KMS is a rare complication of pre-existing hemangiomas first described by Kasabach and Merritt1
in 1940. It is characterized by an enlarging hemangioma, associated with thrombocytopenia and consumptive coagulopathy which may lead to life-threatening bleeding1
. More than 80% of cases occur within the first year of life9
. KMS can be a complication of KHE, tufted angiomas or, rarely, large infantile hemangiomas but most reported cases of KMS were associated with KHE and tufted angiomas2
. A recent retrospective study conducted by Enjolras et al.10
revealed that KMS was due either to KHE and/or tufted angiomas. The residual lesions of patients with cured KMS were predominantly tufted angiomas, whereas KHE was more common during the active phase of KMS. Thus it is possible that KHE and tufted angiomas are the part of the same neoplastic spectrum and histologic continuum11
. Enjolras et al.10
proposed that KMS was not a complication of infantile hemangiomas, but of KHE and tufted angiomas based on their findings.
The trigger factors for the development of KMS include surgical intervention, pregnancy, angiography, and needle aspiration of hemangioma12-14
. In our case, KMS occurred one month after 3 mm skin biopsy from a pre-existing tufted angioma. Minor trauma due to punch biopsy might have triggered KMS in our case.
The pathogenesis of KMS remains unestablished. However, platelet trapping by abnormally proliferating endothelium within the hemangioma has been proposed as a possible mechanism15
. Platelet trapping can result in the activation of platelets with secondary activation of coagulation cascades, eventually leading to consumption of various clotting factors. Immunohistochemical study using monoclonal antibody against CD61, a marker of platelets, and isotope studies using 111
indium-labeled platelets and 51
Cr-labeled platelets support the possible role of platelet trapping in the development of KMS15
. The reason why platelets are trapped within the hemangioma in the patients with KMS remains unelucidated. In addition to platelet trapping, excessive blood flow and sheer stress secondary to arteriovenous shunts within the tumors may cause further platelet activation. Both thrombocytopenic status and reduction in coagulation factors eventually result in bleeding within the tumors that manifests as a rapidly growing hemangioma.
Management of KMS has been challenging because of its rarity and there are no well-established systematic treatment strategies to date. Systemic corticosteroid is considered to be first-line therapy in patients with KMS ()6-8,15-18
. One study demonstrated that treatment with prednisolone at 2 or 3 mg/kg/day achieved response in 30% to 72% of infants16
. However, other data suggested variable response to prednisolone, ranging from no efficacy to significant regression in lesion size, and even complete remission7
. The discrepant results may be due to variation in patient clinical characteristics in the studies, such as different pre-existing tumors, and the possibility that the enrolled patients actually had vascular malformations, rather than hemangiomas. If a lesion responds to steroid, the dose should be reduced slowly to prevent recurrence. High doses of prednisolone (more than 5 mg/kg/day) can be used as an alternative, and it has shown to be more effective than 3 mg/kg/day in a study by Sadan and Wolach17
. Some authors advocate the superiority of high dose oral methylprednisolone therapy to the conventional treatment with prednisolone18
. High rates of initial response and short therapy duration appears to be an advantage, but should be confirmed by a double blind, comparative study between different regimens. The mechanisms of prednisolone in controlling thrombocytopenia, coagulopathy, and eventually stabilization of hemangiomas remain unclear, although it appears to increase platelet longevity, increase vasoconstriction, inhibit fibrinolysis, and disrupt angiogenesis. Side-effects associated with steroid treatment include hypertension, cushingoid appearance, growth suppression and opportunistic infections15,19
. Our patient commenced with 0.32 mg/kg/day of intravenous dexamethasone, equivalent to 2.0 mg/kg/day of prednisolone. The most likely cause of our patient's rapid platelet recovery and lesion stabilization following initiating therapy was the superior bioavailability of intravenous steroids over that of oral administration.
A stepwise approach in the treatment of Kasabach-Merritt syndrome
In cases resistant to systemic corticosteroid, multiple treatment modalities can be used in a stepwise manner, including interferon-alpha, an antiproliferative and antiangiogenic agent, and vincristine, a strong inhibitor of angiogenesis. Radiotherapy is another option which can induce embolization within the hemangiomas. These options are usually recommended as second-line therapies6,7,15
. However, treatment with these regimens can result in severe adverse events. The known adverse effects of interferon therapy include flu-like symptoms, neutropenia, and spastic diplegia in infancy5,7
. Vincristine can be associated with transient peripheral neuropathy, and it is considered a relatively safe regimen with high efficacy7,8,15
. Since radiotherapy has been reported to induce late side effects, including local growth failure, late skin changes, destruction of bone tissue and secondary malignancies, it should be administered to patients with life-threatening lesions, or to patients with lesions that may compromise organ function, or when other therapies fail to achieve response5-7,15
In conclusion, conventional systemic corticosteroid is probably the most cost-effective treatment option in patients with KMS. Systemic corticosteroid may result in variable response in KMS; however, it should be considered first-line treatment since it offers rapid resolution and less complications, compared to other treatment modalities. In addition, intravenous corticosteroid may be more efficacious than oral corticosteroid, most likely due to superior bioavailability. However, due to the rarity of this syndrome, it is difficult to undertake any comparative studies on different modalities.