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Biomedical subjects

M L Randi

Publications and source records attributed to M L Randi.

At least 37 records · Page 2Linked to original sources

Soluble plasma thrombomodulin levels in patients with chronic myeloproliferative disorder.

The plasma levels of soluble thrombomodulin (TM) were measured in 44 patients with chronic myeloproliferative disorder, 15 with polycythemia vera (PV), 29 with essential thrombocythemia (ET), and a group of 62 matched healthy controls. The younger patients had significantly lower TM levels (mean: 15.6 +/- 4.8 ng/mL) than the older patients (mean: 28.6 +/- 8.2 ng/mL, p < .001). Moreover, a significant negative correlation between platelet counts and plasma TM levels in healthy persons was noted (r = 0.317, p < .05). The only significant difference we found in plasma TM levels between patients and controls or among patients was between the young patients with ET (mean: 29.0 +/- 19.2 ng/mL) and young healthy controls (mean: 15.6 +/- 4.8 ng/mL). It is possible that younger ET patients with more active platelets are more susceptible to earlier vascular damage. The lack of any significant difference compared with the older patient population supports this hypothesis.

Adult↗

Aspirin seems as effective as myelosuppressive agents in the prevention of rethrombosis in essential thrombocythemia.

The course of essential thrombocythemia (ET) is complicated by bleeding, major thrombosis, and microvascular complications. Because about one-half of ET patients remain asymptomatic long term, the decision to use aspirin acetylsalicylic acid, (ASA) or myelotoxic drugs has not yet been clearly established. While vasomotor symptoms are improved by small doses of ASA, higher doses (900 mg/day) induce an unacceptable rate of serious hemorrhagic complications in patients with polycythemia vera. This retrospective study evaluates the utility of therapy in preventing thrombosis in ET and the efficacy and a safety of 100 mg/day of ASA in these patients. One hundred ninety-five consecutive patients with ET diagnosed in agreement with the Polycythemia Vera Study Group (PVSG) criteria are evaluated. All vascular complication before, at, or after diagnosis were recorded and related to the treatment used: no therapy, ASA alone, myelosuppressive agents or both. All treated patients had a significant reduction of thrombotic complications without increased hemorrhagic complications, in spite of therapy adopted. In addition, a significant reduction of rethrombosis was obtained in 60 patients with a previous thrombosis. A low rate of thrombosis (5.1%) was observed during the follow-up of the 135 patients previously asymptomatic for major complications. No difference appears to exist between the use of ASA and cytotoxic drugs in preventing thrombosis and rethrombosis in ET patients. However, the possible increase of cancer and leukemia with myelosuppressive drugs is minimized in patients treated with ASA. A low dose of ASA would seem to be a safe and effective agent in ET.

Adolescent↗

Acute coronary disease in essential thrombocythemia and polycythemia vera.

OBJECTIVES: The aim of this study is to report our experience on myocardial infarction (MI) in patients with essential thrombocythemia (ET) and polycythemia vera (PV). DESIGN: Patients with PV and ET consecutively diagnosed and followed in authors' Department between 1 July 1986 and 30 June 1996. SUBJECTS: Over the past 10 years we have followed 170 patients with ET and 149 with PV, diagnosed according to the Polycythemia Vera Study Group (PVSG) criteria. The patients were divided into 3 groups on the basis of the age at diagnosis (group A < 40, B 41-65, C > 65 years). INTERVENTIONS: In all patients with PV phlebotomies and/or myelosuppressive therapy were used to keep haematocrit level lower than 45%. Hydroxyurea was given to patients with ET with a positive history for major vascular complications or with an extreme thrombocytosis. Aspirin therapy (ASA) (100 mg per day) was administered in patients with microvascular disturbances or previous thrombosis (in patients with PV also in the presence of atherosclerotic risk factors). MAIN OUTCOME MEASURES: Frequency of MI in patients with ET and PV with and without ASA therapy. RESULTS: 9.4% of patients with ET and 11.4% of those with PV had MI. 17.6% of patients with PV were younger than 40 years at the moment of MI in contrast to 0% of those with ET. 75% of patients with ET and 70.6% of those with PV with MI had atherosclerotic risk factors such as smoking, hypertension, diabetes, dyslipidaemia. All patients with MI received ASA 100 mg daily after thrombosis and four of the ET group developed a transient ischaemic attack (TIA) afterwards. Four subjects with PV during the follow-up had TIAs and two peripheral arteriopathy in spite of ASA treatment. CONCLUSIONS: MI is less common in patients with ET younger than 40 years than in older patients. Association of MI and cardiovascular risk factors is frequent in patients with ET and PV. A low dose of ASA could be able to reduce the number of coronary thrombosis without increasing bleeding complications in patients with elevated platelet count and common atherosclerotic risk factors. However, a larger population must be evaluated to confirm our hypothesis.

Adult↗

Cerebral vascular accidents in young patients with essential thrombocythemia: relation with other known cardiovascular risk factors.

