Medical and interventional therapy of Kasabach-Merritt phenomenon associated with Kaposiform hemangioendothelioma: A case report

An infant with Kasabach-Merritt Phenomenon (KMP) presented with a giant subcutaneous mass in the right lower limb, severe hypofibrinogenemia, and thrombocytopenia. Glucocorticoids, along with supportive treatments including transfusion of blood products and clotting factors, were administered to reverse fatal disseminated intravascular coagulation and acute hemolysis. The glucocorticoid dose was tapered slowly, and sirolimus was added to treat the hemangiomas. The patient subsequently underwent interventional therapy. After 6 months of medical and interventional therapy, the patient was doing well with a normal platelet count, the tumor volume was markedly reduced, and the primary cutaneous lesion became pale pink. Currently, the patient remains on sirolimus, and no recurrence of thrombocytopenia or further growth of the mass was observed after six months of follow-up.


Introduction
Kasabach-Merritt phenomenon (KMP) is a life-threatening consumptive coagulopathy associated with an underlying vascular tumor.KMP is characterized by severe thrombocytopenia, microangiopathic anemia, hypofibrinogenemia, and elevated fibrin split product levels in the presence of a rapidly enlarging tumor.KMP is usually present in early infancy, and the commonly reported sites of tumors include the extremities, trunk, and neck. 1 Uniform treatment guidelines for neonates with Kaposiform hemangioendothelioma (KHE) are lacking.Thus, many treatment modalities have been tried.Prior to 2016, no prospective studies have demonstrated the efficacy and safety of these modalities.Currently, no single treatment strategy has been consistently successful, and several different modalities are generally required. 2We report the case of an infant with KMP who presented with KHE on the right lower limb and his response to sirolimus and interventional therapy.

Case report
A 2-month-old male infant was admitted to our clinic with a mass in the right lower limb since birth.The mass increased in size with age and without medical treatment.The current size was approximately 5 Â 5 cm, the skin color was purplish red with swelling of the surrounding tissue, and the past history, personal history, and immunization were all normal.No cyanosis, convulsions, or bleeding was observed after birth.No family history of congenital malformations, tumors, or hemorrhagic disease was reported.Upon examination, the vital signs were stable.The infant was alert.Hemorrhagic spots were observed in the upper hard palate.A 5 Â 5 cm mass was observed at the right knee joint (Fig. 1).The mass was warm on palpation, medium in quality, and well-demarcated.
The mass showed an iso-intense signal on T1 weighted image (T1WI) and an iso-to-mild intense signal on T2 weighted image (T2WI) in the subcutaneous fat layer of the inguinal region of the right thigh.Contrastenhanced magnetic resonance imaging (MRI) demonstrated multiple heterogeneous intense enhancement which was considered as a possibility of hemangioma (Fig. 2) (see Fig. 3).
MRI and laboratory investigations strongly suggested a diagnosis of KHE with KMP.Biopsy of the tumor was not attempted, given the potential risk for hemorrhage.The possibility of KMP was considered in view of severe thrombocytopenia, enlarging vascular lesion and coagulopathy, and oral prednisone was started (3.2 mg/kg/day) on day 1 of admission.A compassionate trial of sirolimus is warranted.The risks and benefits were explained to the family, and their consent was obtained.Conventional therapy with steroids was still ongoing and then tapered slowly, and pneumocystis prophylaxis with cotrimoxazole was additionally started owing to the potential risk of immunosuppression.
The results of the blood cell test and coagulation function went well in the first 4 days; however, on day 5, the infant had a sudden seizure.The emergency head computed tomography scan indicated no intracranial hemorrhage, and the coagulation function showed prolonged clotting time and significant hypofibrinogenemia (Table 1).Fresh frozen plasma and fibrinogen were injected to supply blood coagulation factors.The use of sirolimus and corticosteroids was continued at all times.On day 10, the platelet count and coagulation time were normal, and the infant underwent transcatheter embolization of a Kaposiform hemangioendothelioma on the right lower limb under general anesthesia.
The patient continued to show a decrease in the size of the lesion during follow-up on sirolimus therapy at 6 months (Fig. 5) and platelet counts increased above 100 Â 109/L after 3 weeks of steroid and sirolimus therapy.The infant was discharged in good condition and continued on 0.8 mg/m2 of sirolimus per dose twice daily (see Fig. 4).
Follow-up 6 months after surgery indicated that the patient was in good condition, the tumor volume was significantly reduced, and the primary cutaneous lesion had become pale pink.Currently, the patient remains on sirolimus, and no recurrence of thrombocytopenia or further growth of the mass was observed after six months of follow-up.

