Kasabach-Merritt Syndrome

Kasabach-Merritt Syndrome (KMS)

Kasabach-Merritt Syndrome, also known as Hemangioma-thrombocytopenia syndrome, is a rare condition characterized by the combination of a rapidly enlarging vascular tumor and consumptive coagulopathy. It primarily affects infants and young children.

Key Points:

Rare vascular disorder, with an estimated incidence of less than 1 per 100,000 children
Typically presents in infancy, with 80% of cases diagnosed before 1 year of age
Associated with specific vascular tumors: kaposiform hemangioendothelioma (KHE) and tufted angioma (TA)
Characterized by thrombocytopenia, microangiopathic hemolytic anemia, and consumption of clotting factors
Can be life-threatening due to severe bleeding complications
Requires a multidisciplinary approach for management

Pathophysiology

The pathophysiology of Kasabach-Merritt Syndrome involves complex interactions between the vascular tumor and the coagulation system:

Vascular Tumor Growth:
- Rapid proliferation of endothelial cells in KHE or TA
- Abnormal vascular channels with turbulent blood flow
Platelet Trapping:
- Platelets adhere to the abnormal endothelium within the tumor
- Platelet activation and aggregation occur within the lesion
Consumptive Coagulopathy:
- Activation of the coagulation cascade within the tumor
- Consumption of clotting factors, especially fibrinogen
- Formation of fibrin thrombi within and around the tumor
Microangiopathic Hemolytic Anemia:
- Mechanical destruction of red blood cells in the abnormal vasculature
- Presence of schistocytes (fragmented red blood cells) in peripheral blood
Systemic Effects:
- Severe thrombocytopenia due to platelet sequestration and consumption
- Hypofibrinogenemia from ongoing consumption
- Elevated D-dimer levels indicating active fibrinolysis
- Potential for severe bleeding complications

Clinical Presentation

The clinical presentation of Kasabach-Merritt Syndrome can vary but typically includes:

1. Vascular Tumor:

Rapidly enlarging, firm, warm, and violaceous mass
Most commonly located on the trunk, extremities, or retroperitoneum
May cause compression of adjacent structures

2. Hematological Manifestations:

Petechiae and ecchymoses
Prolonged bleeding from minor injuries or invasive procedures
Gastrointestinal or genitourinary bleeding
Intracranial hemorrhage (in severe cases)

3. Systemic Symptoms:

Pallor due to anemia
Fatigue and weakness
Fever (in some cases)
Failure to thrive in infants

4. Complications:

High-output cardiac failure (due to arteriovenous shunting within the tumor)
Compartment syndrome (if tumor is in an extremity)
Respiratory distress (if tumor affects the airway or lung)
Abdominal compartment syndrome (in retroperitoneal tumors)

Diagnosis

Diagnosis of Kasabach-Merritt Syndrome is based on clinical presentation, laboratory findings, and imaging studies:

1. Laboratory Studies:

Complete Blood Count (CBC):
- Severe thrombocytopenia (often <10,000/μL)
- Anemia with evidence of hemolysis
Coagulation Profile:
- Prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT)
- Low fibrinogen levels (<100 mg/dL)
- Elevated D-dimer levels
Peripheral Blood Smear:
- Presence of schistocytes (fragmented red blood cells)

2. Imaging Studies:

Ultrasound:
- Initial imaging modality, especially for superficial lesions
- Shows heterogeneous, hypervascular mass with high-flow vessels
Magnetic Resonance Imaging (MRI):
- Gold standard for diagnosis and staging
- Demonstrates extent of the tumor and its relationship to adjacent structures
- Characteristic findings include infiltrative soft tissue mass with avid enhancement
Computed Tomography (CT):
- May be used for deep-seated lesions or when MRI is not available
- Less preferred due to radiation exposure, especially in infants

3. Biopsy:

Generally not recommended due to risk of bleeding
May be considered in atypical cases or when diagnosis is uncertain
If performed, shows features of kaposiform hemangioendothelioma or tufted angioma

Treatment

Management of Kasabach-Merritt Syndrome requires a multidisciplinary approach and is aimed at controlling the vascular tumor and managing the coagulopathy:

1. Supportive Care:

Transfusion support:
- Platelet transfusions (used judiciously due to risk of tumor growth)
- Packed red blood cells for symptomatic anemia
- Cryoprecipitate or fresh frozen plasma for severe hypofibrinogenemia
Management of bleeding complications
Careful monitoring in an intensive care setting for severe cases

2. Pharmacological Interventions:

Corticosteroids:
- First-line therapy in many centers
- High-dose prednisolone (2-5 mg/kg/day)
Vincristine:
- Often used in combination with steroids or as second-line therapy
- Weekly intravenous administration (0.05-0.1 mg/kg)
Propranolol:
- Increasing evidence for efficacy, especially in combination with steroids
- Typical dose: 2-3 mg/kg/day divided into 3 doses
Sirolimus (mTOR inhibitor):
- Emerging as an effective treatment option
- Oral administration, with dose adjusted based on trough levels
Other agents (used in refractory cases):
- Interferon-alpha (less commonly used due to risk of spastic diplegia)
- Cyclophosphamide
- Actinomycin D

3. Interventional Procedures:

Embolization:
- May be considered for localized, accessible lesions
- Risk of complications, including tissue necrosis
Radiation therapy:
- Reserved for life-threatening cases unresponsive to other treatments
- Long-term risks, especially in infants

4. Surgical Intervention:

Generally not recommended as primary treatment due to risk of severe bleeding
May be considered for small, localized lesions or residual disease after medical therapy

5. Long-term Follow-up:

Regular monitoring of tumor size and coagulation parameters
Gradual tapering of medications once stable response is achieved
Assessment for long-term sequelae, including growth abnormalities and orthopedic issues