Thrombotic thrombocytopenic purpura

Summary

Thrombotic thrombocytopenic purpura (MONDO:0018896) is a disease with 1 cohort gene and 42 clinical trials. Top therapeutic interventions include apadamtase alfa, caplacizumab, and danazol.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 12
• Phenotypes (HPO): 22
• Clinical trials: 42

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 1 000 000	0.35	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

22 HPO clinical features (Orphanet curated; top 22 by frequency):

HPO ID	Term	Frequency
HP:0001873	Thrombocytopenia	Very frequent (80-99%)
HP:0001923	Reticulocytosis	Very frequent (80-99%)
HP:0001937	Microangiopathic hemolytic anemia	Very frequent (80-99%)
HP:0002094	Dyspnea	Very frequent (80-99%)
HP:0003324	Generalized muscle weakness	Very frequent (80-99%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001259	Coma	Frequent (30-79%)
HP:0001289	Confusion	Frequent (30-79%)
HP:0001297	Stroke	Frequent (30-79%)
HP:0002014	Diarrhea	Frequent (30-79%)
HP:0002027	Abdominal pain	Frequent (30-79%)
HP:0002315	Headache	Frequent (30-79%)
HP:0045040	Abnormal lactate dehydrogenase activity	Frequent (30-79%)
HP:0000083	Renal insufficiency	Occasional (5-29%)
HP:0000093	Proteinuria	Occasional (5-29%)
HP:0000707	Abnormality of the nervous system	Occasional (5-29%)
HP:0000790	Hematuria	Occasional (5-29%)
HP:0001658	Myocardial infarction	Occasional (5-29%)
HP:0001945	Fever	Occasional (5-29%)
HP:0011675	Arrhythmia	Occasional (5-29%)
HP:0001919	Acute kidney injury	Very rare (<1-4%)
HP:0012101	Decreased serum creatinine	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	thrombotic thrombocytopenic purpura
Mondo ID	MONDO:0018896
MeSH	D011697
Orphanet	54057
DOID	DOID:10772
ICD-11	1708277768
NCIT	C78797
SNOMED CT	78129009
UMLS	C0034155
MedGen	48266
GARD	0016659
MedDRA	10043648
NORD	1769
Is cancer (heuristic)	no

Also known as: Moschcowitz disease · Moschowitz disease · TTP

Data availability: 12 ClinVar variants · 6 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › hematologic disorder › blood coagulation disease › thrombophilia › thrombotic thrombocytopenic purpura

Related subtypes (3): disseminated intravascular coagulation, protein S deficiency, inherited thrombophilia

Subtypes (2): congenital thrombotic thrombocytopenic purpura, acquired thrombotic thrombocytopenic purpura

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

12 retrieved; paginated sample, class counts are floors:

7 pathogenic, 3 pathogenic/likely pathogenic, 1 benign/likely benign, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1343360	NM_139027.6(ADAMTS13):c.3482T>C (p.Ile1161Thr)	ADAMTS13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2004982	NM_139027.6(ADAMTS13):c.2920_2938del (p.Ile974fs)	ADAMTS13	Pathogenic	criteria provided, multiple submitters, no conflicts
2691362	NM_139027.6(ADAMTS13):c.155del (p.Pro52fs)	ADAMTS13	Pathogenic	criteria provided, single submitter
3251337	NM_139027.6(ADAMTS13):c.799_808del (p.Arg267fs)	ADAMTS13	Pathogenic	criteria provided, single submitter
3907105	NC_000009.11:g.(136295222_136297708)_(136298825_136301948)del	ADAMTS13	Pathogenic	criteria provided, single submitter
559588	NM_139027.6(ADAMTS13):c.2209T>C (p.Cys737Arg)	ADAMTS13	Pathogenic	no assertion criteria provided
5801	NM_139027.6(ADAMTS13):c.587C>T (p.Thr196Ile)	ADAMTS13	Pathogenic	criteria provided, multiple submitters, no conflicts
5803	NM_139027.6(ADAMTS13):c.3070T>G (p.Cys1024Gly)	ADAMTS13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
68805	NM_139027.6(ADAMTS13):c.1787C>T (p.Ala596Val)	ADAMTS13	Pathogenic	criteria provided, multiple submitters, no conflicts
68815	NM_139027.6(ADAMTS13):c.3178C>T (p.Arg1060Trp)	ADAMTS13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
559578	NM_139027.6(ADAMTS13):c.581G>T (p.Gly194Val)	ADAMTS13	Uncertain significance	criteria provided, single submitter
559577	NM_139027.6(ADAMTS13):c.3400+141G>A	ADAMTS13	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ADAMTS13	Orphanet:93583	Congenital thrombotic thrombocytopenic purpura

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ADAMTS13	HGNC:1366	ENSG00000160323	Q76LX8	A disintegrin and metalloproteinase with thrombospondin motifs 13	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ADAMTS13	A disintegrin and metalloproteinase with thrombospondin motifs 13	Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ADAMTS13	Protease	yes	3.4.24.87	TSP1_rpt, Peptidase_M12B, ADAM_Cys-rich

