Lupus anticoagulant and anticardiolipin antibodies in systemic lupus erythematosus.

BACKGROUND. Lupus anticoagulant and anticardiolipin antibodies are antiphospholipid antibodies which have been independently associated with a high incidence of thrombotic diseases. However, the importance of their combined occurrence has not yet been examined. METHODS. We investigated 70 patients with systemic lupus erythematosus for the presence of anticardiolipin antibodies paying particular attention to a history of thrombosis and abortion. Lupus anticoagulant was detected using the kaolin clotting time, its mixing tests with normal plasma and the inosithin neutralization test. Anticardiolipin antibodies were detected using the ELISA technique. RESULTS. Lupus anticoagulant was detected in 11 patients (16%) and anticardiolipin antibodies in 13 (19%). Six patients were positive for both lupus anticoagulant and anticardiolipin antibodies. These patients had a higher incidence of thrombosis or recurrent abortion (5 of 6) compared to those with lupus anticoagulant (2 of 5) or anticardiolipin antibodies alone (1 of 7). The amount of inosithin required to neutralize lupus anticoagulant was greater [mean (SD) 27.5 (20.5) micrograms] in patients with both lupus anticoagulant and anticardiolipin antibodies than in patients with lupus anticoagulant alone [mean (SD) 4.0 (5.4) micrograms]. CONCLUSION. The presence of lupus anticoagulant is associated with thrombosis and recurrent abortion which are more frequent when both lupus anticoagulant and anticardiolipin antibodies are present and these patients probably have more severe disease as the amount of inosithin required to neutralize the lupus anticoagulant was greater.

Platelet function disorders in north India.

BACKGROUND. Platelet function disorders are a fairly common cause of bleeding manifestations. Although their relative types and incidence are well documented, data from India are lacking. METHODS. Between 1970 and 1991, we studied the clinical and laboratory features of 144 north Indian patients who presented to our hospital with a bleeding diathesis in whom coagulation disorders, von Willebrand's disease and a history of drug ingestion were absent. RESULTS. Isolated platelet factor 3 availability defect was the commonest (56 cases) followed by the thrombasthenias (49 cases), arachidonic acid pathway defect (26 cases), storage pool disease (8 cases) and the Bernard-Soulier syndrome (3 cases). Isolated platelet factor 3 deficiency was rare (2 cases). Two varieties of thrombasthenia were seen--the classical Glanzmann's (13 cases) and thrombopathic (36 cases). The latter was characterized by absent or sub-normal platelet aggregation with agonists along with a reduced (to less than 50% of normal) total platelet factor 3 content. This has not been reported from western countries. Patients with classical Glanzmann's thrombopathic thrombasthenia with absent platelet aggregation and isolated platelet factor 3 deficiency were severe bleeders. Their family history suggested an autosomal recessive transmission in Glanzmann's and thrombopathic thrombasthenia and a possible autosomal dominant transmission in isolated platelet factor 3 availability defect and isolated platelet factor 3 deficiency. CONCLUSION. The frequency of various types of platelet function disorders in Indians is similar to that in western populations except that the incidence of thrombopathic thrombasthenias is higher in India.

Efficacy of intrathecal methotrexate with and without cranial radiotherapy in preventing central nervous system relapses in acute lymphocytic leukemia.

Introduction of CNS chemoprophylaxis was a major milestone in the development of current therapy for acute lymphocytic leukemia. However, controversies are still existing for ideal form of CNS chemoprophylaxis. The present study was conducted to determine the efficacy of intrathecal methotrexate (IT-MTX) with and without cranial radiotherapy in preventing CNS relapses in Indian children. CNS chemoprophylaxis comprising of six injections of intrathecal methotrexate (12 mg/M2) was administered alone or along with cranial radiotherapy (2000 GY) in 76 children each after successful induction remission. Cranial radiotherapy (RT) with intrathecal methotrexate (IT-MTX) was observed to be more effective as CNS relapses were seen in 11.8% of children as compared to 16.8% of children receiving IT-MTX alone. IT-MTX along with cranial RT delayed the occurrence of CNS relapses and prolonged the event free survival periods.

A clinico-haematologic profile of paroxysmal nocturnal haemoglobinuria.

