Association of rivaroxaban and rapamycin in patients with intramuscular
venous malformations complicated with pain.
Background: In venous malformations (VM) the altered blood flow
pattern due to a dysfunctional endothelium generates a prothrombotic
state that will lead to localized intravascular coagulopathy (LIC),
noticed by D-dimer elevation, pain, swelling and functional limitation.
Rivaroxaban treatment prevents thrombin formation, preventing the
constant stimulus for angiogenesis within the VM, stabilizing its
growth, avoiding pain and allowing the antiangiogenic action of
rapamycin to be effective. Procedure: A retrospective chart
review was performed , including pediatric patients with
extensive intramuscular VM in lower limbs suffering continuous pain and
functional impotence. We evaluated laboratory values of D-dimer, pre and
post-combined rivaroxaban and rapamycin treatment, VM volume assessed on
magnetic resonance imaging (MRI), and clinical response defined by
disappeared pain. Results: Five patients were included in the
study. All of them had been multi-treated with sclerosis, endovascular
laser and pressotherapy. Pain control was barely achieved by using
anti-inflammatory drugs and low molecular weight heparin (LMWH).
Rapamycin therapy slightly decreases D-dimer values, but they barely
improved the symptoms. Despite all efforts, the clinical evolution was
unsatisfactory worsen by limiting their normal life activity. We decided
to initiate rivaroxaban therapy as a compassionate use regime with
prophylactic dosage (10 mg/daily). All patients presented normal D-dimer
levels after treatment, no side effects or bleeding episodes have been
observed, the malformation volume was significantly reduced and patients
were recovered without recurring pain episodes or functional impotence.
Conclusions: This study suggests that prophylactic dosage of
rivaroxaban in association with rapamycin improves coagulopathy in
intramuscular venous malformations by reducing D-dimer levels,
disappearing pain and reducing malformation volume.