Vascular Liver Disorders, Portal Vein Thrombosis, and Procedural Bleeding in Patients With Liver Disease

Publication Date: November 19, 2020
Last Updated: August 19, 2022

Guidance Statements

Current Understanding of Coagulation and Hemostasis in Cirrhosis

Simultaneous changes in procoagulant and anticoagulant pathways in patients with cirrhosis result in complex hemostatic changes that are not adequately captured by traditional laboratory measures of hemostasis, such as PT, aPTT, and platelet count.
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Distinct hypercoagulable and hypocoagulable features may be present simultaneously in an individual patient and may contribute to thrombosis or bleeding, respectively.
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Global tests of hemostasis, such as thrombin generation or whole‐blood viscoelastic tests, better capture the general hemostatic status of a patient with cirrhosis, but have not been clinically validated.
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Examples of Common Procedure Risk Assessment in Patients With Cirrhosis

Determining procedural bleeding risk is complex and requires collaboration between specialists to determine the level of bleeding risk before procedures and aid in periprocedural hemostasis management.
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Because of conflicting data in the literature, there is no data‐driven specific INR or platelet cutoff in which procedural bleeding risk is reliably increased.
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Identification and correction of modifiable risk factors for bleeding before performing procedures, particularly high‐risk elective procedures, is recommended. Such risk factors include the use of antithrombotic drugs, AKI, and infection.
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Platelet Interventions and Therapies Targeting Primary Hemostasis

Given the low risk of bleeding of many common procedures, potential risks of platelet transfusion, lack of evidence that elevating the platelet count reduces bleeding risk, and ability to use effective interventions, including transfusion and hemostasis if bleeding occurs, it is reasonable to perform both low‐ and high‐risk procedures without prophylactically correcting the platelet count.
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An individualized approach to patients with severe thrombocytopenia before procedures is recommended because of the lack of definitive evidence for safety and efficacy of interventions intended to increase platelet counts in patients with cirrhosis.
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Coagulation Interventions and Therapies Targeting Procoagulant Factor Deficiencies

The INR should not be used to gauge procedural bleeding risk in patients with cirrhosis who are not taking vitamin K antagonists (VKAs).
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Measures aimed at reducing the INR are not recommended before procedures in patients with cirrhosis who are not taking VKAs.
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FFP transfusion before procedures is associated with risks and no proven benefits.
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Fibrinogen and Therapies Targeting Excessive or Inappropriate Fibrinolysis

Low fibrinogen levels have been associated with increased bleeding risk in critically ill patients with cirrhosis.
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Cryoprecipitate and fibrinogen factor replacements are low‐volume products effective at increasing fibrinogen levels.
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Portal Vein Thrombosis

In any patient with PVT, a standardized documentation of initial site, extent, degree of luminal obstruction, and chronicity of clot formation is recommended in order to make objective serial assessments of spontaneous regression or treatment response.
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PVT Prevalence and Risk Factors: Patients With Cirrhosis

In patients with cirrhosis, it is mandatory to rule out malignant venous obstruction attributable to HCC with appropriate contrast‐enhanced imaging studies.
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In patients with cirrhosis, an extensive evaluation for thrombophilic conditions is not necessary unless family history or routine laboratory testing raises other concerns.
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In patients without cirrhosis who have thrombosis of the portal venous system without a clear provoking factor, a full investigation for myeloproliferative disorders or another thrombophilic condition is warranted, usually in consultation with a hematologist.
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Influence of PVT on Mortality in Patients With Cirrhosis

Outside of LT candidates, it is unknown whether PVT in an individual patient with cirrhosis is merely a reflection of progressive portal hypertension or independently causative of increased mortality.
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In LT recipients, the presence of PVT at the time of transplant is associated with increased posttransplant mortality.
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There are insufficient data to recommend pretransplant treatment of PVT with the goal of improving posttransplant outcomes.
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Goals of Therapy and Rationale for Treatment: Patients With Cirrhosis

