Hypoproliferative Anemia Flashcards
What are the characteristic lab findings of hypoproliferative anemias?
Anemia and low reticulocyte count in lab
What are the types of hypocellular bone marrow/hypercellular bone marrow?
Hypocellular bone marrows
- Stem cell disorders
- Drugs/Treatments
Hypercellular bone marrows
- infiltration
- Ineffective erythropoiesis
What should the differential for pancytopenia be?
Stem cell disorders – Aplastic anemia, PNH
Ineffective hematopoiesis – MDS, Megaloblastic anemia
Marrow infiltration – Leukemia/lymphoma, metastatic carcinoma, myelofibrosis
Splenic sequestration – Massive splenomegaly
Drugs/Treatments – Immunosuppressants, Chemotherapy/radiation, other medications
What is associated with hypersplenism?
Variable cytopenias – Estimated that 1/3 of platelets are stored in spleen
What are the major steps involved in the folate pathway?
Purine synthesis
Conversion of dUMP to dTMP
One carbon for S-adenosylmethionine
How is folate activated? What is it inhibited by?
Takes folate which is activated to THF via DHF reductase
Two step
Inhibited by MTX
What does thymidylate synthetase do?
What inhibits it?
What does it require?
Conversion of dUMP to dTMP
Inhibited by 5-FU derivative FdUMP
Requires THF
What are potential etiologies of megaloblastic anemia?
DHF reductase deficiency via MTX
Thymidylate synthetase deficiency – 5FU
Folate deficiency
Vitamin B12 deficiency
What is the prurpose of the folate one-carbon?
What is it required for?
Purine synthesis
Required for thymidylate synthetase for conversion of dUMP to dTMP for DNA synthesis
Synthesis of methionine for SAM
What is 5-Adenosylmethionine used for?
Methyl donation via methyl transferases
What does methionine synthetase require?
Requires methyl THF and Vitamin B12
What is Vitamin B12 bound to and how is it taken and transferred?
Bound to food
Released in stomach by HCl and pepsin
Binds mainly to R-protein but some to IF
In duodenum, R-protein degraded releasing Vitamin B12
Vitamin B12 binds intrinsic factor
Complex binds IF receptor
Vitamin B12 transferred to transcobalamin
What are the causes of vitamin B12 deficiency?
Impaired absorption
IF deficiency
Ileal resection
Pancreatic insufficiency
Increased requirement (Pregnancy) Decreased intake (strict vegans) Tapeworm – Diphyllobothrium latum
What are the clinical manifestations of Vitamin B12?
Megaloblastic anemia, pernicious anemia
Subacute combined degeneration
Dorsal and lateral tract demyelination
Parasthesias
Spastic paraparesis
Sensory ataxia
What is pernicious anemia? What is its etiology?
Secondary B12 def to IF abnormalities
Most frequent cause of B12 deficiency
Autoantibodies against IF – Required for diagnosis