Search PubMed⌕ Search

Biomedical subjects

V Blanchette

Publications and source records attributed to V Blanchette.

At least 19 recordsLinked to original sources
PubMed2006

A laparoscopic approach to partial splenectomy for children with hereditary spherocytosis.

BACKGROUND: Partial splenectomy is sometimes used for children with hereditary spherocytosis (HS) to reduce hemolysis while retaining some splenic immune function. Previous reports have described a partial splenic resection through a laparotomy incision. Whereas laparoscopic total splenectomy for HS is well-established, laparoscopic partial splenectomy (LPS) has not been described. The authors have developed a novel LPS technique that combines the benefits of partial splenectomy with those of a laparoscopic approach. METHODS: A chart review was conducted for three children with HS who underwent LPS, with approximately one-fourth of the spleen left on the basis of the short gastric arterial supply. RESULTS: The mean preoperative spleen size was 17.6 cm. The mean preoperative hemoglobin count was 100 g/l, and the postoperative hemoglobin count was 133 g/l. All three patients reported reduced malaise and increased energy levels. There was no recurrent anemia at the 1- to 2-year follow-up evaluation. CONCLUSION: The LPS procedure is a safe and effective approach to HS that resolves anemia, potentially retains some splenic immunity, and confers the benefits of a minimal access technique.

Adolescent↗
PubMed2006

Overview of the use of implantable venous access devices in the management of children with inherited bleeding disorders.

Frequent infusion of factor concentrates may be challenging in young boys with haemophilia, especially if their disease is complicated by inhibitors. A central venous access device (CVAD) is often placed in young patients in need of repeated infusions for prophylaxis or immune tolerance induction. Although user friendly and capable of providing reliable venous access, these devices are associated with a high complication rate over time. In the haemophilia population, major complications include CVAD-associated infections and deep venous thrombosis, which is most often silent. Established risk factors for catheter-related infection include age less than 6 years at the time of CVAD placement and use of an external CVAD when compared with a totally implantable device such as a port. Avoidance of CVAD-related infections is facilitated by strict adherence to aseptic technique. The risk of deep venous thrombosis appears related to the duration for which the catheter is in place, with the risk increasing beyond 4 years. The promotion of a strict clinic policy in which CVADs are left in place for as short a time as possible should decrease the risk of complications. In rare cases where a totally implantable CVAD cannot be placed for technical reasons, an arteriovenous fistula may provide reliable venous access. In all cases, however, venous access via peripheral veins is preferred over CVADs.

Catheterization, Central Venous↗
PubMed2005

Recombinant FVIIa in the management of intracerebral haemorrhage in severe thrombocytopenia unresponsive to platelet-enhancing treatment.

Intracranial haemorrhage (ICH) is a dramatic and potentially life-threatening presentation of children with thrombocytopenia. Management is limited to supportive care. Recent evidence suggests that ongoing bleeding following the initial ICH may result in greater neurological morbidity and mortality. Haemostatic agents, including recombinant factor VIIa (rFVIIa), a product licensed for use in patients with haemophilia and inhibitors, may be helpful in reducing bleeding in children with refractory thrombocytopenia. We present the case of a 16-year-old girl with severe refractory immune thrombocytopenia, who presented with a major ICH and responded to treatment that included rFVIIa and platelet transfusions. The dose of rFVIIa was empirically chosen and based on reported cases in the literature. The case highlights a number of issues regarding off-label use of rFVIIa and demonstrates the need to prospectively collect accurate information on the off-label use of this new potentially useful medication.

Adolescent↗
PubMed2005

Cost of severe haemophilia in Toronto.