BACKGROUND AND PURPOSE: Since the advent of routine automated blood cell counts, an increased platelet count often is detected fortuitously in asymptomatic individuals. In the past, essential thrombocythemia (ET) was thought to be linked to an increase incidence of hemorrhagic complications, whereas thrombosis is now considered more frequently. Actually, the risk of thrombosis cannot be predicted in an asymptomatic patient with essential thrombocythemia. PATIENTS AND METHODS: A total of 41 young patients (age range, 18 to 45 years) affected by ET and diagnosed in agreement with the Polycythemia Vera Study Group criteria are reported. Common risk factors, such as hypertension, smoke, obesity, dyslipidemia, and diabetes, have been registered. Particular attention has been given to cerebral vascular accidents (CVA) both of the arterial and venous systems. Platelet number, platelet serotonin content, and platelet aggregation under collagen, adenosine diphosphate (ADP), and adrenalin stimuli were evaluated. RESULTS: Nine out of the 41 patients affected by ET had CVAs, four of which occurred in the venous system. No difference in platelet function tests has been observed between patients with or without CVA. Six out of the 9 patients with ET and CVA had at least one atherosclerotic risk factor: four were heavy smokers, one had hypertension, and one had hypertension and obesity. CONCLUSIONS: Cerebral vascular accidents are confirmed to be frequent in patients with essential thrombocythemia, even at a young age. However, the presence of at least one atherosclerotic risk factor associated with increased platelet number seems to favor thrombotic complications. In particular, cigarette smoking seems to be related to arterial CVAs in essential thrombocythemia.

Adult↗

Antiplatelet glycoprotein autoantibodies in patients with autoimmune diseases with and without thrombocytopenia.

The presence and specificity of antiplatelet autoantibodies in 32 patients with primary and 18 patients with secondary autoimmune thrombocytopenic purpura (AITP), as well as 11 non-thrombocytopenic patients with systemic autoimmune diseases, were studied. By means of the direct and indirect monoclonal antibody immobilization of platelet antigen (MAIPA) assay, antiplatelet autoantibodies were detected using monoclonal antibodies specific for platelet glycoproteins (GPs) Ib, IIb/IIIa, Ia/IIa, and IV. Serum antiplatelet autoantibodies were found in 18 of 32 primary AITP patients (56%), 6 of 18 secondary AITP patients (33%), and 5 of 11 nonthrombocytopenic patients (45%). Platelet-associated autoantibodies were detected in five of eight patients with primary (62%) and in four of eight patients with secondary AITP (50%) and in two of four patients without thrombocytopenia (50%). Multiple antibody reactivity, mainly against GPs IIb/IIIa and Ib and, in a few patients, against Ia/IIa, was found. Using MAIPA, platelet xylene eluates from 20 patients were also studied. Antiplatelet elutable autoantibodies were related to thrombocytopenia; autoantibodies against membrane GPs Ib and IIb/IIIa were demonstrable in 84 and 63% of eluates from patients with primary and secondary AITP, respectively, but not in eluates from nonthrombocytopenic patients. The presence of antiplatelet antibodies thus appears to be a common feature of many autoimmune diseases apart from the thrombocytopenia, but the (primary or secondary) etiology of the immune thrombocytopenia cannot be differentiated on the grounds of their specificity.

Adult↗

Essential thrombocythemia following polycythemia vera: an unusual sequence.

Myeloproliferative disorders (MPD) are prone to modification and evolution during the progression of the disease. While post-polycythemia myeloid metaplasia and chronic myelogenous leukemia following polycythemia vera have been frequently described, no report is available about the evolution of polycythemia vera into essential thrombocythemia. Our case is probably the first report on this occurrence. In the course of a fortuitous observation of electrocardiographic alterations, a diagnosis of polycythemia vera was ruled out in accordance with polycythemia vera study group criteria. At the time of diagnosis, RBC was 6 x 10(12)/L, WBC 15 x 10(9)/L, Ht 59% and platelets 1000 x 10(9)/L. The patient was treated with phlebotomies and radioactive phosphorus achieving a good remission or the disease. Five years later, platelets rose to over 3300 x 10(9)/L without significant modification or RBC, WBC and Ht. The restaging or the disease was consistent for an essential thrombocythemia. In particular, RBC mass was within normal levels. During the last ten years, the patient has been followed recurrently and the blood picture remained stationary, without an increase in the hematocrit but with a platelet count between 658 and 800 x 10(9)/L. We conclude that this report may complete data concerning the evolution of MPD in others.

Aged↗

Biotin-avidin immobilization of platelet glycoproteins (BAIPG): a new capture assay for the detection of anti-platelet antibodies.

