Isolated Hepatic Artery Thrombosis Leading to Multiple Liver Infarcts in a Non-transplant Patient

Background

Hepatic artery thrombosis is a common complication of liver transplantation [1,2]; it is a rare complication of various intra-abdominal procedures [3–9], but spontaneous hepatic artery thrombosis is an extremely rare disorder, with only a few cases reported in the literature.

We report a case of spontaneous hepatic artery thrombosis leading to multiple hepatic infarcts in an elderly patient.

Case Report

A 62-year-old African-American woman with a medical history of hypertension, diabetes, chronic kidney disease, and treated stage 3 breast cancer, presented with a 5-day history of constant right upper quadrant abdominal pain, nausea and non-bloody vomiting. Her pain had no relation to food intake, nor was it associated with fever, urinary symptoms, or alterations in bowel habits. She endorsed no history of prior episodes or recent trauma.

Her physical examination revealed a soft abdomen with normoactive bowel sounds, and right upper quadrant tenderness with no evidence of rebound or guarding. There was no hepatosplenomegaly or ascites. The rest of her exam results were unremarkable.

Her initial laboratory work was significant for a hepatocellular process as evidenced by her elevated AST and ALT levels (745 and 431 units per liter, respectively). Her initial liver function tests along with baseline and peak levels are presented in Table 1.

Her CBC was normal, but her BMP showed baseline creatinine of 1.2 mg/dL, and no evidence of electrolyte abnormalities (Tables 2 and 3).

Her coagulation profile on presentation showed slight prolongation in PT to 15.7 seconds, INR of 1.31, and normal PTT (Table 4).

An EKG was done and showed sinus tachycardia and left ventricular hypertrophy. She had no history of atrial fibrillation.

Because of her laboratory findings and persistent abdominal pain, a CT scan of her abdomen with contrast was done. This revealed a thrombus within the hepatic artery, with multiple low attenuating areas present within the liver, which were most compatible with hepatic infarcts. She had no evidence of portal vein thrombosis (Figure 1).

She was started on anticoagulation with subcutaneous enoxaparin.

During her hospital stay, her AST and ALT levels peaked at 2065 and 1217 U/L, respectively, but started trending down thereafter (Figure 2). A workup for underlying chronic liver disease was negative (ANA, anti-smooth muscle antibodies, anti-mitochondrial antibodies, viral hepatitis panel, iron panel, and ceruloplasmin levels).

She also underwent a transthoracic and transesophageal echo-cardiogram, which did not show a thrombus or vegetation as a possible embolic source.

At this point, she was thought to have spontaneous hepatic artery thrombosis with resultant hepatic infarcts. A hypercoagulability workup was initiated and showed slightly low levels of protein C, protein S, and anti-thrombin III levels (which were difficult to interpret in the setting of an acute thrombus). A D-dimer was elevated at 7.87 fibrinogen equivalent units (FEU), while her fibrinogen levels were also elevated to 840 mg/dL.

Her clinical course, however, continued to deteriorate and on the fifth day of hospitalization, she became lethargic and developed severe inflammatory response syndrome (SIRS). Her lab results showed increasing leukocytosis, acute kidney injury, and a new right lower lobe opacity on her chest imaging. She was transferred to the intensive care unit where she was started on broad-spectrum antibiotics for possible hospital-acquired pneumonia leading to severe sepsis.

Shortly thereafter, she suffered a sudden cardiac arrest. Cardiopulmonary resuscitation was not performed as she had already signed DNR/DNI forms prior to her admission. Her family denied permission for autopsy.

Discussion

Hepatic infarcts following hepatic artery compromise are very rare because of the dual blood supply from the portal vein and the hepatic artery, along with the extensive hepatic arterial collateral system. However, localized hepatic infarcts following thrombosis or compression of an intrahepatic branch of the hepatic artery by various etiologies have been described, and typically lead to a transient increase in transaminases (AST, ALT), without compromising the hepatic synthetic function [10].

The vast majority of cases of hepatic artery thrombosis are reported as complications of orthotopic liver transplantation, with incidence rates of 3% to 9% [2]. It is a leading cause of graft loss and mortality during the immediate postoperative period [1].

Multiple risk factors have been identified and include technical difficulties during surgery, older donor age, lack of ABO compatibility, cigarette smoking, hypercoagulable states, preservation damages, regrafts, and a donor positive for cytomegalovirus in a CMV-negative recipient [2,11–14].

The clinical presentation varies depending on the timing of the thrombosis. Early hepatic artery thrombosis (within 4 weeks) may present with acute graft failure, sepsis/liver abscess, and biliary leak/stricture [15].

On the other hand, late hepatic artery thrombosis (after 4 weeks) can be clinically silent, with altered liver function tests. It can also present with biliary complications such as cholangitis with hepatic abscesses, bile leak, biliary strictures, and, eventually, progressive graft failure [16].

Besides liver transplantation, hepatic artery thrombosis has been reported to complicate various other procedures.

Jia et al. reported a case of right hepatic artery thrombosis following debridement and T-tube drainage of the common bile duct for severe pancreatitis and acute suppurative obstructive cholangitis in a patient with polycythemia vera [3]. The patient developed an unexplained rise of ALT and AST levels more than 30 days postoperatively. CT angiography confirmed the diagnosis of right hepatic artery thrombosis.

