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Transformation of inferior vena caval thrombosis to membranous obstruction in a patient with the lupus anticoagulant
GASTROENTEROZOGY 1986:91:219-24
Transformation of Inferior Vena Caval Thrombosis to Membranous Obstruction in a Patient With the Lupus Anticoagulant HIDETAKA TERABAYASHI, KUNIO OKUDA, FUMIO NOMURA, KUNIHIKO OHNISHI, and PAKMING WONG First Department of Medicine and Second Department Medicine, Chiba, Japan
A 24yr-old woman with hemolytic anemia developed multiple thrombosis of the hepatic vein and inferior vena cava. She was found to have circulating lupus anticoagulant that could have been causally related to the thrombosis and hence the Budd-Chiari syndrome. On her first admission to the hospital vena cava and hepatic vein catheterizations revealed partial thrombotic occlusion of the cava at the level of the diaphragm, which was subsequently transformed into complete membranous obstruction. The right hepatic vein, which was patent on the first admission, was also completely occluded. These observations support the theory that membranous obstruction of the inferior vena cava is a sequela to inferior vena caval thrombosis rather than a congenital anomaly. Hepatic vein thrombosis of the Budd-Chiari syndrome is a severe liver disease often terminating in death. It is sometimes complicated by occlusion of the inferior vena cava (IVC) (1-3). By contrast, membranous obstruction of the IVC (MOVC) of an insidious onset in adults has a better prognosis and is more common in Japan (4-8),India (g-11),Israel (121, and South Africa (l3,14). In MOVC, the genesis of the membrane has been speculated upon, but the current leading theory considers it a congenital anomaly (4,6-8,13,15,16). Old theories suggested “mechanical injury” (l7),“infection-phlebitis” (18, 19),and “thrombosis” (2O), but they have been practically forgotten. Received October 11, 1985. Accepted January 29, 1986. Address requests for reprints to: Kunio Okuda, M.D., Ph.D., Department of Medicine, Chiba University Hospital, Chiba, Japan (280). The authors thank Professor Dame S. Sherlock, London, for her suggestion regarding anticoagulant when this case was discussed at a clinical conference in Chiba on November 15, 1983. 0 1986 by the American Gastroenterological Association 0016-5085/86/$3.50
of Medicine,
Chiba University
School of
We have recently studied a woman with autoimmune hemolytic anemia who developed an acute episode of Budd-Chiari syndrome with multiple thrombosis involving the hepatic veins and the IVC. She was found to have several autoantibodies including lupus anticoagulant. Within 2 yr, the IVC, initially patent but narrowed by mural thrombi, turned into a thick, firm membrane with complete obstruction of major hepatic veins. The observation in this patient seems to support the “thrombosis” theory of the cause of MOVC. Case Report A 24yr-old unmarried woman was admitted to the hospital on June 17, 1983 because of epigastric pain and icterus. Four years earlier, she developed ankle edema and was treated. One year later, she again noticed leg edema and laboratory examination showed slightly elevated serum lactic acid dehydrogenase and bilirubin levels. Her hematocrit was 41% at this time. Three weeks before admission, she experienced back and epigastric pain with a low-grade fever. Three days later, jaundice was noted and she was admitted to the hospital, where liver scintiscan was interpreted as showing multiple space-occupying lesions. She was then referred to us. The patient had no history of jaundice, alcoholism, drug abuse, or blood transfusion. On admission, the patient appeared pale and slightly jaundiced. A tender liver edge was palpated 4 cm below the right costal margin and the spleen was felt 2 cm below the left costal margin. There were dilated veins on the abdominal wall and the blood flow was cephalad. There was slight pretibial pitting edema but no ascites. Laboratory examinations on admission revealed the following values: red blood cell count, 2.19 x 10”/mm3; hemoglobin, 7.0 g/dl; hematocrit, 20.9%; white blood cell count, 6100imm3; platelet count, 69,000/mm3; reticulocytes, 11%; prothrombin time, 14.9 s (control, 12 s); Abbreviations used in this paper: WC, inferior vena cava: MOVC, membranous obstruction of the inferior vena cava.
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Figure 1. Real-time linear scan ultrasonogram on admission demonstrating a mass protruding in the inferior vena cava (at arrow].
erythrocyte sedimentation rate, 127 mm/h; fibrinogen, 430 mg/dl; and fibrin degradation products, 380 pg/dl. Both the direct and indirect Coombs’ tests were positive. Serum aspartate aminotransferase was 28 mu/ml; total protein, 6.4 g/dl; albumin, 3.3 g/dl; total bilirubin, 3.3 mg/dl; and unconjugated bilirubin, 1.7 mg/dl. Serum a-fetoprotein, carcinoembryonic antigen, hepatitis B surface antigen, hepatitis B surface antibody, smooth muscle antibody, antimitochondrial antibody, lupus erythematosus and rheumatoid arthritis tests, anti-extractable nuclear antigens, Treponema palladium hemagglutination, and ribonucleoprotein antibody were negative, but antinuclear antibody was positive at a low titer. On admission, ultrasonography demonstrated hepatomegaly and two echogenic materials that were most likely thrombi in the IVC (Figure 1) and in the right hepatic vein near its opening into the IVC (Figure 2). They were not moving in the venous lumen. Enhanced computed tomography scan revealed a thrombus in the IVC and some collateral veins. Hepatic venography and cavography showed partial obstruction of the IVC by a thrombus (Figure 3), but the catheter could be pushed through the stenotic lumen of the IVC. A balloon catheter revealed that the right hepatic vein was also patent, but it was tortuous with several vein-to-vein anastomoses and reduced numbers of branches (Figure 4). Wedged hepatic venous pressure with a reference at 10 cm above the table was 360 mmH,O, free hepatic vein pressure was 350 mmHzO, and the right atria1 pressure was 24 mmHzO. The pressure of the IVC below the thrombus at the level of the first lumbar vertebra was 214 mmHzO.
