high-performance liquid chromatography and radioimmunoassay). The present study has shown that, in laboratories with radioprotected areas, radioimmunoassay of 5-HT is a simple method which correlates well with a standard fluorimetric technique and yields satisfactory results in patients with thrombocytosis.

Adult

Thrombosis and hemorrhage in thrombocytosis: evaluation of a large cohort of patients (357 cases).

We report clinical and laboratory findings in a large cohort of patients with thrombocytosis (357 cases). At the time of study, the patients showed a platelet number greater than 500 x 10(9)/L. The follow-up of patients ranged between 3 and 16 years. 123 patients were affected by polycythemia vera (PV), 97 by essential thrombocythemia (ET), 13 by chronic myeloid leukemia (CML) and 31 by myelofibrosis (MF). In 93 subjects, the thrombocytosis was reactive (ST). We found the highest incidence of thrombosis in PV patients, especially concerning the cerebro-vascular system; thrombosis, but in a lower percentage, was recognized in MF patients. Also, ET patients showed a number of thrombosis in peripheral arteries. Thrombosis of the coronary arteries were quite rare while 25% of MPD subjects showed peripheral vein thrombosis. We take into account that many patients showed thrombocytosis associated to one or more atherosclerotic risk factors. Hemorrhages were present especially in CML and in ET, but were not as frequent as thrombosis. The most common bleeding manifestations affected skin and mucosa. Hemorrhages after surgical procedures were also frequent. Gastro-intestinal bleeding was not strictly related to anti-aggregating therapy and occurred not only in PV but also in ET patients.

Adult

Decrease of fibrinogen in patients with peripheral atherosclerotic disease by ticlopidine.

Ticlopidine (Ticlodone: CAS 55142-85-3) is able to develop a positive effect on claudication in patients affected by peripheral atherosclerotic disease (PAD). It is also known that ticlopidine decreases fibrinogen levels in plasma. 15 PAD patients treated with ticlopidine for 3 months were studied, evaluating the drug's effect both on maximum walking distance and on fibrinogen. Plasma fibrinogen as coagulable protein, fibrinogen antigen (Partigen method), 125I-fibrinogen survival, euglobulin lysis time and plasminogen were determined with the aim of clarifying if the decrease of plasma fibrinogen induced by ticlopidine is due to an increased destruction of a decreased production of the molecule. The normal levels of all tests before and after therapy both in ticlopidine treated patients and in the control group (acetylsalicylic acid + dipyridamol) indicate that the two hypotheses are not true. It is proposed that ticlopidine developing the known effect in decreasing the binding of fibrinogen to platelets induces a decrease only of activated fibrinogen.

Adult

Thrombocytosis in young people: evaluation of 57 cases diagnosed before the age of 40.

Over the past 13 years 57 cases of primary thrombocytosis in young people have been studied. Only patients with a platelet count over 500 x 10(9)/liter and a follow-up longer than 2 years were considered. Thrombocytosis in young people represents approximately 25% of total cases referred to our department during this period. The most common causes are essential thrombocythemia (20 cases) and secondary thrombocytosis (22 cases). The highest platelet counts are found in essential thrombocythemia patients. Most of our patients were discovered by a fortuitous hematological examination. In contrast, 5 out of the polycythemic patients were recognized after a thrombosis. The same was true for 2 out of 20 essential thrombocythemia subjects. Four subjects (2 essential thrombocythemia and 2 secondary thrombocytosis) were diagnosed after hemorrhages. The overall survival was very good except for leukemic patients and thrombocytosis secondary to neoplasms. Vascular complications after diagnosis were scarce: 2 polycythemia vera patients showed bleedings during antiaggregating therapy. None of our patients developed epithelial cancer, malignant lymphoma or myelofibrosis. Vascular traumata seem more frequent in polycythemia vera regardless of age. Therefore, it seems useful to treat polycythemic patients, while no therapy seems to be indicated in other forms of thrombocytosis.

Adult

Multiple, relapsing thrombosis in a young man with primary thrombocytosis.

We report the case of a relatively young man with multiple and fatal thrombosis associated with essential thrombocythaemia. The clinical and laboratory examinations performed before his death were in agreement with the diagnostic criteria proposed by PVSG. The autopsy revealed myocardial infarction and pulmonary embolisms. This case suggests that young patients with primary thrombocytosis should be treated with antiplatelet agents in spite of the absence of other thrombotic risks.

Humans

Haematological complications in polycythaemia vera and thrombocythaemia patients treated with radiophosphorus (32P).

