title: Influenza-associated thrombotic microangiopathy with unbalanced von Willebrand factor and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 levels in a heterozygous protein S-deficient boy.
abstract: Influenza infections often cause pneumonia, but there is limited information on thrombotic microangiopathy (TMA) in these circumstances. We report the case of an 11-year-old boy who developed TMA during the acute phase of H1N1 influenza. Plasma von Willebrand factor (VWF) was elevated, whereas a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity was mildly reduced in the absence of ADAMTS13-neutralizing autoantibody, resulting in low ratio of ADAMTS13 to VWF. The patient was treated intensively, including plasma exchange, and he recovered from the TMA. He developed pulmonary embolism (PE), however, after removal of the central venous catheter. The findings suggested that influenza-associated cytokines enhanced the release of unusually large VWF multimers from vascular endothelial cells and promoted the formation of platelet thrombi and TMA. Subsequent analysis further indicated the presence of familial protein S deficiency, and it seemed likely that the PE was more related to this heterozygous protein S defect.
authors.affiliation: Department of Pediatrics, Nara Medical University, Kashihara, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Tsujii
authors.affiliation: Department of Pediatrics, Nara Medical University, Kashihara, Japan. roc-noga@naramed-u.ac.jp.
authors.forename: Keiji
authors.initials: K
authors.lastname: Nogami
authors.affiliation: Department of Pediatrics, Nara Medical University, Kashihara, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshizawa
authors.affiliation: Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Hayakawa
authors.affiliation: Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan.
authors.forename: Ayami
authors.initials: A
authors.lastname: Isonishi
authors.affiliation: Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Department of Pediatrics, Nara Medical University, Kashihara, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Shima
mesh_terms: D000914:Antibodies, Viral / Q000276:immunology; D002648:Child; D019483:Disintegrins / Q000097:blood*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007251:Influenza, Human / Q000150:complications* / Q000821:virology; D007668:Kidney / Q000098:blood supply / Q000000981:diagnostic imaging; D008297:Male; D045726:Metalloproteases / Q000097:blood*; D017293:Protein S / Q000378:metabolism; D018455:Protein S Deficiency / Q000097:blood / Q000150:complications*; D019700:Thrombospondin 1 / Q000097:blood*; D057049:Thrombotic Microangiopathies / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D014057:Tomography, X-Ray Computed; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D000914:Antibodies, Viral; D019483:Disintegrins; D017293:Protein S; D019700:Thrombospondin 1; D014841:von Willebrand Factor; D045726:Metalloproteases
keywords: ADAMTS13; influenza; protein S deficiency; thrombotic microangiopathy; von Willebrand factor