Biomedical subjects

Manuel D Carcao

Publications and source records attributed to Manuel D Carcao.

6 recordsLinked to original sources

PubMed2004

Prophylactic factor replacement in hemophilia.

Prophylaxis, the regular infusion of coagulation factor concentrates to severe hemophiliacs, has been an evolving therapeutic tool of management for the past three decades. Multiple clinical trials have and continue to be conducted in the field of prophylaxis in an attempt to determine ideal regimens of prophylaxis, its benefits, its risks and costs, and to address still unanswered questions; who to place on prophylaxis, when to start prophylaxis, when (if ever) to stop prophylaxis, etc. We present a detailed review and discussion of the evolution of prophylaxis as a tool in managing patients with hemophilia and we address the major issues and still unanswered questions.

Cost of Illness↗

PubMed2004

Clostridium septicum myonecrosis in congenital neutropenia.

Severe congenital neutropenia (SCN) and Clostridium septicum myonecrosis is an uncommon and life-threatening association requiring urgent combined aggressive medical and surgical management. We report 2 cases of SCN (1 with known Kostmann's syndrome and 1 not known at presentation to have a congenital neutropenic disorder but subsequently received a diagnosis of cyclic neutropenia) who presented with spontaneous C septicum myonecrosis. The cases highlight the importance of response to recombinant human granulocyte colony-stimulating factor in obtaining a satisfactory outcome for these patients. Early, empirical use of recombinant human granulocyte colony-stimulating factor in patients who are suspected of having a congenital neutropenia and who present with life-threatening sepsis is recommended.

Child, Preschool↗

PubMed2003

Fcgamma receptor IIa and IIIa polymorphisms in childhood immune thrombocytopenic purpura.

Fcgamma receptor-mediated destruction of autoantibody-sensitized platelets is central to the immune pathophysiology of childhood immune thrombocytopenic purpura (ITP). Allelic variants exist among the random population for some Fcgamma receptors. The variants represent single nucleotide polymorphisms, leading to functional differences in the ability to bind immunoglobulin (Ig)G or IgG subclasses. The genotypic frequencies for two Fcgamma receptor single nucleotide polymorphisms, FcgammaRIIa-131 arginine (R) versus histidine (H) and FcgammaRIIIa-158 valine (V) versus phenylalanine (F) were examined in 98 children diagnosed with childhood ITP. The genotype frequencies were compared with those of 130 healthy control subjects. Chi-square analysis was used to determine whether the allelic frequencies of the high-affinity receptor variants were associated with childhood ITP. Both the FcgammaRIIa-131H and the FcgammaRIIIa-158V were significantly over-represented in children with ITP versus the control subjects (P-values 0.03). The same statistical difference was noted with the combined FcgammaRIIa-131H and FcgammaRIIIa-158V allelic gene frequencies. There was no statistical difference between children who later developed chronic ITP compared with children with acute ITP, suggesting that additional factors are responsible for the development of the chronic form of the disease. These observations underscore the importance of Fcgamma receptor-mediated cell clearance in childhood ITP.

Adolescent↗

PubMed2003

Desmopressin (DDAVP) responsiveness in children with von Willebrand disease.

PURPOSE: To determine the pattern and predictors of response to desmopressin (DDAVP) in children with von Willebrand disease (VWD). METHODS: The authors reviewed the hospital records of all children with type 1 (n = 70) and type 2A (n = 5) VWD who were followed in the institution's Bleeding Disorders Clinic from January 1989 to June 2001 and who had a DDAVP challenge test after diagnosis. The major outcome evaluated was response to DDAVP, defined as an increase of greater than twofold over baseline of von Willebrand factor, ristocetin cofactor (VWF:RCo), and factor VIII coagulant (FVIII:C) and levels above 0.3 IU/mL. RESULTS: Response to DDAVP was observed in 56 (80%) of the 70 children with type 1 VWD. Age and baseline VWF:RCo and FVIII:C levels were positively associated with DDAVP response. A total of 36 children (28 responders, 8 nonresponders) with type 1 VWD were treated for bleeding episodes or for prophylaxis; of these 75% (6/8) of the nonresponders compared with 7% (2/28) of the responders to a DDAVP challenge test received blood component therapy (P < 0.01). One of the five children with type 2A VWD responded to DDAVP. CONCLUSIONS: DDAVP challenge tests are recommended in children with newly diagnosed VWD to identify responders in whom DDAVP may be used for the prevention or treatment of bleeding, thus avoiding exposure to blood products. The association of DDAVP response with age merits further investigation.

Adolescent↗

PubMed2002

DDAVP challenge tests in boys with mild/moderate haemophilia A.

Desmopressin (DDAVP) increases plasma factor VIII coagulant activity (FVIII:C) levels in patients with mild/moderate haemophilia A. In some subjects, FVIII can be increased to haemostatic levels, thereby avoiding use of factor VIII concentrates. We reviewed our hospital's experience with 62 boys with FVIII:C levels 0.01-0.3 IU/ml who had a DDAVP challenge test (i.v. 0.3 microg/kg) following diagnosis. A therapeutic response was defined as a 1 h post-FVIII:C increase at least twofold over baseline and > 0.3 IU/ml. Of the total group, 29 (47%) boys responded to DDAVP, all of them with mild haemophilia (baseline FVIII:C > or = 0.05 IU/ml), yielding a response rate of 57% in this subgroup. Boys who responded to DDAVP had higher baseline FVIII:C levels (mean +/- SEM, 0.17 +/- 0.01 vs 0.10 +/- 0.01 IU/ml, P < 0.01) and were older (5.2 +/- 0.8 vs 3 +/- 0.4 years, P = 0.02) than those who failed to do so. The association between DDAVP response and age, however, remains unclear: seven boys who failed the initial challenge test responded to re-challenge after a mean of 6.3 years (median 4.9, range 0.5-12.5), increasing the response rate in boys with mild haemophilia to 71%. Age and FVIII:C association with DDAVP response are both important in boys with mild/moderate haemophilia A. Absence of response to DDAVP should therefore be confirmed by later re-challenge.

Adolescent↗

PubMed2002

Assessment of thrombocytopenic disorders using the Platelet Function Analyzer (PFA-100).

The Platelet Function Analyzer (PFA-100) was used to measure platelet function in paediatric patients with destructive versus underproduction thrombocytopenia. Closure time (CT) and total volume (TV) measurements with standard 150 microm apertures discriminated between patients with similar platelet counts from 30 to 150 x 10(9)/l. However, at platelet counts < 30 x 10(9)/l, a 100-microm aperture (experimental) gave the best assessment of platelet function. TV results could be analysed even when CTs were indeterminate. Further investigations are warranted to more fully understand the relationships among platelet function as measured by the PFA-100 in standard/experimental modes, bleeding and transfusion outcome in thrombocytopenia.

Adolescent↗