RESUMO
A 12-month-old boy and his 16-year-old aunt became acutely ill 6 months apart and were diagnosed to have atypical hemolytic uremic syndrome (aHUS). Genetic analysis revealed heterozygous R1215Q mutation in complement factor H (CFH) in both patients. The same mutation was found in five healthy adult relatives indicating incomplete penetrance of the disease. The patients developed terminal renal failure and experienced reversible neurological symptoms in spite of plasma exchange (PE) therapy. In both cases, liver-kidney transplantation was successfully performed 6 months after the onset of the disease. To minimize complement activation and prevent thrombotic microangiopathy or overt thrombotic events due to the malfunctioning CFH, extensive PE with fresh frozen plasma was performed pre- and perioperatively and anticoagulation was started a few hours after the operation. No circulatory complications appeared and all four grafts started to function immediately. Also, no recurrence or other major clinical setbacks have appeared during the postoperative follow-up (15 and 9 months) and the grafts show excellent function. While more experience is needed, it seems that liver-kidney transplantation combined with pre- and perioperative PE is a rational option in the management of patients with aHUS caused by CFH mutation.
Assuntos
Substituição de Aminoácidos/genética , Fator H do Complemento/genética , Síndrome Hemolítico-Urêmica/genética , Síndrome Hemolítico-Urêmica/cirurgia , Transplante de Rim , Transplante de Fígado , Adolescente , Feminino , Triagem de Portadores Genéticos , Síndrome Hemolítico-Urêmica/terapia , Humanos , Lactente , Masculino , Linhagem , Troca PlasmáticaAssuntos
Falso Aneurisma/tratamento farmacológico , Hemartrose/terapia , Hemofilia A , Hemostáticos/uso terapêutico , Prótese do Joelho/efeitos adversos , Membrana Sinovial , Trombina/uso terapêutico , Adulto , Falso Aneurisma/diagnóstico por imagem , Inibidores dos Fatores de Coagulação Sanguínea , Fator VIII/antagonistas & inibidores , Fator VIIa/administração & dosagem , Fator VIIa/uso terapêutico , Hematoma/diagnóstico por imagem , Humanos , Articulação do Joelho/diagnóstico por imagem , Masculino , Complicações Pós-Operatórias , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento , UltrassonografiaRESUMO
The evolution of coagulation and fibrinolysis has not been thoroughly evaluated in allogeneic SCT. In this pilot study, we characterized the adaptive mechanisms of coagulation and fibrinolysis during allogeneic SCT and 3-month follow-up and studied possible associations with outcome, including acute GVHD. Thirty patients underwent SCT for a haematological malignancy after myeloablative conditioning. Nineteen patients received the transplant from an HLA-identical sibling and 11 from an unrelated donor. GVHD prophylaxis consisted of CYA and MTX, with methylprednisolone in sibling transplants. Serial coagulation and fibrinolytic activity markers were assessed, including prothrombin fragments 1+2 (F1+2), thrombin time, D-dimer, tissue-type plasminogen-activator (tPA) and plasminogen-activator inhibitor (PAI-1). Early during conditioning therapy, F1+2 and D-dimer increased threefold indicating thrombin generation and fibrin turnover. TPA activity peaked before engraftment, concurring with diminished PAI-1. At 10 days after transplantation shortened thrombin time (<15 s), F1+2 exceeding 0.7 nmol/L and PAI-1 3.0 IU/mL were associated with the development of GVHD. In conclusion, early maladaptation, that is, upregulated thrombin generation and inhibition of fibrinolysis, occurred in one-third of the SCT patients associating with the development of GVHD, a finding suggesting an interplay between coagulation and immunology during SCT.