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Biomedical subjects

M G Mazzucconi

Publications and source records attributed to M G Mazzucconi.

At least 19 recordsLinked to original sources
PubMed2006

Idiopathic thrombocytopenic purpura (ITP) in the elderly: clinical course in 178 patients.

Idiopathic thrombocytopenic purpura (ITP) is often diagnosed in the elderly (age >or=65 yr), where it generally presents as a chronic disease. The objective of the present study was to describe the natural history of ITP in the elderly and to evaluate the risk of bleeding and the possible occurrence of other pathologies. We retrospectively evaluated 178 ITP patients (82 men, 96 women; mean age: 72 yr) diagnosed between 1981 and 1998. Therapy was started at diagnosis or during follow-up, depending on the platelet count and/or bleeding events. Sixty-six out of one hundred and seventy-eight patients (37%) initiated therapy at diagnosis; whereas in 11 of the 112 untreated patients (9.8%) therapy was necessary during the follow-up. Low-dose of prednisone was the first-line treatment in all patients (mean daily dose of 0.43 mg/kg). Forty-nine (63.6%) of the seventy-seven treated patients showed a response, 14 of these (28.6%) suffered a relapse. Another pathology occurred in 19 of the 178 patients (10.7%). We conclude that low-dose prednisone is an appropriate initial treatment for elderly persons. We also stress that an adequate follow-up is advisable, given that isolated thrombocytopenia could in some cases be the first sign of another underlying pathology.

Aged↗
PubMed2004

Patients with type 3 severe von Willebrand disease are not protected against atherosclerosis: results from a multicenter study in 47 patients.

BACKGROUND: The results of a number of studies in pigs and mice suggest that absence of von Willebrand factor (vWF) protects against the development of atherosclerosis. We studied whether patients with a complete deficiency of vWF (type 3 von Willebrand disease [vWD]) develop fewer atherosclerotic vessel wall changes than healthy controls. METHODS AND RESULTS: This study included 47 individuals with type 3 vWD and 84 healthy controls. Early atherosclerotic changes were assessed by measuring the thickness of the intima-media in the carotid and femoral arteries by B-mode ultrasonography. Advanced atherosclerotic changes were quantified by summing the maximal thickness of atherosclerotic plaques in the carotid and femoral arteries and were expressed as a plaque score. Established risk factors were determined to adjust for possible differences between the groups. We found no substantial difference in intima-media thickness between vWD patients and controls (adjusted difference for carotid artery 0.007 mm, 95% CI -0.022 to 0.036 mm; femoral artery 0.069 mm, 95% CI -0.056 to 0.19 mm). Similar proportions of patients and controls had atherosclerotic plaques (19% and 17%, respectively). No difference was found in the plaque score between groups (adjusted difference -0.22 mm, 95% CI -0.69 to 0.26). Among vWD patients, we found no effect of treatment with vWF concentrates on intima-media thickness or plaque score. CONCLUSIONS: The results of this study indicate that vWF does not play a substantial role in human atherogenesis.

Adult↗
PubMed2002

Clinical efficacy of highly purified, doubly virus-inactivated factor VIII/von Willebrand factor concentrate (Fanhdi) in the treatment of von Willebrand disease: a retrospective clinical study.

