APL과 관련된 coagulopathy는 복잡하며 파종성 혈관내 응고증(DIC)와 primary hyperfibrinolysis와 관련되며 진단시 또는 cytotoxic chemotherapy 직후에 발생합니다. 이 합병증은 치료를 받지 않으면 환자의 40 %에서 폐 또는 뇌혈관 출혈을 일으킬 수 있고 조기 출혈 사망률이 10-20 %이므로 medical emergency입니다. Thrombotic complications은 덜 일반적입니다.
APL에서 복잡한 coagulopathy의 기전은 완전히 알려져 있지 않지만
다음과 같은 요소들이 주로 중요할 수 있습니다.
Tissue factor (TF), which forms a complex with factor VII to activate factors X and IX. The rearranged RARA in APL activates the TF promoter and increases its expression in the leukemic cells resulting in a procoagulant state. TF expression can also be upregulated by cells undergoing apoptosis.
●Death of APL cells by ETosis (a death pathway distinct from apoptosis and necrosis) releases extracellular chromatin and phosphatidylserine, which contribute to a hypercoagulable state by increasing thrombin generation and fibrin formation, damaging endothelial cells and converting them to a procoagulant phenotype, and increasing plasmin generation.
●Primary hyperfibrinolysis is a result of expression of annexin II, tissue and urokinase plasminogen activator as well as an acquired deficiency of alpha-2 antiplasmin and plasminogen activator inhibitor-1. Annexin II expression is increased on the surface of the leukemic promyelocytes . Annexin II binds plasminogen and its activator, tissue plasminogen activator, increasing plasmin formation by a factor of 60.
Retinoic acid로 종양 세포 분화를 유도하고 적절한 supportive therapy를 하면 주로 hypercoagulable state 를 감소시킴으로써 coagulopathy의 급속한 개선을 유도할 수 있지만 hyperfibrinolytic pathwa에는 거의 영향을 미치지 않습니다.
REF. UpToDate 2018.01.21
