14 results on '"Dana V. Devine"'
Search Results
2. Rethinking platelet transfusion practices
- Author
-
Dana V. Devine
- Subjects
Male ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,BLOOD COMMENTARY ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunology ,Platelet Transfusion ,Biochemistry ,ABO Blood-Group System ,Humans ,Medicine ,Hospital Mortality ,Prospective Studies ,Aged ,Cerebral Hemorrhage ,Hematoma ,Platelet Count ,business.industry ,Cell Biology ,Hematology ,Middle Aged ,Virology ,Treatment Outcome ,Platelet transfusion ,Blood Group Incompatibility ,Brain Damage, Chronic ,Female ,business ,Platelet Aggregation Inhibitors - Abstract
Acute platelet transfusion after intracerebral hemorrhage (ICH) given in efforts to reverse antiplatelet medication effects and prevent ongoing bleeding does not appear to improve outcome and may be associated with harm. Although the underlying mechanisms are unclear, the influence of ABO-incompatible platelet transfusions on ICH outcomes has not been investigated. We hypothesized that patients with ICH who receive ABO-incompatible platelet transfusions would have worse platelet recovery (using absolute count increment [ACI]) and neurological outcomes (mortality and poor modified Rankin Scale [mRS 4-6]) than those receiving ABO-compatible transfusions. In a single-center cohort of consecutively admitted patients with ICH, we identified 125 patients receiving acute platelet transfusions, of whom 47 (38%) received an ABO-incompatible transfusion. Using quantile regression, we identified an association of ABO-incompatible platelet transfusion with lower platelet recovery (ACI, 2 × 103cells per μL vs 15 × 103cells per μL; adjusted coefficient β, -19; 95% confidence interval [CI], -35.55 to -4.44; P = .01). ABO-incompatible platelet transfusion was also associated with increased odds of mortality (adjusted odds ratio [OR], 2.59; 95% CI, 1.00-6.73; P = .05) and poor mRS (adjusted OR, 3.61; 95% CI, 0.97-13.42; P = .06); however, these estimates were imprecise. Together, these findings suggest the importance of ABO compatibility for platelet transfusions for ICH, but further investigation into the mechanism(s) underlying these observations is required.
- Published
- 2021
3. Presence in peripheral blood of healthy individuals of autoreactive T cells to a membrane antigen present on bone marrow-derived cells
- Author
-
Francine Décary, Rafick-Pierre Sekaly, Amanda J. Bradley, Dana V. Devine, Mario C. Filion, Pierre Chartrand, and Chantal Proulx
- Subjects
CD40 ,biology ,Immunology ,CD1 ,Cell Biology ,Hematology ,Biochemistry ,Clonal deletion ,Interleukin 21 ,biology.protein ,Cytotoxic T cell ,IL-2 receptor ,Antigen-presenting cell ,Interleukin 3 - Abstract
Intrathymic clonal deletion is thought to be the major mechanism responsible for tolerance to nonsequestered antigens such as the ones expressed by bone marrow-derived cells. In the case of sequestered antigens that potentially do not come in contact with T cells in the thymus, it is thought that autoreactive T cells are present in periphery but are tightly regulated to prevent autoimmune disease. Indeed, autoreactive T cells to sequestered antigens can be isolated in healthy individuals. However, the presence of autoreactive T cells to nonsequestered circulating antigens had not been observed. In this report, we present evidence for the presence, in the periphery of all healthy individuals tested (n = 25), of autoreactive T cells to GpIIb- IIIa, a membrane antigen present on bone marrow-derived cells that is expressed on circulating platelets and on the cell surface of the epithelial cells of the thymic stroma early in intrauterine life. Using an in vitro T-cell proliferation assay, we have demonstrated that activation of these specific GpIIb-IIIa autoreactive alpha beta TCR+ CD4+ CD8- T cells requires internalization and processing of the GpIIb- IIIa by antigen-presenting cells and its presentation by HLA-DR class II molecules in the presence of exogenous interleukin 2 (IL-2). This indicates that some autoreactive T cells directed against membrane antigens present on bone marrow-derived cells and also expressed in the thymus are not necessarily eliminated by intrathymic deletion.
