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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
PubMed2006

Blood oxidative status and selectins plasma levels in healthy donors receiving granulocyte-colony stimulating factor.

Recombinant human G-CSF (rHuG-CSF) is used for hematopoietic progenitor cells (HPC) mobilization and collection. Activation of polymorphonuclear leukocytes (PMN) is present during rHuG-CSF treatment and is associated with endothelial cell dysfunction and hypercoagulation. We evaluated whether PMN activation by rHuG-CSF may alter the blood oxidative status and subsequently affect the vascular cell function. Fourteen healthy individuals received rHuG-CSF for HPC harvesting. Blood was drawn before starting rHuG-CSF (T0), on the last day of rHuG-CSF (T1) and 1 week after stopping rHuG-CSF (T2). Levels of CD11b, myeloperoxidase (MPO), hydroperoxides, nitric oxide (NO), and soluble endothelium (sES), leukocyte (sLS), and platelet (sPS) selectins were measured. During rHuG-CSF, CD11b, MPO and hydroperoxides significantly increased, while NO levels significantly decreased, compared with T0. At T2 all these markers returned to baseline values. Significant increments of all selectins were observed during rHuG-CSF. At T2 sES and sEP significantly decreased back to pre-treatment values, whereas sLS remained significantly high. These data show that rHuG-CSF induces a transient inflammatory status characterized by circulating activated PMN, which release reactive oxygen species and intracellular proteases, promoting the onset of an abnormal oxidative status. This process may modify the hemostatic balance towards a pro-thrombotic state.

Adolescent↗
PubMed2006

Monoclonal gammopathy in human leishmaniasis.

A 64-year-old female with IgGk monoclonal components (total 45 g/l) and 30% abnormal plasma cells and plasmoblasts in bone marrow is reported. After the identification of leishmania in the bone marrow, liposomal amphotericin B was used and a progressive resolution of the gammopathy was documented.

Amphotericin B↗
PubMed2005

Normal thrombopoietin and its receptor (c-mpl) genes in children with essential thrombocythemia.

BACKGROUND: Following the observation of thrombopoietin (TPO) gene abnormalities as the cause of familiar cases of thrombocythemia similar derangements of TPO and/or its receptor (c-mpl) might be surmised to be at the root of increased platelet count also in non-familiar (sporadic) cases. Although this was not demonstrated in adults, little data exist about childhood. PROCEDURES: We studied the molecular biology of TPO and c-mpl in seven children with non-familiar essential thrombocythemia (ET) and one child with secondary thrombocytosis (ST). Plasma TPO content was measured using a commercially available kit. Genomic DNA was extracted from whole blood by standard methods and TPO and c-mpl genes were amplified by polymerase chain reaction (PCR) and sequenced. RESULTS: Plasma TPO levels were normal in all our patients. No alteration was detected in either coding region, including the flanking intronic sequences of TPO and c-mpl genes. As compared to the published normal sequence of the TPO gene, one allelic base change in a non-coding region of intron 1 was found in all children with ET and ST, but this was reported as a common finding in normal subjects as well. CONCLUSIONS: High platelet count in our series of sporadic ET of childhood is not due to an abnormality either of TPO or c-mpl gene.

Adolescent↗
PubMed2005

Myocardial infarction, other arterial thrombosis and invasive coronary procedures, in hemaophilia B: a critical evaluation of reported cases.

Myocardial infarction and other arterial thrombosis are commonly maintained to be rare in hemophilia patients. This, in general, seems true but the occurrence of a thrombotic event in hemophilia B is not exceptional. A thorough search of the literature has yielded 13 patients with myocardial infarction and 1 patient with a cerebrovascular accident. There were three fatalities. In five cases MI occurred after infusion of Prothrombin Complex Concentrates. In three additional patients the event occurred after infusion of plasma, Feiba or cryoprecipitate supernatant. Four patients had an antero-lateral infarction. Two had a non-Q infarction and one each showed a multiple or a posterior-inferior form. Several therapeutic coronary procedures (GABG and PTCA) were carried out in hemophilia B patients without undue complication providing adequate level of FIX were maintained. Heparin prophilaxis was used in all patients but one. The analysis of the literature indicates that (1) MI may occur in hemophilia B patients and (2) that invasive coronary artery therapeutic procedures may be carried out without complications.

Coronary Thrombosis↗
PubMed2004

The occasional venous thromboses seen in patients with severe (homozygous) FXII deficiency are probably due to associated risk factors: a study of prevalence in 21 patients and review of the literature.

