Idiopathic thrombocytopenic purpura pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
No edit summary
 
(22 intermediate revisions by the same user not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
{{ITP}}
{{ITP}}
{{CMG}}
increased platelet destruction{{CMG}}


==Overview==
==Overview==
Auto-immune thrombocytopenic purpura is described by the increased platelet destruction due to production of auto-reactive antibodies against host platelets and suppression of platelet production in the bone marrow.


==Pathophysiology==
==Pathophysiology==
===Physiology===
AAA


'''AAA:'''
=== '''Pathogenesis''' ===
* '''AAAA''':
'''Acute ITP:''' Mainly affects children and usually follows a viral or bacterial infection
*<nowiki/><nowiki/><nowiki/><nowiki/>'''AAA:'''
* Antigenic mimicry - Similar molecular structures on both host cells and infectious agents, inducing a self immune response which cross reacts with the host antigens.
===Pathogenesis===
** In acute ITP - anti-viral or anti-bacterial antibodies cross reacts against the patient's platelets.
 
* Mostly acute ITP is self resolving as infectious agents and antibodies are cleared from the body, causing the loss of anti-platelet reactivity.
'''Increased platelet destruction:'''
* T cells are not involved in the parthenogenesis of acute ITP
* Autoantibody‐induced platelet destruction:
'''Chronic ITP:''' (platelet counts < 150,000 x 10<sup>9</sup> per liter x 6 months) usually in adults
** Abnormal IgG auto-antibody recognizes glycoprotein IIb/IIIa, glycoprotein Ib/IX complex, etc
* '''Increased platelet destruction:'''
** IgG auto-antibody binds to the circulating platelet membranes through glycoproteins
** '''Autoantibody‐induced platelet destruction'''
** Autoantibody-coated platelets induce Fcg receptors and bind to antigen-presenting cells (Splenic macrophages or dendritic cells) where the platelets undergoes phagocytosis.
*** Abnormal IgG auto-antibody recognizes glyco-protein IIb/IIIa, glyco-protein Ib/IX complex, GP Ia/IIa, and GP VI etc<ref name="pmid15720967">{{cite journal |vauthors=McMillan R |title=The role of antiplatelet autoantibody assays in the diagnosis of immune thrombocytopenic purpura |journal=Curr. Hematol. Rep. |volume=4 |issue=2 |pages=160–5 |date=March 2005 |pmid=15720967 |doi= |url=}}</ref>
*** Predominantly IgG auto-antibodies constitute the majority of antibodies but IgM and IgA antibodies can also be found in some of ITP patients.<ref name="pmid157209672">{{cite journal |vauthors=McMillan R |title=The role of antiplatelet autoantibody assays in the diagnosis of immune thrombocytopenic purpura |journal=Curr. Hematol. Rep. |volume=4 |issue=2 |pages=160–5 |date=March 2005 |pmid=15720967 |doi= |url=}}</ref>
*** Auto-antibodies binds to the circulating platelet membranes through glyco-proteins
*** Auto-antibody-coated platelets induce Fcγ receptors and bind to antigen-presenting cells (Splenic macrophages or dendritic cells) in the reticulo-endothelial system<ref name="pmid2939345">{{cite journal |vauthors=Clarkson SB, Bussel JB, Kimberly RP, Valinsky JE, Nachman RL, Unkeless JC |title=Treatment of refractory immune thrombocytopenic purpura with an anti-Fc gamma-receptor antibody |journal=N. Engl. J. Med. |volume=314 |issue=19 |pages=1236–9 |date=May 1986 |pmid=2939345 |doi=10.1056/NEJM198605083141907 |url=}}</ref><ref name="pmid5214832">{{cite journal |vauthors=Shulman NR, Marder VJ, Weinrach RS |title=Similarities between known antiplatelet antibodies and the factor responsible for thrombocytopenia in idiopathic purpura. Physiologic, serologic and isotopic studies |journal=Ann. N. Y. Acad. Sci. |volume=124 |issue=2 |pages=499–542 |date=June 1965 |pmid=5214832 |doi= |url=}}</ref>
*** The auto-antibody-coated platelets undergo phagocytosis by splenic macrophages and peripheral blood neutrophils.