Portal vein thrombosis in systemic lupus erythematosus associated with anticardiolipin antibodies

Dear Editor, A 42-year-old White woman with an 8-year history of systemic lupus erythematosus (SLE) was admitted to the Hospital JB Iturraspe. Santa Fe, Argentina, in July 2003 with acute abdominal pain of 5 days’ duration. She had been diagnosed with SLE in 1997, based on the presence of leukopenia, lymphocytopenia, photosensitivity, malar rash, arthritis, oral ulcers and alopecia. Serology was positive for antinuclear antibodies (HEP-2) 1/5120 homogenous and speckled pattern, anti-double-stranded (ds) DNA (Crithidia luciliae) 1/160, anti-ribonucleoprotein, anti-La/SSB+ and anticardiolipin antibodies (aCL) IgG 20 UGPL and IgM 10 UGML. The patient’s obstetric history included six pregnancies, one of which ended as an abortion at the eighth week and another as a fetal death at the 24th week with no apparent reason. In 1998, a bone marrow biopsy with cytogenetic analysis, conducted after the discovery of cytopenia, was found to be normal. In September 2001 she had been admitted to another hospital with an episode of hematemesis. Digestive endoscopy showed grade 1 esophageal varices and an erosive gastroduodenitis, while abdominal ultrasound revealed mild splenomegaly with no hepatic involvement. On admission to our hospital, physical examination revealed pain on deep palpation in the epigastric region and upper right quadrant, with no signs of peritonism or chronic hepatopathy. No signs of SLE activity were observed. Abdominal ultrasound showed homogeneous splenomegaly, hepatomegaly with irregular shape and signs of gliositis, with echogenic enhancement of portal structures and caput medusae images (Fig. 1). Portal vein dilatation with thickened walls, echogenic formations obstructing vessel lumen and splenic artery dilatation were observed. An echo-Doppler ultrasonography evaluation confirmed the presence of a thrombus in the portal vein lumen occupying right and left branches up to the splenoportal confluence. Hepatic ultrasound displaying the medusae image due to portal vein thrombosis. Laboratory tests at that time showed alanine aminotransferase 59 IU/L (normal: 12–46), aspartate aminotransferase 35 IU/L (3–50), alkaline phosphatase 401 IU/L (65–300), amylasemia 50 IU/L (16–125), aCL IgG 7 UGPL and IgM 12 UMPL. Serological evaluations for hepatitis B, C and HIV virus were negative. Treatment commenced with propranolol and heparin, and anticoagulation was continued with acenocoumarol (with target international normalization ratio 2–3), which resulted in disappearance of abdominal pain. In October 2003, the patient was diagnosed with stage 1B1 squamous carcinoma of the uterine cervix according to International Federation of Gynecology and Obstetrics criteria (clinical lesions confined to cervix and not larger than 4 cm), and received chemotherapy and radiotherapy. In May 2004, the patient was readmitted to hospital with a new episode of digestive bleeding and anticoagulation was discontinued. During the hospital stay, she presented a transient ischemic attack (TIA) and brain computed tomography (CT) scan revealed multiple ischemic injuries. An echocardiogram showed normal cardiac dimensions with no effusions or vegetations. In 2006, she returned, presenting a tumor relapse, without any sign of activity of the SLE. Tests for thrombophilia were done, including lupus anticoagulant, aCL IgG, IgM, anti-β2-glycoprotein-1 (aβ2GPI) IgG and IgM antibodies, protein C, protein S, antithrombin III, factor V, factor VIII, factor IX, factor X, prothrombin 20210 A, activated protein C resistance and homocysteine; all values were in the normal range. In October 2008, the patient died due to complications from the oncologic disease. Up to her death, SLE showed mainly cutaneous, hematological and articular compromise, with a good response to low-dose corticosteroids and chloroquine. Portal vein thrombosis (PVT) is a rare cause of presinusoidal portal hypertension. Many medical and surgical conditions may predispose to PVT, including infections, malignancies, myeloproliferative disorders, pregnancy and postpartum period, oral contraceptives and antiphospholipid syndrome (APS).1 The disease has both an acute and a chronic form. Acute PVT is characterized by abdominal pain of sudden onset, sometimes severe, that may be occasionally associated with nausea and diarrhea. Physical examination often reveals splenomegaly, but ascites is rare.2 Chronic forms of the disease tend to be completely asymptomatic. Clinical manifestations are usually complications of portal hypertension like hematemesis due to ruptured esophageal varices.3 The most used diagnostic methods are color Doppler ultrasonography, CT scan and magnetic resonance imaging (MRI). Color Doppler ultrasonography is generally the first imaging examination to be conducted due to its low cost and efficacy, and it achieves a sensitivity of 73% and a specificity of 99%.4 Our patient presented with diffuse intense abdominal pain of 5 days’ duration. Ultrasound scans revealed splenomegaly and hepatomegaly without ascites, while portal echo-Doppler ultrasonography revealed the presence of a thrombus in the portal vein lumen occupying right and left branches up to the splenoportal confluence. Treatment with anticoagulants and propranolol provided a rapid symptomatic relief. It is important to consider that 3 years earlier the patient had presented an episode of hematemesis and digestive endoscopy revealed grade 1 esophageal varices. For this reason, we thought the patient had previous episodes of PVT that went unnoticed but set off hypertension in the portal system, similar to what may occur in the pulmonary vasculature, and that the last episode prompted her to consult, resulting in the etiologic diagnosis of portal hypertension. In patients with cervical cancer, venous thromboembolism is seen in 0–34% of cases. Risk factors related to this complication are tumor size and the invasion and/or compression of pelvic veins or vessels, procoagulant factors such as tissue factor, and factors related to chemotherapy and radiotherapy.5 Given that thrombotic alterations in our patient had appeared before the tumor was found, and considering the small size of the tumor, the lack of involvement of gynecological organs other than the cervix and the absence of chemotherapy and radiotherapy before abdominal clinical manifestations, we believe that the malignant disease was not related to the portal venous thrombosis. Primary myeloproliferative disorders are the cause of PVT in 30% of cases, whereas APS is found in 11% of these patients.6 On the other hand, PVT was also seen in patients with rheumatoid arthritis7 and SLE, that could be associated8-10 or not11, 12 with antiphospholipid antibodies (Table 1). In addition, although our patient fulfilled the clinical criteria for APS (fetal death, venous and arterial thrombosis),13 she did not meet serological criteria, since her aCL levels were always low. Nonetheless, we believe that the base treatment of the hypercoagulable state should have been long-term anticoagulation, although this therapy had to be interrupted when the patient presented a new episode of digestive bleeding. The presence of signs of portal hypertension in patients with connective tissue diseases, which may be asymptomatic, must alert to the possibility of abdominal vessel thrombosis.

Topic: Systemic Lupus Erythematosus Research
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences