10.11.18 Hypoproliferative Anemias Flashcards
What is on the differential for low reticulocytes?
- Acute blood loss or destruction
- Nutritional anemia
- Bone marrow failure (aplastic anemia)
- RBC production failure (myelodysplasia)
- Destruction of erythroid precursors
- Replacement of normal bone marrow with something else
A group of disorders characterized by a defect in DNA synthesis leading to a characteristic morphology of bone marrow cells
Nucleus immature, cytoplasma mature, increased cell volume
Megaloblastic anemia
What is the most common cause of megaloblastic anemia?
B12 and Folate deficiency
What is the clinical presentation of megaloblastic anemia
- MCV high
- RDW high
- hypersegmented PMN
- Neuro/psychiatric features (only in B12 deficiency)
How is B12 absorbed
- B12 in diet binds to salivary R protein
- Parietal cells secrete IF
- Pancreatic enzymes degrade B12-R complex allowing B12-IF to form
- Complex taken to distal ileum
- In blood B12 carried by transcobalamin II to tissues
What are the causes for B12 deficiency?
- DIET- Vegan diet (no animal products)
- ABSORPTION- Gastric bypass
- Crohn’s disease
- Sprue
- Metformin
- COMPETITION FOR B12- fish tapeworm, bacterial overgrowth
What are the symptoms/signs of B12 deficiency?
- Neurologic changes
- Loss of vibration and position sense
- Macrocytosis
- Hypersegmented PMNs
- Elevated bili and LDH
How do you diagnose B12 deficiency?
- Low B12
- High homocysteine
- High methylmalonic acid
How do you treat B12 deficiency?
Takes year to develop, IM B12 injections generally
Since enterohepatic circulation is important for folate absorption, what causes profound folate deficiency within hours?
Billiary drainage
What is a major source of folate deficiency?
Raw, green leafy vegetables
How can folate deficiency occur?
- Malnutrition (most common)
- Malabsorption
- Drugs
How do you treat folate deficency?
Oral folate
Who should get extra folate?
- Patients with hemolytic anemia
- Women contemplating pregnancy
- Pregnant/lactating women
Pancytopenia in the peripheral blood, with bone marrow biopsy showing hypocellularity arising from a deficiency of hematopoietic stem cells; autoimmune condition
Aplastic anemia
What are secondary causes of aplastic anemia?
- Ionizing radiation
- Cytotoxic chemotherapy
- Benzene exposure
- Virus- EBV, Hepatitis (non A, B, C, D, or E)
- Paroxysmal nocturnal hemoglobinuria (PNH)
What is clinical presentation of aplastic anemia
- Weakness/fatigue
- Bruising
- Infection/fever
- NO sphlenomegaly/adenopathy
How do you diagnose aplastic anemia?
- Rule out other causes of pancytopenia
2. Do a bone marrow biopsy
How do you treat aplastic anemia?
- Supportive care
- Definitive therapy (stem cell transplantation)
- T cell immuno suppression with antithymocyte globulin (ATG) and cyclosporine
What type of stem cell transport should you do with aplastic anemia?
Allogenic (not patient’s own marrow)
An acquired clonal hematologic disorder
Missing the gene for PIG-A that anchors proteins to cell surface
Can’t anchored proteins CD55 and CD59 which are important for inhibiting complement on surface of RBC
Paroxysmal Nocturnal Heoglobinuria (PNH)
What are the clinical manifestations of paroxysmal nocturnal hemglobinuria (PNH)
- Hemolysis
- Thrombosis (Budd Chiari syndrome)
- Bone marrow failure
4 Predisposition to MDS and AML - Esphogeal spasm
- Erectile dysfunction
- Pulmonary hypertension
How should you treat paroxysmal nocturnal hemoglobinuria (PNH)
- Treat hemolysis with eculizumab (susceptible for Neisseria because blocks activation of terminal complement)
- Replete iron
- Anticoagulant
What is the most common form of inherited aplastic anemia?
How is it genetically passed on?
What population is it high in?
Fanconi’s anemia
Autosomal recessive or X-linked
Ashkenazi Jews
What are the clinical manifestations of fanconi’s anemia?
- Pancytopenia
- Somatic abnormalities
- Cafe au lait spots
- Weird thumbs
How do you diagnose fanconi anemia?
Culture lymphocytes or fibroblasts with diepoxybutane (DEB) and look for abnormal chromosomal breakage
How do you treat fanconi anemia?
allogeneic transplant with reduced intensity conditioning (bc have chromosomal sensitivity)
Inherited disorder of telomere shortening involving one of 9 genes. Also an inherited form of AA
Dyskeratosis congenita
What are the clinical characteristics of dyskeratosis congenita
- Bone marrow failure
- Predisposition to acute leukemia and other solid tumors
- Classic triad (hyperpigmentation of skin, abnormal nails, mucosal leukoplakia)
- Pulmonary fibrosis
- Premature gray hair
- Cirrhosis of liver
How do you diagnose dyskeratosis congenita?
- Family/physical history
- Analyze telomere length
- Genetic analysis
How do you treat dyskeratosis congenita?
Allogeneic transplant with reduced intensity conditioning (bc have chromosomal sensitivity)
