Non Cirrhotic Portal Vein Thrombosis: Diagnostic and Therapeutic Challenge

Portal vein thrombosis (PVT), the second most common cause of portal hypertension, can be found in cirrhosis and non-cirrhosis patients. Various factors can cause non-cirrhosis PVT, such as biliary infection. Upper gastrointestinal bleeding without sign of liver failure, must be considered as non-cirrhosis PVT manifestation. Combining physical, laboratory, endoscopic and radiological examination is needed to establish the diagnosis of PVT. The principle of PVT management consists of 3 keypoints. They are prevention and treatment of gastrointestinal bleeding, prevention of recurrent thrombosis and portal cholangiopathy therapy. Many aspect should be considered regarding the administration of anticoagulants in PVT patients, especially chronic PVT with cavernomas.


INTRODUCTION
Portal vein thrombosis (PVT) is a rare case and accounts for 5-10% of all portal hypertension cases 1 . It could be caused by cirrhosis or non-cirrhosis. Noncirrhosis and non-tumor PVT ranged from 0.7 to 3.7 per 100,000 people. Nevertheless, PVT is the second most common cause of portal hypertension.
The diagnosis is established by combining clinical manifestations of portal hypertension such as variseal bleeding without signs of liver failure and confirmed by radiological examination. The risk : benefit of anticoagulant therapy and thrombolysis is important to be considered in PVT patients.

Syifa Mustika, Pratista Adi Krisna
We describe a young woman who experienced PVT. She also experienced gastrointestinal bleeding repeatedly. The patient was cured by successive hystoacryl injection sclerotherapy. This patient's disease course can provide a case study reference in the diagnosis and treatment of PVT.
CT scan shows normal liver, splenomegaly and total portal vein thrombus with cavernomas, confirming the diagnosis of PVT.   After the bleeding stop and hemodynamic was stable, propranolol 2x20 mg was given After the bleeding stop and hemodynamic was stable, propranolol 2x20 mg was given to prevent rebleeding. No anticoagulation was given because the registro informatizado de enfermedad tromboembolica (RIETE) score was equivalent to a moderate risk (2.8%) for major bleeding. Finally, hystoacryl injection sclerotherapy were performed. After hystoacryl injection sclerotherapy, the bleeding was controlled.
there are some drawbacks to the use of ultrasound techniques. If the patient is obese or there is significant bowel gas, the visualisation may be poor. It is also a poor method of identifying thrombi in the splenic and superior mesenteric veins. Finally, assessing bowel ischaemia (which may occur secondary to mesenteric vein thrombosis) is very difficult 7 . CT and MRI have the additional advantages of being able to define the extent of the thrombus, show any evidence of bowel ischaemia/infarction and for looking at other organs surrounding the portal vein. The sensitivity and specificity of these techniques have been shown to be 100% and 98% 5 .
Anticoagulant is the main therapy for acute PVT. Whereas for chronic one, conscientious assessment is needed to assess the benefits and risks of anticoagulation 1,4 . Moreover, there is no study of anticoagulant therapy in chronic PVT with cavernomas 5 . And this is a challenge for clinicians.
In our case, portal hypertension was considered because there was esophageal varices on endoscopic examination, but surprisingly there was no liver failure, leading us to the non-cirrhosis etiology of hematemesis and melena. CT scan with contrast obtained a thrombus in the portal vein accompanied by cavernoma confirmed the diagnosis of PVT.
Biliary infection was thought to be a risk factor for thrombosis. The patient had a previous history of cholecystitis. In patients with cholecystitis, PVT may have been the result of an inflammation or of an infection reaching the cystic vein. Two possible paths of infection are proposed: a connection between the cystic vein and the hepatic sinusoid or a connection between the cystic and portal veins. In cases in which a connection between the cystic vein and the hepatic sinusoid plays an important role in portal vein thrombosis, a direct spread of infection and inflammation from the gallbladder to the portal vein is the main cause of thrombosis 8 . Whereas, myeloproliverative neoplasma (MPN) as the most common cause of PVT was not suspected in this patient because she had anemia and thrombocytopenia which should occur otherwise 1 . Ideally, prothrombin risk factors should be examined such as JAK2 mutations, paroxysmal nocturnal haemoglobinuria test, Leiden factor V, protein C, protein S, antithrombin and prothrombin gene mutations especially if there are similar complaints or thrombosis in a family history 5 . However, due to limited modalities, the inspection was not carried out.
Based on the 2009 AASLD recommendations, the principles of chronic PVT management are the

