Kaposiform Hemangioendotheliomas (KHE) and Tufted Angiomas are very complicated vascular lesions. Until recently they were both misdiagnosed as hemangiomas. These lesions are associated with a phenomenon called Kasabach - Merritt Phenomenon. This phenomenon was first described in 1940 by Kasabach and Merritt. These two practitioners reported an infant with a rapidly enlarging capillary hemangioma and thrombocytopenic purpura (a low platelet count and a very purple firm lesion). The features of this “phenomenon” include an enlarging vascular lesion, a very low platelet count (thrombocytopenia), anemia caused by destruction of red blood cells within the lesion (microangiopathic hemolytic anemia) and consumption of proteins necessary for clotting (consumptive coagulopathy). From 1940 on, this phenomenon was classified as a hemangioma with Kasabach Merritt syndrome.

In 1997, two vascular anomaly groups reported independent research studies showing that these were not true hemangiomas as was previously thought but were associated with vascular lesions pathologically diagnosed as kaposiform hemangioendotheliomas(KHE) or tufted angiomas. (Under the microscope, these lesions do not appear like typical hemangiomas). This phenomenon has been a challenge for physicians because it is very serious and has been associated with a mortality rate of 20 – 30%.

These lesions clinically appear different than hemangiomas. They commonly are found in the upper trunk and extremities, thigh, sacrum or retro peritoneum (back of the abdomen). They usually are present at birth but can appear shortly after birth. They affect both sexes equally. The tumors on MRI scans invade tissues such as the skin, and underlying tissues. They are warm, firm, indurated, purple lesions that can be tense and shiny. The majority of KHE lesions are associated with Kasabach-Merritt phenomenon but there are reports of patients with these lesions that do not have this phenomenon.

Aggressive treatment is necessary for patients that have this phenomenon. Therapy has also been recommended for patients who do not have this phenomenon because patients who receive earlier more aggressive therapy have a decreased amount of tumor mass left in later years.

A number of therapies have been reported in the treatment of Kasabach-Merritt phenomenon but none have been 100% effective. Steroids are often used as a first line therapy with varying results. If these lesions respond to steroids they do so in the first several weeks of therapy. Steroids have the advantage that they can be given by mouth but do have side effects which include delayed growth, cushingoid appearance, high blood pressure and increased risk of infection, to name a few. When steroids do not improve the condition of the patient chemotherapy agents are used.  Vincristine, Interferon, Cytoxan and Amicar are a few.

Chemotherapy agents such as cyclophosphamide, vincristine, and actinomycin have been used with variable improvement. The most promising agent has been vincristine. This is an agent that has well know but limited side effects in young children. It has to be given as an intravenous injection through a special intravenous catheter. Its main complications are constipation and jaw pain but the drug can have some other neurotoxicity. It is given once a week until an improvement is seen and then the interval of administration is increased.

Antifibrinolytic agents (e-aminocaproic acid or tranexamic acid) have been used with mixed response as well as antiplatelet agents such as aspirin or dipyridamole. These drugs are used to improve the coagulopathy (bleeding tendency).

Interferon has been used but its effectiveness also is limited. Interferon needs to be given as an injection once a day and is associated with side effects such as flu-like symptoms (fever, chills) and neurological complications. The use of Interferon is  controversial in infants.

Other medical treatments that have been used are radiation therapy, which should be used as a last resort, compression therapy, and embolization therapy.

Care by an experienced group of physicians is of vital importance. A multidisciplinary team is the optimal approach to managing these tumors.  A pediatric hematologist/oncologist is vital in the care of these patients. Not only is this physician important in the management of the drug therapy but also this physician is important in the management of the bleeding tendency of Kasabach-Merritt phenomenon. At times the administration of blood products such as platelets and red blood cells can make these tumors grow in size because of the release of certain factors.

Recently there has been a report of residual lesions (lesions that are still present) after Kasabach-Merritt phenomenon. Clinical date on 41 patients was reviewed as part of an international cooperative study. The findings revealed residual tumors not “scars” being very common in these lesions after the resolution of thrombocytopenia and coagulopathy. Usually these residual lesions do not cause any problems but there have been reports of a second episode of Kasabach-Merritt phenomenon shortly after it had appeared to resolve.

These are very complex lesions that although benign(not cancer, they do not spread to distant areas) can cause mortality and great morbidity with some limited response to therapy. Presently the standard of therapy is to start with steroid therapy and if there is no response to proceed to therapy with chemotherapy drugs such as vincristine. Research is continuing in the treatment of these lesions. It is vital that these lesions are treated by experiences care-givers.

.

