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P Mannuccio Mannucci

Publications and source records attributed to P Mannuccio Mannucci.

8 recordsLinked to original sources
PubMed2006

Prospective study on the behaviour of the metalloprotease ADAMTS13 and of von Willebrand factor after bone marrow transplantation.

Thrombotic microangiopathies (TMAs) are rare but serious complications of bone marrow transplantation (BMT). Clinical manifestations are similar to those of thrombotic thrombocytopenic purpura (TTP), but prognosis is generally poorer despite plasma exchange. The enzymatic activity of the plasma metalloprotease ADAMTS13, which cleaves ultralarge thrombogenic multimers of von Willebrand factor (VWF) derived from activated endothelial cells, is very low or undetectable in patients with classic TTP, and protease deficiency is thought to play a mechanistic role in the formation of platelet thrombi in the microcirculation. This is the first prospective study to evaluate the incidence of TMA in 46 consecutively recruited patients undergoing autologous or allogeneic BMT and explore in parallel the behaviour of ADAMTS13, VWF antigen and VWF multimer size. The incidence of post-BMT TMA was 6% (three of 46); all cases occurred after allogeneic BMT. Compared with baseline values plasma ADAMTS13 activity was significantly reduced in patients undergoing BMT, particularly after the conditioning regimen (mean values: 50 +/- 22 vs. 77 +/- 32%; P < 0.0001). In the three patients who developed TMA, ADAMTS13 decreased after conditioning, but was very low in one case only (8%). VWF antigen levels progressively increased after the conditioning regimen (228 +/- 75 vs. 178 +/- 76% at baseline, P = 0.002). The mean proportion of high-molecular weight VWF multimers did not change in the various stages of BMT, even though ultralarge multimers were transiently found in same cases with and without TMA. Hence, the measurements evaluated in this study are not clinically useful to predict the occurrence of post-BMT TMA.

ADAM Proteins↗
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↗
PubMed1990

Prognostic significance of fibrinopeptide A in survivors of cerebral infarction.

We measured levels of fibrinopeptide A, beta-thromboglobulin, and fibrinogen in the plasma of 27 patients 2 months after their first stroke. Concentrations of fibrinopeptide A, a sensitive index of in vivo hypercoagulability, were significantly higher in the 18 ischemic stroke patients than in 40 age- and sex-matched controls and in the six patients who experienced recurrence within 5 years than in the 12 who remained asymptomatic. On the contrary, fibrinopeptide A levels had no prognostic significance among the nine patients with hemorrhagic stroke. Concentrations of beta-thromboglobulin, an index of platelet activation, were higher in the 27 stroke patients than in the 40 controls, but this index was not associated with stroke recurrence. Fibrinogen levels were not significantly higher in stroke patients than in controls. In a multivariate regression analysis of hemostatic and clinical variables, only fibrinopeptide A levels of greater than 4 ng/ml were significantly related to cerebral infarction. Our results support the role of hypercoagulability in the recurrence of ischemic stroke and may allow identification of subjects at high risk for it. If confirmed in more patients, our results could provide a rationale for clinical trials of anticoagulant therapy in such patients.

Cerebral Infarction↗
PubMed1986

Low protein C in the neonatal period.

Protein C was measured by electroimmunoassay in 47 infants within 24 h of delivery. Gestational age ranged from 28 to 43 weeks. The mean level was 27% (range less than 10-67%) of the normal adult mean. In the 22 infants who had no clinical problems, protein C levels correlated significantly with gestational age. In the 25 who were sick there was no correlation, and the mean level was significantly lower than that of the healthy infants. Postnatal rise was slow; on day 7 the mean was 32% and on day 28, 31%. Levels of protein C correlated significantly with prothrombin in both the healthy and sick infants. Crossed immunoelectrophoresis in the presence of calcium ions gave one protein C peak of the same electrophoretic mobility as is seen in plasma of healthy adults, indicating that the infants' protein C is gamma carboxylated. It is concluded that: (1) Protein C in neonates is in or below the range associated with thromboembolism in patients congenitally deficient in this protein; (2) protein C levels correlate with gestational age; and (3) the low levels during the neonatal period are not due to decreased gamma carboxylation but may reflect decreased synthesis when compared to the older child or the adult.

Gestational Age↗
PubMedDate not supplied

Recurrent ischemic attacks in two young adults with lupus anticoagulant.

Two young adults with lupus anticoagulant had multiple attacks of cerebrovascular ischemia in different arterial territories. Cerebral angiography was normal. One patient had a new episode during anticoagulant therapy, but has remained asymptomatic on antiplatelet treatment. In the other, further events occurred during treatment with platelet-inhibiting drugs, but there have been no recurrences with adequate anticoagulant therapy. Lupus anticoagulants are possible causes of otherwise unexplained thromboembolic events. Due to the variable mode of action of these immunoglobulins, platelet-inhibiting drugs may in some cases be considered as a prophylactic alternative to anticoagulant treatment.

Adult↗