According to our personal experience and to the study of the literature, 11 cases of venous thrombosis have been described as sporadic reports in patients with severe (homozygous) factor XII (FXII) deficiencies. In every cases but 4, associated risk factors were found to be present (pregnancy, post-partum period, surgery, trauma, in dwelling catheter, AT deficiency, heterozygous factor V Leiden, Burger's disease). In some instances more then one condition was present. The four patients for whom no information is supplied, were cases gathered from old and logically incomplete files and therefore the existence of associated risk factors cannot be excluded. The papers which investigated the presence of venous thrombosis in cohorts of patients with homoxygous FXII deficiency demonstrated the occurrence of venous thrombosis in 2 additional cases out of a total of 63 patients investigated. In these latter cases thrombosis occurred during pregnancy. This brings the total number of patients with FXII deficiency who showed a venous thrombosis to 13. Only a few of these patients were investigated for the presence of concomitant congenital prothrombotic conditions. The conclusion of the study seem to suggest that the role played by FXII deficiency in the pathogenesis of venous thrombosis is minor, if any.

Factor XII Deficiency↗
PubMed2004

Thrombosis-free surgical procedures in severe (Homozygote) factor XII deficiency: report of four additional cases and literature review.

The outcome of various surgical procedures carried out in patients with severe (homozygote) factor XII deficiency were investigated for the appearance of blood coagulation-related complications with particular emphasis on thrombotic complications. The surgical procedures were total mastectomy, tonsillectomy and adenoidectomy, placement of a hip prosthesis, and double hernia repair. None of the patients slowed any complication. Several other reported cases of surgical procedures carried out in several patients ware found in the literature. Bleeding or thrombotic complications were noted in none of these cases. The surgical procedures in some cases were minor such as adenoidectomy, tonsillectomy, or nasal polyp removal. However several major surgical procedures were carried out in some patients (cholecystectomy, gastrectomy, repair of atrial septal defect, coronary bypass). All patients remained asymptomatic. In some cases whole blood and/or plasma were used as requested by the caring surgeons. In a few patients, the plasma was given prophylactically because of the long partial thromboplastin time. Finally, three patients (two for cardiac surgery and one after hip replacement) received heparin prophylaxis as foreseen by accepted procedures without the undue sequels. These data supply further evidence that factor XII deficiency does not only show any bleeding tendency but also can withstand even major surgical procedures without thrombotic complications.

Adolescent↗
PubMed2003

Association of monoclonal gammopathy and polycythemia vera or essential thrombocythemia: study of a large cohort of patients.

Concomitant cases of monoclonal gammopathies with polycythemia vera (PV) and essential thrombocythemia (ET) have been described. We report our experience in a large cohort of patients with ET and PV and the occurrence of M protein in such a population. Retrospective evaluation of clinical and laboratory records of 164 patients with PV and 218 with ET was performed, and 500 subjects matched for sex and age were used as controls. The patients were divided into group A (younger than 55 years), group B (55-70 years), and group C (over 70 years), and the presence of M protein was sought at the time of diagnosis and later during follow-up. M protein was found in 14 patients with myeloproliferative disorders (MPDs), representing 3.6% of patients both with ET and PV, and in 10 subjects of the control group (2%). M protein was detected in 2.1% of MPD patients of group A, in 4.8% of group B, and in 5.7% of group C and in 1.6% of controls of group A, 2.7% of group B, and 2% of group C. No significant statistical difference was observed. The occurrence of M protein in PV and ET does not seem to differ from that observed in the control group. A more relevant increase in the incidence of M protein in MPDs than in the controls was observed by dividing patients and controls by age. However, no statistical significant difference was documented.

Adolescent↗
PubMed2002

Risk factors for thrombosis in patients with immune mediated heparin-induced thrombocytopenia.

