KASABACH-MERRIT SYNDROME

19th Sep 2013

Agenda

Kasabach- Merrit Syndrome (KMS) Epidemiology Treatment of KMS Vincristine Action Mechanism Side effects Uses Cases

Kasabach- Merrit Syndrome (KMS)

Combination of haemangioma, thrombocytopenia and coagulopathy is termed as kasabach- merrit syndrome

Haemangiomas are vascular lesions resulting from abnormal proliferation of blood vessels. They are the most common pediatric neoplasm.

Kasabach-Merritt syndrome is a rare type of vascular lesion with peculiar characteristics.

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

Two types of therapies available are;

First line Second line

First line therapy:

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

Second line or adjuvant therapies;

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.

Experimental therapies (as they become available)

Pulse laser therapy (for cutaneous lesion)

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.

Vincristine binds to tubulin dimers, inhibiting assembly of microtubule structures.

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

Peripheral neuropathy Hyponatremia Constipation Hair loss

Uses

Vincristine is delivered via intravenous infusion for use in various types of

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).

Treatment for nephroblastoma (Wilms tumor, a kidney tumor)

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

8th month (OPD)

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

Vincristine and corticosteroids as first-line treatment of Kasabach-Merritt

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:

To report a case of a newborn with a kaposiform hemangioendothelioma (KHE)

of the right leg associated with KMS treated successfully with vincristine and oral corticosteroids.

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.

Laboratory examinations revealed profound thrombocytopenia and evidence of consumptive coagulopathy.

Case 4

Contd

Treatment:

Six cycles of a chemotherapy regimen consisting of vincristine, cyclophosphamide, and actinomycin D

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.

Thank You