Discussion
Kasabach and Merritt first reported a case of an infant with thrombocytopenic purpura because of what they believed to be a giant capillary hemangioma. 3Thereafter, the association of a capillary hemangioma and thrombocytopenia was labeled Kasabach-Merritt syndrome and this name was later changed to KMP.Kaposiform hemangioendothelioma (KHE) is a rare infiltrative vascular tumor that is typically diagnosed during infancy.KHE, first described in 1993, is characterized by a violaceous cutaneous lesion with ill-defined borders, occurring in childhood and infancy. 4Over 70% of patients with KHE develop the KMP, a potentially life-threatening consumptive coagulopathy.Although the incidence of KHE is low, it can cause morbidity and mortality in both children and adults.6][7][8] Consequently, prompt diagnosis and appropriate management are crucial for improving the long-term prognosis of patients.Uniform guidelines for neonates with KHE are lacking.Therefore, several treatment modalities have been developed.Prior to 2016, no prospective studies had demonstrated the efficacy and safety of these modalities.Historically, KHE treatment has included high-dose steroids, chemotherapy (e.g., cyclophosphamide), antiplatelet therapy (e.g., aspirin), propranolol, embolization, radiotherapy, and sclerotherapy. 9lthough complete surgical resection has been acknowledged as the curative gold standard for KHE, total resection is often not a viable option because of the high risk of bleeding, extent of the tumor, and/or anatomic site of the lesion. 10Embolization can be performed on large tumors that are unsuitable for surgical management.Interventional or percutaneous puncture was used to embolize the nutritional arteries of the tumor. 11,12The clinical management of high-risk patients with KMP is highly challenging.To date, no single treatment regimen has provided consistently Fig. 3.The 1.9 F microcatheter was used for superselective catheterization of the feeding artery.During the procedure, the pingyangmycin-lipiodol emulsion (PLE) was injected slowly through the catheter until the periphery of the hemangioma was completely surrounded.The PLE was made with 2 mg pingyangmycin (diluted in 2 mL of normal saline) plus 2 mL of lipiodol.reproducible results in terms of decreased tumor size and KMP symptom control.Should deterioration ensue during treatment, a combination therapy or an alternative treatment should be considered.However, when sirolimus is ineffective, no clinical data are available to conclusively determine the appropriate second-line management for refractory disease.Furthermore, patients with KMP who have a high probability of long-term sequelae, such as functional deformities or severe life-threatening conditions, should be treated using an aggressive strategy. 13We have presented a case of KHE in an infant with KMP treated with comprehensive therapy.Sirolimus may be considered as a first-line therapy or part of the treatment of KHE and KMP.However, sirolimus can take several weeks to exert its effect.Initial treatment with embolization provides rapid relief from the symptoms of KMP.Image-guided transarterial embolization may, thus, provide a valuable adjunct to sirolimus therapy in KHE/KMP. 14

Fig. 1 .
Fig. 1.The mass on the right knee joint of the baby.

Fig. 2 .
Fig. 2. The enhanced MRI scan of the infant's right lower limb.

Fig. 4 .
Fig. 4. Selective right lower extremity arteriography was performed to judge the degree of embolism of the supplying arteries.

Fig. 5 .
Fig. 5.The resolution of the Kaposiform hemangioendothelioma lesion during treatment: (A) postoperative day 2; (B) after 3 weeks of treatment; (C) after 2 months of treatment; (D) after 6 months of treatment.

Table 1
The trending of test results during the hospitalization.