Pathogenic Effects of Anti-Glycoprotein Ib Antibodies on Megakaryocytes and Platelets

2002 ◽  
Vol 88 (12) ◽  
pp. 1039-1046 ◽  
Author(s):  
Gulie Alimardani ◽  
Josette Guichard ◽  
Serge Fichelson ◽  
Elisabeth Cramer
Keyword(s):  
Electron Microscopy ◽  
Platelet Adhesion ◽  
Potential Mechanism ◽  
Antithrombotic Drugs ◽  
Pathological Effect ◽  
Thrombocytopenic Purpura ◽  
Platelet Recovery ◽  
Platelet Release ◽  
Shed Light ◽  
Pathogenic Effects

SummaryAntibodies directed against the glycoprotein (GP) Ib have been identified as the potential cause of various platelet disorders: Immune thrombocytopenic purpura (ITP) may be caused by such autoantibodies; Anti-thrombotic drugs targeting GPIb also induce thrombocytopenia. In order to elucidate the potential mechanism(s) of the anti-GPIb effects, we have examined by electron microscopy (EM) the effect of several antibodies directed against GPIb and GPIIb-IIIa on human culture megakaryocytes (MK). Virtually all antibodies to GPIb enhanced the interaction of newly formed platelets with MK when compared to other antibodies. These effects were retrieved when antibodies were tested on platelets. We conclude that antibodies to GPIb can potentially inhibit platelet release by MK, and can also induce homotypic platelet adhesion. These results may have implications in the pathophysiology of thrombocytopenia and platelet recovery in ITP, and shed light on the pathological effect of anti-GPIb antibodies used as antithrombotic drugs.

Acquired Disorder of Platelet Function Associated with Autoantibodies against Membrane Glycoprotein IIb-IIIa Complex - 1. Glycoprotein Analysis

1991 ◽  
Vol 65 (05) ◽  
pp. 491-496 ◽  
Author(s):  
M Meyer ◽  
C M Kirchmaier ◽  
A Schirmer ◽  
P Spangenberg ◽  
Ch Ströhl ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Platelet Adhesion ◽  
Bleeding Time ◽  
Membrane Glycoprotein ◽  
Membrane Glycoproteins ◽  
Abnormal Behaviour ◽  
Thrombocytopenic Purpura ◽  
Immunoelectrophoretic Analysis ◽  
Prolonged Bleeding Time

SummaryA patient with idiopathic thrombocytopenic purpura developed after splenectomy a thrombasthenia-like severe haemor-rhagic diathesis characterized by a normal or subnormal platelet count, prolonged bleeding time, strongly reduced platelet adhesion to glass and defective platelet aggregation in response to ADP and collagen. In contrast to hereditary thrombasthenia membrane glycoproteins (GP) lib and Ilia were normally present in the patient’s platelets. Immunoelectrophoretic analysis revealed an abnormal behaviour of the patient’s GP IIb-IIIa complex. Autoantibodies against GP IIb-IIIa were detected in Triton-extracted washed platelets. Incubation of normal platelets with plasma from the patient resulted in a similar immunoelectrophoretic abnormality of the GP IIb-IIIa complex indicating that bound autoantibodies (IgG) are responsible for the abnormal immunoelectrophoretic behaviour of the patient’s GP IIb-IIIa complex. Platelet fibrinogen was severely reduced similar to classical thrombasthenia suggesting that the GP IIb-IIIa complex is involved in platelet fibrinogen storage.

Inhibition of Platelet Adhesion to Collagen as a New Target for Antithrombotic Drugs

2003 ◽  
Vol 3 (2) ◽  
pp. 125-140 ◽  
Author(s):  
K. Vanhoorelbeke ◽  
H. Ulrichts ◽  
A. Schoolmeester ◽  
H. Deckmyn
Keyword(s):  
Platelet Adhesion ◽  
Antithrombotic Drugs

scholarly journals Breathing-driven prefrontal oscillations regulate maintenance of conditioned-fear evoked freezing independently of initiation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sophie Bagur ◽  
Julie M. Lefort ◽  
Marie M. Lacroix ◽  
Gaëtan de Lavilléon ◽  
Cyril Herry ◽  
...  
Keyword(s):  
Functional Role ◽  
Population Analysis ◽  
Conditioned Fear ◽  
Stable State ◽  
Network Activity ◽  
Power Dynamics ◽  
Potential Mechanism ◽  
Physiological Basis ◽  
Dorsomedial Prefrontal Cortex ◽  
Shed Light

AbstractBrain–body interactions are thought to be essential in emotions but their physiological basis remains poorly understood. In mice, regular 4 Hz breathing appears during freezing after cue-fear conditioning. Here we show that the olfactory bulb (OB) transmits this rhythm to the dorsomedial prefrontal cortex (dmPFC) where it organizes neural activity. Reduction of the respiratory-related 4 Hz oscillation, via bulbectomy or optogenetic perturbation of the OB, reduces freezing. Behavioural modelling shows that this is due to a specific reduction in freezing maintenance without impacting its initiation, thus dissociating these two phenomena. dmPFC LFP and firing patterns support the region’s specific function in freezing maintenance. In particular, population analysis reveals that network activity tracks 4 Hz power dynamics during freezing and reaches a stable state at 4 Hz peak that lasts until freezing termination. These results provide a potential mechanism and a functional role for bodily feedback in emotions and therefore shed light on the historical James–Cannon debate.