The goal of therapy in patients with von Willebrand disease (vWD) is to correct the dual defect of primary haemostasis and intrinsic coagulation reflected by low levels of von Willebrand factor (vWF) and factor VIII coagulant activity (FVIII:C). Factor VIII/von Willebrand factor (FVIII/vWF) concentrates are currently the treatment of choice in vWD patients unresponsive to desmopressin (DDAVP). However, only few studies on their clinical use are available so far. The main objective of this study was to retrospectively evaluate the clinical efficacy of a highly purified, doubly virus-inactivated FVIII/vWF concentrate with a high content of FVIII/vWF (Fanhdi). Twenty-two patients with congenital vWD have been treated from 1999 to 2001 at eight specialized centres belonging to the Italian Association of Hemophilia Centers (AICE). Ten males and 12 females, median age 28.5 years, range 5-70 years) had type 3 vWD (six cases), DDAVP-unresponsive type 1 (nine cases) and type 2B (seven cases). The study drug was given to stop or prevent 12 bleeding episodes or to prevent excessive bleeding during 14 surgical or invasive procedures. Overall, replacement therapy with the concentrate showed an excellent to good clinical efficacy in 92% of bleeding episodes and in 93% of surgical procedures. No adverse events occurred during 1,601 infusions, accounting for a total of 304,500 IU of FVIII:C administered. These results confirm the efficacy and safety of this concentrate in the management of bleeding episodes and in the prevention of excessive bleeding during major and minor surgery.

Adolescent↗
PubMed2001

Clonal hemopoiesis and risk of thrombosis in young female patients with essential thrombocythemia.

OBJECTIVE: Several studies demonstrated a high prevalence of nonrandom X-chromosome inactivation pattern (X-CIP) in essential thrombocythemia (ET). This study explored the incidence of clonal hemopoiesis in myeloid precursors and endogenous erythroid colonies (EECs) in ET patients and its correlation with thrombotic manifestations. MATERIALS AND METHODS: Clonal analysis of hemopoiesis using X-CIP was performed in 40 female patients with ET. Median age was 40.5 years (range 20-64), and median platelet count at testing time was 700 x 10(9)/L (range 220-1300 x 10(9)/L). Patients older than 65 years were excluded to reduce age-related skewing. Clonality was assessed on neutrophils, platelets, EECs, and bone marrow CD34(+) cells. RESULTS: Eight (20%) of 40 patients developed thrombosis mainly at diagnosis. Clonal hemopoiesis was found in 17 (42.5%) patients, 15 (37.5%) had polyclonal hemopoiesis, and 8 (20%) were considered uninterpretable due to constitutive skewing. Clonality was confirmed on purified CD34(+) subpopulations from bone marrow, documenting that clonality does not appear lineage-restricted. There were no statistical differences in age at diagnosis, median platelet count at testing time, and length of follow-up. Thrombotic episodes were significantly more frequent in the monoclonal group (p = 0.04, Fisher exact test). CONCLUSIONS: Young female patients with ET exhibiting a clonal pattern of hemopoiesis by X-CIP analysis are at higher risk for thrombosis. X-CIP analysis may contribute to defining the individual risk leading to appropriate treatment. X-CIP will allow a correct diagnosis in patients with latent myeloproliferative disorders and thrombosis in unusual sites. Clonal hemopoiesis is easily recognized by X-CIP, but its applicability is limited to the female sex and is hampered by the presence of age-related or constitutive skewing.

Adult↗
PubMed2001

Postpartum inhibitor to factor VIII: treatment with high-dose immunoglobulin and dexamethasone.

Spontaneous occurrence of an acquired inhibitor to factor VIII (FVIII) is a rare event. About 50% of cases are idiopathic. Among younger people, inhibitors are often found in the postpartum period. Treatment must be administered either to overcome haemorrhagic symptoms or to eradicate the inhibitor. Several approaches have been proposed for inhibitor eradication, based on immunosuppressive drugs such as corticosteroids, cyclophosphamide and azathioprine, with varying results. High-dose immunoglobulin (HDIg) has been recently proposed as first-line therapy. We report on four cases with acquired inhibitor to FVIII occurring 4-8 months after delivery. At diagnosis, inhibitor titre was < 5 Bethesda units mL(-1) (BU mL(-1)) in three cases and > 5 BU mL(-1) in one. Factor VIII coagulant activity (FVIII:C) was < 1 U dL(-1)> in three cases and 12 U dL(-1) in one. We treated the patients with HDIg (400 mg kg-1 day(-1) for 5 consecutive days) and dexamethasone (24 mg day(-1) for 5-7 consecutive days), administered at the same time. In three women, the inhibitor was suppressed in 2-50 weeks. After an off-therapy period ranging from 20 to 104 weeks, the FVIII:C was persistently normal and the inhibitor undetectable. The fourth woman remained unresponsive. In two cases, recombinant activated factor VII administration stopped the bleeding. Thus, intermediate- to high-dose dexamethasone and HDIg given at the same time could be a successful and safe therapeutic approach for a rapid and complete remission from the development of FVIII inhibitors.

