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Biomedical subjects

M L Randi

Publications and source records attributed to M L Randi.

At least 73 records · Page 4Linked to original sources

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↗

Effect of heparin and aspirin on platelet and clotting activation during leukapheresis.

Beta-thromboglobulin (beta TG), serotonin (5HT) and fibrinopeptide A (FPA) were assessed in twenty-two normal donors before, during, and at the end of leukapheresis. Seven procedures were carried out adding heparin to the circuit, and seven adding acetyl salicylic acid (ASA). The remaining eight procedures were carried out using only citrate and served as controls. Plasma beta TG increased both during and after the apheresis, together with a significant decrease of the intra-platelet content. Platelet 5HT did not show significant changes whereas FPA increased significantly. Using heparin, we obtained a complete prevention of FPA cleavage during the entire procedure, while beta TG increased at the middle of the procedure. No significant effects were observed using ASA both on beta TG and FPA levels. These features clearly indicate the activation of platelets and the thrombin generation in the apheresis circuit. Nevertheless, the activation of the clotting system seems to be predominant, as supported by the improved effect of heparin on beta TG and FPA amounts.

Adult↗

The effect of different doses of 32P in the treatment of primary thrombocytosis.

We report on a follow up in 23 patients with primary thrombocytosis treated with two different doses of 32phosphorus phosphate (32P). Ten patients with essential thrombocytosis (ET) received 2 mCi and 13 patients with polycythemia vera (PV) received the standard dose of 0.1 mCi/kg b.w. The patients were listed as having a complete response (CR), partial response (PR) or no response (NR) considering platelet count at 3 and 12 months after 32P injection. The results indicate the existence of a clear correlation of the rate of remission with the 32P injected dose. PV patients show, in fact, a percentage of complete remission higher than ET patients. However, the use of higher doses induces more early and long-term complications.

Adult↗

Effects of ticlopidine on blood fibrinogen and blood viscosity in peripheral atherosclerotic disease.

Ten patients with peripheral atherosclerotic disease(PAD) treated with 750 mg/d of 5-(2-chlorophenylmethyl)-4,5,6,7-tetrahydrothieno (3,5-c-pyridine) hydrochloride (ticlopidine, Tiklid) were studied for three months. As control was studied a similar group of patients treated with a traditional vasodilator (nicotinate). The aim of our study was to evaluate the effect of ticlopidine both on the clinical evolution of the disease and on rheologic, coagulative and platelet parameters. A progressive increase of maximal walking distance was noted during the three months of therapy with ticlopidine and limited to the first 30 days of treatment with nicotinate. The fibrinogen levels resulted significantly lowered during 90 days of treatment with ticlopidine, while that was not evident in the nicotinate group. There was also a slight improvement of blood viscosity in the ticlopidine group (not evident in the nicotinate group), but it was not statistically significant. No further modifications of investigated data were found in the two groups of patients. The clinical benefit of ticlopidine in PAD without adverse reactions can be confirmed at least at the dosage of 750 mg/d instead of the usual dose of 500 mg/d. A direct or indirect action of ticlopidine on plasma fibrinogen is suggested. This observation may supply new clues for the understanding of the mechanism of action of this drug.

Aged↗

Clinical significance of beta-thromboglobulin in patients with high platelet count.

The aim of the study was to investigate the relevance of beta-thromboglobulin (beta tg) measurement in patients with thrombocytosis. We have, therefore, studied the level of plasma and platelet beta tg in 74 patients with high platelet count in addition to the evaluation of platelet aggregation and platelet serotonin (5-HT) content. The determinations of platelet serotonin content and aggregation are confirmed to be useful in the differentiation between primary and secondary forms of thrombocytosis. The mean plasma level of beta tg in patients with myeloproliferative disease was significantly raised, but the amount observed in subjects with secondary thrombocytosis is increased too. Considering the amount of beta tg in relation to whole blood platelet count (beta tg ratio), no difference was observed between all patients and controls. The beta tg ratio allowed the identification of a group of patients with an increased ratio and a decreased beta tg platelet content who showed the highest occurrence of thrombosis (66%).

