What is the appropriate workup for an adult patient with no prior medical history presenting with portal vein thrombosis (PVT) to determine the underlying etiology?

Etiological Workup for Portal Vein Thrombosis

In an adult patient with newly diagnosed portal vein thrombosis and no prior medical history, immediately establish whether cirrhosis is present, as this fundamentally determines the thrombophilia workup—perform comprehensive prothrombotic screening only in non-cirrhotic patients, while limiting testing in cirrhotic patients where inherited thrombophilias rarely contribute to PVT. 1

Initial Critical Assessment

Establish Liver Disease Status First

• Determine presence or absence of cirrhosis immediately, as this is the single most important factor that changes your entire diagnostic approach 1
• If cirrhosis is present, assess Child-Pugh classification (A, B, or C) using albumin, bilirubin, INR, ascites, and encephalopathy 1
• Evaluate for hepatocellular carcinoma with AFP and contrast-enhanced imaging, as malignant thrombus must be excluded in any patient with underlying liver disease 2, 1

Rule Out Local Abdominal Factors

• Screen for intra-abdominal inflammatory conditions (pancreatitis, diverticulitis, inflammatory bowel disease) 2
• Assess for recent abdominal surgery or procedures 2
• Evaluate for hepatobiliary malignancies beyond HCC (cholangiocarcinoma, pancreatic cancer) 2
• Look for intra-abdominal infections or septic pylephlebitis 2

Thrombophilia Workup Based on Cirrhosis Status

For Non-Cirrhotic Patients: Comprehensive Testing Required

Perform extensive thrombophilia workup in all non-cirrhotic PVT patients, as prothrombotic factors are identified in up to 84% of cases and fundamentally alter management decisions. 2

Mandatory Myeloproliferative Neoplasm Screening

• JAK2 V617F mutation testing (most common acquired cause, found in 20-40% of splanchnic vein thrombosis) 3
• Complete blood count with peripheral smear 3
• Consider bone marrow biopsy if JAK2 positive or high clinical suspicion 3

Inherited Thrombophilia Panel

• Factor V Leiden mutation 2, 3
• Prothrombin G20210A mutation 2, 3
• Protein C deficiency (timing critical—avoid testing during acute thrombosis or on warfarin) 2
• Protein S deficiency (timing critical—avoid testing during acute thrombosis or on warfarin) 2
• Antithrombin deficiency (prevalence 0-5% in PVT) 2

Critical pitfall: Protein C and S levels are unreliable during acute thrombosis and on vitamin K antagonists; antithrombin, protein C, and protein S may be falsely low in liver disease due to decreased hepatic synthesis 2

Acquired Thrombophilia Testing

• Antiphospholipid antibody syndrome: lupus anticoagulant, anticardiolipin antibodies, anti-beta-2-glycoprotein I antibodies 3
• Paroxysmal nocturnal hemoglobinuria (PNH) testing via flow cytometry (high propensity for splanchnic thrombosis) 3
• Hyperhomocysteinemia 2

Additional Systemic Disease Screening

• Behçet disease evaluation (especially in patients from endemic areas—Mediterranean, Middle East, Asia) 2
• Autoimmune disorder screening if clinically indicated 3

For Cirrhotic Patients: Limited Testing

Do not perform extensive thrombophilia testing in cirrhotic patients, as inherited thrombophilias are uncommon contributors and testing rarely changes management. 1

• Consider screening for underlying genetic thrombophilic conditions only if there is personal or family history of unprovoked deep vein thrombosis 2
• The pathogenesis in cirrhosis is primarily portal hypertension and reduced portal flow, not hypercoagulability 4
• Focus instead on assessing severity of liver disease (MELD score, Child-Pugh class) as this is the most important modifier of PVT risk 4

Multifactorial Nature Recognition

Recognize that PVT etiology is frequently multifactorial—in the European En-Vie study, 46% of patients had two or more prothrombotic factors, and 60% of those with inherited thrombophilia had an additional risk factor. 2

• Systematically document all identified local AND systemic risk factors 2
• The combination of factors influences decisions about duration of anticoagulation 2

Laboratory Assessment for Baseline and Safety

• Complete blood count: platelet count >50 × 10⁹/L generally safe for anticoagulation 1
• Comprehensive metabolic panel: assess renal function for anticoagulant dosing 1
• Liver function tests: ALT, AST, bilirubin, albumin, INR for Child-Pugh scoring 1
• Do not use INR or PT to assess bleeding risk in cirrhotic patients—these tests do not predict bleeding complications in this population 1

Pre-Anticoagulation Variceal Assessment

• Perform upper endoscopy to screen for esophageal varices before initiating anticoagulation if cirrhosis is present 1
• If varices are identified, ensure adequate prophylaxis with non-selective beta-blockers or endoscopic band ligation before starting anticoagulation 2, 1

Portal Flow Velocity Assessment

• Measure portal vein flow velocity by Doppler ultrasound 1
• Velocities <10-15 cm/s are associated with increased PVT risk and may influence long-term anticoagulation decisions 1