In all patients with recent PVT and concern for intestinal ischemia, immediate consultation with surgery, critical care, interventional radiology, and hematology is advised. Anticoagulation is essential, with the need for surgery in cases of intestinal infarction.
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In patients without cirrhosis and with recent PVT, directed antithrombotic therapy should be considered in order to avoid intestinal ischemia and prevent the development of chronic PVT with portal hypertension.
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In patients with cirrhosis, existing clinical trial data are weak regarding treatment indications for PVT without ischemic symptoms. Treatment should be considered on a case‐by‐case basis. Decisions for treatment of an individual patient should be based on expected benefit and minimization of clot extension risk that could potentially lead to progression of portal hypertension or hinder LT.
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In patients with cirrhosis who have recent thrombosis of small intrahepatic sub‐branches of the PV or minimally occlusive (<50% obstruction of the lumen) thrombosis of the main PV, observation with serial imaging every 3 months without therapy is reasonable. Treatment for progressive clot should then be considered in this setting.
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In patients with cirrhosis with recent occlusive or partially occlusive (>50% obstruction of the lumen) thrombosis of the main PV or mesenteric veins, antithrombotic therapy should be considered to avoid thrombosis progression that may hinder a future LT or cause progression of portal hypertension.
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In patients with chronic complete occlusion of the main PV or cavernous transformation of the PV with established collaterals, there is no established benefit of anticoagulant or interventional therapy, and treatment should be targeted at management of portal hypertension complications.
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Data suggest that EVL can be performed safely without stopping therapeutic anticoagulation. Based on the available safety data, anticoagulation should be initiated as soon as possible and not delayed until variceal eradication or adequate beta‐blockade is achieved.
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PVT Treatment Options

Local or systemic thrombolytic therapy should only be considered in very selected cases of recent PVT in whom intestinal ischemia persists despite anticoagulation.
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PVR followed by TIPS should be considered in LT candidates with chronic PVT that hinders a physiological anastomosis between the graft and recipient PV. This decision is made as part of a multidisciplinary management process, including surgical and interventional radiology expertise.
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PVR followed by TIPS should be considered in patients with chronic PVT and recurrent bleeding and/or refractory ascites not manageable medically or endoscopically.
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Direct Oral Anticoagulants

The choice of agent for anticoagulant therapy (LMWH, VKAs, and DOACs) in PVT should be individualized. Consultation with a hematologist and/or expert hepatologist should be considered in deciding on anticoagulant agents and duration.
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Therapeutic anticoagulation in patients with cirrhosis appears to have similar non‐portal hypertensive bleeding complication rates compared to the general population. Portal hypertension–related bleeding in patients with cirrhosis appears unchanged by the use of anticoagulants.
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DOACs are emerging as a common therapy for general medical patients with thrombosis. PVT data remain limited regarding safety and efficacy of these agents in patients with and without cirrhosis. In patients with cirrhosis, caution is advised in patients with advanced portal hypertension, and expert consultation is recommended.
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Hepatic Vein Thrombosis: Budd‐Chiari Syndrome

HVT‐BCS should be considered in any patient with liver disease (recent or chronic) of unknown etiology. Suspicion should be even higher in a patient with a recognized prothrombotic disorder.
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Doppler ultrasound, performed by an experienced operator, is the first‐line imaging study for HVT/BCS. MR or CT can be used for diagnosis confirmation and interventional planning.
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At the time of HVT/BCS diagnosis, an full thrombophilia workup is recommended, and even when one causal factor is identified, additional factors should be investigated. Consultation with a hematologist is recommended.
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Surveillance for HCC in patients with chronic HVT/BCS is recommended as in the general cirrhosis population, with ultrasound every 6 months with or without alpha‐fetoprotein determination. Because of the perturbed vascularity of the liver, HCC diagnosis in these patients should not rely on imaging criteria alone and should require histological confirmation.
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A progressive “step‐up” therapeutic strategy according to the clinical response from less to more invasive therapies is recommended for HVT/BCS. Early referral to tertiary care centers with expertise in this disorder is recommended.
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All patients with HVT/BCS, even in the absence of a recognized prothrombotic disorder, should receive therapeutic anticoagulation.
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TIPS or DIPS using PTFE‐covered stents is the treatment of choice for HVT/BCS when medical therapy or angioplasty fail or are not feasible. Surgical shunts should only be considered if TIPS/DIPS is not feasible or fails.
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LT is reserved for HVT/BCS patients in whom the medical and vascular interventional approaches fail. LT may be the first step in patients with acute liver failure. In this situation, TIPS/DIPS should be considered while waiting for transplant because it may improve liver function and potentially avoid the need for transplantation.
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Sinusoidal Obstruction Syndrome

SOS should be considered in patients in the appropriate clinical setting, typically 1‐3 weeks after HSCT, with onset of right upper quadrant pain, weight gain attributable to edema, hepatomegaly, and ascites.
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Ursodeoxycholic acid is recommended as prophylactic therapy for SOS in all patients undergoing allogeneic HSCT. The suggested dose is 12 mg/kg divided in two doses starting the day before conditioning and continuing for 3 months after HSCT.
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Defibrotide is the only FDA‐approved treatment for SOS and is recommended for treatment of moderate‐to‐severe SOS. The benefit in prophylaxis in high‐risk cases is not established.
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TIPS is unproven in SOS and cannot be recommended for this indication based on available evidence.
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Liver Vascular Malformations and Hereditary Hemorrhagic Telangiectasia

