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Haemophilia. 2019 Mar;25(2):324-333. doi: 10.1111/hae.13672. Epub 2019 Jan 16.

Bleed volume of experimental knee haemarthrosis correlates with the subsequent degree of haemophilic arthropathy.

Author information

1
Global Drug Discovery, Novo Nordisk A/S, Maaloev, Denmark.
2
Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark.

Abstract

BACKGROUND:

Haemophilic arthropathy is the main morbidity of haemophilia. The individual pathological response to the same number of clinically evident joint bleeds is highly variable; thus, it remains unknown if certain joint bleeding characteristics are critical for the development of arthropathy.

AIM:

To study the relation between bleed volume and subsequent development of arthropathy, we aimed to develop quantitative in vivo imaging of active joint bleeds in a mouse model of haemophilia.

METHODS:

Haemophilia A (F8-KO) and wild-type (WT) mice were IV-dosed with a micro-CT blood pool contrast agent prior to an induced knee haemarthrosis or sham procedure. The mice were micro-CT scanned five times the following 2 days to characterise and quantify the induced haemarthrosis in vivo. On Day 14, the mice were euthanized and pathological changes evaluated by histology and micro-CT. Additionally, bleeding characteristics in vehicle-treated F8-KO mice were compared with those of recombinant FVIII (rFVIII)-treated F8-KO mice.

RESULTS:

F8-KO mice had a significantly larger bleed volume than WT mice at all scan time points. The bleed volume 12 hours after induction of haemarthrosis correlated with the subsequent degree of arthropathy. Presence of µCT-detectable bone pathology was associated with a significantly increased bleed volume among F8-KO mice. rFVIII treatment significantly reduced bleed volume in F8-KO mice.

CONCLUSION:

Quantitative in vivo contrast-enhanced micro-CT imaging can be used to characterize and quantify joint bleeds in a mouse model of haemophilic arthropathy. The bleed volume correlates with the subsequent degree of arthropathy.

KEYWORDS:

animal models; arthropathy; haemarthrosis; haemophilia A; in vivo imaging; micro-CT

PMID:
30648774
DOI:
10.1111/hae.13672

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