Splenic Vein Thrombosis

Splenic vein thrombosis is most often caused by disorders of the pancreas, including acute and chronic

pancreatitis, trauma, pancreatic malignancy, and pseudocysts. This association is related to the location

of the splenic vein behind and close to the pancreas. Other causes include retroperitoneal masses,

abscesses, and inflammatory bowel disease; the remaining cases are idiopathic. Gastric varices are

present in approximately 80% of patients, and esophageal varices in 30% to 40%.187 Isolated “sinistral”

or left-sided portal hypertension occurs in the setting of normal liver function, and patients are readily

cured with splenectomy, although observation for asymptomatic patients is acceptable. The main

indication for splenectomy is variceal hemorrhage.

Complications of Portal Hypertension

9 The most important complications of portal hypertension are gastrointestinal bleeding secondary to

esophageal and gastric varices, ascites, and hepatic encephalopathy. The mortality risk associated with

portal hypertension is primarily related to the functional status of the cirrhotic liver. Child introduced a

scoring system of liver function for the purposes of assessing prognosis after portosystemic shunt

surgery in patients with cirrhosis, which has been subsequently modified several times to the Child–

Turcotte–Pugh (CTP) score (Table 59-9). These indices incorporate clinical and laboratory data as a

means to assess the functional status of the liver, estimate hepatic reserve, and predict morbidity and

mortality. They had been adopted by the United Network for Organ Sharing (UNOS) as a tool for

stratifying pretransplant mortality risk for patients on the waiting list for liver transplantation.188 Over

the last decade, the use of these criteria in transplant has been replaced by the model for end-stage liver

disease (MELD) score, which uses serum bilirubin, creatinine, and the international normalized ratio

(INR) to produce a surprisingly robust prediction of 90-day mortality for patients with cirrhosis on the

transplant list.189 Though the CTP score produces a more complete assessment of the patient, its use of

subjective clinical elements in the score made it unreliable as a verifiable element in assessment

compliance with center behavior in national organ transplant policy.190,191

While the MELD score was initially developed for the prognosis of patients after TIPS, the CTP score

has had long-standing use as a reliable predictor of mortality risk for shunt surgery and, by extension,

mortality risk of patients with cirrhosis undergoing other types of abdominal surgery.192,193 Patients

with normal function, termed “Child A,” have adequate hepatic reserve and survival rates similar to

those of noncirrhotic patients, whereas Child C patients have mortality rates in excess of 50% and may

not tolerate any intervention short of hepatic transplantation.

Varices

One of the most life-threatening complications of portal hypertension is bleeding from esophageal

varices. Esophageal varices are dilated veins found most commonly in the distal 5 cm of the esophagus.

In the normal esophagus, a venous plexus is located in the submucosa; it becomes more superficially

located to the lamina propria in the distal esophagus.194–196 This more superficial location in the distal

esophagus is consistent with the known increased occurrence of bleeding varices in that location. In

addition, 5% to 33% of patients with portal hypertension have gastric varices.197

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The pressure in the portal system is an important determinant of the likelihood for varices to develop.

As noted earlier, portal pressure may be estimated from the hepatic vein wedge pressure, and the

gradient between the wedge pressure and the free hepatic vein pressure is an indirect measure of the

resistance across the liver. In general, varices do not develop in persons with hepatic vein–portal vein

gradients below 12 mm Hg. Pressure gradients above 12 mm Hg are invariably present in patients with

varices, but this pressure does not necessarily produce varices in all patients. Other, undetermined

factors must play a role. Gastroesophageal varices are present in 40% of patients with Child A cirrhosis,

and in up to 85% of patients with Child C cirrhosis.198 Varices may also be present in chronic liver

disease without outright cirrhosis. For example, 16% of patients with chronic hepatitis C and bridging

fibrosis have varices.199

In approximately 10% of all patients presenting with acute upper gastrointestinal bleeding,

esophageal varices are the cause of bleeding. Rates of bleeding from varices vary among studies. In a

study of the natural history of varices in which patients were prospectively followed for 6 years,

esophageal varices developed in approximately 8% of patients with cirrhosis each year during the first 2

years of observation; the percentage increased to 30% by 6 years. Of the patients who had small varices

detected at initial endoscopy, large varices developed in 25%.200 Other studies show an incidence of

varices of up to 90% for patients with cirrhosis.201,202 Once varices are present, bleeding occurs in 25%

to 35% of cases, with the highest risk occurring within the first year after diagnosis.202,203 Patients with

large varices are at the highest risk for an initial bleed. Spontaneous bleeding from varices ceases

spontaneously in up to 40% of patients, although mortality and recurrent bleeding remain high.198 Of

patients who survive an episode of bleeding, 30% experience rebleeding within 6 weeks, and 70% at 1

year.203,204 The correlation between severity of varices and derangement of hepatic function is

inconstant, so mortality rates from bleeding varices range from 5% to 50%, with rates of 5%, less than

