What is the management of Kasabach-Merritt syndrome?

Management of Kasabach-Merritt Syndrome

Kasabach-Merritt phenomenon (KMP) should be treated with a stepwise approach, starting with combination therapy of systemic corticosteroids plus vincristine as first-line treatment, followed by sirolimus for refractory cases. 1

Definition and Clinical Presentation

Kasabach-Merritt phenomenon is a life-threatening consumptive coagulopathy characterized by:

• Profound thrombocytopenia (often <20,000/mm³)
• Hypofibrinogenemia (<1 g/dL)
• Microangiopathic hemolytic anemia
• Consumption of clotting factors
• Elevated D-dimer levels
• Prolonged PT/PTT

KMP occurs exclusively in association with kaposiform hemangioendothelioma (KHE) or tufted angioma (TA), not with common infantile hemangiomas 1. It typically affects infants and young children with a rapidly enlarging vascular tumor.

Diagnostic Approach

1. Laboratory evaluation:

   • Complete blood count with focus on platelet count
   • Coagulation studies (fibrinogen, D-dimer, PT/PTT)
   • Peripheral blood smear to assess for microangiopathic hemolytic anemia

2. Imaging:

   • MRI with and without contrast is the preferred imaging modality 1
   • Helps differentiate KHE/TA from other vascular anomalies

3. Biopsy:

   • May be considered if diagnosis is unclear, but carries risk of bleeding
   • Often unnecessary if clinical and imaging findings are characteristic

Treatment Algorithm

First-line Treatment:

1. Combination therapy: Corticosteroids + Vincristine 1, 2

   • Corticosteroids: Prednisolone/prednisone 2-5 mg/kg/day
   • Vincristine: 0.05 mg/kg weekly (maximum 2 mg)
   • Monitor for hypertension which develops in most children on high-dose steroids 3

2. Alternative first-line options:

   • Corticosteroids alone (if vincristine is contraindicated)
   • Monitor platelet count, fibrinogen, and D-dimer to assess response

Second-line Treatment (for refractory cases):

1. Sirolimus (rapamycin) 1, 2

   • Emerging as effective second-line therapy
   • Dosing based on therapeutic drug monitoring

2. Interferon-alpha 1, 3

   • Used for 12 months, then tapered to alternate-day regimen
   • Monitor for neurotoxicity, especially in infants
   • Successfully induced regression in 6 of 8 steroid-resistant cases in one study 3

Third-line/Adjunctive Treatments:

1. Embolization of feeding vessels 1, 3, 4

   • Particularly useful for localized lesions
   • May require multiple procedures (mean 2.8 procedures per patient) 4
   • Provides partial response in most cases

2. Chemotherapy agents 1, 3

   • Vinblastine or other agents may be useful for refractory cases
   • Limited experience but can be effective when other treatments fail

3. Radiotherapy 1

   • Reserved for life-threatening cases unresponsive to other therapies

Monitoring and Follow-up

1. Laboratory monitoring:

   • Regular assessment of platelet count, fibrinogen, and D-dimer
   • Initially daily, then weekly, then monthly as condition improves

2. Response assessment:

   • Mean time to platelets >20×10⁹/L: 56 days
   • Mean time to platelets >150×10⁹/L: 88 days
   • Mean time to fibrinogen >1 g/dL: 49 days 4

3. Long-term follow-up:

   • Relapse occurs in approximately 50% of cases 1
   • Cases responsive to therapy typically resolve by 6 months of age
   • Refractory cases tend to be therapy-dependent beyond 1 year of age

Prognosis

• Mortality rate: 10-30% 1
• Thrombotic complications occur in approximately 7% of cases 4
• Relapse is common but can be successfully treated with reinstitution of therapy

Important Considerations

• Early intervention is critical - delay in treatment can lead to increased morbidity and mortality
• Propranolol, which is effective for infantile hemangiomas, is not effective for KMP 1, 2
• Differentiation from other vascular anomalies is crucial as treatment approaches differ significantly
• Multidisciplinary approach involving hematology, dermatology, interventional radiology, and vascular anomalies specialists is essential for optimal outcomes

Remember that KMP is a medical emergency requiring prompt diagnosis and aggressive management to prevent life-threatening complications.