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Biomedical subjects

P Petrini

Publications and source records attributed to P Petrini.

At least 19 recordsLinked to original sources
PubMed2003

How to start prophylaxis.

A cohort study was performed to assess the efficacy of a gradual introduction to primary prophylaxis by peripheral vein injections. Bleeding symptoms prior to the initiation of prophylaxis and during the time from the start of home treatment were investigated. Forty-seven boys with severe haemophilia, born between 1987 and 2000, were studied. The mean age at the start of prophylaxis was 16 months and the mean age for the boys on home treatment and full prophylaxis was 30 months. Our results show that primary prophylaxis with injections in a peripheral vein is possible in most patients (83%). Even with this early start, 59% of the children had been treated with clotting factor concentrate before prophylaxis was initiated. Seventy-two percent of the boys had no symptoms from the joints or muscles in the time from initiation to full prophylaxis every second (haemophilia A) or third day (haemophilia B). None of the patients developed cerebral bleeding during this period, but one patient had an epidural bleeding as the presenting symptom of haemophilia.

Child, Preschool↗
PubMed2003

Consensus perspectives on prophylactic therapy for haemophilia: summary statement.

Participants in an international conference on prophylactic therapy for severe haemophilia developed a consensus summary of the findings and conclusions of the conference. In the consensus, participants agreed upon revised definitions for primary and secondary prophylaxis and also made recommendations concerning the need for an international system of pharmacovigilance. Considerations on starting prophylaxis, monitoring outcomes, and individualizing treatment regimens were discussed. Several research questions were identified as needing further investigation, including when to start and when to stop prophylaxis, optimal dosing and dose interval, and methods for assessment of long-term treatment effects. Such studies should include carefully defined cohorts, validated orthopaedic and quality-of-life assessment instruments, and cost-benefit analyses.

Consensus Statements as Topic↗
PubMed2002

Breastfeeding does not influence the development of inhibitors in haemophilia.

Our aim was to test the hypothesis that breastfeeding may reduce development of inhibitors in male infants with haemophilia by inducing an oral immune tolerance to factor VIII. To achieve that goal, we performed a structured epidemiological survey comprising all males born with severe haemophilia A (in all 100 patients, 19 with inhibitors) or haemophilia B (in all 16 patients, six with inhibitors) in Sweden in 1980-99. Our results show no protective effect of breastfeeding.

Autoantibodies↗
PubMed2002

Inhibitors in the Swedish population with severe haemophilia A and B: a 20-year survey.

AIM: To survey the entire population (n = 116) afflicted with severe haemophilia A or B born in Sweden over a 20-y period (1980-1999), and to examine the epidemiological, genetic and clinical aspects of development of inhibitors to factors VIII and IX (FVIII/FIX). METHODS: One hundred of the subjects had haemophilia A and 16 had haemophilia B. All of these subjects had received prophylactic treatment and had a check-up of inhibitor status at least twice a year. Sixty-one were born between 1980 and 1989 and 55 between 1990 and 1999. RESULTS: Nineteen percent (19/100) of those with haemophilia A and 37% (6/16) with haemophilia B developed inhibitors at 12-18 mo of age, after exposure to FVIII/FIX concentrates for an average of 14 d in the case of haemophilia A and 16 d in haemophilia B. All patients with inhibitors carried mutations that impaired protein synthesis. The high incidence of FIX inhibitors may have been due to the large number of complete deletions (13%) in the Swedish haemophilia B population. Patients with haemophilia A showed no significant increase (p = 0.65) in incidence of inhibitors (n = 10/48, total incidence 21%) in the 1990s, when they were treated mainly with recombinant products, as compared to the 1980s (n = 9/52, 17%), when they received intermediate/high-purity plasma-derived concentrates. CONCLUSION: Our population-based study verifies that genotype has a general impact on the incidence of FVIII/FIX inhibitors, and that recombinant FIII/FIX concentrates are not a predisposing factor for inhibitor development.

Adolescent↗
PubMed2001

Use of recombinant factor VIIa (NovoSeven) in patients with Glanzmann thrombasthenia.