DISCUSSION
Portal vein thrombosis (PVT) refers to the complete or partial obstruction of blood flow in the portal vein, due to the presence of a thrombus in the vasal lumen. PVT is responsible for about 5-10% of overall cases of portal hypertension 1 . It could be caused by cirrhosis or non-cirrhosis. Non-cirrhosis and nontumor PVT ranged from 0.7 to 3.7 per 100,000 people. Nevertheless, PVT is the second most common cause of portal hypertension. 2 First, It is important to determine the cause of PVT, cirrhosis or non-cirrhosis then acute or chronic because it is related to the choice of therapy. AASLD recommends to diagnose chronic PVT in all patients with newly found portal hypertension, and acute PVT if there is abdominal pain for more than 24 hours, fever or ileus. 3,4 Meanwhile, according to Haris and Thachil, PVT is categorized into 4 types regarding the presence of cavernomas and the level of occlusion of portal blood supply. 5 The patient was categorized as category 4 PVT because there was complete TVP accompanied by cavernoma.
The diagnosis of PVT is suspected in several conditions such as, abdominal pain, abdominal infection, and gastrointestinal bleeding (due to portal hypertension). Various imaging modalities can be performed to diagnose PVT such as doppler ultrasound, CT with contrast or magnetic resonance angiography (MRA). 6 The most common imaging technique used for the diagnosis of PVT is doppler ultrasound, with a very high sensitivity in most studies. 7 However, prevention and treatment of gastrointestinal bleeding, prevention of recurrent thrombosis and treatment of portal cholangiopathy. 3 The principle of gastrointestinal bleeding prevention and treatment is to reduce portal vein pressure and thus prevent complications such as bleeding due to esophageal varices rupture. Increased portal pressure in patients with portal hypertension can be treated with splanchnic vasoconstrictors. Non-selective β-blockers have a role in secondary prophylaxis because they reduce the risk of rebleeding and increase survival rate. To treat acute bleeding, somatostatin is given to this patient. 9 Other studies showed that the combination of β-blockers with isosorbide mononitrate (ISMN) had a much better effect of reducing portal pressure but we did not give it because of the side effect such as symptomatic hypotension and fluid retention so we gave propranolol only. [9][10][11] To prevent rebleeding, histoacryl injection sclerotherapy was performed. Ligation combined with sclerotherapy has better efficacy than ligation only due to lower rebleeding rates. In one study, sclerotherapy caused 40% portal venous pressure increase and stimulated spontaneous shunt formation which would prevent rebleeding and recurrence of varicose veins. 10 Registro Informatizado de Enfermedad Tromboembolica (RIETE) score was used to evaluate major bleeding risk. Anticoagulant and thrombolysis were not given to our patient, related to RIETE score was 1,5 which was equivalent to moderate risk (2.8%) of major bleeding and the absence of complications such as mesenteric ischemia. 5,12,13 There is insufficient data regarding anticoagulant therapy in chronic PVT with cavernoma 5,10 . If an indication of anticoagulation is obtained, such as in cases of hypercoagubility, malignancy, and extension of the mesenteric vessel we can do early anticoagulation (before 7 days) to minimize the risk of serious complications, such as bowel necrosis leading to peritonitis, developing 5 .

CONCLUSION
Angiographic CT scan is the best choice for assessing thrombus and cavernoma. It is important to determine the cause of PVT related to cirrhosis or non-cirrhosis and the nature of acute or chronic regarding the choice of therapy. Hystoacril injection sclerotherapy and non-selective β-blockers are recommended for the therapy of chronic PVT. Risk of major bleeding should be assessed before applying anticoagulant and thrombolysis. Treatment of portal cholangiopathy is one of PVT treatment principle 3 . For the diagnosis portal cavernoma cholangiopathy we need to established all of the following criteria would have to be