BACKGROUND: As reported by major clinical series in the literature, about 2% of patients receiving unfractionated heparin (UFH) develop immune-mediated (type II) heparin-induced thrombocytopenia (HIT) that may be complicated in 30-75% of cases by a paradoxical thrombotic syndrome (HITTS), either arterial or venous. HITTS carries relevant rates of mortality and morbidity, amongst which cerebral and/or myocardial infarction and limb amputations. It is unclear as yet why some patients suffer from isolated thrombocytopenia (HIT), whilst others have HITTS. The aim of the present study was to look for clinical and laboratory features related to the occurrence of HITTS. PATIENTS AND METHODS: We retrospectively analysed the clinical records of 56 patients with proven HIT, as diagnosed on clinical grounds and by in vitro demonstration of immunoglobulin (IgG)/IgM against the PF4/heparin complex. Thirty-four patients (61%) had HITTS (19 venous thrombosis, seven arterial thrombosis, five arterial and venous thrombosis, two skin necrosis, one diffuse intravascular coagulation), whereas 22 had uncomplicated HIT. Amongst HITTS patients, two had limb amputation, five had recurrent thrombosis and seven died. Amongst HIT patients three died from causes unrelated to HIT. RESULTS: No significant difference in sex, age, previous exposure to heparin, UFH route of administration or dose, duration of therapy, time of onset of thrombocytopenia and platelet count recovery, nor antiheparin/PF4 antibodies subtype (IgG or IgM) was detected when comparing HIT and HITTS. In contrast, in the HITTS group a higher prevalence of orthopaedic surgery (15 of 34 vs. 2/22; P=0.01), a significantly lower platelet count nadir (43 +/- 32 vs. 75 +/- 63 x 109/L; P=0.01) and a significantly higher titre of antiheparin/PF4 antibodies, expressed as optical density of enzyme-linked immunosorbent assay (ELISA); (1989 +/- 1024 vs. 1277 +/- 858; P=0.009), were observed in comparison with the HIT group. Amongst HITTS patients, the prevalence of venous thrombosis was significantly higher in orthopaedic patients and in those being treated for venous thromboembolism (18/24 vs. 1/9 patients, chi2 8.4, P=0.004), whilst arterial thrombosis (ART) occurred more often in heparin treatment for arterial disease (3/4 vs. 4/29 patients, chi2 4.6, P=0.03). CONCLUSIONS: Orthopaedic surgery, the severity of thrombocytopenia and high antiheparin/PF4 antibodies titre are adverse prognostic or concurrent factors in the development of HITTS.

Adult↗
PubMed2001

Age as the major predictive factor of long-term response to splenectomy in immune thrombocytopenic purpura.

Sixty-one consecutive patients undergoing splenectomy for chronic immune thrombocytopenia were retrospectively evaluated. Platelet response was considered as complete (CR) when platelet count rose to > 100 x 109/l, partial (PR) when 30-100 x 109/l or absent (NR) if otherwise. Follow-up (mean time 7.6 years) was possible in 54 patients. Forty-eight patients (88%) had an immediate response to splenectomy (39 CR, 9 PR) whereas six (12%) were NR. Thirty-six responders (67%) had sustained remission (31 CR; 5 PR) without further treatment; thrombocytopenia recurred in 12 patients (33%). The probability curve of continued remission showed a constant relapse-rate during the first 36 months; a further step of relapse was observed beginning 70 months after surgery. The only positive predictive factor for the long-term response to splenectomy was age < 40 (P < 0.005). Neither duration of thrombocytopenia nor previous response to medical treatment (steroids and/or intravenous immunoglobulins) were related to splenectomy response.

Adolescent↗
PubMed2000

Clinical and laboratory factors that affect the post-transfusion platelet increment.

Transfusion of platelet concentrates (PC) reduced the incidence of fatal hemorrhages in several thrombocytopenic conditions. Unfortunately, long-term platelet supportive care may be complicated by the development of a state of refractoriness, resulting in inadequate recovery of functional platelets. PC handling, clinical conditions of the patients and alloimmunization are the main factors affecting refractoriness. We evaluated the post-transfusion platelet increase in 25 patients (M=6, F=19) with hypomegakaryocytic thrombocytopenia receiving random ABO-compatible PC within 24 h after collection. Quality of PC was assessed by platelet count, pH measuring, LDH release, glycocalicin levels, CD-62 and CD-42b expression. Besides history, clinical status and therapy, we searched for the presence of anti-HLA class 1 and anti-HPA 1-4-5 antibodies. Only six patients (24%) were refractory to PC transfusion, as assessed by a corrected count increment (CCI)<5000. Four of such six patients (67%) had anti-HLA antibodies, as compared to zero of 19 responders (P<0.02). No other investigated clinical or laboratory feature was significantly different in refractory and responsive patients. Although post-transfusion bleeding time was shorter in responders than in refractory patients (297.33+/-249.95 versus 673.33+/-409.96; P<0.02), it did not significantly change even in patients with adequate correct count increment. Our data confirm the importance of anti-HLA antibodies in determining adequate post-transfusion recovery or refractoriness.

Adult↗
PubMed2000

Features of essential thrombocythaemia in childhood: a study of five children.

