Hemorrhagic disease

Summary

Hemorrhagic disease (MONDO:0002243) is a disease (an umbrella term covering 28 Mondo subtypes) with 32 GWAS associations across 10 studies and 147 clinical trials. Top therapeutic interventions include eptacog alfa (activated), turoctocog alfa, and catridecacog. A subtype of hematologic disorder — broader associated-gene and molecular evidence is on the parent page (see Disease family below).

At a glance

• Umbrella term: 28 Mondo subtypes
• GWAS associations: 32
• Clinical trials: 147

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hemorrhagic disease
Mondo ID	MONDO:0002243
MeSH	D006474
DOID	DOID:2213
NCIT	C115221
UMLS	C0019087
MedGen	6799
Is cancer (heuristic)	no

Also known as: bleeding diathesis · bleeding disorder · bleeding predisposition · bleeding tendency

Data availability: 32 GWAS associations (10 studies) · 13 cell lines.

Disease family

This is a subtype of hematologic disorder. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.

Classification path: disease › human disease › disease by body system or component › hematologic disorder › hemorrhagic disease

Related subtypes (26): autoimmune disorder of blood, blood coagulation disease, blood platelet disease, anemia, splenic disorder, hematopoietic and lymphoid system neoplasm, blood group incompatibility, bone marrow disorder, thymus gland disorder, leukocyte disorder, monoclonal gammopathy, septicemic plague, hyperamylasemia, alpha thalassemia-intellectual disability syndrome type 1, Bloom syndrome, congenital hematological disorder, alpha-thalassemia-myelodysplastic syndrome, deafness-lymphedema-leukemia syndrome, L-ferritin deficiency, dyskeratosis congenita, autosomal dominant 6, polyclonal hyperviscosity syndrome, parasitemia, erythrocyte disorder, premalignant hematological system disease, GATA1-Related X-Linked Cytopenia, paraneoplastic hematological syndrome

Subtypes (28): inherited bleeding disorder, platelet-type, factor VII deficiency, factor X deficiency, purpura, vascular hemostatic disease, congenital factor V deficiency, congenital high-molecular-weight kininogen deficiency, congenital factor XII deficiency, alpha-2-plasmin inhibitor deficiency, hemophilia A, hemophilia B, East Texas bleeding disorder, congenital factor XI deficiency, inherited prekallikrein deficiency, congenital plasminogen activator inhibitor type 1 deficiency, thrombomodulin-related bleeding disorder, congenital vitamin K-dependent coagulation factors deficiency, hemorrhagic disease due to alpha-1-antitrypsin Pittsburgh mutation, multiple sclerosis-ichthyosis-factor VIII deficiency syndrome, congenital factor XIII deficiency, congenital fibrinogen deficiency, combined deficiency of factor V and factor VIII, acquired hemophilia, fetal and neonatal alloimmune thrombocytopenia, hereditary von Willebrand disease, acquired von willebrand syndrome, prothrombin deficiency, hemophilia B leyden

Genetics & variants

GWAS landscape

32 GWAS associations across 10 studies. Top hits map to 15 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
chr9:5073770	7e-59		T	26.09
rs3747207	7e-42	PNPLA3	G	0.15
rs77375493	1e-38	JAK2	G	1.59
rs41303899	7e-33	TUBB1	G	1.05
chr20:1924066	5e-25		T	0.11
rs1354034	2e-24	ARHGEF3	T	0.11
rs56043070	1e-22	GCSAML	G	0.17
rs73517714	1e-21	TPM4	C	0.23
rs74227709	3e-20	GCSAML	G	0.17
rs6132105	2e-18	SIRPA - PDYN-AS1	G	0.09
rs210140	6e-17	BAK1	C	0.08
rs6141	8e-17	THPO	C	0.08
chr19:16207232	3e-15		C	0.31
chr2:43698753	5e-15		G	0.15
chr6:33547440	1e-14		G	0.08
rs113542380	4e-14	THADA	G	0.15
rs7080386	7e-14	JMJD1C	C	0.07
rs187715179	2e-12	GTF3C5	C	0.41
chr3:12299957	2e-12		G	0.07
rs1331309	6e-12	HBS1L	T	0.08
chr10:65096250	7e-12		C	0.07
rs2811708	1e-11	CDKN2A	G	0.08
rs56395424	3e-11	SYN2 - GSTM5P1	G	0.07
rs34164109	4e-11	HBS1L	C	0.07
rs181186063	2e-09	ZNF475, ZNF474	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90475807	Verma A	2024	21,153	412,574	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90473140	UK Biobank Whole-Genome Sequencing Consortium	2025	5,827	452,613	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90475806	Verma A	2024	4,483	113,706	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90479984	Verma A	2024	4,483	113,706	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90477465	Verma A	2024	2,458	55,595	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90079715	Backman JD	2021	2,456	384,489	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083701	Backman JD	2021	2,456	384,489	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90435819	Zhou W	2018	1,791	406,281	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90651335	Liu TY	2025	1,559	231,777	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90246049	Walters RG	2023	161	75,734	Genotyping and population characteristics of the China Kadoorie Biobank.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	2
Tier 3: regulatory	0
Tier 4: intronic/intergenic	21

