Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Portal and Splenic Vein Thrombosis
Abbreviations
CALR
calreticulin
CT
computed tomography
JAK2
Janus kinase 2
MPN
myeloproliferative neoplasm
MTHFR
methylenetetrahydrofolate reductase
MVT
mesenteric venous thrombosis
PVT
portal vein thrombosis
TIPS
transjugular intrahepatic portosystemic shunt
Introduction
The term portal vein thrombosis (PVT) refers to the development of a thrombus in the portal vein. The thrombus can extend into any of the right and left branches of the portal vein, the superior or inferior mesenteric vein, and the splenic vein. Tumorous occlusion of the portal vein, which is characterized by the intraluminal development of malignant tissue, will not be discussed in this chapter.
PVT can occur in different contexts, each of which should be considered as a distinct disease entity and will be considered successively as follows: PVT occurring in the absence of underlying liver disease, including recent (so-called acute) PVT and long-standing (so-called chronic) PVT; PVT occurring in patients with cirrhosis; and PVT in children. Last, isolated splenic vein thrombosis will be briefly discussed.
Portal Vein Thrombosis in the Absence of Underlying Liver Disease
Epidemiology
Noncirrhotic, nontumorous PVT is the second most frequent cause of portal hypertension worldwide, accounting for a larger proportion of cases in developing countries than in Western countries. A different background prevalence of infectious and inflammatory causes and limited access to medical care are usually proposed to explain this difference.
Etiology
Comprehensive investigations can identify systemic prothrombotic factors in approximately 60% of patients ( Table 45-1 ) but local triggering factors in less than 40% of cases. A combination of two or more prothrombotic factors has been found in 52% of PVT patients, which justifies comprehensive investigations, even when predisposing or precipitating factors have already been shown. Still, currently available investigations fail to identify a causal factor in approximately 20% of patients.
TABLE 45-1
Prevalence of Etiologic Factors in Adults With Portal Vein Thrombosis in the Absence of Underlying Liver Disease and Proposed Diagnostic Workup
| Condition | Prevalence (%) | Recommended Workup |
|---|---|---|
| Systemic Factors | ||
| Myeloproliferative neoplasm | 32 | Genetic testing of the V617F mutation of the JAK2 gene. If negative, discuss genetic testing of the calreticulin gene; discuss bone marrow biopsy |
| JAK2 V617F–positive | 27 | |
| Inherited thrombophilic disorders | 35 | Genetic testing: G20210A prothrombin gene mutation; factor V Leiden mutation; C677T MTHFR mutation. Protein S activity, protein C activity, antithrombin activity. Cautious interpretation if there is impaired liver function |
| G20210A prothrombin gene mutation | 9-22 | |
| Factor V Leiden mutation | 3-9 | |
| Protein S deficiency | 0-30 | |
| Protein C deficiency | 0-7 | |
| Antithrombin deficiency | 0-5 | |
| C677T MTHFR mutation | 11 | |
| Acquired thrombophilic disorders | 19 | |
| Antiphospholipid syndrome | 5-10 | Lupus anticoagulant, anti-cardiolipin, and anti–β 2 glycoprotein 1 antibody testing Repeat testing after 12 wk in the case of a positive test |
| Other systemic factors | Search for clinical and/or biologic features of autoimmune disease, inflammatory bowel disease, vasculitis, sarcoidosis, connective tissue disease, Behçet disease, cytomegalovirus infection | |
| Hormonal Factors | ||
| Oral contraceptive | 44 | |
| Local Factors | ||
| Pancreatitis, diverticulitis, cholecystitis, appendicitis, intraabdominal surgery | 21 | Computed tomography scan, colonoscopy |
| No identified factor | 40 | |
See Denninger et al., Janssen et al., Primignani et al., Plessier et al., and Smalberg et al.
General Risk Factors
Myeloproliferative Neoplasms
Myeloproliferative neoplasms (MPNs) have been found in approximately 30% of patients with PVT. In PVT patients, however, hypersplenism and hemodilution may mask the increased blood cell counts. MPN diagnosis has been facilitated by testing for the V617F mutation of the Janus kinase 2 gene ( JAK2 ). The prevalence of MPNs and JAK2 mutation among patients with noncirrhotic PVT has been estimated at 31.5% and 27.7%, respectively. JAK2 mutation has been detected in 15.4% of PVT patients without typical MPN features in peripheral blood. Thus MPNs should be investigated in all patients with PVT, regardless of peripheral blood cell counts. Somatic mutations of the gene encoding calreticulin ( CALR ) have been identified in approximately 2% of JAK2 V617F–negative patients with PVT. Bone marrow biopsy showing clusters of dystrophic megacaryocytes with or without fibrosis has long been considered the gold standard for the diagnosis of MPN, although recent data challenge this view.
