The results of a rodent model published in Blood Advances suggest that fibrin-specific core-shell nanogels (FSNs) loaded with a tissue-type plasminogen activator (tPA) have the potential to improve outcomes among patients with disseminated intravascular coagulation (DIC), and warrant further study.
DIC, a condition distinguished by pathological coagulopathy, carries a mortality rate of up to 78%. Infection, trauma, cancer, pregnancy, and liver disease are each linked with DIC incidence; this is also true of up to half of cases of sepsis, and of a large proportion of patients infected with SARS-CoV-2. DIC also represents a clinical dilemma, because treatments used, which may be for thrombotic episodes or for bleeding presentation, are incompatibly motivated.
Previous research suggested that targeting fibrin, the formation of which is linked with thrombosis, may be promising for treating thrombotic and hemostatic conditions. The study authors hypothesized that this may also be true of DIC through the reduction excessive thrombi formation and the mitigation of bleeding risk.
To evaluate this hypothesis, the researchers developed tPA-FSNs with the aim of promoting targeted clot dissolution to reduce thrombi formation, and accordingly the consumptive coagulopathy linked with bleeding. This was done on an in vivo rodent model and using plasma from 3 patients with DIC.
The rodent model’s results suggest that tPA-FSNs may help to reduce the formation of multiorgan microthrombi, recover platelet counts, and improve bleeding outcomes. Results using patient plasma were similarly promising, suggesting that the treatment may restore clot structure and clot growth under flow.
“In conclusion, this study has shown that fibrin-targeting nanogels delivering tPA can help dissolve aberrant fibrin deposition to restore coagulation potential and thus mitigate thrombosis and bleeding complications of DIC, which will potentially improve outcomes,” the authors wrote.
Disclosures: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of authors’ disclosures.
Mihalko EP, Sandry M, Mininni N, et al. Fibrin-modulating nanogels for treatment of disseminated intravascular coagulation. Blood Adv. 2021;5(3):613-627. doi:10.1182/bloodadvances.2020003046