Our objective was to determine costs and trends in treating boys with severe haemophilia A before our centre routinely used prophylaxis. One reviewer extracted data from patient charts to determine resource consumption for 17 boys with severe haemophilia A from 1978 to 1998 at Toronto's Hospital for Sick Children. Resources included factor concentrate, doctors and health care professionals (physiotherapists/social workers), tests (laboratory, radiological and diagnostic) and hospitalizations. Subgroup analysis on those patients infected with HIV and/or hepatitis were also performed. Costs in Canadian Dollars were taken from standard lists and discounted at 3%. Total average cost (range) 62 292 dollars (3339-121 738) per year patient(-1); the largest fraction, 59 910 dollars (3103-119 480), 96.2% was accounted for by factor VIII. Hospitalizations accounted for 1832 dollars (0-5217) per patient year(-1) including drugs, nursing care and stay. Doctor and health care professionals visits averaged 252 dollars (36-462) and 72 dollars (0-175) per patient year(-1), laboratory and other tests cost 201 dollars (22-377) and 26 dollars (2-60) per patient year(-1), respectively. The average number of bleeds was 12.9 (2.0-22.0) per patient year(-1), decreasing since 1977 by 0.68 per patient year(-1) (R(2) = 0.56). Hospitalizations averaged 0.22 (0-4) per patient year(-1), lasting 2.3 days. From 1984, hospitalizations decreased by 0.025 patient(-1) year(-1) (R(2) = 0.76). Concurrently, the average treatment costs increased by 5456 dollars patient(-1) year(-1) (R(2) = 0.81). Clotting factor concentrate cost per patient increased by 5521 dollars year(-1) (R(2) = 0.82). Patients with virally transmitted diseases had considerable higher costs. The cost per year was substantial. Costs increased with virally transmitted diseases. Number of bleeds and hospitalizations over the period of study decreased and costs increased because of factor use in secondary prophylaxis.

Adolescent↗
PubMed2004

Hemophilia therapy innovation: development of an advanced category recombinant factor VIII by a plasma/albumin-free method. Proceedings of a Special Symposium at the XIXth Congress of the International Society on Thrombosis and Haemostasis, July 12-18, 2003, Birmingham, UK.

Replacement therapy for hemophilia A has evolved from the early use of whole blood, citrated plasma, and cryoprecipitate, to purified factor VIII (FVIII) concentrates, first derived from plasma, then produced by recombinant DNA technology. Recombinant FVIII (rFVIII) concentrates have provided improved safety for patients with hemophilia A since they significantly reduce the risk of transmission of blood-borne infections. Nevertheless, human- or animal-derived plasma proteins are still included at some step in preparation of all previously licensed rFVIII, thereby introducing the potential for transmission of human or animal pathogens. Anti-hemophilic factor (recombinant), plasma/albumin-free method (rAHF-PFM), a novel advanced category rFVIII produced without the addition of human or animal plasma proteins, has been developed with the goal of providing the greatest possible margin of safety to hemophilia patients. This report, based on a symposium of the XIXth International Society on Thrombosis and Haemostasis Congress, provides an overview of the rAHF-PFM development program as well as current findings from the global clinical evaluation of rAHF-PFM in pediatric and adult previously treated patients.

Adult↗
PubMed2004

Development of a health-related quality of life measure for boys with haemophilia: the Canadian Haemophilia Outcomes--Kids Life Assessment Tool (CHO-KLAT).

Several measures of quality of life (QoL) are available for children with haemophilia. However, most are not disease-specific and few focus on children's perspectives. The purpose of this study was to develop a psychometrically sound measure of QoL that included the perspectives of boys with haemophilia. A list of potential items was developed from the literature, other measures, and input from five discussion sessions with adults with haemophilia, children with haemophilia and their parents and haemophilia nurses. The list was augmented with items generated by three focus groups with children and three focus groups with parents. These groups also prioritized items and recommended a domain structure. Supplemental information was gathered by surveying haematologists. Data from all sources were analysed to reduce the number of items using a two-step approach, based on rules that weighted the children's priorities most heavily. The remaining items were compiled into a questionnaire that was pilot tested with 10 children and their parents. The total item pool contained 228 potential items. Of these, 33 were removed based on three focus groups and survey responses, 72 were removed after the completion of all focus groups and 46 were removed due to redundancy. This resulted in a 77-item version of the CHO-KLAT. Pilot testing identified the need to subdivide two items, resulting in a 79-item CHO-KLAT. The CHO-KLAT is a promising disease-specific measure of QoL that reflects children's unique perspectives. This child-centric focus distinguishes the CHO-KLAT from alternative measures of QoL. Further research will assess the measurement properties of the CHO-KLAT.

