British Journal of Haematology , 2001, 113,649±651 SHORT REPORT Tenyearsofprophylactictreatmentwithfresh-frozenplasmain a child with chronic relapsing thrombotic thrombocytopenic purpuraasaresultofacongenitaldeficiencyofvonWillebrand factor-cleaving protease Jose  Barbot, 1 Elõ Âsio Costa, 1 Marisol Guerra, 1 Maria S. Barreirinho, 1 Pratima Isvarlal, 1 Rodolfo Robles, 2 Helena E. Gerritsen, 2 Bernhard La Èmmle 2 and Miha Furlan 2 1 Servic Ëo de Hematologia do Hospital de Crianc Ëas Maria Pia, Porto, Portugal, and 2 Central Haematology Laboratory, University Hospital, Inselspital, Berne, Switzerland Received 4 December 2000; accepted for publication 22 January 2001 Summary. We report the results of 10 years of prophylactic fresh-frozen plasma FFP) infusion therapy in a 14-year-old girl with chronic relapsing thrombotic thrombocytopenic purpuraTTP),inwhomaseverecongenitalvonWillebrand factor VWF)-cleaving protease deficiency has been docu- mented. Severe haemolytic crises triggered by infections were prevented and her present renal and neurological functions have been preserved. Sequential measurements of proteaseactivityandplateletcountafterFFPinfusionledus toconcludetentativelythat5%maybesufficienttodegrade very large and adhesive VWF multimers. Keywords: VWF-cleaving protease, deficiency, fresh-frozen plasma, chronic haemolytic anaemia, thrombotic thrombo- cytopenic purpura. Thrombotic thrombocytopenic purpura TTP) is a poten- tially fatal disease, characterized by widespread platelet thrombi in the microcirculation. Excessive intravascular platelet agglutination seems to be associated with massive release from endothelial cells of unusually large von Willebrand factor VWF) multimers and/or their impaired degradation to smaller non-agglutinating molecular forms by a specific VWF-cleaving protease. Congenital deficiency of this protease was found in patients with familial forms of the disease while a protease inhibitor has been observed in acquired TTP Furlan et al, 1998; Tsai & Lian, 1998). We describe a patient with congenital deficiency of VWF- cleaving protease and the follow-up after 10 years of prophylactic treatment with fresh-frozen plasma FFP). CASE REPORT The patient was a 14-year-old Caucasian female born in northern Portugal of first-degree cousins Fig 1A). She developed hyperbilirubinaemia within the first 12 h of life, requiring 48 h of phototherapy. She was referred to our hospital at 24 months of age for haemolytic anaemia and thrombocytopeniatriggeredbyaninfectiousevent.Shewas discharged after improvement without an aetiological diagnosis.Subsequently,sheledanormallifewithoutpallor or haemorrhagic symptoms. Nevertheless, her haema- tological findings were not normal. A well-compensated haemolytic anaemia and thrombocytopenia were persist- ently present. Neither morphological red cell abnormalities nor evidence of immunomediated red cell or platelet destruction was found. Attheageof3years,thepatientwasadmittedagain.She was seriously ill with fever, prostration, vomiting and dark urine.Herhaemoglobinlevelhaddroppedto4´8g/dlwitha marked reticulocytosis. The platelet count was 23  10 9 /l and the lactate dehydrogenase level was 2260 IU/l. The presence of numerous schistocytes and microspherocytes in the blood film and massive haemoglobinaemia and haemo- globinuria indicated the intravascular and microangio- pathic nature of the haemolytic process. Mild proteinuria was detected but the renal function was preserved. Coagulationscreeningwasnormal.Noneurologicalimpair- ment was observed. She was discharged after red cell q 2001 Blackwell Science Ltd 649 Correspondence: Jose  Barbot, Servic Ëo de Hematologia, Hospital de Crianc Ëas Maria Pia, Rua da Boavista, 827, 4050±111 Porto, Portugal. E-mail: hematologica@hmaria.min-saude.pt