- Email: [email protected]
The Budd-Chiari syndrome
Journal of Hepatology, 1986;3:83-86 Elsevier
83
HEP 00136
The Budd-Chiari Syndrome Possible Pathogenetic Role of Anti-Phospholipid Antibodies C . G . M a c k w o r t h - Y o u n g l, W . M . M e l i a 2, E . N . H a r r i s 1, A . E . O h a r a v i 1, Y. S i v a t h o n d a n 2, G . D e r u e 1, S. S h e r l o c k 3 a n d G . R . V . H u g h e s 1 1The Rheumatology Unit, Royal Postgraduate Medical School, London W12, 2Departments of Gastroenterology and Pathology, Royal Cornwall Hospital (Treliske), Truro, and 3Professorial Medical Unit, Royal Free Hospital, London NW3 (U.K.) (Received 7 December, 1985) (Accepted 21 January, 1986)
Summary The case of a young woman with the Budd-Chiari syndrome is reported. She first noticed abdominal symptoms following a late spontaneous abortion. Antiphospholipid antibodies were detected in her serum. We suggest that these may have been causally related to the development of her hepatic disease.
Introduction
Case Report
It is often impossible to identify the cause of the Budd-Chiari syndrome, but in some with idiopathic disease thromboses occur in multiple sites suggesting that an increased thrombotic diathesis may exist. At the Royal Postgraduate Medical School, London, a sensitive solid phase radioimmunoassay for anticardiolipin antibodies has recently been developed, and these have been shown to react with other phospholipids [1]. We report the case of a patient with Budd-Chiari syndrome whose serum contained raised titres of these antibodies and in whom no other medical condition known to predispose to an increased thrombotic tendency could be identified.
A 22-year-old woman first presented to the West Cornwall Hospital, Penzance, in July 1981 with ascites. In July 1980 she had been delivered of a dead foetus at six and a half months gestation. She had first noticed abdominal swelling in August 1980; this had lasted for 2 weeks and had then resolved, but had returned again 3 weeks prior to her 1981 admission. It was associated with weakness, anorexia, ankle swelling, occasional fevers and a moderate gain in weight. She had a stable spastic quadriplegia which had been first noticed at the age of 5 weeks and had been attributed to an apnoeic episode during delivery. She drank very little alcohol, was a non-smoker, and had
Correspondence to Dr. Mackworth-Young. Current address: Cancer Research Center, Tufts University, New England Medical Center, 171 Harrison Avenue, Boston, MA 02111, U.S.A. 0168-8728/86/$03.50 l~) 1986 Elsevier Science Publishers B.V. (Biomedical Division)
84 not used oral contraceptive steroids. On examination, there were no stigmata of chronic liver disease. There was a tachycardia, marked oedema of the legs and feet, and marked ascites, with the liver edge palpable 5 cm below the right costal margin and the spleen 4 cm below the left costal margin. She had generalised increased muscle tone with hyper-reflexia, extensor plantar responses and some symmetrical loss of power. Investigations revealed a haemoglobin of 10.7 g/dl, a white count of 6 400 x 106/1 and a platelet count of 350 x 109/1. The MCV was 67 fl and the red cells were hypochromic. The prothrombin time was 3 seconds prolonged, urea and electrolytes were normal and liver function tests were as follows: total protein 67 g/l, albumin 34 g/l, bilirubin 31 ~mol/I (normal less than 13), alkaline phosphatase 288 IU/I (normal less than 100), and SGPT 3 IU/I (normal less than 40). An ascitic tap yielded clear fluid with a protein content of 26 g/l, and occasional lymphocytes on microscopy. Gram and Ziehl-Neelsen stains were both negative and cultures were subsequently proved sterile. A chest X-ray was normal. Abdominal ultrasound confirmed hepatomegaly but was largely unsuccessful due to the large volume of ascites. A technetium sulphur colloid liver scan showed an enlarged liver with reduced colloid uptake. A barium meal did not reveal varices or other abnormality. The serum iron was normal (12.4 g4mol/I), as were serum lgG and IgA levels, but IgM levels were raised (5.8 g/l). HBsAg and alphafoetoprotein were not detected; antimitochondrial antibody was positive in a titre of 1/40 but antinuclear factor and anti-smooth muscle factor were not detected. The ascites responded to dietary salt restriction and oral spironalactone. A liver biopsy was subsequently performed. This showed dilatation of central veins, some of which were thrombosed, with haemorrhage and necrosis of the surrounding liver tissue; the haemorrhage was mainly confined to the liver cell cords. In addition bands of fibrosis were seen, with regenerative activity in adjacent liver tissue, producing distortion of the lobular pattern, but without evidence of cirrhosis. These findings were considered to represent acute and chronic lesions due to the
