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Biomedical subjects

F Rodeghiero

Publications and source records attributed to F Rodeghiero.

At least 109 records · Page 6Linked to original sources
PubMed1995

An acquired hemorrhagic disorder of fibrin crosslinking due to IgG antibodies to FXIII, successfully treated with FXIII replacement and cyclophosphamide.

We report a new case of severe bleeding diathesis due to an acquired inhibitor of fibrin crosslinking. The patient, an 80-year-old woman, was admitted to the hospital for a massive subcutaneous hematoma, with severe anemia requiring red cell transfusion; a subsequent retroperitoneal hematoma developed 2 weeks later. Coagulation studies were normal except for a thromboelastographic pattern suggestive of FXIII deficiency. Clot solubility test was abnormal even after 1:1 mix with normal plasma. Immunochemical studies confirmed the presence of a monoclonal IgG lambda inhibitor directed against FXIII activity (type II FXIII inhibitor). The patient IgG fraction selectively inhibited FXIII transamidating activity but did not inhibit the thrombin-mediated activation of FXIII. The patient was treated with high doses of FXIII concentrate to overcome the inhibitor and immunosuppressive therapy with cyclophosphamide and discharged in good conditions. High doses of commercially available FXIII appear to be a safe and effective method of controlling acute episodes of bleeding in patients with acquired FXIII deficiency.

Aged↗
PubMed1995

Characterization of two cases of acquired transitory von Willebrand syndrome with ciprofloxacin: evidence for heightened proteolysis of von Willebrand factor.

We characterized the cause of two cases of transitory acquired von Willebrand syndrome associated with the administration of ciprofloxacin. Purified Ig from the two patients did not inhibit Ristocetin Cofactor activity or binding to collagen of normal plasma, ruling out the possibility of an inhibitor. The analysis of multimeric pattern of plasma von Willebrand Factor (vWF) showed the lack of larger multimers in both patients, with a relative decrease of all the remaining forms in the first patient. The subunit composition of plasma vWF showed a marked reduction of the native 225 Kd subunit (31.9% and 32.9%; normal range 74-86%) and an increased proportion of the 189, 176, and 140 Kd fragments. These abnormalities disappeared during the follow-up, without any specific therapy. In conclusion, a common pathophysiological basis is demonstrated in both patients, with a heightened proteolysis of plasma vWF by an unknown mechanism.

Bleeding Time↗
PubMed1995

Platelet von Willebrand factor abnormalities in myeloproliferative syndromes.

Plasma and platelet von Willebrand factor (vWF) measurements, multimeric pattern and subunit composition of plasma vWF were obtained in 29 consecutive patients with chronic myeloproliferative syndromes. In the 8 patients with chronic myelogenous leukemia (CML), plasma vWF was significantly higher than in the 11 patients with essential thrombocythemia (ET) and in the 10 patients with polycythemia vera (PV). The RiCof/vWF:Ag ratio was low in all these groups of patients (mean 0.64 +/- 0.1, 0.66 +/- 0.2, and 0.61 +/- 0.2; normal 0.97 +/- 0.2). Bleeding time was prolonged (> 7.5 min) in 1/8 CML patients, 1/10 with PV, and 3/11 with ET. Plasma vWF multimers showed a minor loss of the largest multimers in 3/8 patients with CML, 4/10 with PV, and a more severe reduction in 9/11 ET patients. The latter pattern correlated with an abnormal proteolysis of vWF, expressed by a major increase of the 140-Kd fragment and decrease of the intact 225-Kd subunit in ET patients, whereas the 176-Kd fragment was significantly increased in all the subgroups of patients. Platelet vWF was significantly higher in CML patients in comparison to ET and normal controls. However, minor losses of the larger multimers were evident in all the subsets of patients. In ET patients also the intermediate forms were lacking in platelets, accompanied by a significant decrease of platelet RiCof. This abnormality was significantly correlated with the occurrence of bleeding symptoms in PV and ET patients (P = 0.007; Fisher's exact test). In conclusion, plasma and platelet vWF abnormalities are common findings in myeloproliferative syndromes and are more severe in ET. The more pronounced platelet vWF abnormalities in ET may reflect the more frequent bleeding symptoms observed in this disorder.

