BMF Flashcards
BONE MARROW FAILURE
Rare and serious disorder characterized by a decrease in the number of red blood cells, white blood cells, and platelets in the peripheral blood due to failure of bone marrow production
Congenital - _____
Acquired - _______
Results in low blood cell counts can lead to symptoms of anaemia, thrombocytopaenia and lecopaenia
Treatment involves supportive care, drugs and, in some cases, bone marrow transplantation
Congenital: genetic factors
Acquired: exposure to certain toxins, radiation, chemotherapy, autoimmune disorders
Classify the acquired BMF
Primary Aplastic Anemia:
Idiopathic Aplastic Anemia: The cause is unknown.
Inherited Forms: Examples include Fanconi anemia, which is genetically inherited.
Secondary Aplastic Anemia:
Toxin Exposure: Such as exposure to benzene.
Radiation and Chemotherapy: Can damage bone marrow.
Infections: Viral infections like hepatitis and HIV.
Autoimmune Disorders: Conditions such as systemic lupus erythematosus.
Pathogenesis (How Aplastic Anemia Develops)?
Immune-Mediated Destruction of Hematopoietic Stem Cells:
Cytotoxic T Cells: These immune cells mistakenly attack and destroy the stem cells in the bone marrow.
Autoantibodies: The immune system produces antibodies against the bone marrow cells, leading to their destruction through a process called complement activation.
Disruption of the Bone Marrow Microenvironment:
Overactive Immune Cells: Immune cells and substances like TNF-alpha disrupt the environment in the bone marrow, making it hard for new blood cells to be produced.
Excessive Apoptosis of Hematopoietic Cells:
Programmed Cell Death: Hematopoietic stem cells and their descendants die prematurely due to signals from the immune system and cytokines (chemical messengers).
What’s Clonal Disorders:
Genetic Mutations: Some patients may develop genetic mutations that lead to conditions like Myelodysplastic Syndromes (MDS) or Paroxysmal Nocturnal Hemoglobinuria (PNH), which can co-occur with aplastic anemia
Clinical Features of BMF
Anemia Symptoms: Tiredness, weakness, and pale skin.
Thrombocytopenia Symptoms: Easy bruising and bleeding, such as frequent nosebleeds or heavy menstrual periods.
Neutropenia Symptoms: Frequent infections because of a low white blood cell count.
Petechiae and Ecchymoses: Small red or purple spots and larger bruises on the skin caused by bleeding.
Signs of Secondary Causes: Such as rashes associated with autoimmune diseases.
Diagnosis tests for BMF
Hematologic Parameters:
Full Blood Count (FBC): Blood tests show low levels of hemoglobin (red blood cells), platelets, and white blood cells.
Reticulocytopenia: A low count of reticulocytes, which are immature red blood cells, indicating reduced production.
Bone Marrow Aspiration and Biopsy:
Cellularity and Morphology: A sample of bone marrow is examined under a microscope to check for the number and appearance of cells, helping to rule out other causes.
Cytogenetic and Molecular Testing:
Fanconi Anemia Testing: Genetic tests to identify this specific inherited form of anemia.
Clonal Disorder Assessment: Tests to detect genetic mutations associated with clonal disorders like MDS and PNH.
It’s treatment
Supportive Care:
Blood Transfusions: Providing packed red cells and platelets to manage anemia and prevent bleeding.
Infection Prophylaxis: Taking steps to prevent infections, as the immune system is weakened.
Immunosuppressive Therapy:
Anti-thymocyte Globulin (ATG) and Cyclosporine: Medications that suppress the immune system to stop it from attacking the bone marrow.
Stem Cell Transplantation:
Severe Cases: Transplanting healthy stem cells from a donor to replace the damaged bone marrow.
Treatment of Underlying Causes:
Removing Toxins: Avoiding exposure to harmful chemicals.
Discontinuing Offending Drugs: Stopping medications that are causing the bone marrow to fail.
Emerging Therapies:
New Immunomodulatory Drugs: Developing new treatments to adjust the immune system’s response.
Eltrombopag: A medication that helps increase platelet production.
Gene Therapy: Experimental treatments aimed at correcting genetic defects that cause bone marrow failure.
What’s the prognosis of BMF
Variable Outcomes: The prognosis for bone marrow failure (BMF) can vary greatly.
Spontaneous Remission: In some cases, patients may experience spontaneous improvement without treatment.
Severe Complications: BMF can lead to severe complications like infections, bleeding, and progression to leukemia or other cancers.
Monitoring: Continuous monitoring is necessary to detect any signs of relapse or disease progression.
Explain the Congenital Bone Marrow Failure Syndromes using this method
Inheritance
Symptoms
Diagnosis
Pathophysiology
Treatment/Management
Fanconi Anemia (FA):
Inheritance: Can be autosomal recessive or X-linked.
Symptoms: Short stature, café-au-lait spots (brown skin spots), congenital malformations (thumb, skeletal, renal, cardiac anomalies), and a high risk of developing acute myeloid leukemia (AML) and squamous cell carcinoma.
Diagnosis: Chromosomal breakage tests and genetic testing (at least 22 known FA genes like FANCA, FANCC, FANCG) involved in the FA/BRCA DNA repair pathway.
Pathophysiology: Defective DNA repair leads to chromosomal instability, bone marrow failure, and cancer predisposition.
Management: Supportive care and androgen therapy. Hematopoietic stem cell transplantation (HSCT) is the definitive treatment.
Dyskeratosis Congenita (DC):
Inheritance: Can be X-linked, autosomal dominant, or autosomal recessive.
Symptoms: Skin pigmentation abnormalities, nail dystrophy, oral leukoplakia, pulmonary fibrosis, and a high risk of cancer.
Diagnosis: Telomere length testing and genetic testing.
Management: Supportive care and androgens. HSCT is the definitive treatment.
Shwachman-Diamond Syndrome (SDS):
Inheritance: Autosomal recessive.
Symptoms: Exocrine pancreatic insufficiency, skeletal abnormalities, and an increased risk of myelodysplastic syndrome (MDS) and AML.
Diagnosis: Genetic testing (SBDS gene mutations) and clinical evaluation.
Management: Supportive care and pancreatic enzyme replacement. HSCT is the definitive treatment.
Diamond-Blackfan Anemia (DBA):
Inheritance: Can be autosomal dominant or sporadic.
Symptoms: Severe macrocytic anemia and congenital anomalies (craniofacial, thumb, cardiac), with an increased risk of malignancies.
Diagnosis: Elevated erythrocyte adenosine deaminase (eADA) levels and genetic testing.
Management: Supportive care, corticosteroids, and red cell transfusions. HSCT is the definitive treatment.
Acquired bone marrow failure can be primary or secondary, with primary cases often having unknown causes or being inherited (like Fanconi anemia). Secondary cases are due to external factors like toxins, infections, or autoimmune disorders. The pathogenesis involves immune-mediated destruction, apoptosis of hematopoietic cells, and clonal disorders. Clinical features include symptoms of anemia, thrombocytopenia, and neutropenia, along with diagnostic evaluations through blood tests and bone marrow biopsies. Treatment ranges from supportive care to immunosuppressive therapy and HSCT.
