Dermatology: Practical and Conceptual Observation | Dermatol Pract Concept 2015;5(1):18 91 DERMATOLOGY PRACTICAL & CONCEPTUAL www.derm101.com Case report A full-term male newborn was admitted to our hospital with diagnosis of right latero-cervical vascular mass present at birth (Figure 1). He was transferred to our center one week after his birth due to a progressive increase of tumor size. No prior therapy was given. Physical exam revealed a 12x10 cm mixed (deep and superficial) plaque-like lesion with ecchy- mosis. A severe coagulopathy with profound thrombocyto- penia (27,000x109/L) and elevated D-dimer level (84,369 mcg/L) were observed, all of which supported the diagnosis of Kasabach-Merritt phenomenon (KMP). A Doppler ultra- sound study and magnetic resonance imaging (MRI) revealed The importance of early diagnosis and treatment of kaposiform hemangioendothelioma complicated by Kasabach-Merritt phenomenon Grecia V. Vivas-Colmenares 1, Gema L. Ramirez-Villar2, Jose Bernabeu-Wittel3, Jose A. Matute de Cardenas1, Israel Fernandez-Pineda1 1 Department of Pediatric Surgery, Virgen del Rocio Children’s Hospital, Sevilla, Spain 2 Department of Pediatric Oncology, Virgen del Rocio Children’s Hospital, Sevilla, Spain 3 Department of Pediatric Dermatology, Virgen del Rocio Children’s Hospital, Sevilla, Spain Key words: kaposiform hemangioendothelioma, Kasabach-Merritt phenomenon, vincristine, ticlopidine, aspirin Citation: Vivas-Colmenares GV, Ramirez-Villar GL, Bernabeu-Wittel J, Matute de Cardenas JA, Fernandez-Pineda I. The importance of early diagnosis and treatment of kaposiform hemangioendothelioma complicated by Kasabach-Merritt phenomenon. Dermatol Pract Concept 2015;5(1):18. doi: 10.5826/dpc.050118 Received: August 19, 2014; Accepted: September 22, 2014; Published: January 30, 2015 Copyright: ©2015 Vivas-Colmenares et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: None. Competing interests: The authors have no conflicts of interest to disclose. All authors have contributed significantly to this publication. Corresponding author: Israel Fernandez-Pineda, MD, Department of Pediatric Surgery, Virgen del Rocio Children’s Hospital, Av. Manuel Siurot s/n, Seville, Spain. Tel. 34 955012924. Email: israel.fernandez.pineda@gmail.com Kaposiform hemangioendothelioma (KHE) is a locally aggressive vascular tumor that may be compli- cated by Kasabach-Merritt phenomenon (KMP), a profound thrombocytopenia resulting from platelet trapping within a vascular tumor, either KHE or tufted angioma (TA). Typical features also include low fibrinogen and elevated D-dimers. It is well known that KMP is not caused by infantile heman- giomas. Management of vascular tumors complicated by KMP is challenging, and it is common for referral centers to receive patients in critical medical condition after multimodality treatment failure of vascular anomalies. Our aim is to communicate the importance of early diagnosis and treatment of KHE associated with KMP. A full-term male newborn with KHE complicated by KMP is reported. Treatment with vincristine, aspirin and ticlopidine normalized the coagulation parameters within one week, requiring a total of six doses of vincristine, seven months of ticlopidine and 17 months of as- pirin. Early diagnosis and treatment of KHE complicated by KMP may allow the administration of fewer doses of vincristine and avoid the use of corticosteroids. ABSTRACT mailto:israel.fernandez.pineda@gmail.com 92 Observation | Dermatol Pract Concept 2015;5(1):18 ing KMP [1-5]. In an extensive review of KHE, Croteau et al [6] reported that superficial tumors, tumors isolated to bone, or presentation at an older age are each a characteristic that is asso- ciated with decreased frequency of KMP. Patients with KHE with fascial involvement but not deeper invasion of muscle or bone seem to present with few complications of KMP. The con- sensus-derived practice standards plan for complicated KHE was published in 2013 and reported that 64% of experts’ centers did not think that a tissue biopsy