Adult↗

Failure of sulphinpyrazone to affect platelet survival in patients with rheumatic heart valvular disease: a double blind study using 75Se-methionine labeled platelets.

We have investigated platelet survival time in 18 patients suffering from valvular heart disease. Platelet survival was performed using the 75Se-methionine method modified by us. Nine of our eighteen patients underwent surgery for heart valve replacement. Platelet survival time was performed before treatment and six months afterwards with placebo or sulfinpyrazone in a double blind study. Before treatment and surgery, platelet survival time was significantly reduced in patients with a history of embolism (P less than 0.0048). In patients receiving valve replacement, platelet survival time was shortened both in the sulfinpyrazone and placebo groups six months after surgery. Of the nine patients not receiving prostheses and with a thrombotic history, treatment with placebo and sulfinpyrazone resulted in improved platelet survival times.

Adult↗

Potentiation of anticoagulant response to warfarin by sulphinpyrazone: a double-blind study in patients with prosthetic heart valves.

The effect of Sulphinpyrazone on the anticoagulant response to Warfarin was evaluated by a double-blind study in 11 patients with prosthetic heart valves. Six patients received Warfarin and Sulphinpyrazone and 5 Warfarin and placebo. Sulphinpyrazone potentiated the anticoagulant effect of Warfarin. Patients receiving Sulphinpyrazone needed about half the amount of Warfarin as compared to the control group. There were four bleeding episodes in the Sulphinpyrazone group and one episode in the control group. It was difficult to regulate the dose of Warfarin in patients also receiving Sulphinpyrazone.

Adult↗

75Se-methionine platelet survival studies: a proposal for a mathematical correction of the curve.

We studied platelet survival in 14 cardiac before heart valve replacement using 75Se-methionine 'cohort label'. The temporal variation of plasma and platelet activity was plotted by a continuous curve by means of a computerized interaction of the single points. Then we computed the plasmatic radioactivity fraction used daily for thrombopoiesis and made a subtraction of this aliquot from a experimental activity in the catabolic phase of the slope. Platelet life span obtained after this 'correction' is comparable with the values of random label using 51Cr.

Adult↗

Increased number of pseudodrumsticks in neutrophils and large platelets. A "new' congenital leukocyte and platelet morphological abnormality.

2 members of a family, a child and his father, showed a combined morphological abnormality of leukocytes and platelets. The abnormality consisted of the presence of pseudodrumsticks in the neutrophils and of large platelets. One or more than one pseudodrumstick was present in about 40% of neutrophils. Leukocyte count, differential count and enzymatic stains were normal. Large platelets constituted about 25% of the platelet population. 1 patient also had mild thrombocytopenia which appeared to be unrelated to the basic defect since it appeared after a parotitis infection. Platelet function was normal but for a moderate prolongation of the bleeding time in the patient who had mild thrombocytopenia. No chromosomal abnormality was present in the propositi. The condition seems different from other leukocyte and platelet abnormalities so far described.

Adult↗

Plasma and platelet beta-thromboglobulin levels in patients with May-Hegglin anomaly.

Plasmatic beta-thromboglobulin (BTG) has been assayed in 5 patients with May-Hegglin anomaly. All patients showed a normal BTG plasmatic level. The plasma BTG/number of platelets ratio resulted to be elevated but this was due to the low platelet count typical of the disease. The platelet content in BTG was studied in only 2 patients and was found to be four times the normal value; however, the circulating BTG platelet mass in these patients resulted to be within normal limits.

Adolescent↗

Platelet-specific proteins in patients with transient ischemic attacks. (Effects of anti-platelet drugs).

Levels of beta-thromboglobulin and platelet factor 4 in 46 patients with transient ischemic attacks and the influence of treatment with dipyridamole or aspirin plus dipyridamole were evaluated. Patients not receiving therapy showed levels of beta-thromboglobulin significantly higher than controls. However, patients taking only dipyridamole showed values of beta-thromboglobulin significantly lower than untreated patients or those taking aspirin plus dipyridamole. No significant difference was observed with regard to platelet factor 4 between the patients.