Adolescent↗
PubMed2004

A survey of factor prophylaxis in the Canadian haemophilia A population.

High-dose factor prophylaxis, defined as the infusion of 25-40 factor (F) VIII International Units (IU) kg bodyweight (bw)(-1)> or = x 3 per week, started at age 1-2 years of life in boys with severe haemophilia A prevents the development of significant bleed-related arthropathy. However, programmes of prophylaxis are very expensive and venous access is a challenge. To ascertain patterns of prophylaxis in Canada during the period of a global shortage of recombinant FVIII concentrate a survey was conducted in 2001. The response rate was 83% and the survey identified 247 inhibitor-negative haemophilia A cases receiving prophylaxis, defined as the regular administration of FVIII at least once weekly, from 14 Canadian haemophilia treatment centres. The median age of the group identified was 13 years (range: 1-65) and 95% of cases had severe haemophilia A defined by a circulating factor level of <1%. The median FVIII infusion dose was 26 (range: 16-33) IU kg(-1); infusions were administered > or = x 3 per week in 67% of cases. High-dose factor prophylaxis was used most frequently in boys <5 years of age (23 of 28 cases, 82%) as compared with 56% (56 of 100), 66% (40 of 61) and 62% (36 of 58) of males ages 5-12, 13-18 and >18 years. Prophylaxis accounted for 50% of the annual Canadian FVIII consumption and was a major driving force in the 10% increase (=19.3 million FVIII IU) in the FVIII consumption in Canada in the 4-year period 1999-2003. Given the economic implications of increased use of prophylaxis prospective studies are warranted to better define optimal prophylaxis regimens in the haemophilia A population.

Adolescent↗
PubMed2002

Anti-D (WinRho SD) treatment of children with chronic autoimmune thrombocytopenic purpura stimulates transient cytokine/chemokine production.

Intravenous anti-D is often used in the treatment of autoimmune thrombocytopenic purpura (AITP), but little is known about its mechanisms of action. To investigate anti-D's potential in vivo mechanism(s) of action, a small group (N = 7) of children with chronic AITP was studied. The children initially received either 25 or 50 microg/kg of WinRho-SD in a four-cycle cross-over trial, and peripheral blood samples from the first and third cycles were assessed for cytokine levels at pre-treatment, 3 hr, 1 day, and 8 days post-treatment. Results showed that platelet counts significantly increased in all the children by day 8 post-treatment. Analysis of serum by ELISA showed that there was a significant but transient rise in both pro- and anti-inflammatory cytokine/chemokine levels (e.g., IL1RA, IL6, GM-CSF, MCP-1 alpha, TNF-alpha and MCP-1) by 3 hr post-treatment in both cycles which returned to baseline levels by 8 days post-treatment. These results suggest that anti-D administration may initially activate the RES in the form of cytokine/chemokine secretion, which is subsequently followed by an increase in platelet counts. It is possible that the induced cytokine/chemokine storm may have an effect on several physiological processes such as those mediating either adverse effects or potentially RES phagocytic activity.

Chemokines↗
PubMed2002

Childhood chronic immune thrombocytopenic purpura (ITP).

Chronic immune thrombocytopenic purpura (ITP) develops in approximately 20% of children with acute ITP. Treatment requires differentiating the truly idiopathic state from thrombocytopenias associated with other disorders. Treatment is recommended in cases where platelet counts drop below 20 x 10(9)/L. Therapeutic options include corticosteroids, intravenous immunoglobulin TG(i.v.Ig), and anti-D, as well as splenectomy. The benefits and disadvantages of each modality are reviewed, as well as the management of postsplenectomy failures.