Adult↗
PubMed1995

Molecular bases of CRM+ factor X deficiency: a frequent mutation (Ser334Pro) in the catalytic domain and a substitution (Glu102Lys) in the second EGF-like domain.

The presence of gene lesions in coagulation factor X (FX, Stuart factor) was investigated in asymptomatic subjects with FX deficiency characterized by the presence of dysfunctional molecules in plasma, as demonstrated by the discrepancy between clotting activity and antigen level. A missense mutation (Ser334Pro) in the catalytic domain was found in three unrelated families in both the homozygous and the heterozygous conditions, and also in the compound heterozygous form with the substitution of Lys for 102 Glu. None of the mutations was detected in 40 unrelated subjects from the same geographic area. The Ser334Pro mutation affects a serine protease region characterized by extensive variation in the coagulation factors but conserved in mammalian factor X molecules. The Glu102Lys mutation affects a residue of the second EGF-like module also conserved in protein C. Both mutated residues are surface-exposed and found in protein regions suggested to be involved in macromolecular interactions which are impaired in the dysfunctional molecules.

Base Sequence↗
PubMed1995

A novel candidate mutation (Arg611-->His) in type I 'platelet discordant' von Willebrand's disease with desmopressin-induced thrombocytopenia.

In three affected members of a family with type I 'platelet discordant' von Willebrand's disease displaying desmopressin-induced thrombocytopenia, we have detected in exon 28 of the von Willebrand factor gene a heterozygous G(4121)-->A transition, which predicts an Arg611-->His substitution. The mutated allele was absent in 50 normal individuals. An unrelated patient with a similar phenotype was also found to be heterozygous for this mutation. The mutation is located in the A1 domain of von Willebrand factor, where most type 2B von Willebrand's disease mutations are found. Mutations in this domain result in von Willebrand factor multimers with enhanced affinity for platelet glycoprotein Ib, and this may explain the association of Arg611-->His with the moderate thrombocytopenia observed after desmopressin infusion.

Base Sequence↗
PubMed1995

Factor VIII:C increases after desmopressin in a subgroup of patients with autosomal recessive severe von Willebrand disease.

Patients with severe von Willebrand disease (vWD) usually show no increase of factor VIII/von Willebrand factor (VIII/vWF) after desmopressin (DDAVP) infusion and the bleeding time (BT) remains markedly prolonged. We have tested the biological responsiveness to DDAVP in six patients, belonging to six different families, with phenotypic evidence for severe vWD. Baseline VIII:C ranged from 12 to 32IU/dl, ristocetin cofactor activity (RiCof) was unmeasurable in all the patients, vWF antigen (vWF:Ag) ranged from 0.5 to 3.5 IU/dl, and in all patients the BT was longer than 30 min. No measurable vWF was present in patient's platelets, and plasma and platelet vWF multimers were virtually absent. An autosomal recessive pattern of inheritance was evident in all the propositi. After DDAVP infusion, there was no BT shortening. In four patients, VIII:C increased post-infusion and in three patients levels greater than 50 IU/dl were attained. RiCof reached a maximum of 11 IU/dl and vWF:Ag 9 IU/dl. In one of these four patients, DDAVP allowed a safe dental extraction, without resorting to blood products. In the remaining two patients no VIII/vWF changes were observed after DDAVP. In conclusion, a subgroup of patients with severe vWD shows an increase of VIII:C after DDAVP. A test infusion with this agent is advisable in patients with severe vWD before considering treatment with VIII/vWF concentrates.