Adult↗

Identification of anti-platelet autoantibodies by western blot in 45 patients with idiopathic thrombocytopenic purpura (ITP).

BACKGROUND: In sera and platelet eluates of ITP patients, antigen specificity was widely studied by means of sensitive methods including immunoprecipitation, monoclonal antibody immobilization, and immunoblot. These studies indicated that GPIIb-IIIa were the main epitopes of ITP autoantibodies. METHODS: We studied the specificity of antiplatelet autoantibodies in 45 patients with acute and chronic ITP. Patient sera were tested by Western blot on separated platelet proteins in non-reducing conditions; antibody binding was identified using biotinconjugated anti-human IgG and avidin-peroxidase. RESULTS: Two main nonspecific bands of 200 and 125 kD were visible using normal serum; the first referred to platelet IgG, and the second was due to a naturally occurring antibody towards an internal protein. Twenty-five sera (55%) stained one (n = 11), two (n = 7), three (n = 3) or four (n = 4) specific bands. In patients with chronic ITP there was a prevalence of multiple bands. The relative molecular weights of the recognized antigens were in the range of 140-160, 80-100, 50-70 and 40 kd. The 80-100 epitope was recognized as a membrane protein in only 40% of sera, and it was partially characterized as GPIIIa in 4 patients. The other stained epitopes were absorbed by platelet lysate and then identified as internal proteins. CONCLUSIONS: This finding might be related to sensitization to antigens exposed by platelets during immune damage, and may pose an important problem in the identification with the immunoblot technique of target antigens responsible for immune sequestration.

Adult↗

Sex and age as prognostic factors in essential thrombocythemia.

BACKGROUND: The major causes of morbidity and mortality in essential thrombocythemia (ET) are bleeding and thrombotic accidents, but a prognostic pattern for these complications has not yet been discovered. MATERIALS AND METHODS: In this study we report data from a large cohort of patients with thrombocytosis, distinguished for sex and age, in order to define their thrombotic risk. The prevalence of vascular complications recognized in 86 patients with essential thrombocythemia was studied. In addition, 91 patients with polycythemia vera (PV), 20 with myelofibrosis (MF) and 63 with secondary thrombocytosis (ST) were evaluated. RESULTS: 6.3% of ET subjects younger than 40 (4.6% of males and 7.0% of females), 11.8% of patients between 40 and 65 years old (14.9% of males and 9% of females), and 16.8% of subjects over 65 (14.6% of males and 17.8% of females) showed thrombotic accidents. In the PV and MF groups thromboses occurred more frequently than in the ET groups for all ages and for both sexes. On the contrary, ST subjects showed fewer thromboses than ET patients, but their incidence rose with patient age; moreover the prevalence of males in this group was limited. In ET patients, particularly in females, the incidence of thrombosis was low under 40 years of age, but rapidly increased later. CONCLUSIONS: ET females over 40 must be followed with particular attention in order to prevent thrombotic complications.

Adult↗

The use of fluorescence flow cytometry in the characterization of Bernard-Soulier syndrome and Glanzmann's thrombasthenia.

We have used flow cytometry analysis of fluorescence to study the binding of murine monoclonal antibodies to platelets. Anti-platelet glycoproteins Ib (AP1), the complex IIb-IIIa (LJP9) and the FITC-conjugated second antibody were added directly to the sample of platelet rich plasma without washing. The analysis was performed in normals and in patients affected by the Bernard-Soulier syndrome and Glanzmann's thrombasthenia and compared to the direct binding of radioiodinated monoclonas. Comparable results were obtained. A symmetric profile of fluorescence for both glycoproteins Ib and IIb-IIIa was observed in normals and in the patient group, which indicates homogeneous distribution of these glycoproteins on the platelet surface. The develop technique allows identification of homozygous and heterozygous carriers of the platelet disorders studied and quantification of the defect, which seems to be due to a homogeneous decrease of specific glycoproteins in all platelet populations.

Adult↗