JSM Vascular Medicine and Research

We reported the case of abdominal aortic thrombus as a result of plasminogen activator inhibitor-1 (PAI-1) elevation. The patient was a 65-year-old female who presented with acute left upper quadrant abdominal pain from splenic embolic infarction. A mural thrombus was found in the abdominal aorta rostral to the origin of the celiac and splenic artery. The patient was in a thrombophilic state from elevation of PAI-1. Unfractionated heparin bridge to coumadin resulted in complete resolution of the thrombus within 3 months of treatment.

There are 3 steps in the formation and degradation of a fibrin thrombus. First, formation and stabilization, second, inhibition of fibrinolysis, and third, activation of fibrinolysis [1]. Fibrinolysis is balanced by factors of activation and inactivation (inhibitor). Tissue plasminogen activator (t-PA) activates fibrinolysis and is protected from inactivation by its inhibitor, the plasminogen activator inhibitor-1 (PAI-1) [1]. Literature has shown ischemic cardiovascular events from increased plasma PAI-1 [2], whereas deficiency of PAI-1 results in severe bleeding [3]. Increased PAI-1 is associated with many factors including inflammatory cytokines, interleukins, growth factors, insulin resistance, bacterial endotoxins, race, ethnicity, gender, increased BMI, genetics, stress response, and smoking [4]. We present a patient with embolic splenic infarction as a result of aortic thrombus due to PAI-1 elevation.

The patient was a 65-year-old white female who presented with a three day history of left upper quadrant abdominal pain, worsening after deep breathing. She had a past history of unprovoked pulmonary embolism while taking contraceptive pills 15 years prior, was treated with intravenous unfractionated heparin, and then transitioned to coumadin for a total duration of 6 months. She also had a history of asthma, gout, and hypertension. She had an up-to-date mammogram, Pap smear, and colonoscopy. Her initial vitals were normal with a temperature 37.2 Celsius, blood pressure 131/70 mmHg, respiratory rate 18 per minute, heart rate 75 per minute, and her BMI was 26 kg/m2.There was point tenderness at the left upper abdominal quadrant. Bowel sounds were normal and there was no pleural rub. Admission labs including complete blood count, blood chemistry, and urinalysis were unremarkable. Stat abdominal contrast CT revealed focal segmental splenic infarction (Figure 1) and abdominal aortic thrombus proximal to the take-off of the celiac artery, measuring 2x4 cm in size (Figure 2). At this point, embolic splenic infarction from the aortic thrombus was diagnosed. Further investigations to locate the anatomical sources of the aortic thrombus were negative. Neither thrombus nor embolic origin was found on CTAgated aorta. Transthoracic echocardiogram and echocardiogram with bubble study were negative for intracardiac thrombus, vegetation or patent foramen ovale. Blood cultures were negative for bacteremia. Exploring the infectious cause of splenic infarction, along with hematologic malignancy causes was negative (Cytomegalovirus titer, Human Immunodeficiency Virus antigen, JAK2 mutation, Serum and Urine Protein Electrophoresis). She had no prior recent abdominal trauma and no recent abdominal surgery. Thrombophilia profile including protein C, protein S, factor V Leiden, antiphospholipid, lupus anticoagulant, prothrombin gene mutation, beta-2 glycoprotein, lipoprotein, homocysteine, and fibrinogen were within normal range, except the elevated PAI-1 level of 90 ng/mL (range 4-43 ng/mL, enzyme immunoassay (EIA), Diagnostic Nichols Institute, Capistrano, CA, USA). Provided that no surgery was warranted from general surgeon consultation, unfractionated heparin drip with venous thromboembolism protocol was immediately initiated with a target factor Xa level of 0.3-0.7 IU/mL. The patient was ultimately bridged to coumadin with a target INR 2-3. She promptly reported less abdominal pain within the first 24 hours. Intravenous morphine was discontinued at 48 hours. Follow up contrast abdominal CT at day 6 showed recanalization of the aorta (Figure 3). At 3 months follow up, contrast abdominal CT displayed complete resolution of the aortic thrombi (Figure 4).

The spleen receives 5% of the cardiac output making it prone to ischemic infarction [5]. From an ante mortem series, Frippiat et al., reviewed 64 cases of splenic infarction and found hematologic disorder as a leading etiology [6], whereas Schatter et al., found cardiogenic emboli was the predominant etiology [5]. Schatter et al., also described an autoimmune disease, infection, and hematologic malignancy as the etiologies of splenic infarction from their 32 case series. From the post mortem study, Okefee et al., found embolic source was the most common etiology in their 96 autopsies [7]. The same study found splenic congestion and splenic vein thrombosis were the most common causes of non-embolic source. Taken together, cardiogenic emboli and hematologic disease are among the most common etiology of splenic infarction. Provided a broad range of etiologies, splenic infarction could is the first presentation of a significant underlying disease in an otherwise previously healthy patient [5]. In this case, we explored all the possible causes of splenic infarction as described in the literature. Embolic cause of splenic infarction was established after we discovered thrombus in her abdominal aorta. Further investigation elucidated the thrombophilic state after we uncovered an elevation of PAI-1. To the best of our knowledge, only one case of splenic infarction from aortic thrombus has been previously reported, but not definitively identifying an underlying etiology [8]. We therefore report the unique case of aortic thrombus, as a result of increasing PAI-1 activity, leading to splenic infarction. Regarding the treatment of aortic thrombus, thrombectomy or anticoagulation, no standard guideline has been published yet. The optimal duration of therapeutic anticoagulation is still less defined in the literature. Verma et al., found association between hyper coagulation and occult malignancy in their 88 patients with aortic thrombus who developed either limb or visceral ischemia [9]. All of their hypercoagulable patients were prescribed lifelong therapeutic anticoagulation. Bowdish et al., reported 5 cases with aortic mural thrombus from a hypercoagulable state, all treated with therapeutic anticoagulation [10]. Given its simplicity and familiarity, we chose unfractionated intravenous heparin, venous thromboembolism protocol bridging to coumadin with target INR 2-3 in this case. The success of the treatment is attested by complete resolution of aortic thrombus at 3 months follow up CT scan. Given this was her second episode of unprovoked thrombosis, the patient agreed upon long-term therapeutic anticoagulation. In summary, our case not only demonstrated a clinical presentation and diagnosis of splenic infarction as a result of thrombophillia, but we also demonstrated the effectiveness of anticoagulation protocol in dissolving aortic thrombus from PAI- 1 elevation.