<ref name="pmid5812817">{{cite journal |vauthors=Firkin BG, Wright R, Miller S, Stokes E |title=Splenic macrophages in thrombocytopenia |journal=Blood |volume=33 |issue=2 |pages=240–5 |date=February 1969 |pmid=5812817 |doi= |url=}}</ref>
** '''Autoreactive T lymphocyte‐mediated platelet lysis'''
*** Abnormal cytotoxic T cells defect leads to differentiation of direct autoreactive B cells further leading to secretion of IgG auto-antibodies<ref name="pmid12937414">{{cite journal |vauthors=Olsson B, Andersson PO, Jernås M, Jacobsson S, Carlsson B, Carlsson LM, Wadenvik H |title=T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura |journal=Nat. Med. |volume=9 |issue=9 |pages=1123–4 |date=September 2003 |pmid=12937414 |doi=10.1038/nm921 |url=}}</ref>
*** Abnormal T cells includes cytotoxic T-lymphocyte (CD8+) and natural killer cells (CD3- CD16+ CD56+)<ref name="pmid16480433">{{cite journal |vauthors=Zhang F, Chu X, Wang L, Zhu Y, Li L, Ma D, Peng J, Hou M |title=Cell-mediated lysis of autologous platelets in chronic idiopathic thrombocytopenic purpura |journal=Eur. J. Haematol. |volume=76 |issue=5 |pages=427–31 |date=May 2006 |pmid=16480433 |doi=10.1111/j.1600-0609.2005.00622.x |url=}}</ref>
*** CD4-positive helper T cells react with platelet surface glycoproteins, through co-stimulation involving CD40:CD40L
*** T cells act directly on the megakaryocytes in the bone marrow
***
* '''Autoantibody‐mediated suppression of platelet production:'''
** Decreased platelet turnover<ref name="pmid3597777">{{cite journal |vauthors=Ballem PJ, Segal GM, Stratton JR, Gernsheimer T, Adamson JW, Slichter SJ |title=Mechanisms of thrombocytopenia in chronic autoimmune thrombocytopenic purpura. Evidence of both impaired platelet production and increased platelet clearance |journal=J. Clin. Invest. |volume=80 |issue=1 |pages=33–40 |date=July 1987 |pmid=3597777 |pmc=442198 |doi=10.1172/JCI113060 |url=}}</ref>
** Abnormal thrombopoiesis
** Autoantibody‐induced suppression of megakaryocytopoiesis<ref name="pmid12676790">{{cite journal |vauthors=Chang M, Nakagawa PA, Williams SA, Schwartz MR, Imfeld KL, Buzby JS, Nugent DJ |title=Immune thrombocytopenic purpura (ITP) plasma and purified ITP monoclonal autoantibodies inhibit megakaryocytopoiesis in vitro |journal=Blood |volume=102 |issue=3 |pages=887–95 |date=August 2003 |pmid=12676790 |doi=10.1182/blood-2002-05-1475 |url=}}</ref>
** Megakaryocitic nuclei and cytoplasm shows degenrative changes<ref name="pmid21013546">{{cite journal |vauthors=DAMESHEK W, MILLER EB |title=The megakaryocytes in idiopathic thrombocytopenic purpura, a form of hypersplenism |journal=Blood |volume=1 |issue= |pages=27–50 |date=January 1946 |pmid=21013546 |doi= |url=}}</ref>
**  
**  
**  
**  
** Antigen-presenting cells degrade glycoproteins and and not only degrade glycoprotein IIb/IIIa (light blue oval), thereby amplifying the initial immune response, but also may generate cryptic epitopes from other platelet glycoproteins
*
** Activated antigen-presenting cells
** express these novel peptides on the cell surface along with costimulatory help (represented in part by the interaction between CD154 and CD40) and the relevant cytokines that facilitate the proliferation of the initiating CD4-positive T-cell clones (T-cell clone 1) and those with additional specificities (T-cell clone 2)
** B-cell immunoglobulin receptors that recognize additional platelet antigens (B-cell clone 2) are thereby also induced to proliferate and synthesize anti–glycoprotein Ib/IX antibodies (green) in addition to amplifying the production of anti–glycoprotein IIb/IIIa antibodies (orange) by B-cell clone 1
* Autoreactive T lymphocyte‐mediated platelet lysis
*
'''Decreased platelet production:'''
* abnormal thrombopoiesis
* degenerative changes in both nuclei and cytoplasm
**
 