- Published
- 1996
4. International Validation of a Dithiothreitol (DTT)-Based Method to Resolve the Daratumumab Interference with Blood Compatibility Testing
- Author
-
Claudia I Chapuy, Maria D Aguad, Rachel T Nicholson, James P AuBuchon, Claudia S Cohn, Meghan Delaney, Joan Cid, Walter Dzik, Mark K. Fung, Andreas Greinacher, Ai Leen Ang, Dana V. Devine, Nancy M Dunbar, Henk Garritsen, Lawrence T Goodnough, Ross Herron, Tor A. Hervig, C. Michael Knudson, Jose M Kutner, Frank Nizzi, Suchitra Pandey, Benjamin Rioux-Masse, Kathleen Selleng, Joseph Sweeney, Minoko Takanashi, Aaron A.R. Tobian, Lorna Wall, Silvano Wendel, David A Westerman, Meredith Unger, Parul Doshi, Michael F. Murphy, Larry J. Dumont, Richard M. Kaufman, and The BEST Collaborative
- Subjects
business.industry ,Immunology ,Daratumumab ,Cell Biology ,Hematology ,Dara ,Biochemistry ,Molecular biology ,Dithiothreitol ,Rho(D) immune globulin ,chemistry.chemical_compound ,Agglutination (biology) ,chemistry ,Monoclonal ,medicine ,Screening method ,Blood compatibility ,business ,medicine.drug - Abstract
Introduction Daratumumab (DARA), an IgG1k human monoclonal antibody (Ab) against CD38, is a promising novel therapy for multiple myeloma. However, direct binding of DARA to endogenous CD38 on reagent red blood cells (RBCs) interferes with routine blood bank serologic testing. We recently showed that treating reagent RBCs with DTT eliminates the DARA interference by denaturing cell surface CD38, allowing the safe transfusion of patients on DARA.1 This multicenter international study was aimed at validating the DTT method for use by blood banks worldwide. Methods Participating blood banks received two plasma sample unknowns. Sample 1 was spiked with DARA alone (5 mcg/mL). Sample 2 was spiked with DARA plus a clinically significant RBC Ab (anti-D (Rh immune globulin) or monoclonal anti-Fya or anti-s). Sites were instructed to first perform an Ab screen using their usual method (tube, gel, or solid phase), then to repeat the Ab screen using DTT-treated RBCs (gel or tube). If the Ab screen remained positive with DTT-treated RBCs (Sample 2), sites were to identify the unknown Ab using a DTT-treated RBC panel (gel or tube.) The primary outcome measure was the proportion of sites able to successfully identify the unknown Ab in the presence of DARA. Qualitative data were collected by online survey. Results Paired plasma sample unknowns were shipped to 25 study sites in North America, South America, Europe, Asia, and Australia/New Zealand. Data were received from 23 sites to date (Table). For the initial Ab screen, 10 sites used tube testing, 7 sites used gel, and 6 sites used solid phase. All sites observed DARA interference with the Ab screen (false positive agglutination reactions). All sites reported no DARA interference using DTT-treated RBCs. For Ab identification (Sample 2), 13 sites used tube testing and 10 sites used gel. 23/23 sites (100%) were able to correctly identify the unknown Ab using the DTT method. The Abs identified were: anti-Fya (9/9), anti-s (8/8), and anti-D (6/6). Feedback on the DTT method was mainly positive, with 86% of sites that responded to the survey indicating that they planned to use the DTT method to manage clinical samples from DARA-treated patients. Conclusion DARA consistently interferes with all three Ab screening methods currently used by blood banks (tube, gel, and solid phase.) Using DTT-treated RBCs, 23/23 (100%) of blood bank laboratories from around the world were able to identify a clinically significant Ab initially masked by the presence of DARA. The DTT method is robust, reproducible, and can be implemented by blood banks globally to help provide safe blood products to patients on DARA. As DTT denatures Kell antigens, K- RBC units should be provided when using the DTT method. 1. Chapuy CI, Nicholson RT, Aguad MD, et al. Resolving the daratumumab interference with blood compatibility testing. Transfusion. 2015;55(6pt2):1545-1554. Disclosures Unger: Janssen: Employment. Doshi:Janssen: Employment. Kaufman:Janssen: Consultancy, Research Funding.
