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Agenda
Kasabach- Merrit Syndrome (KMS) Epidemiology Treatment of KMS Vincristine Action Mechanism Side effects Uses Cases
Haemangiomas are vascular lesions resulting from abnormal proliferation of blood vessels. They are the most common pediatric neoplasm.
Epidemiology
Hemangiomas are common vascular tumors that occur in as many as 2.5% of neonates. Most are benign, and 70-80% regress by age 7 years. Some hemangiomas are life threatening, one hemangioma in 300 is associated with coagulopathy
Untreated Kasabach-Merritt syndrome has a 10-37% mortality rate Incidence is slightly increased in females Infants younger than 1 year are most commonly affected
Treatment of KMS
Contd
In simple/single lesions: vascular ligation, embolization or surgical excision In diffuse or extensive disease (not amenable to the above) prednisolone 3mg/kg/d (increase to 5mg/kg/d)
Treatment of KMS
If no response and patient in extremis Vincristine 1.5mg (max. 2mg) for 4 weeks Localized radiotherapy (if accessible) Combination therapy (vincristine, cyclophosphamide, etc.) Antifibrinolytic or antiplatelet agents, i.e. tranexamic acid, amino caproic acid, pentoxifylline, ticlopodine, etc.
Vincristine
Vincristine (brand name, Oncovin), formally known as leurocristine, sometimes abbreviated "VCR.
VCR is a vinca alkaloid from the Catharanthus roseus (Madagascar periwinkle), formerly Vinca rosea and hence its name. It is a mitotic inhibitor, and is used in cancer chemotherapy.
Vincristine is created by the coupling of indole alkaloids vindoline and catharanthine in the vinca plant.
Mechanism of action
Tubulin is a structural protein that polymerizes to microtubules. The cell cytoskeleton and mitotic spindle, among other things, are made of microtubules.
Disruption of the microtubules arrests mitosis in metaphase. Therefore, the vinca alkaloids affect all rapidly dividing cell types including cancer cells, but also those of intestinal epithelium and bone marrow.
Side effects
Uses
chemotherapy regimens.
It is used in combination with prednisone to treat childhood leukemia. Vincristine is occasionally used as an immunosuppressant, for example,
in treating thrombotic thrombocytopenic purpura (TTP) or chronic idiopathic thrombocytopenic purpura (ITP).
Source: http://en.wikipedia.org/wiki/Vincristine
Case 1
Contd
A 5 month old boy was admitted to the Pediatrics department for the management of an abdominal wall mass. He was the first child of consanguineous parents, born in a private hospital following uncomplicated pregnancy and delivery. At birth a bluish birth mark 5 cm 5 cm was noted below the umbilicus. Over the next five months, this birth mark increased in size and evolved into a swelling. As a result, the patient was admitted to Maternal and Child Health (MCH) unit for the management of this swelling
The clinical findings and imagining studies followed by laboratory investigations strongly suggested the diagnosis of Kasabach-Merritt syndrome.
Case 1
Table 1 Hospital stay WBC/cmm 1st day 8000 Hb gm% 10.6 Investigations Platelet/cmm 94000 PT > 100 sec (N = 28.8) PTT > 120 sec (N = 34.8) z4th day 7th day 11900 9300 11.4 9.0 5000 4000 PT > 100 sec (N = 28.8) PTT > 120 sec (N = 34.8) 5th week 7th week 8200 10400 9.7 10.2 6000 19000 Fibrinogen = 42.3 mg/dl (N = 160350) Vincristine Fibrinogen = 19.7 mg/dl (N = 160350) Others
Contd
Relevant haematological investigations carried out during hospital stay and follow-up at outpatients' department of MCH. Treatment
Prednisolone
9th week
11th week 13th week
9500
8500 9500
9.8
10.7 11.2
45000
49000 50000 PT = 16.5 sec (N = 28.8) PTT = 34.2 sec (N = 34.8) Fibrinogen = 236 mg/dl (N = 160350) PT = 16.2 sec (N = 28.8) PTT = 27.8 sec (N = 34.8) Fibrinogen = 251 mg/dl (N = 160350) Surgery
4th
month (OPD)
10200
10.9
278000
5900
11.0
290000
Case 1
Contd
Treatment
Vincristine was initiated after a trial of corticosteroids when the platelet count was 6000/cmm.
One week after the start of vincristine the size of the lesion started to decrease. At the end of 6th week the lesion size decreased to half and the platelet count
increased to 49,000/cmm.
Vincristine was continued for another 2 weeks, no further improvement in lesion size or platelet count was observed.
Vincristine was discontinued and the patient was shifted to the pediatric surgery department. A fresh platelet transfusion was given and the haemangioma was excised completely.
Case 1
Contd
Conclusion:
Six weeks treatment with vincristine in a dose of 0.5 mg/kg/week followed by surgical excision may be the best management in selected cases of KasabachMerritt syndrome.
Case 2
syndrome
Contd
Background:
Historically, patients with the consumptive coagulopathy Kasabach-Merritt syndrome (KMS) have been treated with systemic corticosteroids as first-line
therapy, but many patients do not respond. Recently, there have been increasing
reports of the use of the chemotherapeutic drug vincristine in these patients.
Objective:
Case 2
Results:
Treatment with vincristine and corticosteroids lead to sustained shrinking of the tumor and correction of the thrombocytopenia and coagulopathy through 1 year of age. We believe this is the first report in the North American literature of corticosteroids and vincristine being used concomitantly as first-line therapy for KHE with KMS. Vincristine and corticosteroids should be considered first-line treatment for KMS.
Conclusion:
Source: http://www.ncbi.nlm.nih.gov/pubmed/19426625
Case 3
Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor and has a high mortality in newborns when associated with Kasabach-Merritt syndrome (KMS).
In two newborns with KHE and severe KMS refractory to medical treatment, emergency embolization led to clinical improvement in the acute neonatal setting by reducing tumor volume, increasing the platelet count, and improving other clotting parameters.
Systemic vincristine treatment was added for further tumor control. Both patients remained symptom-free at long-term follow-up.
Source: http://www.ncbi.nlm.nih.gov/pubmed/22365299
Case 4
Contd
A 6-year-old Latina girl with constant pain and edema in her right lower extremity, and severe thrombocytopenia was brought for treatment. Physical examination revealed a large mass in the right lower extremity.
Corticosteroid therapy in Mexico had been ineffective in controlling the tumor size, pain, or thrombocytopenia.
The patient was brought to the United States because of a rapidly enlarging tumor and intractable leg pain, causing inability to ambulate.
Case 4
Contd
Treatment:
Result:
Inoperable kaposiform hemangioendothelioma unresponsive to corticosteroids can be successfully treated with chemotherapy. After five cycles of chemotherapy problem was completely resolved. A follow-up imaging study 9 months later revealed a marked decrease in size of the
vascular tumor.
Case 4
Conclusion:
Inoperable kaposiform hemangioendothelioma unresponsive to corticosteroids can be successfully treated with chemotherapy.
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