Bleeding Disorders Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10425 ABCG5 81479,81479 Order Options and Pricing
ABCG8 81479,81479
ACTN1 81479,81479
ADAMTS13 81479,81479
ANKRD26 81479,81479
ANO6 81479,81479
AP3B1 81479,81479
BLOC1S3 81479,81479
CD36 81479,81479
CYCS 81479,81479
DTNBP1 81479,81479
F10 81479,81479
F11 81479,81479
F12 81479,81479
F13A1 81479,81479
F13B 81479,81479
F2 81479,81479
F5 81479,81479
F7 81479,81479
F8 81407,81406
F9 81238,81479
FGA 81479,81479
FGB 81479,81479
FGG 81479,81479
FLI1 81479,81479
FLNA 81479,81479
GATA1 81479,81479
GFI1B 81479,81479
GGCX 81479,81479
GP1BA 81479,81479
GP1BB 81404,81479
GP6 81479,81479
GP9 81479,81479
HOXA11 81479,81479
HPS1 81479,81479
HPS3 81479,81479
HPS4 81479,81479
HPS5 81479,81479
HPS6 81479,81479
ITGA2 81479,81479
ITGA2B 81479,81479
ITGB3 81479,81479
LMAN1 81479,81479
MASTL 81479,81479
MCFD2 81479,81479
MPL 81479,81479
MYH9 81479,81479
NBEAL2 81479,81479
P2RX1 81479,81479
P2RY12 81479,81479
PLAU 81479,81479
PRKACG 81479,81479
RUNX1 81479,81479
SERPINE1 81479,81479
SERPINF2 81479,81479
TBXA2R 81479,81479
TBXAS1 81479,81479
TUBB1 81479,81479
VKORC1 81479,81479
VWF 81408,81479
WAS 81406,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10425Genes x (61)81479 81238, 81404, 81406, 81407, 81408, 81479 $1060 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

This sequencing panel focuses on inherited bleeding disorders due to impaired platelet function, coagulation factor deficiencies or thrombocytopenia. With many factors contributing to clot formation, differential diagnosis of the various bleeding disorders can be time-intensive, labor-intensive, and difficult to interpret, especially in patients with milder symptoms. Genetic testing provides a means to examine multiple bleeding disorder genes simultaneously to quickly identify potential causes to disease. Differential diagnosis is especially helpful in employing appropriate therapies to mitigate bleeding episodes (Westbury et al. 2015; Simeoni et al. 2016; Lentaigne et al. 2016).

Platelet function disorders (PFDs) tested in this panel include defects in platelet adhesion/coagulation, receptor function, or secretion (Handin et al 2005). PFDs due to defects in platelet adhesion include Bernard-Soulier syndrome and Scott Syndrome; defects in receptor function include Glanzmann’s thrombasthenia, Thromboxane A2 receptor deficiency, GPVI collagen receptor deficiency, and P2Y12 ADP receptor deficiency. Defects in storage granules include Hermansky-Pudlak Syndrome.

Coagulation factor deficiency panel includes testing for a large group of inherited bleeding disorders including three types of hemophilia, von Willebrand disease and rare bleeding disorders (RBD). RBDs include inherited deficiencies in fibrinogen, factor (F) II, FV, FV +FVIII, FVII, FX, FXI, FXIII, plasminogen activator inhibitor, and alpha-s-plasmin inhibitor.

Inherited thrombocytopenias comprise a heterogeneous group of rare disorders characterized by low platelet counts. In adults, low platelet numbers are typically considered below 150,000/microL. Bleeding manifestations of thrombocytopenia include primarily excessive bruising (purpura), petechiae, prolonged bleeding from cuts or from surgical procedures, spontaneous nose bleeds, and in women, heavy menstrual flows. Thrombocytopenia and consequent bleeding diatheses range in severity from mild to severe. About half of the inherited thrombocytopenias are syndromic disorders characterized by physical and neurological anomalies, and immunodeficiencies (Balduini et al. 2013). Some inherited thrombocytopenias are associated with an increased risk of developing myelodysplastic syndrome (MDS) and acute leukemia (AL) (Churpek et al. 2013). It is important to distinguish inherited thrombocytopenias from immune / idiopathic thrombocytopenias (ITP) in order to inform clinical management and identify potential at risk family members.

