Primary Antiphospholipid Syndrome Presenting as Budd-Chiari Syndrome

Abstract

Case ReportsPrimary Antiphospholipid Syndrome Presenting as Budd-Chiari Syndrome Mahgoub B. Ibrahim and MBBS, FRCP Abdulhalim J. KinsaraMD, JBIM Mahgoub B. Ibrahim Address reprint requests and correspondence to Dr. Ibrahim: Department of Medicine, King Khalid National Guard Hospital, P.O. Box 9516, Jeddah 21423, Saudi Arabia. From the Gastroenterology Section, Department of Medicine, King Khalid National Guard Hospital, Jeddah, Saudi Arabia. Search for more papers by this author and Abdulhalim J. Kinsara From the Gastroenterology Section, Department of Medicine, King Khalid National Guard Hospital, Jeddah, Saudi Arabia. Search for more papers by this author Published Online:1 Mar 1998https://doi.org/10.5144/0256-4947.1998.154SectionsPDF ToolsAdd to favoritesDownload citationTrack citations ShareShare onFacebookTwitterLinked InRedditEmail AboutIntroductionMB Ibrahim, AJ Kinsara, Primary Antiphospholipid Syndrome Presenting as Budd-Chiari Syndrome. 1998; 18(2): 154-157We report the case of a young Saudi male who presented with Budd-Chiari syndrome (BCS), with not only hepatic vein thrombosis but also an extensive thrombosis of the inferior vena cava (IVC) and portal vein, associated with anticardiolipin antibodies (antiphospholipid syndrome). No other thrombogenic condition was present as an alternative explanation for the highly unusual site of the venous thrombosis. The patient was managed with prolonged anticoagulation and recovered successfully.The association of antiphospholipids with BCS is well recognized in the literature, but to the best of our knowledge this is the first case to be reported in the Middle East.CASE REPORTA 30-year-old Saudi soldier presented to our hospital with a seven-month history of abdominal pain and progressive abdominal distention associated with mild jaundice. He had no history of gastrointestinal bleeding. He denied any history of blood transfusion, taking medications or alcohol abuse.Physical examination showed an ill-looking man who was generally wasted and jaundiced. Abdominal examination showed distended veins over his abdomen and back, extending up to the thoracic wall, with an upward direction of the flow. There was hepatomegaly and moderate ascites. The rest of the examination was non-contributory.Laboratory tests revealed a normal full blood count, erythrocyte sedimentation rate, alpha fetoprotein, urea and electrolytes, but abnormal liver function tests with a total bilirubin of 67 μmol/L, aspartate transaminase of 153 U/L, alanine transaminase of 90 U/L, alkaline phosphatase of 162 U/L, albumin of 29 g/L and globulin of 40 g/L. The prothrombin time (PT) was 27 seconds, with a control of 16 seconds (international normalizing ratio of 1.8). Activated partial thromboplastin time (APTT) andthrombin time (TT) were normal. Screening for viral hepatitis B, C, and schistosomiasis were negative. Diagnostic abdominal paracentesis showed a straw-colored ascitic fluid with protein content of 24 g/L. There was no evidence of infection or malignancy. The liver biopsy was not done because of prolonged PT. Transjugular liver biopsy was not possible because of the extent of the IVC thrombosis up to the right atrium.Abdominal ultrasound scan showed an enlarged liver with an inhomogeneous echo texture, a very small IVC and very small hepatic veins. The portal vein with its central tributaries was also small, with a very echogenic wall suggestive of portal vein thrombosis. There was moderate ascites. Color Doppler ultrasound of the liver and IVC revealed an abnormal flow pattern with a flat spectrum in the right hepatic vein. No obvious flow could be obtained from the middle and the left hepatic veins. Flow was abnormal in the IVC.Abdominal CT scan further confirmed the ultrasound findings of the inhomogeneous hypodense lesions, mostly in the right lobe of the liver, compatible with abnormal liver perfusion or tumor infiltration (Figure 1). The caudate lobe was moderately enlarged. There was thrombosis of the IVC (Figure 2) from the level of the bifurcation up to the right atrium, however, recanalization was visualized. The right hepatic vein was poorly seen, with no visualization of the left and middle hepatic veins. There was portal vein thrombosis, profuse collateral vessels, ascites and no evidence of splenic enlargement. Gastroscopy showed two grade 1 esophageal varices. The color Doppler ultrasound and the CT scan findings were so convincing that venographic studies were not deemed necessary.Figure 1. Axial post-contrast enhanced dynamic CT showing non-perfusion of most of the right lobe of the liver and a thrombus in the IVC (see short black arrow).Download FigureFigure 2. Axial post-contrast enhanced dynamic CT showing a thrombus in the IVC (see arrow).Download FigureAt