Genetic Testing for Bleeding Disorders and Inherited Bone Marrow Failure Syndromes
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At PreventionGenetics, we believe that rapid, comprehensive, and affordable genetic testing is of utmost importance. We also understand that not all patients are the same, which is why we offer a robust menu of hematologic genetic testing options to help you select the most appropriate test for your patient.
Bleeding Disorders
A bleeding disorder is a condition characterized by the body's inability to normally form blood clots. Typically, when you’re injured, your blood clots to stop the bleeding. However, in individuals with bleeding disorders, this clotting process is impaired, leading to excessive or prolonged bleeding even from minor injuries or spontaneously.
A bleeding disorder can be inherited or acquired and can be acute or chronic. Symptoms can include easy bruising, heavy menstrual cycles, and frequent nosebleeds.1
Inherited Bone Marrow Failure
Bone marrow failure can cause a bleeding disorder. Bone marrow is responsible for producing the essential components of blood. Every day, it generates billions of red blood cells, white blood cells, and platelets.2 Additionally, the bone marrow serves as a storage site for fat, which can be converted into energy as required. Healthy bone marrow makes healthy blood cells.
Inherited bone marrow failure syndromes (IBMFSs) are a group of rare and complex disorders characterized by the inability of the bone marrow to produce an adequate number of blood cells.3
Types of IBMFSs include:
• Amegakaryocytic thrombocytopenia
• Diamond Blackfan anemia (DBA)
• Dyskeratosis congenita (DC)
• Fanconi anemia (FA)
• Severe congenital neutropenia (SCN)
• Shwachman Diamond syndrome (SDS)
• Thrombocytopenia absent radii (TAR)
• Familial Thrombocytopenia – (AML)
Genetic Testing for Inherited Bone Marrow Failure
IBMFSs arise from germline variants, resulting in compromised hematopoietic stem cell progenitors and ineffective hematopoiesis.4
Genetic testing allows for the identification of individuals who may be at risk of developing bone marrow failure syndromes, even before symptoms manifest. This is particularly important for conditions with a hereditary component, such as Fanconi anemia or Diamond-Blackfan anemia. Early identification of at-risk individuals enables proactive monitoring and interventions to prevent or mitigate the onset of symptoms.
Different bone marrow failure syndromes may require different treatment approaches. Genetic testing helps tailor treatment plans, including bone marrow donor selection, based on the underlying genetic abnormalities identified in each patient. For example, some syndromes may benefit from hematopoietic stem cell transplantation, while others may respond better to supportive care or targeted therapies.
Genetic Testing Available at PreventionGenetics
Our team of expert geneticists consistently review new research to identify the latest gene variants linked to various diseases and phenotypes. This includes removing any genes that no longer fit the phenotype. Several of our popular tests available on our hematology menu are outlined below:
Inherited Bone Marrow Failure Panel
This test is suitable for patients with a family history of malignancy, cytopenias, congenital anomalies, or features associated with inherited syndromes such as Fanconi anemia, Shwachman Diamond syndrome, Diamond Blackfan anemia, and dyskeratosis congenita.
Cultured skin fibroblasts are the preferred specimen type when ordering inherited bone marrow failure testing. DNA from cultured fibroblasts reduces the risk for somatic or donor DNA contamination.
We recognize that results of this panel are often clinically urgent. The IBMF Panel can be ordered STAT with a turnaround time (TAT) of two weeks on average.*
This test is suitable for patients with excessive bleeding of unknown etiology due to abnormal platelet count, volume, morphology, function, or impaired coagulation. It is also suitable for patients with low platelet counts of unknown etiology. This panel can aid in a rapid differential diagnosis of phenotypically similar disorders and can help rule out particular syndromes.
Both of these tests can be ordered on an exome or genome platform, allowing you to easily reflex to whole genome or whole exome sequencing.
Our panels are regularly evaluated for disease/gene validity with updates to reflect the current state of scientific evidence. The most recent update to the Inherited Bone Marrow Failure Panel included the addition of 48 genes. Other panels with recent updates include:
• Inherited Bone Marrow Failure Panel
• Inherited Platelet Function Disorder Panel
• Thrombocytopenia Panel
• Thrombocytopenia Panel – Expanded
Genetics Expertise
Our blood disorders expert, Dr. Siwu Peng, joined PreventionGenetics in September 2021 as an Associate Human Molecular Geneticist. Dr. Peng earned his Ph.D. in Biochemistry and Molecular Biology at Shantou University, China and completed an ABMGG Laboratory Genetics and Genomics (LGG) fellowship at Icahn School of Medicine at Mount Sinai in New York in 2021.
Dr. Peng possesses a specialized understanding of the intricacies of hematological disorders, helping him to better identify potential genetic variants.
References
*data on file
1. Bleeding Disorders - What Are Bleeding Disorders | NHLBI, NIH. (2023, August 3). Www.nhlbi.nih.gov. https://www.nhlbi.nih.gov/health/bleeding-disorders
2. Cleveland Clinic. (2022, April 21). Bone Marrow: What it is & Why it is Important. Cleveland Clinic. https://my.clevelandclinic.org/health/body/22818-bone-marrow
3. Inherited Bone Marrow Failure Syndromes (IBMFS) - NCI. (2012, May 17). Dceg.cancer.gov. https://dceg.cancer.gov/research/what-we-study/bone-marrow-failure-syndromes#:~:text=The%20inherited%20bone%20marrow%20failure
4. Park, M. (2022). Overview of inherited bone marrow failure syndromes. Blood Research, 57(S1), S49–S54. https://doi.org/10.5045/br.2022.2022012