Vincristine: a new treatment option for Kasabach-Merritt syndrome.
Kasabach-Merritt syndrome (KMS) is characterized by a rapidly
enlarging hemangioma, thrombocytopenia, microangiopathic hemolytic
anemia and consumption coagulopathy as a result of platelet and red
blood cell trapping and activation of clotting system within the
vasculature of hemangioma. This syndrome is shown to be associated with
kaposiform hemangioendotheliomas or tufted hemangioma.
KEY WORDS: Kasabach-Merritt Syndrome; Microangiopathic hemolytic anemia; Thrombocytopenia; Consumption coagulopathy
|Article Type:||Case study|
Hemangioma (Drug therapy)
Hemangioma (Case studies)
Vincristine (Dosage and administration)
Thrombocytopenia (Drug therapy)
Thrombocytopenia (Case studies)
|Publication:||Name: Internet Journal of Medical Update Publisher: Dr. Arun Kumar Agnihotri Audience: Academic; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2011 Dr. Arun Kumar Agnihotri ISSN: 1694-0423|
|Issue:||Date: July, 2011 Source Volume: 6 Source Issue: 2|
|Geographic:||Geographic Scope: India Geographic Code: 9INDI India|
KMS is a rare disease, usually of infants, in which a vascular tumor leads to decreased platelet counts and sometimes other bleeding problems which can be life-threatening. (1) It is also known as Hemangioma thrombocytopenia syndrome. It carries the names of Dr Haig Haigouni Kasabach and Dr Katharine Krom Merritt, the two pediatricians who first described the condition in 1940. (2) The diagnosis is based upon three basic findings; enlarging hemangioma, thrombocytopenia and consumption coagulopathy. The thrombocytopenia and consumption coagulopathy is known as Kasabach-Merritt phenomenon. (3) Untreated Kasabach-Merritt syndrome has a 10-37% mortality rate. (4)
I present a case of a 4 month old male child admitted to department of Pediatrics for the complaints of swelling on right cheek at right corner of mouth. This child was a product of full term uncomplicated pregnancy and was delivered by lower segment cesarean section. There was no history of consanguinity. According to the mother, there was a bluish purple birth mark of approximately 5cm x 5cms at the right corner of mouth at birth. This mark progressively increased in size and gradually involved whole right cheek with posterior extension up to right ear lobule. Because of this swelling the child was not able to take feeds for the last few days. The developmental milestones were normal as per age and he was on exclusive breast milk feeding. On examination it was a pink colored hemangioma of approximately 15cm x 15cm in size (Figure 1). Because of it, the child was unable to open his mouth sufficient for feeding. We started treatment with oral prednisolone (2mg/kg/day) but there was no reduction in the size of swelling after 2 weeks of therapy. During the hospital stay, one morning, the child developed bleeding from the local swelling site and also multiple petechial spots all over the body. So, coagulation profile of the child was assessed. The investigations showed platelet count - 5000/[mm.sup.3], prothrombin--more than 1 min (control--10.9 Seconds) with Prothrombin concentration < than 10% (reference range 70-130%) and APTT more than 2 minutes (control 26.05 seconds). Keeping the possibility of consumptive coagulopathy in view, the child was further investigated and this showed plasma fibrinogen less than 50 mg/dl and D-dimer levels more than 500 ng/ml. This triad of hemangioma, thrombocytopenia and consumption coagulopathy led to the diagnosis of KMS.
To control the life threatening bleeding, the patient was given 5 units of platelet transfusions, 1 unit of packed red cell transfusions and 2 units of fresh frozen plasma transfusions. After the two weeks of the conventional steroid with no therapeutic benefit, injectable Vincristine was started in dose of 0.05 mg/kg/week. At the time of initiation of Vincristine treatment, the platelet count was 9600/[mm.sup.3]. After 3 weeks of Vincristine, the platelet count increased to 1, 06,000/[mm.sup.3] along with 25% reduction in the size of swelling. Vincristine was continued for a total period of 6 weeks. After starting treatment with Vincristine, no further transfusions were required and child started breast feeding normally. At the end of chemotherapy by Vincristine for 6 weeks, there was a small lesion 6 cm x 4 cms size, which was planned for surgery later in life if it increases in size at all. The patient was followed till 1 year of age; the features of coagulopathy subsided during admission and never recurred after discharge and tumor size reduced.
