Immune Thrombocytopenia pathophysiology: Difference between revisions

Jump to navigation Jump to search
(genetic)
(Pathophysiology complete)
Line 38: Line 38:
*The progression to immune thrombocytopenia usually involves the [[genetic]] predisposition, immune dysregulation and environmental factors which lead to [[autoimmunity]].
*The progression to immune thrombocytopenia usually involves the [[genetic]] predisposition, immune dysregulation and environmental factors which lead to [[autoimmunity]].
*[[Molecular mimicry]] between foreign [[antigens]] and [[autologous]] platelet antigens leads to activation of [[cross-reactive]] [[B cell|B]] and [[T cell]], starting [[autoimmune response]].<ref name="LiSullivan2018">{{cite journal|last1=Li|first1=June|last2=Sullivan|first2=Jade A.|last3=Ni|first3=Heyu|title=Pathophysiology of immune thrombocytopenia|journal=Current Opinion in Hematology|volume=25|issue=5|year=2018|pages=373–381|issn=1065-6251|doi=10.1097/MOH.0000000000000447}}</ref>
*[[Molecular mimicry]] between foreign [[antigens]] and [[autologous]] platelet antigens leads to activation of [[cross-reactive]] [[B cell|B]] and [[T cell]], starting [[autoimmune response]].<ref name="LiSullivan2018">{{cite journal|last1=Li|first1=June|last2=Sullivan|first2=Jade A.|last3=Ni|first3=Heyu|title=Pathophysiology of immune thrombocytopenia|journal=Current Opinion in Hematology|volume=25|issue=5|year=2018|pages=373–381|issn=1065-6251|doi=10.1097/MOH.0000000000000447}}</ref>
*In immune thrombocytopenia , the balance between platelet production and destruction is impaired. Therefore, platelet destruction is accelerated by macrophages in spleen, and moderately impaired platelet production by anti platelet antibody or [[cytotoxic T-cells]].
*Anti platelet antibodies ( anti platelet surface glycoproteins) includes:
<nowiki>**</nowiki> anti GP<math>\Pi</math>b/<math>\Pi\Iota</math>a antibody
<nowiki>**</nowiki> anti GP<math>\Iota</math>b/<math>\Iota</math>X antibody
<nowiki>*</nowiki> Abnormal T-cells:
<nowiki>**</nowiki> Increase Th17 and IL-17 level.
<nowiki>**</nowiki> Increase oligoclonal T-cells.
<nowiki>**</nowiki>Presence of cytotoxic T-cells again autologous platelets.<ref name="KashiwagiTomiyama2013">{{cite journal|last1=Kashiwagi|first1=Hirokazu|last2=Tomiyama|first2=Yoshiaki|title=Pathophysiology and management of primary immune thrombocytopenia|journal=International Journal of Hematology|volume=98|issue=1|year=2013|pages=24–33|issn=0925-5710|doi=10.1007/s12185-013-1370-4}}</ref>


==Genetics==
==Genetics==
Line 50: Line 64:
*Secretory mucin, MUC6. (missense mutation) <ref name="ZhuYuan2020">{{cite journal|last1=Zhu|first1=Jing-jing|last2=Yuan|first2=Dai|last3=Sun|first3=Rui-Jie|last4=Liu|first4=Shu-yan|last5=Shan|first5=Ning-ning|title=Mucin mutations and aberrant expression are associated with the pathogenesis of immune thrombocytopenia|journal=Thrombosis Research|volume=194|year=2020|pages=222–228|issn=00493848|doi=10.1016/j.thromres.2020.08.005}}</ref>
*Secretory mucin, MUC6. (missense mutation) <ref name="ZhuYuan2020">{{cite journal|last1=Zhu|first1=Jing-jing|last2=Yuan|first2=Dai|last3=Sun|first3=Rui-Jie|last4=Liu|first4=Shu-yan|last5=Shan|first5=Ning-ning|title=Mucin mutations and aberrant expression are associated with the pathogenesis of immune thrombocytopenia|journal=Thrombosis Research|volume=194|year=2020|pages=222–228|issn=00493848|doi=10.1016/j.thromres.2020.08.005}}</ref>
*Fc<math>\gamma</math>R [[polymorphism]].<ref name="Johnsen2012">{{cite journal|last1=Johnsen|first1=Jill|title=Pathogenesis in immune thrombocytopenia: new insights|journal=Hematology|volume=2012|issue=1|year=2012|pages=306–312|issn=1520-4391|doi=10.1182/asheducation.V2012.1.306.3798320}}</ref>
*Fc<math>\gamma</math>R [[polymorphism]].<ref name="Johnsen2012">{{cite journal|last1=Johnsen|first1=Jill|title=Pathogenesis in immune thrombocytopenia: new insights|journal=Hematology|volume=2012|issue=1|year=2012|pages=306–312|issn=1520-4391|doi=10.1182/asheducation.V2012.1.306.3798320}}</ref>
*IKZF1 [[haploinsufficiency]] ( [[hematopoietic]] [[zinc finger]] [[transcription factor]] which directly binds to [[DNA]]. presents in familial immune thrombocytopenia.)<ref name="SriaroonChang2019">{{cite journal|last1=Sriaroon|first1=Panida|last2=Chang|first2=Yenhui|last3=Ujhazi|first3=Boglarka|last4=Csomos|first4=Krisztian|last5=Joshi|first5=Hemant R.|last6=Zhou|first6=Qin|last7=Close|first7=Devin W.|last8=Walter|first8=Jolan E.|last9=Kumánovics|first9=Attila|title=Familial Immune Thrombocytopenia Associated With a Novel Variant in IKZF1|journal=Frontiers in Pediatrics|volume=7|year=2019|issn=2296-2360|doi=10.3389/fped.2019.00139}}</ref>  
*IKZF1 [[haploinsufficiency]] ( [[hematopoietic]] [[zinc finger]] [[transcription factor]] which directly binds to [[DNA]]. presents in familial immune thrombocytopenia.)<ref name="SriaroonChang2019">{{cite journal|last1=Sriaroon|first1=Panida|last2=Chang|first2=Yenhui|last3=Ujhazi|first3=Boglarka|last4=Csomos|first4=Krisztian|last5=Joshi|first5=Hemant R.|last6=Zhou|first6=Qin|last7=Close|first7=Devin W.|last8=Walter|first8=Jolan E.|last9=Kumánovics|first9=Attila|title=Familial Immune Thrombocytopenia Associated With a Novel Variant in IKZF1|journal=Frontiers in Pediatrics|volume=7|year=2019|issn=2296-2360|doi=10.3389/fped.2019.00139}}</ref>
*HIF1 [[signaling pathway]].
*HIF1 [[signaling pathway]].
*[[mTOR]] signaling pathway.
*[[mTOR]] signaling pathway.
Line 65: Line 79:


==Associated Conditions==
==Associated Conditions==
Conditions associated with [disease name] include:
Conditions associated with immune thrombocytopenia include:


*[Condition 1]
*[[SLE]]
*[Condition 2]
*[[Primary Sjogren Syndrome]]
*[Condition 3]
*[[HIV AIDS|AIDS]]<ref name="LiuChen2016">{{cite journal|last1=Liu|first1=Yuan|last2=Chen|first2=Shiju|last3=Sun|first3=Yuechi|last4=Lin|first4=Qingyan|last5=Liao|first5=Xining|last6=Zhang|first6=Junhui|last7=Luo|first7=Jiao|last8=Qian|first8=Hongyan|last9=Duan|first9=Lihua|last10=Shi|first10=Guixiu|title=Clinical characteristics of immune thrombocytopenia associated with autoimmune disease|journal=Medicine|volume=95|issue=50|year=2016|pages=e5565|issn=0025-7974|doi=10.1097/MD.0000000000005565}}</ref>
*[[Common variable immunodeficiency|CVID]] <ref name="TinazziOsti2020">{{cite journal|last1=Tinazzi|first1=Elisa|last2=Osti|first2=Nicola|last3=Beri|first3=Ruggero|last4=Argentino|first4=Giuseppe|last5=Veneri|first5=Dino|last6=Dima|first6=Francesco|last7=Bason|first7=Caterina|last8=Jadav|first8=Gnaneshwer|last9=Dolcino|first9=Marzia|last10=Puccetti|first10=Antonio|last11=Lunardi|first11=Claudio|title=Pathogenesis of immune thrombocytopenia in common variable immunodeficiency|journal=Autoimmunity Reviews|volume=19|issue=9|year=2020|pages=102616|issn=15689972|doi=10.1016/j.autrev.2020.102616}}</ref>
*autoimmune thrombocytopenia ([[Evans syndrome]])
*Vaccination side effect
*[[Bone marrow transplant|Bone marrow transplan]]<nowiki/>t associated side effect
*[[Lymphoproliferative disorder]] <ref name="NeunertLim2011">{{cite journal|last1=Neunert|first1=Cindy|last2=Lim|first2=Wendy|last3=Crowther|first3=Mark|last4=Cohen|first4=Alan|last5=Solberg|first5=Lawrence|last6=Crowther|first6=Mark A.|title=The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia|journal=Blood|volume=117|issue=16|year=2011|pages=4190–4207|issn=0006-4971|doi=10.1182/blood-2010-08-302984}}</ref>


==Gross Pathology==
==Gross Pathology==

Revision as of 17:10, 4 February 2021

Immune Thrombocytopenia Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Immune Thrombocytopenia 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

Echocardiography and Ultrasound

CT scan

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Interventions

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Immune Thrombocytopenia pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Immune Thrombocytopenia pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Immune Thrombocytopenia pathophysiology

CDC on Immune Thrombocytopenia pathophysiology

Immune Thrombocytopenia pathophysiology in the news

Blogs on Immune Thrombocytopenia pathophysiology

Directions to Hospitals Treating Psoriasis

Risk calculators and risk factors for Immune Thrombocytopenia pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maryam Barkhordarian, M.D.[2]

Overview

The exact pathogenesis of [disease name] is not fully understood.

OR

It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].

