Treatments and Test for Final Flashcards
Template bleeding time
Evaluates response to vascular injury. Some platelet disorders have a long bleeding time.
Inflate blood pressure cuff –> make incision –> Time how long it takes to stop bleeding
Doesn’t test coagulation, only platelet plug formation.
Only test that tests in vivo platelet funciton.
Closure Time
An alternative to bleeding time
“in-vitro bleeding time”
Better than bleeding time at detecting aspirin-related bleeding and von Willebrand disease.
Platelet Aggregation
Why - to find platelet function abnormalities
How - Add aggregating agents to patient’s sample. See if platelets aggregate. Measure decrease in sample turbidity.
Aways repeat an abnormal test.
Coagulation Lab Tests
How - Draw blood into citrate tube. Spin tube, decant plasma. Add reagants to plasma and watch for formation of fibrin.
Prothrombin Time (PT)
Plasma + Thromboplastin
Measures External pathways.
Always order an INR over a PT.
INR
A corrected PT for various thromboplastin manufacturers. . (International normalized ratio)
Order to:
- Assess liver function
- Monitor Warfarin therapy
- Dx DIC
- To assess pre-op status.
Partial Thromboplastin Time (PTT)
Plasma + Phospholipid
Measure Intrinsic pathway
APTT= same thing
PTT increased: Hemophilia A & B, DIC, heparin, and inhibitors.
Should order when:
- Investigate hx of abnormal bleeding
- Monitor heparin therapy
- Dx DIC
- Dx antiphospholipid antibody
- To assess pre-op status.
Thrombin Time
Plasma + Thrombin
Measures conversion of fibrinogen to fibrin
Bypasses intrinsic and extrinsic pathway.
When to order?:
When PTT is prolonged and you want to rule out fibrinogen problem (Rare!)
PTT Mixing Study
Pooled plasma + patient plasma + phospholipid.
Order when PTT is prolonged, but TT is normal.
If PTT corrects –> something is missing
If PTT doens’t correct –> inhibitor present (antibody that messes up the test)
Fibrin Degredation Product Assay
Measures FDPs (including D-dimers)
Very sensitive! Used to rule out, not rule in.
D-Dimer Assay
Similar to FDP assay, but specific to D-dimers only.
Also very sensitive.
Used to rule out, not rule in.
Fibrinogen Assay
Measure fibrinogen
Decreased in DIC and massive bleed. (think if patient was given packed cells in place of whole blood and patient continued to bleed).
Clopidogrel
Class - Antiplatelet; ADP Receptor Antagonist
MOA: Irreversible ADP P2Y Receptor Antagonist.
PK: Oral drugs w/ duration of days. Activation by CYP2C19.
Use: Used during stenting and recommended for patients that don’t tolerate aspirin.
A.E. Bleeding, nausea, diarrhea, rash, severe leukopenia (1% or patients)
Ticlopidine
Class - Antiplatelet; ADP Receptor Antagonist
MOA: Irreversible ADP P2Y Receptor Antagonist.
PK: Oral drugs w/ duration of days.
Use: Used during stenting and recommended for patients that don’t tolerate aspirin.
A.E. Bleeding, nausea, diarrhea, rash, severe leukopenia (1% or patients), TTP (very rare)
Worst A.E. of the 3.
Prasugrel
Class - Antiplatelet; ADP Receptor Antagonist
MOA: Irreversible ADP P2Y Receptor Antagonist.
PK: Oral drugs w/ duration of days.
Use: Used during stenting and recommended for patients that don’t tolerate aspirin.
A.E. Bleeding, nausea, diarrhea, rash, severe leukopenia (1% or patients)
Abciximab
Class - Antiplatelet; GPIIB/IIIA Receptor Inhibitors
MOA - Humanized MAB against GPIIB/IIIA receptor. Inhibits the final common pathway of platelet aggregation.
PK: IV
Uses: With aspirin and heparin during angioplasty. For acute coronary syndromes.
Adverse effects: Bleeding, thrombocytopenia (chronic use)
Eptifibatide
Class - Antiplatelet; GPIIB/IIIA Receptor Inhibitors
MOA - Fibrinogen analogue that inhibits the GPIIB/IIIA receptor. Inhibits the final common pathway of platelet aggregation.
PK: IV
Uses: With aspirin and heparin during angioplasty. For acute coronary syndromes.
Adverse effects: Bleeding, thrombocytopenia (chronic use)
Tirofiban
Class - Antiplatelet; GPIIB/IIIA Receptor Inhibitors
MOA - Non-peptide competitive inhibitor of GPIIB/IIIA receptor. Inhibits the final common pathway of platelet aggregation.
PK: IV
Uses: With aspirin and heparin during angioplasty. For acute coronary syndromes.
Adverse effects: Bleeding, thrombocytopenia (chronic use)
Dipyridamole
Class - Antiplatelet
MOA: Increases cAMP and inhibits platelet activation. Phosphodiesterase 3 inhibitor. Inhibits platelet uptake of adenosine and thus increases adenosine interaction with Adenosine A2 recpetor –> increases cAMP.
Also a vasodilator.
Little to no beneficial effect by itself –> used in combination with aspirin or warfarin.
Unfractionated Heparin
= High molecular weight heparin (HMW). Often just called heparin.
