What is the likely diagnosis for a patient with myelodysplastic syndrome (MDS) post bone marrow transplant, who presents with hematuria and clots in urine after receiving defibrotide (defibrotide) therapy?

Hemorrhagic Cystitis Post-Defibrotide Therapy

You should strongly suspect hemorrhagic cystitis as a delayed complication of defibrotide therapy, occurring approximately 17 days after treatment completion. This presentation of blood clots in urine followed by dark-colored urine is characteristic of hemorrhagic cystitis, which is a recognized adverse effect of defibrotide treatment 1, 2.

Primary Differential Diagnosis

Defibrotide-Associated Hemorrhagic Cystitis (Most Likely)

• Hemorrhagic cystitis is a documented complication of defibrotide therapy, with hematuria occurring in up to 43% of patients treated with defibrotide for VOD/SOS 2
• The temporal relationship is significant: your patient received defibrotide until October 26,2025, and presents with hematuria on November 12,2025 (17 days post-treatment) 1, 2
• Hemorrhagic complications can occur as a delayed effect after defibrotide discontinuation, as documented in pediatric MDS post-transplant patients 1
• The progression from clots to dark urine suggests active bleeding with possible clot formation in the bladder 2

Key Clinical Features Supporting This Diagnosis

• Post-bone marrow transplant status (September 11,2025) places the patient at higher risk for hemorrhagic complications 1, 2
• MDS patients post-transplant have baseline thrombocytopenia risk, which may be exacerbated by defibrotide's anticoagulant properties 1
• The specific presentation of "passing clots" followed by dark urine is pathognomonic for hemorrhagic cystitis rather than simple hematuria 2

Critical Immediate Evaluation Required

Laboratory Assessment

• Complete blood count with platelet count - essential to assess for thrombocytopenia that may contribute to bleeding 1, 2
• Coagulation profile (PT/INR, aPTT) - defibrotide has anticoagulant and fibrinolytic properties 2, 3
• Urinalysis with microscopy - quantify RBCs and assess for infection 2
• Urine culture - exclude infectious cystitis as contributing factor 2

Imaging and Endoscopic Evaluation

• Cystoscopy should be considered if bleeding is severe or persistent to identify the source and rule out other pathology 4
• Renal ultrasound or CT scan if upper tract bleeding is suspected (though less likely given the clot passage) 4

Alternative Diagnoses to Consider (Less Likely)

BK Virus-Associated Hemorrhagic Cystitis

• Common in post-transplant patients, typically occurs 1-3 months post-transplant 2
• Your patient is approximately 2 months post-transplant (transplant September 11, presentation November 12)
• However, the temporal relationship with defibrotide cessation makes drug-related hemorrhagic cystitis more likely 1, 2

Thrombocytopenia-Related Bleeding

• MDS patients commonly have thrombocytopenia (present in ~30% of lower-risk MDS) 5
• Post-transplant thrombocytopenia could contribute to bleeding manifestations 1
• Check platelet count immediately - if <50,000/mm³, this significantly increases bleeding risk 5

Graft-versus-Host Disease (GVHD) of Bladder

• Rare manifestation but possible in allogeneic transplant recipients 1
• Would typically present with other GVHD manifestations
• Less likely given isolated urinary symptoms

Management Approach

Immediate Supportive Care

• Aggressive hydration to promote clot passage and prevent clot retention 2
• Continuous bladder irrigation if clot retention occurs 2
• Platelet transfusion if platelets <50,000/mm³ or active bleeding with platelets <100,000/mm³ 5
• Avoid anticoagulants and antiplatelet agents 2

Monitoring Strategy

• Serial hemoglobin measurements to assess ongoing blood loss 2
• Daily platelet counts until bleeding resolves 1, 2
• Monitor for signs of clot retention (inability to void, suprapubic pain, bladder distension) 2

Treatment Considerations

• Most defibrotide-associated hemorrhagic cystitis resolves spontaneously within 36-48 hours after drug discontinuation 1, 2
• Severe cases may require cystoscopy with clot evacuation and fulguration of bleeding sites 2
• Consider antifibrinolytic agents (aminocaproic acid or tranexamic acid) only if bleeding is life-threatening, as these may increase thrombotic risk 2

Critical Pitfalls to Avoid

• Do not restart defibrotide - hemorrhagic complications are a known adverse effect and recurrence risk is high 1, 2
• Do not delay platelet transfusion if thrombocytopenic - this is a potentially life-threatening hemorrhagic complication 1
• Do not assume infection without culture - empiric antibiotics are not indicated unless infection is documented 2
• Do not overlook the possibility of multiple contributing factors - defibrotide effect plus thrombocytopenia plus BK virus can coexist 1, 2

Prognosis and Expected Course

• Hemorrhagic cystitis from defibrotide typically resolves within days to weeks after drug discontinuation with supportive care 2
• Severe hemorrhagic events requiring intervention occurred in only 7% of defibrotide-treated patients in real-world data 2
• The key to successful management is early recognition and prompt supportive intervention 2