Divide based on size of the red blood cell. MCV tells you this!
Mean corpuscular volume (MCV) The average volume of red blood cells (RBC), calculated from the hematocrit (Hct) and the RBC count, in RBC indices.
The calculation is: MCV = Hct × 10 ÷ RBC.
Microcytic, hypochromic (MCV <80)
Normocytic, normochromic anemia
- Aplastic anemia
- Kidney disease
HEMOLYTIC: Intrinsic and Extrinsic
- RBC membrane defect: hereditary spherocytosis
- RBC enzyme deficiency: G6PD, PK
Macrocytic anemia (MCV >100)
- Folate deficiency
- B12 deficiency
- Liver disease
- Metabolic disorders
total iron binding capacity = transferrin x 1.4. Anything that elevates transferrin will elevate TIBC
Ferritin is an acute phase reactant and is elevated in any type of inflammatory processes: Infection, cancer.
Stored iron inside cells. In Iron deficiency, you've used up all of the iron so ferritin stores will be low. In Anemia of chronic disease, ferritin stores are high.
Differentiating Iron deficiency vs Chronic disease
hang your hat on % transferrin saturation (Serum Fe/TIBC).
In Iron deficiency, your transferrin saturation will be markedly decreased b/c you have a lot of transferrin out there but little iron. Usually < 12% with Iron Deficinecy.
For chronic disease, it will either be normal or elevated usually >18, but anywhere from 12-45.
Too much iron, transferrin is saturated, body is not making a lot of transferrin.
If normal ferritin, you can almost rule out hemochromatosis.
Elevated ferritin doesn't prove hemochromatosis b/c it can be elevated for many reasons, it's an acute phase reactant.
Lab findings that allow you to distinguish iron deficiency anemia from a microcytic, hypochromic anemia resulting from thalassemia
Iron deficiency will have
- ↓ Serum iron
- ↑TIBC ( a lot of transferrin)
- ↓ Ferritin
Thalassemia will have
- normal iron
- normal TIBC
- Normal ferritin
- target cells.
Any anemia in which there is a predominant number of megaloblastic erythroblasts, and relatively few normoblasts, among the hyperplastic erythroid cells in the bone marrow (as in pernicious anemia).
Cell cycle cannot progress from G2 to M stage, and continued growth without division presenting as macrocytosis.
Megaloblasts - dysfuncitonal RBCs in bone marrow
Bone marrow filled with adipocytes
Anemia + hypersegmented neutrophils + Neurological symptoms
Causes of aplastic anemia
"AA -> RV FIne" Failure or destruction of myeloid stem cells due to:
- RADIATION; drugs (Benzene, Chloramphenicol, Alkylating agents, Antimetabolites);
- Viral agents (parvovirus B19, EBV, HIV, HCV);
- Fanconi's anemia (DNA repair defect);
- Idiopathic (Immune mediated, primary stem cell defect); may follow acute hepatitis.
"why take flight on AA when the RV is FIne"
Converts Vitamin K to activated vitamin K?
Effect of activated vitamin K?
Acts as cofactor for II, VII, IX, X, C, S to help coagulate
Antithrombin inactivates factors II, VII, IX, X, XI, XII
Protein C -> activated by thrombomodulin in endothelial cells to activated protein C (APC) -> Protein S acts on which cleaves and inactivates Va, VIIIa
Plasminogen is activated by tPA to plasmin -> cleaveage of fibrin mesh
PT - tests extrinsic (Tissue factor pathway) - I, II, V, VII, X
PTT - tests all factors except VII and XIII (intrinsic)
Most common hereditary thrombosis syndrome leading to hypercoagulability?