Recombinant factor VIIa (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) appears effective and relatively safe for the treatment of bleeding and for surgical prophylaxis in patients with Glanzmann thrombasthenia as reported to the International Registry on rFVIIa and Congenital Platelet Disorders. One of the shortcomings of the Registry data is the heterogeneity of treatment protocol, including dosage, number of doses used, duration of treatment before declaration of failure, and mode of rFVIIa administration (bolus v continuous infusion). The data are not yet sufficient to define optimal regimens for various indications such as the type of bleeding or the type of procedures. The place of this drug compared to platelet transfusion in the overall management of patients with Glanzmann thrombasthenia will need to be determined in relationship to a number of challenges and unresolved issues in the clinical care of these patients. These issues include: how to improve local measures for patients with mucosal bleeds, optimal management of young women during menarche, optimal platelet transfusion regimens for various indications, the relationship between antiplatelet antibodies detected by monoclonal antibody-specific immobilization of platelet antigens (MAIPA) and effectiveness of platelet transfusion, whether there are other biological tests that may correlate with effectiveness of platelet transfusion, and management of pregnancy and delivery regarding antiplatelet immunization.

Coagulants↗
PubMed2001

Haemophilia B mutations in Sweden: a population-based study of mutational heterogeneity.

The present series comprises all families (n = 77) with haemophilia B in Sweden and may be considered to be representative for the purposes of a population-based study of mutational heterogeneity. The 77 families (38 severe, 10 moderate, 29 mild) had 51 different mutations in total. Thirteen families had total, partial or small deletions, two had mutations in the promoter, eight families had splice site mutations, 14 had nonsense and the remaining 41 had missense mutations. Ten of the mutations, all C-->T or G-->A, recurred in 1--6 other families. Using haplotype analysis of seven polymorphisms in the factor IX (FIX) gene, we found that the 77 families carried 65 unique, independent mutations. Of the 48 families with severe or moderate haemophilia, 23 (48%) had a sporadic case of haemophilia compared with 31 families out of 78 (40%) in the whole series. Five of those 23 sporadic cases carried de novo mutations, 11 out of 23 of the mothers were proven carriers and, in the remaining seven families, it was not possible to determine carriership. Eleven of the 48 patients (23%) with severe haemophilia B developed inhibitors and all of them had deletions or nonsense mutations. Thus, 11 out of 37 (30%) patients with severe haemophilia B as a result of deletion/nonsense mutations developed inhibitors compared with 0 out of 11 patients with missense mutations. The ratio of male to female mutation rates was 5.3 and the overall mutation rate was 5.4 x 10(-6) per gamete per generation.

Age Factors↗
PubMed2001

What factors should influence the dosage and interval of prophylactic treatment in patients with severe haemophilia A and B?

In order to prevent arthropathy, prophylaxis has to start at a young age before recurrent joint bleedings have taken place. The use of central venous lines has facilitated an early beginning to treatment, but due to side-effects, most European paediatricians prefer peripheral injections whenever possible. By starting primary prophylaxis at the age of 1--2 years with one injection weekly, the need for surgical implants may be reduced. In this study, only four of 34 boys born 1988--98 with severe haemophilia A or B needed a Port-a-Cath for primary prophylaxis. Trough levels were measured in these patients and 79% showed a trough level < 1%, while 21% reached a level > 1%. Despite this, joint bleedings during 1998 were rare in both groups [0--4] and 59% of the boys with trough levels < 1% did not report any haemartroses during that year. Mean annual joint bleedings were the same in both groups [0.70, 0.71]. The lowest effective level of factors VIII and IX must be determined individually for each patient on primary or secondary prophylaxis.

Child, Preschool↗
PubMed2001

An approach to study the viral safety of plasma-derived products in previously treated, non-infected patients.

