Abstract Number: PB0836
Meeting: ISTH 2021 Congress
Background: Thrombotic thrombocytopenic purpura (TTP) is caused by deficiency of plasma ADAMTS13 activity. However, ADAMTS13 deficiency alone is often not sufficient to cause acute TTP; additional environmental factors may be necessary to trigger the disease.
Aims: Present study aims to determine if malignancy triggers TTP and whether malignancy-induced TTP depends on plasma ADAMTS13 and its substrate von Willebrand factor (VWF) in zebrafish models.
Methods: Zebrafish melanoma (ZMEL) cells expressing mCherry were subcutaneously injected into transgenic zebrafish (cd41/GFP and gata1/dsRed) at age of 6-10 weeks (wt, a13-/-, vwf-/-, and a13-/-/vwf-/-), three days after total body gamma irradiation; tumor growth, blood cells count, and survival rate were determined. All mutant zebrafish were generated in our laboratory using CRISPR/Cas9 technique and bred for multiple generations before use.
Results: Our results demonstrated that a13-/- zebrafish developed a higher tumor burden, metastasized earlier and more wide-spread, developed more severe and persistent thrombocytopenia (Fig. 1A & 1B), and exhibited a higher and earlier mortality rate (Fig. 2A) than the wt zebrafish after irradiation and inoculation of ZMEL cells. Surprisingly, the incidence and severity of thrombocytopenia (i.e. TTP) (Fig. 1C & 1D) and the early mortality rate (Fig. 2B) in a13-/-/vwf–/- zebrafish were dramatically reduced compared with those in a13-/- zebrafish after irradiation and inoculation of ZMEL cells.
Conclusions: Melanoma-induced thrombocytopenia (or TTP) and early death are highly dependent on both ADAMTS13 and VWF in zebrafish. Our findings provide scientific basis for targeting the ADAMTS13/VWF axis as a novel therapeutic strategy for malignancy-induced TTP.
To cite this abstract in AMA style:Zheng L, Cao L, Zheng XL. Melanoma Triggers Severe Thrombotic Thrombocytopenic Purpura and Results in a High Mortality Rate in adamt13-/- Zebrafish [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/melanoma-triggers-severe-thrombotic-thrombocytopenic-purpura-and-results-in-a-high-mortality-rate-in-adamt13-zebrafish/. Accessed November 29, 2021.
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