We have evaluated 230 patients with myeloproliferative disorders treated in the last 15 years with 32P. None of the patients affected by essential thrombocythaemia developed haematological complications. In the larger group of polycythaemia patients (214 subjects) only 38 patients (17 males and 21 females) developed complications. 60.5% of these subjects had a minor complications: 1.8% showed a thrombocytopenia lower than 100.10e9/lt, 2.3% anaemia with Hb lower than 10 g%, 2.6% leukopenia lower than 40.10e9/lt and 2.3% a pancytopenia. All these complications were transient and eventually treated with limited blood transfusions. We could not identify a correlation between the dose used and the development of such complications. We noted only that the occurrence of anaemia, given a similar dose, was more frequent in females. Only 7% of all patients presented a major complication after 32P administration. In this case too, there was no correlation with the dose administered. Myelofibrosis and chronic myeloid leukaemia resulted to be the more frequent complication (9 out of 15) but we could not clarify if they represented a natural evolution of polycythaemia vera or were due to the treatment with 32P. Acute leukaemia developed only in 5 patients and again we could not recognized a correlation with the dose administered. Moreover, the time from the diagnosis of polycythaemia vera the onset of acute leukaemia ranged widely. 32P has a definite effect on the prevention of thrombotic and haemorrhagic complications in polycythaemia patients since it prolongs their life but it also increases the incidence of acute leukaemia.

Anemia

Response to splenectomy in idiopathic thrombocytopenic purpura: prognostic value of the clinical and laboratory evaluation.

Sixteen patients with chronic idiopathic thrombocytopenic purpura underwent splenectomy after failure of steroid therapy. The average time of follow-up was 69 months. Immediately after splenectomy, complete response (platelets above 150 x 10(9)/l) was obtained by 68% of patients while 25% had partial response (platelets from 50 to 150 x 10(9)/l) and only in 1 patient splenectomy failed. During the long-term follow-up, 2 patients relapsed 9 and 20 years, respectively, after splenectomy (20% of non-responders). Partial recurrence of thrombocytopenia (partial response) was observed in 33% of the patients. The persistent complete response rate was then 47%. The young patient age appears to be the only positive predictive factor both for short-term and long-term response to splenectomy. The platelet recovery rate and postsplenectomy thrombocytosis are also early features of lasting response. Positive serum and platelet-associated immunoglobulins became negative after splenectomy, but there is no correlation with clinical response.

Adult

Low incidence of familial occurrence of thrombocythaemia and/or thrombocytosis.

Several reports have been published about familial polycythaemia vera (PV) but no information is available about the incidence of thrombocytosis in the same family. In our population of thrombocytosic patients, both with primary thrombocytosis (133 cases) and secondary (37 cases), we found only two family related subjects. One of them had PV and the other essential thrombocytosis (ET). Our results seem to indicate that familial thrombocytosis is a rare phenomenon, much less frequent then familial thrombocytopenia.

Adolescent

The significance of thrombocytosis in old age.

We performed a retrospective study on 21 patients, aged 70 years or more, affected by polycythemia vera (PV) or essential thrombocythemia (ET). As controls, we evaluated 10 younger ET patients. The results indicate that in older ET subjects there was a lower incidence of hemorrhagic and thrombotic complications than in younger patients and PV patients. However, platelet number and platelet function tests were similar in all the patients studied. We suppose that an increase in hematocrit as seen in PV is much more dangerous as compared to an isolated increase in platelet count, and that thrombocytosis alone in old age can be an isolated expression of a natural involution of blood marrow similar to myelofibrosis.

Adult

Evaluation of platelet function in postsplenectomy thrombocytosis.

The usually transient post-splenectomy thrombocytosis has no well defined effect on the development of thromboembolism. We studied 14 patients submitted to splenectomy for different causes: portal vein thrombosis (PVT), idiopathic thrombocytopenia purpura (ITP) and lymphoma. The mean platelet count in PVT patients was significantly higher than in all other subjects. In PVT group we demonstrated various alterations in platelet aggregation curves and a frequent increase of platelet 5-HT levels. In effect, we noted that all the PVT patients showed a myeloproliferative disease (MPD) before the surgical procedure. We therefore conclude that the increased incidence of thromboembolism in the patients who underwent splenectomy is probably caused by a preexisting MPD rather than the post-splenectomy thrombocytosis.

Adult

Clinical significance of surface and internal pools of platelet-associated immunoglobulins in immune thrombocytopenia.

We have investigated serum platelet bindable IgG(SPBIgG) and platelet-associated IgG(PAIgG) in patients with immune thrombocytopenia (IT) to ascertain the significance of the larger amounts of PAIgG reported both in normals and in patients using homogenized (Total:T-PAIgG) instead of intact platelets (Surface:S-PAIgG). 12 patients, during active immune thrombocytopenia (A-IT), and 18 patients in steroid-induced remission (S-IT), were studied. As control we considered 20 patients with non-immune thrombocytopenia (N-IT) and 29 subjects with normal platelet count. The average positivity of SPBIgG was 41% with a higher percentage in A-IT (66%) than in S-IT (16%). The results of PAIgG also indicate a different behaviour in A-IT and S-IT of surface and cytoplasmatic pools. During A-IT both pools are enhanced with prevalence towards the surface one (S-PAIgG). On the contrary, during steroid-induced remission, despite the normal amount of the S-PAIgG present the internal pool still increases, indicating a steady-state of IT and the possible existence of a platelet phagocytic activity.

Adult