Using the polymerase chain reaction (PCR), we designed a study concept to evaluate the safety of plasma derivatives in previously treated patients who are non-infected by the specific viruses studied. Several product lots can be studied in a single patient, with a study period for each lot of 3 months. In the present study 19 patients were included for treatment with Baxter Hyland Immuno's PCR-screened factor VIII concentrate Immunate (n=7), factor IX concentrate Immunine (n=10), the by-passing agent FEIBA plus Immunine (n=1), and the protein C concentrate Ceprotin (n=1). PCR testing for hepatitis B, C or HIV genomic material in patient samples was done as well as serological testing. All patients remained negative for the tested markers. All seven Immunate patients completed three treatment periods with three different lots of the study drug. The median study period was 282 days and the median dose 115 000 units, with a median of 115 exposure days. Five of the 10 Immunine patients completed three treatment periods and four patients, two treatment periods. One Immunine patient was discontinued from the study for reasons unrelated to the study drug administration. The median study period was 305 days and the median total dose 82 200 units, with a median of 88 exposure days. Our study presents a new design to approach the evaluation of viral safety of new plasma derivatives in previously treated, non-infected patients (NIPs) and offers several advantages over the currently recommended studies using testing for serological markers of infection in previously untreated patients (PUPs).

Blood Coagulation Factors↗
PubMed2000

Treatment of children with haemophilia in Europe: a survey of 20 centres in 16 countries.

A survey was made of the current status of treatment of haemophilic boys at 20 centres in 16 European countries and includes approximately 1500 of the estimated 6500 haemophiliacs in the participating countries. Many mild haemophiliacs are not seen, or seen infrequently, at haemophilia centres and this requires study. Nine of 18 centres provide continuous prophylaxis to 80-100% of their patients, five centres provide it to 55-80% and the remaining four centres to 15-40% of the boys. The median dose given was 6240 U kg-1 year-1 (range 3120-7800). Four centres administered only recombinant concentrates to children with severe haemophilia A, while seven centres administered recombinant concentrates to 75-90% and the remaining centres to less than 50% of the boys (two centres < 10%). When asked for the choice of concentrate for a newly diagnosed boy with severe haemophilia A, all but one centre preferred recombinant concentrate. Most boys below 6 years received concentrates via a peripheral vein but three centres preferred a central venous line for 80-100% of the boys. Thirteen of 18 centres applied home treatment to 84-100% of the boys and the remaining five centres to 57-77% of the boys.

Adolescent↗
PubMed2000

Novel poly(urethane-aminoamides): an in vitro study of the interaction with heparin.

In order to obtain heparin-binding polyurethanes, tertiary amino-groups have been introduced in the polymer backbone by attributing a key-role to the chain extender, i.e. substituting butanediol, commonly used in polyurethane synthesis, with a tailor-made diamino-diamide-diol. In this work a poly(ether-urethane-aminoamide) (PEU/PIME/al) was obtained with poly(oxytetramethylene) glycol 2000, 1,6-hexamethylene-diisocyanate and the new chain extender, in the molar ratio 1:2:1. The heparin binding capacity of PEU/PIME/al was evaluated with 125I labelled heparin, using for comparison the analogous polymer obtained with a diamide-diol (i.e. the poly(ether-urethane-amide) PEU/PIBLO/al), and two commercially available biomedical polyurethanes (Pellethane 2363 and Corethane). pH and ionic strength dependence of the heparin uptake were investigated by treating all the polyurethanes with solutions of 125I heparin into buffers from pH 4 to 9 or NaCl molarity from 0.0 to 1.0. The stability of the interaction with bound heparin was investigated by sequential washing treatments (PBS, 1 N NaOH, 2% SDS solution), then analysing the residual radioactivity on the materials. Results indicated that the heparin binding of PEU/PIME/al is significantly higher and more stable than that of the other polyurethanes, with a time-dependent kinetic. The interaction with heparin appears to be prevalently ionic, with the contribution of other electrostatic and hydrophobic interactions. Activated partial thromboplastin time (APTT), performed on human plasma with polyurethane-coated, heparinized test tubes, indicated that bound heparin maintains its biological activity after the adsorption.

Animals↗
PubMed2000

In vitro stability of polyether and polycarbonate urethanes.

