Abstract
BACKGROUND: Slow-flow vascular malformations such as multifocal or extensive venous (VM), venous-lymphatic (VLM), capillary-venous (CVM) and capillary-lymphatic-venous malformations (CLVM), are commonly associated with spontaneous thrombosis and thrombolysis, a phenomenon termed localized intravascular coagulopathy (LIC). LIC is characterized by elevated D-dimer, low fibrinogen, and/or mild thrombocytopenia and may progress to disseminated intravascular coagulopathy. Individuals with LIC are at an increased risk for hematological complications, particularly when undergoing surgical procedures on or near the vascular malformation. The pathogenesis of this coagulopathy is unknown but thought to be secondary to slow blood flow, consumption of coagulation factors, abnormal endothelium and loss of protective anticoagulant factors. The exact mechanism of dysregulation of the coagulation pathway and the resultant hematologic complications remains largely unstudied. Furthermore, many institutions are empirically using peri-procedural LMWH in attempt to decrease morbidity in individuals with LIC despite supportive evidence. This work will be the largest retrospective study investigating post-procedural hematologic complications in children and young adults with vascular malformations as only case reports and series have been published to date.
METHOD: Retrospective chart review was conducted of medical records of adult and pediatric patients with slow-flow vascular malformations with LIC who underwent a surgical intervention and/or sclerotherapy procedure at Cincinnati Children's Hospital Medical Center from 7/1/2008 to 12/31/2016. LIC was defined by high D-dimer (5 times upper limit of normal), fibrinogen <150mg/dL and/or platelet count <150K/mcL. Hematologic complications included any clinically relevant bleeding or clotting abnormality that occurred intra-operatively, 2 weeks post-procedure and/or while on LMWH prophylaxis, up to 2 weeks, prior to surgery. Use of LMWH including dose, frequency and course length was evaluated.
RESULTS: Thirty-nine patients with slow-flow vascular malformations with associated LIC (24 with extensive VM/VLM, 9 with multiple VM/VLM, 4 with CLVM, 2 with localized VM/VLM) underwent a total of 236 sclerotherapy procedures with 86% occurring in individuals under 18 years of age. At our institution, LMWH was administered at 0.5mg/kg/dose once daily for 2 weeks before and after sclerotherapy in 87% of sclerotherapy cases. No thrombotic complications occurred in children. One adult patient on LMWH at treatment dosing developed pulmonary emboli (PE), presumably from deep vein thrombosis (DVT) of the treated extremity; the patient was a known smoker with a history of DVT/PE. In 5 patients fibrinogen levels dropped below 100 mg/dL post-sclerotherapy for which cryoprecipitate was administered and no bleeding complications occurred. No intra-op bleeding or thrombotic events occurred.
Total of 104 patients with slow flow malformations underwent 265 procedures represented by all major surgical subspecialties, excluding sclerotherapy. Twenty-seven (26%) of these patients had evidence of LIC prior to surgery. Eight significant bleeding episodes and 3 thrombotic events occurred; seven (64%) of which occurred in patients with known LIC. Two patients had both a clotting and hemorrhagic event. Although complications occurred similarly in both children and adults, 100% of the hematogic complications occurred in patients with extensive combined vascular malformations , most with venous ectasias. The dosing, course length and frequency of LMWH use was highly variable among patients undergoing surgery.
CONCLUSIONS: Prophylactic LMWH use was common in this patient population and did not appear to increase the risk of significant bleeding before, during or after sclerotherapy. Thrombotic events after sclerotherapy appear rare but may still occur. In patients with known LIC, attempts to correct coagulation abnormalities should be made prior to undergoing major surgical interventions. Further studies evaluating peri-procedural LMWH are needed to determine benefit and optimal dosing. Collaborative plans exist to combine data with Boston Children's Hospital so that future studies will allow for comparative effectiveness analysis of LMWH use at different doses in this patient population.
No relevant conflicts of interest to declare.