For the treatment of KMS there are no consensus guidelines as it is uncommon and thus no large trials are available to guide treatment. Multiple modalities have been used by various workers including surgical excision (if possible), laser photocoagulation, high dose corticosteroids, antineoplastic agents and anti-angiogenic agent such as interferon-[alpha].
On reviewing the literature, corticosteroids are the drugs used commonly for treatment, although the results were not satisfactory. There is a case report of successful treatment of abdominal wall mass associated KMS with Vincristine along with surgery. (3) In a recently published case series of 4 cases, the authors recommend that Vincristine should be considered early in the management of KMS. (5) In another case report, the authors have successfully used Vincristine to treat a 1 month old infant with KMS. (6) In our case, we were able to treat Kasabach Merritt phenomenon along with considerable reduction in the size of swelling with Vincristine. In all the previous case reports, surgery was done in conjunction with treatment with Vincristine. We have deferred surgery at present and it is planned if on follow up the swelling again increases in size.
In addition to conventional doses, high-dose steroids, pulsed or intravenous steroids have also been used with variable results. Interferon-[alpha] (1-3 MU/[m.sup.2]/day) has been also used as initial therapy and especially in patients who do not respond to corticosteroid therapy. There is a case report of treatment of an infiltrating angiolipoma with KMS with complete disappearance of mass after 6 months treatment with interferon-[alpha]. (7) Similarly there is a case report where after the conventional doses and pulsed high doses of methylprednisolone, authors have successfully used interferon-[alpha] in a 1 month old infant with tumor regression. Radiotherapy in combination with interferon-[alpha] can also be used as a treatment modality after the failure of conventional steroid. (8) Intermittent pneumatic compression has also been used as a treatment modality to treat angiomatous nevus of leg with KMS in a 6 week old infant. (9) Pentoxifylline and Tranexamic acid have also been used to treat KMS. Komiyama et al have done endovascular treatment which constituted transfemoral embolization using polyvinyl alcohol particles and resulted in rapid clinical improvement. (10) There are some other case reports where authors have used Vincristine to treat KMS. (11-14) This treatment is used nowadays with increasing frequency. There are several case reports of successful treatment of KMS with disappearance of bleeding and shrinkage of the size of the tumor by treatment with Vincristine alone or in conjunction with some other agents as given in table 1.
Hemangioma associated with KMS is a rare entity. We found a rapid rise in platelet count following Vincristine treatment which was life-saving for the infant. Therefore, it is concluded that Vincristine is a good treatment modality for KM syndrome especially to treat the consumption coagulopathy refractory to conventional doses of steroid. In addition, Vincristine will help to reduce the size of the swelling, which can then be surgically excised.
(1.) Hall G. Kasabach-Merritt syndrome: pathogenesis and management. B J Haematol. 2001;112(4):851-62.
(2.) Kasabach HH, Merritt KK. Capillary hemangioma with extensive purpura: report of a case. Am J Dis Child. 1940;59:1063.
(3.) Abbas K, Saad H, Kherala M, et al. Successful treatment of Kasabach-Merritt syndrome with vincristine and surgery: a case report and review of literature. Cases J. 2008 May;1(1):9.
(4.) Cheerva AC, Bertolone S, Raj AB. Pediatric Kasabach-Meritt Syndrome. Drugs Diseases & Procedures. Medscape Reference. 2009 Feb; http://emedicine.medscape.com/article/956136 -overview
(5.) Thomson K, Pinnock R, Teague L, et al. Vincristine for the treatment of Kasabach-Merritt syndrome: recent New Zealand case experience. N Z Med J. 2007 Feb;120(1249):U2418.
(6.) Hara K, Yashida T, Kajiume T, et al. Successful treatment of Kasabach-Merritt syndrome with Vincristine and diagnosis of haemangioma using three dimensional imaging. Pediatr hematol Oncol. 2009 Jul Aug;26(5):375-80.
(7.) Akyuz C, Emir S, Buyukpamuku M, et al. Successful treatment with interferon alfa in infiltrating angiolipoma: a case presenting with Kasabach-Merritt syndrome. Arch Dis child. 2003 Jan;88(1):67-8.