C.G. MACKWORTH-YOUNG et al. Budd-Chiari syndrome. The patient was discharged from hospital in August 1981 and remained well over the next year. However, in December 1981, it was noticed that she had started oral contraceptive steroids; she was advised to stop these and had an intra-uterine contraceptive device inserted instead. She next presented to the Royal Cornwall Hospital, Treliske Hospital in December 1982 following a haematemesis. On examination, she was found to have scattered spider naevi, prominent veins on the anterior abdominal and thoracic walls, and hepatosplenomegaly. She was haemodynamically stable and did not have any ascites or peripheral oedema. Her haemoglobin was 10.9 g/dl and endoscopy revealed the presence of three cords of grade 1I oesophageal varices and no other abnormality. At the time of endoscopy there was no evidence of bleeding. She did not require transfusion, and obliteration of her varices was not attempted. She was referred to the Liver Unit, Royal Free Hospital, London for assessment in February 1983. Liver function tests then were as follows: albumin 43 g/l, bilirubin 32 umol/l, Asp-T 57 IU/I, alkaline phosphatase 159 IU/I, and gamma GT 166 IU/I. Prothrombin time was 5 seconds prolonged. On upper abdominal ultrasound, the spleen was seen to be enlarged and the splenic vein was identified. However, the portal vein was not demonstrated and a normal hepatic vein pattern could not be identified. A computerised tomographic scan of the liver confirmed gross enlargement, particularly in the region of the caudate lobe. The portal vein appeared patent. Hepatic venography revealed a pattern typical of long standing Budd-Chiari syndrome. It was not considered that any specific treatment was indicated at that time. She remained well until January 1984 when she suffered a further haematemesis, which did not respond to a vasopressin infusion, insertion of a Sengstaken-Blakemore tube, or endoscopic injection sclerotherapy of large distal oesophageal varices. Operative porto-azygos disconnection was therefore performed. At surgery the portal vein was not identified; there were two ulcers in the mid portion of the stomach posteriorly which had penetrated
THE BUDD-CHIARI SYNDROME
85
to the serosa. A sleeve resection of the part of the stomach containing the ulcers was performed and the upper stomach and oesophagus were devascularized. There was no further bleeding following surgery but she developed tense ascites, deep jaundice and moderately severe hepatic encephalopathy. Liver function tests then showed an albumin of 26 g/l, bilirubin 3001~mol/1, alkaline phosphatase 170 IU/I and SGPT of 80 IU/I. Despite parenteral vitamin K the prothrombin time was 8 seconds prolonged. She was treated with salt restriction, diuretics, lactulose and neomycin. Further complications included bacterial peritonitis, mild renal failure, and a left-sided pleural effusion. She gradually recovered to the extent that she was able to take her own discharge from hospital in mid-February 1984. Subsequently there was a complete clearing of her pleural effusion and a marked reduction in the amount of her ascites. Liver function tests showed: albumin 27 g/1, bilirubin 691~mol/1, alkaline phosphatase 375 IU/I, and a SGPT of 25 IU/I. In February 1984 antinuclear factor and antismooth muscle and antimitochondrial antibodies were all normal. Antibodies to extractable nuclear antigens were not detected. V D R L precipitin test was negative and a T P H A test was also negative. Anti-phospholipid antibodies (APA) were detected in the IgM fraction of her serum using a solid-phase radioimmunoassay [i]; (using the same assay, we were unable to detect APA in the serum of 4 patients with chronic active hepatitis, 6 with alcoholic cirrhosis, and 2 with Budd-Chiari syndrome secondary to polycythaemia rubra vera). Tests for lupus anticoagulant activity were negative in the Coagulation Laboratory, Royal Cornwall Hospital, and the Coagulation Laboratory, Hammersmith Hospital, according to the method of Proctor and Rapaport [2], and in the Rheumatology Laboratory, Hammersmith Hospital according to the method of Boey et al. [3]. Endoscopy in May 1984 showed some residual interrupted small varices.
