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P Rebulla

Publications and source records attributed to P Rebulla.

At least 37 records · Page 2Linked to original sources
PubMed2001

Revisitation of the clinical indications for the transfusion of platelet concentrates.

Platelet transfusion is indicated when the expected benefits of increasing the number of functional platelets in the patient's circulation outweigh the potential risks generated by exposing the patient to allogeneic, manipulated and stored blood products such as platelet concentrates. Although reassuring evidence has been collected indicating that current risks associated with blood transfusion are lower than those of several voluntary and involuntary human activities, balancing benefits and risks of platelet transfusion may not be easy in a proportion of patients and in a number of conditions. To facilitate this task, guidelines have been developed, with particular attention to cancer patients. As witnessed by the most recent guidelines, over the last few years there has been a progressive, although not absolute, consensus on: (i) the routine use of platelets as a tool to prevent hemorrhage in oncohematology (the so called 'prophylactic approach') as opposed to limiting platelet transfusion to actual bleeding episodes (the so-called 'therapeutic approach') and (ii) lowering the trigger for prophylactic platelet transfusion in stable oncohematology recipients from 20 x 109 to 10 x 109 platelets/L. This has been accompanied by a reduction of platelet use per oncohematology patient of about 20%, an important outcome in view of the progressive increase of platelet demand due to more aggressive therapy in cancer patients. In selected clinical conditions, specific triggers ranging from 30 x 10(9) to 100 x 10(9) platelets/L have been recommended, with higher values when surgical procedures are required for the patient's treatment. Indications and trigger values proposed in the guidelines must be considered within the context of careful clinical evaluation of each patient, with a clear appreciation of the power of discrimination of automated platelet counters at low counts, and of the quality and local availability of platelet products for emergency.

Guidelines as Topic↗
PubMed2001

Outcomes of a program to evaluate mother and baby 6 months after umbilical cord blood donation.

BACKGROUND: A routine program of evaluating mothers and infants 6 months after umbilical cord blood donation was started at the Milano Cord Blood Bank (MCBB) in 1996. This study evaluated the main outcomes of this program. STUDY DESIGN AND METHODS: All mothers donating cord blood at this bank from February 1996 through May 1999 were invited to visit the bank or the collection suite 6 months after delivery to report on the health condition of their babies and to provide a fresh blood sample for repeat basal serologic tests (HBsAg, anti-HCV, anti-HIV-1/2, and syphilis). A bank volunteer contacted the mothers by telephone to schedule their visits just before the expiration of the 6-month period. Before collection of the new sample, a trained operator interviewed the mothers to review the mother's medical history information collected at donation and to obtain the baby's postnatal medical history. RESULTS: Of the 2450 mothers enrolled in the study, 2315 (94.5%) attended the bank in agreement with the program, 4 promised to attend, 95 could not be traced, 26 declined the invitation, and 10 were unable to attend. Of the 135 mothers who could not be traced, 29 (21.4%) belonged to non-European ethnic groups. The average time spent with each mother was approximately 20 minutes. In serologic testing, one indeterminate anti-HCV seroconversion (c22) was detected. Collection of the baby's postnatal history reported one case of congenital urinary malformation not known at delivery, one of protein C deficiency, one of phenylketonuria, one of mucoviscidosis, and one of 10q- chromosomal abnormality. The cord blood components from all these births were discarded. CONCLUSION: These data support the feasibility of a routine 6-month program of evaluating mothers and babies giving cord blood at a cord blood bank. Such programs may increase the quality of components stored for transplantation.

Adult↗
PubMed2001

Current status of cord blood banking and transplantation in the United States and Europe.

Cord blood (CB) transplantation has expanded the ability of the transplantation community to meet the growing needs of their patients. Clinical data over the last decade show promising results in CB transplantation using blood from related as well as unrelated donors. Basic science continues to look for ways to expand the quality and quantity of CB. CB banks are now established around the world, with major efforts to standardize banking to facilitate regulation, collection, processing, and distribution as a way of providing the highest-quality CB for patient use. This review article discusses the current status of CB transplantation and banking in the United States and Europe.

Blood Banks↗
PubMed2001

Ultrastructural features of CD34+ hematopoietic progenitor cells from bone marrow, peripheral blood and umbilical cord blood.