(8.) Hesselmann S, Micke O, Marquardt T, et al. Case report: Kasabach-Merritt syndrome: a review of the therapeutic options and a case report of successful treatment with radiotherapy and interferon alpha. Br J Radiol. 2002 Feb;75(890):180-4.
(9.) Aylett SE, Williams AF, Bevan DH, et al. The Kasabach-Merritt syndrome: treatment with intermittent pneumatic compression. Arch Dis Child. 1990 Jul;65(7):790-1.
(10.) Kamiyama M, Nakajima H, Kitano S, et al. Endovascular treatment of huge cervicofacial hemangioma complicated by Kasabach-Merritt syndrome. Pediatric Neurosurg. 2000 Jul;33(1):26-30.
(11.) Lopez V, Marti N, Pereda C, Martin JM, et al. Successful management of Kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon using vincristine and ticlopidine. Pediatr Dermatol. 2009 May-Jun;26(3):365-6.
(12.) Drucker AM, Pope E, Mahant S, et al. Vincristine and corticosteroids as first-line treatment of Kasabach-Merritt syndrome in kaposiform hemangioendothelioma. J Cutan Med Surg. 2009 May-Jun;13(3):155-9.
(13.) Hu B, Lachman R, Phillips J, et al. Kasabach-Merritt syndrome-associated kaposiform hemangioendothelioma successfully treated with cyclophosphamide, vincristine, and actinomycin D. J Pediatr Hematol Oncol. 1998 Nov-Dec;20(6):567-9.
(14.) Haisley-Royster C, Enjolras O, Frieden IJ, et al. Kasabach-Merritt phenomenon: a retrospective study of treatment with vincristine. J Pediatr Hematol Oncol. 2002 Aug-Sep;24(6):459-62.
Shalini Avasti ([PSI]) MD
Lecturer, Department of Pediatrics, Era,s Medical College, Lucknow, Uttar Pradesh, India
(Received 17 May 2010 and accepted 24 July 2010)
([PSI]) Correspondence at: Department of Pediatrics, Era,s Medical College, Lucknow, Uttar Pradesh, India; Email: email@example.com
Table 1: Treatment modalities used in conjunction of Vincristine Studies Age of patient No. of patient Hu et al (13) Six year 1 (1998) Komiyama et 2 months 1 al (10) (2000) Haisley- 15 Royster et al (14) (2002) Thomson et Birth--11 4 al (5) (2007) months Abbas et al (3) 5 months 1 (2008) Hara et al (6) 1month 1 (2009) Lopez et al (11) Newborn 1 (2009) Drucker AM Newborn 1 et al (12) (2009) Present 4 months 1 Study Studies Lesion location Hu et al (13) Right leg (1998) Komiyama et Cervicofacial- al (10) (2000) Causing airway compromise Haisley- Five- kaposiform Royster et hemangioendotheliomas, al (14) 3 tufted angiomas, 1 (2002) both kaposiform hemangioendothelioma Thomson et al (5) (2007) Abbas et al (3) Abdominal wall mass (2008) Hara et al (6) Cutaneous Right axilla (2009) Lopez et al (11) Skin (2009) Drucker AM Right leg et al (12) (2009) Present Right Cheek Study Studies Other/ancillary treatment Outcome Hu et al (13) Vincristine 9 months (1998) Actinomycin follow up Cyclophosphamide decrease in size of tumor Komiyama et Vincristine with Rapid clinical al (10) (2000) transfemoral improvement embolization & patency of airway Haisley- Vincristine In 13 patients' Royster et significant al (14) decrease in (2002) size of lesion, 4 relapsed. Thomson et Vincristine Regression of al (5) (2007) mass Abbas et al (3) Vincristine with Excised (2008) surgery completely Hara et al (6) Vincristine with Regression of (2009) Corticosteroid mass Lopez et al (11) Vincristine with Progressive (2009) Ticlopedine remission Drucker AM Vincristine with Tumour et al (12) (2009) Corticosteroid shrinkage- 1 yr of age Present Vincristine 6 weeks follow Study up--decrease in tumor size
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