Inherited Thrombophilia
Deficiency in antithrombin, protein C, or protein S, and factor V Leiden or G20210A prothrombin gene mutation have been found in patients with PVT. The diagnosis of inherited deficiencies of antithrombin, protein C, and protein S is difficult to establish in such patients because PVT per se appears to induce a nonspecific decrease. In a recent meta-analysis, the pooled prevalence of antithrombin, protein C, and protein S deficiency in patients with PVT was 3.9%, 5.6%, and 2.6%, respectively. Not all patients with isolated low levels of protein C or protein S appear to have deficiency causing mutation in the PROC gene or the PROS gene, respectively. The prevalence of factor V Leiden mutation among patients with PVT ranges from 3% to 9%, corresponding to a twofold increase in the risk of PVT among carriers of at least one allele. The G20210A prothrombin gene mutation is more common among PVT patients than factor V Leiden mutation, having been found in 9% to 22% of them, which corresponds to a 4.5-fold increase in the risk of PVT among carriers.
The role of hyperhomocysteinemia as a risk factor for PVT is difficult to assess because homocysteine levels are highly influenced by diet and by vitamin B 12 or folic acid deficiencies. The average prevalence of homozygous C677T methylene tetrahydrofolate reductase gene ( MTHFR ) polymorphism is approximately 11%, which is not higher than expected in the general population.
Acquired Prothrombotic Disorders
Antiphospholipid syndrome refers to the occurrence of venous and arterial thromboses, or recurrent fetal losses, in the presence of antiphospholipid antibodies. However, antiphospholipid antibodies can be found in the absence of antiphospholipid syndrome; for example, in up to 5% of healthy subjects, and also in patients with rheumatologic diseases, infections, and cancer. In patients with PVT, the reported prevalence for antiphospholipid antibodies was approximately 5% to 10%. However, except for IgG anticardiolipin antibodies, antiphospholipid antibodies were not associated with PVT according to a recent meta-analysis.
Other autoimmune-mediated diseases, vasculitis, sarcoidosis, and connective tissue disease, may also be associated with PVT. This is particularly relevant to Behçet disease in the Mediterranean area. PVT was frequently diagnosed in patients with inflammatory bowel disease in an active phase or after surgery. The diagnosis was fortuitous in 40% of inflammatory bowel disease patients.
The incidence of PVT was 6.4% in hospitalized patients with acute cytomegalovirus infection, being higher in immune-competent than in immune-compromised patients. Inherited prothrombotic disorders and oral contraceptive use were both found in 25% of patients with cytomegalovirus infection and PVT.
Alone, exposure to female hormones does not appear to cause PVT. A female predominance among patients with PVT has not been found. Oral contraceptive use and pregnancy have been reported to trigger PVT only when local or other general prothrombotic factors were present.
Local Factors
Local risk factors (i.e., surgery or infectious or inflammatory conditions in the splanchnic area) were found in 21% of patients. In patients with alcoholic pancreatitis, underlying thrombophilia does not appear to increase the risk of PVT. In other patients, the identification of a local factor should not prevent the investigation of a systemic prothrombotic factor because one third of patients with a local factor also had a general prothrombotic disorder. Septic thrombophlebitis of the portal vein (so-called pylephlebitis) is usually related to an infection in the region drained by the portal venous system, mostly diverticulitis and appendicitis. Bacteremia (often polymicrobial) is present in 88% of patients, and the most common blood isolate is Bacteroides fragilis .
Manifestations
Clinical and Laboratory Features
Acute Portal Vein Thrombosis
Acute portal vein thrombosis (PVT) refers to the recent formation of a thrombus within the portal vein and/or its branches and/or its radicles. Abdominal pain is present in most patients. Other features include fever, high leukocyte count, and high C-reactive protein level, all related to a systemic inflammatory response syndrome developing in the absence of infection. Liver blood test results are normal or show only moderate and transient changes. Some patients might present with mild or nonspecific symptoms.
Ischemia or infarction of the small bowel should be suspected in patients with persisting intense pain despite adequate anticoagulation; hematochezia; guarding; ascites; or multiorgan failure with increased lactate levels or metabolic acidosis. In a recent study of 57 patients with acute mesenteric venous thrombosis (MVT), circulatory shock (36%) and clinically detectable ascites (75%) were more frequently observed in patients who had intestinal resection than in those who did not. Intestinal resection was also more frequent in patients with underlying diabetes mellitus.
