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Biomedical subjects

S M Knowles

Publications and source records attributed to S M Knowles.

13 recordsLinked to original sources
PubMed2002

The United Kingdom National External Quality Assessment Scheme (blood transfusion laboratory practice): trends in proficiency and practice between 1985 and 2000.

Proficiency in blood transfusion laboratory practice has improved over the last 15 years (1985-2000). Error rates for ABO grouping have fallen from 0 x 19 to 0 x 02% (P = 0 x 003). A similar trend is evident for antibody screening, with error rates for false negative antibody screens falling from 3 x 2 to 0 x 5% (P < 0 x 001), and for antibody identification, for sera containing a single alloantibody, with error rates falling from 8 x 8% to 0 x 9% over the last 10 years (P < 0 x 001). Proficiency in serological crossmatching to detect clinically significant non-ABO incompatibilities (other than Kidd), has also improved (P < 0 x 001). However, error rates for RhD grouping have not changed and there has been a recent decline in proficiency in detecting weak ABO incompatibilities and Kidd antibodies with heterozygous cells. Procedures for pretransfusion testing have also been rationalized over this time. The indirect antiglobulin test (IAT) is used in isolation by 73% of laboratories for antibody screening, and 10% rely on the direct room temperature (DRT), immediate spin (IS) crossmatch in the absence (current and/or historical) of clinically significant antibodies. Despite the improvements in error rates that have occurred alongside the rationalizations, there is still evidence of noncompliance with current published BCSH guidelines and manufacturers' instructions.

Antibodies↗
PubMed1997

Pilot study of HLA alloimmunization after transfusion with pre-storage leucodepleted blood products in aplastic anaemia.

We have performed a pilot study to examine the incidence of alloimmunization using pre-storage leucocyte-depleted blood products (PLDP) in 16 previously transfused aplastic anaemia (AA) patients with no detectable HLA antibodies. A further eight AA patients with HLA antibodies received HLA-matched PLDP. Leucodepleted apheresed platelets were obtained using either Cobe spectra or Haemonetics system with an integral pall filter. Pall BPF4 filters were used for red cell preparation. Patients' sera were tested for HLA antibodies using lymphocytotoxicity (LCT). Patients who were HLA antibody negative by LCT at study entry were further tested with enzyme-linked immunoassay (ELISA). Out of 16 patients, two (12%) formed anti-HLA antibodies with a median follow-up of 9 months (range 1-15), but did not display platelet refractoriness to random donor platelets. Two patients were inadvertently transfused with non-leucodepleted blood products when later referred back to their local hospital. Both subsequently demonstrated HLA antibodies by LCT and became platelet refractory. These results contrast with a 50% incidence of HLA alloimmunization in a control group of AA patients transfused prior to this study with non-PLDP. HLA antibodies could no longer be detected by LCT in follow-up of three out of eight patients with HLA antibodies at study entry. Only one patient experienced non-haemolytic febrile transfusion reactions (NHFTR). We conclude that PLDP reduce the risk of alloimmunization even in previously transfused AA patients, PLDP are associated with a low incidence of NHFTR, and all new AA patients should receive PLDP from diagnosis.

Adolescent↗
PubMed1987

Differentiation induction in myelodysplasia and acute myeloid leukaemia: use of synergistic drug combinations.

DNA synthesis inhibitors and vincristine greatly enhance the response of leukaemic and dysplastic cells to differentiation inducing agents such as retinoic acid (RET). Differentiation induction therapy is an attractive therapeutic approach in myelodysplasia (MDS) and in acute myeloid leukaemia (AML) in the elderly, since it should be possible to increase the production of mature cells, at the expense of precursor cells, without incurring the complications of intensive cytotoxic therapy. Single agent differentiation therapy has, however, not been highly successful. We have therefore investigated the use of synergistic combinations of agents. We treated nine patients (6 with MDS, 3 with AML) with 13-cis-retinoic acid (up to 100 mg/m2/day) in combination with either 6-thioguanine (20-40 mg/day in 14-57 day courses) or with vincristine (1-2 mg as a single injection during a four-day course of RET). Seven patients responded with an increase in the mature cells of at least one haemopoietic lineage. A concomitant decrease in marrow blasts was observed in 3/4 responding patients. The retention of dysplastic and karyotypic abnormalities and lack of a hypoplastic phase all suggested that differentiation induction was occurring in vivo. Prior failure to respond to therapy with single agents (RET in two and cytosine arabinoside in five patients) suggests that the synergy observed in vitro operates in vivo. In-vitro studies on marrow cells from seven patients demonstrated synergistic differentiation induction in 6/7 samples. The seventh patient was one of the two who did not respond clinically. The second of these clinically unresponsive patients had cells which were relatively refractory to RET in vitro, suggesting that in-vivo and in-vitro responses may be related.

Adult↗
PubMed1986

Haemolysis after T-cell depleted bone marrow transplantation involving minor AB0 incompatibility.

9 recipients of T-cell depleted allogeneic bone marrows (8 group A, 1 group AB) from group 0 donors were monitored after transplantation. Free anti-A/B was demonstrable in 8 of the 9 recipients 10-19 d post-transplant, 5 patients developed a positive direct anti-globulin test and 7 showed a rise in bilirubin. The presence of antibody was generally unrelated to the infusion of incompatible plasma, although 2 patients who also received anti-CMV immunoglobulin subsequently shown to contain high titre IgG anti-A/B were more severely affected, sustaining a fall in Hb of up to 2 g/d. These observations suggest that, after T-cell depleted bone marrow transplantation, immunocompetent B lymphocytes of donor origin are transferred, secrete antibody in the recipient, and may be responsible for self-limiting haemolytic episodes.

ABO Blood-Group System↗
PubMed1986

Extramedullary haemopoiesis in the small bowel.

A patient with myelofibrosis developed repeated gastrointestinal haemorrhage from the small intestine, which was found to be infiltrated with extramedullary haemopoiesis. Nineteen months later he presented with subacute intestinal obstruction; radiology and laparotomy documented progressive infiltration of the small bowel. Histological examination of the resected terminal ileum showed patchy mucosal ulceration, with underlying submucosal and serosal extramedullary haemopoiesis.

Gastrointestinal Hemorrhage↗
PubMed1983

Defective spectrin dimer-dimer association in a family with transfusion dependent homozygous hereditary elliptocytosis.

Red cell membrane proteins have been examined in a family in which three children have severe transfusion-dependent homozygous hereditary elliptocytosis. The membranes in all three show a considerable excess of spectrin dimers over tetramers in spectrin extracts. The red cell membranes of their parents with heterozygous hereditary elliptocytosis show a lesser but significant increase in spectrin dimers. Some of the family members also have an alpha-globin gene deletion and haemoglobin D trait. The present results are the first demonstration of a defect of spectrin dimer-dimer association in homozygous elliptocytosis and provide strong support for the concept that this defect is the primary cause of the red cell abnormality in at least some families of hereditary elliptocytosis.

Blood Transfusion↗