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T Kickler

Publications and source records attributed to T Kickler.

16 recordsLinked to original sources
PubMed2001

Single-donor platelets reduce the risk of septic platelet transfusion reactions.

BACKGROUND: Septic platelet transfusion reactions (SPTRs) are the most common, serious risk of transfusion. Because SPTRs result from donor skin flora or asymptomatic bacteremia, the use of single-donor platelets (SDPs) has been proposed to reduce the risk of SPTRs from the risks with pools of platelet concentrates (PCs). STUDY DESIGN AND METHODS: Beginning in 1986, all febrile transfusion reactions were evaluated by culture of the platelet bag. Confirmed SPTRs were identified by isolation of the same bacteria from the bag and the patient's blood or by positive Gram's stain of the bag that confirmed a positive platelet culture. In 1987, a program to minimize PC use in favor of SDP use was initiated as a means of reducing SPTRs. RESULTS: In 12 years, the use of SDPs increased from 51.7 percent to 99.4 percent of all platelet transfusions at one institution. SPTRs fell from three events in 1 year to the current rate of one event per year. The incidence of SPTRs decreased from 1 in 4,818 transfusions to 1 in 15,098 transfusions. The rate of SPTRs due to PCs was 5.39 times higher than that of SPTRs due to SDPs (95% CI, 1.89,12.9). CONCLUSION: The use of SDPs is a simple means of reducing SPTRs. Other measures such as sterilization will be required to eliminate all SPTRs.

Adult↗
PubMed2000

Platelet GP IIIa Pl(A) polymorphisms display different sensitivities to agonists.

BACKGROUND: Both inherited predisposition and platelet hyperreactivity have been associated with ischemic coronary events, but mechanisms that support genetic differences among platelets from different subjects are generally lacking. Associations between the platelet Pl(A2) polymorphism of GP IIIa and coronary syndromes raise the question as to whether this inherited variation may contribute to platelet hyperreactivity. METHODS AND RESULTS: In this study, we characterized functional parameters in platelets from healthy donors with the Pl(A) (HPA-1) polymorphism, a Leu (Pl(A1)) to Pro (Pl(A2)) substitution at position 33 of the GP IIIa subunit of the platelet GP IIb/IIIa receptor (integrin alpha(IIb)beta(3)). We studied 56 normal donors (20 Pl(A1,A1), 20 Pl(A1,A2), and 16 Pl(A2,A2)). Compared with Pl(A1,A1) platelets, Pl(A2)-positive platelets showed a gene dosage effect for significantly greater surface-expressed P-selectin, GP IIb/IIIa-bound fibrinogen, and activated GP IIb/IIIa in response to low-dose ADP. Surface expression of GP IIb/IIIa was similar in resting platelets of all 3 genotypes but was significantly greater on Pl(A2,A2) platelets after ADP stimulation (P=0.003 versus Pl(A1,A1); P=0.03 versus Pl(A1,A2)). Pl(A1,A2) platelets were more sensitive to inhibition of aggregation by pharmacologically relevant concentrations of aspirin and abciximab. CONCLUSIONS: Pl(A2)-positive platelets displayed a lower threshold for activation, and platelets heterozygous for Pl(A) alleles showed increased sensitivity to 2 antiplatelet drugs. These in vitro platelet studies may have relevance for in vivo thrombotic conditions.

Abciximab↗
PubMed2000

Tissue factor activity in patients with systemic lupus erythematosus: association with disease activity.

OBJECTIVE: Tissue factor (TF) is the major intrinsic initiator of clotting. TF expression on monocytes has been associated with high titers of anticardiolipin antibodies (aCL) in patients with antiphospholipid syndrome (APS) with thrombosis. We investigated the influence of clinical factors on TF activity in blood from patients with systemic lupus erythematosus (SLE) and examined the relationship between aCL and TF. METHODS: In this cross sectional study, consecutive patients with SLE from one rheumatology clinic gave blood samples for measurement of TF activity, aCL, and Russell viper venom time. We assessed disease activity by measuring sedimentation rate, anti-dsDNA, and complement components C3 and C4, and measured clinical indices. Associations were investigated with the Wilcoxon rank-sum test and linear regression. RESULTS: Sixty-nine patients contributed blood samples. The median age was 38 years, and 10 of the SLE patients had a history of thrombosis. Patients with active arthritis had TF activity 1.3 times that in patients without arthritis (p = 0.028). Users of nonsteroidal antiinflammatory drugs (NSAID) had TF activity significantly lower than nonusers (p = 0.010). Patients with previous thrombosis had TF activity significantly lower than patients without thrombosis (p < 0.001). Overall, aCL and TF activity were not associated when we adjusted for these clinical factors. CONCLUSION: Arthritis, previous thrombosis, and use of NSAID significantly modified TF activity in patients with SLE. Unlike previous reports, we found no association between aCL titer and TF activity, which may be due to our adjusting for other important clinical factors.

Adolescent↗
PubMed1997

Indicators of platelet turnover in thrombocytopenic infants.