Adolescent↗
PubMed1995

Current management of von Willebrand's disease.

von Willebrand's disease (vWD) is the most frequent inherited disorder and is the result of a deficiency and/or abnormality of von Willebrand factor (vWF). As a consequence, the level of factor VIII, the presence of which reflects the ability of vWF to stabilise it, is usually low. Bleeding time, which reflects the ability of vWF to promote platelet adhesion to subendothelium, is therefore prolonged. However, from a therapeutic point of view, it appears that the correction of factor VIII and bleeding time is sufficient to prevent or treat bleeding in these patients. There are 2 main therapeutic tools to improve or normalise these major determinants of the bleeding tendency in this disorder. The majority of patients, identified by a test infusion, can be successfully treated by giving desmopressin (DDAVP), a synthetic analogue of vasopressin. Desmopressin is able to induce the increase of autologous vWF released from endothelial cells, leading to the correction of factor VIII levels and of bleeding time. In the remaining cases, blood products, namely factor/vWF concentrates, are required to accomplish haemostasis. All these concentrates are able to correct factor VIII levels, whereas their effect on bleeding time may not be consistent. The modern virucidal techniques abolish the risk of transmission of blood-borne viruses (e.g. hepatitis viruses and HIV) and make these products safer than blood-bank cryoprecipitate.

Female↗
PubMed1994

Epidemiology of hemophilia and of HIV infection in Italy. GICC. Gruppo Italiano Coagulopatie Congenite.

To evaluate the incidence and prevalence of hemophilia in Italy and the impact of HIV infection on the Italian hemophiliac population, data from a computerized national registry of patients from 95% of the hemophilia care centers in Italy were analyzed. A total of 4643 patients were included in the registry. The prevalence of hemophilia A was 8.2 per 100,000 males, with no significant regional differences; for hemophilia B the corresponding figure was 1.5 per 100,000. Temporal trends in hemophilia incidence suggest that the diagnosis of mild and moderate hemophilia has improved. The overall HIV prevalence was 26% and was significantly (p < 0.001) higher in patients with hemophilia B (47.1%) compared to those with hemophilia A (26.8%) or other diseases (16.5%). The highest rate of HIV seropositivity was among patients 20-29 years of age. The annual amount of clotting factor concentrates received was significantly (p < 0.001) higher in HIV seropositive patients than in those who were seronegative. Antibody testing was never performed on 10.1% of severely affected patients. The number of patients in the Italian registry was similar to the number that would have been expected based on prevalence estimates from other countries. In comparison with other countries, the prevalence of HIV infection recorded in Italy was lower in persons with hemophilia A, but higher in those with hemophilia B. Our study demonstrates the usefulness of a registry in delineating the epidemiology of hemophilia and in studying risk factors for HIV infection. It also underlines the need for continuing surveillance of this population.

Adult↗
PubMed1994

The role of platelet von Willebrand factor in platelet adhesion and thrombus formation: a study of 34 patients with various subtypes of type I von Willebrand disease.

In order to investigate the respective role of plasma and platelet von Willebrand factor (vWF) in mediating platelet adhesion and thrombus formation, we performed ex vivo perfusion studies with native blood from patients with various subtypes of type I von Willebrand disease (vWD). We studied 34 patients with type I vWD (19 'platelet normal', five 'platelet low', two 'platelet discordant', eight 'Vicenza'). Parallel studies were carried out on nine patients with severe vWD (type III). At high shear rate (2600 s-1) we found that the defect in platelet-vessel wall interactions in patients having a normal platelet vWF content ('platelet normal' and 'Vicenza') involved thrombus formation, whereas platelet adhesion was normal. At this high shear rate, platelet adhesion and thrombus volume were significantly decreased in patients with subtypes 'platelet low' and 'platelet discordant', i.e. when platelet vWF is either low or dysfunctional. These results indicate that platelet vWF may substitute for plasma vWF to promote platelet adhesion, emphasizing the important role of platelet vWF. They also confirm the role of vWF in thrombus formation at high shear rate because an abnormal thrombus volume was observed in all patients, even when platelet adhesion was normal.

Blood Platelets↗