== Genetics ==
== Genetics ==
==Associated Conditions==
==Associated Conditions==
Line 40: Line 44:
==Gross Pathology==
==Gross Pathology==
On [[gross pathology]], characteristic findings of itp include:
On [[gross pathology]], characteristic findings of itp include:
* '''Acute atopic dermatitis''':
* '''Acute'''
**
* '''Chronic atopic dermatitis:'''
**  
**  
* '''Chronic'''


==Microscopic Pathology==
==Microscopic Pathology==
On microscopic [[histopathological]] analysis, characteristic findings of itp include:
On microscopic [[histopathological]] analysis, characteristic findings of itp include:
* '''Acute vesicular lesions''':
* '''Acute'''  
* '''Chronic lichenified plaque''':
* '''Chronic'''  


==References==
==References==

Latest revision as of 18:27, 2 November 2018

Idiopathic thrombocytopenic purpura Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Idiopathic thrombocytopenic purpura from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X Ray

CT

MRI

Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Radiation

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Idiopathic thrombocytopenic purpura pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Idiopathic thrombocytopenic purpura pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Idiopathic thrombocytopenic purpura pathophysiology

CDC on Idiopathic thrombocytopenic purpura pathophysiology

Idiopathic thrombocytopenic purpura pathophysiology in the news

Blogs on Idiopathic thrombocytopenic purpura pathophysiology

Directions to Hospitals Treating Idiopathic thrombocytopenic purpura

Risk calculators and risk factors for Idiopathic thrombocytopenic purpura pathophysiology

increased platelet destructionEditor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Auto-immune thrombocytopenic purpura is described by the increased platelet destruction due to production of auto-reactive antibodies against host platelets and suppression of platelet production in the bone marrow.

Pathophysiology

Pathogenesis

Acute ITP: Mainly affects children and usually follows a viral or bacterial infection

  • Antigenic mimicry - Similar molecular structures on both host cells and infectious agents, inducing a self immune response which cross reacts with the host antigens.
    • In acute ITP - anti-viral or anti-bacterial antibodies cross reacts against the patient's platelets.
  • Mostly acute ITP is self resolving as infectious agents and antibodies are cleared from the body, causing the loss of anti-platelet reactivity.
  • T cells are not involved in the parthenogenesis of acute ITP

Chronic ITP: (platelet counts < 150,000 x 109 per liter x 6 months) usually in adults

  • Increased platelet destruction:
    • Autoantibody‐induced platelet destruction
      • Abnormal IgG auto-antibody recognizes glyco-protein IIb/IIIa, glyco-protein Ib/IX complex, GP Ia/IIa, and GP VI etc[1]
      • Predominantly IgG auto-antibodies constitute the majority of antibodies but IgM and IgA antibodies can also be found in some of ITP patients.[2]
      • Auto-antibodies binds to the circulating platelet membranes through glyco-proteins
      • Auto-antibody-coated platelets induce Fcγ receptors and bind to antigen-presenting cells (Splenic macrophages or dendritic cells) in the reticulo-endothelial system[3][4]
      • The auto-antibody-coated platelets undergo phagocytosis by splenic macrophages and peripheral blood neutrophils.[5]
    • Autoreactive T lymphocyte‐mediated platelet lysis
      • Abnormal cytotoxic T cells defect leads to differentiation of direct autoreactive B cells further leading to secretion of IgG auto-antibodies[6]
      • Abnormal T cells includes cytotoxic T-lymphocyte (CD8+) and natural killer cells (CD3- CD16+ CD56+)[7]
      • CD4-positive helper T cells react with platelet surface glycoproteins, through co-stimulation involving CD40:CD40L
      • T cells act directly on the megakaryocytes in the bone marrow
  • Autoantibody‐mediated suppression of platelet production:
    • Decreased platelet turnover[8]
    • Abnormal thrombopoiesis
    • Autoantibody‐induced suppression of megakaryocytopoiesis[9]
    • Megakaryocitic nuclei and cytoplasm shows degenrative changes[10]