this stage, the working diagnosis was chronic hepatic venous thrombosis (Budd-Chiari syndrome), including a long segment IVC thrombosis associated with portal vein thrombosis. This led us to screen for a hypercoagulablestate. Kaolin clotting time (KCT) and diluted Russell's viper venom time (d RVVT) tests were negative for lupus anticoagulant. Ham's test, serology for syphilis and antinuclear antibodies were negative. Protein C, protein S and antithrombin III activities were normal. However, screening for anticardiolipin (aCL) antibodies by ELISA technique showed that aCLIgG antibodies were negative (6.5 U/mL, normal <12.4), but aCLIgMantibodies were positive (16.5 U/mL, normal <9) and aCL IgAantibodies were also positive (30.3 U/mL, normal <12). This led to the diagnosis of primary antiphospholid syndrome as the underlying cause of the extensive venous thrombosis.The patient was treated with a short course of diuretics which easily controlled his ascites, and was commenced on warfarin therapy aiming to an INR of about three. The patient was eventually discharged home and followed up satisfactorily as an outpatient for two years. He showed dramatic improvement and remained asymptomatic with no further recurrence of his ascites. His liver function test showed marked improvement. The latest results were only mildly abnormal, a total bilirubin of 29 μmol/L, aspartate transaminase of 45 U/L, alanine transaminase of 35 U/L, alkaline phosphatase of 110 U/L and albumin of 35 g/L. Repeat color Doppler ultrasound and CT showed better hepatic perfusion and hepatic venous flow with better recanalization of the IVC and hepatic veins. His condition remained under satisfactory control while on prolongedcoagulation.We suggest that the anticardiolipin antibodies IgM and IgA may have been causally related to the development of the patient's hepatic disease and extensive thrombosis.DISCUSSIONBudd-Chiari syndrome (BCS) is a well-known entity that results from obstruction of the major hepatic veins Ascites, hepatomegaly and abdominal pain constitute the classic triad of BCS of hepatic vein or IVC obstruction This condition was first mentioned by Budd in the mid 1800s, and additional information was provided by Chiar in the 1890s. Primary BCS is a rare disorder but relatively prevalent in the Far East, Northern India and Africa.1 The syndrome has been associated with hypercoagulable states neoplasms, trauma, medications, including oral contraceptives, congenital webs in the IVC and/or hepatic veins.2 There are two major clinical forms of BCS. The acute syndrome is invariably associated with extensive blockage of the major hepatic veins, resulting in congestive liver cell necrosis. In a small but significant number of patients, the IVC is also occluded. The important etiological factors are related to hypercoagulability of the blood. Immediate placement of shunt improves survival.3 The chronic syndrome is characterized by portal hypertension, and is associated with a variable abnormal vascular anatomy. Shunt surgery is effective but procedures aimed at the primary pathology are likely to be even more so.3 Until quite recently, BCS was regarded as idiopathic in a large proportion of cases.4 Several observations of hepatic vein thrombosis associated with antiphospholipid antibodies have been described.6,7 The precise mechanism by which anticardiolipin antibody acts is not known. Abnormal platelet aggregation, decreased endothelial cell prostacyclin production, inhibition ofprotein C, possibly by eliminating the enhancing effect of phospholipids on thrombomodulin, and decreased fibrinolysis by unopposed tissue plasminogen activator-inhibitor, or prekallikrein inhibition have all been proposed.8 Antiphospholipid syndrome can increase thromboxane A2 and act as plasminogen activator-inhibitor (PAI) type III. It is also associated with reduced prostacycline, AT III, protein C, protein S and factor XII, all of which are thrombogenic. Of late, interest has been shown in the role of the serum protein β2-glycoprotein I as a mediator of antiphospholipid antibody effects.9 The link between arterial or venous thrombosis and the presence of antiphospholipid antibodies has been clearly demonstrated in systemic lupus erythematosus.10 Harris et al. in 1987 individualized the antiphospholipid syndrome (APS),11 which covers patients with at least one type of antiphospholipid antibody (lupus anticoagulant and/oranticardiolipin antibodies), and arterial or venous thrombosis and/or recurrent fetal loss. APS can be associated with systemic lupus erythematosus and other connective tissue diseases, malignant tumors, or prolonged treatment with various drugs. However, APS has increasingly been recognized in the absence of all these conditions, and the concept of a “primary” syndrome has been proposed by Ashersonet al.12 It has