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Flashcards in Heme Deck (37):
1

Anemias

  • 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.

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Microcytic, hypochromic (MCV <80)

  • Iron deficiency
  • ACD
  • Thalassemias
  • Lead poisoning
  • Sideroblastic anemia

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Normocytic, normochromic anemia

NONHEMOLYTIC

  • ACD
  • Aplastic anemia
  • Kidney disease

HEMOLYTIC: Intrinsic and Extrinsic

Intrinsic 

  • RBC membrane defect: hereditary spherocytosis
  • RBC enzyme deficiency: G6PD, PK
  • HBC
  • SCA
  • PNH

Extrinsic

  • Autoimmune
  • MIHA
  • MAHA
  • Infections

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Macrocytic anemia (MCV >100)

MEGALOBLASTIC

  • Folate deficiency
  • B12 deficiency

 

NON-MEGALOBLASTIC

  • Liver disease
  • Alcoholism
  • Reticulocytosis
  • Metabolic disorders
  • Drugs

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TIBC

total iron binding capacity = transferrin x 1.4. Anything that elevates transferrin will elevate TIBC

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Ferritin

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.

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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.

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Hemochromatosis

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.

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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.

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Megaloblastic anemia

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

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Bone marrow filled with adipocytes

Aplastic anemia

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Anemia + hypersegmented neutrophils + Neurological symptoms

B12 Deficinecy

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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"

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Converts Vitamin K to activated vitamin K?

Effect of activated vitamin K?

  • Epoxide reductase
  • Acts as cofactor for II, VII, IX, X, C, S to help coagulate

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Anti-coagulation

  • 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

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PT

PTT

PT - tests extrinsic (Tissue factor pathway) - I, II, V, VII, X

PTT - tests all factors except VII and XIII (intrinsic)

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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

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#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"

 

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Effects of bradykinin

  • ↑ vasodilation
  • ↑ vascular permeability
  • ↑ pain

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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.)

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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)
  • Short half-life

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Clinical use of heparin

  • Immediate anticoagulation for PE, stroke, Acute coronary syndrome, MI, DVT
  • Used during pregnancy (does not cross placenta)
  • Follow PTT

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Toxicity of Heparin

Antidote for OD?

  • Bleeding
  • Thrombocytopenia (HIT)
  • Osteoporosis
  • Drug-drug interactions

 

  • Rapid reversal - protamine sulfate (positively charged molecule that binds negatively charged heparin)

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LMWH

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

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Lepirudin, Bivalirudin, Desirudin

  • Directly inhibit thrombin (thrombin converts fibrinogen to fibrin)
  • Alternative to heparin for anticoagulatin with HIT

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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.

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What do you use to monitor Heparin? LMWHs? (if you wanted to?

  • PTT
  • anti Xa activity

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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)

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Clinical use of warfarin

Toxicity 

(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.

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Rivaroxaban

  • new anticoagulant that inhibits factor Xa.
  • Used in atrial fibrillation, prevent DVTs in knee or hip replacements.

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Thrombolytics

MOA

Reversal

  • Streptokinase
  • urokinase
  • tPA (alteplase)
  • APSAC (anistreplase)

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

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Treatments for overdose of heparin

Protamine sulfate

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Treatment for overdose of warfarin

Fresh frozen plasma (FFP) +  Oral vitamin K

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Lab values to monitor the following medications:

  • Heparin
  • Warfarin
  • Enoxaparin

  • 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)

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Treatment for heparin-induced thrombocytopenia (HIT)

Direct thrombin inhibitor (lepirudin, bivalirudin, desirudin or argatroban, dabigatran) -> monitor platelets until >100-150k -> begin Warfarin oral

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Hereditary thrombosis syndromes

  • Factor V Leiden
  • Prothrombin gene mutation
  • Antithrombin III deficiency
  • Protein C deficiency
  • Protein S deficiency

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