Thrombotic thrombocytopenic purpura pathophysiology: Difference between revisions
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* ADAMTS13 is a plasma reprolysin-like metalloprotease divides von Willebrand factor (VWF).<ref name="pmid23809107">{{cite journal |vauthors=Zheng XL |title=Structure-function and regulation of ADAMTS-13 protease |journal=J. Thromb. Haemost. |volume=11 Suppl 1 |issue= |pages=11–23 |date=June 2013 |pmid=23809107 |pmc=3713533 |doi=10.1111/jth.12221 |url=}}</ref> | * ADAMTS13 is a plasma reprolysin-like metalloprotease divides von Willebrand factor (VWF).<ref name="pmid23809107">{{cite journal |vauthors=Zheng XL |title=Structure-function and regulation of ADAMTS-13 protease |journal=J. Thromb. Haemost. |volume=11 Suppl 1 |issue= |pages=11–23 |date=June 2013 |pmid=23809107 |pmc=3713533 |doi=10.1111/jth.12221 |url=}}</ref> | ||
* The von Willebrand factor (VWF) is produced by the endothelial cells as an ultra-high-molecular-weight multimers. Normally, VWF is sliced by a plasma metalloproteinase called ADAMTS13 into smaller multimers. When the activity or the amount of the protease is not enough, the ultra-high-molecular-weight multimers of VWF commence platelet aggregation and thrombosis in small vessels.<ref name="pmid20058209" /> | * The von Willebrand factor (VWF) is produced by the endothelial cells as an ultra-high-molecular-weight multimers. Normally, VWF is sliced by a plasma metalloproteinase called ADAMTS13 into smaller multimers. When the activity or the amount of the protease is not enough, the ultra-high-molecular-weight multimers of VWF commence platelet aggregation and thrombosis in small vessels.<ref name="pmid20058209" /> | ||
==Microscopic Pathology== | |||
On microscopic [[Histopathological|histopathologica]]<nowiki/>l analysis finding of [[Hemolytic-uremic syndrome|HUS]]. | |||
*Granular (muddy brown) casts | |||
*Characteristic fibrin thrombi in glomerular and interstitial capillaries | |||
*Slough into [[tubular]] [[lumen]] | |||
[[File:Acute thrombotic microangiopathy - pas - high mag.jpg|300px|thumb|none|High magnification microscopy of HUS Source:By Nephron [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], from Wikimedia Commons]] | |||
== Genetics == | == Genetics == | ||
Genes involved in the pathogenesis of TTP include:<ref name="pmid28678087">{{cite journal |vauthors=Conboy E, Partain PI, Warad D, Kluge ML, Arndt C, Chen D, Rodriguez V |title=A Severe Case of Congenital Thrombotic Thrombocytopenia Purpura Resulting From Compound Heterozygosity Involving a Novel ADAMTS13 Pathogenic Variant |journal=J. Pediatr. Hematol. Oncol. |volume=40 |issue=1 |pages=60–62 |date=January 2018 |pmid=28678087 |doi=10.1097/MPH.0000000000000895 |url=}}</ref> | Genes involved in the pathogenesis of TTP include:<ref name="pmid28678087">{{cite journal |vauthors=Conboy E, Partain PI, Warad D, Kluge ML, Arndt C, Chen D, Rodriguez V |title=A Severe Case of Congenital Thrombotic Thrombocytopenia Purpura Resulting From Compound Heterozygosity Involving a Novel ADAMTS13 Pathogenic Variant |journal=J. Pediatr. Hematol. Oncol. |volume=40 |issue=1 |pages=60–62 |date=January 2018 |pmid=28678087 |doi=10.1097/MPH.0000000000000895 |url=}}</ref> | ||
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==Microscopic Pathology== | ==Microscopic Pathology== | ||
On microscopic [[Histopathological|histopathologica]]<nowiki/>l analysis finding of [[Hemolytic-uremic syndrome|TTP]]. | On microscopic [[Histopathological|histopathologica]]<nowiki/>l analysis finding of [[Hemolytic-uremic syndrome|TTP]]. | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sogand Goudarzi, MD [2]
Overview
Pathophysiology
- The exact pathogenesis of TTP is not completely understood.[1]
- It is understood that TTP is caused by either deficiency of a plasma metalloprotease, ADAMTS13( (A Disintegrin And Metalloprotease with a ThromboSpondin type 1 motif, member 13). ADAMTS13 is member of human family the ADAMTS.[2]
- ADAMTS13 is a plasma reprolysin-like metalloprotease divides von Willebrand factor (VWF).[3]
- The von Willebrand factor (VWF) is produced by the endothelial cells as an ultra-high-molecular-weight multimers. Normally, VWF is sliced by a plasma metalloproteinase called ADAMTS13 into smaller multimers. When the activity or the amount of the protease is not enough, the ultra-high-molecular-weight multimers of VWF commence platelet aggregation and thrombosis in small vessels.[1]
Microscopic Pathology
On microscopic histopathological analysis finding of HUS.
- Granular (muddy brown) casts
Genetics
Genes involved in the pathogenesis of TTP include:[4]
- mutations in the ADAMTS13 gene.
- The development of TTP is the result of inherited ADAMTS13 deficiency but mild phenotype with increased von Willebrand factor level. Upshaw–Schulman syndrome is hereditary of TTP.
- Among some patients with severe, hereditary ADAMTS13 deficiency do not have signs or symptoms of TTP until their adulthoods .[5]
Microscopic Pathology
On microscopic histopathological analysis finding of TTP.
- Granular (muddy brown) casts
References
- ↑ 1.0 1.1 Tsai HM (January 2010). "Pathophysiology of thrombotic thrombocytopenic purpura". Int. J. Hematol. 91 (1): 1–19. doi:10.1007/s12185-009-0476-1. PMC 3159000. PMID 20058209.
- ↑ Porter S, Clark IM, Kevorkian L, Edwards DR (February 2005). "The ADAMTS metalloproteinases". Biochem. J. 386 (Pt 1): 15–27. doi:10.1042/BJ20040424. PMC 1134762. PMID 15554875.
- ↑ Zheng XL (June 2013). "Structure-function and regulation of ADAMTS-13 protease". J. Thromb. Haemost. 11 Suppl 1: 11–23. doi:10.1111/jth.12221. PMC 3713533. PMID 23809107.
- ↑ Conboy E, Partain PI, Warad D, Kluge ML, Arndt C, Chen D, Rodriguez V (January 2018). "A Severe Case of Congenital Thrombotic Thrombocytopenia Purpura Resulting From Compound Heterozygosity Involving a Novel ADAMTS13 Pathogenic Variant". J. Pediatr. Hematol. Oncol. 40 (1): 60–62. doi:10.1097/MPH.0000000000000895. PMID 28678087.
- ↑ Fujimura Y, Matsumoto M, Isonishi A, Yagi H, Kokame K, Soejima K, Murata M, Miyata T (July 2011). "Natural history of Upshaw-Schulman syndrome based on ADAMTS13 gene analysis in Japan". J. Thromb. Haemost. 9 Suppl 1: 283–301. doi:10.1111/j.1538-7836.2011.04341.x. PMID 21781265.