Back To Search Results

Kasabach-Merritt Syndrome

Editor: Ruben Vaidya Updated: 7/17/2023 9:12:30 PM

Introduction

Kasabach-Merritt phenomenon (KMP), first described in 1940, is a rare but life-threatening coagulopathy of infancy which presents with thrombocytopenia, microangiopathic hemolytic anemia, and consumptive coagulopathy in the setting of a rapidly enlarging vascular tumor. It is exclusively associated with the vascular tumors kaposiform hemangioendothelioma (KHE) and tufted angioma (TA), which exist along the same neoplastic spectrum. Treatment includes supportive therapy and management of the underlying tumor.[1][2][3][4]

Etiology

Register For Free And Read The Full Article
Get the answers you need instantly with the StatPearls Clinical Decision Support tool. StatPearls spent the last decade developing the largest and most updated Point-of Care resource ever developed. Earn CME/CE by searching and reading articles.
  • Dropdown arrow Search engine and full access to all medical articles
  • Dropdown arrow 10 free questions in your specialty
  • Dropdown arrow Free CME/CE Activities
  • Dropdown arrow Free daily question in your email
  • Dropdown arrow Save favorite articles to your dashboard
  • Dropdown arrow Emails offering discounts

Learn more about a Subscription to StatPearls Point-of-Care

Etiology

KMP occurs exclusively as a complication of KHE and TA, which are rare, benign vascular tumors that typically present in infancy.[5] KHE and TA are classified as having intermediate malignant potential as they are locally aggressive but are not known to metastasize.[6][7][8]

Epidemiology

While the precise incidence of KHE and TA are not known, they are noted to be rare and estimated to be 0.07/100,000 in one article based on observed cases at a large center.[9] However, KMP may affect up to 70% of all patients with KHE and up to 10% of patients with TA.[10][5][9][11] Both genders and all ethnicities appear to be affected equally. Tumors typically present in early infancy, with a mean age of diagnosis in one case series of 2 months.[9] Rarely KHE may present in adulthood, and in adulthood is typically not associated with KMP.

Pathophysiology

Both KHE and TA have a convoluted vascular architecture that likely contributes to the pathophysiologic mechanisms of KMP. It is theorized platelets become trapped in the lesion, leading to platelet activation and fibrinogen consumption.[5][12] This theory is supported by positive immunohistochemistry staining for the platelet marker CD61 within the vascular lumen of lesions, as well as localized consumption of radiolabeled fibrinogen.[5] It is noted that the risk of KMP increases with increasing depth of the lesion and with intrathoracic or retroperitoneal involvement.[9]

The morbidity and mortality of KMP are high with reported mortality up to 30%.[10][13][5] Death usually occurs from life-threatening hemorrhage, cardiac failure, or invasion of the underlying vascular lesion into local structures. Retroperitoneal lesions are associated with increased mortality, potentially due to delay in diagnosis.

Histopathology

KHE and TA have similar histopathologic features but differ in their clinical behavior. KHE is locally aggressive and may involve multiple tissue planes; whereas, TA is benign and typically confined to a single tissue plane.[10] They both arise from capillary and lymphatic endothelium and are notable for their convoluted vascular architecture. Both have identical histopathologic staining, including staining positive for D2-40, LYVE1, Prox-1, and negative for GLUT-1. Because of this KHE and TA are thought to exist on the same neoplastic spectrum.[10][5]

History and Physical

KHE typically presents as an enlarging, firm, purpuric cutaneous or soft tissue lesion. It may be indurated, with a pebbly texture and poorly defined margins. KHE may involve the trunk, extremities, or retroperitoneum. Up to 10% of all KHE cases are not cutaneous.[5] TA is typically described as a series of violaceous macules and papules and usually involves the trunk. Both lesions may be associated with overlying hypertrichosis or hyperhidrosis.

Infants affected by KMP who have cutaneous involvement of KHE or TA will present with a rapidly enlarging pre-existing lesion that becomes tense, purpuric, or ecchymotic, is markedly painful. The swelling may be dramatic. Of note, if the lesion involves the retroperitoneum, the enlarging lesion may not be readily apparent on physical exam.

Evaluation

Diagnosis of KMP requires laboratory evaluation and identification of an underlying vascular tumor. Laboratory evaluation should include a complete blood count, coagulation panel, and PTT and PTT. Thrombocytopenia may be severe. Coagulation studies will reveal a prolonged PT and PTT, hypofibrinogenemia, and increased D-dimer. [11][5]

When identifying the underlying, cutaneous lesion, physical examination may be sufficient. If a visceral tumor is suspected, further imaging such as MRI may be useful in establishing both the presence of the tumor and its local extent. MRI may show significant gadolinium enhancement with dermal and subcutaneous thickening. [10][11]Biopsy of the suspected underlying lesion should be considered to establish the identity of the underlying lesion but is typically not possible if KMP is already present due to the risk of bleeding.

