Continuing Education Activity

Pylephlebitis is a rare disease process that is associated with a high rate of morbidity and mortality, especially if it is not recognized early in the course of care. It is crucial to have an understanding of the common conditions associated with pylephlebitis. Additionally, the foundation of management is antibiotic therapy, but it is imperative to realize that further additions to the treatment paradigm, including anticoagulation, must be individualized on a case by case basis. This activity reviews the clinical presentation, diagnosis, and management of pylephlebitis and highlights the role of the interprofessional team in evaluating and treating patients with this condition.

Objectives:

• Describe the pathophysiology of pylephlebitis.
• Explain the role of anticoagulation in a patient diagnosed with pylephlebitis.
• Outline the appropriate management for a patient with pylephlebitis.

Introduction

Pylephlebitis, defined as septic thrombophlebitis of the portal veins, is a rare but deleterious complication of an intra-abdominal or pelvic infection of any etiology.[1] Prior to the advent of widespread antibiotic use, this affliction was almost universally fatal, but advances in imaging technology have aided in the earlier detection and diagnosis of this disease process. It is imperative to consider this in the differential diagnosis of any patient presenting with intra-abdominal sepsis with polymicrobial bacteremia since disastrous complications such as small bowel infarction, hepatic abscesses, and septic pulmonary emboli can occur.[2]

Etiology

Nearly any intra-abdominal or pelvic infection involving viscera with drainage via the portal venous system can be complicated by pylephlebitis. In the early 20th century, appendicitis was a common inciting infection, but owing to antibiotics, this is rarely the case today.[1] Currently, diverticulitis is one of the most common sources, though cases have been associated with other inflammatory and infectious conditions including inflammatory bowel disease, pancreatitis, gastroenteritis, cholangitis, peptic ulcer disease, liver abscess, amoebiasis, and even cases associated with umbilical vein catheters, and migration of an adjustable gastric band.[3][4]

Epidemiology

Unfortunately, due to the rarity fo this condition, the existing epidemiological statistics are scare. From one article that reviewed 100 case reports from 1971 to 2009, the age range included patients as young as 20 days old to 77 years old with a mean of 42.3 years. It is not clear if there is a gender predominance.[4]

Pathophysiology

Pylephlebitis starts with thrombophlebitis of the small veins which drain the site of infection. This process extends to larger veins leading to septic thrombophlebitis involving the portal vein. In some cases, this process extends even further with the involvement of the large mesenteric veins. If this occurs, the potential exists to result in bowel ischemia, a fatal complication if not identified early. In one review of 19 cases of pylephlebitis, bacteremia was identified in 88% of the cases with the most frequent isolates including Bacteroides fragilis and Escherichia coli.[4]

In another review of 100 cases, a microorganism was identified 92% of the time from blood culture, tissue sample, liver abscess, or portal veinous aspirate. Infections were more frequently polymicrobial with the most commonly implicated organisms including Bacteroides species, Escherichia coli, and Streptococcus species.[5]

History and Physical

Although rather nonspecific, common presenting symptoms of patients with pylephlebitis include fatigue, fever, abdominal pain, nausea, vomiting, diarrhea, and weight loss. Important physical examination findings though not always present, include abdominal tenderness, splenomegaly, hepatomegaly, ascites, and jaundice, usually seen with disseminated hepatic involvement.[6]

Evaluation

Laboratory studies are usually significant for early leukocytosis, but both leukopenia and a normal white blood cell count have been reported in the literature.[2][6][7] Abnormal liver chemistries, including elevation in alkaline phosphatase, AST, ALT, and gamma-glutamyl transferase, are seen in most patients, usually without a concurrent increase in bilirubin unless widespread hepatic involvement is present.[8]  

No diagnostic criteria for pylephlebitis currently exist. As such, the diagnosis is usually made after imaging shows a portal vein thrombus in a patient with sepsis and a clinical picture consistent with pylephlebitis.[9] Notably, the presence of a thrombus alone is not sufficient to make the diagnosis of pylephlebitis. Both computed tomography and color flow Doppler ultrasonography have the ability to demonstrate a portal vein thrombus. Still, CT may prove more useful given the ability to detect complications, including hepatic abscesses and intestinal ischemia.[2][6] 

In one study, CT and US were the most common imaging modalities utilized, but other less used modalities included MRI and PET/CT. Previously, a subset of patients has been diagnosed at autopsy, but more advanced imaging techniques have aided in facilitating an earlier diagnosis.[10]

Treatment / Management

The cornerstone of treatment involves an appropriate antibiotic regimen, remembering that the infection is often polymicrobial and frequently caused by gram-negative aerobes, anaerobes, and streptococcus species. No randomized controlled trials have been performed evaluating empiric antibiotic regimens, and numerous studies advocate for broad-spectrum coverage even if bacteremia is absent.[2][4][6]  

Once culture results and susceptibility data become available, antibiotics should be narrowed accordingly. Initially, antibiotics should be administered via a parenteral route, but ultimately, consideration may be given to transitioning to an oral route pending antimicrobial susceptibility data and clinical complications. The typical duration of antibiotics is approximately four to six weeks, but consultation with an infectious disease specialist is advised.

