Lupus anticoagulant and late onset seizures.

Lupus anticoagulant was found in the plasma of 4 patients who presented with late-onset epileptic seizures. Three of the patients had clinical or electroencephalographic evidence of focality. No significant cerebral pathological findings were detected by the computed tomogram except for an old infarction in one case. None of the patients fulfilled the diagnostic criteria for systemic lupus erythematosus. The relationship between late-onset seizures and the presence of lupus anticoagulant is discussed. The possible etiology of an ischemic episode due to hypercoagulability, expressed uniquely by seizures, is suggested.

Myocardial infarction, persistent coronary artery thrombosis and lupus anticoagulant.

A 40-year-old man who presented with exertional angina had had two myocardial infarctions within the same myocardial distribution several years earlier. Coronary arteriography revealed a large intramural thrombus in the right coronary artery and minimal atherosclerotic disease. Special coagulation studies detected a circulating lupus anticoagulant. The association of repeated episodes of thrombosis and lupus anticoagulant is important. In patients with repeated thrombotic events, the lupus anticoagulant should be sought, particularly in those less than 40 years of age.

Lupus anticoagulant, antiphospholipid antibodies and migraine.

The records of fifteen patients referred for neurological assessment and found to have lupus anticoagulant or elevated anticardiolipin antibodies were reviewed. The mean age for females in the group was 29.4 years and for males was 35. A diagnosis of migraine, either as an acute or chronic problem, was made in 10 (66%) of these patients. Seven of the 15 patients had ischemic stroke and two patients had other thrombotic complications associated with lupus anticoagulant. Three of the nine female patients with migraine had histories of spontaneous abortions. All migraine patients experienced transient or more prolonged neurological deficits with their headaches. An association between lupus anticoagulant and migraine can only be suggested. Data on the incidence of migraine in patients with lupus anticoagulant in the general medical population does not exist. Furthermore the prevalence of lupus anticoagulant in migraine sufferers is unknown. Therefore further studies are required to investigate this possible association.

Monitoring lupus anticoagulant-positive pregnancies with umbilical artery flow velocity waveforms.

The presence of the "lupus anticoagulant" in maternal blood is associated with thrombosis in the placental vessels and a high rate of fetal loss. We followed six pregnancies in four mothers positive for lupus anticoagulant autoantibody with Doppler umbilical flow studies. The women were not treated with any drugs, and clinical management was guided by close fetal surveillance including umbilical flow studies. Umbilical artery flow velocity waveforms detect vascular abnormalities in the fetal umbilical placental circulation and were used as an early indicator of developing disease. All pregnancies produced live-born infants. These cases indicate the potential value of such studies in the management of this group at high risk of fetal loss.

Endothelial-dependent fibrinolysis in subjects with the lupus anticoagulant and thrombosis.

To investigate the hypothesis that diminished endothelial fibrinolytic activity contributes to the pathogenesis of thrombosis in patients with the lupus anticoagulant (LA), we assessed the ability of endothelium to release tissue-type plasminogen activator (t-PA) in response to standardized venous occlusion (VO) of the arm, and the extent of inhibition of t-PA, in 11 subjects with LA and a history of thrombosis and in 36 healthy normal subjects. The mean rise in plasma t-PA antigen after VO, the mean plasma free t-PA activity after VO, and the mean plasma t-PA inhibitor level prior to VO were not significantly different in subjects with LA and thrombosis and in normal subjects. Four subjects with LA and thrombosis (36%), and five of 36 healthy control subjects (14%) generated no detectable free t-PA activity after VO ("non-responders"); this difference was not statistically significant. All four "non-responders" with LA and thrombosis had normal t-PA antigen release after VO, indicating that the lack of detectable free t-PA activity after VO was due to increased inhibition of released t-PA. We conclude that abnormally reduced endothelial fibrinolytic activity is not present in the majority of subjects with LA and thrombosis. In the subset of subjects with LA and thrombosis who generate no detectable t-PA activity after VO, a stimulatory effect of LA on endothelial production of t-PA inhibitor cannot be excluded.

Time dependency of lupuslike anticoagulants.

Fifty-two patients (29 female and 23 male) with lupuslike anticoagulants were reviewed retrospectively to determine whether their inhibitors were time dependent (TD). In 21 cases (40%), a TD pattern emerged: when patient plasma was added to normal plasma and an activated partial thromboplastin time (APTT) test was performed on the mixture, the patient/control ratio after incubation for one hour at 37 degrees C (60-minute ratio) exceeded significantly the respective preincubation ratio (zero-minute ratio). In four cases (8%), anticoagulant activity would have gone undetected if mixing studies had been restricted to the preincubation phase. The TD anticoagulants appeared to be more potent than their time-independent (TI) counterparts (mean APTT, 74.1 vs 58.5 s, respectively). An APTT greater than 63 s was 85% predictive of TD behavior. Greater overlap between the two groups was seen when zero-minute ratios were compared; an equivalent cutoff of 1.36 for the zero-minute ratio was only 65% predictive of TD behavior. The separation between the two groups was most striking when 60-minute ratios were compared. Nineteen TD patients (90%) had 60-minute ratios that exceeded the mean TI ratio of 1.33, while 30 TI patients (97%) had 60-minute ratios that were lower than the mean TD ratio of 1.89. Collectively, these findings indicate that many potent lupuslike anticoagulants require incubation to express maximal anticoagulant activity. Indeed, in some cases, anticoagulant activity might not be detected if mixing studies are restricted to the preincubation phase. The APTT can be helpful in predicting which anticoagulants will show TD behavior.