GASTROENTEROLOGY Vol. 91. No. 1
On the 60th hospital day, a repeat hepatic venography was performed. It showed a complete obstruction of the IVC with a new thrombus adherent to the IVC. The catheter could no longer be passed through the previously narrowed portion of the IVC, neither from below nor from above. The patient was started on a regimen of warfarin sodium and urokinase. One month later, repeat ultrasonography showed that the thrombi that had previously been present in the right hepatic vein and the IVC had disappeared. After the patient was discharged from the hospital, her leg edema became apparent again, and she was placed on furosemide and spironolactone therapy. Warfarin was discontinued after 1 yr and prednisolone was gradually reduced to the maintenance dose of 5 mg. During the follow-up period, the association of lupus anticoagulant and thrombosis (21) and Budd-Chiari syndrome (22) came to our attention. We then tested stored plasma for anticoagulant by the methods of Exner et al. (23) and Boxer et al. (24). The test was positive, and the results of the coagulation study fulfilled the criteria for lupus anticoagulant (25). Subsequent plasma samples during the follow-up period were also positive. The patient entered the hospital on August 19, 1985 for evaluation. On admission, her blood counts were normal. Her total bilirubin was 1.9 mg/dl, direct bilirubin 6.9 mg/dl, haptoglobin 49 mg/dl; antinuclear antibody (1:80), direct and indirect Coombs’ tests, and the rapid plasma reagin card test were positive, but other tests for autoantibodies were
Figure
2. Ultrasonogram showing a mass protruding in the right hepatic vein near its opening into the inferior vena cava (at arrow).
FORMATION
July 1986
OF MEMBRANOUS
OBSTRUCTION
IN IVC
221
negative. Hepatic vein catheterization revealed complete obstruction of the IVC at the level of the diaphragm (Figure 5). The obstruction measured 9 mm in thickness, with narrowing of the lumen of the IVC immediately below the obstruction compared with the previous caliber on admission (cf. Figure 3). The pressure was 52 mmHzO in the superior vena cava and 290 mmH,O in the IVC at the level of the first lumbar vertebra. Shortly after discharge, the patient developed thrombophlebitis of the legs and her prednisolone dosage has since been increased to 30 mg.
Summary of Clinical Findings This young woman had a number of autoantibodies, including anticoagulant, and presented with autoimmune hemolytic anemia and multiple thrombosis involving the hepatic veins and IVC. On admission, there was a large mural thrombus at the level of the diaphragm in the IVC. This thrombus expanded and eventually occluded the IVC, which was still patent on admission. Judging from her past history of ankle edema, thrombosis of IVC perhaps was not a new occurrence; she could have had repeated mild thrombosis at this site or the thrombus at this location could have been growing. The presence of distinct collaterals demonstrated by the first venography attests to such an assumption. The major thrombus at the level of
Figure 4. Right hepatic vein catheterization with a balloon catheter. Marked tortuosity of the right hepatic vein and vein-to-vein anastomoses are apparent: the tortuosity could be due to parenchymal structural distortion secondary to circulatory disturbances.
the diaphragm slowly transformed into a firm obstruction that is generally called MOVC. During the course, another thrombus formed along the wall of the IVC caudad to the occluding thrombus and it subsequently disappeared. However, the right hepatic vein, which could be catheterized on admission, as well as the left hepatic vein were eventually occluded. Thus, there were dynamic changes in the size of the thrombi, with disappearance, new formation, growth, and transformation into a fibrous tissue. Contraction of the thrombus due to organization and fibrosis was apparent from reduction of the diameter of the IVC near the membrane (cf. Figures 3 and 5).
Discussion
Figure
3. Inferior sion of through left side
vena cavography demonstrating a partial occluthe inferior vena cava. The catheter passed the stenotic area when it was passed along the (inset).