Discussion
The
presence
of
antiphospholipid
antibodies
(APA) has been shown to be associated with a tendency to thrombosis in patients with SLE and other disorders [1]. The incidence of venous thrombosis [4], stroke [5] and other arterial thrombosis [6] is considerably raised in patients with these antibodies. We have recently reported the case of a patient with SLE who developed portal and pulmonary hypertension, and who demonstrated the lupus anticoagulant (LA) [7]; we suggested that this antibody may have been causally related to the development of these unusual features of lupus. A case of SLE with hepatic veno-occlusive disease has previously been reported [8]; this patient had a false positive VDRL. APAs are also associated with multiple abortions, thrombocytopenia, and a biological false-positive VDRL [9]. In addition they are strongly associated with the presence of the lupus .anticoagulant (LA) [1]. There is good evidence that the latter may have antiphospholipid antibody activity [10,11], and it has been suggested that it may promote thrombosis by cross-reacting with endothelial phospholipids [12]. The typical clinical manifestations of the BuddChiari syndrome in our patient were supported by the liver biopsy findings and the classical appearances on hepatic venography. None of the known risk factors associated with the Budd-Chiari syndrome could be identified. We suggest that in this case the syndrome may be linked causally to the presence of APAs in her serum. The recent report of a case of Budd-Chiari syndrome supports this view: in this patient the LA was detected in the absence of any other predisposing factor to thrombosis [13]. The authors suggest that the presence of the LA may provide an explanation for the patient's hypercoagulability and the development of the Budd-Chiari syndrome. Three different laboratories failed to detect the LA in our patient. Our previous results suggest that a solid-phase radioimmunoassay provides a more sensitive method of detecting APAs than the LA method [1]. In this study 40 out of 65 patients with connective tissue diseases (predominately SLE) had raised anticardiolipin levels of at least one immunoglobulin class, 29 of whom had the LA; only 3 patients had the
C.G. MACKWORTH-YOUNG et al.
86 LA and normal anticardiolipin levels. We therefore feel that our patient may represent the subset of individuals in whom the m e a s u r e m e n t of A P A s by radio° immunoassay represents a diagnostic advance. Our suggestion as to the possible role of A P A s in our patient's hepatic disease is supported by the fact that we were unable to detect raised levels of A P A s in a small sample of patients with chronic active hepatitis and alcoholic cirrhosis, and in 2 patients with B u d d - C h i a r i syndrome secondary to polycythaemia rubra vera. In a recent series of 36 patients with the B u d d Chiari syndrome, causes could not be identified in 9 patients, in 3 of whom other thromboses at multiple sites were reported [14]. It is interesting to speculate as to whether some of these may have possessed A P A s or the LA. It is of interest that our patient first developed abdominal symptoms during the puerperium following a late spontaneous abortion. It is well described that SLE may present or be exacerbated during the puer-
References 1 Harris EN, Gharavi AE, Boey ML, Patel DM, MackworthYoung CG, Loizou S and Hughes GRV. Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in SLE. Lancet 1983; 2:1211-1214. 2 Proctor RR and Rapaport SI. The partial thromboplastin time with kaolin: A simple screening test for first stage plasma clotting factor deficiencies. Am J Clin Pathol 1961; 36:212-219. 3 Boey ML, Colaco CB, Gharavi AE. Elkon KB, Loizou S and Hughes GRV. Thrombosis in SLE: striking association with the presence of circulating 'lupus anticoagulant'. Brit Med J 1983; 287: 1021-1023. 4 Harris EN, Gharavi AE. Boey ML, Patel DM, MackworthYoung CG, Loizou S and Hughes GRV. Anticardiolipin antibodies: detection by a new solid phase radioimmunoassay: striking association with thrombosis (abstract). Ann Rheum Dis 1984; 43:(i)122. 5 Harris EN, Gharavi AE, Asherson R, Boey ML and Hughes GRV. Cerebral infarction in systemic lupus: association with anticardiolipin antibodies. Clin Exp Rheum 1984; 2:47-51. 6 Asherson RA, Mackworth-Young CG, Harris EN, Gharavi AE, Boey ML and Hughes GRV. Multiple venous and arterial thromboses associated with the lupus anticoagulant and antibodies to cardiolipin in the absence of SLE. Rheumatol Int 1984; 4:1-3.
perium; this may well be due to hormonal factors [15]. Furthermore A P A s are associated with an increased risk of abortion. It may be, therefore, that A P A s were present in our patient's serum before or at the time of her abortion, and that subsequent hormonal changes allowed the expression of disease, in the form of hepatic thrombosis, to be initiated.
