What is Kasabach-Merritt phenomenon and how is it managed?

Kasabach-Merritt Phenomenon: Diagnosis and Management

Kasabach-Merritt phenomenon (KMP) is a life-threatening consumptive coagulopathy characterized by profound thrombocytopenia and hypofibrinogenemia that occurs exclusively in association with kaposiform hemangioendothelioma (KHE) or tufted angioma (TA), not with common infantile hemangiomas. 1

Pathophysiology and Clinical Presentation

KMP is characterized by:

• Severe thrombocytopenia (often <20,000/mm³)
• Hypofibrinogenemia (<1 g/dL)
• Microangiopathic hemolytic anemia
• Consumption of clotting factors

The clinical presentation typically includes:

• Rapidly enlarging vascular tumor (KHE or TA)
• Purpura, petechiae, or active bleeding
• Cardiac failure (in approximately 20% of cases) 2
• Typically affects infants and young children
• Acute onset with rapid progression 3

Diagnosis

The diagnosis of KMP is based on:

1. Clinical features: Rapidly enlarging vascular tumor with associated coagulopathy

2. Laboratory findings:

   • Profound thrombocytopenia
   • Hypofibrinogenemia
   • Elevated D-dimer
   • Prolonged PT/PTT
   • Microangiopathic hemolytic anemia

3. Imaging:

   • MRI with and without contrast is the preferred imaging modality 4
   • Helps distinguish KHE/TA from other vascular anomalies

4. Histopathology: When clinically feasible, biopsy can confirm KHE or TA

Important Distinctions

• KMP is not associated with common infantile hemangiomas but occurs exclusively with KHE or TA 1
• Terms like "cavernous hemangioma" are outdated and contribute to diagnostic confusion 4
• Differential diagnosis includes other causes of thrombocytopenia and coagulopathy (DIC, sepsis, malignancy)

Management

No standardized treatment protocol exists for KMP, as evidenced by a survey showing 92% of vascular anomaly centers lack a standard practice 5. However, a stepwise approach is recommended:

First-Line Therapy:

1. Corticosteroids + Vincristine:

   • Most centers (50%) use this combination as initial therapy 5
   • Corticosteroids: Prednisolone/prednisone 2-5 mg/kg/day 6
   • Vincristine: Weekly doses for 4-6 weeks 2

2. Corticosteroids alone:

   • Used by 29% of centers as first-line 5
   • Response rate is variable (33-50%) 2, 6
   • Mean time to platelet count >20,000/mm³: 6.2 days in responders 2
   • Mean time to fibrinogen >1 g/dL: 25.6 days in responders 2

Second-Line Therapy (for steroid-resistant cases):

1. Vincristine (if not used initially):

   • Used by 38% of centers as second-line 5
   • Response in approximately 40% of cases 2

2. Interferon-alpha:

   • Used for 3-12 months 6
   • Effective in some steroid-resistant cases
   • Caution: risk of spastic diplegia in infants

3. Sirolimus (rapamycin):

   • Emerging as effective second-line therapy (21% of centers) 5
   • Shows promise in recent studies

Third-Line/Adjunctive Therapies:

1. Embolization:

   • Partial response in approximately 80% of cases 2
   • May require multiple procedures (average 2.8) 2
   • Risk of thrombotic complications (7%) 2

2. Chemotherapy:

   • Vincristine or vinblastine for refractory cases 6, 7
   • Most effective salvage therapy in some series 7

3. Radiotherapy:

   • Reserved for life-threatening, refractory cases 7

Monitoring and Follow-up

• Regular monitoring of platelet count, fibrinogen, and D-dimer
• Mean time to platelet count >150,000/mm³: 88 days 2
• Mean time to fibrinogen >1 g/dL: 49 days 2
• Relapse occurs in approximately 50% of cases 2

Prognosis

• Mortality rate: approximately 10-30% 2, 6
• Refractory cases tend to be therapy-dependent beyond 1 year of age 7
• Cases responsive to therapy typically resolve by 6 months of age 7

Pitfalls and Caveats

1. Misdiagnosis: Confusing KMP with other vascular anomalies leads to inappropriate treatment. KMP is not associated with common infantile hemangiomas.

2. Delayed treatment: Failure to increase antithrombotic therapy with rapidly expanding aneurysms can lead to sudden cardiovascular events.

3. Monitoring complications: Watch for hypertension with high-dose steroids 6 and neurologic complications with interferon.

4. Treatment duration: Premature discontinuation of therapy can lead to relapse, which occurs in approximately 50% of cases 2.