References

•  Albright Al, Gartner JC, Weiner GS. Limbar cutaneous hemangiomas as indicators of teheredc spinal cords. Pediatrics:83:977-980, 1989

•  Goldberg NS , Hevert AA, Ester;u MB>Saacral hemangiomas and multiple congenital anomalies. Arch Dermatol. 122:684-687,198

•  McAtee-Smeith J, Hebert AA, Rapini RR et al. Skin lesions of the spinal axis and spinal syraphism. Arch Pediatric Adolesc Med. 148:740-748,1994

•  Reese V, Frieden IF, Paller AS, et al. The association of facial hemangiomas with Dandy-Walker and other poswterior faossa malformations. Jpediatr.122:379-384,1993

•  Frieden IF, Reese V, Cohen D. PHACE syndrome:the assiciation of posterior fassa brain malformations, hamangiomas , arterial anolmalies, coarctaion of trhe aorta and cardiac defects and eye abnormalities. Arch Dermatol. 132:307-311,1996

•  EnjolarasO, Riche Mc, Merland JJ, et al. Mangagement of alarming hemangiomsas in infancy: areview of 25 cases. Pediatrics. 85:491-498, 1990

•  Enjolras O, Wassef M, Mazoyer E, eta al. Infants with Kasabach-Kmerritt syndrome do not have “true” hemangiomas. J Pediatr .130:631-640,1997

•  Ezekowitz RA, Mulliken JB, FolkmanJ. Interferon alfa-2a therapy for life-threatening hamangiomas ofn infancy N Engl J MED .326:1456-1463, 19992

•  Hurvitz CH, Alkalay AL, Sloninsky L, et ag. Cyclopphosphamide therapy ih life-threatening vascular timors. J Pediatr.109:360-363,1986

•  Zuckerberg LR, Nickoloff BF, Weiss SW. Kaposifrom hemangioendothelioma of infancy and childhood. Am J Sug Pathol. 17:321-328,1993

11. Chang E, Boyd A, Nelson CC, et al. Sucessful treatmemt of infantile   hemangiomas with interfone alphja-2b. J pediatr Hematol Oncol. 19:”237-   244,1997

12. Hanna BD, Bernstein M. Tranexamic acid in the treatment of Kasabach-Merrtitt   syndrome in infants. Am J Pediar Hematol Oncol. 1989;11:191-195

13. Shulkin BH, Argenta LC, Cho KJ et al. Kasabach-Merritt syndrome:treatment   with wpsilin-aminocaproic acid and assessment b indium 111 platelet   scintigraphy. J pediatr.1990;117:746-749

14. Morad A, McClain K. Ogden A. the role of tranexamic acid in the treatment of   giant hemangiomas in newborns. A treatment of cavernous hemangioma with   vincristine. Ann Pharmacother.19993;27:981

15. Payarols Jp, Masferrer JP, Bellvert CG. Treatment of life-threatening infantile   hemangiomas with vincristine.Nengl J Ved.19995;333:69

16. Stahl RL, Hendersion JM, Hooks Maet al. Therapy of Kasabach-Merritt   syndrome with cryoprecipitate plus intra-arterial thromin and aminocaroic acid.   Am J Hematol. 1991;36:272-274

17. Henley JD, Danielson CFM, Rothenvberger SS et al. Kasabach-Merritt syndrome   with profound platelet support., Am J Clin Pathol. 1993;99:628-630

18. Phillips WG, Marsden JR. Kasabach-Mettitt syndrome exacerbated by platelet   transfusion.l JRSocdMEd 1993;86:231-232

19. Kaplan M, Paller AS. Clinical pearl: use of self-adhesive, compressive wraps in   the treatment of limb hemangiomas. Jam Acad Dermatol.1995;32:117-118

20. Bistolfi F, Bonacci W, Zullino E et al. Role of low-dose radiotherapy in the   multimodal treatment of Kasabach-Merritt syndrome. Radiol-Med( Torino ). 1995;   90:162-166

21. Lu. ndell M, Mattsson A, Hakulinen T et al, Breast cancer after radiotherapy for   skin hemangioma in infancy. Radiat Res 1996;145:225-230

22. Enjolras O, Mulliken JB, Wasseg M et al. Residual lesions after Kasabach-   Merritt phenomenon in 41 patients. J Am Acad Dermatol 2000; 42:225-235

NOVA PROVIDES THIS INFORMATION TO FAMILIES AS A RESOURCE. IT IS NOT INTENDED TO ENGAGE IN THE PRACTICE OF MEDICINE OR TO REPLACE THE PHYSICIAN. NOVA DOES NOT CLAIM TO HAVE MEDICAL KNOWLEDGE. NOVA DOES NOT ENDORSE ANY PARTICULAR PHYSICIAN, TREATING FACILITY OR TREATMENT PROTOCAL. IN ALL CASES NOVA AND ITS BOARD OF DIRECTORS RECOMMENDS THAT YOU SEEK THE OPINION OF A PHYSICIAN EXPERIENCED IN THE MANAGEMENT OF HEMANGIOMAS AND VASCULAR MALFORMATIONS. 

THIS WEB SITE IS OPERATED BY THE NATIONAL ORGANIZATION OF VASCULAR ANOMALIES BOARD OF DIRECTORS.  NOVA BOARD .  CONTACT WEB MASTER AT admin@mail.novanews.org.