Treating SVT: more than just a “gut feeling”

In this issue of Blood, in the largest meta-analysis on the topic to date, Valeriani et al identify 4 clear benefits of the use of anticoagulation to treat splanchnic vein thrombosis (SVT). These include increased recanalization, decreased thrombosis progression, decreased major bleeding, and decreased mortality, providing some much needed objective evidence for the management of these events.¹ 

SVT, including thrombosis of the portal, mesenteric, splenic, or hepatic (ie, Budd-Chiari syndrome) veins, is a unique entity with a distinct natural history as compared with deep vein thrombosis (DVT) of the limbs or pulmonary embolism (PE). Although resolution of the thrombus is a hoped-for outcome, the primary goal of treatment in most cases of acute lower-extremity DVT or PE is prevention of embolization or progression of PE and the associated morbidity and mortality. In contrast, for patients with acute SVT, the primary focus is the prevention and management of the consequences of venous flow obstruction. These consequences may include mesenteric ischemia, in the case of mesenteric vein thrombosis,²  and liver failure, potentially fulminant, in the rare case of Budd-Chiari syndrome.³  Patients with splenic or portal vein thrombosis, the most common type of SVT, may experience new or worsened portal hypertension and associated sequelae, including gastric or esophageal varices.⁴  For those who may be liver transplantation candidates, obstruction of the portal vein by chronic thrombosis can also interfere with effective vascular anastomosis and even result in increased morbidity and mortality posttransplantation.⁵  As a result, recanalization of the affected vessel is a highly desired outcome for individuals with SVT. Until now, the limited scope of available data, consisting largely of observational studies with inconsistent treatments, outcomes, and findings, has left the hematologist attempting to manage these clots with little more than a gut feeling to inform their clinical judgment.

The risk of serious bleeding further complicates the management of these events, particularly in patients with underlying liver disease or new portal hypertension. The bleeding associated with gastric or esophageal varices can be catastrophic and may be intensified by thrombocytopenia and deficiencies of clotting factors. Although the abnormal coagulation of advanced liver disease does not protect against pathological thrombosis, it does complicate the management of anticoagulation. Baseline prolonged prothrombin times in those with affected synthetic function render vitamin K antagonist (VKA) management a near-Sisyphean task, and patients with clinically significant liver disease were excluded from registry trials of direct oral anticoagulants (DOACs). Parenteral anticoagulants, although perhaps easier to manage, are more invasive and objectionable to many patients. Therefore, the clinician attempting to manage SVT is left with a plethora of questions, including not only which anticoagulant is safest and most effective but whether the benefits of any anticoagulation outweigh the risks.

Valeriani et al combined and analyzed data from 97 studies including 7969 patients with SVT who used a variety of treatment strategies, including anticoagulation with VKAs, parenteral anticoagulants or DOACs, antiplatelet agents with or without anticoagulation, and no antithrombotic therapy at all. The combination of these data provides much-needed clarity regarding the benefits of anticoagulation in this population. Patients who received anticoagulation experienced higher rates of desired outcomes, including recanalization, as well as decreased rates of major bleeding and mortality. Clinicians who struggle with the decision of whether to treat SVT patients with anticoagulation should find these latter 2 findings especially reassuring.

Although imperfect and subject to bias as a result of the large number of observational studies, the results of this analysis do support the theory that the benefits of reduction in variceal and other types of bleeding, presumably related to reduced portal hypertension, outweigh the potential increase in bleeding resulting from anticoagulation. The applicability of these findings, however, is limited by the likelihood that those patients judged to be at highest risk of bleeding were overrepresented in the nonanticoagulation population. These findings also potentially support the specific use of not only low molecular weight heparin but also DOACs in the treatment of SVT. Although most outcomes were similar between anticoagulants, the superior rates of recanalization with these agents, as compared with VKAs, should be taken into consideration when selecting an anticoagulant.

The findings of Valeriani et al provide the best support to date for the use of anticoagulation in selected patients with SVT. Remaining uncertainties, including optimal type and duration of anticoagulation and identification of patients most likely to experience benefit or harm from treatment, can best be answered in randomized clinical trials, which are still needed. For now, clinicians are best advised not only to go with their gut feeling but also to consider the evidence supporting the use of anticoagulation in many of these patients.