3 Abstracts on ITP

[Guest guest]

These abstracts are from 'Blood Reviews'. There are a

few more, which I will also send out in a packet.

Pathophysiology of platelet destruction in immune

(idiopathic) thrombocytopenic purpura

J. McFarland

p 1-2, Volume 16, Number 1, March 2002

Abstract

The mechanism of platelet destruction in immune

(idiopathic) thrombocytopenic purpura (ITP) is thought

to involve production of autoantibody to platelet

surface antigens. Once coated with antibody,

circulating platelets undergo sequestration via

interaction with Fc receptors of macrophages in the

reticuloendothelial system. A number of questions

remain about the mechanism of platelet destruction in

this disease: 1) What is the nature of the stimulus to

the immune system that generates antiplatelet

antibodies? 2) What is the role of interactions

between T-helper lymphocytes and antigen-presenting

cells in ITP? 3) What role, if any, is played by the

targeting of single or multiple platelet surface

glycoproteins by the autoimmune response? 4) Is the

site of platelet destruction, intravascular or

extravascular, or the state of activation of platelets

important in the destruction of platelets? Copyright

2002, Elsevier Science Ltd. All rights reserved

Pathophysiology and thrombokinetics in autoimmune

thrombocytopenia

T. Gernsheimer

p 7-8, Volume 16, Number 1, March 2002

Abstract

Studies that have measured platelet survival by

autologous platelet labeling with 111In and 51Cr have

differed in their results. Although all studies have

revealed a significant decrease in platelet life span,

the rates of platelets entering the circulation, a

calculated and inferred determination, have been found

to be moderately decreased to as much as five times

normal. Several mechanisms have been proposed to

explain an apparent decrease in platelet production,

including a true decrease due to damage to the

megakaryocytes by autoantibody, versus a decrease only

in 'effective' production due to intramedullary

destruction by the reticuloendothelial system.

Recently, the identification of the cytokine,

thrombopoietin, has allowed the evaluation of another

aspect of the pathophysiology of thrombocytopenic

states. Megakaryocyte growth factor levels are

increased 10 to 20 times in patients who are

thrombocytopenic due to chemotherapy or aplastic

anemia, but may be decreased, normal, or only modestly

raised in patients with immune platelet destruction.

Autologous platelet survival measurements, prior to

and while on therapy with a stable platelet count,

reveal that removal of part of the reticuloendothelial

system with splenectomy leads to increased platelet

survival and platelet number. Similar studies reveal

that corticosteroid treatment for immune

thrombocytopenic purpura (ITP) effectively increases

the rate of platelet production but does not change

platelet survival. It may be that other therapies are

effective by a combination of these mechanisms.

Stimulation of thrombopoietin production or

administering exogenous cytokine may have a role to

play in future management of patients with ITP.

Copyright 2002, Elsevier Science Ltd. All rights

reserved.

Novel approaches to refractory immune thrombocytopenic

purpura

J. B. Bussel

p 31-36, Volume 16, Number 1, March 2002

Abstract

Chronic immune thrombocytopenic purpura (ITP) is an

organ-specific autoimmune bleeding disorder in which

autoantibodies are directed against the individual's

own platelets, resulting in increased Fc-mediated

platelet destruction by macrophages in the

reticuloendothelial system. Although ITP is primarily

mediated by IgG autoantibodies, the production of

these autoantibodies is regulated by the influence of

T lymphocytes and antigen-presenting cells (APC).

There is evidence that enhanced T-helper cell/APC

interactions in patients with ITP may play an integral

role in IgG antiplatelet autoantibody production. New

therapies may improve platelet production, decrease

platelet antibody production, and decrease monocyte

function and/or B-cell and T-cell activities.

Understanding these cellular immune responses in ITP

may lead to the development of more specific

immunoregulatory therapies for the management of this

disease.

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