ABSTRACT
The aim of this study was to characterize the variability of bleeding phenotype and its association with plasma factor IX coagulant activity (FIX:C) in haemophilia B carriers in a large Amish pedigree with a unifying genetic mutation, C-to-T transition at base 31008 of the factor IX gene (Xq27.1-27.2). A cross-sectional survey of haemophilia B carriers included a multiple choice questionnaire evaluating symptoms of mucocutaneous bleeding, joint bleeding and bleeding after haemostatic stress [menstruation, postpartum haemorrhage (PPH), dental extractions and invasive surgeries]. Severity of bleeding was graded as 0 to 4, 0 being no bleeding whereas 4 being severe bleeding. Association between total bleeding scores and the FIX:C was evaluated. Sixty-four haemophilia B carriers participated in this study. Median age: 18 years (range 1-70 years); median bleeding score: 1 (range 0-8). Besides PPH, isolated symptoms of bruising, epistaxis, menorrhagia and postsurgical bleeding including dental extraction were not associated with lower FIX:C. Bleeding score >/=3 was associated with involvement of at least two bleeding sites and a lower mean FIX:C of 42 +/- 10.3% (95% CI 36.4-47.7) while a score >3 had involvement of /=3. Phenotypic variability existed among the carriers of haemophilia B who belonged to a single pedigree carrying a single unifying mutation. The utility of bleeding scores to define bleeding phenotype precisely in haemophilia B carriers needs further evaluation.
Subject(s)
Factor IX/genetics , Hemophilia B/genetics , Hemorrhage/genetics , Mutation , Adolescent , Adult , Aged , Child , Child, Preschool , Contusions/etiology , Contusions/genetics , Cross-Sectional Studies , Epistaxis/etiology , Epistaxis/genetics , Factor IX/metabolism , Female , Hemophilia B/blood , Hemophilia B/complications , Hemorrhage/blood , Hemorrhage/etiology , Heterozygote , Humans , Infant , Menorrhagia/etiology , Menorrhagia/genetics , Middle Aged , Pedigree , Phenotype , Postoperative Hemorrhage/etiology , Postoperative Hemorrhage/genetics , Severity of Illness Index , Young AdultABSTRACT
Two pairs of plasma-perfused human cadaver kidneys were rejected in a hyperacute manner by recipients who had not previously received a transplant. Crossmatches between recipient sera and donor lymphocytes were negative in all cases. A fifth kidney was plasma-perfused but not transplanted because the perfusate was shown to be cytotoxic to donor lymphocytes. IgM and complement, but not IgG, were demonstrated in these kidneys by immunofluorescent microscopy and confirmed by further immunological studies. The IgM was broadly reactive against multiple HL-A specificities and was present in 11 percent of sera from normal, healthy male donors. It appears from our studies that cytotoxic IgM may be present in homologous plasma and cause immune injury to the kidney during ex vivo pulsatile preservation. This may be responsible for some cases of otherwise unexplained accelerated allograft rejection.
Subject(s)
Cadaver , Graft Rejection/etiology , Kidney Transplantation , Transplantation, Homologous/adverse effects , Blood Donors , Chemotherapy, Cancer, Regional Perfusion , Complement C3/analysis , Cross Reactions , Cytotoxicity Tests, Immunologic , Disseminated Intravascular Coagulation/etiology , Fluorescent Antibody Technique , HLA Antigens/analysis , Humans , Immune Complex Diseases/etiology , Immunoglobulin M/analysis , Immunoglobulins/isolation & purification , Kidney/injuries , Kidney Glomerulus/pathology , Lymphocytes/analysis , Male , Organ PreservationABSTRACT
Infected Thomas shunts pose a problem for the surgeon treating end-stage renal failure patients. Complete removal of the prosthesis with ligation of the femoral vessels may jeopardize the limb. Removal of the shunt without the Dacron patch usually will not eradicate the infection. The present article describes a two-stage approach in six patients with arterial bypass of the infected area and complete removal of the prosthesis. There were no postoperative complications. Arterial circulation was maintained, and all operative sites healed completely.