MAF distribution

Bucket	Variants
common (>=0.05)	19
low_freq (0.01-0.05)	1
rare (<0.01)	3
unknown	2

Functional consequences

Consequence	Count
intron_variant	11
unknown	7
intergenic_variant	3
missense_variant	2
splice_donor_variant	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
chr9:5073770							7e-59	Tier 4: intronic/intergenic
rs3747207	22	43928975	G>A,C,T	0.219	intron_variant	PNPLA3	7e-42	Tier 4: intronic/intergenic
rs77375493	9	5073770	G>A,C,T	0	missense_variant	JAK2	1e-38	Tier 1: coding
rs41303899	20	59023753	G>A	0.001	missense_variant	TUBB1	7e-33	Tier 1: coding
chr20:1924066				0.266			5e-25	Tier 4: intronic/intergenic
rs1354034	3	56815721	T>C	0.429	intron_variant	ARHGEF3	2e-24	Tier 4: intronic/intergenic
rs56043070	1	247556467	G>A,T	0.061	splice_donor_variant	GCSAML	1e-22	Tier 2: splice/UTR
rs73517714	19	16092494	C>A	0.034	intron_variant	TPM4	1e-21	Tier 4: intronic/intergenic
rs74227709	1	247559286	G>A	0.069	intron_variant	GCSAML	3e-20	Tier 4: intronic/intergenic
rs6132105	20	1943028	G>A,C	0.292	intergenic_variant	SIRPA - PDYN-AS1	2e-18	Tier 4: intronic/intergenic
rs210140	6	33576516	C>T	0.392	intron_variant	BAK1	6e-17	Tier 4: intronic/intergenic
rs6141	3	184372478	C>A,G,T	0.457	3_prime_UTR_variant	THPO	8e-17	Tier 2: splice/UTR
chr19:16207232				0.076			3e-15	Tier 4: intronic/intergenic
chr2:43698753				0.071			5e-15	Tier 4: intronic/intergenic
chr6:33547440				0.389			1e-14	Tier 4: intronic/intergenic
rs113542380	2	43237679	G>A	0.058	intron_variant	THADA	4e-14	Tier 4: intronic/intergenic
rs7080386	10	63288546	C>A	0.385	intron_variant	JMJD1C	7e-14	Tier 4: intronic/intergenic
rs187715179	9	133044809	C>T	0.007	intron_variant	GTF3C5	2e-12	Tier 4: intronic/intergenic
chr3:12299957				0.34			2e-12	Tier 4: intronic/intergenic
rs1331309	6	135085040	T>C,G	0.254	intergenic_variant	HBS1L	6e-12	Tier 4: intronic/intergenic
chr10:65096250				0.416			7e-12	Tier 4: intronic/intergenic
rs2811708	9	21973423	G>A,T	0.248	intron_variant	CDKN2A	1e-11	Tier 4: intronic/intergenic
rs56395424	3	12194223	G>A	0.254	intron_variant	SYN2 - GSTM5P1	3e-11	Tier 4: intronic/intergenic
rs34164109	6	135100038	C>T	0.225	intergenic_variant	HBS1L	4e-11	Tier 4: intronic/intergenic
rs181186063	5	122175997	C>A,T		intron_variant	ZNF475, ZNF474	2e-09	Tier 4: intronic/intergenic

Genes & proteins

No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).