Hematopoietic progenitor cells from different sources have been widely characterized, but their ultrastructural morphology has never been described in detail. In this study, imunomagnetically separated CD34+ cells from normal bone marrow (BM), mobilized peripheral blood (PBSC) and human umbilical cord blood (CB) were studied by transmission electron microscopy (TEM) using a cytochemical method which reveals endogenous myelo-peroxidase (MPO) activity. This technique is particularly suited for detecting early signs of the myeloid commitment. The CD34+ cells from PBSC were morphologically very homogeneous and 94.7+/-4.5% of these cells were MPO-: these ultrastructural features are generally considered typical of immature cells. The CD34+ BM cells were instead more heterogeneous, with 24.6+/-7.4% showing intense MPO activity. The ultrastructural characteristics of CB cells fell between those observed in PBSC and BM, but there was a high percentage of morphologically immature cells with no evidence of MPO activity (about 83%). The number of apoptotic cells within samples from different sources was also examined both by TEM and flow cytometry. The percentage of apoptotic cells was 0.7% in PBSC, 2.3% in BM, 2.9% in CB from vaginal delivery and 11.6% in CB from cesarean section. These observations confirm the relative phenotypic immaturity of CB in comparison with BM cells; they also suggest that CB collected after cesarean section may be associated with reduced stem cells viability.

Antigens, CD34↗
PubMed2000

In vitro quantification of anti-red blood cell antibody production in idiopathic autoimmune haemolytic anaemia: effect of mitogen and cytokine stimulation.

The immunopathogenic mechanisms underlying idiopathic autoimmune haemolytic anaemia (AIHA) are still unknown, although regulatory cytokines are thought to play an important role. We investigated cytokine production by mitogen-stimulated whole blood cultures from 21 patients with AIHA and from 22 age- and sex-matched controls. In parallel experiments, we studied the effect of mitogen and cytokine stimulation on anti-red blood cell (RBC) IgG antibody production, assessed as both binding on autologous RBCs and secretion in culture supernatants. To quantify anti-RBC antibody, we set up a sensitive and quantitative solid phase competitive immunoassay. The results showed that in AIHA patients production of interleukin (IL)-4, IL-6 and IL-13 was significantly increased, whereas that of interferon (IFN)-gamma was reduced. Multivariate analysis showed that IFN-gamma was the only independent factor significantly associated with the reduced T-helper-1-like cytokine profile. Patients with active haemolysis showed further reduction of IFN-gamma and IL-2 production and increased secretion of transforming growth factor (TGF)-beta. In AIHA patients, mitogen stimulation, as well as IL-6, significantly increased autologous anti-RBC-binding relative to unstimulated cultures. Mitogen stimulation and addition of IL-4, IL-6, IL-10, IL-13 and TGF-beta significantly increased both autologous anti-RBC binding and antibody secretion in AIHA patients compared with controls. The results suggest that a reduced T-helper-1- and a predominant T-helper-2-like profile and elevated TGF-beta levels might play a role in the immunopathogenesis of AIHA. Furthermore, our competitive anti-RBC antibody was able to detect anti-RBC antibody production in some direct antiglobulin test (DAT)-negative AIHA patients.

Adult↗
PubMed2000

Interleukin-6 and interleukin-11 act synergistically with thrombopoietin and stem cell factor to modulate ex vivo expansion of human CD41+ and CD61+ megakaryocytic cells.

BACKGROUND AND OBJECTIVE: Thrombopoietin (TPO), the ligand for the c-mpl receptor, regulates in vivo platelet production and increases the number of colony-forming unit megakaryocytes (CFU-MK). Other cytokines including interleukin (IL) -3, IL-6, IL-11 and stem cell factor (SCF) can stimulate megakaryopoiesis. The aim of this study was to evaluate the effects of different combinations of cytokines involved in megakaryocytopoiesis on stroma-free liquid cultures of purified human CD34+ cells. DESIGN AND METHODS: Peripheral blood cells were collected after mobilization with granulocyte colony-stimulating factor (G-CSF). Purified CD34+ cells were then cultured with different combinations of TPO, SCF, IL-3, IL-6 and IL-11. RESULTS: The addition of TPO and SCF alone generated a population positive for the antigens CD41 (5.5+/-2.9%) and CD61 (6. 1+/-2.2%) but induced a low amplification of cell number (8.1+/-0.9 fold expansion). The presence of IL-6 or IL-11 was associated with MK progenitor cell expansion, and up to 7-10% of cultured cells were found to be CD41 and CD61 positive by flow cytometry. Conversely, the addition of IL-3 to this cytokine combination was associated with a prominent expansion of the myeloid lineage (70+/-10% of CD33+ cells) but only 0.9% and 2% of cultured cells were positive for CD61 and CD41 respectively. INTERPRETATION AND CONCLUSIONS: Our study supports the idea that IL-6 and IL-11 play crucial roles in the proliferation of MK progenitors and the use of SCF, TPO, IL-6 and IL-11 for ex vivo expansion of this cell population.

Antigens, CD↗
PubMed2000

Trigger for platelet transfusion.

