Effect of sirolimus on coagulopathy of slow‐flow vascular malformations

Abstract

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.

Analyzing coagulation dynamics during treatment of vascular malformations with thromboelastography

“…A previous study that included 15 patients on sirolimus with slowflow vascular malformations demonstrated a significant decrease in D-dimer, suggesting that sirolimus therapy could improve the coagulopathy often seen in their disease. 20 Although we had no patient with severe LIC (definition <150 fibrinogen and D-dimer >2) in this current study, four patients were on sirolimus during the time of the procedures. This may have prevented these patients having significant changes in TEG parameters and/or bleeding/clotting complications.…”

Retrospective study of hematologic complications in patients with slow‐flow vascular malformations undergoing sclerotherapy

“…Two patients also had normalization of fibrinogen on treatment. Thirteen patients (87%) self‐reported clinical improvement, primarily with reduction of pain and swelling within one to three months of starting sirolimus 23 . Although these results are encouraging, further studies are needed to determine if targeted therapies such as sirolimus not only improve coagulation laboratory abnormalities but also short‐ and long‐term hematologic complications in individuals with SFVM.…”

Effective surgical treatment of life-threatening huge vascular anomalies associated with thrombocytopenia and coagulopathy in infants unresponsive to drug therapy

“…Pharmacological management is often the first line option to achieve hemostatic stability in KMP. According to the literature, the response time of Sirolimus is 1 day to 4 weeks for KHE and 1-3 months for vascular malformations [7] [13] [18] [19]. KHE or VMs are the main lesions that cause coagulopathy and thrombocytopenia.…”