OR

[Pathogen name] is usually transmitted via the [transmission route] route to the human host.

OR

Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.

OR


[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].

OR

The progression to [disease name] usually involves the [molecular pathway].

OR

The pathophysiology of [disease/malignancy] depends on the histological subtype.

Pathophysiology

Pathogenesis

  • Immune thrombocytopenia arises from platelets, which are blood cells that are normally involved in hemostasis.
  • It is understood that Immune thrombocytopenia is caused by destruction of one's own platelets and megakaryocytes.
  • The progression to immune thrombocytopenia usually involves the genetic predisposition, immune dysregulation and environmental factors which lead to autoimmunity.
  • Molecular mimicry between foreign antigens and autologous platelet antigens leads to activation of cross-reactive B and T cell, starting autoimmune response.[1]
  • In immune thrombocytopenia , the balance between platelet production and destruction is impaired. Therefore, platelet destruction is accelerated by macrophages in spleen, and moderately impaired platelet production by anti platelet antibody or cytotoxic T-cells.
  • Anti platelet antibodies ( anti platelet surface glycoproteins) includes:

** anti GP<math>\Pi</math>b/<math>\Pi\Iota</math>a antibody

** anti GP<math>\Iota</math>b/<math>\Iota</math>X antibody

* Abnormal T-cells:

** Increase Th17 and IL-17 level.

** Increase oligoclonal T-cells.

**Presence of cytotoxic T-cells again autologous platelets.[2]

Genetics

[Disease name] is transmitted in [mode of genetic transmission] pattern.

OR

Genes involved in the pathogenesis of immune thrombocytopenia include:

OR

The development of [disease name] is the result of multiple genetic mutations such as:

  • [Mutation 1]
  • [Mutation 2]
  • [Mutation 3]

Associated Conditions

Conditions associated with immune thrombocytopenia include:

Gross Pathology

On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Microscopic Pathology

On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

References

  1. Li, June; Sullivan, Jade A.; Ni, Heyu (2018). "Pathophysiology of immune thrombocytopenia". Current Opinion in Hematology. 25 (5): 373–381. doi:10.1097/MOH.0000000000000447. ISSN 1065-6251.
  2. Kashiwagi, Hirokazu; Tomiyama, Yoshiaki (2013). "Pathophysiology and management of primary immune thrombocytopenia". International Journal of Hematology. 98 (1): 24–33. doi:10.1007/s12185-013-1370-4. ISSN 0925-5710.
  3. Zhu, Jing-jing; Yuan, Dai; Sun, Rui-Jie; Liu, Shu-yan; Shan, Ning-ning (2020). "Mucin mutations and aberrant expression are associated with the pathogenesis of immune thrombocytopenia". Thrombosis Research. 194: 222–228. doi:10.1016/j.thromres.2020.08.005. ISSN 0049-3848.
  4. Johnsen, Jill (2012). "Pathogenesis in immune thrombocytopenia: new insights". Hematology. 2012 (1): 306–312. doi:10.1182/asheducation.V2012.1.306.3798320. ISSN 1520-4391.
  5. Sriaroon, Panida; Chang, Yenhui; Ujhazi, Boglarka; Csomos, Krisztian; Joshi, Hemant R.; Zhou, Qin; Close, Devin W.; Walter, Jolan E.; Kumánovics, Attila (2019). "Familial Immune Thrombocytopenia Associated With a Novel Variant in IKZF1". Frontiers in Pediatrics. 7. doi:10.3389/fped.2019.00139. ISSN 2296-2360.
  6. Sun, Ruijie; Liu, Shu-Yan; Zhang, Xiao-Mei; Zhu, Jing-Jing; Yuan, Dai; Shan, Ning-Ning (2020). doi:10.21203/rs.3.rs-131436/v1. Missing or empty |title= (help)
  7. Liu, Yuan; Chen, Shiju; Sun, Yuechi; Lin, Qingyan; Liao, Xining; Zhang, Junhui; Luo, Jiao; Qian, Hongyan; Duan, Lihua; Shi, Guixiu (2016). "Clinical characteristics of immune thrombocytopenia associated with autoimmune disease". Medicine. 95 (50): e5565. doi:10.1097/MD.0000000000005565. ISSN 0025-7974.
  8. Tinazzi, Elisa; Osti, Nicola; Beri, Ruggero; Argentino, Giuseppe; Veneri, Dino; Dima, Francesco; Bason, Caterina; Jadav, Gnaneshwer; Dolcino, Marzia; Puccetti, Antonio; Lunardi, Claudio (2020). "Pathogenesis of immune thrombocytopenia in common variable immunodeficiency". Autoimmunity Reviews. 19 (9): 102616. doi:10.1016/j.autrev.2020.102616. ISSN 1568-9972.
  9. Neunert, Cindy; Lim, Wendy; Crowther, Mark; Cohen, Alan; Solberg, Lawrence; Crowther, Mark A. (2011). "The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia". Blood. 117 (16): 4190–4207. doi:10.1182/blood-2010-08-302984. ISSN 0006-4971.

Template:WH Template:WS