Glycocalicin has been found to be a marker of increased platelet turnover, while interleukin-6 may be increased in response to thrombocytopenia. We used these markers to study the pathophysiology of thrombocytopenia in newborn infants. Cord blood platelet counts were obtained from 499 infants. Thrombocytopenic infants (< 100,000/mm3) and a control group had ELISA assays for interleukin-6 and glycocalicin performed. The mean levels of glycocalicin and interleukin-6 were elevated in cord blood of thrombocytopaenic infants. Infants with intrauterine growth restriction and thrombocytopaenia had no detectable glycocalicin in their plasma, despite elevated levels of interleukin-6. This probably reflects impaired thrombopoiesis in these infants.

Blood Platelets↗
PubMed1994

Rapid genotyping of the five major platelet alloantigens by reverse dot-blot hybridization.

Amino acid substitutions in platelet membrane glycoproteins result in alloantigens. Identifying these polymorphisms is important in alloimmune-mediated platelet disorders. Immunophenotyping platelet antigens can be limited by the unavailability of specific antisera. The goal of this work was to identify human platelet antigen genotypes in individuals using a technique that would circumvent the limitations of immunophenotyping and be clinically applicable. We have successfully applied the reverse dot-blot (RDB) technique to the genotyping of the five major human platelet alloantigen systems. Allele-specific oligonucleotides (ASOs) representing each allele of these alloantigens were covalently linked to a filter. Biotinylated oligonucleotides flanking the polymorphic sequences in genomic DNA were used to amplify genomic DNA by the polymerase chain reaction (PCR), and these products were hybridized to the filters containing the ASOs. Reactivity was detected with a chromogenic substrate. This nonradioactive methodology identifies all 15 possible genotypes in a well-defined control group of individuals and requires only two PCR reactions per patient sample. RDB analysis was used to successfully genotype women and family members with neonatal alloimmune thrombocytopenia and with posttransfusion purpura and to prenatally genotype the amniocytes from a fetus at risk for thrombocytopenia. The RDB methodology is specific, sensitive, and rapid and should enhance our ability to accurately diagnose disorders of alloimmune platelet destruction.

Alleles↗
PubMed1993

Sequential measurement of anti-platelet antibodies in a patient who developed EDTA-dependent pseudothrombocytopenia.

Ethylenediaminetetraacetic acid (EDTA)-dependent pseudothrombocytopenia is the occurrence of a falsely low platelet count caused by antibodies that agglutinate platelets in the presence of EDTA. If unrecognized, it may result in the erroneous diagnosis of thrombocytopenia and possible inappropriate therapy. It has been noted that this phenomenon tends to appear in hospitalized patients after an initially normal platelet count, but sequential measurements of anti-platelet antibody have not been reported. The case of a patient who developed EDTA-dependent pseudothrombocytopenia approximately 1 week after being hospitalized for severe trauma is described. Anti-platelet antibodies were not detected on admission by a radiolabeled antiglobulin technique but were shown to increase in titer concurrent with the appearance of EDTA-dependent pseudothrombocytopenia.

Autoantibodies↗
PubMed1992

The effect of prestorage white cell reduction on the function and viability of stored platelet concentrates.

The role of residual donor white cells (WBCs) in producing the storage lesion of platelets used for transfusion was studied. The effect of prestorage WBC reduction on in vitro and in vivo measurements of the quality of stored platelet concentrates (PCs) was examined by using a newly developed WBC-reduction filter capable of preparing PCs with a mean residual WBC concentration of less than 1 per microL. For in vitro studies, a triplet study design was used, in which WBC-reduced PCs were matched to standard PCs and to WBC-enriched PCs obtained from the same donor at the same phlebotomy. Twelve donors were studied. Prestorage WBC reduction resulted in a higher pH and pO2 and a lower pCO2 than in standard PCs. In accord with previous in vitro studies, a significant rise in plasma glycocalicin and lactate dehydrogenase was measured during storage, but the levels were not significantly different in WBC-reduced PCs and standard PCs. Platelet aggregation and ATP release in response to graded doses of thrombin was similar in WBC-reduced and standard PCs. In vivo recovery and survival studies were comparable in WBC-reduced and standard PCs. Although the residual donor WBC content of PCs has a significant impact on storage pH, pO2, and pCO2, prestorage WBC reduction does not affect platelet structure, function, or viability as assessed by in vitro or in vivo measurements.

Adenosine Triphosphate↗
PubMed1990

A randomized, placebo-controlled trial of intravenous gammaglobulin in alloimmunized thrombocytopenic patients.

In a placebo-controlled, randomized blinded study, we evaluated the efficacy of intravenous gammaglobulin (IV-IgG) in alloimmunized thrombocytopenic patients. IV-IgG was administered at a dose of 400 mg/kg for 5 days. An incompatible platelet transfusion from the same donor was used before and after treatment. Seven patients received IV-IgG and five patients received placebo. Although platelet recovery in 1 to 6 hours was satisfactory in five patients after IV-IgG treatment, 24-hour survival was not improved in most patients. None of the patients receiving the placebo achieved satisfactory 1-hour platelet-corrected count increments (CCIs). By t test, the posttreatment mean values 1 hour after transfusion CCIs in the IV-IgG group were significantly greater than in the control group (8,413 v 1,050, P less than .007). Using a regression model to adjust for any distributional assumptions of the study population, the parameter estimate for IV-IgG treatment was positive, indicating that IV-IgG treatment is associated with higher CCIs. Although IV-IgG may improve 1-hour platelet recovery, clinical benefit was not demonstrated since 24-hour survival was not improved. IV-IgG treatment before unmatched platelet transfusions should not be considered as a replacement for HLA-compatible platelets in alloimmunized patients.