Several 'capture' assays are currently employed to identify specific platelet antibodies, but all require the use of murine monoclonal antibodies (MoAbs) against the antigen of interest. We have developed a new antigen capture assay for the detection of platelet reactive antibodies, based on platelet surface sialoglycoprotein labelling with biotin hydrazide, and a following immobilization of the biotinylated platelet proteins to microtiter wells that had been coated with streptavidin. The resulting solid phase can then be used in a simple ELISA to detect serum and platelet associated antibodies. We describe here two versions of this biotin-avidin immobilization of platelet glycoproteins (BAIPG) assay. In BAIPG assay type I, the test sera are directly incubated in microtiter wells previously coated with streptavidin plus biotinylated platelet proteins. The BAIPG type II procedure involves the incubation of sera with biotinylated platelets before platelet solubilization, and, after platelet lysis, the immobilization of the immune complexes to streptavidin-coated wells. In both cases, the bound antibodies are determined by alkaline phosphatase conjugated anti-human IgG. Using BAIPG type I, positive results were obtained in 7/33 patients with idiopathic thrombocytopenic purpura (ITP), 1/10 patients with secondary immune thrombocytopenia (SIT) and 4/17 with non-immune thrombocytopenia (NIT). The BAIPG type II test was positive in 13 out of 33 patients with ITP, in six out of ten patients with SIT, and in three out of the 17 patients with NIT. A comparison between BAIPG and monoclonal antibody immobilization of platelet antigens (MAIPA) assays showed a high degree of correlation between the two methods. These results suggest that the BAIPG assay is a valuable new tool for the detection of anti-platelet antibodies.

Autoantibodies↗

Atopic dermatitis and allergic diseases with thrombocytosis: a possible link.

BACKGROUND: Thrombocytosis can be present in patients with myeloproliferative disorders or can accompany various conditions, in particular chronic inflammatory diseases, namely chronic bowel diseases, rheumatoid arthritis, and nephritis. OBJECTIVE: We report our experience in 55 patients younger than 45 years of age with increased platelet counts (over 500 X 10(9)/L). Thirty-three were affected by essential thrombocytemia in agreement with polycytemia vera study group criteria and 22 by reactive thrombocytosis. Serotonin concentration has been determine in all the patients. RESULTS: Serotonin was decreased as expected in 23 out of the 33 patients with essential thrombocytemia. In the remaining ten subjects, serotonin was within normal limits as in reactive thrombocytosis. Eight of these subjects had positive histories for allergic rhinitis and two for atopic dermatitis. CONCLUSIONS: Chronic inflammation, present in patients with diseases of the immune system may cause an increased platelet number. One should consider with caution patients with thrombocytosis and positive histories for diseases of the immune system; probably a diagnosis of essential thrombocytemia is not justified.

Adult↗

Essential thrombocythemia and pregnancy: a report of six normal pregnancies in five untreated patients.

OBJECTIVE: To report our experience with essential thrombocythemia complicating pregnancy. METHODS: Over a 5-year period, we studied 21 women of reproductive age affected by essential thrombocythemia. Diagnoses were based on previously published Polycythemia Vera Study Group criteria. RESULTS: Five of our 21 patients became pregnant (total six pregnancies). All pregnancies were carried to term, with uncomplicated deliveries of normally formed infants. No thrombotic or hemorrhagic complications were encountered. CONCLUSION: Normal pregnancy and delivery is readily possible in patients with essential thrombocythemia.

Adult↗

Specific antiplatelet autoantibodies in patients with antiphospholipid antibodies and thrombocytopenia.

By means of immunoblotting and monoclonal antibody immobilization of platelet antigens (MAIPA) we have studied the specificity of antiplatelet antibodies in patients with antiphospholipid antibodies and thrombocytopenia defined as presence of anticardiolipin IgG and a platelet count below 100 x 10(9)/l. The study group consisted of 10 patients with systemic lupus erythematosus (SLE), 8 patients with primary anti-phospholipid syndrome (PAPS) and 16 patients with idiopathic thrombocytopenic purpura (ITP). The comparison group was formed by 17 patients with classical chronic ITP without anticardiolipin IgG. We identified the 80-100, 130-150 and 150-170 KD surface proteins that comigrate with GPIIIa, GPIIb and GPIb and a 50-70 KD cytoplasm band by immunoblot. In patients with classical chronic ITP, the prevalence of the antiplatelet antibodies against GPIIIa was 53% on immunoblot assay and 47% on MAIPA. In ITP patients who had also anti-phospholipid antibodies in serum, the percentage of reactivity to GPIIIa declined to 37% on immunoblot and 21% on MAIPA but it was not statistically different from the percentage observed in patients with classical ITP. Autoantibodies to platelet surface glycoproteins were almost absent in SLE and PAPS patients, who showed a significant prevalence (78%) of IgG reactivity to the 50-70 KD internal platelet protein which was frequently encountered also in patients with ITP and aPL (56%). Our study provides additional evidence that platelet antigens in patients with phospholipid-associated secondary immune thrombocytopenia are different from those of primary ITP, and that surface glycoproteins were not involved.

Adult↗

Post-polycythemia myeloid metaplasia: experience with a large cohort of patients.

The common origin of myeloproliferative disorders can explain the possible evolution of polycythemia vera to post-polycythemia myeloid metaplasia (PPMM). Such a possible event is usually considered linked to the use of myelosuppressive agents in particular 32P. Occasionally, myelofibrosis following essential thrombocythemia has also been described. We report here 19 cases of post-polycythemia myeloid metaplasia out of 214 polycythemia vera patients (8.8%). The majority of these patients received 32P therapy. However, busulfan also seems to have some role in the modification of polycythemia vera. In particular, the association of more than one myelosuppressive agent may favour the evolution of PPMM.

Adult↗