Extensive Portal Vein Thrombosis (EPVT) refers to the thrombosis of the main trunk and two or more branches of the portal vein due to various causes, including inflammation, tumor, coagulation dysfunction and trauma, etc. EPVT is rare and the conventional treatment is ineffective, and patients are often at risk of death if they do not receive timely treatment. With the development and popularization of diagnostic techniques such as color Doppler, CT and angiography, some patients with EPVT presenting as acute abdomen can be diagnosed in a timely and clear manner, and their condition can be rapidly and effectively improved after active interventional thrombolytic therapy. We retrospectively analyzed three cases of EPVT admitted from November 2006 to March 2009, which were successfully treated with timely diagnosis and thrombolysis via superior mesenteric artery and splenic artery placement, and we report them below and review the literature. Li Zhen, Department of Vascular Surgery, First Affiliated Hospital of Zhengzhou University
Clinical data and methods
General data One male case and two female cases, aged 22, 35 and 46 years old, respectively. Abdominal distension and abdominal pain after eating were the main complaints. The duration of the disease ranged from 10 days to 21 days. EPVT was confirmed by color Doppler, abdominal CT and indirect portal venography. 2 patients had normal renal function and serum electrolytes on admission, and liver function was Child 1. 1 case was transferred to our hospital after 4 days of thrombolysis (250,000 units/day) by superior mesenteric artery cannulation, and most of the small intestine was already ischemic and necrotic. case, liver function Child grade 2, D dimer was 5.580mg/l.
Treatment The catheter was left in the superior mesenteric artery and splenic artery respectively by bilateral femoral artery puncture and contrast clarification. Urokinase 250,000 units were diluted to lOOml with saline through the catheter and injected at a rate of 2ml/min. The catheters were left in place, and poppine 10 mg + saline 5 ml was given daily through the catheters on each side first, followed by continuous infusion of urokinase 100,000-150,000 units + saline 50 ml micropump over 6 hours for 7 days. The coagulation time and D-dimer changes were monitored during this period. 7 days later, the catheter was removed and the puncture sites of both femoral arteries were closed with prolene sutures under local anesthesia. Low-molecular heparin sodium 4000 units were injected subcutaneously every 12 h. After 3 days, warfarin sodium tablets were given orally, and the warfarin sodium dose was adjusted to keep the INR between 2.0 and 2.5. After discharge, the maintenance dose of warfarin sodium was continued orally until 6 months, and liver function and clotting time were monitored regularly.
In one case, 230 cm of necrotic intestine was resected during emergency surgery, with 90 cm of proximal jejunum and 60 cm of distal ileum remaining. end-to-end small bowel anastomosis was performed, and the abdomen was closed after repeated cleaning of the abdominal cavity. 250,000 units of urokinase was given via peripheral vein twice/day after surgery, and heparin was micro-pumped to maintain ACT at about 200. 24 hours later, the abdominal cavity was cleaned again, and the remaining small intestine was observed to have good blood flow, and the abdomen was closed with adequate drainage. Peripheral sedation of urokinase 500,000 units/day was continued until 1 week and heparin was pumped continuously to maintain ACT at about 200 until 14 days after surgery when warfarin was switched to oral dosing to maintain INR at about 2.0.
Results
Thrombolysis with indwelling catheters was successful in 2 patients, and there were no adverse effects during the imaging and thrombolysis. In one case, the portal vein was completely recanalized, and in the other case, about 80% of the portal vein was recanalized and the formation of collateral circulation was seen around it (Figure 1 and Figure 2). After treatment, the clinical symptoms gradually disappeared, the abdominal pain was completely relieved after eating, and the liver function improved. The INR was maintained at 2.0-2.5 with continuous heparin anticoagulation for 14 days and oral warfarin. 14 days of continuous heparin anticoagulation after small bowel resection was observed in one case of intestinal necrosis, and the abdominal drainage flow was less than 20 ml/day from 2600 ml/day to 10 days postoperatively. Recovery was smooth.2 At 18, 30 and 2 months of follow-up, the patient had returned to normal life.
Discussion
EPVT often leads to intestinal ischemia with portal hypertension, intestinal necrosis and gastrointestinal bleeding. Because of the complex etiology, the misdiagnosis and mortality rate are high. The main causes are cirrhosis, cancer, abdominal surgery or trauma, and intra-abdominal infection. There are reports of 6.5% portal vein embolism in patients with cirrhosis and 22.2% incidence of portal vein thrombosis after splenectomy in 247,778 patients with autopsy results. The hypercoagulable state of the blood is another important factor, such as protein S and C deficiency, factor gene mutation or antithrombin deficiency. One patient’s father had a history of unexplained pulmonary embolism death, and the patient also had a history of unexplained lower extremity deep vein thrombosis, showing a significant hypercoagulable state of the blood. EPVT has also been reported to be caused by ischemic disease of the small intestine, so a detailed medical history is important for early diagnosis. Abdominal pain and fever are the most common manifestations in the acute phase. Some patients may be asymptomatic due to the establishment of collateral circulation, or the primary disease may cause insidious disease, which can be easily misdiagnosed and lose the opportunity for early and good treatment. In the past few years, the widespread use of ultrasound Doppler in clinical practice has led to a significant increase in the diagnosis of early portal vein thrombosis. Its risk in the population has been reported to be 1%.