Platelet aggregations, fatty acids, clotting factors and serum lipids in rural and urban blacks, and urban whites in South Africa.

Platelet fatty acids, platelet aggregations, and coagulation factors were measured in 27 rural blacks, 27 urban blacks and 39 urban whites. Platelets were significantly less aggregable to collagen and arachidonic acid in in both black groups as compared to whites (p less than 0.01), but there were no significant differences in ADP or epinephrine aggregation between these groups. Factor VIII coagulant activity was much higher in rural and urban blacks than whites (p less than 0.001), and the partial thromboplastin times were shorter (p less than 0.005). Platelet arachidonic acid showed a marked difference between the groups, being 16.4 +/- 5.4% of total platelet fatty acids in the rural blacks, 19.9 +/- 4.2% in the urban blacks and 22.6 +/- 3.3% in the whites (p less than 0.001). Whites had higher LDL and lower HDL cholesterol than blacks (p less than 0.005). These findings suggest that in addition to the well known association of raised LDL cholesterol and acute myocardial infarction, platelet aggregation patterns and platelet arachidonic acid levels may be associated risk factors in coronary thrombosis.

Monoclonal IgM with lupus anticoagulant activity in a case of Waldenström's macroglobulinaemia.

Strong lupus anticoagulant activity was detected in the plasma of a 73-yr-old woman with Waldenström's macroglobulinaemia. Purified patient IgM caused significant prolongation of the APTT in concentrations as low as 30 micrograms/ml, and its activity was inhibited by intact or (more effectively) by frozen-thawed blood platelets. Employing varying concentrations of cephalin in the APTT assay, it was demonstrated that the macroglobulin had a direct cephalin-neutralizing effect. When tested in an ELISA system using phospholipid-coated microtiter wells, the IgM was shown to possess antibody activity against cephalin. With purified phospholipids as antigens, the protein was found to display antibody activity against phosphatidyl serine and phosphatidyl ethanolamine, which are main constituents of cephalin. These observations were confirmed in absorption experiments.

A quantitative study of monocyte procoagulant activity in acute monoblastic and chronic myelomonocytic leukaemias.

Monoblasts from 7 patients with acute monoblastic leukaemia produced significantly less procoagulant activity (PCA) in response to endotoxin (mean 0.7 U/10(6) monocytes, range 0.4-1.4) than monocytes from 6 patients with chronic myelomonocytic leukaemia (mean 6.0 U/10(6) monocytes, range 1.25-10.7) and 15 normal subjects (mean 8.9 U/10(6) monocytes, range 3.1-21.2). However, when expressed as the quantity of monocyte-related PCA generated per millilitre of blood, there was no significant difference between patients with acute monoblastic or chronic myelomonocytic leukaemias, though both types of patients generated significantly higher amounts of PCA than normal subjects or patients in haematological remission. The relationship of these findings to the occurrence of disseminated intravascular coagulation is discussed.

Transient lupus anticoagulant and fansidar therapy.

A case of the Stevens-Johnson syndrome following Fansidar therapy is reported in which a marked feature was the presence of a circulating anticoagulant of the lupus inhibitor type. Treatment with steroids resulted in complete recovery and disappearance of the anticoagulant.

Tombosis venosa profunda en un paciente con brucelosis y un probable inhibidor lupico: informe de un caso / Deep venous thrombosis in a patient with brucellosis and a probable lufoid inhibitor: report of a case

Se presenta el caso de una paciente de 18 años de edad que ingresó al hospital por un padecimiento de 15 días de evolución caracterizada por dolor y edema de los miembros inferiores. En su estudio intra-hospitalario se demostró brucelosis aguda por un título sérico de 1:800 y cultivos positivos para brucella sp.; trombosis venosa profunda iliofemoral en asociación con un tiempo de protrombina normal y de tromboplastina parcial prolongado. Haciendo una mezcla del plasma de la enferma con un volumen igual d eun plasma normal, se demostró un anticoagulante ciruclante y mediante el tiempo de coagulación con caolina, se identificó un inhibidor tipo lúpico. La paciente recibió tratamiento con tetraciclinas orales y anticoagulación sistémica y cuatro meses después de su egreso del hospital se encontraba asintomática y no recibía tratamiento alguno. Sus estudios de control, tanto para la brucellosis como de coagulación estaban normales. Se hacen algunas consideraciones acerca de una posible asociación entre la brucelosis y el anticoagulante circulante

Autoimmunity, fetal losses, lupus anticoagulant: beginning of systemic lupus erythematosus or new autoimmune entity with gynaeco-obstetrical expression?

Among the various autoantibodies commonly found in women with systemic lupus erythematosus, the so-called lupus anticoagulant has been described in association with fetal losses. Recently, women with repeated spontaneous abortions and lupus anticoagulant, but no apparent systemic lupus erythematosus have been described. We have studied prospectively the possible connections between fetal losses and autoimmunity in a large control study of 130 idiopathic habitual aborters. These non-pregnant patients without any antecedent autoimmune disease were explored for the presence for autoantibodies especially lupus anticoagulant. Ten percent of the patients exhibit an antithromboplastin antibody (lupus anticoagulant) and half of this group possesses a striking association of biological manifestations of autoimmunity. In conclusion, two points appear: firstly, statistical correlation is demonstrated between antithromboplastin antibody and habitual abortion; secondly, doubt remains about the significance of the association between autoimmunity, fetal losses and antithromboplastin: beginning of systemic lupus erythematosus or new autoimmune entity with gynaeco-obstetrical expression.