Section of Clinical Biochemistry, University Hospital of Verona, Verona, Italy.
Division of Oncology, Hematology and Bone Marrow Transplantation with the Section Pneumology, Department of Internal Medicine, Hubertus Wald Tumorzentrum - University Cancer Center Hamburg, University Medical Center Eppendorf, Hamburg, Germany.
Semin Thromb Hemost. 2020 Jun;46(4):457-464. doi: 10.1055/s-0039-3402478. Epub 2019 Dec 26.
Disseminated intravascular coagulation (DIC) is a relatively rare but life-threatening condition, the outcome of which depends largely on timely and accurate therapeutic management. Inhibiting the activation of blood coagulation is an effective option for limiting the burden of diffuse intravascular thrombosis for attenuating consumption of clotting factors and platelets and ultimately preventing massive bleeding. Direct oral anticoagulants (DOACs) are a relatively new generation of drugs that specifically inhibit activated factors II (thrombin) and X, thus providing effective anticoagulation while concomitantly limiting the hemorrhagic risk compared with other conventional anticoagulant agents. The peculiar mechanism of action would hence at least theoretically support their usage in patients with DIC, especially in those with a more pronounced thrombotic phenotype. A comprehensive literature search on the use of DOACs in patients with intravascular coagulopathies currently yielded only 15 documents, all case reports, totaling 21 patients (dabigatran, = 5; rivaroxaban, = 13; apixaban, = 3; edoxaban, = 0). Taken together, the current literature data suggest that these drugs may have low prophylaxis efficacy and thereby their indication for preventing DIC in high-risk patients may be limited. Nevertheless, DOACs seem at least therapeutically equivalent to heparin in some forms of DIC, especially in those with prevalent thrombotic phenotype, while having more favorable oral administration. The inherent risk of hemorrhages from heparin injection is also shared by DOACs; therefore, their use in DIC patients with a prevalent bleeding phenotype will probably remain unwarranted. Major caution should also be used in patients with impaired drug metabolism, especially those progressing toward liver or renal failure or receiving aggressive antimicrobial treatment. Where potentially indicated, further clinical trials should be planned to test the therapeutic efficacy of these drugs in patients with different types or forms of DIC.
弥散性血管内凝血（DIC）是一种相对罕见但危及生命的疾病，其结局在很大程度上取决于及时、准确的治疗管理。抑制血液凝固的激活是限制弥漫性血管内血栓形成负担、减轻凝血因子和血小板消耗、最终预防大出血的有效选择。直接口服抗凝剂（DOACs）是新一代药物，专门抑制激活的因子 II（凝血酶）和 X，因此在提供有效抗凝作用的同时，与其他常规抗凝剂相比，出血风险降低。其独特的作用机制至少在理论上支持其在 DIC 患者中的应用，尤其是在血栓形成表型更为明显的患者中。目前，对 DOACs 在血管内凝血疾病患者中的应用的全面文献检索仅产生了 15 篇文献，均为病例报告，共 21 例患者（达比加群， = 5；利伐沙班， = 13；阿哌沙班， = 3；依度沙班， = 0）。综合来看，目前的文献数据表明，这些药物的预防效果可能较低，因此其用于预防高危患者 DIC 的适应证可能有限。然而，在某些形式的 DIC 中，DOACs 似乎至少在治疗上与肝素等效，尤其是在血栓形成表型为主的患者中，同时具有更有利的口服给药方式。肝素注射引起出血的固有风险也存在于 DOACs 中；因此，在具有明显出血表型的 DIC 患者中使用它们可能仍然是不必要的。在药物代谢受损的患者中，特别是在进展为肝或肾功能衰竭或接受强化抗菌治疗的患者中，应特别谨慎使用。在有潜在适应证的情况下，应计划进一步临床试验，以测试这些药物在不同类型或形式的 DIC 患者中的治疗效果。