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
liver	1
right hemisphere of cerebellum	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ADAMTS13	132	tissue_specific	marker	right lobe of liver, liver, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ADAMTS13	1,125

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ADAMTS13	Q76LX8	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defects of platelet adhesion to exposed collagen	1	11420.0×	0.001	ADAMTS13
Diseases of hemostasis	1	2855.0×	0.001	ADAMTS13
Enhanced cleavage of VWF variant by ADAMTS13	1	2855.0×	0.001	ADAMTS13
Defective VWF cleavage by ADAMTS13 variant	1	2855.0×	0.001	ADAMTS13
Platelet Adhesion to exposed collagen	1	671.8×	0.005	ADAMTS13
Defective B3GALTL causes PpS	1	308.6×	0.008	ADAMTS13
O-glycosylation of TSR domain-containing proteins	1	300.5×	0.008	ADAMTS13
Regulation of clotting cascade	1	233.1×	0.008	ADAMTS13
Diseases associated with O-glycosylation of proteins	1	215.5×	0.008	ADAMTS13
O-linked glycosylation	1	144.6×	0.011	ADAMTS13
Diseases of glycosylation	1	131.3×	0.011	ADAMTS13
Diseases of metabolism	1	80.4×	0.017	ADAMTS13
Hemostasis	1	36.0×	0.034	ADAMTS13
Post-translational protein modification	1	19.2×	0.060	ADAMTS13
Disease	1	13.1×	0.081	ADAMTS13
Metabolism of proteins	1	12.4×	0.081	ADAMTS13

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
response to potassium ion	1	2106.5×	0.004	ADAMTS13
response to amine	1	1872.4×	0.004	ADAMTS13
glycoprotein metabolic process	1	1123.5×	0.004	ADAMTS13
peptide catabolic process	1	1053.2×	0.004	ADAMTS13
cellular response to interleukin-4	1	648.1×	0.005	ADAMTS13
platelet activation	1	267.5×	0.008	ADAMTS13
protein catabolic process	1	237.3×	0.008	ADAMTS13
response to toxic substance	1	210.7×	0.008	ADAMTS13
cellular response to type II interferon	1	208.1×	0.008	ADAMTS13
blood coagulation	1	173.7×	0.008	ADAMTS13
protein processing	1	170.2×	0.008	ADAMTS13
cell-matrix adhesion	1	163.6×	0.008	ADAMTS13
cellular response to tumor necrosis factor	1	163.6×	0.008	ADAMTS13
integrin-mediated signaling pathway	1	160.5×	0.008	ADAMTS13
extracellular matrix organization	1	122.1×	0.009	ADAMTS13
cellular response to lipopolysaccharide	1	98.0×	0.011	ADAMTS13
proteolysis	1	34.2×	0.029	ADAMTS13

