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Biomedical subjects

M G Mazzucconi

Publications and source records attributed to M G Mazzucconi.

At least 37 records · Page 2Linked to original sources
PubMed1993

Evidence of a hypercoagulable state in patients with acute lymphoblastic leukemia treated with low dose of E. coli L-asparaginase: a GIMEMA study.

Blood coagulation abnormalities induced by administration of E. coli L-asparaginase were investigated in 25 patients with acute lymphoblastic leukemia treated according to the GIMEMA ALL 0288 trial. Dosage of L-asparaginase was relatively low (6,000 U/m2/day for 7 days total dose 42,000 U/m2) as compared to the conventional dosages (120,000-140,000 U/m2 over 10-14 days). A significant decrease in fibronogen, plasminogen, alpha2-antiplasmin and antithrombin III was observed from day IV of L-asparaginase and it was maximum on day VIII, with return to the baseline levels on day XV. Protein C levels had only a borderline reduction, while no modification of protein S or factor VII was observed. Two of the patients investigated developed thrombosis. The presence of a prothrombotic state induced even by this low dosage of E. coli L-asparaginase was suggested by a significant increase of sensitive markers of hypercoagulability such as fibrinopeptide A, thrombin-antithrombin complexes, and prothrombin fragment F1 + 2.

Adolescent↗
PubMed1993

Recombinant alpha-interferon 2b in the treatment of HIV-related thrombocytopenia.

OBJECTIVE: To assess the efficacy and the mechanism of action of alpha-interferon (alpha-IFN) in the treatment of HIV-related thrombocytopenia. METHODS: Thirteen HIV-positive subjects [nine men and four women with severe thrombocytopenia (platelets, < or = 30 x 10(9)/l)] were treated with alpha-IFN 2b alone at a dose of 3 x 10(6) U three times a week for 5 weeks. Haematological parameters, platelet kinetic and bone-marrow myeloid progenitor cultures [megakaryocyte colony-forming units (CFU-MK); granulocyte macrophage CFU (CFU-GM) and erythroid burst-forming units (BFU-E)] were evaluated before and after treatment in responsive subjects. RESULTS: Seven out of 13 subjects showed a partial response (platelets, 50-149 x 10(9)/l) after alpha-IFN 2b therapy. Platelet survival as evaluated by 111In-oxine significantly increased, while platelet turnover showed a slight but not statistically significant increase after treatment. The growth of bone-marrow myeloid progenitor cells decreased after alpha-IFN 2b therapy, again without statistical significance. CONCLUSION: alpha-IFN 2b may increase the platelet count in HIV-positive subjects with severe symptomatic thrombocytopenia by prolonging platelet survival. The immunomodulatory and antiviral action of this drug may be responsible for prolonged platelet survival.

AIDS-Related Complex↗
PubMed1993

Autoimmune thrombocytopenic purpura in pregnancy: maternal risk factors predictive of neonatal thrombocytopenia.

Pregnancy in ATP women is not unusual. The problem of this association concerns the possibility of disease transmission to the fetus due to the crossing of maternal antiplatelet antibodies through the placenta. Maternal risk factors predictive of neonatal thrombocytopenia, can be identified as follows: severe thrombocytopenia, previous splenectomy, high titre of PA-IgG and/or SPB-IgG. In 63 pregnancies in ATP patients, we have evaluated whether the above maternal risk factors, considered in the third trimester, can provide useful criteria for the prediction of neonatal thrombocytopenia. In the third trimester, the distribution of maternal risk factors was as follows: 0 in 7 cases, 1 in 27 cases, 2 in 15 cases, 3 in 12 cases, 4 in 2 cases. From a statistical evaluation, the neonatal platelet values and the maternal risk factors seem inversely correlated (r -0.437; p = 0.0005). In particular, neonatal and maternal platelet count correlated positively (r = 0.249; p = 0.025); moreover, neonatal platelet count correlated negatively with Splenectomy (r = -0.209; p = 0.05), PA-IgG (r = -0.401; p < 0.0005) and SPB-IgG (r = -0.338; p < 0.005). We tried to apply a multiple regression model for all the above parameters which appears statistically significant (p = 0.001); the variability was about 30%. This regression model could be validated if applied to a larger number of cases, and it could represent an alternative to the invasive methods used for the diagnosis of neonatal thrombocytopenia.

Adolescent↗
PubMed1992

Markers of procoagulant imbalance in patients with inherited thrombophilic syndromes.