HLA Antigens↗
PubMed1990

Alloimmunization to platelet-specific antigens on glycoproteins IIb-IIIa and Ib/IX in multiply transfused thrombocytopenic patients.

The rate of alloimmunization to platelet-specific antigens associated with platelet glycoproteins (GPs) IIb-IIIa and Ib/IX was studied in 293 multiply transfused thrombocytopenic patients. Antibodies to platelet-specific antigens were measured with a solid-phase assay using platelet GP IIb-IIIa or Ib/IX as the antigenic targets. Nine patients were found to have antibodies to platelet GP IIb-IIIa, and no patients had antibodies to platelet GP Ib/IX. In six of these nine patients, the specificity of the antibody was shown by using GP IIb-IIIa from donors with different platelet-specific antigen phenotypes. In the remaining three patients with antibodies to platelet GP IIb-IIIa, no specificity could be identified. These patients had autoimmune thrombocytopenia in association with lymphoma. The alloimmunization rate to platelet-specific antigens associated with GP IIb-IIIa was 2 percent, whereas the rate of alloimmunization to HLA antigens was 23 percent. Of the patients alloimmunized to HLA antigens, 9 percent also had antibodies to platelet-specific antigens. A poor response to HLA-identical platelet transfusions was observed only in those patients with positive assays in the solid-phase test. These results suggest that the incidence of antibodies to platelet-specific antigens carried on GP IIb-IIIa is low. Platelet-specific antibodies may be found more frequently in patients alloimmunized to HLA antigens than in those not so alloimmunized.

Antigens, Human Platelet↗
PubMed1988

Thrombocytopenia in the neonatal lupus syndrome.

Thrombocytopenia has been documented infrequently in association with congenital heart block or lupus dermatitis in the neonatal lupus erythematosus syndrome. We report the cases of two infants with transient neonatal thrombocytopenia born to mothers with connective-tissue disease. Both mother/infant pairs were Ro(SS-A) antibody positive. Although the finding of neonatal thrombocytopenia in the presence of maternal connective-tissue disease suggests an autoimmune thrombocytopenia, platelet antibody studies were negative in both mother/infant pairs. We have found the Ro (SS-A) antibody with increased frequency in idiopathic thrombocytopenic purpura and thrombocytopenia associated with Sjögren's syndrome, but the nature of the association is unknown. We suggest that thrombocytopenia in our patients is a manifestation of the neonatal lupus erythematosus syndrome. This syndrome should be included in the differential diagnosis of neonatal thrombocytopenia.

Adult↗
PubMed1984

Platelet-associated IgG in patients with lymphoma.

Levels of platelet-associated IgG (PA-IgG) were studied in 72 patients with Hodgkin's (HD) and non-Hodgkin's lymphoma (NHL). Thirty-nine percent of patients with HD and 20% of patients with NHL had elevated PA-IgG levels. There was a positive correlation between disease activity and the presence of PA-IgG in HD and NHL. In patients with HD, PA-IgG strongly correlated with extent of disease and may serve as a marker of disease activity. PA-IgG may have facilitated platelet destruction in 5 of 11 thrombocytopenic patients with HD and increased PA-IgG and in 2 patients with HD and increased PA-IgG who developed severe thrombocytopenia when treated with chemotherapy.

Adult↗
PubMed1977

False-negative test for fibrinogen--fibrin degradation products.

The tanned red cell hemagglutination inhibition immunoassay has proved to be a sensitive test for the measurement of fibrinogen-fibrin degradation products (FDP-fdp). The case of a patient who initially had a negative test for FDP-fdp due to the presence of an anti-D antibody and the use of O-positive tanned erythrocytes in the hemagglutination inhibition immunoassay is presented. When a control consisting of buffer substituted for the anti-fibrinogen antiserum, tanned erythrocytes and patient's serum is used, the agglutination due to incompatibility will be recognized. The irregular antibody can then be removed by absorption, and the titer for FDP-fdp can be accurately measured.

Adult↗
PubMedDate not supplied

A prospective study of the effect of dextran administration on compatibility testing.

The effects of dextran therapy on pretransfusion compatibility testing were evaluated in 24 patients with a variety of vascular disorders. Specimens were drawn before, during, and after the administration of low-molecular-weight dextran (average molecular weight, 40 kd). Forty-three specimens were studied extensively with several immunohematologic techniques. Dextran levels were measured to determine whether the concentration influenced the results of serologic tests. In no instance could we demonstrate any interference by dextran with pretransfusion tests, even at high serum levels of dextran.

Blood Banks↗