Anemia II - Macrocytic Anemias and Blood Transfusions Flashcards
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
What is FFP used for?
Prevent or treat coagulation factor deficiencies
- Vitamin K deficiency
- Specific factor deficiencies (although cryoprecipitate is used more)
- When Hct is too high from packed RBC transfusions
- Thrombotic thrombocytopenic purpura
What is cryoprecipitate used for?
Prevent or treating due to specific factor deficiencies
i.e. DIC causing low fibrinogen, or von Willebrand’s disease
When is tranfusion with packed RBCs generally indicated and what is the target hemoglobin level?
No absolute level indicates it: consider patient’s symptoms, rapidity of decline, and baseline Hgb
Shoot for 7-8 g/dL, >10 may be dangerous
What is the process of pre-tranfusion compatibility testing?
- Forward ABO typing - test patient’s RBCs
- Reverse ABO typing - test patient’s blood type based on what antibodies they have in their serum
- Rh Typing - positive or negative
- Identification of allo-antibodies in patient’s plasma (if present)
- Selecting appropriate blood components
- Cross-match
How does cross-matching generally work?
Mix patient’s blood with donor blood
If agglutination occurs -> they are incompatible
What happens if you give ABO incompatible blood to a patient?
Acute hemolytic tranfusion reaction
- > intravascular hemolysis
- > anti-A or anti-B antibodies are IgM and fix complement very well
What plasma can you transfuse to patients with the following blood types
- Group A
- Group B
- Group AB
- Group O
- Group A - A or AB
- Group B - B or AB
- Group AB - AB only (A, B, or O would have antibodies to A or B)
- Group O - universal receiver
Who are the universal RBC donors and universal plasma donors?
RBC - Type O
-> no antigens to react with anti A or anti B antibodies in plasma
O-neg given in emergencies
Plasma - Type AB
-> no antibodies to react with any blood type surface antigens
What are the signs and symptoms of an acute hemolytic transfusion reaction?
Within hours of transfusion:
Back / flank pain (from kidney failure), dark urine, DIC, jaundice, nausea / vomiting, hypotension / shock
How is acute hemolytic transfusion reaction treated?
Stop transfusion,
Give patient IV fluids / pressors for hypotension, Furosemide / mannitol to promote urine output, treat DIC
What test is used to check for an acute hemolytic transfusion reaction?
Direct Coomb’s test -> look for antibodies on RBC surface
What causes a delayed hemolytic transfusion reaction?
IgG antibodies to minor antigens (i.e. Rh antigens, usually D antigen) on RBC surface, which you are sensitized to during transfusion or childbirth
When does delayed hemolytic transfusion reaction onset What type of hemolysis is it?
Extravascular hemolysis - takes place 5-14 days after transfusion (due to time taken for circulating antibodies to recover (anamnestic response of B cells))
What are the symptoms of delayed hemolytic transfusion reaction? Treatment?
Worsening anemia after transfusion, bilirubin / jaundice, hemolysis evidence
renal failure / death are rare in this cause (extravascular, not as severe)
Treatment: supportive care
What is an anaphylactoid reaction to blood tranfusions?
Shock, bronchospasm, and respiratory distress due to allergy to some comoponent of donor plasma
Give epinephrine and IV fluids
A patient was given several transfusions and now has dyspnea, cough, hypxoia, edema, and pulmonary congestion on CXR. What do they have and how do you treat them?
TACO - tranfusion associated circulatory overload
Presents like CHF
Give diuretics to reduce blood volume
What is tranfusion associated acute lung injury (TRALI)? Treatment?
Siimilar to TACO, but no edema or cardiomegaly
- > noncardiogenic pulmonary edema due to donor antibodies against recipient neutrophils resulting in capillary leak
- > give supportive therapy and mechanical ventilation if needed
How can multiple myeloma and cold agglutinins alter the MCV?
Look like a macrocytic anemia
Multiple myeloma causes RBCs to agglutinate -> Rouleaux formation -> read as high MCV
Cold agglutinins (as in Mycoplasma or mononucleosis) can also cause aggregation read as high MCV
