Details of Disease

General Information of Disease (ID: DIS3LDOU)

• Disease Name: Thrombotic thrombocytopenic purpura
• Synonyms: Moschcowitz disease; TTP; Moschowitz disease; Moschcowitz's syndrome
• Disease Class: 3B64: Thrombocytopenia
• Definition: Thrombotic thrombocytopenic purpura (TTP) is an aggressive and life-threatening form of thrombotic microangiopathy (TMA) characterized by profound peripheral thrombocytopenia, microangiopathic hemolytic anemia (MAHA) and organ failure of variable severity and is comprised of congenital TTP and acquired TTP.
• Disease Hierarchy:
  DISQR7U7: Thrombophilia
  DISZI5Z8: Thrombocytopenic purpura
  DIS3LDOU: Thrombotic thrombocytopenic purpura
• ICD Code:
  ICD-11: ICD-11: 3B64.14
  ICD-10: ICD-10: M31.1
  Expand ICD-11: '3B64.14
  Expand ICD-10: 'M31.1
• Disease Identifiers:
  MONDO ID: MONDO_0018896
  MESH ID: D011697
  UMLS CUI: C0034155
  MedGen ID: 48266
  Orphanet ID: 54057
  SNOMED CT ID: 78129009

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 2 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Caplacizumab	DMPUKA7	Approved	Antibody	[1]
Rituximab	DM1YVZT	Approved	Antibody	[2]

This Disease is Treated as An Indication in 3 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
ALX-0081	DM7EBH9	Phase 3	NA	[3]
TAK-755	DMVYXFK	Phase 3	Enzyme replacement	[4]
BAX-930	DM3UG12	Phase 1	NA	[3]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 7 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CACNA1S	TT94HRF	Disputed	Genetic Variation	[5]
CD248	TTYJWT7	Disputed	Biomarker	[6]
F3	TT38MDJ	Strong	Biomarker	[7]
PLG	TTP86E2	Strong	Altered Expression	[8]
TFPI	TT068JH	Strong	Biomarker	[7]
THBD	TTAPV67	Strong	Biomarker	[7]
MAPKAPK2	TTMUG9D	Definitive	Biomarker	[9]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC25A10	DTJYKDQ	Definitive	Altered Expression	[10]