The classical Budd-Chiari syndrome and MOVC in the hepatic portion have been considered separately by most authors in the past decade (3-16). The membranous state of the occlusion in the latter was so emphasized that many reports in recent years treated the two as if they were different diseases, with the assumption that MOVC was a congenital abnormality more common in the Orient (4-11). However, past studies on hepatic vein thrombosis frequently recognized the coexistence of thrombosis in the IVC, most commonly in its hepatic portion. According to Parker (l), who analyzed the etiologic factors in 236 cases of hepatic vein occlusion, 11 of 14 idiopathic cases involved lesions in the IVC. The first case of MOVC in the Western literature was that reported by Thompson and Turnbull (20) in 1912; in
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GASTROENTEROLOGY Vol. 91, No. 1
5. A. Inferior vena cavogram obtained 2 yr after the patient’s first admission. Complete obstruction of the inferior vena cava at the level of the diaphragm with newly formed collaterals is shown. The obstruction measured 9 mm. B. Schema of A. Catheters are shown by straight thick lines and collaterals by dotted lines.
this patient, there was a fibrous diaphragm with a narrow central hole constricting the IVC. Subsequent and Japan (4-8) reports from the West (15,16,26-28) emphasized the membranous occlusion of the IVC in the hepatic portion and proposed that it had a specific etiology. In 1970, after reviewing 150 cases from the literature including 8 of their own, Hirooka and Kimura (6) postulated that abnormal embryonic development creates a gap between the IVC and the heart, and the gap turns into a membrane. They included the cases with occlusions much thicker than a membrane and divided them into seven groups according to the pattern of occlusion. More recently, Simson (13) from Pretoria studied 101 autopsy cases of MOVC that also included thick obstructions, and suggested that it is a congenital anomaly and that somehow it frequently gives rise to
hepatocarcinogenesis. The reported membranes varied a great deal in size, from a very thin membrane to occlusions several centimeters thick. Some thin membranes had a central opening and were also called webs, with no clear distinction being made between “membrane” and “web.” Along with the congenital theory, there have been several other suggestions or speculations: the socalled “mechanical injury” (li’), “infection-phlebitis” (18,19), and “thrombosis” (20) theories. Because of the inconstant anatomic changes, variable thicknesses of the membrane, and irregular involvement of the hepatic veins, the present authors maintained that this is an acquired disorder associated with thrombosis (29,303. We also described membranous obstruction of the portal vein associated with multiple thrombosis of the portal vein system (31). The
July 1986
current case provides evidence that thrombosis of the IVC at the level of the diaphragm will turn into a fibrous occlusion. The congenital anomaly theory cannot explain the adult onset of MOVC. The reason for the hepatic portion of the IVC being the most common site of membrane formation is still unclear. Mechanical endothelial injury due to diaphragmatic movements in its relation to the heavy liver may invite thrombosis as the mechanical injury theory suggests (IT), or the turbulence of blood flow as a result of hepatic venous flow perpendicular to the IVC may predispose this area to thrombosis (20). However, there still is a possibility that MOVC has multiple origins or etiologies. The association of anticoagulant with BuddChiari syndrome is a relatively recent observation, first described by Pdmeroy et al. (22) in 1984, but association of Budd-Chiari syndrome with systemic lupus erythematosus and other autoimmune diseases had been reported sporadically (32-34). Spontaneous acquired anticoagulant occurs most frequently in systemic lupus erythematosus, but it also occurs in a number of other clinical states including autoimmune hemolytic anemia, as in our case (35,36). Lupus anticoagulant is an immunoglobulin that interferes with the conversion of prothrombin to thrombin by the phospholipid prothrombin activator complex (25,37), but paradoxically it seems to be associated with venous thrombosis (22,36,38-40).
FORMATION OF MEMBRANOUS
11.
12.
13.
14. 15.
16.
17. 18. 19.
20. 21.
22.
References Parker RGF. Occlusion of the hepatic veins in man. Medicine 1959;38:369-402. RB. Thrombosis of the hepatic veins. The 2. Thompson Budd-Chiari syndrome. Arch Intern Med 1947;80:602-15. syndrome. In: Schiff L, 3. Reynolds TB, Peters RL. Budd-Chiari Schiff ER, eds. Diseases of the liver. 5th ed. Philadelphia: Lippincott, 1982:1622-30. S, Yokoyama T, Takeshige K, Iwatsuki S. 4. Yamamoto Budd-Chiari syndrome with obstruction of the inferior vena cava. Gastroenterology 1968;54:1070-84. 5. Nakamura T, Nakamura S, Aikawa T, Suzuki 0, Onodera A, Karoji N. Obstruction of the inferior vena cava in the hepatic portion and the hepatic veins. Angiology 1968;19:479-98. 6. Hirooka M, Kimura C. Membranous obstruction of the hepatic portion of the inferior vena cava. Surgical correction and etiological study. Arch Surg 1970;100:656-63. 7. Kimura C, Matsuda S, Koike H, Hirooka M. Membranous obstruction of the hepatic portion of the inferior vena cava; clinical study of nine cases. Surgery 1972;72:551-9. 8. Takeuchi J, Takada A, Hasumura Y, Matsuda Y, Ikegami F. Budd-Chiari syndrome associated with obstruction of the inferior vena cava. Am J Med 1971;51:11-20. 9. Datta DV, Samanta SS, Singh A, Gupta BB, Aikat BK, Chhuttani PN. Clinical spectrum of Budd-Chiari syndrome in Chandigarh with particular reference to obstruction of intrahepatic portion of inferior vena cava. Indian J Med Res 1972;60:385-402. 10. Datta DV, Vashishta S, Samanta AK, Chhuttani PN. Diagnostic value of combined transhepatic venography and inferior 1.
23.
24. 25.
26.
27. 28.
29.