In 107 asymptomatic and untreated patients with inherited syndromes associated with thrombophilia (antithrombin III, protein C and protein S deficiencies), we compared in parallel two plasma peptides which reflect activation of the common coagulation pathway: the prothrombin fragment 1 + 2 (F1 + 2) and fibrinopeptide A (FPA). Both F1 + 2 and FPA were measured with simple, commercially available ELISA methods. High levels of F1 + 2 or FPA were found in about one fourth of the patients as a whole. When patients were divided according to the type of inherited thrombophilic syndrome, it appeared that F1 + 2 was more frequently elevated in protein C and protein S deficiencies than in antithrombin deficiency; and that, in general, it was no more frequently elevated than FPA. Although our data confirm the existence of a procoagulant imbalance in inherited thrombophilic syndromes due to defects of natural anticoagulant proteins, they do not confirm that such imbalance can be more frequently diagnosed by measuring F1 + 2 levels, particularly in patients with antithrombin deficiency.

Adolescent↗
PubMed1992

Incidence of thrombotic complications in adult patients with acute lymphoblastic leukaemia receiving L-asparaginase during induction therapy: a retrospective study. The GIMEMA Group.

The incidence of thrombotic complications chronologically related to L-asparaginase administration is retrospectively analyzed in 238 adult ALL patients treated according to the GIMEMA protocol ALL 0288. The patients (126 males and 112 females, aged 12-68 years, median 29) received E. coli L-asparaginase (L-ase) in the induction phase at a dosage of 6000 U/m2/day x 7 d starting on d 15, as well as vincristine, prednisone, daunorubicin and cyclophosphamide, the last-named by random 1:1. Ten patients (4.2%) developed thrombotic complications 5-15 d (median 11 d) after the start of L-ase treatment. The thrombotic events, which were lethal in 5 patients, involved the cerebral sinus (5 cases), the cerebral arteria (2 cases), the portal vein (1 case), the pulmonary district (1 case), and a deep vein in the lower extremity (1 case). The occurrence of these complications was not related to the general thrombotic risk factors, nor to the main clinical and laboratory data registered at diagnosis and immediately before the start of L-asparaginase treatment. The present study documents for the first time in a sufficiently large series of adult ALL patients that the incidence and the severity of thrombotic events related to L-ase administration are relevant and need further consideration.

Adolescent↗
PubMed1991

Studies of von Willebrand factor in essential thrombocythemia patients treated with alpha-2b recombinant interferon.

The crucial role of the von Willebrand Factor (vWF) and its interaction with platelets in myeloproliferative disorders (MPD) have emerged in recent years. Recently, many authors have reported the therapeutical efficacy of interferon (IFN) in MPD with thrombocytosis in decreasing platelet number. The purpose of our report is to study the modifications of vWF in a series of 20 patients affected by essential thrombocythemia (ET) or MPD with thrombocytosis, treated with alpha 2b recombinant IFN (alpha 2b-rIFN). Patients were studied before treatment and after complete or partial response: vWF-related properties, bleeding time (BT) and ristocetin-induced platelet aggregation (RIPA) were evaluated. Before treatment, we found prolonged BT in 5 patients (25%), abnormal RIPA in 8 (40%), reduced factor VIII coagulant activity (VIII:C) in 2 (10%), reduced vWF-related antigen (vWF:Ag) in 5 (25%) and low vWF:ristocetin cofactor (vWF:Ricof) in 5 (25%). Twelve subjects were evaluated after hematologic remission: in all patients, BT, VIII:C, vWF:Ag and vWF:Ricof were within normal range or upper normal limits. RIPA was abnormal in 7 subjects. Multimer patterns of vWF were performed in 3 patients before and after treatment: 2 of them showed loss of high-molecular-weight multimers that seemed to recover at remission. IFN seems to induce improvement of platelet number and their functions in MPD with thrombocytosis.

Adult↗
PubMed1991

Intranasal DDAVP: biological and clinical evaluation in mild factor VIII deficiency.

We report a study undertaken to test the biological effect of intranasal 1-deamino-8-D-arginine vasopressin (DDAVP) and its efficacy in the treatment of bleedings in patients with mild factor VIII deficiency. The biological study was carried out in 20 patients: an increase of factor VIII:C and von Willebrand factor antigen levels was observed after inhalation of DDAVP at average post/pre inhalation ratios of 2.80 and 1.72, respectively. No relevant alterations of fibrinolysis were noted. In fact, we only observed a simultaneous increase of tissue plasminogen activator and plasminogen activator inhibitor, without modification of D-dimer. In 10 cases intranasal DDAVP has been used in the prevention or in the treatment of bleeding complications: no bleedings were observed.

Administration, Intranasal↗
PubMed1990

Disseminated intravascular coagulation and myocardial infarction in a haemophilia B patient during therapy with prothrombin complex concentrates.