At the present time, there is no clear consensus on the role of anticoagulation in pylephlebitis, mainly due to the paucity of randomized controlled trials and high-quality data. In one review of 100 cases, 35 patients received anticoagulation in addition to antibiotics, compared to antibiotics alone, and a lower mortality rate was observed.[4] In a separate review of 44 cases, a similar outcome was observed with lower mortality in the group receiving anticoagulation.[11] 

Due to the lack of high-quality evidence, it is reasonable to consider anticoagulation in a patient with an underlying neoplasm, inherited thrombophilia, or extension of the thrombus into the mesenteric veins. It should also be considered when bacteremia is due to a Bacteroides species as it possesses surface components that enhance fibrin clotting in addition to the ability to elaborate enzymes that degrade heparin.[1] As the clot burden increases, thrombolytic therapy can be considered, but there is no definite evidence of efficacy.[12]

Differential Diagnosis

The differential diagnosis for pylephlebitis mainly includes other causes of non-infectious portal vein thrombophlebitis including malignancy, decompensated cirrhosis, inherited thrombophilia, and connective tissue disease.

Prognosis

In one review of case reports, prior to 1990 the mortality rate was 75% compared to a 25% mortality rate in cases after 1990.[4] Despite earlier detection of pylephlebitis through advances in imaging technology and treatment with newer antibiotics, the diagnosis still carries a significant mortality rate cited in several studies ranging from 11% to 32 %.[6][11]

Complications

Pylephlebitis itself is considered a complication of an inciting infectious or inflammatory process, but subsequent complications include chronic thrombosis, an extension of the clot into a mesenteric vein, bowel ischemia, hepatic abscess, hepatic infarction,  splenic infarction, and death. One review of 95 cases cited an overall complication rate of 20%.[6][13]

Consultations

It is very common to have an infectious disease physician as a part of the treatment team in addition to internist as treatment options and the route of delivery can be quite complex.

Deterrence and Patient Education

Education for patients diagnosed with pylephlebitis should include the importance of compliance with antibiotics, primary causes of this disorder, and possible complications especially if treatment recommendations are not followed. If a chronic predisposing condition to this disorder is present such as an inherited thrombophilia or cirrhosis, counseling regarding appropriate management and follow up for these conditions is warranted as well.

Enhancing Healthcare Team Outcomes

Due to its rarity, the diagnosis of pylephlebitis requires a high clinical suspicion and often times will go undiagnosed for an extended period of time. The radiologist is a key member in identifying the presence of a portal vein thrombus on ultrasound or cross-sectional imaging, but ultimately the diagnosis requires the knowledge and expertise of other physicians to include this in their initial differential diagnosis. It is imperative to secure the diagnosis in a timely manner in order to execute an appropriate treatment plan, ideally created by a team of multi-specialty physicians and other providers. Due to the paucity of high-level evidence in the literature, expert opinion from different specialists grounded in clinical experience will ultimately guide the therapeutic paradigm and the decision whether or not to include anticoagulation in addition to antibiotics.

Communication between physicians from various specialties, including gastroenterology, infectious disease, internal medicine, and general surgery, is paramount to effective, safe, patient-centered care. Other members of the healthcare team, especially nurses, play a vital role in facilitating inter-team communication and coordinating care for the patient. Additionally, nurses are crucial to identifying this disease process early in the clinical course as it is usually a complication of a more common disorder such as appendicitis or diverticulitis. Often times, it can be initially recognized by nursing staff as a patient failing to improve clinically (persistently febrile, unrelenting abdominal pain, unchanging elevation in transaminases, etc.) despite what is believed to be adequate treatment. The pharmacist is also an essential member of the healthcare team to ensure that the patient is receiving the correct dose of the appropriate antibiotic to successfully treat the patient with pylephlebitis in a safe manner. Each member of the healthcare team should complete their assigned tasks but should also focus on effective inter-team communication to provide the highest level of patient care.