25%, and more than 50% for Child A, B, and C patients, respectively.204

The propensity for varices to bleed has been extensively studied. When combined with clinical data

such as the presence of active alcohol consumption, certain endoscopic characteristics of varices have

been correlated with initial episodes of bleeding (Table 59-10). These factors include variceal size,

Child–Pugh class, and the presence of red wale markings (longitudinal dilated venules that resemble

whip marks).202 Direct and indirect measurements of portal pressure have been used to predict the

likelihood of bleeding, with hemorrhage occurring only in patients with portal–hepatic venous gradients

above 12 mm Hg.205,206

Table 59-10 Endoscopic Signs That Correlate with Risk for Variceal Rupture

TREATMENT

Table 59-11 Prevention/Treatment Options for Variceal Bleeding

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Diagnosis of Varices and Prevention of Initial Variceal Bleeding. Because of the severe

consequences of variceal bleeding, methods to diagnose varices prior to bleeding and to prevent first

(primary prophylaxis) and recurrent (secondary prophylaxis) episodes of bleeding have been developed.

Esophagogastroduodenoscopy (EGD) is the gold standard for the diagnosis of gastroesophageal varices,

and should be performed in all patients upon the initial diagnosis of cirrhosis. If no varices are present

upon initial screening, an EGD should be repeated in 2 to 3 years for patients with compensated

cirrhosis. If small (<5 mm) varices are present, EGD should be repeated in 1 to 2 years. Patients with

decompensated cirrhosis should undergo yearly screening EGD based on current recommendations from

the AASLD.198 After varices are diagnosed, methods of primary and secondary bleeding prophylaxis

include control of the underlying cause of cirrhosis (i.e., alcohol consumption) and pharmacologic and

surgical interventions to lower portal pressure. The next section discusses methods of primary

prophylaxis to prevent initial episodes of bleeding (Table 59-11).

Beta Blockade. The use of nonspecific β-adrenergic blockade has been studied extensively in

randomized controlled trials of the primary prophylaxis of variceal bleeding. The mechanism of action

of these drugs (propranolol, nadolol) involves effects of both β1

-adrenergic and β2

-adrenergic

blockades, including decreased cardiac output and increased splanchnic arteriolar vasoconstriction as a

result of the loss of opposing β2

-adrenergic dilation.206,207 The combined effects decrease portal blood

flow and subsequently portal pressure.

These drugs are effective in portal hypertension associated with prehepatic, intrahepatic, and

posthepatic conditions,208 regardless of whether ascites is present.209 Not all patients respond to

therapy, however. Two meta-analyses have evaluated seven randomized controlled trials comparing

propranolol or nadolol with placebo in the prevention of initial variceal bleeding. Both analyses

concluded that beta blockade is significantly correlated with a reduced incidence of bleeding.210,211 A

reduction of 40% was noted overall after all trial results were combined, with bleeding developing in

approximately 16% of treated and 27% of untreated patients. The goal of therapy is to reduce the

hepatic vein–portal vein gradient to below 12 mm Hg or to more than 20% below baseline.212 Patients

who meet these goals not only have a lower risk of variceal bleeding, but also of developing ascites,

spontaneous bacterial peritonitis, and death.213 In addition to reducing the number of first episodes of

bleeding, beta blockade therapy has been shown to reduce mortality in most clinical trials.214 A metaanalysis of these studies concluded that mortality from bleeding is reduced in patients with large

varices.

Despite their known benefits, beta blockers are also associated with significant side effects that limit

their universal application in patients with cirrhosis. There is no role for beta blockade to prevent

formation of varices in patients who do not already have them, based on a large randomized study by

Groszmann et al.215 In this study, serious adverse events were significantly more common in patients

undergoing timolol therapy compared to placebo. For patients with small (<5 mm) varices without

high-risk features (decompensated cirrhosis, red wale markings), current guidelines from the AASLD

state that beta blockers may be used, although convincing evidence of substantial benefits in this setting

is lacking.198

Surgical Intervention. In the 1950s and 1960s, surgeons created prophylactic portosystemic shunts in

an attempt to prevent variceal bleeding. These procedures were studied in a randomized controlled

fashion and, although effective in preventing variceal bleeding, they caused an increased incidence of

hepatic failure and encephalopathy and had no effect on overall survival.216,217 These results provided

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