Adult↗
PubMed2000

HAART and Mycobacterium avium complex in an HIV infected patient with severe factor VII deficiency.

A clinical syndrome represented by the association of Mycobacterium avium complex (MAC) infection with initiation of highly active antiretroviral therapy (HAART) has been recently described in patients with advanced HIV disease. HAART-associated improvement of the immune status might convert a clinically silent MAC infection into an active mycobacterial disease. A 40-year-old man with severe factor VII deficiency, advanced HIV-1 disease, a CD4 + lymphocyte count of 15 cells microL-1 (CDC stage A3) and 470,000 HIV-RNA copies mL-1 (measurement by NASBA system) underwent standard HAART (lamivudine, stavudine and ritonavir). Two weeks after HAART onset, the patient developed enlargement of the lymph nodes throughout the mesentery and after seven weeks a rapidly enlarging mass on the left side of the neck. Culture from a needle aspirate specimen revealed MAC. His CD4 + count had increased to 97 cells microL-1 and viraemia dropped to undetectable HIV-RNA copies. While continuing antiviral therapy, multidrug therapy for MAC infection (clarithromycin, ciprofloxacin, ethambutol, amikacin) was started with progressive improvement and cure of the neck mycobacterial infection and disappearance of the abdominal lymph nodes. HAART has been shown to offer significant clinical and laboratory benefits in terms of HIV disease with limited side-effects in Haemophiliacs. However, the clinical manifestation of an opportunistic infection should be mentioned as a possible complication of HAART in these patients, as well as in other categories of HIV infected patients, and in patients with congenital coagulopathies.

AIDS-Related Opportunistic Infections↗
PubMed2000

Identification and three-dimensional structural analysis of nine novel mutations in patients with prothrombin deficiency.

Prothrombin deficiency is an autosomal recessive disorder associated with a moderately severe bleeding tendency. In this study, 13 patients with prothrombin deficiency were screened for the presence of alterations in the prothrombin gene, and nine novel candidate mutations were identified. Of 11 patients with hypoprothrombinemia, ten are homozygous for five mutations and one patient is a compound heterozygote. The two patients with dysprothrombinemia are homozygous for two mutations. Eight of nine mutations are missense ones associated with single amino acid substitutions in the propeptide (Arg-1Gln, Arg-2Trp), the kringle-1 (Asp118Try) and kringle-2 (Arg220Cys) domains and the catalytic serine protease domain (Gly330Ser, Ser354Arg. Arg382His and Arg538Cys). The ninth mutation is an in-frame deletion of 3 bp that results in the omission of one amino acid (del Lys 301/302). The combination of these missense mutations with crystal structures for alpha-thrombin and the prothrombin fragments 1 and 2 resulted in new insight into the function of alpha-thrombin. The hypoprothrombinemia mutations were inferred to affect either the cleavage of the propeptide from the Gla domain, the stability of the kringle-1 and -2 domains, or the close association of the A and B chains of the serine protease domain. The dysprothrombinemia mutations were inferred to directly affect catalytic function through their location at the active site crevice or exosite 1 within the serine protease domain.

Adolescent↗
PubMed1999

Long-term follow-up of autoimmune thrombocytopenic purpura (ATP) patients submitted to splenectomy.

