Elevation of Factor VIII in Acute Liver Necrosis

Baele, G; Vermeire, P.; Demeulenaere, L; Barbier, F

doi:10.1159/000197336

Cited by 8 publications

(6 citation statements)

References 18 publications

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“…[16][17][18][19]38 In contrast, all other hepatic coagulation and fibrinolytic factors, including fibrinogen; prothrombin; factors V, VII, IX, X, XI, XII, and XIII; prekallikrein; high-molecular-weight kininogen; protein C; plasminogen; antithrombin III; and ␣ 2 -antiplasmin are decreased in FHF. 39 Elevated levels of factor VIII also have been observed in cirrhosis in some, 38,40,41 but not all, 42 studies.…”

Section: Discussionmentioning

confidence: 99%

“…[16][17][18][19] This increase can be more than 14 times normal levels and occurs simultaneously with profound decreases in the circulating levels of vitamin K-dependent and fibrinolytic plasma proteins. 16,20,21 The analysis of this phenomenon has been hindered by the lack of a reproducible animal model of FHF. However, a murine model of FHF recently was developed using the hepatotoxin azoxymethane (AOM), which is found in cycad palm nuts on the island of Guam.…”

Section: Introductionmentioning

confidence: 99%

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Factor VIII expression in azoxymethane-induced murine fulminant hepatic failure

Doering

Josephson

Craddock

et al. 2002

Blood

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Fulminant hepatic failure (FHF) in humans produces a bleeding diathesis due in large part to a reduction in the biosynthesis of liver-derived coagulation factors. Remarkably, factor VIII procoagulant activity is elevated in most of these patients despite widespread liver cell death. FHF can be modeled in mice by administration of azoxymethane, the active ingredient found in cycad palm nuts. We compared the expression of factor VIII to other hepatic hemostatic factors in azoxymethane-induced murine FHF. Mice displayed dose-dependent decreases in all coagulation factor activities measured, including factors V, VII, VIII, and IX. At the highest dose of azoxymethane (50 g/g body weight), factor VIII activity in plasma decreased by 98% within 36 hours after treatment, which was associated with an 80% reduction in hepatic factor VIII messenger RNA (mRNA). In contrast, factor VIII mRNA levels in spleen, kidney, and lung tissue of azoxymethane-treated mice were unchanged. Cellular damage in these mice appeared to be limited to hepatocytes as evident by histologic examination. This finding is supported by 2 observations. First, hepatic mRNA levels of von Willebrand factor, which is synthe- IntroductionDespite more than 50 years of investigation, the nature of factor VIII biosynthesis in vivo remains poorly understood. [1][2][3][4] Factor VIII messenger RNA (mRNA) is present in nearly every tissue examined, including liver, spleen, lymph node, heart, brain, lung, kidney, testes, muscle, and placenta. [5][6][7] The liver clearly is an important site of synthesis because liver transplantation cures human and canine hemophilia A. [8][9][10] However, the relative contribution of hepatocytes and liver sinusoidal endothelial cells remains uncertain. 7,[11][12][13][14][15] Furthermore, the contribution of extrahepatic biosynthesis of factor VIII in health and disease states is not known.Paradoxically, there usually is a significant rise in plasma factor VIII activity in human fulminant hepatic failure (FHF). [16][17][18][19] This increase can be more than 14 times normal levels and occurs simultaneously with profound decreases in the circulating levels of vitamin K-dependent and fibrinolytic plasma proteins. 16,20,21 The analysis of this phenomenon has been hindered by the lack of a reproducible animal model of FHF. However, a murine model of FHF recently was developed using the hepatotoxin azoxymethane (AOM), which is found in cycad palm nuts on the island of Guam. 22 AOM-treated mice develop hepatocellular necrosis, elevated liver transaminase and ammonia levels in blood and hepatic encephalopathy. They die within days, with death related to the dose of AOM. In this study, we examined the expression of factor VIII and several other hemostatic factors, including factors V, VII, and IX, and von Willebrand factor (VWF) in AOM-induced murine FHF. Materials and methods MaterialsMale C57BL/6 mice (22-30 g body weight) were purchased from Charles River Laboratory (Wilmington, MA). AOM and TriReagent were purchased from Sigma (St Lou...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Factor VIII expression in azoxymethane-induced murine fulminant hepatic failure

Doering

Josephson

Craddock

et al. 2002

Blood

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“…[5][6][7] However, during the course of fulminant hepatic failure (FHF) induced by acetaminophen or viral hepatitis, plasma fVIII activity can increase to more than 10 times normal levels. 8,9 The cellular source of this superphysiologic fVIII activity is currently unknown. We previously reported that fVIII levels were decreased in a murine model of FHF induced by the hepatotoxin, azoxymethane.…”

Section: Introductionmentioning

confidence: 99%

Decreased factor VIII levels during acetaminophen-induced murine fulminant hepatic failure

Doering

Parker

Nichols

et al. 2003

Blood

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“…Οί ένεργοποιητές του πλασμινογόνου τό μετατρέπουν σέ πλα σμίνη (Σχήμα 5). Ένεργοποιητές τοΰ πλασμινογόνου βρίσκονται στους ιστούς συνδεδεμένοι μέ τά λυσοσώματα καί ή εϊσοδός τους στό αίμα είναι ανάλογη μέ τό μηχανισμό του εξωγενούς συστήματος της πήξεως" 9 . Ό παράγοντας XII βρέθηκε, ότι ενεργοποιεί τό πλασμινογόνο έμμεσα κατα λύοντας τό σχηματισμό ένεργοποιητοΰ από πρόδρομη ουσία 149 .…”

Section: β ρολος των αιμοπεταλιων στην αιμοστασηunclassified

Διαταραχες Αιμοστασης Σε Παιδια Με Ομοζυγη Β-Μεσογειακη Αναιμια

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Elevation of Factor VIII in Acute Liver Necrosis

Cited by 8 publications

References 18 publications

Factor VIII expression in azoxymethane-induced murine fulminant hepatic failure

Factor VIII expression in azoxymethane-induced murine fulminant hepatic failure

Decreased factor VIII levels during acetaminophen-induced murine fulminant hepatic failure

Διαταραχες Αιμοστασης Σε Παιδια Με Ομοζυγη Β-Μεσογειακη Αναιμια

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