Genetics

Inherited platelet function disorders are inherited in an autosomal recessive manner due to pathogenic variants in the ITGB3, ITGA2B, AP3B1, BLOCK1S3, DTNBP1, HPS1, HPS3, HPS4, HPS5, HPS6, ANO6, GP1BA, GP9, GP1BB, P2RY12, CD36 and GP6 genes (Handin et al. 2005; Watson et al. 2013). Autosomal dominant forms include pathogenic variants in the TBXA2R, PLAU, PTGS1, and TBXAS1 genes.

Hemophilia A and B are inherited through an X-linked recessive manner through pathogenic variants in the F8 and F9 genes respectively and primarily affect males. VWD is inherited in both autosomal dominant and recessive manners through pathogenic variants in the VWF gene. RBDs are all inherited in an autosomal recessive manner with deficiencies in FVII, FXI, or FV accounting for ~80% of cases. RBD genes include FGA, FGB, FGG, F2, F5, F7, F10, F11, F12, F13A1, F13B, MCFD2, LMAN1, SERPINE1, SERPINF2, VKORC1, and GGCX. See individual test descriptions for additional information on the molecular biology of each gene.

Thrombocytopenia genes included in this panel have been associated with both syndromic and non-syndromic forms of inherited thrombocytopenia and represent the most well-documented forms of inherited thrombocytopenia reported in the literature. Thrombocytopenias are typically divided into three distinct groups based upon platelet size: large / macrothrombocytopenias, small / microthrombocytopenias, and thrombocytopenias with normal sized platelets (Westbury et al. 2015; Simeoni et al. 2016; Lentaigne et al. 2016).

Testing Strategy

This panel typically provides ≥98% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Clinical Sensitivity - Sequencing with CNV PGxome

This test is designed to identify variants in genes associated with a variety of bleeding phenotypes. In a recent study of patients with excessive bleeding, a next generation sequencing approach was used for differential diagnosis. Of the 61 patients with a suspected etiology, a corresponding pathogenic variant was identified in 91.8% of cases. In 76 patients with an unknown etiology, a causative pathogenic variant was identified in 10.5% of cases (Simeoni et al. 2016).

Large deletions in various inherited platelet disorders represent ~20% of causative variants found within AP3B1 and HPS3, ~10% in HPS6 and GP1BB, 2% in GP1BA, 5% in ITGA2B, 2% in ITGB3, and 100% in PLAU (Human Gene Mutation Database).

For coagulation deficiency genes, large deletions are represent 5% of causative variants in the F10, 2% in F11, 3% in F13A1, 2% in F5, 2% in F7, 6% in F8, 3% in F9, 15% in FGA, and 5% in VWF (Human Gene Mutation Database).

The majority of variants reported in the thrombocytopenia genes in this panel are missense and nonsense variants. Large deletions account for ~24% of the reported RUNX1 gene variants, but in general, large, multi-exon and whole gene deletions are rare among the thrombocytopenia panel genes. In addition to the RUNX1 gene, large deletions have also been reported in the GP1BB, MYH9, and WAS genes (Human Gene Mutation Database).

Indications for Test

Candidates for testing include patients with excessive bleeding of unknown etiology due to abnormal platelet count, volume, morphology, function, or impaired coagulation. This test especially aids in a rapid differential diagnosis of phenotypically similar disorders, rules out particular syndromes, and provides the analysis of multiple genes simultaneously. Individuals who are suspected of any of these disorders, especially if clinical diagnosis is unclear and individuals who have been found to be negative by mutation analysis for a single gene test are candidates (Othman 2013; Peyvandi et al. 2012).