was necessary to confirm diagnosis of KMP [7]. As in our case, most of the patients present are diagnosed based on clinical, imaging and laboratory find- ings (profound thrombocytopenia and elevated serum D-dimer). Diagnosis of KHE associated with KMP is usually delayed, and several factors may be implicated such as lack of experience in clinical diagnosis of vascular anomalies, deep tumor loca- tion (mediastinum, retroperitoneum) and/or the coagulation abnormalities that makes the biopsy challenging. Dif- ferential diagnosis with other tumors that may cause coagulopathy should be performed. Baselga et al [8] described that rapidly involuting congenital hem- angioma (RICH) may present with thrombocytopenia and coagulopathy similar to mild KMP early in the neo- a multichanneled fast-flowing vascular tumor. Clinical appearance of the tumor, radiological findings, and the coexisting KMP supported the diagnosis of kapo- siform hemangioendothelioma (KHE). Treatment was according to SEOP (Spanish Society of Pediatric Oncology) guidelines for vascular tumors compli- cated by KMP and included vincristine, aspirin and ticlopidine (VAT therapy). The patient received VAT therapy with vincristine: 0.05 mg/kg weekly; aspirin: 10 mg/kg/day; and ticlopidine: 10 mg/ kg/day. Treatment response was based on platelet count and classified as good response (increase of >50% of platelet count) observed in obtained blood tests no longer than three weeks since the treatment was started and repeated every two weeks. Coagulation parameters nor- malized within one week, along with the decrease in size of the tumor. The patient required a total of six doses of vincris- tine, seven months of ticlopidine and 17 months of aspirin. Twelve months after discontinuation of aspirin, the patient remains asymptomatic with no tumor regrowth and normal platelet count. Discussion KHE involves a spectrum of lesions from small, superficial tumors without KMP to large, infiltrative lesions with life-threatening complications includ- Figure 1. Right latero-cervical kaposiform hemangioendothelioma at birth (A) and 17 months later, after completion of therapy (B). (Copyright: ©2015 Vivas-Colmenares et al.) natal period. However, in contrast to true KMP, these abnormal laboratory findings are self-limited and are usually not complicated by bleeding problems. RICH is fully formed at birth and it does not enlarge within the first weeks of life. Clinical appearance of RICH is characterized by superficial prominent veins and is encircled by a pale halo, while KHE is a plaque-like lesion with ecchymosis. A biopsy would have been useful to obtain a histological diagnosis in our case, but the patient presented a profound thrombocytopenia and severe abnormalities in coagulation param- eters, which made the biopsy a high-risk bleeding procedure. On imaging studies (MRI, Doppler-US), both tumors are highly vascularized lesions with high- flow, but KHE has a more infiltrative pattern compared to RICH. Evaluation of treatment outcomes is difficult and based on personal opin- ions, isolated case reports and small series. Most of the patients receive mul- timodality therapy, and some delays of initiation of therapy may cause sig- nificant morbidity and mortality. The literature describes a variable response to corticosteroid therapy (20–70%), and depending on the dosage can cause several adverse side effects such as severe hypertension, growth restriction, and osteoporosis [9,10]. Although case reports have described the efficacy of propranolol for the treatment of KHE, Chiu et al [11] found that propranolol was ineffective in seven of their eleven patients and recommend clinicians to proceed cautiously before treating these life-threatening conditions with pro- pranolol. Recently, sirolimus has been described to be effective and safe in patients with life-threatening KHE and may represent a promising tool in treat- ing refractory KHE [12]. Vincristine is usually used in combination with other therapies for severe, life-threatening cases because of its good tolerance and response. Several studies used vincris- tine monotherapy for KMP with good response rates of 86-100% [13,14]. In Observation | Dermatol Pract Concept 2015;5(1):18 93 is associated with kaposiform hemangioendothelioma and not with common infantile hemangioma. Plast Reconstr Surg 1997;100:1377–86. 