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Biomedical subjects

D M Keeling

Publications and source records attributed to D M Keeling.

36 records · Page 2Linked to original sources
PubMed1997

Cryoprecipitate prepared from plasma virally inactivated by the solvent detergent method.

There remains a small risk of viral transmission from single-donor blood components such as fresh frozen plasma (FFP) and cryoprecipitate which have not been subjected to a viral inactivation procedure. It is now possible to subject pooled FFP to viral inactivation by the solvent detergent (SD) treatment method, but with some loss of coagulation factors. To establish whether cryoprecipitate prepared from SD plasma would be suitable for the treatment of hypofibrinogenaemia and von Willebrand's disease (VWD), control and SD cryoprecipitate were assayed for factor VIII. von Willebrand factor (VWF) and fibrinogen content. In SD cryoprecipitate, levels of VWF activity and antigen were only 36% and 37% of control values respectively, whereas fibrinogen was 72%. The highest molecular weight multimer of VWF:Ag were absent from both SD plasma and SD cryoprecipitate. SD cryoprecipitate would thus be unsuitable for treating VWD, but would provide an alternative to untreated individual donor units of cryoprecipitate for the treatment of hypofibrinogenaemic states.

Blood Preservation↗
PubMed1994

Platelet aggregation in response to four low molecular weight heparins and the heparinoid ORG 10172 in patients with heparin-induced thrombocytopenia.

A simple rapid platelet aggregation test was used to evaluate cross-reactivity of four low molecular weight heparins and the heparinoid ORG 10172 in three patients with heparin-induced thrombocytopenia. The low molecular weight heparins cross-reacted in 11 out of 12 tests. The heparinoid ORG 10172 did not cross-react in any of the patients. One patient was treated with ORG 10172 and thrombocytopenia resolved.

Adult↗
PubMed1993

Haematological manifestations of systemic lupus erythematosus.

Haematological involvement is common in systemic lupus erythematosus (SLE). Whilst anaemia is most often due to chronic disease, other causes such as autoimmune haemolytic anaemia and hypoplastic anaemia need to be considered. The increased risk of infection in patients with SLE is due in part to changes in the white blood cells though treatments do not yet aim to modify these. Thrombocytopenia occurs frequently and is almost invariably autoimmune. It is often of little consequence, but may occasionally be severe and serious, requiring aggressive treatment. Patients with SLE have an increased risk of thrombosis, increased further in the presence of antiphospholipid antibodies (aPL). Changes in the haemostatic system and new insights into the nature of aPL are described.

Anemia↗
PubMed1993

Role of beta 2-glycoprotein I and anti-phospholipid antibodies in activation of protein C in vitro.

AIMS: To investigate the effect of beta 2-glycoprotein I (beta 2 GPI) on the thrombin/thrombomodulin dependent activation of protein C; and to determine whether beta 2 GPI dependent anticardiolipin antibodies have any effect. METHODS: Protein C was activated by thrombin in the presence of thrombomodulin and phospholipid vesicles in an in vitro system. The effect of adding purified beta 2 GPI to this system was observed. Affinity purified anticardiolipin antibodies and total IgG from patients with anticardiolipin antibodies and the lupus anticoagulant were studied for their effects on protein C activation in the presence and absence of beta 2 GPI. RESULTS: beta 2-Glycoprotein I had no effect on the activity of preformed activated protein C. When the phospholipid vesicles were incubated with beta 2 GPI before the addition of protein C, the activation of protein C was inhibited in a dose dependent manner. With phosphatidylserine:phosphatidylcholine vesicles at a concentration of 1 microM:2 microM, beta 2 GPI began to inhibit the reaction at a concentration of 15 nM, and at 4 microM (the normal plasma concentration) the activation of protein C was reduced to 40%. Anticardiolipin antibodies had no demonstrable effect. CONCLUSIONS: beta 2-Glycoprotein I inhibits protein C activation in an in vitro system. Its physiological role is unknown but it has potential procoagulant as well as anticoagulant properties. An effect of antiphospholipid antibodies on protein C activation, which might explain their association with thrombosis, could not be shown.

Antibodies, Antiphospholipid↗
PubMed1993

Lupus anticoagulant activity of some antiphospholipid antibodies against phospholipid bound beta 2 glycoprotein I.

AIMS: To determine whether beta 2 glycoprotein I (beta 2GPI) dependent anticardiolipin (aCL) antibodies detected in solid phase enzyme linked immunosorbent assays can also have lupus anticoagulant activity. METHODS: Six anticardiolipin antibodies were affinity purified from patients with these antibodies and lupus anticoagulant activity in their plasma. RESULTS: The anticardiolipin antibodies bound only to anionic phospholipids in the presence of beta 2GPI and bound to beta 2GPI in the absence of phospholipids. Four out of six had lupus anticoagulant activity in the dilute Russell viper venom time test. CONCLUSIONS: The results show that some beta 2GPI dependent aCL are lupus anticoagulants. It is unclear why only some should have lupus anticoagulant activity while others do not.

Anions↗
PubMed1992

Treponemal infection coexisting with systemic lupus erythematosus.

A patient with systemic lupus erythematosus (SLE)/erosive arthritis overlap is described who was also shown to have late latent treponemal infection. The possibility of serological reactivation is discussed. Since antiphospholipid antibodies are the basis of the reagin tests for syphilis as well as being present in patients with SLE, difficulties with diagnosis may ensue.