We studied the general outcome in 94 adult patients with autoimmune thrombocytopenic purpura (ATP) submitted to splenectomy. Of 84/94 patients who presented a complete or partial response 30 d after splenectomy, 16 (19%) showed one or more relapses. The clinical situation of the 81 patients still under observation is as follows: 13 unresponsive, 60 completely or partially responsive, without relapses during the follow-up, 8 completely or partially responsive after one or more relapses. No correlation was found between the favourable splenectomy outcome and age at splenectomy, the diagnosis-splenectomy interval and initial response to corticosteroids. The probability of disease-free survival is 83%, projected at 10 yr, while the overall survival is 93%, projected at 10 yr. PAIgG levels of the normal subjects and of responding patients were found to be similar, while in the groups of non-responding/relapsing patients, significantly higher values of PAIgG were detected, as compared to the control group.

Adolescent↗
PubMed1999

Autoimmunity in multiple sclerosis: study of a wide spectrum of autoantibodies.

The aim of this study was to assess the frequency of organ- and nonorgan-specific autoantibodies in MS patients and evaluate whether the presence of autoantibodies is an indicator of disease activity and/or a prognosis factor. One hundred and five definite MS patients in different stages and with different course and 75 blood donors were tested for the autoantibodies TgA, TMA/TPO-A, PCA, ANA, aCl, SMA, AMA and ANCA. All patients were screened for the LAC. Autoantibodies to at least one autoantigen were found in 66.6% MS patients and in 13.3% controls (P < 0.001). The frequency of TgA, TMA/TPO-A, ANA, aCl and SMA was statistically higher in patients than in controls. Circulating ANCAs were found in seven MS, a never reported finding. An early onset of MS (< 20 years) was associated with a lower autoantibody frequency (P < 0.01) Primary and secondary progressive MS had a higher antibody frequency than relapsing-remitting (P < 0.05) or benign (P < 0.001) MS. Up to 86% of patients were autoantibody-positive during the acute stage, but only 30% of them remained positive during the remission stage (P < 0.001). A generalised immune dysregulation occurs in MS patients, mostly during the acute stages and in the progressive courses, involving activation of both autoreactive Th1-cells (mainly linked to CNS lesions) and B-cells via Th2 cells.

Adolescent↗
PubMed1999

Acquired inhibitor against factor IX in a child: successful treatment with high-dose immunoglobulin and dexamethasone.

The occurrence of acquired inhibitor against factor IX:C is infrequent in haemophilia B patients and is very rare in previously healthy subjects, in whom it is often related to underlying diseases. We describe the case of a 2-year-old girl, who was referred to our hospital with haematomas, without previous bleeding history. Prolonged APTT, normal PT and a factor IX:C level below 1% were found. An inhibitor against factor IX:C was detected (5.5 U mL(-1)). Her father and mother showed normal factor IX:C levels. Treatment with high-dose immunoglobulin (400 mg kg(-1) day(-1) for 5 consecutive days by intravenous infusion) and dexamethasone (4 mg three times a day by intravenous injection for 4 consecutive days) normalized factor IX:C levels and overcame the inhibitor. In conclusion, high-dose immunoglobulin and high-dose dexamethasone are a successful and safe immunosuppressive approach for recovery from inhibitor occurrence.

Child, Preschool↗
PubMed1999

HIV-HCV RNA loads and liver failure in coinfected patients with coagulopathy.