- Published
- 2015
5. Factor XIIIa binding to activated platelets is mediated through activation of glycoprotein IIb-IIIa
- Author
-
Alison D. Cox and Dana V. Devine
- Subjects
biology ,Chemistry ,Immunology ,Fibrinogen binding ,Cell Biology ,Hematology ,Biochemistry ,Molecular biology ,Fibrin ,Thrombin ,Platelet degranulation ,biology.protein ,medicine ,Platelet ,Factor XIIIa ,Platelet activation ,Glycoprotein IIb/IIIa ,medicine.drug - Abstract
Stabilization of a clot is dependent on fibrin cross-linking mediated by the transglutaminase, factor XIIIa (FXIIIa). In addition to fibrin stabilization, FXIIIa acts on a number of platelet-reactive proteins, including fibronectin and vitronectin, as well as the platelet proteins, glycoprotein (GP) IIb-IIIa, myosin, and actin. However, conditions inducing the platelet-activation dependent binding of FXIIIa have not been characterized nor have the sites mediating FXIIIa binding been identified. The generation of FXIIIa and consequent detection of FXIIIa on the platelet surface were compared with other thrombin- induced activation events; the rate at which FXIIIa bound to activated platelets was much slower than platelet degranulation or fibrin(ogen) binding. Whereas platelets could be rapidly induced to express a functional receptor for FXIIIa, the rate of FXIIIa binding to platelets is limited by the rate of conversion of FXIII to FXIIIa. Immunoprecipitation of radiolabeled platelets using polyclonal anti- FXIII A-chain antibody identified two proteins corresponding to GPIIb and GPIIIa. Preincubation of intact platelets with 7E3, a monoclonal antibody that blocks the fibrinogen binding site, or GRGDSP peptide inhibited FXIIIa binding by about 95% when measured by flow cytometry; FXIIIa binding to purified GPIIb-IIIa was also inhibited by 7E3. The binding of FXIIIa to purified GPIIb-IIIa was enhanced by the addition of fibrinogen, but not by that of fibronectin or thrombospondin, suggesting that FXIIIa also binds to fibrinogen associated with the complex. These observations suggest that activated platelets bearing FXIIIa may enhance stabilization of platelet-rich thrombi through surface-localized cross-linking events.
- Published
- 1994
6. From Venus and Mars: Gender Specific Analysis of Blood Platelets
- Author
-
Geraldine M. Walsh, Danielle Coupland, Peter Schubert, Dana V. Devine, and Cindy Chen
- Subjects
medicine.diagnostic_test ,Immunology ,Cell Biology ,Hematology ,Buffy coat ,Biology ,Biochemistry ,Andrology ,Gene expression profiling ,Western blot ,Proteome ,medicine ,Platelet ,Platelet activation ,Signal transduction ,Platelet factor 4 - Abstract
Cardiovascular disease epidemiological studies reveal compelling evidence that this disease is strongly influenced by gender. Other laboratory based studies have suggested that gender disparities can also be detected in platelet physiological measurements. These observations have led us to ask whether gender differences may play a role in platelet quality and integrity during storage. We have applied proteomic approaches to gain an understanding of the molecular mechanisms of gender-specific platelet signal transduction and its potential significance to transfusion medicine. Buffy coat platelet concentrates (N=4) pooled from four male or female donors, respectively, were analyzed by 2D gel electrophoresis and revealed 15 reproducible protein differences between their individual platelet proteomes. Validation by western blot analysis confirmed the proteomic data demonstrating differences in the expression profiling of proteins including 14-3-3, myosin, platelet factor 4 and SH3-domain binding protein glutamic acid-rich like protein as well as in posttranslational modification of proteins including pleckstrin and 14-3-3. These findings spurred a more detailed gender-specific analysis of single donors. In vitro measures (N=28 of each gender) for platelet function revealed that female platelets showed an averaged 15% higher level of activation as well as GPIIb/IIIa activation monitored by CD62P or Pac-1 binding, respectively. This point towards differences in signal transduction and western blot analyses of the platelet proteome of these individuals showed an averaged two to three-fold higher expression of signaling proteins including 14-3-3, Rap1, RhoA and RhoGDI. Furthermore, female platelets contain a two-fold higher level of activated Rap1 supporting the gender-influenced signaling hypothesis. To test whether these gender-specific results might have an impact on transfusion medicine, biochemical analyses of buffy coat platelet concentrates during storage were carried out. Preliminary data indicate that female platelets maintain the higher level of platelet activation during a 7-day storage period paralleled with elevated metabolic activity as monitored by glucose and lactate levels, respectively. These data can be used to assess other potential molecular mechanisms underlying the differences in the gender-specific signaling platelet proteome. Thus far, the clinical significance of these findings in transfusion medicine is unknown.