Acknowledgements We wish to acknowledge: Dr. Richard Machel, Consultant Gastroenterologist, West Cornwall Hospital, Penzance, who looked after this patient on her initial presentation; Mr. Ian Hamilton, Consultant Surgeon, Royal Cornwall Hospital (Treliske), Truro, who carried out difficult surgery; and the anaesthetic and nursing staff. We are also very grateful to Dr. A n d r e w Plaut, New England Medical Center, Boston, U.S.A. for sera from patients with chronic active hepatitis and alcoholic cirrhosis.
7 Mackworth-Young CG, Gharavi AE, Boey ML and Hughes GRV. Portal and pulmonary hypertension in a case of systemic lupus erythematosus: possible relationship with clotting abnormality. Eur J Rheum lnflamm (in press). 8 Pappas SC, Malone DG, Rabin L, Hoofnagle JH and Jones EA. Hepatic veno-occlusive disease in a patient with systemic lupus erythematosus. Arth Rheum 1984; 27:( 1), 104-108. 9 Hughes GRV. Thrombosis, abortion, cerebral disease and the lupus anticoagulant. Brit Med J 1983;287:1088-1089. 10 Lee SL and Mioni AB. Disorders of haemostatic function in patients with systemic lupus erythematosus. Semin Arthr Rheum 1975;4:241-252. 11 Byron MA. The clotting defect in SLE. Clin Rheum Dis 1982; 8:137-15 I. 12 Carreras LA. Defreyn G, Machin SJ. Vermelyn J, Deman R, Spitz B and Van Assiche A. Arterial thrombosis, intrauterine death, and lupus anticoagulant. Lancet 1981; 1:244-246. 13 Pomeroy C, Kinodell RG, Swaion WR, Arneson P and Mahowald ML. Budd-Chiari syndrome in a patient with the lupus anticoagulant. Gastroenterology 1984; 86:158-161. 14 PowelI-Jackson PR, Melia W, Canalese J, Pickford RB. Portmann B, Williams R. Budd-Chiari syndrome: clinical patterns and therapy. Quarterly Journal of Medicine 1982; 51:79-88. 15 Zurier RB. Systemic lupus and pregnancy. Clin Rheum Dis 1975; 1:613.
83
HEP 00136
The Budd-Chiari Syndrome Possible Pathogenetic Role of Anti-Phospholipid Antibodies C . G . M a c k w o r t h - Y o u n g l, W . M . M e l i a 2, E . N . H a r r i s 1, A . E . O h a r a v i 1, Y. S i v a t h o n d a n 2, G . D e r u e 1, S. S h e r l o c k 3 a n d G . R . V . H u g h e s 1 1The Rheumatology Unit, Royal Postgraduate Medical School, London W12, 2Departments of Gastroenterology and Pathology, Royal Cornwall Hospital (Treliske), Truro, and 3Professorial Medical Unit, Royal Free Hospital, London NW3 (U.K.) (Received 7 December, 1985) (Accepted 21 January, 1986)
Summary The case of a young woman with the Budd-Chiari syndrome is reported. She first noticed abdominal symptoms following a late spontaneous abortion. Antiphospholipid antibodies were detected in her serum. We suggest that these may have been causally related to the development of her hepatic disease.
Introduction
Case Report
It is often impossible to identify the cause of the Budd-Chiari syndrome, but in some with idiopathic disease thromboses occur in multiple sites suggesting that an increased thrombotic diathesis may exist. At the Royal Postgraduate Medical School, London, a sensitive solid phase radioimmunoassay for anticardiolipin antibodies has recently been developed, and these have been shown to react with other phospholipids [1]. We report the case of a patient with Budd-Chiari syndrome whose serum contained raised titres of these antibodies and in whom no other medical condition known to predispose to an increased thrombotic tendency could be identified.