30. 31.
32.
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vena cavography in chronic Budd-Chiari syndrome. Am J Dig Dis 1978;23:1031~1. Khuroo MS, Datta DV. Budd-Chiari syndrome following pregnancy. Report of 16 cases, with roentgenologic, hemodynamic and histologic studies of the hepatic outflow tract. Am J Med 1980;68:113-21. Adar R, Rosenthal T, Mozes M. Vena caval obstruction: some epidemiological observations in 76 patients. Angiology 1974; 25:43340. Simson IW. Membranous obstruction of the inferior vena cava and hepatocellular carcinoma in South Africa. Gastroenterology 1982;82:171-8. Van der Merwe SF, Arts MSC. Primary liver cancer in the Transvaal. Hepatogastroenterology 1981;28:233-5. Rogers MA, Chesler E, du Plessis L, Jaffe N, Joubert E. Membranous obstruction of the hepatic segment of the inferior vena cava. Br J Surg 1964;54:221-5. Sen PK, Kinare SG, Kelkar MD. Congenital membranous obstruction of the inferior vena cava: report of a case and review of the literature. J Cardiovasc Surg 1967;8:344-52. Kretz R. Pathologie der Leber. Ergeb allg Path01 u path01 Anat 1902;82:473-94. Kelsey MP, Comfort MW. Occlusion of the hepatic veins; review of twenty cases. Arch Intern Med 1945;75:175-83. Kibel MA, Marsden HB. Inferior vena caval and hepatic vein thrombosis: the Chiari syndrome in childhood. Arch Dis Child 1956;31:225-8. Thompson T, Turnbull HM. Primary occlusion of the ostia of the hepatic veins. Q J Med 1912;5:277-96. Boey ML, Colaco CG, Fharavi AE, Elkon KB, Loizou S, Hughes GRV. Thrombosis in systemic lupus erythematosus: striking association with the presence of circulating anticoagulant. Br Med J 1983;287:1021-3. Pomeroy C, Knodell RG, Swaim WR, Arneson P, Mahowald ML. Budd-Chiari syndrome in a patient with the lupus anticoagulant. Gastroenterology 1984;86:158-61. Exner T, Rickard KA, Kronenberg H. A sensitive test demonstrating lupus anticoagulant and its behavioural patterns. Br J Haematol 1978;40:143-51. Boxer M, Ellman L, Carvalho A. The lupus anticoagulant. Arthritis Rheum 1976;19:1244-8. Carreras LO, Vermylen JG. “Lupus” anticoagulant and thrombosis-possible role of inhibition of prostacyclin formation. Thromb Haemostasis 1982;48:38-40. Lam CR, Green E, Gale H. Transcardiac membranatomy for obstruction of the hepatic portion of the inferior vena cava. Circulation 1965;31,32(Suppl):188-91. Smith L. A case of congenital stenosis of the inferior vena cava with portal hypertension. Br J Surg 1965;52:913-6. Johansson L, Moberg A, Soderlund K, et al. Congenital obstruction of the inferior vena cava. Acta Chir Stand 1966; 131:509-15. Okuda K. Membranous obstruction of the inferior vena cava: etiology and relation to hepatocellular carcinoma. Gastroenterology 1982;82:376-9. Okuda K, Ostrow JD, Clinical conference: membranous type of Budd-Chiari syndrome. J Clin Gastroenterol 1984;6:81-8. Kimura K, Okuda K, Takara K, Matsutani S, Lesmana L. Membranous obstruction of the portal vein. A case report, Gastroenterology 1985;88:571-5. Disney TF, Sullivan SN, Haddad RG, Lowe D, Goldbach MM. Budd-Chiari syndrome with inferior vena cava obstruction associated with systemic lupus erythematosus. J Clin Gastroenter01 1984;6:253-6.
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33. Comes J, Robert A, Levy VG, Darnis F. Budd-Chiari syndrome in a patient with mixed connective-tissue disease. Dig Dis Sci 1980;25:467-9. 34. Matsuura H, Matusmoto T, Hashimoto T. Budd-Chiari syndrome in a patient with Sjogren’s syndrome. Am J Gastroenterol 1983178:822-5. 35. Schleider MA, Nachman RL, Jaffe EA, Coleman M. A clinical study of the lupus anticoagulant. Blood 1976;48:499-509. 36. Mueh JR, Herbsi KD, Rapaport SI. Thrombosis in patients with the lupus anticoagulant. Ann Intern Med 1980;92(Part 1):156-9.
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37. Shapiro SS, Thiagarajan R. Lupus anticoagulant. In: Spaet TH, ed. Progress in hemostasis and thrombosis. New York: Grune & Stratton, 1982:263-83. 38. Walker Bowie EJ, Thompson JH Jr, Pascuzzi CA, Owen CA. Thrombosis in systemic lupus erythematosus despite circulating anticoagulant. J Lab Clin Med 1963;62:416-30. 39. Peck B, Hoffman GS, Franck WA. Thrombophlebitis in systemic lupus erythematosus. JAMA 1978;240:1723-30, 40. Landi G, Calloni MV, Sabbadini MG, Mannucci PM, Candelise L. Recurrent ischemic attack in two young adults with lupus anticoagulant. Stroke 1983;14:377-9.