The in vitro structural stability of poly-ether-urethanes (PEUs) and poly-carbonate-urethanes (PCUs) was examined under strong acidic (HNO3) or alkaline (NaClO) oxidative conditions and in presence of a constant strain state. Polyurethane (PU) samples were represented by sheets solvent-cast from commercial pellets or by tubular specimens cut from commercial catheters. The specimens were strained at 100% uniaxial elongation over appropriate extension devices and completely immersed into the oxidative solutions at 50 degrees C for 7-14 days. The changes induced by the oxidative treatments were then evaluated by molecular weight analysis, tensile mechanical tests, and scanning electron microscopy. In the experiments with solvent-cast samples, the PEU Pellethane was degraded more in the alkaline oxidative conditions and mainly in the absence of an applied uniaxial stress. All the tested PCUs were, on the contrary, more affected by the acidic oxidative agent. All the PCUs proved to have overall better stability than the PEU. The susceptibility to oxidation was also dependent on the shape and bulk/surface organisation acquired by the same polymer during its processing. When the oxidative test was applied to catheters made of a PEU and a PCU, the results confirmed the better stability of poly-carbonate-urethanes.

Biocompatible Materials↗
PubMed1999

[Centralized care is the basis of care programs for hemophilia patients].

Haemophilia is a rare and potentially life-threatening disease. In Sweden, with a population of approximately 8.5 million, about 350 people suffer from the more severe forms of haemophilia or von Willebrand disease. Meticulous management is important if the patients are to be spared chronic disability and serious treatment complications. The disease is lifelong and affects psychosocial aspects of life among patients and their families. With the help of a grant from the Swedish Board of Halth and Welfare, a care programme has been designed to guarantee Swedish haemophiliacs comparable and optimal care. The programme has been drawn up by representatives of the three haemophilia centres in Sweden (at University Hospital, Malmö, Sahlgrenska University Hospital, Gothenburg, and Karolinska Hospital, Stockholm) in co-operation with the World Federation of National Haemophilia Organisations. To ensure optimal individual application of the programme, individualised management strategies and patient information leaflets have been prepared.

Centralized Hospital Services↗
PubMed1999

Synergistic effects of oxidative environments and mechanical stress on in vitro stability of polyetherurethanes and polycarbonateurethanes.

The in vitro structural stability of polyetherurethanes (PEUs) and polycarbonateurethanes (PCUs and PCUUs) was examined under strong oxidative conditions (0.5N HNO3, pH 0.3; and NaClO, 4% Cl2 available, pH approximately 13) and in the presence of a constant strain state. Solvent-cast dog-bone shaped specimens were strained at 100% uniaxial elongation over extension devices and completely immersed in the oxidative solutions at 50 degrees C for 15 days. Unstrained polyurethane (PU) samples were treated in the same way for comparison. The modification of the PU molecular structure was determined by DSC, GPC, ATR-FTIR, static contact angle, and surface roughness analyses. The incubation in nitric acid and sodium hypochlorite brought about a greater degradation of samples tested under the applied strain with the exception of PEU treated with nitric acid. PEU was the most affected material, showing bulk deterioration in NaClO and significant modifications in nitric acid, with the appearance of new IR bands, which were assigned to oxidation products. A higher phase separation between soft and hard domains occurred in PCUs upon incubation in nitric acid, the treatment with NaClO gave rise to new bands in the IR spectra, denoting the presence of oxidation products at the surface. The surface roughness greatly increased in strained PCUs with SEM evidence of deep cracks and holes or ragged and stretched fractures perpendicular to the direction of stress. PCUU underwent complex chemical modifications with a marked decrease of N-H and urea IR absorptions and showed a lower degradation than PEU and PCUs under mechanical constraint. From these results, sodium hypochlorite appears to be able to create an ESC-like degradation for PUs that are resistant to other aggressive chemical environments.

Microscopy, Electron, Scanning↗
PubMed1999

Primary prophylaxis in severe haemophilia should be started at an early age but can be individualized.

