Thrombocytopenia
Disease synonyms
THC
Inheritance pattern
Autosomal recessive, autosomal dominant, X-linked recessive, somatic
Clinical features
Thrombocytopenia is a disorder of haematopoetic cells with predominant defects of platelets and it is defined as having a platelet count of less than 150,000 in mL of circulating blood, while the normal number of platelets ranges between 150,000 and 450,000 cells per mL of blood 1. Platelets are haemopoetic cells that play a primary role in haemostasis, interacting with subendothelium-bound von Willebrand factor (vWF) via the membrane glycoprotein complexes.
Platelet adhesion is the initial interaction in blood coagulation and control of bleeding. The estimated incidence of X-linked thrombocytopenia and Wiskott-Aldrich Syndrome is between 1 and 10 per million males worldwide 2. The prevalence of thrombocytopenia absent radius syndrome is estimated at 1:200,000-1:100,000 3. Causes of thrombocytopenia include decreased platelet production, increased platelet destruction, increased splenic sequestration, and dilution.
The major clinical signs and symptoms of thrombocytopenia may include the following:
- Easy or excessive bruising (“purpura”)
- Superficial bleeding into the skin (“petechiae”) (typically most evident on the lower legs)
- Scattered small ecchymosis at sites of minor trauma
- Prolonged bleeding
- Bleeding from gums or nose
- Blood in urine or stool
- Fatigue
- Enlarged spleen
- Jaundice.
Thrombocytopenia usually presents in infancy or early childhood, most commonly with intensive and frequent mucosal bleeding, bloody diarrhea, intermittent petechiae and purpura, and recurrent bacterial and viral infections 4. At least 40% of affected individuals also develop one or more autoimmune conditions, including hemolytic anemia, immune thrombocytopenic purpura, immune-mediated neutropenia, rheumatoid arthritis, vasculitis, and immune-mediated damage to the kidneys and liver 1, 4.
Clinical expression of thrombocytopenia has broad spectrum of variations ranging from asymptomatic to life-threatening bleeding conditions. Various syndromes and diseases are associated with thrombocytopenia, including the following:
Wiskott-Aldrich syndrome caused by mutations in the WAS gene should be suspected in males affected with:
- Profound thrombocytopenia (<70,000 platelets/mL)
- Small platelet size (>2 SD below the mean)
- Recurrent bacterial or viral infection
- Eczema
- Autoimmune disorder
- Lymphoma
- Family history of one or more maternally related males with a WAS-related phenotype or disorder.
X-linked thrombocytopenia (XLT) also caused by mutations in the WAS gene 4 should be suspected in affected males with:
- Congenital thrombocytopenia (5,000-50,000 platelets/mL) 4
- Small platelet size
- Absence of other clinical findings of Wiskott-Aldrich syndrome
- Family history of one or more maternally related males with a WAS-related phenotype or disorder.
X-linked congenital neutropenia (XLN) also caused by mutation in the WAS gene 5 characterized with the following clinical features in affected males:
- Recurrent bacterial or viral infections
- Persistent neutropenia
- Arrested development of the bone marrow in the absence of other clinical findings of Wiskott-Aldrich syndrome TAR syndrome is thrombocytopenia-related disorder characterized by thrombocytopenia and absence of radius 6.
TAR syndrome is caused by mutations in RBM8A, encoding RNA regulatory protein. Diagnosis of TAR syndrome is established in a patient who has both of the following features:
- Bilateral absence of the radii with the presence of both thumbs
- Thrombocytopenia (usually <50,000 platelets/mL) 6.
Bernard Soulier syndrome (BSS) is an inherited platelet disorder characterized by mild to severe bleeding tendency, macrothrombocytopenia and absent ristocetin-induced platelet agglutination. BSS is caused by mutations in the GP1BA, GP1BB, or GP9 genes 7.
Glanzmann thrombasthenia platelet-type bleeding disorder is a congenital macrothrombocytopenia associated with platelet anisocytosis mildly increased bleeding tendency. Glanzmann thrombasthenia can be caused by mutations in the integrin-related genes ITGA2B or ITGB3 8.
Thrombocytopenia with beta-thalassemia is a hereditary thrombocytopenia caused by mutations in the GATA1 gene, encoding transcription factor GATA binding protein 9. The major clinical features of this thrombocytopenia subtype include variable thrombocytopenia, hemolytic anemia, splenomegaly, and abnormalities in hemoglobin chain synthesis.
