Treatment of the Kasabach-Merritt syndrome with pegylated recombinant human megakaryocyte growth and development factor in mice: Elevated platelet counts, prolonged survival, and tumor growth inhibition

Henk M W Verheul, Dipak Panigrahy, Evelyn Flynn, Herbert M. Pinedo, Robert J. D'Amato

Research output: Contribution to journalArticle

Abstract

Kasabach-Merritt Syndrome (KMS) is seen in children with large vascular tumors. KMS is characterized by very low platelet counts and a consumption of coagulation factors causing life-threatening complications. It has been proposed that thrombopenia in these patients is caused by intratumoral trapping of platelets. The truncated form of the cMp1-receptor ligand thrombopoietin, pegylated human megakaryocyte growth and development factor (Peg-rHuMGDF), is an agent that stimulates platelet production. We hypothesized that stimulation of the platelet production would prevent the life-threatening complications of patients with KMS owing to low platelet counts. In a mouse model of KMS, with tumors derived from a hemangioendothelioma cell line, we studied the effect of Peg-rHuMGDF. Treatment with Peg-rHuMGDF (10 μg/kg/day intraperitoneally) increased platelet counts by 7-8-fold compared with control tumor-bearing mice after 11 d of treatment (p <0.001, n = 8). Survival was significantly increased, with 50% of treated animals alive at 1 mo versus 0% in untreated controls. Interestingly, we also observed an inhibition of tumor growth by 75% (p <0.001, n = 8). Hematoxylin and eosin staining showed fresh fibrin clots in the treated tumors, suggesting that higher platelet counts caused intravascular thrombosis of tumor vessels. We conclude that increased platelet production in this model of KMS resulted in an antivascular tumor effect via platelet trapping. Further, we propose that thrombopoietin may be of critical value in preventing life-threatening complications from KMS.

Original languageEnglish (US)
Pages (from-to)562-565
Number of pages4
JournalPediatric Research
Volume46
Issue number5
StatePublished - Nov 1999
Externally publishedYes

Fingerprint

Kasabach-Merritt Syndrome
Platelet Count
Survival
Blood Platelets
Growth
Neoplasms
Thrombopoietin
Therapeutics
Thrombopoietin Receptors
Hemangioendothelioma
Blood Coagulation Factors
Hematoxylin
Eosine Yellowish-(YS)
polyethylene glycol-recombinant human megakaryocyte growth and development factor
Fibrin
Thrombocytopenia
Blood Vessels
Thrombosis
Staining and Labeling
Ligands

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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Treatment of the Kasabach-Merritt syndrome with pegylated recombinant human megakaryocyte growth and development factor in mice : Elevated platelet counts, prolonged survival, and tumor growth inhibition. / Verheul, Henk M W; Panigrahy, Dipak; Flynn, Evelyn; Pinedo, Herbert M.; D'Amato, Robert J.

In: Pediatric Research, Vol. 46, No. 5, 11.1999, p. 562-565.

Research output: Contribution to journalArticle

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abstract = "Kasabach-Merritt Syndrome (KMS) is seen in children with large vascular tumors. KMS is characterized by very low platelet counts and a consumption of coagulation factors causing life-threatening complications. It has been proposed that thrombopenia in these patients is caused by intratumoral trapping of platelets. The truncated form of the cMp1-receptor ligand thrombopoietin, pegylated human megakaryocyte growth and development factor (Peg-rHuMGDF), is an agent that stimulates platelet production. We hypothesized that stimulation of the platelet production would prevent the life-threatening complications of patients with KMS owing to low platelet counts. In a mouse model of KMS, with tumors derived from a hemangioendothelioma cell line, we studied the effect of Peg-rHuMGDF. Treatment with Peg-rHuMGDF (10 μg/kg/day intraperitoneally) increased platelet counts by 7-8-fold compared with control tumor-bearing mice after 11 d of treatment (p <0.001, n = 8). Survival was significantly increased, with 50{\%} of treated animals alive at 1 mo versus 0{\%} in untreated controls. Interestingly, we also observed an inhibition of tumor growth by 75{\%} (p <0.001, n = 8). Hematoxylin and eosin staining showed fresh fibrin clots in the treated tumors, suggesting that higher platelet counts caused intravascular thrombosis of tumor vessels. We conclude that increased platelet production in this model of KMS resulted in an antivascular tumor effect via platelet trapping. Further, we propose that thrombopoietin may be of critical value in preventing life-threatening complications from KMS.",
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