Treatment / Management

Treatment of KMP is largely supportive and aimed at preventing life-threatening complications while addressing the underlying tumor. While the thrombocytopenia of KMP may be profound, life-threatening hemorrhage is, in fact, rare, and platelet transfusion is not recommended except in the cases of active bleeding. Transfused platelets may become trapped in the tumor and lead to further abnormal coagulation, worsening KMP. [5] Symptomatic anemia should be treated with red blood cell transfusion. In cases of bleeding or as preparation for surgery, cryoprecipitate may be administered.[14][15][16](B3)

Treatment of the underlying tumor is critical in KMP. Surgery is the definitive management for both KHE and TA. However, it is often not possible given ill-defined tumoral borders and the invasion of multiple tissue planes and local structures. Furthermore, once KMP develops, surgery is inadvisable given the hemodynamic risks. Embolization may be possible if a single feeding vessel is present. However, tumors usually have multiple feeding vessels. Embolization also carries the risk of necrosis of local structures. Radiation therapy can induce regression, however, carries the risk of developmental delay, growth delay, and secondary malignancy. [5][17][18](B3)

Multiple medical therapies have demonstrated promise in the treatment of KHE and TA. Historically steroids are typically first-line treatment. For patients who respond, clinical response is usually seen within 2 weeks, after which steroids should be tapered slowly.[13][17] If regression cannot be achieved, seen in approximately one-third of patients, vincristine and mTOR inhibitors such as sirolimus may be used. In 2013 the Journal of Pediatrics published expert consensus guidelines which recommended combination steroid and vincristine as first-line therapy, with steroid monotherapy recommended if vincristine is not readily available.[16](B2)

Differential Diagnosis

  • Angiosarcoma
  • Arteriovascular malformations
  • Consumption coagulopathy
  • Hemangioblastoma
  • Hepatic hemangiomas
  • Immune thrombocytopenic purpura
  • Infantile hemangioma
  • Teratoma
  • Neuroblastoma
  • Subcutaneous fat necrosis

Pearls and Other Issues

Congenital hemangiomas (CH) may also present with thrombocytopenia and a disturbed coagulation profile; however, this phenomenon is transient and distinct from KMP which is progressive and not expected to resolve spontaneously. 

Enhancing Healthcare Team Outcomes

The diagnosis and management of KMP is with an interprofessional team that includes a hematologist, radiologist, intensivist, pediatrician, nurse practitioner, and the primary care provider. Once the diagnosis is made, the treatment is largely supportive and includes prevention of life threatening complications like hemorrhage. The underlying tumor must be treated. Both surgery and embolization have been used but both carry high risk of injury to adjacent structures. In some children, radiation may induce regression of the mass, but the therapy can also lead to growth retardation and induction of secondary malignancies.

Many potent chemotherapeutic agents have been used but the response is variable and not always predictable. The outlook for most children with KMP is guarded.[10][19] (Level V)

References


[1]

Gözdaşoğlu S. Kasabach-Merritt Syndrome in an Adult: A Comment. Turkish journal of haematology : official journal of Turkish Society of Haematology. 2019 Feb 7:36(1):52-53. doi: 10.4274/tjh.galenos.2018.2018.0356. Epub 2018 Oct 22     [PubMed PMID: 30345972]

Level 3 (low-level) evidence

[2]

Ji Y, Chen S, Li L, Yang K, Xia C, Li L, Yang G, Kong F, Lu G, Liu X. Kaposiform hemangioendothelioma without cutaneous involvement. Journal of cancer research and clinical oncology. 2018 Dec:144(12):2475-2484. doi: 10.1007/s00432-018-2759-5. Epub 2018 Oct 6     [PubMed PMID: 30293120]


[3]

Ji Y, Chen S, Yang K, Xia C, Peng S. Development of Kasabach-Merritt phenomenon following vaccination: More than a coincidence? The Journal of dermatology. 2018 Oct:45(10):1203-1206. doi: 10.1111/1346-8138.14598. Epub 2018 Aug 17     [PubMed PMID: 30118141]


[4]

Schmid I, Klenk AK, Sparber-Sauer M, Koscielniak E, Maxwell R, Häberle B. Kaposiform hemangioendothelioma in children: a benign vascular tumor with multiple treatment options. World journal of pediatrics : WJP. 2018 Aug:14(4):322-329. doi: 10.1007/s12519-018-0171-5. Epub 2018 Jul 27     [PubMed PMID: 30054848]


[5]

Mahajan P, Margolin J, Iacobas I. Kasabach-Merritt Phenomenon: Classic Presentation and Management Options. Clinical medicine insights. Blood disorders. 2017:10():1179545X17699849. doi: 10.1177/1179545X17699849. Epub 2017 Mar 16     [PubMed PMID: 28579853]


[6]

Gültekin ND, Yilmaz FH, Altunhan H, Findik S, Tokgöz H, Çalişkan Ü. Coexistence of Kasabach-Merritt Syndrome and placental chorioangioma in a premature infant. Journal of neonatal-perinatal medicine. 2018:11(2):209-213. doi: 10.3233/NPM-181754. Epub     [PubMed PMID: 29991142]


[7]