A case of disseminated intravascular coagulation (DIC) and fatal myocardial infarction in a haemophilia B patient is described. DIC occurred after 4 days of therapy with unactivated prothrombin complex concentrates during the post-operative period. Therapy with fresh frozen plasma, heparin and antithrombin III concentrates was started without efficacy; after autopsy myocardial infarction was evident.

Blood Coagulation Factors↗
PubMed1988

Consumption coagulopathy and low-dose heparin in the surgical repair of abdominal aortic aneurysm: a study of fifteen cases.

Surgical repair of abdominal aortic aneurysm (AAA) is frequently associated with DIC. 15 patients affected by AAA were studied to evaluate the risk of consumption coagulopathy and the efficacy of daily low-dose calcium heparin prophylaxis. The coagulation parameters investigated showed a postoperative decrease of AT III activity levels and platelet count the other laboratory tests did not show any significant modifications. Low dose heparin was effective in preventing coagulation activity or thrombotic episodes. No thromboembolic complications were observed, except nonfatal myocardial infarction.

Aged↗
PubMed1987

Evaluation of the nature of mildly prolonged prothrombin times.

Twenty-one asymptomatic individuals with a mildly prolonged prothrombin time (greater than 2 SD from the prothrombin time of the reference plasma) were found to have a mild isolated factor VII (F VII) defect (mean 38.8 U/dl; SD 13.2). Factor VII antigen levels were also found to be reduced (mean 45.5 U/dl; SD 7.8) in 13 of them. These figures were compared with those of 50 normals and 28 obligatory heterozygotes for F VII deficiency. The phenotypical behaviors in the propositi were found to be equal to those of the F VII congenital deficiency heterozygotes: the discrepant one (VII+) and the nondiscrepant one (VII-/R). Fifteen families of the propositi could also be studied, totalling 55 additional individuals; in 25 of them (ten pedigrees) a mild F VII deficiency was found showing the same phenotypical features of the corresponding propositi. We therefore believe that these individuals with mild F VII deficiency can be considered as heterozygotes for the defect, since the other vitamin K-dependent clotting factors were normal; the defect is transmitted throughout the kindred with the same mode of inheritance as F VII congenital deficiency; and F VII:C and F VII:Ag levels are highly comparable with those of known obligatory heterozygotes for F VII deficiency. On the grounds of a careful statistical analysis we propose a formula which allows a discrimination between the two phenotypes of the heterozygotes for F VII congenital deficiency. In addition it is suggested that sensitive tissue thromboplastins should be used to pick up these mild defects.

Adolescent↗
PubMed1987

Evaluation of factor VII antigen in factor VII congenital deficiencies with a new ELISA assay.

An evaluation of a new Enzyme Linked Immunosorbent Assay (ELISA) factor VII:Ag assay in factor VII congenital deficiencies was carried out. This assay was compared to factor VII:C assay and the Inhibitor Neutralization Assay (INA) for factor VII:Ag, both in normals and F VII-deficient patients. The correlations between ELISA F VII:Ag and VII:C, as well as the one between INA F VII:Ag and VII:C, were good (r = .86 and .81, respectively). The correlation between the two immunologic methods of assay in normals was fairly good (r = 0.73, P less than 0.001); whereas in mild F VII deficiencies (heterozygotes for F VII deficiencies), the two methods correlated very well (r = .96). In the severe deficiencies, ELISA F VII:Ag assay allowed the evaluation of F VII protein levels below 1 u/dl. The sensitivities of the INA and ELISA assays were evaluated by creating artificially prepared plasmas containing serial amounts of purified F VII: INA was unable to pick up F VII protein levels lower than 75 ng/ml, whereas the ELISA assay could detect up to 5 ng of F VII.

Adult↗
PubMed1987

Danazol therapy in refractory chronic immune thrombocytopenic purpura.

We report our experience with danazol in the treatment of patients with refractory immune thrombocytopenic purpura (ITP). The effects of this drug were investigated in 10 patients, 6 males and 4 females, aged from 40 to 85 years, (median 58 years), with a platelet count below 50 X 10(9)/l. The patients had previously been treated with steroids; one of them had also been unsuccessfully splenectomized. Danazol was administered at a dosage of 600 mg/day for 3 months. Before and after treatment, detection of antiplatelet antibodies was performed. Seven patients were treated for 3 months. One of them showed a transient increase of platelet count, in the others, no significant rise was noted. Six patients experienced side effects during treatment. We think that danazol does not appear to be an alternative therapeutical approach in refractory ITP.

Adult↗