Child↗
PubMed2000

Approach to the investigation and management of immune thrombocytopenic purpura in children.

Childhood immune thrombocytopenic purpura (ITP) is typically a benign, self-limiting disorder occurring in young (<10 years of age) previously healthy children. More than 80% of such children enter a complete sustained remission within a few weeks to a few months of initial presentation, irrespective of any therapy given. The major concern is the small but finite (0.1 to 0.9%) risk of intracranial hemorrhage, which occurs in children with very low platelet counts (<20 x 10(9)/L), and is the justification for treatment to increase the circulating platelet count. Effective treatment strategies are single-dose intravenous immunoglobulin G (IVIgG; approximately 1 g/kg) and medium to high-dose corticosteroids, administered orally or parenterally. The necessity for initial bone marrow aspiration and hospitalization continues to be debated. In children with chronic ITP, defined by persistence of thrombocytopenia for > or =6 months, splenectomy should be considered for the relatively small subgroup with symptomatic, severe thrombocytopenia who have either failed an adequate trial (> or = 12 months) of primary therapy (IVIgG, intravenous anti-D, corticosteroids) or are intolerant of such therapy. Laparoscopic splenectomy is preferred over open splenectomy. Children who fail to respond to splenectomy ( < or = 20% of cases) should be evaluated for the presence of accessory spleens; their management is often difficult and must be individualized. In severe refractory cases, second-line therapies (such as azathioprine or vinca alkaloids) need to be considered. Secondary ITP in children is relatively rare and is sometimes associated with other autoimmune cytopenias (Evan's syndrome, ITP with autoimmune neutropenia). These cases often respond poorly to conventional medical therapies and response rates to splenectomy are considerably lower than in children with primary chronic ITP.

Acute Disease↗
PubMed2000

Improved survival in severe acquired aplastic anemia of childhood.

Multi-agent immunosuppressive therapy has produced improved survival for severe acquired aplastic anemia in children. Recently, some investigators have suggested that immunosuppressive therapy may replace bone marrow transplantation as first-line therapy for this disorder. To assess its validity, we compared the outcomes of bone marrow transplantation vs immunosuppressive therapy in one institution from 1987 to 1997. We studied 46 consecutive patients less than 18 years of age who presented between January 1987 and April 1997. Inherited marrow failure syndromes and myelodysplastic syndromes were excluded. Patients received immunosuppressive therapy vs bone marrow transplantation based on availability of HLA-matched donors. The main outcome measures were survival, complete marrow and hematological remission, or partial remission but achieving independence from transfusional support. Twenty patients received multi-agent immunosuppressive therapy (cyclosporine, antithymocyte globulin and methylprednisolone); 11 attained complete remission and three partial remission for a transfusion-independent survival of 70%. Six patients died of infectious and hemorrhagic complications. Twenty-six patients were transplanted and 24 (93%) achieved complete remission; one achieved a PR, 25 remain transfusion independent with a median follow-up of 5.9 years or 70 months. One patient developed AML 34 months after successful transplant and one patient died due to graft failure and complications of transplant. There has been a striking improvement in survival for pediatric patients treated with multi-agent immunosuppression in the last decade. However, transplantation results have also improved and this remains the definitive first-line therapy for severe acquired aplastic anemia in this age group.

Adolescent↗
PubMed2000

Effect of premedication guidelines and leukoreduction on the rate of febrile nonhaemolytic platelet transfusion reactions.

