Venous malformations: Coagulopathy control and treatment methods

Abstract

Venous malformations (VMs) are ectatic channels which arise as a result of vascular dysmorphogenesis, commonly caused by activating mutations in the endothelial tyrosine kinase receptor (TIE2)/phosphatidylinositol 3-kinase (PI3Kinase) pathway. With a prevalence of 1% in the general population, and a diverse clinical presentation depending on site, size and tissue involvement, their treatment requires a personalised and multidisciplinary approach. Larger lesions are complicated by local intravascular coagulopathy (LIC) causing haemorrhagic and/or thrombotic complications which can progress to disseminated intravascular coagulopathy (DIC). Methods We performed a literature review using a PubMed® search and identified 15 articles to include. References of these texts were examined to further expand the literature review. Principle findings: Several treatment options have been explored, including compression, sclerotherapy, laser therapy, cryoablation and surgery in addition to the management of LIC with low-molecular-weight-heparin (LMWH) and other anticoagulants. Targeted molecular therapies acting on the phosphatidylinositol 3-kinase (PI3Kinase)/Protein Kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway are newly emerging. Conclusion Despite a wealth of literature, larger, multi-centric, randomised and prospective trails are required to offer further clarification on the therapeutic management of coagulopathy control and to provide symptomatic benefit to patients with VMs. There should be efforts to provide long term follow up and to use standardised risk stratification tools and quality of life (QOL) questionnaires to aid comparison of agents and treatment protocols.

Hematologic complications in vascular malformations: A case study of 2 patients

“…Coagulopathy is common in patients with slow-flow vascular malformations, and LIC occurs in approximately 58% of patients with VMs. LIC is characterized by elevated D-dimers and fibrin degradation products (14), low levels of fibrinogen, factors V, VIII, XIII, and antithrombin, and sometimes mild to moderate thrombocytopenia. (15) LIC rarely leads to serious bleeding or severe thrombosis.…”

Interventional Treatment Options in Children with Extracranial Vascular Malformations

“…In addition, LIC increases the children's risk for intralesional thrombosis as well as the peri-interventional risk for hemorrhage. [27][28][29] VMs with LIC show all components of the Virchow's triad including abnormality of the vascular wall, stasis of blood flow, and activation of the coagulation cascade. 30 Here, a multidisciplinary approach and experienced hemostaseological management including extended coagulation function indexes, such as prothrombin time, thrombin time, activated partial thromboplastin time, international normalized ratio, fibrinogen, antithrombin, platelets, and D-dimers, as primary indicators of LIC are crucial.…”

Assessing coagulopathy and endothelial dysfunction in pediatric venous malformation: A thromboelastometry and syndecan‐1 study

“…23 Despite the identification of the initial genetic error, thrombosis phenomena are still based on Virchow's classical triad. 24,25 In this regard, different research groups have analyzed conventional coagulation parameters using extralesional blood samples 6,[26][27][28] although the use of new tools for a more complete analysis of the clot-formation process has recently been reported. 28 Viscoelastic tests allow us to quickly identify the function of different elements involved in coagulation and fibrinolysis processes, which has popularized their use in situations that require rapid response.…”

“…These advances have enabled the application of targeted therapies that inhibit hyperfunctioning signaling pathways, such as sirolimus and mTOR proteins, 20,21 alpelisib and PIK3CA proteins, 22 and rebastinib and TIE receptors 23 . Despite the identification of the initial genetic error, thrombosis phenomena are still based on Virchow's classical triad 24,25 . In this regard, different research groups have analyzed conventional coagulation parameters using extralesional blood samples 6,26–28 although the use of new tools for a more complete analysis of the clot‐formation process has recently been reported 28 .…”