- Published
- 2008
7. A Novel Marker for Blood Platelet Storage Lesion: Newly Synthesized Rap1 in Integrin Signaling
- Author
-
Geraldine M. Walsh, Katherine Serrano, Edwin D.W. Moore, Jonathan N. Thon, Juergen Kast, Dana V. Devine, and Peter Schubert
- Subjects
P-selectin ,Immunology ,Integrin ,Cell Biology ,Hematology ,Biology ,Biochemistry ,Platelet Glycoprotein GPIIb-IIIa Complex ,Andrology ,Thrombin ,Platelet transfusion ,medicine ,biology.protein ,Platelet ,Platelet activation ,CD61 ,medicine.drug - Abstract
Platelet transfusion is a standard live-saving medical procedure for patients with platelet-deficient diseases like leukemia. Platelets have a limited shelf-life of 5–7 days for transfusion purposes. This is in part due to a storage-related deterioration typified by altered morphology features and platelet metabolism as well as increased platelet activation. While the manifestations of the platelet storage lesion (PSL) are well known, the precise biochemical pathways involved in the initiation or exacerbation of this process have yet to be identified. Recently, we analyzed protein changes in the platelet proteome at day 1 and day 7 of storage by using a comprehensive proteomic approach. Out of 503 proteins, twelve were identified as significantly and consistently changing in relative concentration across all proteomic probes, including glycoprotein (GP) IIb/IIIa, Rap1 and talin, which showed an increase in their concentration paralleled with an increase in surface expression of GPIIb/IIIa. Synthesis of Rap1 in stored platelets could be demonstrated after incubation with the translational inhibitor rapamycin at a final concentration of 10 nM for twelve hours and subsequent activation with thrombin. Flow cytometry revealed that storage lead to a moderate level of platelet activation (10.5 ± 1.4% at day1 and 28.8 ± 1.3% at day 7 of storage) compared to ADP-treated controls (73.7 ± 1.2%) monitored by CD62P surface expression, in a rapamycin-independent manner. Microscopic analyses revealed similar re-localization patterns for GPIIIa, Rap1 and talin comparing changes during platelet storage and agonist induced activation. A significant correlation (p=0.007) between Rap1 activation and CD62P surface expression was seen. This observation is in strong agreement with a model for platelet GP IIb/IIIa activation [Han et al., Current Biology, 16, 1796–1806, 2007] also suggesting a calcium-dependent initiation of signal transduction. To analyze this hypothesis in more detail, treatment of platelets sampled at days 1, 4 and 7 of storage with 1 mM EDTA for 2 hours resulted in decreased Rap1 activation, in reduced surface expression of CD41 (GPIIb) and CD61 (GPIIIa) as well as in a lower level of platelet activation compared to untreated controls, respectively. This study unravels one aspect of the PSL, showing involvement of integrin signaling and identifying Rap1 as a novel marker for PSL. Therefore, this pathway offers potential targets for intervention which might lead to a reduction in platelet activation during storage, and may enable platelets to be stored for longer periods of time. From a transfusion point of view, however, extending the shelf-life of platelet units will ultimately need to be balanced with maintaining the quality of transfused platelets, their functionality, and efficacy in the patient.