Transformation of Inferior Vena Caval Thrombosis to Membranous Obstruction in a Patient With the Lupus Anticoagulant HIDETAKA TERABAYASHI, KUNIO OKUDA, FUMIO NOMURA, KUNIHIKO OHNISHI, and PAKMING WONG First Department of Medicine and Second Department Medicine, Chiba, Japan
A 24yr-old woman with hemolytic anemia developed multiple thrombosis of the hepatic vein and inferior vena cava. She was found to have circulating lupus anticoagulant that could have been causally related to the thrombosis and hence the Budd-Chiari syndrome. On her first admission to the hospital vena cava and hepatic vein catheterizations revealed partial thrombotic occlusion of the cava at the level of the diaphragm, which was subsequently transformed into complete membranous obstruction. The right hepatic vein, which was patent on the first admission, was also completely occluded. These observations support the theory that membranous obstruction of the inferior vena cava is a sequela to inferior vena caval thrombosis rather than a congenital anomaly. Hepatic vein thrombosis of the Budd-Chiari syndrome is a severe liver disease often terminating in death. It is sometimes complicated by occlusion of the inferior vena cava (IVC) (1-3). By contrast, membranous obstruction of the IVC (MOVC) of an insidious onset in adults has a better prognosis and is more common in Japan (4-8),India (g-11),Israel (121, and South Africa (l3,14). In MOVC, the genesis of the membrane has been speculated upon, but the current leading theory considers it a congenital anomaly (4,6-8,13,15,16). Old theories suggested “mechanical injury” (l7),“infection-phlebitis” (18, 19),and “thrombosis” (2O), but they have been practically forgotten. Received October 11, 1985. Accepted January 29, 1986. Address requests for reprints to: Kunio Okuda, M.D., Ph.D., Department of Medicine, Chiba University Hospital, Chiba, Japan (280). The authors thank Professor Dame S. Sherlock, London, for her suggestion regarding anticoagulant when this case was discussed at a clinical conference in Chiba on November 15, 1983. 0 1986 by the American Gastroenterological Association 0016-5085/86/$3.50
of Medicine,
Chiba University
School of
We have recently studied a woman with autoimmune hemolytic anemia who developed an acute episode of Budd-Chiari syndrome with multiple thrombosis involving the hepatic veins and the IVC. She was found to have several autoantibodies including lupus anticoagulant. Within 2 yr, the IVC, initially patent but narrowed by mural thrombi, turned into a thick, firm membrane with complete obstruction of major hepatic veins. The observation in this patient seems to support the “thrombosis” theory of the cause of MOVC. Case Report A 24yr-old unmarried woman was admitted to the hospital on June 17, 1983 because of epigastric pain and icterus. Four years earlier, she developed ankle edema and was treated. One year later, she again noticed leg edema and laboratory examination showed slightly elevated serum lactic acid dehydrogenase and bilirubin levels. Her hematocrit was 41% at this time. Three weeks before admission, she experienced back and epigastric pain with a low-grade fever. Three days later, jaundice was noted and she was admitted to the hospital, where liver scintiscan was interpreted as showing multiple space-occupying lesions. She was then referred to us. The patient had no history of jaundice, alcoholism, drug abuse, or blood transfusion. On admission, the patient appeared pale and slightly jaundiced. A tender liver edge was palpated 4 cm below the right costal margin and the spleen was felt 2 cm below the left costal margin. There were dilated veins on the abdominal wall and the blood flow was cephalad. There was slight pretibial pitting edema but no ascites. Laboratory examinations on admission revealed the following values: red blood cell count, 2.19 x 10”/mm3; hemoglobin, 7.0 g/dl; hematocrit, 20.9%; white blood cell count, 6100imm3; platelet count, 69,000/mm3; reticulocytes, 11%; prothrombin time, 14.9 s (control, 12 s); Abbreviations used in this paper: WC, inferior vena cava: MOVC, membranous obstruction of the inferior vena cava.
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Figure 1. Real-time linear scan ultrasonogram on admission demonstrating a mass protruding in the inferior vena cava (at arrow].
erythrocyte sedimentation rate, 127 mm/h; fibrinogen, 430 mg/dl; and fibrin degradation products, 380 pg/dl. Both the direct and indirect Coombs’ tests were positive. Serum aspartate aminotransferase was 28 mu/ml; total protein, 6.4 g/dl; albumin, 3.3 g/dl; total bilirubin, 3.3 mg/dl; and unconjugated bilirubin, 1.7 mg/dl. Serum a-fetoprotein, carcinoembryonic antigen, hepatitis B surface antigen, hepatitis B surface antibody, smooth muscle antibody, antimitochondrial antibody, lupus erythematosus and rheumatoid arthritis tests, anti-extractable nuclear antigens, Treponema palladium hemagglutination, and ribonucleoprotein antibody were negative, but antinuclear antibody was positive at a low titer. On admission, ultrasonography demonstrated hepatomegaly and two echogenic materials that were most likely thrombi in the IVC (Figure 1) and in the right hepatic vein near its opening into the IVC (Figure 2). They were not moving in the venous lumen. Enhanced computed tomography scan revealed a thrombus in the IVC and some collateral veins. Hepatic venography and cavography showed partial obstruction of the IVC by a thrombus (Figure 3), but the catheter could be pushed through the stenotic lumen of the IVC. A balloon catheter revealed that the right hepatic vein was also patent, but it was tortuous with several vein-to-vein anastomoses and reduced numbers of branches (Figure 4). Wedged hepatic venous pressure with a reference at 10 cm above the table was 360 mmH,O, free hepatic vein pressure was 350 mmHzO, and the right atria1 pressure was 24 mmHzO. The pressure of the IVC below the thrombus at the level of the first lumbar vertebra was 214 mmHzO.