Clinico-haematological parameters in sixteen patients of paroxysmal nocturnal haemoglobinuria (PNH) are presented. Their modes of presentation included recurrent episodes of cola-coloured urine (6/16), refractory anaemia (9/16) and predominant thrombotic manifestations (1/16). Laboratory investigations revealed the presence of anaemia (16/16), reticulocytosis (14/16), thrombocytopenia (11/16), leucopenia (5/16) and cellular bone marrow (14/16). Two patients had hypoplastic bone marrow initially but subsequently developed PNH. The patients were treated with haematinics, prednisolone (16/16) and oxymethalone (2). Prednisone was effective in suppressing haemolytic episodes. Oxymethalone given to the 2 patients with hypoplastic bone marrow resulted in amelioration of anaemia in one but no effect in the other patient.

Effect of calcium channel blocker (diltiazem) on platelet aggregation.

Platelet aggregation with collagen, ADP and sodium arachidonate was significantly inhibited by 0.48 and 0.24 mg/ml of diltiazem but no significant effect occurred with 0.024 mg/ml of diltiazem. It is suggested that the antiplatelet property of diltiazem may be utilized in clinical setting and diltiazem may be tried synergistically with other antiplatelet drugs.

Congenital factor XIII deficiency: two case reports.

Two patients with factor XIII deficiency, presenting with bleeding disorder since birth, are reported. The condition is rare and is likely to be missed unless clot solubility in 5 M urea is performed as a screening test in all patients with bleeding disorders. A correct diagnosis is essential as prophylactic management is practicable in this disorder.

Evaluation of factors predisposing to arterial thrombosis in coronary artery disease.

Estimation of antithrombin III, alpha 2 macroglobulin and alpha 1 antitrypsin in patients with stable and unstable angina and acute myocardial infarction (15 cases each) were carried out. Twenty age, sex and weight matched healthy subjects were included as controls. Mean platelet factor 4(PF4) levels measured in 10 cases of each subgroup were significantly elevated in myocardial infarction (MI) (48.4 +/- 15.16 ng/ml) and III unstable angina patients (44.7 +/- 15.9 ng/ml) as compared to controls (25.42 +/- 12.47 ng/ml; P less than 0.01). Mean antithrombin III (AT III) levels were markedly reduced in all patients with MI (39.65 +/- 12.8% of normal pooled plasma) and unstable angina (37.9 +/- 16.6% of normal pooled plasma) and in 9 patients with stable angina. Alpha I antitrypsin and alpha 2 macroglobulin levels in these cases showed no significant difference compared to normals. Reduced AT III in coronary artery disease suggests a prethrombotic tendency in these patients. Raised PF4 levels in acute phase of the disease suggests heightened platelet activation.

Evaluation of a micromethod for detection of G-6-PD deficiency.

A simple and inexpensive micromethod based on methaemoglobin reduction technique (MRT) for screening of glucose-6 phosphate dehydrogenase deficiency has been studied using reagent-impregnated curvettes incubated in a makeshift waterbath. The cuvettes shelf life has been tested upto nine months. As the test can be done with finger prick blood, it promises to be more acceptable in the field. The sensitivity of this is similar to classical MRT.

Coagulation abnormalities in systemic lupus erythematosus.

Coagulation profile was studied in 55 patients of systemic lupus erythematosus (SLE). Abnormal kaolin clotting time (KCT) was observed in fewer patients (12.9%) as compared to abnormal Russel's viper venom time (RVVT, 20.4%) or activated partial thromboplastin time (APTT, 32.7%). Prolonged prothrombin time (PT), observed in 7.3 per cent patients was not found to be a sensitive test for lupus anticoagulant (LAC). The correction of RVVT and KCT on addition of inosithin suggested a deficiency of platelet lipid factor in these patients. The initial value of uncorrected KCT in patient's plasma did not correlate with the amount of inosithin required for neutralisation. Occurrence of thromboembolic events was significantly associated with prolonged KCT. No other clinical feature showed significant association with any coagulation abnormality.

Platelet function in type I (insulin dependent) diabetes without vascular disease.

In 10 patients of type I diabetes who were free from clinically apparent vascular disease, platelet functions were studied prior to control, and 10 days and 3 months after strict metabolic control. Platelet hyperactivity, seen as significant shortening of latent period and increase in rate and degree of aggregation, present in patients in the initial uncontrolled state, but absent at the subsequent two periods did not correlate with glycosylation of haemoglobin. Thus control of diabetes mellitus, capable of reversing platelet hyperactivity, is reflected by blood sugar levels, and not by the glycosylation status of haemoglobin.