Platelet transfusion reactions were prospectively studied in haematology/oncology patients at five university teaching hospitals over three consecutive summers. The initial summer study provided baseline information on the use of premedications and the rate of platelet transfusion reactions (fever, chills, rigors and hives). Most (73%) platelet recipients were premedicated and 30% (95% CI 28-33%) of transfusions were complicated by reactions. The second study followed implementation of guidelines for premedicating platelet transfusions. Despite a marked reduction in premedication (50%), there was little change in the platelet transfusion reaction rate, 26% (95% CI 24-29%), or the type of reactions. The third study followed implementation of prestorage platelet leukoreduction while maintaining the premedication guidelines. The reaction rate decreased to 19% (95% CI 17-22%). For nonleukoreduced platelets, there was a statistically significant association between the platelet age and reaction rate (P = 0.04). For leukoreduced platelets, there was no statistically significant association between platelet age and reaction rate (P = 0.5). Plasma reduction of nonleukoreduced platelet products also reduced the reaction rate. These prospective studies document a high rate of platelet transfusion reactions in haematology/oncology patients and indicate premedication use can be reduced without increasing the reaction rate. Prestorage leukoreduction and/or plasma reduction of platelet products reduces but does not eliminate febrile nonhemolytic platelet transfusion reactions.

Blood Preservation↗
PubMed1999

Antibody-mediated inhibition of the human alloimmune response to platelet transfusion in Hu-PBL-SCID mice.

Severe combined immune deficient (SCID) mice were engrafted with human (Hu) peripheral blood lymphocytes (PBL) from a previously alloimmunized donor and transfused with HLA-mismatched platelets. We have previously shown this to be a useful model for platelet transfusion. These engrafted mice (Hu-PBL-SCID mice) produced high levels of alloantibody in response to standard platelet preparations. However, when the first platelet challenge was presensitized with anti-HLA antibody and then transfused there was a marked reduction in the amount of alloantibody produced to five subsequent untreated platelet transfusions. Platelets pretreated with platelet-specific anti-HPA-1a (PL(A1)) sera did not induce a decrease in the anti-HLA alloantibody response. This demonstrated that platelet-induced HLA alloimmunization can be blocked by anti-HLA antibody-sensitized cells.

Animals↗
PubMed1999

Characterization of platelet glycoproteins and platelet/endothelial cell antibodies in patients with thrombotic thrombocytopenic purpura.

Platelets and sera from 12 patients with thrombotic thrombocytopenic purpura (TTP) and 12 healthy normal control subjects were examined. As determined by quantitative flow cytometry, prior to plasma exchange therapy platelet surface glycoprotein (GP) Ib levels were similar in TTP patients and normal controls (mean 20 188 and 20 226 molecules/platelet, respectively). Platelets from patients with TTP did, however, have significantly reduced levels of GPIIb/IIIa prior to plasmapheresis (mean 36 348 v 52 505 molecules/platelet in controls; P = 0.0004) and of GPIV (mean 13 321 v 26 212 molecules/platelet in controls; P = 0.0002). An increase in activated platelets, as determined by CD62 expression, was observed in 82% of patients. Increased platelet-associated immunoglobulins and/or complement was also seen in approximately 60% of the patients. In general, with return of platelet counts to normal levels following seven plasmaphereses, the above abnormalities were reversed, although often not to normal levels. Western blot analysis indicated the presence of antibodies reactive to platelet GPIV (88 kD) in 70% of pretreatment sera from patients with TTP; a similar band was observed in 80% of patient sera against microvascular endothelial cells. Immunofluorescence microscopic examination indicated the presence of antibody in pretreatment sera from patients with TTP to microvascular (73%) and large vessel (36%) endothelial cells. As measured by an indirect flow cytometric assay, pretreatment sera from 55% of patients with TTP were reactive with large vessel endothelial cells and 100% reacted with microvascular endothelial cells; reactivity was significantly greater against the microvascular endothelial cells (P = 0.0048) and was reduced following plasma exchange therapy. These results indicate abnormalities in platelet glycoprotein expression in TTP and suggest that anti-platelet and anti-endothelial cell antibodies play a role in the thrombocytopenia and vasculitis characteristic of this disorder.

Adult↗