- Published
- 2007
8. Comparative Proteome Analysis To Study Novel Markers of the Blood Platelet Lesion
- Author
-
Katherine Serrano, Dana V. Devine, Peter Schubert, Marie Duguay, Juergen Kast, and Jonathan N. Thon
- Subjects
Gel electrophoresis ,Cell signaling ,Immunology ,Cell Biology ,Hematology ,Biology ,Tandem mass spectrometry ,Biochemistry ,Platelet transfusion ,Proteome ,Platelet ,Platelet activation ,Quantitative analysis (chemistry) - Abstract
Platelet transfusion is a very common live-saving medical procedure for patients with platelet-deficient diseases like leukemia. In contrast to other blood components, the availability of platelets is restricted since they have a limited shelf-life of 5 days for transfusion purposes. This is due to storage-related deterioration in product quality resulting in the clearance from circulation. To overcome this problem, it is important to understand the molecular mechanisms leading to blood platelet lesion during storage. We were using two different proteomic approaches combined with functional biochemistry to investigate time-dependent changes in the blood platelet proteome. One type of analysis consisted of the separation of the platelet proteome at two different time points of storage, day 1 and day 8, using 2-dimensional (2D) gel electrophoresis for qualitative and DIGE technology for quantitative analysis. The identification of proteins changing in spot intensity was carried out by liquid chromatography and tandem mass spectrometry. The second method was based on stable isotope labeling with ITRAQ/ICAT reagents in combination with protease treatment, equivalent mixing, separation of the resulting peptides and quantitative analysis by mass spectrometry. Taken together, for the 2D/DIGE approach we analyzed 977 spots corresponding to 103 different proteins and for the ITRAQ approach 1428 peptides corresponding to 355 proteins, resulting in 37 proteins significantly changing both quantitatively due to protein synthesis or degradation and qualitatively due to post-translational modification and enzymatic activity. The high degree of correlation between the two approaches validates the experimental set-up and confirmed the requirement for complementary tools to enhance proteome coverage. Among others, increased amounts of integrins and other proteins known to form receptor signaling complexes with these integrins as well as proteins observed in platelet activation were detected. This proves, for the first time, that there is an apparent link between blood platelet storage lesion and cell signaling.
- Published
- 2006
9. The population of paroxysmal nocturnal hemoglobinuria neutrophils deficient in decay-accelerating factor is also deficient in alkaline phosphatase
- Author
-
Graeme Browne, Susan F. Burroughs, Manuel E. Kaplan, and Dana V. Devine
- Subjects
medicine.medical_specialty ,education.field_of_study ,fungi ,Immunology ,Population ,Phosphatase ,Clone (cell biology) ,chemical and pharmacologic phenomena ,Cell Biology ,Hematology ,Biology ,medicine.disease ,Biochemistry ,Molecular biology ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Internal medicine ,Paroxysmal nocturnal hemoglobinuria ,medicine ,Alkaline phosphatase ,Platelet ,Phosphatidylinositol ,education ,Decay-accelerating factor - Abstract
In patients with paroxysmal nocturnal hemoglobinuria (PNH) the RBCs, neutrophils (PMNs), monocytes, and platelets derived from the abnormal clone are deficient in the complement-regulatory protein decay- accelerating factor (DAF). RBC acetylcholinesterase (AChE) and leukocyte alkaline phosphatase (LAP) activities are also characteristically low. DAF, AChE, and LAP are known to be anchored within cell membranes to glycophospholipid-containing phosphatidylinositol (PI).Because PNH progenitors contain DAF that appears to be lost with maturation, it has been proposed that this disorder results from abnormal tethering of these and possibly other proteins to membrane PI. We were puzzled, therefore, that our two PNH patients consistently had normal LAP levels. Consequently, we studied their isolated PMNs to compare DAF and LAP activities in individual cells.PMNs were separated by flow cytometry into DAF-positive and - negative populations by using rabbit anti-DAF antiserum and fluorescein- conjugated goat antirabbit IgG. In both patients the majority of PMNs were DAF deficient, and these cells contained very little alkaline phosphatase activity. In contrast, the smaller, DAF-positive cell populations were phosphatase replete. This is the first demonstration that abnormalities in DAF and LAP activity occur in the same PNH PMN population and strengthens the hypothesis that defective anchoring of proteins to membrane glycophospholipid underlies the pathophysiology of this disorder.