Early systemic thrombolytic anticoagulation is a feasible treatment for acute portal vein systemic thrombosis, but the efficacy and duration of administration through peripheral veins is poor, and complications such as bleeding are often associated with higher doses of drugs. With the continuous development of interventional techniques, thrombolysis via unilateral femoral artery placement in the superior mesenteric artery, although minimally invasive and safe, is limited in scope for EPVT. In two patients, we used bilateral femoral artery puncture with separate catheters in the superior mesenteric artery and splenic artery to enable thrombolytic drugs to be thrombolized through the physiological route, expanding the range of thrombolytic drugs, increasing the effective local drug concentration in the thrombus, reducing the drug dosage, and effectively preventing the risk of bleeding due to thrombolytic drugs. The successful treatment of acute EPVT with sequential infusion of tissue-type thrombolytic plasminogen activator (t-PA) via superior mesenteric and splenic arteries has also been reported. In our patient, although early thrombolytic treatment at an outside hospital was unsatisfactory and resulted in partial small bowel necrosis, thrombolytic anticoagulation therapy still allowed the survival of nearly 2 m of small bowel. We believe that early and continuous injection of thrombolytic anticoagulant drugs is important for the remission of the disease and prevention of recurrence of thrombosis, and the selection of the dose of thrombolytic drugs still needs further observation.
In two patients, abdominal pain, nausea and vomiting disappeared after thrombolytic anticoagulant therapy. The results showed that the portal vein and its branches were completely recanalized in one patient with a disease duration of 1 week, and about 80% of the patients with a disease duration of 2 weeks were recanalized with the formation of collateral circulation, which was considered as incomplete thrombolysis due to long disease duration and thrombus mechanization. This suggests the importance of early diagnosis and treatment of portal vein thrombosis. Furthermore, it is particularly important to rationalize the chronology and continuity of drug therapy. All patients were treated with urokinase 250,000 units of thrombolysis via catheterization immediately after successful puncture placement. Then, 10 mg of poppine was sequentially pumped through the catheter on each side daily to relieve vasospasm, followed by 100,000-150,000 units of urokinase. Because of the short half-life of urokinase, which is only 15 minutes, the advantage of continuous pumping of small doses is to achieve the best time-effective thrombolytic effect with smaller doses and avoid the risk of bleeding. In order to effectively prevent intravascular thrombosis, it is believed that the commonly used thrombolytic agents, including urokinase, can activate thrombin by activating fibrin, which enhances the coagulation activity of the body and becomes one of the causes of thrombolysis failure or re-embolization, so it is necessary to continue pumping common heparin until the next thrombolytic treatment after thrombolysis. The American College of Chest Physicians (ACCP) also recommends that when deciding on anticoagulation therapy, the risk of bleeding should not be the only consideration, and that the pros and cons of reducing thromboembolism versus the increased risk of bleeding must be weighed. The use of low molecular heparin sodium with a long half-life and minimal bleeding side effects is another important therapeutic measure to prevent recurrence of thrombosis after thrombolysis. Continue oral warfarin anticoagulation for at least 6 months. It is appropriate to maintain INR between 2.0-2.5 in the national population, monitor coagulation indicators, and adjust the dosage at any time to ensure the effectiveness of treatment.
Bilateral femoral artery placement for interventional thrombolysis for EPVT leaves some aspects unsatisfactory. First, bilateral femoral artery placement restricts the patient’s activity. Second, the catheter must be tightly secured to avoid intra-arterial catheter displacement, as the catheter may dislodge into the abdominal aorta, reducing the effectiveness of thrombolysis. Furthermore, due to the long duration of the arterial sheath, the femoral artery puncture site needs to be closed under direct vision after treatment to prevent the formation of a femoral artery pseudoaneurysm.
There is no uniform guideline on the route, amount and type of EPVT intervention, but there is a consensus that portal vein thrombosis should be treated actively once it is diagnosed. It is generally believed that if the disease duration is long, the collateral circulation has been formed, and the patient presents with portal hypertension and ruptured esophagogastric variceal bleeding as the first symptoms, the thrombus is considered to be mechanized and the effect of interventional thrombolysis is poor, so the treatment of complications should be the main focus. Patients with contraindications to thrombolytic anticoagulation can also be treated with surgical procedures aimed at reducing portal hypertension, such as portal vein thrombectomy, splenic-renal shunt, and intestinal-luminal shunt. Single-center follow-up of large numbers of cases has shown that the mortality rate within one year in patients with portal vein thrombosis after conventional treatment for non-cancer and cirrhosis is still as high as 8%, but the cause is mainly due to the primary lesion rather than secondary portal hypertension, so the treatment of the primary lesion is also very important.
Since the body is in a hypercoagulable state, thrombosis consumes a large amount of coagulation factors and prothrombin complexes, and then the fibrinolytic system comes into play, and the patient’s coagulation and fibrinolytic processes are disturbed. Therefore, the monitoring of plasma prothrombin time (PT), activated partial thromboplastin time (APTT) and D-dimer is very important in the treatment process. In our patients, PT and APTT were different from normal values at the time of admission, but there was no significant difference, while D-dimer was significantly higher, and in two patients, D-dimer was several times higher than normal, and in the intestinal resection patient, D-dimer was still nearly 10 times higher than normal after surgery, but decreased to normal range 9 and 12 days after thrombolysis and anticoagulation, so D-dimer is the most valuable pointer for dynamic observation of fibrinolytic activity.
In conclusion, for patients with extensive portal vein thrombosis, early diagnosis is the key to treatment, especially if the disease duration is within 1 week, active interventional thrombolytic anticoagulation therapy should be considered first. Interventional thrombolytic anticoagulation via superior mesenteric artery and splenic artery EPVT is simple, minimally invasive, thrombolysis via physiological route, reduces the risk of thrombolytic dose and bleeding, and maximizes the efficacy of the drug. It is a safe and effective method for the treatment of early extensive portal vein thrombosis.