Hematology Oncology · Year 2 · from Hematology Oncology
Case 2: Acute Promyelocytic Leukemia (APL)
Patient Presentation
Demographics: 34-year-old female
Chief Complaint: Heavy menstrual bleeding, nosebleeds, and bruising for 1 week
History of Present Illness: The patient noticed unusually heavy menstrual bleeding this cycle requiring pad changes every 1-2 hours. She has had multiple episodes of prolonged nosebleeds and spontaneous bruising. She reports fatigue and mild shortness of breath. She has no prior bleeding history. She developed a large hematoma on her thigh after minor trauma 3 days ago that is still expanding.
Physical Examination:
- Vital signs: BP 105/62, HR 108, RR 20, Temp 37.6C
- General: Pale, anxious woman with dried blood at nares
- HEENT: Nasal packing in place, conjunctival pallor
- Cardiac: Tachycardic, flow murmur
- Lungs: Clear
- Abdomen: Soft, no organomegaly
- Skin: Extensive ecchymoses, expanding thigh hematoma
- Neurologic: Normal (no signs of intracranial bleeding)
Workup and Results
Complete Blood Count:
- WBC: 2,800/uL
- Differential: 45% abnormal promyelocytes
- Hemoglobin: 8.5 g/dL
- Platelets: 32,000/uL
Coagulation Studies:
- PT/INR: 16.5 sec / 1.4 (prolonged)
- aPTT: 42 sec (prolonged)
- Fibrinogen: 85 mg/dL (low; normal 200-400)
- D-dimer: 12,500 ng/mL (markedly elevated)
Peripheral Blood Smear:
- Hypergranular promyelocytes with abundant azurophilic granules
- Multiple Auer rods in some cells (faggot cells)
- Bilobed nuclei in some cells
Bone Marrow:
- 75% abnormal promyelocytes
- Flow cytometry: CD13+, CD33+, CD117+, HLA-DR negative, CD34 negative
FISH/RT-PCR:
- PML-RARA fusion: POSITIVE (confirms t(15;17))
Clinical Image
Peripheral blood smear in acute promyelocytic leukemia showing hypergranular promyelocyte with bundled Auer rods (faggot cell), virtually pathognomonic for APL with t(15;17).
Diagnosis
Acute Promyelocytic Leukemia (APL) with DIC
Key features:
- Hypergranular promyelocytes with faggot cells
- HLA-DR negative, CD34 negative immunophenotype
- PML-RARA fusion positive (defines APL)
- DIC with low fibrinogen and elevated D-dimer
- Low/normal WBC = standard risk APL
Treatment Plan
- IMMEDIATE (do not wait for genetic confirmation):
- Start ATRA (all-trans retinoic acid) 45 mg/m2/day divided BID
- Clinical suspicion of APL is sufficient to initiate ATRA
- DIC management (aggressive support):
- Transfuse cryoprecipitate to maintain fibrinogen >150 mg/dL
- Platelet transfusion to maintain >30,000-50,000/uL
- FFP as needed for active bleeding
- Definitive therapy (once diagnosis confirmed):
- ATRA + Arsenic trioxide (ATO) for standard-risk APL
- Consider adding idarubicin if high-risk (WBC >10,000)
- Monitoring:
- Daily CBC, coags, fibrinogen until DIC resolves
- Watch for differentiation syndrome (fever, dyspnea, weight gain, pulmonary infiltrates)
- If differentiation syndrome: Start dexamethasone 10 mg BID immediately
- Prognosis:
- APL is the most curable adult AML subtype (>90% cure rate)
- Early death from hemorrhage is main risk if not promptly treated
Teaching Points
- APL is a medical emergency - start ATRA on clinical suspicion before genetic confirmation
- DIC is characteristic of APL due to release of procoagulant substances from granules
- Maintain fibrinogen >150 mg/dL and platelets >30-50K until coagulopathy resolves
- ATRA + ATO combination achieves >90% cure without traditional chemotherapy in standard-risk APL
- Differentiation syndrome occurs when promyelocytes differentiate into neutrophils and release cytokines
- HLA-DR and CD34 negativity help distinguish APL from other AML subtypes
- Faggot cells (bundles of Auer rods) are virtually pathognomonic for APL