Shimizu Y, Komura T, Seike T, Omura H, Kumai T, Kagaya T, Ohta H, Kawashima A, Harada K, Kaneko S, Unoura M. A case of an elderly female with diffuse hepatic hemangiomatosis complicated with multiple organic dysfunction and Kasabach-Merritt syndrome. Clinical journal of gastroenterology. 2018 Oct:11(5):411-416. doi: 10.1007/s12328-018-0871-3. Epub 2018 May 29     [PubMed PMID: 29845554]

Level 3 (low-level) evidence

[8]

Erdem Toslak I, Stegman M, Reiter MP, Barkan GA, Borys D, Lim-Dunham JE. Atypically presenting kaposiform hemangioendothelioma of the knee: ultrasound findings. Journal of medical ultrasonics (2001). 2018 Oct:45(4):653-656. doi: 10.1007/s10396-018-0878-x. Epub 2018 Apr 10     [PubMed PMID: 29637402]


[9]

Croteau SE, Liang MG, Kozakewich HP, Alomari AI, Fishman SJ, Mulliken JB, Trenor CC 3rd. Kaposiform hemangioendothelioma: atypical features and risks of Kasabach-Merritt phenomenon in 107 referrals. The Journal of pediatrics. 2013 Jan:162(1):142-7. doi: 10.1016/j.jpeds.2012.06.044. Epub 2012 Aug 4     [PubMed PMID: 22871490]

Level 2 (mid-level) evidence

[10]

Putra J, Gupta A. Kaposiform haemangioendothelioma: a review with emphasis on histological differential diagnosis. Pathology. 2017 Jun:49(4):356-362. doi: 10.1016/j.pathol.2017.03.001. Epub 2017 Apr 21     [PubMed PMID: 28438388]


[11]

Kelly M. Kasabach-Merritt phenomenon. Pediatric clinics of North America. 2010 Oct:57(5):1085-9. doi: 10.1016/j.pcl.2010.07.006. Epub 2010 Aug 21     [PubMed PMID: 20888459]


[12]

O'Rafferty C, O'Regan GM, Irvine AD, Smith OP. Recent advances in the pathobiology and management of Kasabach-Merritt phenomenon. British journal of haematology. 2015 Oct:171(1):38-51. doi: 10.1111/bjh.13557. Epub 2015 Jun 30     [PubMed PMID: 26123689]

Level 3 (low-level) evidence

[13]

Ryan C, Price V, John P, Mahant S, Baruchel S, Brandão L, Blanchette V, Pope E, Weinstein M. Kasabach-Merritt phenomenon: a single centre experience. European journal of haematology. 2010 Feb 1:84(2):97-104. doi: 10.1111/j.1600-0609.2009.01370.x. Epub 2009 Nov 3     [PubMed PMID: 19889011]

Level 2 (mid-level) evidence

[14]

Jiang RS, Zhao ZY. Multimodal treatment of Kasabach-Merritt syndrome arising from tufted angioma: A case report. Oncology letters. 2017 Jun:13(6):4887-4891. doi: 10.3892/ol.2017.6064. Epub 2017 Apr 20     [PubMed PMID: 28599491]

Level 3 (low-level) evidence

[15]

Croteau SE, Gupta D. The clinical spectrum of kaposiform hemangioendothelioma and tufted angioma. Seminars in cutaneous medicine and surgery. 2016 Sep:35(3):147-52. doi: 10.12788/j.sder.2016.048. Epub     [PubMed PMID: 27607323]


[16]

Drolet BA, Trenor CC 3rd, Brandão LR, Chiu YE, Chun RH, Dasgupta R, Garzon MC, Hammill AM, Johnson CM, Tlougan B, Blei F, David M, Elluru R, Frieden IJ, Friedlander SF, Iacobas I, Jensen JN, King DM, Lee MT, Nelson S, Patel M, Pope E, Powell J, Seefeldt M, Siegel DH, Kelly M, Adams DM. Consensus-derived practice standards plan for complicated Kaposiform hemangioendothelioma. The Journal of pediatrics. 2013 Jul:163(1):285-91. doi: 10.1016/j.jpeds.2013.03.080. Epub     [PubMed PMID: 23796341]

Level 3 (low-level) evidence

[17]

Zhou SY, Li HB, Mao YM, Liu PY, Zhang J. Successful treatment of Kasabach-Merritt syndrome with transarterial embolization and corticosteroids. Journal of pediatric surgery. 2013 Mar:48(3):673-6. doi: 10.1016/j.jpedsurg.2012.12.049. Epub     [PubMed PMID: 23480932]

Level 3 (low-level) evidence

[18]

Wang Z, Li K, Dong K, Xiao X, Zheng S. Refractory Kasabach-Merritt phenomenon successfully treated with sirolimus, and a mini-review of the published work. The Journal of dermatology. 2015 Apr:42(4):401-4. doi: 10.1111/1346-8138.12797. Epub 2015 Feb 24     [PubMed PMID: 25728547]

Level 3 (low-level) evidence

[19]

Wang H, Duan Y, Gao Y, Guo X. Sirolimus for Vincristine-Resistant Kasabach-Merritt Phenomenon: Report of Eight Patients. Pediatric dermatology. 2017 May:34(3):261-265. doi: 10.1111/pde.13077. Epub 2017 Feb 15     [PubMed PMID: 28198567]