BACKGROUND AND OBJECTIVES: The terms 'platelet transfusion trigger' are used in the scientific literature to indicate a value of the platelet count above which prophylactic platelet transfusion is usually not indicated. Most clinicians share the currently prevalent consensus published in several guidelines that a platelet transfusion trigger of 10,000 platelets per microliter is safe in stable oncohematology recipients carefully monitored at both the clinical and laboratory levels, whereas higher values may be necessary in patients with high fever, infection, splenomegaly, rapid platelet count decrease, on drugs able to affect platelet function and survival, in cases undergoing invasive maneuvers and in some pediatric patients such as premature newborns. The safety of this policy is supported by the results obtained in several randomized clinical trials and prolonged observational studies. Lowering the platelet transfusion trigger from the traditional value set at 20,000 platelets per microliter to the currently recommended value of 10,000 per microliter further stresses the importance of high-quality, sufficient and prompt platelet availability and close cooperation between clinicians and blood transfusion specialists. Furthermore, it requires a clear understanding of the discriminatory power of current automated hematology counters at very low platelet counts. In the surgical setting, where randomized clinical trials on the most appropriate platelet transfusion trigger are largely missing, current guidelines propose to maintain higher platelet count values (50,000-100,000 per microliter) during surgery and in the early postoperative period.

Hematologic Diseases↗
PubMed2000

Blood donors with 'medium' or 'minor' risk factors for human immunodeficiency virus infection: are they eligible for donation?

BACKGROUND AND OBJECTIVES: We conducted a longitudinal prospective study to assess the eligibility to blood donation of donors with 'minor' risk factors (i.e. minor surgery, professional exposure, cohabitation with 'high risk' people, occasional use of light drugs) or 'medium' risk factors for human immuno-deficiency virus (HIV) infection (i.e. casual sexual relationship, multiple heterosexual exposure, sexual partnership with subjects at risk, regular use of light drugs). DESIGN AND METHODS: During a 4-year period we administered a psychosocial questionnaire to all donors attending our Center. In addition we determined anti-HIV, anti-hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg) and syphilis serology (TPHA) at entry to the study and at 6-month intervals. RESULTS: Of 25,367 donors, 1,535 (6%) reported medium and 8,761 (34%) minor risk. At enrollment into the study, 4 medium risk donors were anti-HIV positive and there was a significantly higher rate of positivity for TPHA (0.33% vs 0.07%) and anti-HCV (1.17% vs 0.63%) in this group than in donors reporting no risk. No anti-HIV positivity was observed in minor or no risk donors. During a median follow-up of 18 months, none of 24,404 donors undergoing 106,503 visits seroconverted to HIV. The incidences of novel HCV and syphilis infections were almost one log greater in donors at medium risk (3 and 1x10-4/yr, respectively) than in no risk donors (0.4 and 0.1x10-4/yr, respectively). Medium risk donors were more frequently males (Odds Ratio=3.2, 95% confidence interval= 2.8-3.7), aged 26-35 yrs (1.52; 1.3-1.78), single (1.4; 1.2-1.6), divorced (2; 1.4-2.8), freelance workers (1.43; 1.1-1.9) and first-time donors (1.8; 1.6-2.1) than no risk donors. INTERPRETATION AND CONCLUSIONS: The only 4 HIV positive subjects of the cohort were medium risk donors picked up at enrollment. No HIV seroconversion was observed during the study. On the basis of this study we will continue to defer 'medium' risk donors.

Adolescent↗
PubMed1999

A prospective study on TT virus infection in transfusion-dependent patients with beta-thalassemia.

A novel DNA virus designated TT virus (TTV) has been reported to be involved in the development of posttransfusion non-A-C hepatitis. We evaluated the frequency and natural course of TTV infection in a cohort of transfusion-dependent thalassemic patients in a 3-year follow-up study. Ninety-three serum hepatitis C virus (HCV) antibody-negative patients (median age of 8 years; range, 0 to 25) from eight centers were studied. Of them, 34 (37%) had an abnormal alanine-aminotransferase (ALT) baseline pattern, and the other 12 (13%) showed ALT flare-ups during the follow-up. TTV DNA in patient sera collected at the time of enrollment and at the end of follow-up was determined by polymerase chain reaction (PCR). In parallel, serum samples from 100 healthy blood donors were also tested. At baseline, 87 patient sera (93.5%) tested positive for the TTV DNA. Of these TTV DNA-positive patients, 84 (96.5%) remained viremic at the end of the study period. Of the 6 TTV DNA-negative patients, 3 acquired TTV infection during follow-up. However, no definite relation was observed between the results of TTV DNA determination and ALT patterns. TTV viremia was also detectable in 22% of blood donors. In conclusion, TTV infection is frequent and persistent among Italian transfusion-dependent patients. The high rate of viremia observed in healthy donors indicates that the parenteral route is not the only mode of TTV spread.

Adolescent↗
PubMed1999

Cost of umbilical cord blood units released for transplantation.