Helicobacter pylori infection and chronic immune thrombocytopenic purpura: long-term results of bacterium eradication and association with bacterium virulence profiles

Blood ◽  
2007 ◽  
Vol 110 (12) ◽  
pp. 3833-3841 ◽  
Author(s):  
Giovanni Emilia ◽  
Mario Luppi ◽  
Patrizia Zucchini ◽  
Monica Morselli ◽  
Leonardo Potenza ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Chronic Gastritis ◽  
Immune Thrombocytopenic Purpura ◽  
Long Term Results ◽  
Platelet Response ◽  
Related Factors ◽  
Thrombocytopenic Purpura ◽  
Platelet Recovery ◽  
Chronic Immune Thrombocytopenic Purpura ◽  
H Pylori

AbstractEradication of Helicobacter pylori may lead to improvement of chronic immune thrombocytopenic purpura (ITP), although its efficacy over time is uncertain. We report the results of H pylori screening and eradication in 75 consecutive adult patients with ITP. We also used molecular methods to investigate lymphocyte clonality and H pylori genotypes in the gastric biopsies from 10 H pylori–positive patients with ITP and 19 H pylori–positive patients without ITP with chronic gastritis. Active H pylori infection was documented in 38 (51%) patients and successfully eradicated in 34 (89%) patients. After a median follow-up of 60 months, a persistent platelet response in 23 (68%) of patients with eradicated infection was observed; 1 relapse occurred. No differences in mucosal B- or T-cell clonalities were observed between patients with ITP and control participants. Of note, the frequency of the H pylori cagA gene (P = .02) and the frequency of concomitant H pylori cagA, vacAs1, and iceA genes (triple-positive strains; P = .015) resulted statistically higher in patients with ITP than in control participants. All asymptomatic H pylori–positive patients with ITP were suffering from chronic gastritis. Our data suggest a sustained platelet recovery in a proportion of patients with ITP by H pylori eradication alone. Overrepresentation of specific H pylori genotypes in ITP suggests a possible role for bacterium-related factors in the disease pathogenesis.

Effect of eradication ofHelicobacter pylori on platelet recovery in patients with chronic idiopathic thrombocytopenic purpura: A controlled trial

2008 ◽  
Vol 83 (5) ◽  
pp. 376-381 ◽  
Author(s):  
Nematollah Rostami ◽  
Maryam Keshtkar-Jahromi ◽  
Mohammad Rahnavardi ◽  
Marzieh Keshtkar-Jahromi ◽  
Fatemeh Soghra Esfahani
Keyword(s):  
Idiopathic Thrombocytopenic Purpura ◽  
Controlled Trial ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Platelet Recovery

Helicobacter pylorieradication can induce platelet recovery in chronic idiopathic thrombocytopenic purpura

Platelets ◽  
2006 ◽  
Vol 17 (4) ◽  
pp. 227-230 ◽  
Author(s):  
Nada Suvajdžić ◽  
Boris Stanković ◽  
Vera Artiko ◽  
Tanja Cvejić ◽  
Vladislava Bulat ◽  
...  
Keyword(s):  
Idiopathic Thrombocytopenic Purpura ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Platelet Recovery

scholarly journals Beyond plasma exchange: novel therapies for thrombotic thrombocytopenic purpura

Hematology ◽  
2018 ◽  
Vol 2018 (1) ◽  
pp. 539-547 ◽  
Author(s):  
Kathryn Dane ◽  
Shruti Chaturvedi
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Relapse Prevention ◽  
Tissue Injury ◽  
Novel Therapies ◽  
Thrombocytopenic Purpura ◽  
Platelet Recovery ◽  
Adamts13 Deficiency ◽  
Prophylactic Use ◽  
Von Willebrand

Abstract The advent of plasma exchange has dramatically changed the prognosis of acute thrombotic thrombocytopenic purpura (TTP). Recent insights into TTP pathogenesis have led to the development of novel therapies targeting pathogenic anti-ADAMTS13 antibody production, von Willebrand factor (VWF)–platelet interactions, and ADAMTS13 replacement. Retrospective and prospective studies have established the efficacy of rituximab as an adjunct to plasma exchange for patients with acute TTP, either upfront or for refractory disease. Relapse prevention is a major concern for survivors of acute TTP, and emerging data support the prophylactic use of rituximab in patients with persistent or recurrent ADAMTS13 deficiency in clinical remission. Capalcizumab, a nanobody directed against domain A1 of VWF that prevents the formation of VWF–platelet aggregates, recently completed phase 2 (TITAN) and 3 (HERCULES) trials with encouraging results. Compared with placebo, caplacizumab shortened the time to platelet recovery and may protect against microthrombotic tissue injury in the acute phase of TTP, though it does not modify the underlying immune response. Other promising therapies including plasma cell inhibitors (bortezomib), recombinant ADAMTS13, N-acetyl cysteine, and inhibitors of the VWF–glycoprotein Ib/IX interaction (anfibatide) are in development, and several of these agents are in prospective clinical studies to evaluate their efficacy and role in TTP. In the coming years, we are optimistic that novel therapies and international collaborative efforts will usher in even more effective, evidence-based approaches to address refractory acute TTP and relapse prevention.

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