- Published
- 1988
10. Identification of platelet proteins that bind alloantibodies and autoantibodies
- Author
-
Dana V. Devine and Wendell F. Rosse
- Subjects
chemistry.chemical_classification ,biology ,medicine.diagnostic_test ,Chemistry ,medicine.drug_class ,Immunology ,Autoantibody ,Cell Biology ,Hematology ,Monoclonal antibody ,Biochemistry ,Molecular biology ,Thrombasthenia ,Membrane protein ,Western blot ,biology.protein ,medicine ,Platelet ,Antibody ,Glycoprotein - Abstract
We have used the techniques of radioimmunoprecipitation (RIP) and Western blot to identify the membrane proteins that bind certain alloantibodies. Anti-PlA1 sera precipitated two bands, corresponding to platelet glycoproteins IIb and III, whether or not calcium was present during the procedure. By Western blot, this antibody bound only glycoprotein III. Anti-PlA1 serum does not precipitate proteins from the platelets of a patient with Glanzmann's thrombasthenia. Two monoclonal antibodies reacting with lymphocyte HLA antigens, as well as sera from highly allosensitized patients, precipitated bands of 38,500 and 13,500 daltons. These bands correspond to the molecular weights of the two subunits of the HLA antigen, as it has been described for other cell types. The patients' sera also precipitated a protein of 72,000 daltons from some platelets. The sera of two patients with quinidine- induced thrombocytopenia precipitated a 138,000-dalton band (glycoprotein Ib-alpha) in the presence of quinidine. The purified IgG antibody from one patient did not require other plasma factors to bind to platelets in the presence of quinidine, while purified antibody from a second patient required plasma factors other than, or in addition to von Willebrand factor. Although several sera from patients with idiopathic thrombocytopenic purpura (ITP) were tested, only one precipitated membrane proteins by the RIP method; this serum identified binding proteins corresponding to glycoproteins IIb and III.
- Published
- 1984
11. Pseudo-Bernard-Soulier syndrome: thrombocytopenia caused by autoantibody to platelet glycoprotein Ib
- Author
-
M S Currie, Wendell F. Rosse, Charles S. Greenberg, and Dana V. Devine
- Subjects
medicine.medical_specialty ,biology ,business.industry ,Immunology ,Autoantibody ,Cell Biology ,Hematology ,Platelet membrane glycoprotein ,medicine.disease ,Biochemistry ,Immunoglobulin G ,Bernard–Soulier syndrome ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Von Willebrand factor ,hemic and lymphatic diseases ,Internal medicine ,biology.protein ,Medicine ,Platelet ,Refractory Thrombocytopenia ,business ,Ristocetin - Abstract
The Bernard-Soulier syndrome is an inherited bleeding disorder that is due to a deficiency in platelet glycoprotein Ib. Bernard-Soulier platelets fail to agglutinate in response to ristocetin despite normal levels of factor VIII:von Willebrand factor. We report a patient who developed severe refractory thrombocytopenia postsurgically while receiving procainamide therapy. Thrombocytopenia was immune mediated since the patient's platelets bore high levels of antiplatelet antibody. Radioimmunoprecipitation studies demonstrated that the autoantibodies had specificity for platelet glycoproteins Ib and V as well as platelet HLA. The patient's plasma as well as purified immunoglobulin G completely inhibited the ristocetin-induced aggregation of normal platelets but did not inhibit adenosine diphosphate-induced aggregation. The laboratory studies revealed that this patient suffered from antibody-mediated thrombocytopenia with unusual characteristics that we have called pseudo-Bernard-Soulier syndrome.
