Effect of sirolimus on coagulopathy of slow-flow vascular malformations.
hematology
hemostasis
pain
thrombosis
vascular malformations
Journal
Pediatric blood & cancer
ISSN: 1545-5017
Titre abrégé: Pediatr Blood Cancer
Pays: United States
ID NLM: 101186624
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
10
02
2019
revised:
25
05
2019
accepted:
10
06
2019
pubmed:
30
6
2019
medline:
6
2
2020
entrez:
29
6
2019
Statut:
ppublish
Résumé
Stagnant blood flow present in slow-flow vascular malformations can lead to localized intravascular coagulopathy (LIC), measured by elevated D-dimer levels, low fibrinogen, and/or thrombocytopenia. LIC can lead to localized thrombosis and/or bleeding, resulting in pain, swelling, and functional limitations. Patients with complex vascular malformations treated with sirolimus show clinical improvement in these symptoms. We hypothesized that the clinical benefits of sirolimus may correlate with improvements in coexisting LIC. A retrospective chart review was performed, including D-dimer, fibrinogen, and platelet count, in patients with slow-flow vascular malformations treated with sirolimus. Laboratory values were assessed at three time points (presirolimus, 1-3 months postsirolimus, and last clinic visit). Clinical response, as defined by decreased pain and swelling, was extracted from the record. Thirty-five patients at our vascular anomalies center had been prescribed sirolimus between 2014 and 2017. Fifteen patients (12 combined slow-flow vascular malformations and three pure venous malformations) remained after excluding patients that did not have adequate records or a venous component to their vascular malformation. Patients who did not adhere to the treatment were also excluded. All 15 had elevated D-dimer levels prior to treatment and there was a statistically significant decrease in D-dimer levels following treatment with sirolimus. Symptomatic improvement of pain and swelling was reported after 3 months of starting sirolimus in 13/15 patients. This study suggests that sirolimus improves coagulopathy in slow-flow vascular malformations, as evidenced by reduced D-dimer levels. Improvement in LIC symptoms also correlates with sirolimus-corrected coagulopathy.
Sections du résumé
BACKGROUND/OBJECTIVES
Stagnant blood flow present in slow-flow vascular malformations can lead to localized intravascular coagulopathy (LIC), measured by elevated D-dimer levels, low fibrinogen, and/or thrombocytopenia. LIC can lead to localized thrombosis and/or bleeding, resulting in pain, swelling, and functional limitations. Patients with complex vascular malformations treated with sirolimus show clinical improvement in these symptoms. We hypothesized that the clinical benefits of sirolimus may correlate with improvements in coexisting LIC.
DESIGN/METHODS
A retrospective chart review was performed, including D-dimer, fibrinogen, and platelet count, in patients with slow-flow vascular malformations treated with sirolimus. Laboratory values were assessed at three time points (presirolimus, 1-3 months postsirolimus, and last clinic visit). Clinical response, as defined by decreased pain and swelling, was extracted from the record.
RESULTS
Thirty-five patients at our vascular anomalies center had been prescribed sirolimus between 2014 and 2017. Fifteen patients (12 combined slow-flow vascular malformations and three pure venous malformations) remained after excluding patients that did not have adequate records or a venous component to their vascular malformation. Patients who did not adhere to the treatment were also excluded. All 15 had elevated D-dimer levels prior to treatment and there was a statistically significant decrease in D-dimer levels following treatment with sirolimus. Symptomatic improvement of pain and swelling was reported after 3 months of starting sirolimus in 13/15 patients.
CONCLUSION
This study suggests that sirolimus improves coagulopathy in slow-flow vascular malformations, as evidenced by reduced D-dimer levels. Improvement in LIC symptoms also correlates with sirolimus-corrected coagulopathy.
Substances chimiques
Sirolimus
W36ZG6FT64
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e27896Informations de copyright
© 2019 Wiley Periodicals, Inc.
Références
International Society for the Study of Vascular Anomalies. ISSVA classification of vascular anomalies. 2018. https://www.issva.org/classification [Accessed January 28, 2019].
di Blasio L, Puliafito A, Gagliardi PA, et al. PI3K/mTOR inhibition promotes the regression of experimental vascular malformations driven by PIK3CA-activating mutations. Cell Death Dis. 2018;9(2):45.
Dompmartin A, Ballieux F, Thibon P, et al. Elevated D-dimer level in the differential diagnosis of venous malformations. Arch Dermatol. 2009;145(11):1239-1244.
Dompmartin A, Acher A, Thibon P, et al. Association of localized intravascular coagulopathy with venous malformations. Arch Dermatol. 2008;144(7):873-877.
Zhuo KY, Russell S, Wargon O, Adams S. Localised intravascular coagulation complicating venous malformations in children: associations and therapeutic options. J Paediatr Child Health. 2017;53(8):737-741.
Dompmartin A, Vikkula M, Boon LM. Venous malformation: update on aetiopathogenesis, diagnosis and management. Phlebology. 2010;25(5):224-235.
Nakano TA, Zeinati C. Venous thromboembolism in pediatric vascular anomalies. Front Pediatr. 2017;5:158.
Ji Y, Chen S, Xiang B, et al. Sirolimus for the treatment of progressive kaposiform hemangioendothelioma: a multicenter retrospective study: sirolimus for the treatment of kaposiform hemangioendothelioma. Int J Cancer. 2017;141(4):848-855.
Adams DM, Trenor CC, Hammill AM, et al. Efficacy and safety of sirolimus in the treatment of complicated vascular anomalies. Pediatrics. 2016;137(2):e20153257.
Law BK. Rapamycin: an anti-cancer immunosuppressant? Crit Rev Oncol Hematol. 2005;56(1):47-60.
Presbitero P, Asioli M. [Drug-eluting stents do they make the difference?]. Minerva Cardioangiol. 2002;50(5):431-442.
Hage AN, Chick JFB, Srinivasa RN, et al. Treatment of venous malformations: the data, where we are, and how it is done. Tech Vasc Interv Radiol. 2018;21(2):45-54.
Boscolo E, Limaye N, Huang L, et al. Rapamycin improves TIE2-mutated venous malformation in murine model and human subjects. J Clin Invest. 2015;125(9):3491-3504.
Hammill AM, Wentzel M, Gupta A, et al. Sirolimus for the treatment of complicated vascular anomalies in children. Pediatr Blood Cancer. 2011;57(6):1018-1024.
Hammer J, Seront E, Duez S, et al. Sirolimus is efficacious in treatment for extensive and/or complex slow-flow vascular malformations: a monocentric prospective phase II study. Orphanet J Rare Dis. 2018;13(1):191.
Goines J, Li X, Cai Y, et al. A xenograft model for venous malformation. Angiogenesis. 2018;21(4):725-735.
Castel P, Carmona FJ, Grego-Bessa J, et al. Somatic PIK3CA mutations as a driver of sporadic venous malformations. Sci Transl Med. 2016;8(332):332ra42.