Balance between von Willebrand factor and ADAMTS13 following major partial hepatectomy

Groeneveld, Dafna; Alkozai, Edris M.; Adelmeijer, Jelle; Porte, Robert J.; Lisman, Ton

doi:10.1002/bjs.10107

Cited by 21 publications

(25 citation statements)

References 41 publications

(89 reference statements)

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“…Indeed, both platelet accumulation and liver regeneration were strongly dependent on VWF, although we have not conclusively shown that LSEC (and not plasma or platelet VWF) mediates these processes. We have recently demonstrated that plasma VWF levels increase and levels of the VWF‐cleaving protease ADAMTS13 decrease following partial hepatectomy in humans . Acute VWF release within the liver accompanied by inadequate or delayed removal of reactive VWF molecules by decreased ADAMTS13 levels may explain the transient VWF‐dependent platelet accumulation after partial hepatectomy.…”

Section: Discussionmentioning

confidence: 99%

Transient von Willebrand factor‐mediated platelet influx stimulates liver regeneration after partial hepatectomy in mice

Kirschbaum

Jenne

Veldhuis

et al. 2017

Liver International

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Section: Discussionmentioning

confidence: 99%

Transient von Willebrand factor‐mediated platelet influx stimulates liver regeneration after partial hepatectomy in mice

Kirschbaum

Jenne

Veldhuis

et al. 2017

Liver International

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“…Plasma VWF antigen levels were determined by ELISA as described previously (Groeneveld et al , 2016) and pooled normal human plasma was utilized to develop a standard curve. Thiobarbituric acid reactive substances (TBARS) were determined using a commercially available kit (Cayman Chemical, Ann Arbor, MI).…”

Section: Methodsmentioning

confidence: 99%

Von Willebrand factor deficiency reduces liver fibrosis in mice

Joshi

Kopec

Ray

et al. 2017

Toxicology and Applied Pharmacology

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Liver diseases are associated with complex changes in the hemostatic system and elevated levels of the platelet-adhesive protein Von Willebrand factor (VWF) are reported in patients with acute and chronic liver damage. Although elevated levels of VWF are associated with fibrosis in the general population, the role of VWF in acute and chronic liver injury has not been examined in depth in experimental settings. We tested the hypothesis that VWF deficiency inhibits experimental liver injury and fibrosis. Wild-type (WT) and VWF-deficient mice were challenged with carbon tetrachloride (CCl4) and the impact of VWF deficiency on acute liver injury and chronic liver fibrosis was determined. VWF deficiency did not significantly affect acute CCl4-induced hepatocellular necrosis in mice. Chronic CCl4 challenge, twice weekly for 6 weeks, significantly increased hepatic stellate cell activation and collagen deposition in livers of WT mice. Interestingly, hepatic induction of several profibrogenic and stellate cell activation genes was attenuated in VWF-deficient mice. Moreover, birefringent sirius red staining (indicating type I and III collagens) and type I collagen immunofluorescence indicated a reduction in hepatic collagen deposition in CCl4-exposed VWF-deficient mice compared to CCl4-exposed WT mice. The results indicate that VWF deficiency attenuates chronic CCl4-induced liver fibrosis without affecting acute hepatocellular necrosis. The results are the first to demonstrate that VWF deficiency reduces the progression of liver fibrosis, suggesting a mechanistic role of elevated plasma VWF levels in cirrhosis.

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“…In addition, the hypercoagulable state and imbalance between von Willebrand factor (VWF) and ADAMTS13 shortly after a partial hepatectomy has been suggested to contribute to venous and perhaps also portal vein thrombosis. 50 This thrombotic risk may be exacerbated by elevated platelet counts, in particular in the context of the VWF/ADAMTS13 imbalance. Also, elevation of the platelet count in patients with cirrhosis has been shown to elevate the risk of portal vein thrombosis, 51 which may also be linked to the VWF/ADAMTS13 imbalance of cirrhosis.…”

Section: Prospectsmentioning

confidence: 99%

Mechanisms of platelet-mediated liver regeneration

Lisman

Porte

2016

Blood

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Platelets have multiple functions beyond their roles in thrombosis and hemostasis. Platelets support liver regeneration, which is required after partial hepatectomy and acute or chronic liver injury. Although it is widely assumed that platelets stimulate liver regeneration by local excretion of mitogens stored within platelet granules, definitive evidence for this is lacking, and alternative mechanisms deserve consideration. In-depth knowledge of mechanisms of platelet-mediated liver regeneration may lead to new therapeutic strategies to treat patients with failing regenerative responses.

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Balance between von Willebrand factor and ADAMTS13 following major partial hepatectomy

Abstract: There are changes in the balance between VWF and ADAMTS13 levels and activity in patients after both PH and PPPD. Changes in the VWF-ADAMTS13 axis were more pronounced and of longer duration after PH than following PPPD.

Cited by 21 publications

References 41 publications

Transient von Willebrand factor‐mediated platelet influx stimulates liver regeneration after partial hepatectomy in mice

Transient von Willebrand factor‐mediated platelet influx stimulates liver regeneration after partial hepatectomy in mice

Von Willebrand factor deficiency reduces liver fibrosis in mice

Mechanisms of platelet-mediated liver regeneration

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