Approach Considerations
Management of Kasabach-Merritt syndrome (KMS) involves hastening vascular lesion regression, interfering with platelet trapping within the lesion, and supporting the patient with transfusions. [21]
Patients with KMS are admitted to the hospital with profound thrombocytopenia and evidence of coagulopathy. They are commonly treated with drug therapy initially [22, 23, 24, 25, 26, 27, 28, 29, 30] and with surgical or interventional radiologic measures either simultaneously or subsequently. [18, 31, 32, 33, 34]
Selected patients who have KMS with absent or mild thrombocytopenia and coagulopathy may be evaluated on an outpatient basis. However, as vascular lesions grow, these infants often require inpatient evaluation and treatment because most develop significant thrombocytopenia and disseminated intravascular coagulation (DIC).
Pharmacologic Therapy
No single therapy has been proved most effective in patients with KMS. Multiple treatments have been used in many infants. Success rates have varied. Treatments that are effective in some patients have no benefit for others. Many of these medications have serious adverse effects, especially in patients with thrombocytopenia and DIC, and should be administered only by physicians with expertise in this area. Most of them are not specifically approved by the US Food and Drug Administration (FDA) for treatment of KMS.
Corticosteroids are the drugs most commonly used and have been successful in many cases, though they do not always yield satisfactory results. [35, 33] In addition to high-dose oral steroids, pulsed or intravenous (IV) steroids have also been used.
Some success with interferon alfa-2a (3 million U/m2/day or 3 times weekly) has been reported, though the failure rate is high. [36, 37, 38] The subcutaneous injection may result in nausea, fever, or neutropenia. Interferon alfa has been associated with neurologic problems in certain patients [39, 40] ; some infants have developed spastic diplegia after receiving this agent.
Other medications, including ε-aminocaproic acid, aspirin, dipyridamole, [25] ticlopidine, pentoxifylline, [40] cryoprecipitate, and heparin, have also been used to treat KMS, with varying degrees of efficacy.
Chemotherapy, including vincristine, cyclophosphamide, and actinomycin D, has been successfully employed in some patients. [41, 24, 42, 43, 44] In particular, vincristine is increasingly often being given to treat KMS. [26, 27, 28, 30, 45, 46, 47] Nevertheless, there have been treatment failures.
In 2008, Leaute-Labreze et al reported using propranolol in 2 infants with severe hemangiomas. [48] Potential explanations of the therapeutic effect included vasoconstriction, decreased expression of VEGF and bFGF genes, and the triggering of apoptosis of capillary endothelial cells.
A study by Su et al found that transcatheter arterial embolization with polyvinyl alcohol particles combined with drug therapy achieved good results in six infants with KMS. The patients, with lesions in the temporal region, parotid region, or submandibular region and neck, experienced shrinkage and/or lightening of the hemangioma, while the mean platelet count reached over 80,000/L in five patients; one patient achieved a platelet count of 102,000/L. Neither hemangioma rebound growth nor platelet count reduction were found at 12- to 18-month follow-up. [49]
Surgical and Endovascular Interventions
Surgical management often is not feasible in KMS, because the lesions are too large. When the lesions are sufficiently small, surgery has resulted in a rapid normalization of the platelet count and other blood abnormalities. Complete surgical resection, when possible, is the most effective treatment of vascular lesions complicated by KMS. [50] Thrombocytopenia and DIC resolve after the lesion has been resected. [51]
Depending on the location of the tumor, general surgery, thoracic surgery, or neurosurgery may be needed for excision or ligation of the vessels feeding the vascular lesion. Wide local excision is recommended but may be difficult. The large size and infiltrative growth pattern of the vascular lesion may cause complications (eg, hemorrhage, obstruction, and respiratory compromise). Amputation may be necessary for intractable lesions involving a limb.
Some lesions are surgically inaccessible and thus call for nonsurgical treatment modalities. Interventional radiologic procedures use polyvinyl alcohol or absolute ethanol to embolize or sclerose the vessels of the vascular lesion. [34, 52] Another technique involves injecting polyvinyl beads to stop the feeder blood supply. Endovascular treatment (eg, transfemoral arterial embolization) has yielded good results in a number of cases. [53, 54, 55, 35, 56]
Treatment with the tunable dye laser (TDL) may help patients with diffuse cutaneous vascular lesions. [57]
Pneumatic Compression
Treatment with intermittent pneumatic compression, either alone or in combination with other therapies, has helped some patients. [58] This modality is most useful when the vascular lesion is located on an extremity.
Encircle the lesion with a blood pressure cuff, and gradually increase the pressure to midway between the systolic and diastolic blood pressures. Inflate the cuff intermittently (eg, 90 seconds of compression, then 30 seconds of rest). A cuff may be used for an extended period. Compression with surgical hose stockings may help. It is often worthwhile to attempt pneumatic compression to see if it helps before attempting other potentially more toxic treatments.
Radiation Therapy
Radiation therapy has been used in patients with severe disease. [18, 59] It has also been combined with interferon alfa therapy, with some success. [60] Although low radiation doses have been reported to offer benefit in some cases, the long-term adverse effects of radiotherapy must be carefully weighed against the problems caused by the vascular lesion—especially in very young children, who are at risk for malignancy or decreased bone growth in the radiated field with this treatment.
Currently, because of the long-term adverse effects of radiation therapy in survivors, this mode of therapy is no longer favored for KMS, and many practitioners have abandoned it.
Nonetheless, a study by Kim et al indicated that low-dose radiotherapy (6-10 Gy) can quickly and effectively control cases of KMS that do not respond to other treatments. In the study, nine patients received a single course of radiotherapy, the total dose being 4.5-8 Gy (1.5-2 Gy/fraction), while two patients were treated with multiple courses of radiotherapy, the cumulative total doses being 12 Gy (2 Gy/fraction) and 18 Gy (1.5 Gy/fraction). All 11 of the study’s patients achieved normal platelet counts at a median 20 days post radiotherapy. Moreover, following radiotherapy, complete hematologic remission occurred in all patients suffering from coagulopathy. However, seven patients were found to have long-term radiation-related complications, with the two patients who underwent multiple radiotherapy courses demonstrating leg-length discrepancy. [61]
Consultations
A pediatric hematology consultation is required for management of the complex hemostatic problems of KMS patients and for administration and management of many of the medications needed for the most fulminant cases. Additional consultations that may be advisable are as follows:
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Dermatologist
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Surgeon
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Pediatrician
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Interventional radiologist
Consultations with neonatal or pediatric intensive care specialists may be required, depending on the age of the patient.
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Leg with a Kaposiform hemangioendothelioma, lesion associated with Kasabach-Merritt Syndrome.
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Back of an arm showing the typical bruising associated with Kasabach-Merritt Syndrome.