Factor V Leiden
- Most common cause of inherited hypercoagulability, 45-50% of all hypercoagulable states
- Production of mutant factor V - cannot be degraded by protein C
- Factor V is an accelerating factor that helps factor X convert prothrombin to thrombin (factor 5 is normally inhibited by protein C
#2 most common inherited hypercoagulability disorder
Prothrombin gene mutation
- Prothrombin G20210A Mutation
- Mutation of Guanine (G) to Alanine (A) in 3' untranslated region -> predisposes to thrombosis, associated with venous clots
- "Like 90210 except its 20210"
Effects of bradykinin
↑ vascular permeability
Clinical consequence of deficiency in either protein C or protein S
hypercoagulability and make too many blood clots
(b/c C and S are anticoagulants, C can't inactivate factors 5 and 8 which shut down clotting cascade.)
MOA of Heparin
Supercharges antithrombin! (Antithrombin inactivates factors II, VII, IX, X, XI, XII)
Cofactor for activation of antithrombin
↓ thrombin (thrombin converts fibrinogen to fibrin which is then activated by XIIIa to fibrin mesh)
↓ Xa (Xa converts prothrombin to thrombin)
Clinical use of heparin
Immediate anticoagulation for PE, stroke, Acute coronary syndrome, MI, DVT
Used during pregnancy (does not cross placenta)
Toxicity of Heparin
Antidote for OD?
- Rapid reversal - protamine sulfate (positively charged molecule that binds negatively charged heparin)
Newer low-molecular-weight heparins
- Enoxaparin (Lovenox) acts more on Xa
- Dalteparin (newer) inactivates factor Xa (Xa converts prothrombin to thrombin)
- Better bioavailability
- 2-4 times longer half-life
- administered subcutaneously
- No laboratory monitoring - dosage based on weight
Lepirudin, Bivalirudin, Desirudin
Directly inhibit thrombin (thrombin converts fibrinogen to fibrin)
Alternative to heparin for anticoagulatin with HIT
If a patient gets HIT and you must take off heparin, how do you maintain anticoagulation?
Put them on a direct thrombin inhibitor: Lepirudin, Bivalirudin, Desirudin (all direct thrombin inhibitors)
Newer drugs that aren't derivatives of hirudin but are direct thrombin inhibitors - Argatroban, Dabigatran.
These are all IV, wait for platelets to get above 100 or 150k, then put on Warfarin (oral) since they need extended anticoagulation for at least a month.
What do you use to monitor Heparin? LMWHs? (if you wanted to?
anti Xa activity
MOA Warfarin (Coumadin)
Interferes w/ normal synthesis and gamma=carboxylation of vitamin K -dependent clotting factors II, VII, IX, and X and protein C and S.
Metabolized by p-450
Monitor PT or INR (2-3) (extrinsic)
Clinical use of warfarin
(precaution you must make when starting warfarin!)
Chronic anticoagulation (venous thromboembolism prophylaxis, Atrial fibrillation, prevent stroke
Bleeding, teratogenic (NOT used in pregnancy, crosses placenta) drug-drug interactions
Skin-tissue necrosis: Warfarin first started, proteins C and S first affected -> transient hypercoagulable-> skin necrosis. Thus need to be on heparin or enoxaparin (lovenox) first! Then once INR is in therapeutic range (2-3), Stop H or E, continue just warfarin.
new anticoagulant that inhibits factor Xa.
Used in atrial fibrillation, prevent DVTs in knee or hip replacements.
ACTIVATE PLASMIN! - directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots, increases PT and PTT
Aminocaproic acid to reverse
Treatments for overdose of heparin
Treatment for overdose of warfarin
Fresh frozen plasma (FFP) + Oral vitamin K
Lab values to monitor the following medications:
Heparin -> PTT (intrinsic)
Warfarin -> PT or INR (2-3) (extrinsic) "The EX-PresidenT went to WARfarin"
Enoxaparin -> check factor Xa (usually don't need to check)
Treatment for heparin-induced thrombocytopenia (HIT)
Direct thrombin inhibitor (lepirudin, bivalirudin, desirudin or argatroban, dabigatran) -> monitor platelets until >100-150k -> begin Warfarin oral
Hereditary thrombosis syndromes