5. Enjolras O, Wassef M, Mazoyer E, et al. Infants with Kasabach- Merritt syndrome do not have “true” hemangiomas. J Pediatr 1997;130:631–40. 6. Croteau SE, Liang MG, Kozakewich HP, et al. Kaposiform He- mangioendothelioma: atypical features and risks of Kasabach- Merritt phenomenon in 107 referrals. J Pediatr 2013;162:142-47. 7. Drolet BA, Trenor CC, Brandão LR, et al. Consensusderived practice standards plan for complicated Kaposiform hemangio- endothelioma. J Pediatr 2013;163(1):285-91. 8. Baselga E, Cordisco MR, Garzon M, et al. Rapidly involuting con- genital haemangioma associated with transient thrombocytopenia and coagulopathy: a case series. Br J Dermatol 2008;158:1363. 9. Fahrtash F, McCahon E, Arbuckle S. Successful treatment of kaposiform hemangioendothelioma and tufted angioma with vincristine. J Pediatr Hematol Oncol 2010;32(6):506-10. 10. Hall GW. Kasabach-Merritt syndrome: pathogenesis and manage- ment. Br J Haematol 2001 Mar;112(4):851-62. 11. Chiu YE, Drolet BA, Blei F, et al. Variable response to propranolol treatment of kaposiform hemangioendothelioma, tufted an- gioma, and Kasabach-Merritt phenomenon. Pediatr Blood Cancer 2012;59(5):934-8. 12. Kai L, Wang Z, Yao W, Dong K, Xiao X. Sirolimus, a promising treatment for refractory Kaposiform hemangioendothelioma. J Cancer Res Clin Oncol 2014;140(3):471-76. 13. Hermans DJ, van Beynum IM, van der Vijver RJ, et al. Kaposiform hemangioendothelioma with Kasabach-Merritt syndrome: a new indication for propranolol treatment. J Pediatr Hematol Oncol 2011;33(4):171-73. 14. Haisley-Royster C, Enjolras O, et al. Kasabach-Merritt phenom- enon: a retrospective study of treatment with vincristine. J Pediatr Hematol Oncol 2002;24(6):459-62. 15. Monagle P, Chalmers E, Chan A, et al. Antithrombotic therapy in neonates and children: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133(6Suppl):887S–968S. our protocol, antiaggregant therapy (aspirin and ticlopidine) in combination with vincristine is used as primary treatment for KMP associated with KHE (VAT therapy). This therapy is continued until normal platelet count is obtained; then, vincristine is generally discontinued and antiaggregant agents are continued, although the optimal duration of treatment has not been defined. The interest of the case lies in the benefit of the early management of KHE complicated by KMP, avoiding the use of corticosteroids and allowing the administration of fewer doses of vincristine. However, some discussion should be highlighted; early referral of patients with KHE to centers with expertise in vascular anomalies is uncommon and diag- nosis is delayed in most of the cases. Also, there are poten- tial side effects associated with early treatment in younger patients. Vincristine may cause neuropathy and antiaggregant agents may cause bleeding. Chronic use of aspirin has been associated with the development of Reye syndrome, but the current recommendation is to discontinue the use of aspirin only during suspected influenza or varicella infections [15]. References 1. Zukerberg LR, Nickoloff BJ, Weiss SW. Kaposiform hemangio- endothelioma of infancy and childhood. An aggressive neoplasm associated with Kasabach-Merritt syndrome and lymphangioma- tosis. Am J Surg Pathol 1993;17:321-28. 2. Sarkar M, Mulliken JB, Kozakewich HP, Robertson RL, Burrows PE. Thrombocytopenic coagulopathy (Kasabach-Merritt phe- nomenon) is associated with kaposiform hemangioendothelioma and not with common infantile hemangioma. Plast Reconstr Surg 1997;100:1377-86. 3. Kelly M. Kasabach-Merritt phenomenon. Pediatr Clin North Am 2010;57:1085–89. 4. Sarkar M, Mulliken JB, Kozakewich HPW, et al. Thrombocy- topenic coagulopathy (Kasabach-Merritt 129 phenomenon)