Details of Disease

General Information of Disease (ID: DIS27CUA)

• Disease Name: Bleeding disorder
• Synonyms: hemorrhagic disease; hemorrhagic diathesis; bleeding tendency; bleeding predisposition; bleeding disorder; bleeding diathesis
• Disease Class: GA20-GA21: Bleeding disorder
• Definition: Spontaneous or near spontaneous bleeding caused by a defect in clotting mechanisms (blood coagulation disorders) or another abnormality causing a structural flaw in the blood vessels (hemostatic disorders).
• Disease Hierarchy:
  DIS9XD9A: Hematologic disease
  DIS27CUA: Bleeding disorder
• ICD Code:
  ICD-11: ICD-11: GA20-GA21
  ICD-10: ICD-10: R58
  Expand ICD-11: 'MG27
  Expand ICD-10: 'R58
  Expand ICD-9: 444453
• Disease Identifiers:
  MONDO ID: MONDO_0002243
  MESH ID: D006474
  UMLS CUI: C0019087
  MedGen ID: 6799

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 14 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Aminocaproic Acid	DMFGND4	Approved	Small molecular drug	[1]
Aprotinin	DM0QD4W	Approved	Small molecular drug	[2]
Baquting	DME1DJX	Approved	NA	[3]
Carbazochrome salicylate	DM4MW27	Approved	Small molecular drug	[3]
Dicumarol	DMFQCB1	Approved	Small molecular drug	[4]
Ethanolamine oleate	DM3B654	Approved	Small molecular drug	[3]
Human prothrombin complex concentrate	DMPHVQ1	Approved	NA	[3]
Human thrombin	DM9NTWT	Approved	NA	[3]
Microfibrillar collagen hemostat	DML4XT2	Approved	NA	[3]
Pentastarch	DM9530T	Approved	NA	[3]
Phytonadione	DM8HDOL	Approved	Small molecular drug	[5]
Protamine	DM1FEIY	Approved	NA	[3]
Recombinant Factor IX	DMY7ESM	Approved	NA	[6]
Thrombin-JMI	DMA8C5Q	Approved	NA	[3]

This Disease is Treated as An Indication in 6 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
PRT4445	DMVU8RW	Phase 3	NA	[7]
Vatreptacog alfa (activated)	DMANKTO	Phase 3	NA	[8]
MOD-5014	DMTHWDM	Phase 2	NA	[9]
TT-173	DMSIXG4	Phase 2	NA	[10]
MEDI8111	DME3YDT	Phase 1	NA	[11]
TDM-621	DMBER9H	Phase 1	NA	[12]

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
CU-2010	DM9SGX8	Discontinued in Phase 2	NA	[13]
Infusible platelet membrane	DMJD62H	Discontinued in Phase 2	NA	[14]
BCX-1470	DMN2XR7	Discontinued in Phase 1	Small molecular drug	[15]

This Disease is Treated as An Indication in 1 Preclinical Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Andexanet alfa	DMZK4DY	Application submitted	NA	[9]

This Disease is Treated as An Indication in 11 Investigative Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Haempatch	DMO6MGJ	Investigative	NA	[16]
HXTC-901	DMDTSRT	Investigative	NA	[1]
Long-acting Factor VII conjugate	DMAH0RZ	Investigative	NA	[17]
PeproStat	DM06ILP	Investigative	NA	[1]
PM-102	DMVDJPY	Investigative	NA	[1]
PRT-064445	DMOVE31	Investigative	NA	[18]
TB-101	DMCZIFS	Investigative	NA	[16]
TB-102	DMUN8CG	Investigative	NA	[16]
Textilinin	DMHBMJZ	Investigative	NA	[19]
TT-111	DM3NVGM	Investigative	Small molecular drug	[1]
TT-112	DM6FPG6	Investigative	NA	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 6 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
F9	TTFEZ5Q	Limited	Genetic Variation	[21]
VWF	TT3SZBT	Limited	Genetic Variation	[22]
TBXA2R	TT2O84V	Disputed	Biomarker	[23]
F7	TTF0EGX	Strong	Biomarker	[24]
F8	TT1290U	Strong	Biomarker	[25]
VKORC1	TTEUC8H	Strong	Altered Expression	[26]