A 22-year-old woman first presented to the West Cornwall Hospital, Penzance, in July 1981 with ascites. In July 1980 she had been delivered of a dead foetus at six and a half months gestation. She had first noticed abdominal swelling in August 1980; this had lasted for 2 weeks and had then resolved, but had returned again 3 weeks prior to her 1981 admission. It was associated with weakness, anorexia, ankle swelling, occasional fevers and a moderate gain in weight. She had a stable spastic quadriplegia which had been first noticed at the age of 5 weeks and had been attributed to an apnoeic episode during delivery. She drank very little alcohol, was a non-smoker, and had
Correspondence to Dr. Mackworth-Young. Current address: Cancer Research Center, Tufts University, New England Medical Center, 171 Harrison Avenue, Boston, MA 02111, U.S.A. 0168-8728/86/$03.50 l~) 1986 Elsevier Science Publishers B.V. (Biomedical Division)
84 not used oral contraceptive steroids. On examination, there were no stigmata of chronic liver disease. There was a tachycardia, marked oedema of the legs and feet, and marked ascites, with the liver edge palpable 5 cm below the right costal margin and the spleen 4 cm below the left costal margin. She had generalised increased muscle tone with hyper-reflexia, extensor plantar responses and some symmetrical loss of power. Investigations revealed a haemoglobin of 10.7 g/dl, a white count of 6 400 x 106/1 and a platelet count of 350 x 109/1. The MCV was 67 fl and the red cells were hypochromic. The prothrombin time was 3 seconds prolonged, urea and electrolytes were normal and liver function tests were as follows: total protein 67 g/l, albumin 34 g/l, bilirubin 31 ~mol/I (normal less than 13), alkaline phosphatase 288 IU/I (normal less than 100), and SGPT 3 IU/I (normal less than 40). An ascitic tap yielded clear fluid with a protein content of 26 g/l, and occasional lymphocytes on microscopy. Gram and Ziehl-Neelsen stains were both negative and cultures were subsequently proved sterile. A chest X-ray was normal. Abdominal ultrasound confirmed hepatomegaly but was largely unsuccessful due to the large volume of ascites. A technetium sulphur colloid liver scan showed an enlarged liver with reduced colloid uptake. A barium meal did not reveal varices or other abnormality. The serum iron was normal (12.4 g4mol/I), as were serum lgG and IgA levels, but IgM levels were raised (5.8 g/l). HBsAg and alphafoetoprotein were not detected; antimitochondrial antibody was positive in a titre of 1/40 but antinuclear factor and anti-smooth muscle factor were not detected. The ascites responded to dietary salt restriction and oral spironalactone. A liver biopsy was subsequently performed. This showed dilatation of central veins, some of which were thrombosed, with haemorrhage and necrosis of the surrounding liver tissue; the haemorrhage was mainly confined to the liver cell cords. In addition bands of fibrosis were seen, with regenerative activity in adjacent liver tissue, producing distortion of the lobular pattern, but without evidence of cirrhosis. These findings were considered to represent acute and chronic lesions due to the
C.G. MACKWORTH-YOUNG et al. Budd-Chiari syndrome. The patient was discharged from hospital in August 1981 and remained well over the next year. However, in December 1981, it was noticed that she had started oral contraceptive steroids; she was advised to stop these and had an intra-uterine contraceptive device inserted instead. She next presented to the Royal Cornwall Hospital, Treliske Hospital in December 1982 following a haematemesis. On examination, she was found to have scattered spider naevi, prominent veins on the anterior abdominal and thoracic walls, and hepatosplenomegaly. She was haemodynamically stable and did not have any ascites or peripheral oedema. Her haemoglobin was 10.9 g/dl and endoscopy revealed the presence of three cords of grade 1I oesophageal varices and no other abnormality. At the time of endoscopy there was no evidence of bleeding. She did not require transfusion, and obliteration of her varices was not attempted. She was referred to the Liver Unit, Royal Free Hospital, London for assessment in February 1983. Liver function tests then were as follows: albumin 43 g/l, bilirubin 32 umol/l, Asp-T 57 IU/I, alkaline phosphatase 159 IU/I, and gamma GT 166 IU/I. Prothrombin time was 5 seconds prolonged. On upper abdominal ultrasound, the spleen was seen to be enlarged and the splenic vein was identified. However, the portal vein was not demonstrated and a normal hepatic vein pattern could not be identified. A computerised tomographic scan of the liver confirmed gross enlargement, particularly in the region of the caudate lobe. The portal vein appeared patent. Hepatic venography revealed a pattern typical of long standing Budd-Chiari syndrome. It was not considered that any specific treatment was indicated at that time. She remained well until January 1984 when she suffered a further haematemesis, which did not respond to a vasopressin infusion, insertion of a Sengstaken-Blakemore tube, or endoscopic injection sclerotherapy of large distal oesophageal varices. Operative porto-azygos disconnection was therefore performed. At surgery the portal vein was not identified; there were two ulcers in the mid portion of the stomach posteriorly which had penetrated