- Published
- 1987
12. Structural and functional differences between decay-accelerating factor and red cell acetylcholinesterase [published erratum appears in Blood 1987 Jul;70(1):339]
- Author
-
J Sugarman, Dana V. Devine, and Wendell F. Rosse
- Subjects
chemistry.chemical_classification ,biology ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Acetylcholinesterase ,C3-convertase ,Complement system ,chemistry.chemical_compound ,Classical complement pathway ,chemistry ,hemic and lymphatic diseases ,biology.protein ,Paroxysmal nocturnal hemoglobinuria ,medicine ,Antibody ,Glycoprotein ,Decay-accelerating factor - Abstract
The abnormal erythrocytes in paroxysmal nocturnal hemoglobinuria, both PNH II (the moderately abnormal cells) and PNH III (the markedly abnormal cells), lack both acetylcholinesterase (AChE) activity and decay-accelerating factor (DAF) activity. Both of these activities are found on glycoprotein molecules with a molecular weight of about 70 Kd. To demonstrate that these two activities are in fact on different proteins, we have shown that binding to normal red cells of antibody to DAF does not inhibit the subsequent binding of monoclonal antibody to AChE nor AChE activity. Inhibition of DAF activity by polyclonal antibody increases the susceptibility of normal erythrocytes to lysis by complement but inhibition of AChE activity by antibody does not. The rate of decay of the C3 convertase complex of the classical pathway of complement activation was inhibited by DAF added in the fluid phase but not by AChE. When DAF was exhaustively immunoprecipitated from a solution of the erythrocyte membrane proteins, AChE remained and vice versa. These studies indicate that acetylcholinesterase and decay- accelerating factor are two different proteins, both of which are lacking on PNH II and PNH III erythrocytes.
- Published
- 1986
13. Fragment D-dimer levels: an objective marker of vaso-occlusive crisis and other complications of sickle cell disease
- Author
-
Wendell F. Rosse, Charles S. Greenberg, Thomas R. Kinney, Patricia F. Thomas, and Dana V. Devine
- Subjects
medicine.medical_specialty ,Aseptic necrosis ,biology ,business.industry ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Asymptomatic ,Gastroenterology ,Fibrin ,Surgery ,Latex fixation test ,Internal medicine ,D-dimer ,medicine ,biology.protein ,Coagulation testing ,medicine.symptom ,Complication ,business ,Vaso-occlusive crisis - Abstract
Although abnormalities in coagulation tests have been reported during vaso-occlusive crises in patients with sickle cell disease, objective, readily performed laboratory tests that document the occurrence of this complication have not been available. We examined the relationship between fibrin D-dimer levels and the occurrence of complications in patients with sickle cell disease, using a commercially available latex bead agglutination assay. The patients were either asymptomatic, hospitalized for vaso-occlusive crisis, or had other complications of sickle cell disease including leg ulcers, chronic cholecystitis, aseptic necrosis, joint pain and infection. Fifty-seven percent of 187 samples on 96 patients had elevated levels of fibrin D-dimer. Ninety percent of 75 samples from asymptomatic patients were negative for fibrin D-dimer (less than 1 microgram/ml) but 97% of 29 samples from patients with vaso-occlusive crisis and 85% of 83 samples from patients with other complications of sickle cell disease were positive. In serial studies, worsening or amelioration in clinical complications were reflected in increasing or decreasing levels of fibrin D-dimer, respectively. The molecular species of fibrin identified by the latex agglutination test was shown to be fragment D-dimer by successive immunoprecipitation and protein blot analysis. We conclude that the complications of sickle cell disease, including vaso-occlusive crisis, result in the production of fibrin D-dimer, and its detection may be used as a marker for the presence of the complication.
- Published
- 1986
14. Pseudo-Bernard-Soulier Syndrome: Thrombocytopenia Caused by Autoantibody to Platelet Glycoprotein lb
- Author
-
Dana V., Devine, Mark S., Currie, Wendell F., Rosse, and Charles S., Greenberg
- Abstract
The Bernard-Soulier syndrome is an inherited bleeding disorder that is due to a deficiency in platelet glycoprotein lb. Bernard-Soulier platelets fail to agglutinate in response to ristocetin despite normal levels of factor Vll:von Wille-brand factor. We report a patient who developed severe refractory thrombocytopenia postsurgically while receiving procainamide therapy. Thrombocytopenia was immune mediated since the patient's platelets bore high levels of antiplatelet antibody. Radioimmunoprecipitation studies demonstrated that the autoantibodies had specificity for platelet glycoproteins lb and V as well as platelet HLA. The patient's plasma as well as purified immunoglobulin G completely inhibited the ristocetin-induced aggregation of normal platelets but did not inhibit adenosine diphosphate-induced aggregation. The laboratory studies revealed that this patient suffered from antibody-mediated thrombocytopenia with unusual characteristics that we have called pseudo-Bernard-Soulier syndrome.
- Published
- 1987
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.