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Biomedical subjects

R M Sandler

Publications and source records attributed to R M Sandler.

15 recordsLinked to original sources

Heparin-induced thrombocytopenia and thrombosis: detection and specificity of a platelet-aggregating IgG.

A 46-year-old female who died as a result of thrombocytopenia associated with multiple arterial occlusions and septicemia while on heparin therapy was found to have a platelet-aggregating factor present in several plasma samples and in a sample of serum. This factor was subsequently shown to be an IgG with aggregating properties toward normal platelets that were enhanced by, but not dependent on, the presence of heparin. Further studies showed that heparin was unlikely to have acted as a hapten in initiating the IgG production but that its role was significant in aggravating the ensuing arterial thrombosis. The necessity of substitution of heparin with alternative anticoagulant/antithrombotic therapy to avoid the worst sequelae of this potentially catastrophic syndrome is discussed.

Blood Coagulation Factors↗

Reduced alpha-2-antiplasmin levels in the nephrotic syndrome.

Venous and arterial thromboembolism frequently complicate the nephrotic syndrome. Increased platelet aggregation, high levels of fibrinogen and other procoagulants, and depressed levels of antithrombin III and plasminogen are commonly cited as reasons. Less attention has been paid to changes in the hemostatic system which might protect against thrombosis. We found a high frequency of reduced alpha 2-antiplasmin levels in 40 patients with nephrotic syndrome, correlating with serum albumin and with antithrombin III levels. Since alpha 2-antiplasmin is a major determinant of the sensitivity of fibrin thrombi to lysis, and since reduced levels would be expected to promote fibrinolysis, we conclude that in many patients with nephrotic syndrome depressed antiplasmin levels may help reduce the risk of thrombosis posed by diminished antithrombin III levels.

Antithrombin III↗

Use of noninvasive laboratory testing in the prediction of thrombosis in the nephrotic syndrome.

A noninvasive method for diagnosing thrombosis in the nephrotic syndrome could be useful clinically. We measured hematocrit, fibrinogen, creatinine, antithrombin III, plasminogen, and alpha-2-plasmin inhibitor levels in 20 patients with nephrotic syndrome objectively studied for the presence of thrombosis, and found that by using combinations of three or more of these variables good discrimination could be obtained between those patients with and without thrombosis. We conclude that it is possible to predict risk of thrombosis in nephrotic syndrome using relatively simple noninvasive laboratory tests.

Antithrombin III↗

Antithrombin III and anti-activated factor X activity in patients with acute promyelocytic leukemia and disseminated intravascular coagulation treated with heparin.

Two patients diagnosed as having acute promyelocytic leukemia (APL) and disseminated intravascular coagulation (DIC) were closely followed from the day of admission until completion of the first course of chemotherapy with serial coagulation studies including plasma levels of functional antithrombin III activity (AT III) by fluorometric analysis and anti-activated Factor X activity (anti-Xa) by coagulation assay. Both patients were treated with intravenous heparin and the presence of heparin in plasma was followed by the thrombin time. Consistently normal levels of AT III (greater than 80%) were found despite evidence of intravascular coagulation. However, plasma levels of anti-Xa were often low (less than 70%) and increased only in the presence of heparin. The significance of these results in relationship to heparin therapy for disseminated intravascular coagulation of APL is discussed.

Adolescent↗

Antithrombin III and anti-activated factor X activity in patients with acute promyelocytic leukemia and disseminated intravascular coagulation treated with heparin.

Two patients diagnosed as having acute promyelocytic leukemia (APL) and disseminated intravascular coagulation (DIC) were closely followed from the day of admission until completion of the first course of chemotherapy with serial coagulation studies including plasma levels of functional antithrombin III activity (AT III) by fluorometric analysis and anti-activated Factor X activity (anti-Xa) by coagulation assay. Both patients were treated with intravenous heparin and the presence of heparin in plasma was followed by the thrombin time. Consistently normal levels of AT III (greater than 80%) were found despite evidence of intravascular coagulation. However, plasma levels of anti-Xa were often low (less than 70%) and increased only in the presence of heparin. The significance of these results in relationship to heparin therapy for disseminated intravascular coagulation of APL is discussed.

Adolescent↗

Variable presentation of thrombocytopenia in Graves' disease.

An association between thrombocytopenia and thyrotoxicosis has been reported but its mechanism is unclear. We describe five patients in whom thrombocytopenia accompanied Graves' disease. The thrombocytopenia resembled idiopathic thrombocytopenic purpura and responded to prednisone therapy in cases 1 and 2. In case 3, thrombocytopenia remitted with treatment of the thyrotoxicosis, while, in case 4, remission occurred despite persistent hyperthyroidism. In case 5, thrombocytopenia persisted despite correction of the hyperthyroidism but remained clinically insignificant. We conclude that there is a clear association between the two conditions but the clinical patterns of presentation and pathogenesis seem heterogenous. This variability must be considered during management.

Adult↗

A simple method for detecting complement-fixation by autologous platelets in autoimmune thrombocytopenic purpura.

A new modification of the microtitre complement fixation test, (CFT), is described for the detection of platelet-bound antibodies (PBA). The test was positive in 12 out of 16 patients, (75%), with active autoimmune thrombocytopenic purpura (AITP). It was negative in four patients who were in remission of AITP when tested, in 10 patients with non-immune thrombocytopenia and in 51 normal blood donors. This is a semi-quantitative method in which suspensions of the patients' own platelets consume complement and therefore prevent the lysis of sensitised sheep red cells (SRBC). Sera from some of these cases were also tested for serum anti-platelet antibody (SPA) and immune complexes. The possible mechanisms and the relevance of positive results are discussed.

Adenosine Diphosphate↗

Null-cell properties of a lymphoid cell line from a child with acute lymphoblastic leukaemia.

Cultured cells established from the bone marrow of a child with null-cell acute lymphoblastic leukaemia (ALL) have been studied. After 8 months in vitro, the cytological, cytochemical and immunological properties of the cultured cells were very similar to those of the patient's cells. Many of the cultured cells had morphological and cytogenetic abnormalities often found in acute leukaemia. The cells were EBNA-negative. This unique culture of ALL-derived null cells might provide information as to the aetiology and origin of malignant cells.

Antigens, Viral↗

Treatment of acute myeloid leukaemia with a triple cytotoxic regime: DAT.

Twenty patients with acute myeloid leukaemia (AML) were treated with a combination of chemotherapy which included daunorubicin, cytosine arabino-side and 6-thioguanine (DAT). The complete remission rate was 85% and was achieved, in responsive cases, after an average of 2 courses of therapy. Patients remained in hospital for an average of 37.5 days during remission-induction therapy and 3.7 days per month thereafter. The median remission period was 48 weeks and median survival was 70 weeks. A disappointing feature was the high relapse rate. This feature of the results re-affirms the need for a more effective form of remission therapy.

Adolescent↗