BACKGROUND AND OBJECTIVE: The aim of this study was to measure contemporaneously HCV-RNA load, HIV-RNA load and CD4+ lymphocyte count in HCV/HIV coinfected patients with coagulopathy and to examine the relationship between these parameters and the liver failure. DESIGN AND METHODS: A cross-sectional study was performed on 54 patients with severe coagulopathy: 39 HCV/HIV coinfected and 15 HCV+/HIV- comparable for age and HCV exposure time. HCV-RNA and HIV-RNA load, CD4+ lymphocyte count, biochemical and ultrasonographic parameters were evaluated at the time of entry to the study. RESULTS: Mean HCV-RNA load was significantly higher in coinfected patients (643,872 717,687 copies/mL) than in HCV+/HIV- (mean 161,573 276,896 copies/mL) (p = 0.01). The 39 HCV/HIV coinfected patients had a mean HIV-RNA load of 205,913 456,311 copies/mL (range 4,000-2,500,000) and a mean CD4+ lymphocyte count of 206.5171/microL (range 5-693). Five of the 39 (12.8%) coinfected patients had liver failure. In these five patients the mean HCV-RNA load (770,200 996,426 copies/mL) was high but not significantly different from that in the 34 HCV+/HIV+ patients (623,496 682,239 copies/mL) without liver failure (p = 1.0). Coinfected patients with liver failure had a significantly higher HIV-RNA load (mean 764, 599 978,542 copies/mL) and lower CD4+ lymphocyte count (mean 52.655. 6/microL) than those observed in coinfected patients without liver failure (p = 0.007 and p = 0.03, respectively). A significant inverse correlation was found between CD4+ lymphocyte count and HIV-RNA load (r = -0.37, p = 0.01). INTERPRETATION AND CONCLUSIONS: HCV-RNA load is significantly higher in HIV+ than in HIV- patients with coagulopathy. Liver failure was found only in the HCV/HIV coinfected patients with severe immunodepression, expressed either by low CD4+ lymphocyte count or by high HIV-RNA load.

Adult↗
PubMed1996

Natural history and risk factors for thrombosis in 360 patients with antiphospholipid antibodies: a four-year prospective study from the Italian Registry.

PURPOSE: To assess the natural history and risk factors for thrombosis in a large cohort of unselected patients with antiphospholipid antibodies. PATIENTS AND METHODS: Three hundred sixty consecutive patients (118 males, 242 females, median age 39 years [range 2 to 78]) fulfilling the currently accepted criteria for diagnosis of lupus anticoagulant (LAC) (n = 326) and/or raised immunoglobulin G anticardiolipin antibodies (IgG ACA) (n = 185) were collected from 16 Italian institutions and prospectively observed for a median of 3.9 years (range 0.5 to 5). Main endpoints were the occurrence of arterial or venous thrombosis, the outcome of pregnancies, and any severe complications leading to hospitalization or death. RESULTS: Thirty-four patients developed a thrombotic complication, with a total incidence of 2.5% patient-years. Multivariate logistic regression analysis identified two independent risk factors for thrombotic events: a previous thrombosis (RR 4.9; 95% CI, 1.76 to 13.7; P < 0.005) and IgG ACA titer above 40 units (RR 3.66; 95% CI, 1.24 to 10.8; P < 0.01). A total of 28 pregnancies were observed in 25 women and 11 (39%) were abortive. Adverse pregnancy outcomes were significantly more frequent in women with a history of miscarriage or vascular occlusion (9/16, 56%) than in asymptomatic women (2/12, 17%) (P = 0.035). Four patients developed non-Hodgkin's lymphoma during the follow-up. Eighteen patients died. Vascular events and hematological malignancies represented the most frequent causes of death (n = 5 for each). CONCLUSIONS: The present study shows that: (a) previous thrombosis and ACA titer > 40 U are independent predictors of thrombosis; (b) history of miscarriage or vascular disease is significantly associated with adverse pregnancy outcome; (c) hematological malignancies can develop during follow-up in patients with antiphospholipid antibodies.

Adolescent↗
PubMed1994

Antithrombin III infusion suppresses the hypercoagulable state in adult acute lymphoblastic leukaemia patients treated with a low dose of Escherichia coli L-asparaginase. A GIMEMA study.

