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 | Conditions associated with immune thrombocytopenia include: | ||
*[ | *[[SLE]] | ||
*[ | *[[Primary Sjogren Syndrome]] | ||
*[ | *[[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 |
|
Diagnosis |
|---|
|
Treatment |
|
Case Studies |
|
Immune Thrombocytopenia pathophysiology On the Web |
|
American Roentgen Ray Society Images of Immune Thrombocytopenia pathophysiology |
|
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:
- Transmembrane mucin, MUC3A. (missense mutation)
- Secretory mucin, MUC5B. ( missense mutation)
- Secretory mucin, MUC6. (missense mutation) [3]
- Fc<math>\gamma</math>R polymorphism.[4]
- IKZF1 haploinsufficiency ( hematopoietic zinc finger transcription factor which directly binds to DNA. presents in familial immune thrombocytopenia.)[5]
- HIF1 signaling pathway.
- mTOR signaling pathway.
- PI3K/Akt signaling pathway.[6]
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:
- SLE
- Primary Sjogren Syndrome
- AIDS[7]
- CVID [8]
- autoimmune thrombocytopenia (Evans syndrome)
- Vaccination side effect
- Bone marrow transplant associated side effect
- Lymphoproliferative disorder [9]
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
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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) - ↑ 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.
- ↑ 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.
- ↑ 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.