Essential thrombocythaemia (ET) is usually considered a disease of the middle-aged but, with the advent of automated platelet counting, ET is diagnosed with increasing frequency in young adults and, even more rarely, in children. We report five paediatric patients (four girls and one boy, mean age 89 months) diagnosed with ET in agreement with Polycythaemia Vera Study Group criteria. The patients had a persistent thrombocytosis over 900 x 10(9)/l and, at the time of diagnosis, their platelet count ranged between 1,112 and 3,178 x 10(9)/l. A 9-month-old girl had thrombosis of the inferior cava vein, two children had headaches and two others remained asymptomatic throughout the follow-up period. Megakaryocytes in the bone marrow were increased in number. The chromosomal analysis was normal, and bcr rearrangement was always negative. None of the patients had spontaneous BFU-E or altered levels of serum erythropoietin and thrombopoietin. Two patients showed alteration of platelet aggregation, and all had decreased levels of intraplatelet serotonin. In spite of the diagnosis of ET in our patients, we are not sure that the cases reported here are really myeloproliferative disorders. The features could suggest that the cases observed may be affected by an 'idiopathic thrombocytosis' without myeloproliferation. Possible variants of ET are described in young adults, and the heterogeneous nature of ET is also suggested by our paediatric patients. Only careful long-term follow-up of patients such as these will clarify the natural history of these disorders and suggest therapeutic management.

Bone Marrow Cells↗
PubMed2000

Essential thrombocythemia in young adults: major thrombotic complications and complications during pregnancy--a follow-up study in 68 patients.

OBJECTIVES: Although essential thrombocythemia (ET) is usually primarily considered a disorder of middle age, it has been observed in children and young adults. However, the real risk for thrombosis in these patients has not been clearly established. DESIGN: Prospective analysis of consecutive patients younger than 40 at the time of the diagnosis of ET and followed in our department between 1980 and 1998. SUBJECTS: Sixty-eight patients (28 males and 40 females, median follow-up 99.14 months) affected by ET diagnosed in agreement with the Polycythemia Vera Study Group criteria. INTERVENTIONS: Asymptomatic ET patients were not treated. In contrast, patients with associated atherosclerotic risk factors, microvascular disturbances, or a previous major arterial thrombosis were given acetyl salicylic acid (ASA 100 mg/day). Only patients with major thrombotic complications and a platelet count > 1,000 x 10(9)/L received cytoreductive therapy. OUTCOME MEASURES: (1) to evaluate thrombotic complications in young patients with ET, (2) to relate thrombotic risk to the presence of general atherosclerotic risk factors, and (3) to adopt treatment, and (4) to report the outcome of the pregnancies monitored in our population. RESULTS: Fifteen patients had major thrombosis, 11 of which were the presenting features of ET. No rethrombosis has been observed. Only one patient with thrombotic complications was under efficient treatment. Atherosclerotic risk factors are more common in patients with major arterial thrombosis than in asymptomatic subjects. Thirteen normal babies were delivered out of 16 pregnancies, 6 of the pregnant women were on ASA therapy. CONCLUSIONS: Most thrombosis in young ET patients occurred at the time of the diagnosis, and venous thrombotic events represent one-third of total thrombosis. Cardiovascular risk factors seem to be concurrent stimuli for arterial thrombosis in ET. The thrombotic complication rate was 2.6/100 patients/year ASA reduces microvascular disturbances, thrombosis, and rethrombosis and possibly reduces obstetric complications in women with ET.

Acute Disease↗
PubMed2000

Leukemia and myelodysplasia effect of multiple cytotoxic therapy in essential thrombocythemia.

Essential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by increased risk of thrombosis and/or hemorrhages. Cytotoxic drugs are mostly used in patients at high risk for thrombotic complications, while their use is still debated in low risk patients because of the risk of leukemia or secondary neoplasm. We discuss the leukemic risk of available treatment strategies in a large cohort of patients. Over a 12 years period we treated 23 patients with busulfan (BU), 1 with pipobroman (Pi), 6 with 32P, 48 with hydroxyurea (HU) in 62 cases associated with acetyl salicylic acid (ASA) while 77 patients received ASA alone and 33 did not receive any therapy. We observed 2 cases of acute leukemia (AL) and 1 of myelodysplastic syndrome (MDS). One of these patients had been treated with 32P and Pi these after with and the other two with BU and HU. They represented 23% of all patients treated with more than 1 cytotoxic agent, 16.6% of 32P treated subjects, 4% of those with HU and 6.4% of those with BU. The case of MDS occurred in a 81 years old female and represents 4% of cases of ET over the 70 years of age. No cases of AL or MDS were observed in patients not receiving cytotoxic therapy (with or without ASA). According to our experience the use of more than one cytotoxic agent in ET confirms the increase in the risk of leukemia in these cases. However, none of the patients treated with HU alone, even for more than 10 years (12 cases) developed AL. No treatment or therapy with ASA alone may be the best choice in young patients with ET with a low risk of thrombotic complications.

Aged↗