Additional thrombocytopenia-related conditions are caused by mutations in MYH9, encoding nonmuscular myosin heavy chain 9 protein:
Epstein syndrome is an autosomal dominant disorder characterized by thrombocytopenia, giant platelets, nephritis, and deafness 10.
Fechtner syndrome is an autosomal dominant disorder characterized by the triad of thrombocytopenia, giant platelets, and Dohle-like body inclusions in peripheral blood leukocytes, with the additional features of nephritis, hearing loss, and eye abnormalities, mostly cataracts 10.
Sebastian syndrome is an autosomal dominant disorder characterized by the triad of thrombocytopenia, giant platelets, and inclusions in peripheral blood leukocytes 10.
May-Hegglin anomaly is an autosomal dominant disorder characterized by the triad of thrombocytopenia, giant platelets, and Dohle-like body inclusions in peripheral blood leukocytes. About 25-50% of affected individuals have mild to moderate episodic bleeding 11.
Gene | OMIM (Gene) | Associated diseases (OMIM) | Inheritance |
---|---|---|---|
ABCB7 | 300135 | Anemia, Sideroblastic, and Spinocerebellar Ataxia | XLR |
ACTN1 | 102575 | Bleeding disorder, platelet-type, 15 | AD |
ADAMTS13 | 604134 | thrombotic thrombocytopenic purpura | AR |
AK2 | 103020 | Reticular dysgenesis | AR |
ALAS2 | 301300 | X-linked sideroblastic anemia; Protoporphyria, erythropoietic, X-linked | XL, XLR |
AMN | 605799 | AR | |
ANK1 | 612641 | Spherocytosis, type 1 | AD, AR |
ANKRD26 | 610855 | thrombocytopenia type 2 | AD |
AP3B1 | 603401 | Hermansky-Pudlak syndrome type 2 | AR |
ATM | 607585 | familial breast-ovarian cancer type 2; ataxia-telangiectasia | AD, AR |
ATRX | 300032 | Alpha-Thalassemia Myelodysplasia Syndrome; Alpha-Thalassemia/Mental Retardation Syndrome, X-Linked; Mental retardation-hypotonic facies syndrome, X-linked | XLD, XLR |
BLM | 604610 | Bloom syndrome | AR |
BLOC1S3 | 609762 | Hermansky-Pudlak syndrome 8 | AR |
BRCA1 | 113705 | familial breast-ovarian cancer type 1; pancreatic cancer type 4; Fanconi anemia, complementation group S | AD, AR |
BRCA2 | 600185 | familial breast-ovarian cancer type 2; Medulloblastoma; Prostate Cancer; Wilms tumor, type 1; Fanconi anemia complementation group D1; pancreatic cancer type 2 | AD, AR |
BRIP1 | 605882 | familial breast-ovarian cancer type 2; Fanconi anemia of complementation group J | AD |
CASP10 | 601762 | Autoimmune lymphoproliferative syndrome, type II; Lymphoma, non-Hodgkin; Gastric Cancer | AD |
CBL | 165360 | Leukemia, juvenile myelomonocytic; Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia | AD |
CBLIF | 609342 | Intrinsic factor deficiency | AR |
CD36 | 173510 | Platelet glycoprotein IV deficiency; resistance to malaria | AR |
CD40LG | 300386 | Immunodeficiency With Hyper-Igm, Type 1 | XLR |
CDAN1 | 607465 | congenital dyserythropoietic anemia 1 | AR |
CDIN1 | 615626 | congenital dyserythropoietic anemia 1b | AR |
CENPJ | 609279 | primary microcephaly 6; Seckel syndrome 4 | AR |
CEP152 | 613529 | Seckel syndrome 5; primary microcephaly 9 | AR |
CLCN7 | 602727 | Osteopetrosis, autosomal dominant 2; Osteopetrosis, autosomal recessive 4 | AD, AR |
CLPB | 616254 | 3-methylglutaconic aciduria type VII with cataracts, neurologic involvement and neutropenia | AR |
CSF3R | 138971 | Neutropenia, severe congenital, 7, autosomal recessive | AR |
CTC1 | 613129 | Cerebroretinal microangiopathy with calcifications and cysts | AR |
CUBN | 602997 | megaloblastic anemia 1 | AR |
CXCR4 | 162643 | WHIM syndrome | AD |
CYB5R3 | 613213 | methemoglobinemia type I | AR |
CYCS | 123970 | Thrombocytopenia 4 | AD |
DHFR | 126060 | AR | |