This Disease Is Related to 3 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
SERPINF2	OTZGAF8B	Limited	Biomarker	[27]
AK3	OTM59ZGG	Strong	Genetic Variation	[28]
GNAS	OTMH8BKJ	Strong	Biomarker	[29]

References

• [1] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6570).
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6808).
• [5] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5286).
• [6] DAILYMED.nlm.nih.gov:IXINITY- coagulation factor ix (recombinant)
• [7] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031853)
• [8] ClinicalTrials.gov (NCT01392547) Efficacy and Safety of NNC 0078-0000-0007 in Patients With Congenital Haemophilia and Inhibitors. U.S. National Institutes of Health.
• [9] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [10] ClinicalTrials.gov (NCT02012569) Determine the Haemostatic Efficacy of TT-173, Reducing the Bleeding Time in the Donor Site of Skin Grafting. U.S. National Institutes of Health.
• [11] ClinicalTrials.gov (NCT01958645) To Assess Safety, Tolerability and Pharmacodynamics of Intravenous MEDI8111 After Single Ascending Doses.. U.S. National Institutes of Health.
• [12] Initial clinical trial of a novel hemostat, TDM-621, in the endoscopic treatments of the gastric tumors. J Gastroenterol Hepatol. 2014 Dec;29 Suppl 4:77-9.
• [13] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800028691)
• [14] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009054)
• [15] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009938)
• [16] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2362).
• [17] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2363).
• [18] Semuloparin for the prevention of venous thromboembolic events in cancer patients. Drugs Today (Barc). 2012 Jul;48(7):451-7.
• [19] Tranexamic acid in trauma: how should we use it. J Trauma Acute Care Surg. 2013 Jun;74(6):1575-86.
• [20] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4459).
• [21] Genetic diagnosis of haemophilia and other inherited bleeding disorders.Haemophilia. 2006 Jul;12 Suppl 3:82-9. doi: 10.1111/j.1365-2516.2006.01263.x.
• [22] Genome-Wide Association Transethnic Meta-Analyses Identifies Novel Associations Regulating Coagulation Factor VIII and von Willebrand Factor Plasma Levels.Circulation. 2019 Jan 29;139(5):620-635. doi: 10.1161/CIRCULATIONAHA.118.034532.
• [23] A novel thromboxane A2 receptor D304N variant that abrogates ligand binding in a patient with a bleeding diathesis. Blood. 2010 Jan 14;115(2):363-9. doi: 10.1182/blood-2009-08-236976. Epub 2009 Oct 14.
• [24] Intracellular readthrough of nonsense mutations by aminoglycosides in coagulation factor VII.J Thromb Haemost. 2006 Jun;4(6):1308-14. doi: 10.1111/j.1538-7836.2006.01915.x.
• [25] Acquired hemophilia A in chronic lymphocytic leukemia: A case report.Transfus Apher Sci. 2019 Aug;58(4):447-448. doi: 10.1016/j.transci.2019.04.030. Epub 2019 Jul 10.
• [26] VKCFD2 - from clinical phenotype to molecular mechanism.Hamostaseologie. 2016 Nov 8;36(Suppl. 2):S13-S20.
• [27] A single thymine nucleotide deletion responsible for congenital deficiency of plasmin inhibitor.Thromb Haemost. 2002 Jul;88(1):144-8.
• [28] Carrier detection and prenatal diagnosis of hemophilia in developing countries.Semin Thromb Hemost. 2005 Nov;31(5):544-54. doi: 10.1055/s-2005-922226.
• [29] Genetic variation of the extra-large stimulatory G protein alpha-subunit leads to Gs hyperfunction in platelets and is a risk factor for bleeding.Thromb Haemost. 2001 Sep;86(3):733-8.