THE BUDD-CHIARI SYNDROME
85
to the serosa. A sleeve resection of the part of the stomach containing the ulcers was performed and the upper stomach and oesophagus were devascularized. There was no further bleeding following surgery but she developed tense ascites, deep jaundice and moderately severe hepatic encephalopathy. Liver function tests then showed an albumin of 26 g/l, bilirubin 3001~mol/1, alkaline phosphatase 170 IU/I and SGPT of 80 IU/I. Despite parenteral vitamin K the prothrombin time was 8 seconds prolonged. She was treated with salt restriction, diuretics, lactulose and neomycin. Further complications included bacterial peritonitis, mild renal failure, and a left-sided pleural effusion. She gradually recovered to the extent that she was able to take her own discharge from hospital in mid-February 1984. Subsequently there was a complete clearing of her pleural effusion and a marked reduction in the amount of her ascites. Liver function tests showed: albumin 27 g/1, bilirubin 691~mol/1, alkaline phosphatase 375 IU/I, and a SGPT of 25 IU/I. In February 1984 antinuclear factor and antismooth muscle and antimitochondrial antibodies were all normal. Antibodies to extractable nuclear antigens were not detected. V D R L precipitin test was negative and a T P H A test was also negative. Anti-phospholipid antibodies (APA) were detected in the IgM fraction of her serum using a solid-phase radioimmunoassay [i]; (using the same assay, we were unable to detect APA in the serum of 4 patients with chronic active hepatitis, 6 with alcoholic cirrhosis, and 2 with Budd-Chiari syndrome secondary to polycythaemia rubra vera). Tests for lupus anticoagulant activity were negative in the Coagulation Laboratory, Royal Cornwall Hospital, and the Coagulation Laboratory, Hammersmith Hospital, according to the method of Proctor and Rapaport [2], and in the Rheumatology Laboratory, Hammersmith Hospital according to the method of Boey et al. [3]. Endoscopy in May 1984 showed some residual interrupted small varices.
Discussion
The
presence
of
antiphospholipid
antibodies
(APA) has been shown to be associated with a tendency to thrombosis in patients with SLE and other disorders [1]. The incidence of venous thrombosis [4], stroke [5] and other arterial thrombosis [6] is considerably raised in patients with these antibodies. We have recently reported the case of a patient with SLE who developed portal and pulmonary hypertension, and who demonstrated the lupus anticoagulant (LA) [7]; we suggested that this antibody may have been causally related to the development of these unusual features of lupus. A case of SLE with hepatic veno-occlusive disease has previously been reported [8]; this patient had a false positive VDRL. APAs are also associated with multiple abortions, thrombocytopenia, and a biological false-positive VDRL [9]. In addition they are strongly associated with the presence of the lupus .anticoagulant (LA) [1]. There is good evidence that the latter may have antiphospholipid antibody activity [10,11], and it has been suggested that it may promote thrombosis by cross-reacting with endothelial phospholipids [12]. The typical clinical manifestations of the BuddChiari syndrome in our patient were supported by the liver biopsy findings and the classical appearances on hepatic venography. None of the known risk factors associated with the Budd-Chiari syndrome could be identified. We suggest that in this case the syndrome may be linked causally to the presence of APAs in her serum. The recent report of a case of Budd-Chiari syndrome supports this view: in this patient the LA was detected in the absence of any other predisposing factor to thrombosis [13]. The authors suggest that the presence of the LA may provide an explanation for the patient's hypercoagulability and the development of the Budd-Chiari syndrome. Three different laboratories failed to detect the LA in our patient. Our previous results suggest that a solid-phase radioimmunoassay provides a more sensitive method of detecting APAs than the LA method [1]. In this study 40 out of 65 patients with connective tissue diseases (predominately SLE) had raised anticardiolipin levels of at least one immunoglobulin class, 29 of whom had the LA; only 3 patients had the
C.G. MACKWORTH-YOUNG et al.