Diseases

Name Inheritance OMIM ID
Afibrinogenemia, congenital AR 202400
Anti-Plasmin Deficiency, Congenital AR 262850
Bernard Soulier Syndrome AR 231200
Bleeding Disorder, Platelet-Type, 11 AR 614201
Bleeding Disorder, Platelet-Type, 13, Susceptibility To AD 614009
Bleeding Disorder, Platelet-Type, 14 AD 614158
Bleeding Disorder, Platelet-Type, 15 AD 615193
Bleeding Disorder, Platelet-Type, 17 AD 187900
Bleeding Disorder, Platelet-Type, 19 AR 616176
Bleeding Disorder, Platelet-Type, 8 AR 609821
Bleeding Disorder, Platelet-Type, 9 AD 614200
Cardiac Valvular Dysplasia, X-Linked XL 314400
Congenital Amegakaryocytic Thrombocytopenia AR 604498
Factor V And Factor VIII, Combined Deficiency Of, 1 AR 227300
Factor V And Factor VIII, Combined Deficiency Of, 2 AR 613625
Factor V Deficiency AR 227400
Factor VII Deficiency AR 227500
Factor X Deficiency AR 227600
Factor XII Deficiency Disease AR 234000
Factor XIII, A Subunit, Deficiency Of AR 613225
Factor XIII, B Subunit, Deficiency Of AR 613235
GATA-1-Related Thrombocytopenia With Dyserythropoiesis XL 300367
Glanzmann's Thrombasthenia AR 273800
Gray Platelet Syndrome AR 139090
Hemophilia A, Congenital XL 134500
Hemophilia A, Congenital XL 306700
Hereditary Factor IX Deficiency Disease XL 306900
Hereditary Factor XI Deficiency Disease AR 612416
Hermansky-Pudlak Syndrome 1 AR 203300
Hermansky-Pudlak Syndrome 2 AR 608233
Hermansky-Pudlak Syndrome 3 AR 614072
Hermansky-Pudlak Syndrome 4 AR 614073
Hermansky-Pudlak Syndrome 5 AR 614074
Hermansky-Pudlak Syndrome 6 AR 614075
Hermansky-Pudlak Syndrome 7 AR 614076
Hermansky-Pudlak Syndrome 8 AD 614077
Macrothrombocytopenia, Autosomal Dominant, TUBB1-Related AD 613112
May-Hegglin Anomaly AR 155100
Plasminogen Activator Inhibitor Type 1 Deficiency AR 613329
Platelet Glycoprotein IV Deficiency AR 608404
Prothrombin Deficiency, Congenital AR 613679
Pseudoxanthoma Elasticum-Like Disorder With Multiple Coagulation Factor Deficiency AD 610842
Quebec Platelet Disorder AD 601709
Radioulnar Synostosis With Amegakaryocytic Thrombocytopenia AR 605432
Scott Syndrome AR 262890
Sitosterolemia AD 210250
Thrombocytopenia 2 AD 188000
Thrombocytopenia 4 AD 612004
Thrombocytopenia, Familial, With Propensity To Acute Myelogenous Leukemia AD 601399
Thrombocytopenia, Paris-Trousseau Type AR 188025
Thrombotic Thrombocytopenic Purpura AR 274150
Vitamin K-Dependent Clotting Factors, Combined Deficiency Of, 2 AD 607473
Von Willebrand Disease, Type 1 AD, AR 193400

Related Test

Name
PGxome®

Citations

  • Balduini C.L. et al. 2013. Journal of Thrombosis and Haemostasis. 11: 1006-19. PubMed ID: 23510089
  • Churpek J.E. et al. 2013. Leukemia & Lymphoma. 54: 28-35. PubMed ID: 22691122
  • Handin R.I. 2005. Hematology. American Society of Hematology Education Program. 396-402. PubMed ID: 16304410
  • Human Gene Mutation Database (Bio-base).
  • Klopocki E. et al. 2006. European Journal of Human Genetics. 14: 1274-9. PubMed ID: 16896345
  • Lentaigne C. et al. 2016. Blood. 127: 2814-23. PubMed ID: 27095789
  • Othman. 2013. PubMed ID: 23982907
  • Papoulidis .I et al. 2014. Molecular Medicine Reports. 9: 163-5. PubMed ID: 24220582
  • Peyvandi F. et al. 2012. Haemophilia. 18 Suppl 4: 148-53. PubMed ID: 22726099
  • Simeoni I. et al. 2016. Blood. 127: 2791-803. PubMed ID: 27084890
  • Watson S.P. et al. 2013. Journal of Thrombosis and Haemostasis. 11 Suppl 1: 351-63. PubMed ID: 23516995
  • Westbury S.K. et al. 2015. Genome Medicine. 7: 36. PubMed ID: 25949529

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

loading Loading... ×

ORDER OPTIONS

View Ordering Instructions

1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Total Price: $
×
Copy Text to Clipboard
×