Chronic Portal Vein Thrombosis
Following acute thrombosis, in the absence of recanalization, the portal venous lumen obliterates, whereas tortuous collateral vessels bypassing the thrombosed portion of the portal vein develop and together form the so-called cavernoma. Portal hypertension, recurrent thrombosis, and cholangiopathy are the main complications of chronic PVT.
Portal Hypertension.
Gastrointestinal bleeding has become a rare mode of presentation, compared with a fortuitous uncovering of portal hypertension by examinations performed for an unrelated reason. Such features include enlarged spleen, low blood cell counts, gastroesophageal varices on endoscopy, or cavernoma or portosystemic collaterals on abdominal imaging. Portal hypertension typically contrasts with little evidence for liver dysfunction. However, liver dysfunction may be revealed by sensitive tests, such as plasma protein C determination showing decreased levels.
Bleeding is the most frequent portal hypertension–related complication. Varices may belong to the portosystemic collateral circulation (in the esophagus and the gastric fundus) or to the portal cavernoma (in the gastric antrum and the duodenum). Ectopic varices, in the duodenum, anorectal region, and gallbladder wall, are more common than in patients with cirrhosis. Bleeding-related mortality in patients with PVT is lower than in patients with cirrhosis, probably because of the preserved liver function.
Ascites is uncommon, and is usually (but not constantly) triggered by recent gastrointestinal bleeding or infection. Ascites purely related to hepatic dysfunction occurs late in the course of PVT. Overt hepatic encephalopathy is rare in the absence of a concurrent precipitating factor. By contrast, subclinical encephalopathy appears to be common. Its actual impact on mental performance and quality of life warrants further evaluation.
Recurrent Thrombosis.
Recurrent thrombosis is the next most frequent complication behind bleeding. It mostly affects the splanchnic area. Prothrombotic conditions constitute an independent risk factor for recurrent thrombosis. The impact of recurrent thrombosis on the outcome remains to be evaluated. However, it is clear that the involvement of the superior mesenteric vein is associated with a worse outcome.
Portal Cavernoma Cholangiopathy.
The term portal cavernoma cholangiopathy refers to abnormalities of the entire biliary tract, including intrahepatic and extrahepatic bile ducts, the cystic duct, and the gallbladder in patients with portal cavernoma. It is attributed to imprinting on the bile ducts or their lumen by collaterals composing the cavernoma. Ischemic damage to the biliary tree has also been suggested to explain part of portal cavernoma cholangiopathy.
When magnetic resonance cholangiography was routinely performed, bile duct changes were found in 92% of consecutive patients. However, clinical impact is more limited than morphologic changes. Elevated serum alkaline phosphatase levels, elevated serum bilirubin levels in and elevated serum alanine aminotransferase levels were observed in 30% to 80%, 50%, and 30% of patients with portal cavernoma cholangiopathy, respectively. Severe and life-threatening manifestations (cholecystitis, cholangitis, obstructive jaundice) were even less common, and occurred in 5% to 35% of the patients. Such complications developed only in patients with grade III cholangiopathy (namely, strictures with dilatations), in whom the risk was 41%.
Imaging Features
Acute Portal Vein Thrombosis
The direct visualization of a hyperechogenic thrombus in the portal lumen is inconstant. Therefore duplex ultrasonography is needed to show an absence of flow within the portal vein. Contrast-enhanced computed tomography (CT) in the portal phase shows the absence of enhancement of the lumen corresponding to the portal vein thrombus ( Fig. 45-1 ). A spontaneously hyperattenuating thrombus dates back to less than 30 days after the onset of symptoms. The absence of a well-developed cavernoma is an additional feature suggesting that PVT is recent, because a cavernoma is visible as early as 15 days after the onset of abdominal pain.
CT scan provides additional information on extension to the mesenteric veins and arches, potential local factors, and impact on the bowel, as illustrated in Fig. 45-1 . Distal thrombosis (occlusion of second-order radicles of the superior mesenteric vein), large ascites, pneumatosis intestinalis, and portal venous gas are more frequently observed in patients who will need intestinal resection. Diffuse homogeneous wall thickening and mesentery abnormalities have been found in 31% and 63% of patients with acute MVT, respectively, and are probably more suggestive of congestion related to acute portal hypertension than of ischemia in the context of venous thrombosis.
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here