BACKGROUND: A large number of institutions have started programs banking umbilical cord blood (UCB) for allogeneic unrelated-donor and related-donor transplantation. However, limited information is available on the financial issues surrounding these activities. STUDY DESIGN AND METHODS: The aim of this study was to determine the fee per UCB unit released for transplantation that would allow cost recovery after 10 years. Three organizational models were considered suitable to provide units for five UCB transplants per 1 million population per year, a figure that would translate into an annual need for 280 units in Italy. Models A, B, and C included, respectively, seven networked banks, each with an inventory of 1,500 units; two networked banks, each with an inventory of 5,000 units; and one bank with an inventory of 10,000 units. It was estimated that it would take 3 years to develop the cryopreserved inventory and that approximately 3 percent of the inventory could be released and replaced each year during the 7-year interval between the fourth and tenth years of activity. The data on the costs of labor, reagents and diagnostics, disposables, depreciation and maintenance, laboratory tests, and overhead, as well as the operational data used in the analysis were collected at the Milano Cord Blood Bank in 1996. RESULTS: Fees of US $15,061, $12,666, and $11,602 per unit released during the fourth through the tenth years of activity allow full cost recovery (principle and interest) under Models A, B, and C, respectively. CONCLUSION: Although UCB procurement costs compare favorably with those of other hematopoietic cell sources, these results and the current fee of US $15,300 used in some institutions show that UCB is an expensive resource. Therefore, judicious planning of banking programs with high quality standards is necessary to prevent economic losses. The advantages of lower fees associated with the centralized banking approach of Model C should be balanced with the more flexible collection offered by Model A.

Blood Banks↗
PubMed1999

Placental/umbilical cord blood transplantation.

In this article we summarize the clinical outcome of unrelated placental/umbilical cord blood (CB) transplantation, discuss the biological characteristics of CB hematopoietic progenitor/stem cells (HPC) and balance the relative advantages and disadvantages of this therapy as compared with transplantation of other HPC sources. Moreover, we discuss CB banking programs at local, national and international levels. The data reported by the investigators of the New York Placental/Umbilical Cord Blood Program and of the Eurocord group indicate that the clinical outcome of allogeneic unrelated CB transplantation is significantly related to cell dose, being more effective in children than in adults, and is highly dependent on disease stage at transplantation. Furthermore, both studies show lower graft-versus-host disease (GvHD) frequency and severity and prolonged time intervals for platelet engraftment as compared to those of bone marrow and mobilized peripheral blood recipients. Although the data from the New York Placental/Umbilical Cord Blood Program seem to support a negative effect of HLA differences, the latter were not significantly associated with survival in the Eurocord series. Additional observations are therefore necessary to collect conclusive evidence in this regard. Currently available data show that CB contains a higher proportion of primitive HPC and that CB-HPC possess higher proliferation and expansion potentials as compared to adult bone marrow. Furthermore, there is some evidence indicating that CB-HPC are more adequate than HPC from other sources for genetic manipulation and gene therapy. Despite the significant advances in the knowledge of the biology and in the clinical use of CB, a number of problems remain unsolved, including the standardization of banking procedures and unit quality and the development of suitable protocols for transplantation of adult patients.

Adult↗
PubMed1998

A multicenter prospective study on the risk of acquiring liver disease in anti-hepatitis C virus negative patients affected from homozygous beta-thalassemia.

Although the risk of transfusion-transmitted hepatitis has been recently reduced, transfusion-dependent beta-thalassemia patients may still develop liver disease due to viral infection or iron overload. We assessed the frequency and causes of liver dysfunction in a cohort of anti-hepatitis C virus (HCV) negative thalassemics. Of 1,481 thalassemics enrolled in 31 centers, 219 (14.8%) tested anti-HCV- by second-generation assays; 181 completed a 3-year follow-up program consisting of alanine-aminotransferase (ALT) measurement at each transfusion and anti-HCV determination by third-generation enzyme-immunoassay (EIA-3) at the end of study. Serum ferritin levels were determined at baseline and at the end of follow-up. Ten patients were anti-HCV+ by EIA-3 at the end of follow-up. Of them, seven were already positive in 1992 to 1993 when the initial sera were retested by EIA-3, one tested indeterminate by confirmatory assay, and two had true seroconversion (incidence, 4. 27/1,000 person years; risk of infection, 1/7,100 blood units, 95% confidence interval [CI], 1 in 2,000-1 in 71,000 units). At baseline, 67 of 174 thalassemics had abnormal ALT. Of those with normal ALT, seven subsequently developed at least one episode of moderate ALT increase (incidence, 24.6/1,000 person-years). All of the 20 patients with ferritin values >/=3,000 ng/mL had clinically relevant ALT abnormalities, as compared with 53 of 151 with <3,000 ng/mL (P < .005). Hepatic dysfunction is still frequent in thalassemics. Although it is mainly attributable to siderosis and primary HCV infection, the role of undiscovered transmissible agents cannot be excluded.

Adolescent↗