Changes in the dynamics of flow can lead to venous thrombosis—evident, for instance, in arteriovenous grafts, where turbulence predisposes to in situ thrombosis. In MVT, cirrhosis with portal hypertension, reversal of flow (hepatofugal flow), and relative stasis all appear to predispose to MVT. Indeed, the presence of portal hypertension is a not uncommon clinical disorder in patients presenting with MVT. These local, intraluminal disturbances in blood flow with the associated turbulence appear to alter the endothelial microenvironment, acting functionally as a form of endothelial injury/dysfunction [1]; this dysfunction then sets up a thrombophilic microenvironment within the vein and especially at the endothelium that can progress to venous thrombosis. This process is much less well understood than for disorders in arterial flow dynamics. Congestive heart failure can lead to a functional, posthepatic portal hypertension, again associated with presumed portal stasis and disruption of normal flow dynamics.

Changes in the surrounding environment of the mesenteric veins can lead to in situ thrombosis. Probably the most common causes in this regard are local inflammatory conditions. While not common when considering a patient with MVT, one should always at least entertain the possibility of appendicitis, diverticulitis, and peritonitis when MVT involves the superior mesenteric venous system. Other noninfective inflammatory conditions affecting the superior mesenteric system may be related to blunt mesenteric trauma, operative trauma (especially laparoscopic) [2], or inflammatory bowel disease, which has an as yet unexplained pathogenesis of MVT; indeed, MVT is a well-known, albeit uncommon, complication of surgery for inflammatory bowel disease [3]. Probably the most common etiologies are acute and chronic pancreatitis, but these inflammatory conditions affect primarily the splenic vein to cause splenic vein thrombosis. Because the splenic vein is so intimately associated with the posterior pancreas, effects of the local acute inflammation or the chronic cicatricial, fibrotic occlusion of the splenic vein alters the luminal microenvironment of the endothelium or actually occludes the vessel leading to local thrombosis.

Probably the most common causes of MVT are the thrombophilic disorders—some of which are “acquired” (both non-hematologic and hematologic) and others are “inherited” genomic abnormalities in the germ line. These will be discussed in depth in Chap. 24. For the purposes of this chapter for the clinician, we at least need to consider these possibilities in patients without an obvious etiology.

The acquired, non-hematologic thrombophilic states include use of birth control pills, the nephrotic syndrome, certain malignancies with a systemic state of thrombophilia (especially pancreatic and gastric cancers), and states of hyperhomocysteinemia. These coagulopathies are potentially reversible. The acquired hematologic thrombophilias are more serious and include polycythemia vera (PCV), myelofibrosis, certain states of thrombocythemia, antiphospholipid antibodies, and paroxysmal nocturnal hemoglobinuria (PNH) (JAK 2 mutation is a diagnostic marker for PCV and thrombocythemia).

The inherited disorders of thrombophilia are hematologic and genomic in origin. These more commonly appreciated disorders of coagulation include deficiencies in protein S, protein C, antithrombin III (the current appropriate terminology is “antithrombin”), and factor V Leiden mutations; the heterozygote state of factor V Leiden is relatively common, and most hematologists do not consider the heterozygote state alone as a meaningful thrombophilic state, but the homozygote state is clinically relevant. Other less common variants will be entertained in Chap. 24.