DIAPH1 | 602121 | Deafness, autosomal dominant 1; Seizures, cortical blindness, microcephaly syndrome | AD, AR |
DKC1 | 300126 | X-linked dyskeratosis congenita | XLR |
DTNBP1 | 607145 | Hermansky-Pudlak syndrome 7 | AR |
ELANE | 130130 | Neutropenia, cyclic; Neutropenia, severe congenital 1, autosomal dominant | AD |
EPB42 | 177070 | Spherocytosis, type 5 | |
ERCC4 | 133520 | xeroderma pigmentosum complementation group F; XFE prpgeroid syndroem; Fanconi anemia of complementation group Q | AR |
FANCA | 607139 | Fanconi anemia complementation group A | AR |
FANCB | 300515 | Fanconi anemia of complementation group B | XLR |
FANCC | 613899 | Fanconi anemia of complementation group C | AR |
FANCD2 | 613984 | Fanconi anemia of complementation group D2 | AR |
FANCE | 613976 | Fanconi anemia of complementation group E | AR |
FANCF | 613897 | Fanconi anemia of complementation group F | |
FANCG | 602956 | Fanconi anemia of complementation group G | |
FANCI | 611360 | Fanconi anemia of complementation group I | AR |
FANCL | 608111 | Fanconi anemia of complementation group L | AR |
FANCM | 609644 | Spermatogenic failure 28 | AR |
FAS | 134637 | Autoimmune lymphoproliferative syndrome | AD |
FASLG | 134638 | Lung Cancer; Autoimmune lymphoproliferative syndrome | AD |
G6PC3 | 611045 | Neutropenia, severe congenital 4, autosomal recessive | AR |
G6PD | 305900 | glucose-6-phosphate dehydrogenase deficiency; resistance to malaria | XLD |
GATA1 | 305371 | X-linked congenital dyserythropoietic anemia with thrombocytopenia; Anemia, X-linked, with/without neutropenia and/or platelet abnormalities; beta-thalassemia - X-linked thrombocytopenia | XLR |
GFI1 | 600871 | Neutropenia, severe congenital 2, autosomal dominant | AD |
GFI1B | 604383 | Bleeding disorder, platelet-type, 17 | AD, AR |
GLRX5 | 609588 | Anemia, sideroblastic, 3, pyridoxine-refractory | AR |
GNE | 603824 | Sialuria; Nonaka myopathy | AD, AR |
GP1BA | 606672 | Bernard-Soulier syndrome, type A2 (dominant); platelet type von Willebrand disease; Bernard-Soulier syndrome, type C | AD, AR |
GP1BB | 138720 | Bernard-Soulier syndrome, type C | AR |
GP9 | 173515 | Bernard-Soulier syndrome, type C | AR |
GPI | 172400 | nonspherocytic hemolytic anemia due to glucose phosphate isomerase deficiency | AR |
GSS | 601002 | Glutathione synthetase deficiency | AR |
HAX1 | 605998 | autosomal recessive severe congenital neutropenia type 3 | AR |
HBA1 | 141800 | Heinz Body Anemias; alpha-Thalassemia; Hemoglobin H Disease | AD |
HBA2 | 141850 | Heinz Body Anemias; alpha-Thalassemia; Hemoglobin H Disease | AD |
HBB | 141900 | Heinz Body Anemias; Delta-beta thalassemia; dominantly inherited inclusion body beta-thalassemia; sickle cell anemia; resistance to malaria; beta-thalassemia | AD, AR |
HFE | 613609 | Alzheimer Disease; hepatoerythropoietic porphyria; variegate porphyria; hemochromatosis type 1; susceptibility to microvascular complications of diabetes type 7; Transferrin serum level QTL2 | AD, AR |
HOXA11 | 142958 | Radioulnar synostosis with amegakaryocytic thrombocytopenia 1 | AD |
HPS1 | 604982 | Hermansky-Pudlak syndrome type 1 | AR |
HPS3 | 606118 | Hermansky-Pudlak syndrome type 3 | AR |
HPS4 | 606682 | Hermansky-Pudlak syndrome type 4 | AR |
HPS5 | 607521 | Hermansky-Pudlak syndrome type 5 | AR |
HPS6 | 607522 | Hermansky-Pudlak syndrome type 6 | AR |
HSPA9 | 600548 | Sideroblastic anemia type 4 | AD, AR |
IL2RG | 308380 | Severe X-linked combined immunodeficiency; moderate X-linked combined immunodeficiency | XLR |
ITGA2B | 607759 | Bleeding disorder, platelet-type, 16, autosomal dominant; Glanzmann thrombasthenia | AD, AR |
ITGB3 | 173470 | Bleeding disorder, platelet-type, 16, autosomal dominant; Glanzmann thrombasthenia; Myocardial infarction, decreased susceptibility to | AD, AR |