Thrombotic events have been reported in acute lymphoblastic leukaemia patients, especially during or after L-asparaginase administration. A so-called L-asparaginase associated coagulopathy has been well recognized, being characterized by a hypercoagulable state (decrease of antithrombin III, plasminogen, protein C, protein S and increase of prothrombin fragment F1 + 2, thrombin-antithrombin complexes and fibrinopeptide A). The aim of this study was to determine whether the supplementation of antithrombin III (AT-III) concentrates could improve the L-asparaginase associated coagulopathy, thereby blocking the activation of the haemostatic system. In 25 adult patients with acute lymphoblastic leukaemia (M 19, F6, mean age 34 years) antithrombin III (AT-III) concentrates were administered at daily doses of 50 U/kg for 10 consecutive days from the beginning of L-asparaginase therapy (6,000 U/m2/day s.c. for 7 days), given according to the GIMEMA ALL 0288 trial. A marked increase of antithrombin III was recorded on days IV-VIII-XI (P < 0.001). No changes in protein C, protein S, plasminogen, alpha 2-antiplasmin, factor VII and platelet count were observed and there was no increase in markers of hypercoagulability. There was no evidence of disseminated intravascular coagulation. In conclusion, AT-III concentrate supplementation during L-asparaginase therapy, by the achievement of high levels of antithrombin III, is associated with a lack of activation of the haemostatic system and appears to overcome the complex coagulopathy associated with L-asparaginase.

Adolescent↗
PubMed1994

Clinical factors associated with progression to AIDS in the Italian cohort of HIV-positive hemophiliacs. G.I.C.C. Gruppo Italiano Coagulopatie Congenite.

This study updates estimates of the cumulative incidence of AIDS among Italian patients with congenital coagulation disorders (mostly hemophiliacs), and elucidates the role of age at seroconversion, type and amount of replacement therapy, and HBV co-infection in progression. Information was collected both retrospectively and prospectively on 767 HIV-1 positive patients enrolled in the on-going national registry of patients with congenital coagulation disorders. The seroconversion date was estimated as the median point of each patient's seroconversion interval, under a Weibull distribution applied to the overall interval. The independence of factors associated to faster progression was assessed by multivariate analysis. The cumulative incidence of AIDS was estimated using the Kaplan-Meier survival analysis at 17.0% (95% CI = 14.1-19.9%) over an 8-year period for Italian hemophiliacs. Patients with age greater than or equal to 35 years exhibited the highest cumulative incidence of AIDS over the same time period, 32.5% (95% CI = 22.2-42.8%). Factor IX recipients (i.e. severe B hemophiliacs) had higher cumulative incidence of AIDS (23.3% vs 14.2%, p = 0.01) than factor VIII recipients (i.e. severe A hemophiliacs), as did severe A hemophiliacs on less-than-20,000 IU/yearly of plasma-derived clotting factor concentrates, as opposed to A hemophiliacs using an average of more than 20,000 IU (18.8% vs 10.9%, p = 0.02). No statistically significant difference in progression was observed between HBsAg-positive vs HBsAg-negative hemophiliacs (10.5% vs 16.4%, p = 0.10). Virological, immunological or both reasons can account for such findings, and should be investigated from the laboratory standpoint.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Pharmacokinetics of monoclonally-purified and recombinant factor VIII in patients with severe von Willebrand disease.

A monoclonally-purified factor VIII (FVIII) concentrate, containing little von Willebrand factor (vWF), was infused to 11 patients with severe von Willebrand disease and unmeasurable levels of plasma vWF. In comparison with the historical data obtained infusing hemophiliacs in the same conditions, monoclonally-purified FVIII had a significantly shorter half-life and faster clearance from plasma but similar in vivo recovery and volume of distribution. Two additional patients with severe von Willebrand disease were also infused with recombinant FVIII totally devoid of vWF. Half-life was very short and in vivo recovery low, with a larger volume of distribution than for monoclonally-purified FVIII. We conclude that in patients with severe von Willebrand disease the small amounts of vWF contained in the monoclonally-purified FVIII concentrate are not sufficient to stabilize infused FVIII, nor to support the normal circulation of endogenous FVIII that these patients produce at a normal rate.

Adolescent↗