Female↗
PubMed1992

Some 'antiphospholipid antibodies' bind to beta 2-glycoprotein I in the absence of phospholipid.

Some antiphospholipid antibodies (aPL) only bind to anionic phospholipids in the presence of a serum cofactor, beta 2-glycoprotein I (beta 2GPI). Whether these aPL can bind to beta 2GPI in the absence of phospholipid is controversial. We have purified anticardiolipin antibodies (aCL) from the plasma of four patients and beta 2GPI from normal plasma by solid phase affinity methods. All four aCL bound to cardiolipin and phosphatidylserine in the presence of beta 2GPI but not in its absence. The binding of two of the antibodies to cardiolipin and phosphatidylserine at various concentrations of human beta 2GPI was compared with that obtained using 10% bovine serum. The two antibodies responded differently to increasing beta 2GPI concentrations, and binding to phosphatidylserine was relatively greater than to cardiolipin using human beta 2GPI. All four aCL bound to plastic plates coated with beta 2GPI in the absence of phospholipid, and beta 2GPI in the fluid phase had no effect on binding. Binding to beta 2GPI coated plates was increased equally when bovine serum or bovine albumin were used as the sample diluent in place of gelatine. These findings and those of others have important implications for the design of assays for antiphospholipid antibodies.

Antibodies, Anticardiolipin↗
PubMed1991

The fibrinolytic response to venous occlusion and the natural anticoagulants in patients with antiphospholipid antibodies both with and without systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) have an increased risk of thrombosis and this is increased in the presence of antiphospholipid antibodies (APA). These APA are also associated with thrombosis in patients who do not have SLE. We compared haemostatic parameters in SLE patients with and without APA, and also compared patients who had APA but not SLE with healthy normal controls. No relationships between the natural anticoagulants, antithrombin III, heparin cofactor II, protein C and protein S, and the presence of APA were found. In the patients with SLE both tissue plasminogen activator antigen and plasminogen activator inhibitor (PAI) were increased, but these changes were not due to APA which had no effect on fibrinolysis in these patients. In the patients with APA who did not have SLE the fibrinolytic response to venous occlusion was reduced due to raised levels of PAI; similar changes have, however, been reported in some patients with idiopathic thrombosis.

Adolescent↗
PubMed1990

Multiple transient ischaemic attacks and a mild thrombotic stroke in a HIV-positive patient with anticardiolipin antibodies.

Antiphospholipid antibodies (APA) have been reported to be associated with thrombosis in systemic lupus erythematosus (SLE) and in many other clinical groups. However, although these antibodies have been identified in a substantial number of patients infected with the human immunodeficiency virus (HIV), in this case an association with thrombosis has not been evident. We describe a patient with HIV infection who had anticardiolipin antibodies (ACA) but no lupus anticoagulant (LA) who had recurrent transient ischaemic attacks (TIAs) and a mild stroke.

Adult↗
PubMed1990

Sezary cell-like leukemia: a distinct type of mature T cell malignancy.

We describe the clinical, ultrastructural, and immunophenotypical characteristics of four cases of an unusual type of T cell leukemia. Clinical features included high WBC, ranging from 26-148 x 10(9)/liter, bone marrow infiltration, splenomegaly, and lymphadenopathy. Skin involvement was not documented at presentation, but it was seen as a terminal event in one patient with a pattern of dermal lymphocytic infiltration different from that usually seen in Sezary syndrome. By ultrastructural analysis, the circulating lymphoid cells were indistinguishable from small Sezary cells in two cases, resembled large Sezary cells in one case, and consisted of a mixture of small Sezary cells and prolymphocytes in the remaining case. The cells from all cases had a mature T cell phenotype, TdT-, CD1a-, CD2+/-, CD3+, CD5+. In addition, the cells were either CD8+, CD4- or CD8+, CD4+ or CD4-, CD8-; and, in only one case, the findings were similar to those of Sezary syndrome cells: CD4+, CD8-, CD7-, BE-2+. In the latter case, serological and immunological assays were positive for HTLV-I while these were negative in two other patients investigated. The features of these patients suggest that Sezary cell leukemia is a distinct clinico-pathological entity although the alternative diagnosis of adult T cell leukemia/lymphoma could not be excluded in the HTLV-I+ case. Sezary cell leukemia appears to be resistant to current chemotherapy regimens and is associated with an aggressive clinical course and short survival.

Adult↗
PubMed1988

Haemolytic uraemic syndrome after bone marrow transplantation: an adverse effect of total body irradiation?

Eight cases of haemolytic uraemic syndrome occurring after bone marrow transplantation are presented and the other 15 reported cases are reviewed. Two patients were recipients of autologous marrow whereas all cases previously reported occurred after allogeneic transplantation. Six patients had not received cyclosporin and two had no evidence of cytomegalovirus infection. The roles of cyclosporin, cytomegalovirus infection, graft-versus-host disease, total body irradiation (TBI) and chemotherapeutic drugs as aetiological agents are discussed. It is postulated that TBI, perhaps potentiated by cyclophosphamide, is likely to be the most important factor but that other agents may act additively with TBI and influence the time course and severity of the disease.

Adolescent↗