Acute Promyelocytic Leukemia (APL)
Acute promyelocytic leukemia (APL) is the blood cancer most notorious for causing severe, life-threatening bleeding due to hyperfibrinolytic disseminated intravascular coagulation (DIC). 1, 2
Why APL Causes Catastrophic Bleeding
APL presents with a unique hyperfibrinolytic form of DIC where activation of the fibrinolytic system dominates the clinical picture, leading to widespread consumption of clotting factors. 1 The bleeding manifestations are severe and include:
- Widespread bruising and bleeding from mucosal surfaces 1
- Central nervous system hemorrhage 2
- Pulmonary and gastrointestinal bleeding 1, 2
- Bleeding from sites of trauma 1
Hemorrhage is the most common cause of induction mortality in APL, and catastrophic bleeding can occur even before the diagnosis is confirmed. 1 Population-based studies demonstrate that nearly 30% of patients experience early death during induction chemotherapy, with hemorrhage being the leading cause. 3
Critical Diagnostic Features
The laboratory profile of APL with DIC differs markedly from other AML subtypes with DIC:
- Markedly elevated fibrinolytic markers: FDP ≥27 µg/mL and D-dimer ≥2,071 ng/mL 4
- Profoundly low fibrinogen: ≤279 mg/dL (mean 133.8 mg/dL in APL vs. 373.2 mg/dL in other AML) 4
- Lower white blood cell counts: Mean 14,988×10⁹/L compared to 70,755×10⁹/L in other AML subtypes 4
- Prolonged PT is the most accurate predictor of bleeding: PT ≥5 seconds confers a relative risk of 6.14 for bleeding events 5
A critical pitfall: Approximately 90% of APL patients present with DIC, but coagulation screens (PT/PTT) may remain normal in up to 50% of cases, particularly in early or subclinical DIC. 1, 6 A declining platelet count trend (≥30% drop) is diagnostic even when absolute values remain normal. 1, 6
Immediate Management Approach
The International Society on Thrombosis and Haemostasis recommends that when APL is suspected, all-trans retinoic acid (ATRA) treatment should be initiated immediately, even before molecular confirmation by PML-RARA testing. 4, 3 This is because:
- Prompt ATRA administration is crucial in preventing hemorrhagic events 5
- Seven patients in one series experienced severe bleeding before ATRA initiation 5
- ATRA has dramatically improved overall survival, transforming APL from the most malignant to the most curable form of acute leukemia 7
Treatment of hyperfibrinolytic DIC in APL consists of:
- Treating the underlying cancer with ATRA (and arsenic trioxide in modern regimens) 1, 2
- Supportive care with blood products 1, 2
- Fresh frozen plasma to correct coagulopathy, particularly when PT is prolonged 5
- Platelet transfusions as needed 5
Anticoagulation with heparin is not recommended for hyperfibrinolytic DIC, in contrast to procoagulant DIC where it may be beneficial. 1, 2
Other Blood Cancers Associated with Bleeding
While APL is the prototype, metastatic prostate cancer can also present with hyperfibrinolytic DIC and bleeding complications. 1 However, the bleeding tendency and early mortality risk are far less dramatic than in APL.