This Disease Is Related to 11 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
SH3BP4	OTVIRKW7	Limited	Genetic Variation	[11]
ADAMTSL4	OTBILJMW	Disputed	Biomarker	[12]
CFHR1	OT72R16T	Disputed	Biomarker	[13]
CFHR3	OTYL8SDO	Disputed	Biomarker	[13]
DGKE	OTWS86AS	Disputed	Genetic Variation	[14]
HLA-DRB3	OT5PM9N7	Disputed	Altered Expression	[15]
PHEX	OTG7N3J7	Disputed	Biomarker	[16]
SERPINF2	OTZGAF8B	Disputed	Altered Expression	[17]
BRF1	OTQC6DMG	Definitive	Biomarker	[18]
CLEC1B	OTO38TRG	Definitive	Altered Expression	[10]
KCNH8	OT3I5FLB	Definitive	Altered Expression	[19]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [2] Thrombotic Thrombocytopenic Purpura: Pathophysiology, Diagnosis, and Management. J Clin Med. 2021 Feb 2;10(3):536.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] ClinicalTrials.gov (NCT03393975) A Phase 3, Prospective, Randomized, Controlled, Open-label, Multicenter, 2 Period Crossover Study With a Single Arm Continuation Evaluating the Safety And Efficacy of BAX 930 (rADAMTS13) in the Prophylactic And On-demand Treatment of Subjects With Severe Congenital Thrombotic Thrombocytopenic Purpura (cTTP, Upshaw-Schulman Syndrome [USS], Hereditary Thrombotic Thrombocytopenic Purpura [hTTP]). U.S.National Institutes of Health.
• [5] The alpha(1S) subunit of the L-type calcium channel is not a predisposition gene for thyrotoxic periodic paralysis.Clin Endocrinol (Oxf). 2007 Feb;66(2):229-34. doi: 10.1111/j.1365-2265.2006.02713.x.
• [6] Rapid isolation of high-affinity human antibodies against the tumor vascular marker Endosialin/TEM1, using a paired yeast-display/secretory scFv library platform.J Immunol Methods. 2011 Jan 5;363(2):221-32. doi: 10.1016/j.jim.2010.09.001. Epub 2010 Sep 15.
• [7] Decreased plasma tissue factor pathway inhibitor levels in patients with thrombotic thrombocytopenic purpura.Thromb Haemost. 1995 Jan;73(1):10-4.
• [8] Comparison of ADAMTS13 and Von Willebrand factor levels and activities, and plasminogen levels, in plasma products currently available for the treatment of thrombotic thrombocytopenic purpura in South Africa.Transfus Apher Sci. 2019 Feb;58(1):72-78. doi: 10.1016/j.transci.2018.11.005. Epub 2018 Dec 5.
• [9] The Role of TTP Phosphorylation in the Regulation of Inflammatory Cytokine Production by MK2/3.J Immunol. 2019 Oct 15;203(8):2291-2300. doi: 10.4049/jimmunol.1801221. Epub 2019 Sep 16.
• [10] Elevated plasma levels of soluble C-type lectin-like receptor 2 (CLEC2) in patients with thrombotic microangiopathy.Thromb Res. 2019 Jun;178:54-58. doi: 10.1016/j.thromres.2019.03.018. Epub 2019 Mar 28.
• [11] Genetic polymorphisms in RNA binding proteins contribute to breast cancer survival.Int J Cancer. 2013 Feb 1;132(3):E128-38. doi: 10.1002/ijc.27789. Epub 2012 Sep 18.
• [12] The ADAMTS(L) family and human genetic disorders.Hum Mol Genet. 2011 Oct 15;20(R2):R163-7. doi: 10.1093/hmg/ddr361. Epub 2011 Aug 31.
• [13] Autoimmune forms of thrombotic microangiopathy and membranoproliferative glomerulonephritis: Indications for a disease spectrum and common pathogenic principles.Mol Immunol. 2009 Sep;46(14):2801-7. doi: 10.1016/j.molimm.2009.05.018. Epub 2009 Jul 28.
• [14] Complement activation in diseases presenting with thrombotic microangiopathy.Eur J Intern Med. 2013 Sep;24(6):496-502. doi: 10.1016/j.ejim.2013.05.009. Epub 2013 Jun 4.
• [15] Human leukocyte antigen association in idiopathic thrombotic thrombocytopenic purpura: evidence for an immunogenetic link.J Thromb Haemost. 2010 Feb;8(2):257-62. doi: 10.1111/j.1538-7836.2009.03692.x. Epub 2009 Nov 17.
• [16] Management of thrombotic thrombocytopenic purpura without plasma exchange: the Jehovah's Witness experience.Blood Adv. 2017 Oct 30;1(24):2161-2165. doi: 10.1182/bloodadvances.2017012351. eCollection 2017 Nov 14.
• [17] Plasmin cleavage of von Willebrand factor as an emergency bypass for ADAMTS13 deficiency in thrombotic microangiopathy.Circulation. 2014 Mar 25;129(12):1320-31. doi: 10.1161/CIRCULATIONAHA.113.006727. Epub 2014 Jan 21.
• [18] IL-33 regulates cytokine production and neutrophil recruitment via the p38 MAPK-activated kinases MK2/3.Immunol Cell Biol. 2019 Jan;97(1):54-71. doi: 10.1111/imcb.12200. Epub 2018 Oct 19.
• [19] ApoA-1 Mimetic Peptide ELK-2A2K2E Decreases Inflammatory Factor Levels Through the ABCA1-JAK2-STAT3-TTP Axis in THP-1-Derived Macrophages.J Cardiovasc Pharmacol. 2018 Jul;72(1):60-67. doi: 10.1097/FJC.0000000000000594.