ITK | 186973 | Lymphoproliferative syndrome 1 | AR |
JAGN1 | 616012 | Neutropenia, severe congenital, 6, autosomal recessive | AR |
KLF1 | 600599 | Blood group--lutheran inhibitor; Fetal hemoglobin quantitative trait locus 6; Anemia, congenital dyserythropoietic, type iv | AD |
KRAS | 190070 | Arteriovenous malformations of the brain; Bladder Cancer; familial breast-ovarian cancer type 2; Gastric Cancer, Hereditary Diffuse; Schimmelpenning-Feuerstein-Mims Syndrome; Lung Cancer; Pancreatic Cancer; acute myeloid leukemia; Noonan syndrome 3; Autoimmune lymphoproliferative syndrome type IV; Cardiofaciocutaneous syndrome 2 | AD |
LIG4 | 601837 | LIG4 syndrome | AR |
LPIN2 | 605519 | Majeed syndrome | |
LYST | 606897 | Chediak-Higashi syndrome | AR |
MLH1 | 120436 | Muir-Torre syndrome; mismatch repair cancer syndrome; hereditary nonpolyposis colorectal cancer-2 | AD, AR |
MPL | 159530 | somatic myelofibrosis with myeloid metaplasia; thrombocythemia type 2; congenital amegakaryocytic thrombocytopenia | AD, AR |
MRE11 | 600814 | Ataxia-telangiectasia-like disorder type 1 | AR |
MSH2 | 609309 | Lynch syndrome; Muir-Torre syndrome; mismatch repair cancer syndrome | AD, AR |
MSH6 | 600678 | mismatch repair cancer syndrome; endometrial cancer; hereditary nonpolyposis colorectal cancer-5 | AD, AR |
MTR | 156570 | homocystinuria-megaloblastic anemia, cblG complementation type; folate-sensitive neural tube defects | AR |
MTRR | 602568 | Homocystinuria-Megaloblastic Anemia, Cble Complementation Type; folate-sensitive neural tube defects | AR |
MYH9 | 160775 | Fechtner syndrome; Macrothrombocytopenia and progressive sensorineural deafness; May-Hegglin anomaly; Sebastian syndrome; deafness type 17 | AD |
NBN | 602667 | Nijmegen breakage syndrome; Aplastic Anemia; Acute lymphoblastic leukemia | AR |
NF1 | 613113 | neurofibromatosis type 1; Neurofibromatosis-Noonan syndrome; Leukemia, juvenile myelomonocytic | AD |
NHP2 | 606470 | Dyskeratosis Congenita, Autosomal Recessive, 2 | AR |
NOP10 | 606471 | Dyskeratosis Congenita, Autosomal Recessive, 1 | AR |
NRAS | 164790 | colorectal cancer; Melanocytic nevus syndrome, congenital, somatic; Nevus, Epidermal; Schimmelpenning-Feuerstein-Mims Syndrome; Thyroid Carcinoma, Follicular; Neurocutaneous melanosis, somatic; Noonan syndrome 6; Autoimmune lymphoproliferative syndrome type IV | AD |
PALB2 | 610355 | familial breast-ovarian cancer type 2; Fanconi anemia of complementation group N; Pancreatic cancer, susceptibility to, 3 | AD |
PARN | 604212 | Dyskeratosis congenita, autosomal recessive 6; telomere-related pulmonary fibrosis and/or bone marrow failure type 4 | AD, AR |
PC | 608786 | pyruvate carboxylase deficiency | AR |
PDHA1 | 300502 | Pyruvate dehydrogenase E1-alpha deficiency | XLD |
PDHX | 608769 | Lacticacidemia due to PDX1 deficiency | AR |
PKLR | 609712 | pyruvate kinase deficiency | AD, AR |
PMS2 | 600259 | mismatch repair cancer syndrome; hereditary nonpolyposis colorectal cancer-4 | AR |
PRF1 | 170280 | familial hemophagocytic lymphohistiocytosis 2; Lymphoma, non-Hodgkin; Aplastic Anemia | AR |
PTPN11 | 176876 | LEOPARD syndrome 1; Noonan syndrome 1; Leukemia, juvenile myelomonocytic | AD |
PUS1 | 608109 | myopathy, lactic acidosis and sideroblastic anemia type 1 | AR |
RAC2 | 602049 | Neutrophil immunodeficiency syndrome | |
RAD51C | 602774 | Fanconi anemia of complementation group O; Breast-ovarian cancer, familial, susceptibility to, 3 | AR |
RBBP8 | 604124 | Jawad syndrome / Microcephaly with mental retardation and digital anomalies; Seckel syndrome 2 | AR |
