THE KURUME Vo1.36, MEDICAL JOURNAL p.113-116, 1989 Lupus Anticoagulant as a Risk and Habitual Factor for Cerebral Infarction Abortions KATSUHIRO MIZOGUCHI*, SHINICHI KAKISAKO, MASAMITSU TANAKA , HIDEKI YANG, TOMOMI SHIMIZU , YUHJI GONDOH, HIROSHI SHOJI AND MASA RO KA JI Department of Internal Medicine, Kurume University Kurume, 830 Japan Received for publication July 5, School of Medicine , 1989 Summary : A case involving a 34-year-old female with a progressive hemiparesis is described. She had a history of repeated spontaneous abortions. The CT and magnetic resonance imaging (MRI) showed a multiple cerebral infarction. A 99mTc perfusion lung scintigram demonstrated diffuse bilateral perfusion defects in the lungs. The presence of lupus anticoagulant (LA) was detected from the laboratory data and the thrombosis in the genital organ . The repeated abortions were probably due to thrombosis in the placental vessels caused by LA. High dose steroid therapy was effective in suppressing the LA activity and in preventing progression of the clinical symptoms . Key words:lupus anticoagulant-thrombosis-cerebral abortions-pulmonary Introduction LA Also, is an acquired munoglobulin which by interfering with tion IgG or inhibits the of prothrombin associated with positive as a risk patients. factor for The importance cerebral infarction habitual abortions due the placental Case Report activator vessels A 34-year-old hospital limbs on a left hemiparesis nosed as 830 Japan to with April 1988. in had investigation por- progressed. spontaneous was It She use, hypertension, of LA and heart disease. in She 1981 a cerebral address : Department had and to all was four noticed diag- infarction. of Pharmacology had appeared in 1983. to the hospital for because her symptoms She had abortions LA admitted in admitted in thrombosis weakness 11, ther described. female the having is im - complex. thrombosis hemiparesis was coagulation phospholipid a right She IgM is often * Present infarction-habitual infarction no history a history from 1976 of oral diabetes fur - of four to 1979. contraceptive mellitus or On admission, the blood pressure was 140/96 mmHg, and the pulse was 92. The chest and abdomen were normal. There was no lesion in the genital organ. Neurological examination revealed that she had a slight reduction of mental state, bleeding in the corpus vitreum, a slight pseudobulbar palsy and a slightly spastic tetraparesis. Her deep tendon reflexes were increased with pathological reflexes. The urine was normal. The hematocrit was 35.0 percent; the white-cell count was , Kurume University School of Medicine, Kurume, MIZOGUCHI, 114 Fig. 1 Technetium-99m bilateral perfusion defects Fig. infarction 2 Magnetic and bleeding ET (99mTc) perfusion in the lungs. resonance in the imaging corpus AL. lung scintigrams, (MRI), vitreum. showing showing diffuse a multiple cerebral LUPUS ANTICOAGULANT 8000. The platelet count was 430, 000, and the erythrocyte sedimentation rate was 36 mm per hour. Liver and renal functions were normal. Serological tests for syphilis, anti-nuclear antibodies, anti-DNA antibodies, LE preparation and rheumatoid factor were negative. The cerebrospinal fluid (CSF) was waterly clear with a pressure of 80mmH2O. The CSF contained 3 cells per mm3. The sugar content was 55 mg/dl and the protein content was 86 mg /dl. The EKG and echocardiography disclosed no abnormalities. A technetium99m (99mTc) perfusion lung scintigram showed diffuse bilateral perfusion defects in the lungs, although chest X-rays disclosed no abnormalities (Fig. 1). The CT scan and MRI showed multiple cerebral infarctions and bleeding in the corpus vitreum, probbably due to a left retinal central vein thrombosis (Fig. 2). Coagulation study: The bleeding and coagulation times, fibrin degradation product (FDP) and anti-thrombin III were within the normal limits. The prothrombin time (PT) was 13.1 seconds (normal <15 seconds). The activated partial thromboplastin time (APTT) was 57.9 seconds (norma1<43 seconds) and when incompletely corrected (51.2 seconds) with a 1:1 dilution with normal plasma, it was at least 5 seconds longer than normal plasma. The presence of LA was recognized because the coag ulation factors (II, V, VIII,IA, X, XI, XII) were within the normal limits. Clinical course: This case was diagnosed as a juvenile cerebral infarction due to LA. Pulse therapy (methylprednisolone, 1000mg/day) was performed for three days because the symptoms progressed. The APTT returned to the normal range (41 seconds) after three days. There as been no recurrence, and the patient has been maintained on prednisolone, 20mg/day. AND THROMBOSIS 115 Discussion This was considered an idiopathic positive case of LA from the laboratory data, which was not associated with collagen disease. LA is an acquired IgG or IgM immunoglobulin which inhibits coagulation by interfering with the phospholipid portion of the prothrombin activator complex. Despite an in vitro anticoagulant activity, LA is most often paradoxically associated with thrombosis and not abnormal bleed ing (Lechner and Pabinger-Fasching, 1985). Elias and Eldor (1984) reported that bleeding occurred in only five of forty patients, four of whom had severe thrombocytopenia; while excessive bleeding did not occur in thirty-five LA positive patients. Thrombosis was observed in both the arterial and venous systems, with deep venous thrombosis in the venous system and pulmonary infarction and cerebral inf arction in the arterial system. In a case with a complicated pulmonary infarction (Anderson and Ali, 1984), a technetium99m (99mTc) perfusion lung schintigram demonstrated perfusion defects, as in the present case. With pulmonary arteriography, most of the pulmonary arterial branches were either occluded or stenosed which was consistent with multiple pulmonary thromboemboli. That patient also had pulmonary hypertension and died of heart failure. At necropsy there were widespread organizing thrombi with focal intimal proliferation and medial hypertrophy within the pulmonary vasculature. The cerebral infarction indicated that the main cerebral arteries tended to be occluded (Hamada et al. 1987). Thrombosis also tends to occur in the placental vessels and may cause an abortion due to infarction and necrosis (Firkin et al. 1980; DeWolf et al. 1982). Since the present patient had frequent abortions, it is possible that thrombosis was occurring in the placental and decidual vessels resulting in the abortions; because there 116 M IZOGUCHI, was no lesion in the genital organ that could induce an abortion and thrombosis had also occurred in other organs (brain, lung, eye). There was also no underlying disease that could cause only frequent abortions (Firkin et al. 1980). Accordingly, Lubbe et al. (1985) emphasized that the demonstration of LA in the plasma of a pregnant woman, even in the absence of other clinical or serologic evidence of connective tissue disease, should be re garded as a marker not only for potential intrauterine death but also for a high risk of maternal thrombotic complications. Regarding therapy, anticoagulants may be needed (Elias and Eldor, 1984), and a successful pregnancy can be obtained on combination therapy with prednisolone and aspirin (Lubbe et al. 1983). Although combination therapy with prednisolone and aspirin is effective, it takes 4-8 weeks to develop a normal APTT, even with 4060 mg of prednisolone, daily. Therefore pulse therapy (methylprednisolone, 1000 mg/day) was performed, because the symptoms were progressing. The APTT returned to the normal range after three days of pulse therapy. There has been no change of APTT, since the patient has been maintained on prednisolone, 20 mg /day daily. There is no agreement LA, as mentioned above. roid therapy tient did APTT, by reduce at on an early LA activity and recurrences maintenance doses time of therapy for dose ste- this pa- High in and normalize were prevented prednisolone. ET AL. References ANDERSON, N. E, and ALI, M. R. (1984). The lupus anticoagulant, pulmonary thromboembolism, and fatal pulmonary hypertension. Ann. Rheum. Dis. 43, 760-763. DE WOLF, F., CARRERAS,L. 0., MOERMAN,P., VERMYLEN, J., VAN ASSCHE,A, and RENAER,M. (1982). Decidual vasculopathy and extensive placental infarction in a patient with repeated thromboembolic accidents, recurrent fetal loss, and a lupus amticoagulant. Am. J. Obstet. Gynecol. 142, 829-834. ELIAS, M, and ELDER,A. (1984). Thromboembolism in patients with the lupus-type circulating anticoagulant. Arch. Intern. Med. 144, 510-515. FIRKIN, B. G., HOWARD,M. A, and RADFORD,N. (1980). Possible relationship between lupus inhibitor and recurrent abortion in young women. Lancet 2. 366. 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