Is Hereditary Hemorrhagic Telangiectasia (HHT) or Polycythemia Vera (PV) more likely to cause a large inferior mesenteric venous varix?

HHT is More Likely to Cause Inferior Mesenteric Venous Varix

Hereditary Hemorrhagic Telangiectasia (HHT) is substantially more likely than Polycythemia Vera to cause a large inferior mesenteric venous varix, as HHT creates direct arteriovenous shunting through vascular malformations that lead to portal hypertension and variceal formation, whereas PV causes thrombotic portal vein occlusion rather than variceal enlargement. 1

Pathophysiologic Mechanisms

HHT Creates Varices Through Arteriovenous Shunting

• HHT produces three distinct types of intrahepatic shunting (hepatic artery to portal vein, hepatic artery to hepatic vein, and portal vein to hepatic vein) that directly cause portal hypertension through arterioportal shunts 1
• Portal hypertension from arterioportal shunts manifests with severe recurrent variceal bleeding, creating the hemodynamic conditions for large venous varices including inferior mesenteric varices 1
• The arteriovenous malformations in HHT lack a capillary bed, resulting in direct artery-to-vein connections that increase portal venous pressure and promote varix formation 2
• Complicated portal hypertension occurs at a rate of 1.2 per 100 person-years in HHT patients with hepatic vascular malformations 1

PV Causes Thrombosis, Not Variceal Enlargement

• Polycythemia Vera is a myeloproliferative neoplasm that leads to hyperviscosity and thrombosis, with portal vein thrombosis being the characteristic vascular complication 1, 3
• PV patients develop occlusion of the portal vein and collateral vessels through thrombotic mechanisms, not through direct variceal enlargement 3
• The underlying myeloproliferative neoplasm in PV requires indefinite anticoagulation for splanchnic vein thrombosis, indicating the primary pathology is thrombotic occlusion 1

Clinical Presentation Differences

HHT Variceal Bleeding Pattern

• Gastrointestinal bleeding in HHT patients with liver vascular malformations occurs more often from gastrointestinal telangiectasias than from variceal bleeding, though varices do form from portal hypertension 1
• Only 8% of HHT patients with liver vascular malformations are symptomatic in cross-sectional surveys, but 25% develop hepatic vascular malformation-related morbidity over median 44-month follow-up 1

PV Thrombotic Presentation

• PV presents with portal vein occlusion and splenomegaly from thrombotic mechanisms, with esophageal varices developing as a consequence of chronic portal vein thrombosis 3
• The JAK2V617F mutation is present in PV patients and should be tested in splanchnic vein thrombosis patients 1

Diagnostic Approach for Inferior Mesenteric Varix

When HHT is Suspected

• Apply Curaçao diagnostic criteria: spontaneous/recurrent epistaxis, multiple telangiectasias at characteristic sites (lips, oral cavity, fingers, nose), visceral lesions, and first-degree relative with HHT—diagnosis is definite with 3 criteria 4
• Perform Doppler ultrasonography as first-line imaging for hepatic vascular malformations, assessing hepatic artery diameter (>6 mm abnormal), peak flow velocity (>80 cm/sec abnormal), and resistivity index (<0.55 abnormal) 1
• Never perform liver biopsy in any patient with proven or suspected HHT due to catastrophic hemorrhage risk from vascular malformations 1, 4
• Genetic testing for ENG, ACVRL1, and SMAD4 mutations identifies causative mutations in 97% of clinically definite HHT cases 4

When PV is Suspected

• Test for JAK2V617F mutation in patients with splanchnic vein thrombosis, even with normal peripheral blood cell counts 1
• In JAK2V617F mutation-negative patients, perform calreticulin mutation screening, and if both negative, consider bone marrow histology 1
• Abdominal CT demonstrates portal vein occlusion and collateral vessels in PV, contrasting with the patent but dilated vessels seen in HHT 3

Critical Clinical Pitfalls

• Do not assume portal hypertension equals cirrhosis—HHT causes non-cirrhotic portal hypertension through arteriovenous shunting, with generally preserved liver synthetic function 1
• Recognize that hepatic involvement in HHT has marked female predominance and is more common in HHT type 2 (ACVRL1 mutations) than HHT type 1 (ENG mutations) 1, 4
• Avoid transjugular intrahepatic portosystemic shunt (TIPS) in HHT patients with portal hypertension, as it increases shunting and worsens the hyperdynamic circulatory state 1
• In PV patients with portal vein thrombosis, anticoagulation with vitamin K antagonists should be given indefinitely, and hematocrit should be maintained <45% with hydroxyurea or alpha interferon 1