Abstract Number: PB0130
Meeting: ISTH 2021 Congress
Background: Circulating DNA modify fibrin degradability (Longstaff C et al. The journal of biological chemistry 2013)
Aims: To analyse the degradability of t-PA induced plasma clots formed in vitro in patients with peritoneal carcinomatosis.
Methods: i) Clot degradation: 200 mL of citrated plasma from normal pool plasma (NPP) or from patients with peritoneal carcinomatosis of several origins (7 ovarian, 3 pseudomyxoma, 3 mesothelioma, 2 colon) were clotted in absence or in presence of 10 ng of t-PA, by 0.04 units of calcic thrombin. After 25 min incubation at 37°C, degradation was stopped by adding 20mL of aprotinin. The supernatants were kept for D dimer determination. The residual clots were transferred in a 24 well plate containing 400 mL of NaCl 0,15 M in each well, that was placed above a light source, to be photographed.
ii) Purified DNA was added before clotting in some experiments in NPP.
iii) Clot structure was determined by confocal microscopy, the fibrin fibers being detected in green after perfusion with glutaraldehyde and DNA being detected in blue using DAPI.
Results: i) After action of t-PA on the fibrin clot formed from plasma controls, the residual clot is very small, while in all patients suffering from peritoneal cancer – except one – the residual clot is large associated to a lower D dimer concentration[CPG1] .
ii) Clot structure of patient’s plasmas was compared to the one of normal plasmas to which purified DNA was added before clotting. We observed that in both cases, DNA stained in blue was incorporated into Fibrin fibres that appear in green.
Conclusions: In peritoneal carcinomatosis patients[CPG1] , clot degradation by t-PA is defective. This phenomenon is due to the impact of DNA on the Fibrin clot structure. We observed that DNA was incorporated into Fibrin fibres, down regulating clot degradation by fibrinolytic enzymes.
To cite this abstract in AMA style:Mirshahi S, Aldybiat I, Contant G, Pocard M, Soria J, Mirshahi M. Impact of DNA on the Fibrin Clot Structure in Peritoneal Carcinomatosis Patients [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/impact-of-dna-on-the-fibrin-clot-structure-in-peritoneal-carcinomatosis-patients/. Accessed September 24, 2021.
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