Class - Indirect Thrombin Inhibitors
MOA: Bind to antithrombin III which causes it to do a better job incactivating thrombin and factor Xa and IIA.
PK - Parenteral; binds to plasma proteins (highly variable anticoagulant response). Short half life (1 hour)
Requires close monitoring of PTT.
A.E. - Bleeding, thrombocytopenia (2x likely in women)
Low molecular weight heparin
Class - Indirect Thrombin Inhibitors
Commonly used form: Lovenox = Enoxaparin sodium
PK - Parenteral; more predictable than HMW (less plasma protein binding) Medium half life (4 hours)
MOA: Bind to antithrombin III which causes it to do a better job incactivating thrombin and factor Xa amd IIA.
Monitoring of PTT (less than HMW)
A.E. - Bleeding, thrombocytopenia (2x likely in women)
Fondaparinux
Class - Indirect Thrombin Inhibitors
PK - Parenteral
MOA: Bind to antithrombin III which causes it to do a better job incactivating thrombin and factor Xa.
Synthetic. Longer half life (17 hours).
Bivalirudin
Class - Direct Thrombin Inhibitors
PK - Parenteral
MOA- Directly binds and inhibits thrombin.
Argatroban
Class - Direct Thrombin Inhibitors
PK - Parenteral
MOA - Directly binds and inhibits thrombin.
Dabigatran etexilate
Class - Direct Thrombin Inhibitors
PK - Oral
MOA - Directly binds and inhibits thrombin.
Protamine
MOA - Binds heparin to form a stable complex that lacks anitcoagulant activity. Completely reverses HMW; paritally LMW; and no reversal activity of Fondaparinux.
Warfarin
Class- Anticoagulant
PK - Oral. MANY DRUG-DRUG INTERACTIONS. Requires constant monitoring. Very narrow TI. Dosing varies based on VKORC1 and CYP2C9 polymorphisms,
MOA: Inhibits Vitamin K dependent epoxide reductase in turn blocking synthesis of Vitamin K dependent clotting factors. Inhibits gamma-carboxylation of factors II, VII, IX, and X and protein C and S.
Crucial note: Initially creates hypercoaguable state due to blocking protein C and S; thus we must use a “bridge” to treatment.
Adverse effects: BLEEDING, flatulence and diarrhea, cutaneous necrosis, chondrodysplasia punctata.
Racemic mixture of R and S enantiomers. S is the more active enantiomer. They are metabolized differently.
If bleeding too much: Stop the drug. Add vitamin K (phytonadione), prothrombin complex concentrates, recombinant factor VIIa
Rivaroxaban
Class - Xa inhibitor
PK - Oral
MOA: Inhibit factor Xa
PK: Rapid onset of action and shorter half-life than warfarin. Don’t require monitoring.
No antidote!
Apixaban
Class - Xa inhibitor
PK - Oral
MOA: Inhibit factor Xa
PK: Rapid onset of action and shorter half-life than warfarin. Don’t require monitoring.
No antidote!
Edoxaban
Class - Oral Xa inhibitor
PK - Oral
MOA: Inhibit factor Xa
PK: Rapid onset of action and shorter half-life than warfarin. Don’t require monitoring.
No antidote!
Phytonadione
Vitamin K
Class - Coagulant
Antidote for Warfarin caused bleeding
Streptokinase
Class - Fibrinolytic
Rarely used clinically.
Complexes w/ plasminogen wherever it is and facilitates formation of plasmin.
Can only be used once due to antibody formation?
From Strep bacteria.
Urokinase
Class - Fibrinolytic
MOA: Kidney enzyme that directly converts plasminogen to plasmin. Occurs primarily in response to inflammatory stimuli. Promotes extravascular fibrinolysis.
Alteplase
Class - TPA
MOA - Preferentially acitvates plasminogen to plasmin that is bound to firbrin which confines it to the thrombus rather than systemic activation.
Dissolve EXISTING life-threatening thrombi. Given IV. 3-4 hour window.
Only thrombolytics approved for use in stroke
PK: Given IV; can be given with IR
A.E. Bleeding, Cost
Reteplase
Class - TPA
MOA - Preferentially acitvates plasminogen to plasmin that is bound to firbrin which confines it to the thrombus rather than systemic activation.
Dissolve EXISTING life-threatening thrombi. Given IV. 3-4 hour window.
Only thrombolytics approved for use in stroke
PK: Given IV; can be given with IR
A.E. Bleeding, Cost
Tenecteplase
Class - TPA
MOA - Preferentially acitvates plasminogen to plasmin that is bound to firbrin which confines it to the thrombus rather than systemic activation.
Dissolve EXISTING life-threatening thrombi. Given IV. 3-4 hour window.
Only thrombolytics approved for use in stroke
PK: Given IV; can be given with IR
A.E. Bleeding, Cost
Fresh Frozen Plasma
All coag factors in normal levels.
Used to reverse warfarin’s effect (very high INR/risk of hemorrhage patients) or replace factors missing due to liver disease or DIC.
Cryoprecipitent
1U = 10 FFP
-Provides fibrinogen, vWF, factor VIII, factor XIII, fibronectin.
Use when very deficient and volume for FFP is going to be a problem.