RBM8A | 605313 | Thrombocytopenia-absent radius syndrome | AR |
RIT1 | 609591 | Noonan syndrome 8 | AD |
RPL11 | 604175 | Diamond-Blackfan anemia 7 | AD |
RPL15 | 604174 | Diamond-Blackfan anemia 12 | AD |
RPL26 | 603704 | Diamond-Blackfan anemia 11 | AD |
RPL27 | 607526 | AD | |
RPL35A | 180468 | Diamond-Blackfan anemia 5 | AD |
RPL5 | 603634 | Diamond-Blackfan anemia 6 | AD |
RPS10 | 603632 | Diamond-Blackfan anemia 9 | AD |
RPS17 | 180472 | Diamond-Blackfan anemia 4 | AD |
RPS19 | 603474 | Diamond-Blackfan anemia 1 | AD |
RPS24 | 602412 | Diamond-blackfan anemia type 3 | AD |
RPS26 | 603701 | Diamond-Blackfan anemia 10 | AD |
RPS27 | 603702 | Diamond-Blackfan anemia 17 | AD |
RPS28 | 603685 | Diamond-Blackfan anemia 15 with mandibulofacial dysostosis | AD |
RPS29 | 603633 | Diamond-Blackfan anemia 13 | AD |
RPS7 | 603658 | Diamond-Blackfan anemia 8 | AD |
RTEL1 | 608833 | dyskeratosis congenita; that telomere-related pulmonary fibrosis and/or bone marrow failure type 3 | AD, AR |
RUNX1 | 151385 | Platelet disorder, familial, with associated myeloid malignancy; acute myeloid leukemia | AD |
SAMD9 | 610456 | normophosphatemic familial tumoral calcinosis; MIRAGE syndrome | AD, AR |
SBDS | 607444 | Shwachman-Bodian-Diamond syndrome; Aplastic Anemia | AR |
SEC23B | 610512 | congenital dyserythropoietic anemia 2; Cowden syndrome 7 | AD, AR |
SH2D1A | 300490 | Lymphoproliferative Syndrome, X-Linked, 1 | XLR |
SLC19A2 | 603941 | Thiamine-responsive megaloblastic anemia syndrome | AR |
SLC19A3 | 606152 | biotin-thiamine-responsive basal ganglia disease | AR |
SLC25A19 | 606521 | Microcephaly, Amish type; Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type) | AR |
SLC25A38 | 610819 | Anemia, sideroblastic, 2, pyridoxine-refractory | AR |
SLC4A1 | 109270 | Autosomal dominant distal renal tubular acidosis; resistance to malaria; Renal tubular acidosis, distal, with hemolytic anemia; Spherocytosis, type 4 | AD, AR |
SLX4 | 613278 | Fanconi anemia of complementation group P | AR |
SPTA1 | 182860 | Elliptocytosis type 2; Pyropoikilocytosis; Spherocytosis, type 3 | AD, AR |
SPTB | 182870 | Spherocytosis, type 2; Elliptocytosis 3 | AD |
SRP72 | 602122 | Bone marrow failure, familial | AD |
STIM1 | 605921 | Myopathy, tubular aggregate, 1; Immunodeficiency 10 | AD, AR |
STX11 | 605014 | Hemophagocytic lymphohistiocytosis, familial, 4 | AR |
STXBP2 | 601717 | Hemophagocytic lymphohistiocytosis, familial, 5 | |
TCN2 | 613441 | Transcobalamin II deficiency | AR |
TERT | 187270 | acute myeloid leukemia; Dyskeratosis congenita 4; Bone marrow failure, telomere-related, 1 | AD, AR |
TINF2 | 604319 | Revesz syndrome; Dyskeratosis congenita, autosomal dominant 3 | AD |
TP53 | 191170 | familial breast-ovarian cancer type 2; colorectal cancer; Hepatocellular Carcinoma; Glioma susceptibility 1; Li-Fraumeni syndrome 1; Osteogenic Sarcoma; Pancreatic Cancer | AD |
TPK1 | 606370 | Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type) | AR |
TRNT1 | 612907 | Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay | AR |
UBE2T | 610538 | Fanconi anemia of complementation group T | AR |
UNC13D | 608897 | familial hemophagocytic lymphohistiocytosis 3 | AR |
VPS13B | 607817 | Cohen syndrome | AR |
VPS45 | 610035 | Severe congenital neutropenia type 5 | AR |
WAS | 300392 | Neutropenia, severe congenital, X-linked; Wiskott-Aldrich syndrome; Thrombocytopenia 1 | XLR |
WRAP53 | 612661 | Autosomal recessive dyskeratosis congenita type 3 | AR |
XIAP | 300079 | X-linked lymphoproliferative disease 2 | XLR |
XRCC2 | 600375 | Fanconi anemia, complementation group U | AR |
YARS2 | 610957 | Myopathy, lactic acidosis, and sideroblastic anemia 2 | AR |