Genetics

Associated Conditions

Conditions associated with

Gross Pathology

On gross pathology, characteristic findings of itp include:

  • Acute
  • Chronic

Microscopic Pathology

On microscopic histopathological analysis, characteristic findings of itp include:

  • Acute
  • Chronic

References

Template:WH Template:WS


References

  1. ↑ McMillan R (March 2005). "The role of antiplatelet autoantibody assays in the diagnosis of immune thrombocytopenic purpura". Curr. Hematol. Rep. 4 (2): 160–5. PMID 15720967.
  2. ↑ McMillan R (March 2005). "The role of antiplatelet autoantibody assays in the diagnosis of immune thrombocytopenic purpura". Curr. Hematol. Rep. 4 (2): 160–5. PMID 15720967.
  3. ↑ Clarkson SB, Bussel JB, Kimberly RP, Valinsky JE, Nachman RL, Unkeless JC (May 1986). "Treatment of refractory immune thrombocytopenic purpura with an anti-Fc gamma-receptor antibody". N. Engl. J. Med. 314 (19): 1236–9. doi:10.1056/NEJM198605083141907. PMID 2939345.
  4. ↑ Shulman NR, Marder VJ, Weinrach RS (June 1965). "Similarities between known antiplatelet antibodies and the factor responsible for thrombocytopenia in idiopathic purpura. Physiologic, serologic and isotopic studies". Ann. N. Y. Acad. Sci. 124 (2): 499–542. PMID 5214832.
  5. ↑ Firkin BG, Wright R, Miller S, Stokes E (February 1969). "Splenic macrophages in thrombocytopenia". Blood. 33 (2): 240–5. PMID 5812817.
  6. ↑ Olsson B, Andersson PO, Jernås M, Jacobsson S, Carlsson B, Carlsson LM, Wadenvik H (September 2003). "T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura". Nat. Med. 9 (9): 1123–4. doi:10.1038/nm921. PMID 12937414.
  7. ↑ Zhang F, Chu X, Wang L, Zhu Y, Li L, Ma D, Peng J, Hou M (May 2006). "Cell-mediated lysis of autologous platelets in chronic idiopathic thrombocytopenic purpura". Eur. J. Haematol. 76 (5): 427–31. doi:10.1111/j.1600-0609.2005.00622.x. PMID 16480433.
  8. ↑ Ballem PJ, Segal GM, Stratton JR, Gernsheimer T, Adamson JW, Slichter SJ (July 1987). "Mechanisms of thrombocytopenia in chronic autoimmune thrombocytopenic purpura. Evidence of both impaired platelet production and increased platelet clearance". J. Clin. Invest. 80 (1): 33–40. doi:10.1172/JCI113060. PMC 442198. PMID 3597777.
  9. ↑ Chang M, Nakagawa PA, Williams SA, Schwartz MR, Imfeld KL, Buzby JS, Nugent DJ (August 2003). "Immune thrombocytopenic purpura (ITP) plasma and purified ITP monoclonal autoantibodies inhibit megakaryocytopoiesis in vitro". Blood. 102 (3): 887–95. doi:10.1182/blood-2002-05-1475. PMID 12676790.
  10. ↑ DAMESHEK W, MILLER EB (January 1946). "The megakaryocytes in idiopathic thrombocytopenic purpura, a form of hypersplenism". Blood. 1: 27–50. PMID 21013546.

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Idiopathic_thrombocytopenic_purpura_pathophysiology&oldid=1501575"