In 2009, Herrera Melero et al. reported a case of hepatic artery thrombosis and portal vein thrombosis complicating the postoperative course of a patient with Klatskin’s tumor, who underwent left hepatectomy, cholecystectomy, and roux en y cholangiojejunostomy [4].

In their case report published in 2004, Poggi et al. described the development of a massive hepatic infarction following an ultrasound-guided percutaneous radiofrequency thermal ablation of hepatocellular carcinoma. Color Doppler US revealed right portal vein thrombosis and right hepatic artery occlusion, confirmed by abdominal computed tomography [5].

Other procedures reported to lead to hepatic artery thrombosis include:Placement of hepatic catheters/Port systems for intra-arterial chemotherapy of liver tumors [6–8].Hepatic artery reconstruction following ablative surgery for hepatobiliary and pancreatic malignancies [9].

Our review of the literature revealed only 2 case reports of hepatic artery thrombosis in the absence of a recent abdominal intervention.

O’Connor et al. reported the first case of “spontaneous hepatic artery thrombosis with infarction of the liver” in 1976 [17].

Their patient presented with symptoms of congestive heart failure and bronchitis. His hospital stay was complicated by left lower extremity gangrene, requiring an above-the-knee amputation. Two weeks later, he developed fever and right upper quadrant pain; his laboratory work was remarkable for SGOT (serum glutamic oxaloacetic transaminase) of 3500 mU/ml, which peaked to 5100 U/ml, then slowly trended down to 250 U/ml 9 days later, when the patient suffered a myocardial infarction and died.

Autopsy showed thrombosis of the celiac trunk with extension to splenic, common hepatic, and right and left hepatic arteries.

In 2004, Francque et al. reported a case of left hepatic artery and portal vein thrombosis leading to hepatic infarction in a 73-year-old patient who suffered blunt abdominal trauma; his liver function tests were remarkable for massive elevations of AST and ALT (2518 U/L and 1334 U/L, respectively) with slight elevation in the levels of alkaline phosphatase, gamma glutamyltransferase, and bilirubin.

Doppler ultrasound disclosed a heterogeneous area in the left lobe and thrombosis of the left branch of the portal vein. No arterial signal could be recorded in the left lobe. Computerized tomography scan showed a well-marginated, peripheral perfusion defect without visualization of a left arterial branch or a left portal branch. Angiography confirmed the above findings.

The levels of transaminases decreased slowly and eventually normalized 3 months later [18].

In the absence of a recent surgical intervention or trauma, a workup for an underlying hypercoagulable state is essential as this may determine the course of management. Although there are no guidelines in the management of isolated hepatic artery thrombosis, the duration of anticoagulation may be influenced based on the precipitating event. Two important factors that may have played a role in the development of spontaneous thrombosis in this patient are a history of advanced cancer and sepsis.

In the case of cancer, a hypercoagulable or prothrombotic state occurs due to the ability of tumor cells to activate the coagulation system. It has been estimated that hypercoagulation accounts for a significant percentage of mortality and morbidity in cancer patients. Prothrombotic factors in cancer include the ability of tumor cells to produce and secrete procoagulant/fibrinolytic substances and inflammatory cytokines, and the physical interaction between tumor cells and blood (monocytes, platelets, neutrophils) or vascular cells. Other mechanisms of thrombus promotion in malignancy include nonspecific factors such as the generation of acute phase reactants and necrosis (e.g., inflammation), abnormal protein metabolism (e.g., paraproteinemia), and hemodynamic compromise (e.g., stasis). In addition, anticancer therapy (e.g., surgery/chemotherapy/hormone therapy) may significantly increase the risk of thromboembolic events by similar mechanisms, such as procoagulant release, endothelial damage, or stimulation of tissue factor production by host cells. However, not all of the mechanisms for the production of a hypercoagulable state of cancer are entirely understood [19].

On the other hand, sepsis is often associated with hemostatic changes ranging from subclinical activation of blood coagulation (hypercoagulability), which may contribute to localized venous thromboembolism, to acute disseminated intravascular coagulation (DIC), characterized by widespread microvascular thrombosis and subsequent consumption of platelets and coagulation proteins, eventually causing bleeding manifestations. The key event underlying this life-threatening complication is the overwhelming inflammatory host response to the infectious agent, leading to the overexpression of inflammatory mediators. The latter, along with the micro-organism and its derivatives, are now believed to drive the major changes responsible for massive thrombin formation and fibrin deposition, namely: 1) the aberrant expression of the TF by different cells (especially monocytes-macrophages), 2) the impairment of physiological anticoagulant pathways, orchestrated mainly by dysfunctional endothelial cells (ECs), and 3) the suppression of fibrinolysis due to overproduction of plasminogen activator inhibitor-1 (PAI-1) by ECs and likely also to thrombin-mediated activation of thrombin-activatable fibrinolysis inhibitor (TAFI) [20].

Conclusions

Hepatic artery thrombosis in the absence of a recent intra-abdominal surgical intervention is rare. There are very few cases of spontaneous hepatic artery thrombosis reported in the medical literature.

We believe that our case is unique for 2 reasons:Our patient did not undergo any procedure that may have precipitated hepatic artery thrombosis.Despite the absence of concurrent portal vein thrombosis, she had biochemical and imaging findings of hepatic ischemia.

We believe the precipitating factor of her presentation was malignancy-related hypercoagulability. However, it is felt that her frustrating outcome was not directly related to hepatic artery thrombosis, but rather to severe sepsis in an unfortunate patient with multiple co-morbidities.