GASTROENTEROLOGY Vol. 91. No. 1
On the 60th hospital day, a repeat hepatic venography was performed. It showed a complete obstruction of the IVC with a new thrombus adherent to the IVC. The catheter could no longer be passed through the previously narrowed portion of the IVC, neither from below nor from above. The patient was started on a regimen of warfarin sodium and urokinase. One month later, repeat ultrasonography showed that the thrombi that had previously been present in the right hepatic vein and the IVC had disappeared. After the patient was discharged from the hospital, her leg edema became apparent again, and she was placed on furosemide and spironolactone therapy. Warfarin was discontinued after 1 yr and prednisolone was gradually reduced to the maintenance dose of 5 mg. During the follow-up period, the association of lupus anticoagulant and thrombosis (21) and Budd-Chiari syndrome (22) came to our attention. We then tested stored plasma for anticoagulant by the methods of Exner et al. (23) and Boxer et al. (24). The test was positive, and the results of the coagulation study fulfilled the criteria for lupus anticoagulant (25). Subsequent plasma samples during the follow-up period were also positive. The patient entered the hospital on August 19, 1985 for evaluation. On admission, her blood counts were normal. Her total bilirubin was 1.9 mg/dl, direct bilirubin 6.9 mg/dl, haptoglobin 49 mg/dl; antinuclear antibody (1:80), direct and indirect Coombs’ tests, and the rapid plasma reagin card test were positive, but other tests for autoantibodies were
Figure
2. Ultrasonogram showing a mass protruding in the right hepatic vein near its opening into the inferior vena cava (at arrow).
FORMATION
July 1986
OF MEMBRANOUS
OBSTRUCTION
IN IVC
221
negative. Hepatic vein catheterization revealed complete obstruction of the IVC at the level of the diaphragm (Figure 5). The obstruction measured 9 mm in thickness, with narrowing of the lumen of the IVC immediately below the obstruction compared with the previous caliber on admission (cf. Figure 3). The pressure was 52 mmHzO in the superior vena cava and 290 mmH,O in the IVC at the level of the first lumbar vertebra. Shortly after discharge, the patient developed thrombophlebitis of the legs and her prednisolone dosage has since been increased to 30 mg.
Summary of Clinical Findings This young woman had a number of autoantibodies, including anticoagulant, and presented with autoimmune hemolytic anemia and multiple thrombosis involving the hepatic veins and IVC. On admission, there was a large mural thrombus at the level of the diaphragm in the IVC. This thrombus expanded and eventually occluded the IVC, which was still patent on admission. Judging from her past history of ankle edema, thrombosis of IVC perhaps was not a new occurrence; she could have had repeated mild thrombosis at this site or the thrombus at this location could have been growing. The presence of distinct collaterals demonstrated by the first venography attests to such an assumption. The major thrombus at the level of
Figure 4. Right hepatic vein catheterization with a balloon catheter. Marked tortuosity of the right hepatic vein and vein-to-vein anastomoses are apparent: the tortuosity could be due to parenchymal structural distortion secondary to circulatory disturbances.
the diaphragm slowly transformed into a firm obstruction that is generally called MOVC. During the course, another thrombus formed along the wall of the IVC caudad to the occluding thrombus and it subsequently disappeared. However, the right hepatic vein, which could be catheterized on admission, as well as the left hepatic vein were eventually occluded. Thus, there were dynamic changes in the size of the thrombi, with disappearance, new formation, growth, and transformation into a fibrous tissue. Contraction of the thrombus due to organization and fibrosis was apparent from reduction of the diameter of the IVC near the membrane (cf. Figures 3 and 5).
Discussion
Figure
3. Inferior sion of through left side
vena cavography demonstrating a partial occluthe inferior vena cava. The catheter passed the stenotic area when it was passed along the (inset).