LVMs associated with HHT should be suspected in the presence of a liver bruit and a CT scan or MR with enlarged HA and heterogeneous enhancement of the liver, particularly in the setting of a family or personal history of recurrent nosebleeds, heart failure, unspecified liver disease, or brain hemorrhage.
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Asymptomatic LVMs do not warrant therapy or imaging surveillance.
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Management of symptomatic LVMs consists of standard therapy of specific complications, including heart failure, portal hypertension, and biliary ischemia.
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Symptomatic patients should be managed at a specialized center with a multidisciplinary team. In this setting, consideration for the use of bevacizumab and/or LT is warranted in nonresponders to standard therapy.
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Idiopathic Noncirrhotic Portal Hypertension

INCPH should be considered in any patient with evidence of portal hypertension but without cirrhosis or other known causes of noncirrhotic portal hypertension.
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Liver biopsy is required to exclude cirrhosis and may show specific histological changes. A reticulin stain may be helpful for histological diagnosis, and referral to specialized liver pathologists is recommended.
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In patients with INCPH, underlying risk factors for venous thrombosis, immune disorders, and inherited disorders known to be associated with this condition should be routinely considered.
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PVT may be more frequent in INCPH compared to patients with cirrhosis, but routine screening for PVT cannot be recommended based on available data. HCC is rare in this population.
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Hepatic and Splenic Artery Aneurysms

Doppler ultrasound or CT scan should be used for the detection of HAAs or SAAs and multidetector CT angiography for characterization and treatment planning.
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In patients with HAAs or SAAs, using a multidisciplinary approach, if an intervention is deemed necessary, endovascular repair should be considered first and, if inappropriate, open repair. These decisions should be made in consultation with vascular surgical and interventional radiology specialists.
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For recently diagnosed HAAs or SAAs of <2 cm in size, early follow‐up imaging (e.g., 3 and 12 months) should be performed to assess spontaneous growth rate. Any significant growth of an aneurysm on serial imaging should prompt consideration of intervention in consultation with other specialists.
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Urgent intervention should be considered for symptomatic or complicated HAAs or SAAs.
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In patients with pregnancy plans or LT candidates, elective interventions in patients with HAAs or SAAs should be considered. In other patients, intervention has not been proven superior to expectant management.
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Issues Specific to Children and Congenital Disorders

In children with congenital or acquired vascular diseases of the liver, early referral to centers with expertise in pediatric liver disease, hepatobiliary surgery, and LT is recommended.
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In children with EHPVO, evaluation for early intervention in the presymptomatic stage is recommended at a center with expertise in treating this disorder.
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Glutathione expression may occur in as many as 30%‐50% of cases of infantile hemangiomata, and the use of beta‐blockers such as propranolol is recommended in these patients.
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Recommendation Grading

Overview

Title

Vascular Liver Disorders, Portal Vein Thrombosis, and Procedural Bleeding in Patients With Liver Disease

Authoring Organization

American Association for the Study of Liver Diseases

Publication Month/Year

November 19, 2020

Last Updated Month/Year

August 30, 2024

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Inclusion Criteria

Female, Male, Adult, Older adult

Health Care Settings

Ambulatory, Emergency care, Hospital

Intended Users

Physician, nurse, nurse practitioner, physician assistant

Scope

Assessment and screening, Diagnosis, Management, Treatment

Diseases/Conditions (MeSH)

D020246 - Venous Thrombosis, D014652 - Vascular Diseases, D011169 - Portal Vein

Keywords

hereditary hemorrhagic telangiectasia (HHT), Vascular Liver Disorders, Portal Vien Thrombosis, Procedural Bleeding, Thrombosis in cirrhosis, sinusoidal obstruction syndrome, hepatic vien thrombosis

Source Citation

Northup PG, Garcia-Pagan JC, Garcia-Tsao G, Intagliata NM, Superina RA, Roberts LN, Lisman T, Valla DC. Vascular Liver Disorders, Portal Vein Thrombosis, and Procedural Bleeding in Patients With Liver Disease: 2020 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021 Jan;73(1):366-413. doi: 10.1002/hep.31646. Epub 2021 Jan 20. PMID: 33219529.