Anemia II - Macrocytic Anemias and Blood Transfusions Flashcards
(42 cards)
What is the DDx for macrocytic anemias?
Megaloblastic anemias (b9/b12) chronic liver disease / alcoholism hypothyroidism drugs bone marrow disorders red cell agglutination (warm or cold) very brisk reticulocytosis
What drugs are associated with macrocytic anemias?
Phenytoin, zidovudine, methotrexate, other chemo drugs impairing DNA synthesis (i.e. 5-FU)
Describe the pathway by which B12 is ingested and absorbed.
Ingested in animal products. Stomach enzymes detach B12 from protein and attach it to R-binder which was released by salivary glands.
In the duodenum, proteases detach R-binder from B12
B12 binds intrinsic factor released from parietal cells in the duodenum
IF-B12 complex attaches to receptor in terminal ileum for absorption
How is B12 stored and carried in the blood?
Stored in liver, sometimes secreted in bile but reuptaken by enterohepatic circulation
Carried in the blood via transcobalamin II
Where is folate absorbed? In what form?
Polyglutamate form from green vegetables is cleaved to monoglutamate form which is absorbed in the jejunum
What blood levels are increased in both B9/B12 deficiency, and what in just B12? How does this relate to the effects of deficiency?
B9/B12 - homocysteine
B12 only - Methymalonic acid, in conversion of propionyl CoA to succinyl-CoA
Both cause megaloblastic anemia, but only B12 deficiency causes buildup of methylmalonic acid which is toxic to myelin and causes subacute combined degeneration
What is the most common etiology of B12 deficiency and what conditions are associated with it?
Pernicious anemia - most common - autoimmune to instrinsic factor or parietal cells
Associated with autoimmune conditions such as thyroiditis, Type 1 diabetes, autoimmune atrophic gastritis, and vitiligo
What is a very common cause of B12 deficiency in he elderly?
Atrophic gastritis or use of PPI’s and H2 blockers causes achlorhydria
-> defective splitting of B12 from food
What surgeries and intestinal disorders can cause B12 deficiency?
Surgeries - gastrectomy / gastric bypass (loss of parietal cells), ileal resection (loss of absorption)
Intestinal disorders:
Pancreatic insufficiency - can’t cleave off R-binder
Malabsorption - Crohn’s, Celiac, diphyllobothrium latum, bacterial overgrowth
What drugs an cause folate deficiencies?
Methotrexate, trimethoprim, pyrimethamine - all inhibit dihydrofolate reductase
What are the usual causes of folate deficiency?
Alcoholism - inhibits absorption and poor diet
Intestinal malabsorptive disorers
High demand states: Hemolytic anemias, pregnancy
What can be seen on blood smear due to B9/B12 deficiencies?
Macro-ovalocytes (not round as in liver or hypothyroidism)
Hypersegmented neutrophils 5% with >5 lobes or any with >6
What are the neurological features of B12 deficiency and do the symptoms appear before or after anemia?
Generally appear before anemia
Subacute combined degeneration
Symmetrical polyneuropathy affecting legs more than arms
- > paresthesias happen more than motor
- > loss of proprioception and vibratory sense due to DC-ML loss
- > spastic paresis due to loss of lateral corticospinal tract
Can also affect memory / personality
How is a B9/B12 deficiency diagnosed?
B9 - RBC folate (serum folate is too short-term)
B12 - check levels
If levels are inconclusive, check homocysteine / methylmalonic acid levels
What is the Schilling test?
Historical B12 deficiency test:
Give radiolabelled B12, if >10% is detected in urine, absorption is normal, otherwise there is malabsorption or pernicious anemia
What oral symptoms occur in B9/B12 deficiency?
Aphthous stomatitis (recurrent canker sores) and glossitis
What things do we typically screen our blood donations for nowadays?
Bacterial contamination, Hep B/C, HIV, HTLV, T. cruzi, syphilis, and Zika
What process is done to prevent transfusion reactions in immunocompetent hosts? What type of tranfusion reaction is this normally?
Leukoreduction
-> filter out WBCs
Usually a febrile, non-hemolytic reaction due to Abs against donor leukocytes/platelets or cytokines present in donor plasma
What is done to prevent transfusion-associated graft-versus-host disease (TA-GVD)?
Gamma-irradiation -> need to make sure there are no competent donor WBCs in the sample otherwise immunocompromised patient may die
-> condition is usually fatal, causing cytopenias and hepatitis
What is meant by washing RBCs and what is this meant to prevent?
Remove donor plasma, wash RBCs, replace plasma with saline
Prevents allergic reactions to a substance in donor plasma
When do we freeze RBCs?
When we have a rare blood type we need to store away
What typically has a longer shelf-life, platelets or RBCs? Why? What’s apheresis vs pooled platelets?
RBCs do, since platelets must be stored at room temperature
Apheresis is the process by which you remove someone’s blood, centrifuge out the serum, remove platelets, and replace with normal saline (all comes from one donor)
Pooled platelets comes from spinning down plasma from a normal red cell donation
What is fresh frozen plasma and cryoprecipitate?
Fresh frozen plasma is made from heavily spinning platelet-rich plasma, and removing platelets
Cryoprecipitate is composed of specific components of FFP
When are platelets tranfused?
To prevent or treat bleeding due to thrombocytopenia
-> <10,000 platelets/uL or if active bleeding