86 LA and normal anticardiolipin levels. We therefore feel that our patient may represent the subset of individuals in whom the m e a s u r e m e n t of A P A s by radio° immunoassay represents a diagnostic advance. Our suggestion as to the possible role of A P A s in our patient's hepatic disease is supported by the fact that we were unable to detect raised levels of A P A s in a small sample of patients with chronic active hepatitis and alcoholic cirrhosis, and in 2 patients with B u d d - C h i a r i syndrome secondary to polycythaemia rubra vera. In a recent series of 36 patients with the B u d d Chiari syndrome, causes could not be identified in 9 patients, in 3 of whom other thromboses at multiple sites were reported [14]. It is interesting to speculate as to whether some of these may have possessed A P A s or the LA. It is of interest that our patient first developed abdominal symptoms during the puerperium following a late spontaneous abortion. It is well described that SLE may present or be exacerbated during the puer-
References 1 Harris EN, Gharavi AE, Boey ML, Patel DM, MackworthYoung CG, Loizou S and Hughes GRV. Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in SLE. Lancet 1983; 2:1211-1214. 2 Proctor RR and Rapaport SI. The partial thromboplastin time with kaolin: A simple screening test for first stage plasma clotting factor deficiencies. Am J Clin Pathol 1961; 36:212-219. 3 Boey ML, Colaco CB, Gharavi AE. Elkon KB, Loizou S and Hughes GRV. Thrombosis in SLE: striking association with the presence of circulating 'lupus anticoagulant'. Brit Med J 1983; 287: 1021-1023. 4 Harris EN, Gharavi AE. Boey ML, Patel DM, MackworthYoung CG, Loizou S and Hughes GRV. Anticardiolipin antibodies: detection by a new solid phase radioimmunoassay: striking association with thrombosis (abstract). Ann Rheum Dis 1984; 43:(i)122. 5 Harris EN, Gharavi AE, Asherson R, Boey ML and Hughes GRV. Cerebral infarction in systemic lupus: association with anticardiolipin antibodies. Clin Exp Rheum 1984; 2:47-51. 6 Asherson RA, Mackworth-Young CG, Harris EN, Gharavi AE, Boey ML and Hughes GRV. Multiple venous and arterial thromboses associated with the lupus anticoagulant and antibodies to cardiolipin in the absence of SLE. Rheumatol Int 1984; 4:1-3.
perium; this may well be due to hormonal factors [15]. Furthermore A P A s are associated with an increased risk of abortion. It may be, therefore, that A P A s were present in our patient's serum before or at the time of her abortion, and that subsequent hormonal changes allowed the expression of disease, in the form of hepatic thrombosis, to be initiated.
Acknowledgements We wish to acknowledge: Dr. Richard Machel, Consultant Gastroenterologist, West Cornwall Hospital, Penzance, who looked after this patient on her initial presentation; Mr. Ian Hamilton, Consultant Surgeon, Royal Cornwall Hospital (Treliske), Truro, who carried out difficult surgery; and the anaesthetic and nursing staff. We are also very grateful to Dr. A n d r e w Plaut, New England Medical Center, Boston, U.S.A. for sera from patients with chronic active hepatitis and alcoholic cirrhosis.
7 Mackworth-Young CG, Gharavi AE, Boey ML and Hughes GRV. Portal and pulmonary hypertension in a case of systemic lupus erythematosus: possible relationship with clotting abnormality. Eur J Rheum lnflamm (in press). 8 Pappas SC, Malone DG, Rabin L, Hoofnagle JH and Jones EA. Hepatic veno-occlusive disease in a patient with systemic lupus erythematosus. Arth Rheum 1984; 27:( 1), 104-108. 9 Hughes GRV. Thrombosis, abortion, cerebral disease and the lupus anticoagulant. Brit Med J 1983;287:1088-1089. 10 Lee SL and Mioni AB. Disorders of haemostatic function in patients with systemic lupus erythematosus. Semin Arthr Rheum 1975;4:241-252. 11 Byron MA. The clotting defect in SLE. Clin Rheum Dis 1982; 8:137-15 I. 12 Carreras LA. Defreyn G, Machin SJ. Vermelyn J, Deman R, Spitz B and Van Assiche A. Arterial thrombosis, intrauterine death, and lupus anticoagulant. Lancet 1981; 1:244-246. 13 Pomeroy C, Kinodell RG, Swaion WR, Arneson P and Mahowald ML. Budd-Chiari syndrome in a patient with the lupus anticoagulant. Gastroenterology 1984; 86:158-161. 14 PowelI-Jackson PR, Melia W, Canalese J, Pickford RB. Portmann B, Williams R. Budd-Chiari syndrome: clinical patterns and therapy. Quarterly Journal of Medicine 1982; 51:79-88. 15 Zurier RB. Systemic lupus and pregnancy. Clin Rheum Dis 1975; 1:613.