Function

No pathway enrichment — requires an associated-gene cohort.

Therapeutics

Drugs indicated for this disease

1 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Idecabtagene Vicleucel	Approved (phase 4)
Eptacog Alfa (Activated)	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Argatroban, Catridecacog, Heparin.

Clinical trials & evidence

Clinical trials

Clinical trials: 147.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	59
PHASE1	34
PHASE3	25
PHASE2	21
PHASE4	6
PHASE2/PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00108797	PHASE4	COMPLETED	Trial of NovoSeven® in Haemophilia - Joint Bleeds
NCT00571584	PHASE4	COMPLETED	High Dose of Activated Recombinant Human Factor VII for Treatment of Mild/Moderate Joint Bleeds in Haemophilia Patients With Inhibitors
NCT01561391	PHASE4	COMPLETED	Safety and Efficacy of Activated Recombinant Human Factor VII in Haemophilia Patients With Inhibitors During and After Major Surgery
NCT02822599	PHASE4	COMPLETED	Human Fibrinogen Concentrate in Pediatric Cardiac Surgery
NCT02864875	PHASE4	COMPLETED	Early Administration of Fibrinogen in Polytraumatized Patients With Hypofibrinogenemia: a Randomized Feasibility Trial
NCT03449342	PHASE4	COMPLETED	Research Study to Look at Side Effects During Regular Injection With Factor VIII Medicine Named Turoctocog Alfa for a 8 Weeks Period
NCT00127283	PHASE3	COMPLETED	Recombinant Factor VIIa in Acute Intracerebral Haemorrhage
NCT00184548	PHASE3	TERMINATED	Evaluation of Recombinant Factor VIIa in Patients With Severe Bleeding
NCT00323570	PHASE3	WITHDRAWN	Evaluation of Recombinant Factor VIIa in Patients With Severe Bleeding Due to Trauma
NCT00713648	PHASE3	COMPLETED	Evaluation of Recombinant Factor XIII for Prevention of Bleeding in Patients With FXIII Inherited Deficiency
NCT00840086	PHASE3	COMPLETED	Safety and Efficacy of Turoctocog Alfa in Haemophilia A Subjects
NCT00978380	PHASE3	COMPLETED	Safety of Monthly Recombinant Factor XIII Replacement Therapy in Subjects With Congenital Factor XIII Deficiency: An Extension to Trial F13CD-1725
NCT00984126	PHASE3	COMPLETED	Safety and Efficacy of Turoctocog Alfa (N8) in Prevention and On-demand Treatment of Bleeding Episodes in Subjects With Haemophilia A: An Extension to Trials NN7008-3543, NN7008-3545, NN7008-3600, NN7008-3893 and NN7008-4015
NCT01138501	PHASE3	COMPLETED	Safety and Efficacy of Turoctocog Alfa in Previously Treated Male Children With Haemophilia A
NCT01230021	PHASE3	COMPLETED	Safety of a Single Intravenous Dose of Recombinant Factor XIII in Children With Congenital FXIII A-subunit Deficiency
NCT01253811	PHASE3	COMPLETED	Safety and Efficacy of Monthly Replacement Therapy With Recombinant Factor XIII (rFXIII) in Paediatric Subjects With Congenital Factor XIII A-subunit Deficiency
NCT01333111	PHASE3	COMPLETED	Safety and Efficacy of NNC-0156-0000-0009 in Haemophilia B Patients
NCT01386528	PHASE3	COMPLETED	Efficacy and Safety of NNC-0156-0000-0009 During Surgical Procedures in Subjects With Haemophilia B
NCT01392547	PHASE3	COMPLETED	Efficacy and Safety of NNC 0078-0000-0007 in Patients With Congenital Haemophilia and Inhibitors
