Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anticoagulation monitoring in pediatric patients can be problematic because of the immaturity of the coagulation system in this population. In addition, the hemodilution required to place a small patient on bypass can interfere with standard monitoring methods. In this institution, the Hemochron Jr. ACT (activated clotting time)+ assay has been the standard of care for anticoagulation monitoring since 1997. This assay, with a target ACT of 400 s for initiating bypass, was compared to both the Medtronic HMS system (N = 7) and the Hemochron HiTT assay (N = 6) in pediatric patients. All three assays were then employed to monitor a pediatric Hemophilia A patient (Factor VIII <1%) with high inhibitor titer. Both the HiTT clotting time and the HMS heparin level showed statistically significant correlation to the ACT+ (HiTT, N = 24, r = 0.761; HMS, N = 31, r = 0.818). An HMS target heparin level of 1.5 mg/kg and a HiTT target clotting time of 180 s were found to be clinically equivalent to the 400-s ACT+ as indicators of the need for additional heparin. When a 7-year-old male with severe hemophilia A and high inhibitor titer required tricuspid valve replacement, all three assays were used to ensure appropriate anticoagulation management. During bypass, this patient's ACT+ remained out of range (>1005 s). The HiTT was maintained at >180 s and the HMS heparin level at >1.5 mg/kg. Heparin was administered when any single parameter was below the cutoff value. The use of the combination of three distinct monitoring assays for this patient allowed the surgical team an added level of confidence that appropriate anticoagulation had been maintained.
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PMID:Alternative methods for anticoagulation monitoring in pediatric patients with applicability to a patient with severe hemophilia A and circulating inhibitor. 1180 36

Menorrhagia at the time of menarche is relatively common and historically attributed primarily to immaturity of the pituitary-ovarian-uterine axis. Intuitively, a proportion of these patients should have an underlying disorder of haemostasis, given the 5-20% prevalence of von Willebrand's disease and the > or =20% prevalence of platelet dysfunction in light of recent epidemiological studies in menorrhagia, although the average age of the patients in those studies has been approximately 35 years. However, there are a few comprehensive studies in the adolescent population determining whether widespread haemostasis evaluation should be carried out in adolescents presenting with menorrhagia. A retrospective chart review study of disorders of haemostasis was carried out in 61 consecutive adolescent patients, ages 11-19 at the time of evaluation referred to the Hemophilia Treatment Center (HTC)/Hematology unit. The mean and median ages were 15 +/- 2.2 and 14 years (11, 19), respectively. Standard evaluation included complete blood count, prothrombin time, partial thromboplastin time, von Willebrand factor (VWF) levels and platelet aggregation. The proportion of patients with VWF deficiency was 22/61 (36%) [95% confidence interval (CI), 24-49%]; the proportion of patients with platelet aggregation abnormalities was 4/61 (7%) (95% CI, 2-16%). There was no difference in the frequency of additional muco-cutaneous bleeding symptoms. A relatively high proportion of adolescents are identified with an underlying disorder of haemostasis when referred to an HTC for evaluation of menorrhagia. This involves in part a selective referral bias, but underscores the role of the HTC in evaluating adolescents referred with menorrhagia for an underlying bleeding disorder, given the relatively high yield of haemostatic disorders detected in this setting.
Haemophilia 2007 Sep
PMID:The prevalence of disorders of haemostasis in adolescents with menorrhagia referred to a haemophilia treatment centre. 1788 Apr 54

Neonatal gene therapy is a promising strategy for treating a number of congenital diseases diagnosed shortly after birth as expression of therapeutic proteins during postnatal life may limit the pathologic consequences and result in a potential "cure." Hemophilia A is often complicated by the development of antibodies to recombinant protein resulting in treatment failure. Neonatal administration of vectors may avoid inhibitory antibody formation to factor VIII (FVIII) by taking advantage of immune immaturity. A helper-dependent adenoviral vector expressing human factor VIII was administered i.v. to neonatal hemophilia A knockout mice. Three days later, mice produced high levels of FVIII. Levels declined rapidly with animal growth to 5 wk of age with stable factor VIII expression thereafter to >1 y of age. Decline in factor VIII expression was not related to cell-mediated or humoral responses with lack of development of antibodies to capsid or human factor VIII proteins. Subsequent readministration and augmentation of expression was possible as operational tolerance was established to factor VIII without development of inhibitors; however, protective immunity to adenovirus remained.
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PMID:Neonatal helper-dependent adenoviral vector gene therapy mediates correction of hemophilia A and tolerance to human factor VIII. 2124 23

Heavy menstrual bleeding (HMB) is a frequent complaint in adolescence. Although HMB is often caused by immaturity of the hypothalamic-pituitary-ovarian axis, bleeding disorders are another common yet often unidentified cause. The aim of this study was to examine the bleeding patterns and prevalence of inherited bleeding disorders among females referred for HMB to a multidisciplinary adolescent haematology clinic. We retrospectively reviewed the first 105 patients (ages 8-18 years) referred to this specialty clinic from February 2009 to December 2011. Using menstrual bleeding questionnaires and medical records, data were extracted regarding demographics, bleeding patterns, frequency and types of bleeding disorders identified, and prescribed interventions. Sixty-two per cent of patients were diagnosed with a bleeding disorder, including platelet storage pool deficiency (36%), von Willebrand's disease (9%), other platelet function defect (8%), Ehlers-Danlos syndrome (7%) and combined bleeding disorders (2%). Comparison of the bleeding profiles for females with and without a bleeding disorder revealed only three factors that were significantly different, including the reported regularity of patients' periods (P = 0.02), description of period flow (P = 0.04) and number of days of each period that the bleeding was described as 'heavy' (P = 0.007). Bleeding disorders are prevalent in adolescent females presenting to a specialty clinic. Specifically, a relatively high proportion of adolescents were diagnosed with platelet storage pool deficiency. In our small population, menstrual bleeding profiles, as examined by a standardized questionnaire, could not identify females with an underlying bleeding disorder, demonstrating the important role of haemostasis testing in the evaluation of adolescents with HMB.
Haemophilia 2013 Jan
PMID:Menstrual bleeding patterns and prevalence of bleeding disorders in a multidisciplinary adolescent haematology clinic. 2300 46