Can polycythemia vera (a myeloproliferative disorder) cause an inferior mesenteric venous varix in a patient?

Can Polycythemia Vera Cause an Inferior Mesenteric Venous Varix?

Yes, polycythemia vera directly causes inferior mesenteric venous varices through splanchnic vein thrombosis, which leads to portal hypertension and subsequent collateral vessel formation including mesenteric venous varices. 1

Mechanism of Varix Formation

Polycythemia vera is the most common acquired risk factor for splanchnic vein thrombosis, which encompasses portal, mesenteric, and splenic vein thrombosis. 1 The pathophysiology involves multiple interconnected mechanisms:

Primary Thrombotic Mechanism

• Hyperviscosity from elevated hematocrit creates low shear rates in large veins, enhancing thrombogenic interactions between platelets, leukocytes, and endothelial cells. 2, 1
• At low shear rates comparable to flow in large veins like the mesenteric vessels, endothelial displacement of platelets and leukocytes from axial migration of red blood cells enhances thrombogenic interaction. 2
• The baseline prothrombotic state in PV involves qualitative platelet defects including increased thromboxane A2 production, abnormal platelet activation, reduced levels of physiologic anticoagulants (antithrombin III, proteins C and S), and decreased fibrinolytic activity. 2, 1

Genetic Contribution

• The JAK2V617F mutation, present in >95% of PV patients, is detected in 20-40% of patients with splanchnic vein thrombosis even without overt myeloproliferative disease. 1, 3
• This mutation helps distinguish PV from secondary causes of erythrocytosis and has both diagnostic and prognostic implications. 1, 3

Progression to Varix Formation

• Chronic thrombosis of mesenteric veins leads to formation of collateral veins and portal hypertension, which manifests as splenomegaly and varices including esophageal and mesenteric venous varices. 1
• Chronic splanchnic vein thrombosis is often asymptomatic due to collateral vein formation, but the presence of splenomegaly and/or varices indicates established portal hypertension. 1
• The presence of portal cavernoma on imaging indicates chronic thrombosis. 1

Clinical Significance

Venous thrombotic events occur in 7% of patients prior to or at the time of PV diagnosis, and these can involve unusual sites such as splanchnic veins. 3 A case report documented a patient diagnosed with PV after rupture of esophageal varices, with imaging showing splenomegaly, portal vein occlusion, and collateral vessels. 4 Gastrointestinal bleeding from variceal complications occurs in 5% of cases. 1

Diagnostic Approach

When evaluating a mesenteric venous varix in a PV patient:

• Confirm the diagnosis with CT angiography or MR venography, as these modalities best evaluate vascular structure, venous patency, and identify complications. 1
• Test for JAK2V617F mutation if not previously done, as it has diagnostic and prognostic implications. 1
• Document the extent of portal hypertension and collateral vessel formation. 1

Management Implications

All PV patients require therapeutic phlebotomy to maintain hematocrit <45% and low-dose aspirin to reduce thrombotic risk. 1, 3 The risk of vascular complications is best controlled by maintaining hematocrit below 0.45, as levels above this threshold are associated with progressive vascular occlusive episodes. 1, 5

For established splanchnic vein thrombosis with underlying myeloproliferative neoplasm:

• Anticoagulation should be given indefinitely with vitamin K antagonists. 1
• High-risk patients (≥60 years old or with prior thrombosis) require cytoreductive therapy with hydroxyurea or interferon-alpha in addition to phlebotomy and aspirin. 1, 3
• The highest rates of thrombosis occur shortly before or at diagnosis and decrease over time with treatment. 6

Critical Pitfalls

• Do not dismiss mesenteric venous varices as unrelated to PV—they represent a direct complication of the disease's prothrombotic state. 1
• Phlebotomy alone substantially reduces but does not abolish thrombosis risk, so additional interventions including anticoagulation are necessary for established splanchnic vein thrombosis. 2, 1
• Maintaining hematocrit <45% is critical, as suboptimal cerebral blood flow and increased thrombotic risk occur at hematocrit values between 46% and 52%. 7