NCT01395810	PHASE3	COMPLETED	Safety and Efficacy of NNC-0156-0000-0009 After Long-Term Exposure in Patients With Haemophilia B: An Extension to Trials NN7999-3747 and NN7999-3773
NCT01467427	PHASE3	COMPLETED	Safety, Efficacy and Pharmacokinetics of NNC-0156-0000-0009 in Previously Treated Children With Haemophilia B.
NCT01480180	PHASE3	COMPLETED	Evaluation of Safety and Efficacy, Including Pharmacokinetics, of NNC 0129-0000-1003 When Administered for Treatment and Prophylaxis of Bleeding in Subjects With Haemophilia A
NCT01489111	PHASE3	COMPLETED	Evaluating the Haemostatic Effect of NNC 0129-0000-1003 During Surgical Procedures in Subjects With Haemophilia A.
NCT01493778	PHASE3	COMPLETED	Safety and Efficacy of Turoctocog Alfa in Prevention and Treatment of Bleeds in Previously Untreated Children With Haemophilia A
NCT01562574	PHASE3	COMPLETED	Activated Recombinant Human Factor VII Following Cardiac Bypass Surgery for Paediatric Congenital Heart Disease
NCT01731600	PHASE3	COMPLETED	A Multinational, Open-Label, Non-Controlled Trial on Safety, Efficacy and Pharmacokinetics of NNC 0129-0000-1003 in Previously Treated Paediatric Patients With Severe Haemophilia A
NCT02137850	PHASE3	COMPLETED	Safety and Efficacy of Turoctocog Alfa Pegol (N8-GP) in Previously Untreated Patients With Haemophilia A
NCT02141074	PHASE3	COMPLETED	Safety and Efficacy of Nonacog Beta Pegol (N9-GP) in Previously Untreated Patients With Haemophilia B
NCT02938585	PHASE3	COMPLETED	Efficacy and Safety of Turoctocog Alfa for Prophylaxis and Treatment of Bleeding Episodes in Previously Treated Chinese Patients With Haemophilia A
NCT03444324	PHASE3	COMPLETED	Adjusted Fibrinogen Replacement Strategy
NCT03528551	PHASE3	COMPLETED	A Research Study Looking at How a Factor VIII Medicine Called Turoctocog Alfa Pegol (N8-GP) Works in People With Haemophilia A
NCT04188171	PHASE2/PHASE3	UNKNOWN	Sclerotherapy With Polidocanol Foam In The Treatment Of Hemorrhoidal Disease In Patients With Bleeding Disorders
NCT00102037	PHASE2	COMPLETED	Use of Activated Recombinant FVII in Spinal Surgery
NCT00108758	PHASE2	COMPLETED	Efficacy of NovoSeven® in Bleeding Prophylaxis in Hemophilia
NCT00123591	PHASE2	COMPLETED	Safety and Preliminary Efficacy of Recombinant Activated Factor VII in Subjects With Traumatic Brain Injury
NCT00154427	PHASE2	TERMINATED	Use of Activated Recombinant Human Factor VII in Cardiac Surgery
NCT00154492	PHASE2	COMPLETED	Use of NovoSeven® in Active Variceal Bleeding
NCT00266006	PHASE2	COMPLETED	Factor VIIa in Acute Intracerebral Haemorrhage
NCT00426803	PHASE2	COMPLETED	Recombinant Factor VIIa in Acute Intracerebral Haemorrhage
NCT00486278	PHASE2	COMPLETED	Haemophilia Patients With Inhibitors Being Treated for Acute Joint Bleeds

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
EPTACOG ALFA (ACTIVATED)	4	51
TUROCTOCOG ALFA	4	15
CATRIDECACOG	4	12
TUROCTOCOG ALFA PEGOL	4	8
NONACOG BETA PEGOL	4	6
CONCIZUMAB	4	5
NORETHINDRONE ACETATE	4	1
SODIUM CHLORIDE	4	1
THROMBIN	4	1
VATREPTACOG ALFA (ACTIVATED)	3	3
FIBRINOGEN, HUMAN	3	1
PLATELETS	3	1
EPTACOG ALFA PEGOL (ACTIVATED)	2	3
CHEMBL3638292	0	1
CHEMBL255682	0	1
CHEMBL4091490	0	1