The frequency of joint bleeds and orthopaedic joint scores were evaluated in 121 patients with severe haemophilia who had started prophylactic treatment with clotting factor concentrates at least once weekly before the age of 10. 75 of the patients started before the age of 3, 31 at the age of 3-5 and 15 at the age of 6-9. Each subgroup was evaluated separately. In addition, a regimen of one infusion weekly was compared with that of two (haemophilia B) or three (haemophilia A) infusions weekly in each patient. A significant decrease in the overall number of joint bleeds per year was found after shortening the infusion interval (P<0.005), but the individual bleeding pattern varied. In survival analysis of the first pathologic joint score event, those who started prophylaxis before the age of 3 had a better outcome overall than those starting at later ages (P=0.001). However, in subgroup analysis, no significant difference was seen in the annual number of joint bleeds and the development of arthropathy between those starting with, or shifting to, the more intensive regimen before the age of 3 and those that were put on this regimen at the age of 3-5. Age at start of prophylaxis was found to be an independent predictor for the development of arthropathy (P=0.0002), whereas dose and infusion interval at start were not. Our data emphasize the importance of starting replacement therapy during the first years of life. However, it seems that when beginning the regimen it can be individualized and adjusted according to the bleeding pattern. In this way, the need for a venous access system may be assessed on an individual basis.

Age Factors↗
PubMed1998

Hepatitis C virus-infected, HCV-RNA-negative patients with bleeding disorders--relationship to age, HIV and treatment.

All 155 anti-hepatitis C-virus (HCV) positive patients with haemostatic disorders at our unit were tested for HCV-RNA in order to determine the prevalence of a negative result. The patients were also characterized in order to find predictors for a negative HCV-RNA test. The prevalence of a negative HCV-RNA test was 15.5% (24 of 155) and this was similar among anti-HIV positive and negative patients. A common denominator for the 4 HIV-infected, HCV-RNA negative haemophiliacs was treatment with azidothymidin prior to the first test. Among the anti-HIV negative patients, those < 40 y of age had a significantly greater chance of being HCV-RNA-negative than the older ones (27.3 vs 3.6%). They also had a lower consumption of plasma products than age-matched HCV-RNA positive cases. Absence of co-infection with hepatitis B was not correlated with a negative HCV-RNA test. Young age and a low requirement for factor concentrates thus seem to be predictors for a negative HCV-RNA test in patients with bleeding disorders.

Adolescent↗
PubMed1998

Port-A-Cath usage in children with haemophilia: experience of 53 cases.

Experience of the Port-A-Cath implantable venous access system in 53 children with severe or moderate haemophilia A or B from seven centres in five countries is reviewed. The cumulative duration of follow-up was 1578 months (median 30 months, range 1-114). Of the devices implanted, 70% (37/53) were used without complications (median follow-up 32 months; range 1-114) and the remaining 30% (16/53) were associated with various types of complication: infection, bacteraemia or septicaemia in 56% (9/16) of cases, i.e. a rate of 0.07 per follow-up year or 0.19 per 1000 patient days, or various technical complications occurring after a median of 32 months (range 4-75) of uncomplicated use in the remaining 44% (7/16). Of the patients with inhibitors, 64% (7/11) manifested complications. Both doctors and parents considered that the Port-A-Cath device can be used with an acceptable frequency and severity of complications, and that it enables regular prophylactic or on-demand home treatment of children with haemophilia to be begun at an early age.

Catheterization, Central Venous↗
PubMed1998

Experiences with continuous infusion of recombinant activated factor VII.

A questionnaire was sent to 28 haemophilia treatment centres known to have used recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark), to collect data on continuous infusion of this product. This mode of administration was recently introduced for rFVIIa but there are several questions which remain to be answered in order to optimize this technique. Of the 26 responding centres, 14 had used rFVIIa in continuous infusion for 40 treatment episodes over a total of 283 days. In most of the cases the treatment was targeted at a factor VII level of 10 IU/ml, monitored by the one-stage clotting assay. This seemed to be adequate for most of the haemorrhagic and surgical procedures. Pretreatment pharmacokinetic evaluation was performed in only a minority of the cases but is probably of great importance given the wide variation observed in the clearance values. A strategy was necessary to prevent local thrombophlebitis, at least for infusions in peripheral veins; parallel infusion of heparin, saline or dextrose-saline proved effective. The question of optimal monitoring needs further attention. Haemorrhagic complications were significantly less frequent when treatment was combined with the antifibrinolytic tranexamic acid.

Drug Monitoring↗