The classical Budd-Chiari syndrome and MOVC in the hepatic portion have been considered separately by most authors in the past decade (3-16). The membranous state of the occlusion in the latter was so emphasized that many reports in recent years treated the two as if they were different diseases, with the assumption that MOVC was a congenital abnormality more common in the Orient (4-11). However, past studies on hepatic vein thrombosis frequently recognized the coexistence of thrombosis in the IVC, most commonly in its hepatic portion. According to Parker (l), who analyzed the etiologic factors in 236 cases of hepatic vein occlusion, 11 of 14 idiopathic cases involved lesions in the IVC. The first case of MOVC in the Western literature was that reported by Thompson and Turnbull (20) in 1912; in
222
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5. A. Inferior vena cavogram obtained 2 yr after the patient’s first admission. Complete obstruction of the inferior vena cava at the level of the diaphragm with newly formed collaterals is shown. The obstruction measured 9 mm. B. Schema of A. Catheters are shown by straight thick lines and collaterals by dotted lines.
this patient, there was a fibrous diaphragm with a narrow central hole constricting the IVC. Subsequent and Japan (4-8) reports from the West (15,16,26-28) emphasized the membranous occlusion of the IVC in the hepatic portion and proposed that it had a specific etiology. In 1970, after reviewing 150 cases from the literature including 8 of their own, Hirooka and Kimura (6) postulated that abnormal embryonic development creates a gap between the IVC and the heart, and the gap turns into a membrane. They included the cases with occlusions much thicker than a membrane and divided them into seven groups according to the pattern of occlusion. More recently, Simson (13) from Pretoria studied 101 autopsy cases of MOVC that also included thick obstructions, and suggested that it is a congenital anomaly and that somehow it frequently gives rise to
hepatocarcinogenesis. The reported membranes varied a great deal in size, from a very thin membrane to occlusions several centimeters thick. Some thin membranes had a central opening and were also called webs, with no clear distinction being made between “membrane” and “web.” Along with the congenital theory, there have been several other suggestions or speculations: the socalled “mechanical injury” (li’), “infection-phlebitis” (18,19), and “thrombosis” (20) theories. Because of the inconstant anatomic changes, variable thicknesses of the membrane, and irregular involvement of the hepatic veins, the present authors maintained that this is an acquired disorder associated with thrombosis (29,303. We also described membranous obstruction of the portal vein associated with multiple thrombosis of the portal vein system (31). The
July 1986
current case provides evidence that thrombosis of the IVC at the level of the diaphragm will turn into a fibrous occlusion. The congenital anomaly theory cannot explain the adult onset of MOVC. The reason for the hepatic portion of the IVC being the most common site of membrane formation is still unclear. Mechanical endothelial injury due to diaphragmatic movements in its relation to the heavy liver may invite thrombosis as the mechanical injury theory suggests (IT), or the turbulence of blood flow as a result of hepatic venous flow perpendicular to the IVC may predispose this area to thrombosis (20). However, there still is a possibility that MOVC has multiple origins or etiologies. The association of anticoagulant with BuddChiari syndrome is a relatively recent observation, first described by Pdmeroy et al. (22) in 1984, but association of Budd-Chiari syndrome with systemic lupus erythematosus and other autoimmune diseases had been reported sporadically (32-34). Spontaneous acquired anticoagulant occurs most frequently in systemic lupus erythematosus, but it also occurs in a number of other clinical states including autoimmune hemolytic anemia, as in our case (35,36). Lupus anticoagulant is an immunoglobulin that interferes with the conversion of prothrombin to thrombin by the phospholipid prothrombin activator complex (25,37), but paradoxically it seems to be associated with venous thrombosis (22,36,38-40).
FORMATION OF MEMBRANOUS
11.
12.
13.
14. 15.
16.
17. 18. 19.
20. 21.
22.
References Parker RGF. Occlusion of the hepatic veins in man. Medicine 1959;38:369-402. RB. Thrombosis of the hepatic veins. The 2. Thompson Budd-Chiari syndrome. Arch Intern Med 1947;80:602-15. syndrome. In: Schiff L, 3. Reynolds TB, Peters RL. Budd-Chiari Schiff ER, eds. Diseases of the liver. 5th ed. Philadelphia: Lippincott, 1982:1622-30. S, Yokoyama T, Takeshige K, Iwatsuki S. 4. Yamamoto Budd-Chiari syndrome with obstruction of the inferior vena cava. Gastroenterology 1968;54:1070-84. 5. Nakamura T, Nakamura S, Aikawa T, Suzuki 0, Onodera A, Karoji N. Obstruction of the inferior vena cava in the hepatic portion and the hepatic veins. Angiology 1968;19:479-98. 6. Hirooka M, Kimura C. Membranous obstruction of the hepatic portion of the inferior vena cava. Surgical correction and etiological study. Arch Surg 1970;100:656-63. 7. Kimura C, Matsuda S, Koike H, Hirooka M. Membranous obstruction of the hepatic portion of the inferior vena cava; clinical study of nine cases. Surgery 1972;72:551-9. 8. Takeuchi J, Takada A, Hasumura Y, Matsuda Y, Ikegami F. Budd-Chiari syndrome associated with obstruction of the inferior vena cava. Am J Med 1971;51:11-20. 9. Datta DV, Samanta SS, Singh A, Gupta BB, Aikat BK, Chhuttani PN. Clinical spectrum of Budd-Chiari syndrome in Chandigarh with particular reference to obstruction of intrahepatic portion of inferior vena cava. Indian J Med Res 1972;60:385-402. 10. Datta DV, Vashishta S, Samanta AK, Chhuttani PN. Diagnostic value of combined transhepatic venography and inferior 1.
23.
24. 25.
26.
27. 28.
29.
30. 31.
32.
