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Fulminant sepsis/meningitis due to Haemophilus influenzae in a protein C-deficient heterozygote treated with activated protein C therapy

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Abstract

A 13-month-old Japanese female with Haemophilus influenzae type b meningitis presented with unusually severe septic shock and cerebral infarction in half a day of fever. The initial therapy of plasma-derived activated protein C (Anact C®) led to an impressive effect on the aggressive condition. However, purpura fulminans and the consistent decline of plasma protein C activity (<20%) required prolonged activated protein C therapy and gene analysis. The patient carried a novel heterozygous mutation of PROC (exon 4; 335 GAC>TAC, Asp46Tyr). This is the first report of infectious purpura fulminans in a protein C-deficient heterozygote. The clinical onset and treatment course adequately corroborated the aggravated immune/hemostatic reactions and the cytoprotective effects of activated protein C replacement in human heterozygous protein C deficiency. The monitoring of plasma protein C activity and sufficient administration of activated protein C product could improve the outcome of severe sepsis in children.

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Abbreviations

aPC:

Activated protein C

APTT:

Activated partial thromboplastin time

CSF:

Cerebrospinal fluid

CRP:

C-reactive protein

CT:

Computed tomography

DIC:

Disseminated intravascular coagulopathy

FVL:

Factor V Leiden

FDP:

Fibrinogen and fibrin degradation products

Hib:

Haemophilus influenzae type b

PC:

Protein C

PIC:

Plasmin α2–antiplasmin complex

PS:

Protein S

PT:

Prothrombin time

SIRS:

Systemic inflammatory response syndrome

TAT:

Thrombin–antithrombin complex

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Acknowledgments

This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan, and by a research grant from the Japan Society for the Promotion of Science (JSPS).

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Authors and Affiliations

  1. Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Masataka Ishimura, Mitsumasa Saito, Shouichi Ohga, Takayuki Hoshina, Haruhisa Baba, Ryutaro Kira, Hidetoshi Takada, Koichi Kusuhara & Toshiro Hara

  2. Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Hospital, Fukuoka, Japan

    Michiyo Urata & Dongchon Kang

Authors
  1. Masataka Ishimura
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  2. Mitsumasa Saito
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  3. Shouichi Ohga
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  11. Toshiro Hara
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Correspondence to Masataka Ishimura.

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Ishimura, M., Saito, M., Ohga, S. et al. Fulminant sepsis/meningitis due to Haemophilus influenzae in a protein C-deficient heterozygote treated with activated protein C therapy. Eur J Pediatr 168, 673–677 (2009). https://doi.org/10.1007/s00431-008-0816-9

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  • DOI: https://doi.org/10.1007/s00431-008-0816-9

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