Advances in the diagnosis and treatment of disseminated intravascular coagulation in haematological malignancies

Abstract

Haematological malignancies, including acute leukaemia and non-Hodgkin lymphoma, are one of the underlying diseases that frequently cause disseminated intravascular coagulation (DIC), an acquired thrombotic disorder. Concomitant DIC is associated with the severity of the underlying disease and poor prognosis. The Japanese Society on Thrombosis and Hemostasis released the new DIC diagnostic criteria in 2017. This criteria include coagulation markers such as soluble fibrin and the thrombin-antithrombin complex to more accurately evaluate the hypercoagulable state in patients. Among several groups of anticoagulants available, recombinant human soluble thrombomodulin is most frequently used to treat DIC caused by haematological malignancies in Japan. DIC is remitted in parallel with the improvement of the underlying haematological diseases; thus, there is room for debate regarding whether the treatment of DIC would improve the prognosis of patients. Haematopoietic stem cell transplantation as well as the recently introduced chimeric antigen receptor (CAR)-T-cell therapy are innovative therapies to produce a cure in a subset of patients with haematological malignancies. However, coagulopathy frequently occurs after these therapies, which limits the success of the treatment. For example, DIC is noted in approximately 50% of patients after CAT-T-cell therapy in conjunction with cytokine release syndrome. Hematopoietic stem cell transplantation (HSCT) causes endotheliitis, which triggers coagulopathy and the development of potentially lethal complications, such as sinusoidal obstruction syndrome/veno-occlusive disease and transplant-associated thrombotic microangiopathy. This review article describes the pathogenesis, clinical manifestation, diagnosis, and treatment of DIC caused by haematological malignancies, CAR-T-cell therapy, and HSCT.

Reactions Related to CAR-T Cell Therapy

“…Mechanisms of CAR-T-related coagulation disorders are not fully known, and may be linked to the following mechanisms: (a) Blood from patients with malignant tumors is in a hypercoagulable state ( 126 ); (b) High levels of cytokines like IL-6 and TNF-α in the blood cause activation and lesions of vascular endothelial cells, resulting in increased release of tissue factor (TF) ( 127 , 128 ). Coagulation factor VII (FVII) combines with TF to form FVII/TF complex.…”

Disseminated intravascular coagulopathy in non-promyelocytic acute myeloid leukemia: Incidence, clinical and laboratory features and prognostic significance

“…U akutnim leukemijama, veoma je pojačana i primarna fibrinoliza. Sve ovo dovodi do izražene hipofibrinogenemije i porasta fibrinogen/ fibrin degradacionih proizvoda (FDP) i D-dimera [18]. Oko 15% bolesnika sa ne-APL AML-om dodatno razvije DIK u toku indukciono-remisione terapije.…”

“…In acute leukemias, primary fibrinolysis is also very intensified. All of this leads to marked hyperfibrinogenemia and the increase in fibrinogen/fibrin degradation products (FDP) and D-dimer [18]. Around 15% of patients with non-APL AML additionally develop DIC during induction remission therapy.…”

Diagnosis and treatment of disseminated intravascular coagulation in COVID-19 patients: a scoping review

“…In addition, a high dose of heparin was shown to inhibit the interaction of histone, a major component of NETs, with platelets [25]. Given that the lectin-like domain of rTM possesses antiinflammatory function [26] and rTM degrades histones via activated protein C [27], we assume that the use of rTM is the reasonable option to cope with DIC in CVID-19 patients.…”