OBSTRUCTION
IN IVC
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vena cavography in chronic Budd-Chiari syndrome. Am J Dig Dis 1978;23:1031~1. Khuroo MS, Datta DV. Budd-Chiari syndrome following pregnancy. Report of 16 cases, with roentgenologic, hemodynamic and histologic studies of the hepatic outflow tract. Am J Med 1980;68:113-21. Adar R, Rosenthal T, Mozes M. Vena caval obstruction: some epidemiological observations in 76 patients. Angiology 1974; 25:43340. Simson IW. Membranous obstruction of the inferior vena cava and hepatocellular carcinoma in South Africa. Gastroenterology 1982;82:171-8. Van der Merwe SF, Arts MSC. Primary liver cancer in the Transvaal. Hepatogastroenterology 1981;28:233-5. Rogers MA, Chesler E, du Plessis L, Jaffe N, Joubert E. Membranous obstruction of the hepatic segment of the inferior vena cava. Br J Surg 1964;54:221-5. Sen PK, Kinare SG, Kelkar MD. Congenital membranous obstruction of the inferior vena cava: report of a case and review of the literature. J Cardiovasc Surg 1967;8:344-52. Kretz R. Pathologie der Leber. Ergeb allg Path01 u path01 Anat 1902;82:473-94. Kelsey MP, Comfort MW. Occlusion of the hepatic veins; review of twenty cases. Arch Intern Med 1945;75:175-83. Kibel MA, Marsden HB. Inferior vena caval and hepatic vein thrombosis: the Chiari syndrome in childhood. Arch Dis Child 1956;31:225-8. Thompson T, Turnbull HM. Primary occlusion of the ostia of the hepatic veins. Q J Med 1912;5:277-96. Boey ML, Colaco CG, Fharavi AE, Elkon KB, Loizou S, Hughes GRV. Thrombosis in systemic lupus erythematosus: striking association with the presence of circulating anticoagulant. Br Med J 1983;287:1021-3. Pomeroy C, Knodell RG, Swaim WR, Arneson P, Mahowald ML. Budd-Chiari syndrome in a patient with the lupus anticoagulant. Gastroenterology 1984;86:158-61. Exner T, Rickard KA, Kronenberg H. A sensitive test demonstrating lupus anticoagulant and its behavioural patterns. Br J Haematol 1978;40:143-51. Boxer M, Ellman L, Carvalho A. The lupus anticoagulant. Arthritis Rheum 1976;19:1244-8. Carreras LO, Vermylen JG. “Lupus” anticoagulant and thrombosis-possible role of inhibition of prostacyclin formation. Thromb Haemostasis 1982;48:38-40. Lam CR, Green E, Gale H. Transcardiac membranatomy for obstruction of the hepatic portion of the inferior vena cava. Circulation 1965;31,32(Suppl):188-91. Smith L. A case of congenital stenosis of the inferior vena cava with portal hypertension. Br J Surg 1965;52:913-6. Johansson L, Moberg A, Soderlund K, et al. Congenital obstruction of the inferior vena cava. Acta Chir Stand 1966; 131:509-15. Okuda K. Membranous obstruction of the inferior vena cava: etiology and relation to hepatocellular carcinoma. Gastroenterology 1982;82:376-9. Okuda K, Ostrow JD, Clinical conference: membranous type of Budd-Chiari syndrome. J Clin Gastroenterol 1984;6:81-8. Kimura K, Okuda K, Takara K, Matsutani S, Lesmana L. Membranous obstruction of the portal vein. A case report, Gastroenterology 1985;88:571-5. Disney TF, Sullivan SN, Haddad RG, Lowe D, Goldbach MM. Budd-Chiari syndrome with inferior vena cava obstruction associated with systemic lupus erythematosus. J Clin Gastroenter01 1984;6:253-6.
224
TERABAYASHI
ET AL.
33. Comes J, Robert A, Levy VG, Darnis F. Budd-Chiari syndrome in a patient with mixed connective-tissue disease. Dig Dis Sci 1980;25:467-9. 34. Matsuura H, Matusmoto T, Hashimoto T. Budd-Chiari syndrome in a patient with Sjogren’s syndrome. Am J Gastroenterol 1983178:822-5. 35. Schleider MA, Nachman RL, Jaffe EA, Coleman M. A clinical study of the lupus anticoagulant. Blood 1976;48:499-509. 36. Mueh JR, Herbsi KD, Rapaport SI. Thrombosis in patients with the lupus anticoagulant. Ann Intern Med 1980;92(Part 1):156-9.
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37. Shapiro SS, Thiagarajan R. Lupus anticoagulant. In: Spaet TH, ed. Progress in hemostasis and thrombosis. New York: Grune & Stratton, 1982:263-83. 38. Walker Bowie EJ, Thompson JH Jr, Pascuzzi CA, Owen CA. Thrombosis in systemic lupus erythematosus despite circulating anticoagulant. J Lab Clin Med 1963;62:416-30. 39. Peck B, Hoffman GS, Franck WA. Thrombophlebitis in systemic lupus erythematosus. JAMA 1978;240:1723-30, 40. Landi G, Calloni MV, Sabbadini MG, Mannucci PM, Candelise L. Recurrent ischemic attack in two young adults with lupus anticoagulant. Stroke 1983;14:377-9.