Therapeutics

Drugs indicated for this disease

2 approved, 5 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Apadamtase Alfa	Approved (phase 4)
Caplacizumab	Approved (phase 4)
Cyclosporine	Phase 3 (in late-stage trials)
Magnesium Sulfate Anhydrous	Phase 3 (in late-stage trials)
Prednisolone	Phase 3 (in late-stage trials)
Prednisone	Phase 3 (in late-stage trials)
Rituximab	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Aspirin, Danazol, Dexamethasone, Methylprednisolone, Romiplostim.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ADAMTS13	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ADAMTS13	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ADAMTS13	3.4.24.87	ADAMTS13 endopeptidase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	ADAMTS13
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ADAMTS13	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 42.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	21
PHASE2	9
PHASE3	7
PHASE2/PHASE3	2
PHASE4	1
PHASE1/PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04767828	PHASE4	UNKNOWN	A Single Arm Study of Brain Metastasis in Patients With HER2-positive Breast Cancer
NCT04683003	PHASE3	ACTIVE_NOT_RECRUITING	A Study of TAK-755 in Participants With Congenital Thrombotic Thrombocytopenic Purpura
NCT05568147	PHASE2/PHASE3	NOT_YET_RECRUITING	Aspirin for Prophylaxis of TTP
NCT00411801	PHASE3	TERMINATED	Safety and Efficacy Study to Compare Uniplas With Cryosupernatant Plasma in Thrombotic Thrombocytopenic Purpura (TTP)
NCT00713193	PHASE3	COMPLETED	Study of Cyclosporine or Corticosteroids as an Adjunct to Plasma Exchange in Thrombotic Thrombocytopenic Purpura (TTP)
NCT00799773	PHASE3	TERMINATED	Evaluating the Effectiveness of Adding Rituximab to Standard Treatment for Thrombotic Thrombocytopenic Purpura (TTP)
NCT03237819	PHASE3	UNKNOWN	Magnesium Sulfate in Thrombotic Thrombocytopenic Purpura in Intensive Care
NCT03393975	PHASE3	COMPLETED	A Study of BAX 930 in Children, Teenagers, and Adults Born With Thrombotic Thrombocytopenic Purpura (TTP)
NCT04074187	PHASE2/PHASE3	COMPLETED	A Trial of Caplacizumab in Japanese Patients With Acquired Thrombotic Thrombocytopenic Purpura (aTTP)
NCT05468320	PHASE3	COMPLETED	Caplacizumab and Immunosuppressive Therapy Without Firstline Therapeutic Plasma Exchange in Adults With Immune-mediated Thrombotic Thrombocytopenic Purpura
NCT00251277	PHASE1/PHASE2	WITHDRAWN	Use of Rituximab Treatment in Addition to Standard Care for Newly Presenting Thrombotic Thrombocytopenic Purpura
NCT00531089	PHASE2	UNKNOWN	Rituximab in Patients With Relapsed or Refractory TTP-HUS
NCT00726544	PHASE2	TERMINATED	Clinical Outcome Study of ARC1779 Injection in Patients With Thrombotic Microangiopathy
NCT00907751	PHASE2	COMPLETED	Rituximab in Adult Acquired Idiopathic Thrombotic Thrombocytopenic Purpura
NCT00937131	PHASE2	COMPLETED	The Use of Rituximab in Acute Thrombotic Thrombocytopenic Purpura (TTP)
NCT00953771	PHASE2	TERMINATED	Safety Study of Danazol With Plasma Exchange and Steroids for the Treatment of Thrombotic Thrombocytopenic Purpura (TTP)
NCT01554514	PHASE2	COMPLETED	Low Dose Rituximab in Thrombotic Thrombocytopenic Purpura
NCT04588194	PHASE2	UNKNOWN	Romiplostim, Rituximab and Dexamethasone as Frontline Treatment for Immune Thrombocytopenia
NCT05393999	PHASE2	WITHDRAWN	SABRE: A Single-arm Prospective Study Measuring Safety and Tolerability of SARS-CoV-2 Neutralising Antibodies in High-risk Populations
NCT05714969	PHASE2	COMPLETED	A Study of TAK-755 (rADAMTS13) With Little to No Plasma Exchange (PEX) Treatment in Adults With Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP)
NCT01808521	EARLY_PHASE1	COMPLETED	A Pilot Study of N-acetylcysteine in Thrombotic Thrombocytopenia Purpura
NCT01257269	Not specified	RECRUITING	Genotype and Phenotype Correlation in Hereditary Thrombotic Thrombocytopenic Purpura (Upshaw-Schulman Syndrome)
NCT05004493	Not specified	RECRUITING	Biorepository and Registry for Plasma Exchange Patients
NCT06441578	Not specified	RECRUITING	A Survey of Recombinant ADAMTS13 in Participants With Congenital Thrombotic Thrombocytopenic Purpura
NCT06727669	Not specified	RECRUITING	Longitudinal Cohort of Thrombosis and Hemostasis Diseases
NCT06945861	Not specified	RECRUITING	Immunological Aspect of Thrombotic Thrombocytopenic Purpura (TTP)
NCT07205861	Not specified	RECRUITING	Retrospective Epidemiological Study of Patients in the National Cohort of the French TMA Center
NCT07353099	Not specified	NOT_YET_RECRUITING	A Study in Children and, Adults With Congenital Thrombotic Thrombocytopenic Purpura (cTTP) Treated With Adzynma
NCT07429942	Not specified	NOT_YET_RECRUITING	A Study to Learn More About the Treatment of People With Congenital Thrombotic Thrombocytopenic Purpura (cTTP) Who Received Recombinant ADAMTS13 (rADAMTS13) as Part of the Early Access Program
NCT00426686	Not specified	COMPLETED	ADAMTS13 in Thrombotic Thrombocytopenic Purpura
NCT00593229	Not specified	TERMINATED	International Registry and Biorepository for TMA(Thrombotic Microangiopathy)
NCT01931644	Not specified	COMPLETED	At-Home Research Study for Patients With Autoimmune, Inflammatory, Genetic, Hematological, Infectious, Neurological, CNS, Oncological, Respiratory, Metabolic Conditions
NCT01938404	Not specified	TERMINATED	Octaplas Adult TTP Trial
NCT02134171	Not specified	COMPLETED	Early Predictive Factors of Cardiac and Cerebral Involvement in TMA
NCT02626663	Not specified	WITHDRAWN	The Role of Microparticles as a Biomarker
NCT03187652	Not specified	UNKNOWN	A Prospective Study on the Long-Term Vascular Burden in Thrombotic Thrombocytopenic Purpura Patients
NCT03369314	Not specified	COMPLETED	Observational Study of the Use of octaplasLG®.
NCT03605511	Not specified	UNKNOWN	TTP and aHUS in Complicated Pregnancies
NCT04981028	Not specified	UNKNOWN	The ConNeCT Study: Neurological Complications of TTP
NCT05389007	Not specified	UNKNOWN	.German TTP-Registry (Thrombotic Thrombocytopenic Purpura)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
APADAMTASE ALFA	4	4
CAPLACIZUMAB	4	3
DANAZOL	4	1
ROMIPLOSTIM	4	1
MAGNESIUM	3	1
CREXAVIBART	2	1
EGAPTIVON PEGOL	2	1
OGALVIBART	2	1
CHEMBL15720	0	1
CHEMBL406352	0	1
SULFURIC ACID	-1	1