recently been demonstrated that patients with antiphospholipid antibodies are prone to thrombotic complications.13There is no general agreement on the definition of APS. The initial definition proposed by Harris et al. has been adopted in the three largest published series, and is still commonly used.11–13 The association of BCS with APS seems to be rare. Thus, in a recently published series of 177 patients with BCS, no such association was reported.3 Nevertheless, there were 35 patients with “idiopathic” BCS. The authors suggest that BCS is a primary vascular disorder and the presence of a high hypercoagulable state appears likely. The fact that most patients had no evidence of coagulopathy at presentation suggests that some of these mechanisms may be intermittent or transient. In a prospective study of 22 patients with non-tumorous BCS, Pelletier et al. found that four patients had APS with no other cause of hepatic vein thrombosis. APS was secondary to systemic lupus erythematosus in one case, to a lupus-like disease in another, and apparently primary in the remaining two cases. The authors concluded that APS is a frequent cause, after myeloproliferative disorders, of non-tumorous BCS. In such patients, long-term anticoagulation may prevent recurrence or extension of thrombosis.14 An active search for the antiphospholipid antibodies should be performed to lower the percentage of apparently idiopathic cases of BCS.7 BCS resulting from this cause may have a good response to treatment with oral anticoagulant, and this treatment should be maintained permanently.15It is interesting that thrombosis in our patient was associated with aCLIgM and aCL IgA classes. Although thrombotic events are usually associated with aCLIgG class, thrombosis in patients with aCLIgM class has been described as well.16 Harris et al. demonstrated that aCLIgM and aCL IgA are also associated with thrombosis. The presence of any one anticardiolipin antibody, a combination of two, or indeed all three together may be associated with thrombosis and thromboembolism.17In our patient, thrombosis was seen in the portal circulation, the hepatic veins and a long segment of the IVC. It is known that concomitant portal vein thrombosis may be seen in 20% of patients with BCS. The CT findings of our patient were initially reported as suspicious of a hepatic tumor. The findings of a space-occupying lesion in CT or MRI may not always indicate a tumor in a patient with BCS. It may be an area of hemorrhagic necrosis, as demonstrated by Shapiro et al.19 Antiphospholipid antibodies titer may be low or fluctuate,20 and may fall below the detection limit duringthrombotic episodes.21 For these reasons, it may be advisable to repeat the tests for antiphospholipid antibodies some time after the acute episode.Prophylaxis of venous thrombosis in APS has not yet been clearly defined. Steroids, immunosuppressive agents, high-dose immunoglobulin infusions and/or plasmapheresis have not been able to eliminate antiphospholipid antibodies.22 Moreover, their adverse effects and high costs make them inappropriate for long-term treatment. However, a consensus is being reached on some aspects of treatment. Patients with high antiphospholipid concentrations and previous major thrombosis require long-term, possibly permanent, warfarin anticoagulation.6,23 The clinical course after hepatic vein thrombosis cannot be properly estimated from the available data. The high risk of recurrent thrombotic events after warfarin withdrawal has been reported in patients with APS. The efficacy of antiplatelet agents has not been clearly established.23In conclusion, patients with BCS should be tested for lupus anticoagulants and anticardiolipin antibodies. BCS resulting from this cause may have a good response to treatment with oral anticoagulants. This treatment should be maintained permanently.15ARTICLE REFERENCES:1. Sakugawa H, Higashionna A, Oyakawa T, Kadena K, Kinjo F, Sauto A. "Ultrasound study in the diagnosis of primary Budd-Chiari syndrome" . Gastroenterol (Japan). 1992; 27: 69–77. Google Scholar2. Powell-Jackson PR, Melia W, Canalese J, Pickford RB, Portmann B, Williams R. "Budd-Chiari syndrome: clinical patterns and therapy" . Quart J Med. 1982; 201: 78–82. Google Scholar3. Dilawari JB, Bamberg P, Chawla Y, Kaur U, Bhusnurmath SR, Malhotra HS, et al. 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Google Scholar Previous article Next article FiguresReferencesRelatedDetails Volume 18, Issue 2March 1998 Metrics History Received11 May 1997Accepted4 December 1997Published online1 March 1998 ACKNOWLEDGMENTSWe would like to acknowledge the contribution and support of Dr. Gerald Tevaarwerk, Chair of Medicine, King Khalid National Guard Hospital, and Ms. Belle Almoro, Research Secretary.InformationCopyright © 1998, Annals of Saudi MedicinePDF download