Treatment of thrombocytopenia usually includes platelet transfusion used to provide an immediate platelet increase. Furthermore, treatment should be focused on the etiology of thrombocytopenia (e.g. discontinuation of the drug that caused the thrombocytopenia, treatment of the underlying infection, chemotherapy, and others). Hematopoietic cell transplantation (HCT) is the only known curative treatment. Topical steroids and antibiotics should be considered for infected eczema. Immunosuppressants should be used for autoimmune disease and granulocyte colony stimulating factor and appropriate antibiotics for neutropenia.
CENTOGENE offers sequencing and deletion/duplication analysis for the genes in the Thrombocytopenia panel (ADAMTS13, ANKRD26, CYCS, GATA1, GP1BA, GP1BB, GP9, ITGA2B, ITGB3, MASTL, MPL, MYH9, RUNX1, WAS).
Differential diagnosis
The differential diagnosis of thrombocytopenia-related disorders – depending on the major symptoms in the initial case – includes the following diseases:
- Disseminated intravascular coagulation liver disease
- Thrombotic Thrombocytopenic Purpura (TTP)
- Drug-induced immune thrombocytopenia (alcohol, heparin, quinine/quinidine, sulfonamides)
- Infection/sepsis
- Acute leukemia, myelodysplastic syndrome or related malignancy
- Megaloblastic anemia.
Testing strategy
CENTOGENE offers an advanced, fast and cost-effective strategy to test large NGS panels and diagnose complex phenotypes based on PCR-free whole genome sequencing and NGS technology. This approach offers an unparalleled advantage by reducing amplification/capture biases and providing sequencing of the entire gene with more uniform coverage
To confirm/establish the diagnosis, CENTOGENE offers the following testing strategy for thrombocytopenia using NGS Panel Genomic targeted towards this specific phenotype:
Step 1: Whole genome sequencing from a single filter card. The sequencing covers the entire gene (coding region, exon/intron boundaries, intronic and promoter) for all the genes included in the Thrombocytopenia panel. Copy Number Variants analysis derived from NGS data is also included.
Step 2: If no mutation is identified after analysis of the thrombocytopenia panel, we further recommend continuing the bioinformatics analysis of the data with whole genome sequencing to cover those genes which are either implicated in an overlapping phenotype or could be involved in a similar pathway but are not strongly clinically implicated based on the current information in literature.
Referral reasons
The following individuals are candidates for thrombocytopenia testing:
- Individuals with a family history of thrombocytopenia and presentation of the most common symptoms
- Individuals without a positive family history, but with symptoms resembling thrombocytopenia
- Individuals with a negative but suspected family history of thrombocytopenia, in order to perform proper genetic counseling.
Test utility
Sequencing, deletion/duplication of the panel genes should be performed in all individuals suspected of having thrombocytopenia and suspected phenotypes. In parallel, other genes reported to be related with this clinical phenotype should also be analyzed for the presence of mutations, due to the overlap in many clinical features caused by those particular genes.
Confirmation of a clinical diagnosis through genetic testing can allow for genetic counseling and may direct medical management. Genetic counseling can provide a patient and/or family with the natural history of the thrombocytopenia and related disorders identify at-risk family members, provide disease risks as well as appropriate referral for patient support and/or resources.