Wk 12: Coagulation- Procoagulants and Anticoagulants Flashcards by Ashley Campbell

Perioperative hemostasis requires consideration of the postoperative _____________ that may follow

hypercoagulability

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________ and ________ injury are important contributors to bleeding

Vascular and tissue

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With significant hemorrhage and resuscitation with crystalloids/colloids, a _________ _______ can occur resulting from significant reduction in platelet counts/dilutional thrombocytopenia and factor deficiencies

dilutional coagulopathy

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The two tests most frequently used in the perioperative setting, other than blood counts are:

Prothrombin time (PT)
Activated partial thromboplastin time (aPTT)

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Prothrombin time (PT) evaluates

Extrinsic coagulation cascade

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Activated partial thromboplastin time (aPTT) evaluates

Intrinsic coagulation cascade

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The _________ _________ time is another widely used coagulation test that assesses the intrinsic coagulation cascade, and is used to monitor low doses of unfractionated heparin (up to 1.0 units/mL)

Partial thromboplastin

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At higher heparin concentrations used during cardiac surgery, the ______ _______ ______ ( ____ ) is used

activated clotting time (ACT)

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Although PT, aPTT, PTT, and ACT coagulation tests are used to evaluate bleeding, they only examine _________ components of the overall coagulation cascade and may not be useful to determine the exact _______ of the coagulopathy

specific
cause

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The only test that definitely tells us how the system is overall working is the ______ time

bleeding

(time consuming, don’t usually do anymore)

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Whole blood viscoelastic tests including ____________ and __________ provide multiple insights into coagulation factor interaction and allow assessment of individual characteristics of either individual limbs of hemostasis or global monitoring of coagulation

Widely used in the perioperative and trauma setting

thromboelastography
thromboelastometry

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Commonly used thromboelastometric variables: (5)

-Coagulation time (onset in sec)
-Clot formation time (initial rate of fibrin polymerization in sec)
-Angle (a; in degrees)
-Maximum clot firmness (in mm)
-Lysis time (in sec., used for the diagnosis of premature lysis or hyperfibrinolysis)

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Tranexamic Acid (TXA) is an:

Antifibrinolytic agent: Lysine Analog

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Tranexamic Acid (TXA) MOA:

Competitively inhibit activation of _______ to _______, which degrades ______ clots, ______, and other plasma proteins

plasminogen to plasma

fibrin clots, fibrinogen

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Tranexemic acid (TXA) is not prothrombotic but rather a ______ ______

clot stabalizer

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Tranexemic acid (TXA) metabolism

Minimal

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Tranexemic acid (TXA) off-label uses and doses common in anesthesia (3)

-Trauma 1 g (IV)
-Total joints 1 g (IV)
-Cardiac 50mg/kg for a dose (IV)

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Desmopressin (DDAVP) MOA:

____ analog of arginine vasopressin that stimulates the release of ultra-large ____ _______ ______ (___) multimers from _______ _______

V2
von Willebrand factor (vWF)
endothelial cells

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Desmopressin (DDAVP) shortens the bleeding time of patients with mild forms of __________ or _________

Hemophilia A
von Willebrand disease

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Desmopressin (DDAVP) metabolism

Minimal

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Desmopressin (DDAVP) dose

0.3 mg/kg (IV) over 15 to 30 mins

-Hypotension possible with faster administration

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Desmopressin (DDAVP) is given over ____ to ____ minutes to avoid _______

15 to 30
hypotension (d/t vasodilation)

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Protamine is a polypeptide containing approximately ___% _________ residues

70%
arginine

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What is the only available agent to reverse unfractionated heparin

Protamine

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Protamine MOA: Inactivates the _____ heparin molecule via a simple ____ -_____ interaction

acidic acid-base

Protamine adverse reactions (4)

-Anaphylaxis -Acute pulmonary vasoconstriction -Right ventricular failure -Hypotension

Patients at risk for adverse reactions to protamine: (4)

-NPH insulin -Vasectomy -Multiple drug allergies -Prior protamine exposure

Protamine dose

1-1.5 mg (IV) per 100 units heparin MAX: 50mg/dose

Idarucizumab is the anticoagulant reversal for _________

dabigatran (Pradaxa)

Idarucizumab MOA: Binds to ___________ and its metabolites, neutralizing its anticoagulant effects

dabigatran

Idarucizumab metabolism

not clearly understood

Idarucizumab half life

10.3 h

Idarucizumab dose

5mg (IV) x 1 May consider repeat dose

Andexanet alfa reverses _________

Apixaban (Eliquis) Rivaroxaban (Xarelto)

Andexanet alfa MOA; Binds and sequesters _______ ______ inhibitor and inhibits ______ _____ pathways. Restores ______ generation

factor Xa tissue factor thrombin

Andexanet alfa metabolism

Not clearly understood

Andexanet alfa half life

1.9-4h

Andexanet alfa dose

Based on timing of last dose and anticoagulant

Fibrinogen ______-kDa plasma glycoprotein synthesized in the ________, and a critical component of effective _____ formation

340 liver clot

Fibrinogen is a substrate to 3 important enzymes involved in clot formation:

Thrombin Factor XIIIa Plasmin

Low fibrinogen levels (<_____mg/dL) can increase laboratory measures of hemostasis, including PT and PTT that may not be corrected with transfusing ___________

100 fresh frozen plasma (FFP)

Fibrinogen Transfusion guidelines often recommend increasing levels to _____ -_____-mg/dL (____ - ____g/L)

150-200 mg/dL 1.5-2.0 g/L

Fibrinogen can be repleted with __________: __ unit per ___ kg increases fibrinogen by ____ to ____mg/dL

cryoprecipitate 1 unit per 10 kg increases fibrinogen by 50-70mg/dL

Prothrombin complex concentrates are concentrates of coagulation factors that include factors: ____, ____, ____ , and ____ in variable concentrates

II, VII, IX, and X 2,7,9, and 10

Prothrombin complex concentrates are approved for use in _________ and contain mainly factor ____

hemophilia IX

Prothrombin complex concentrates are used worldwide for ______ ____ ______- induced (i.e. ______) reversal

vitamin K antagonist-induced Warfarin

Kcentra Octaplex FEIBA VH Profilnine SD Bebulin VH are examples of

Prothrombin complex concentrates

It is preferable to give Prothrombin complex concentrates which contain ______ ______ vitamin K-dependent coagulation factors and the natural anticoagulants ________ and activated __________ for warfarin reversal

all 4 antithrombin protein C

Only ______ contains factor VII in an activated form, and _______ and ______ contain low levels of factor VII

FEIBA Profilnine Bebulin

______ _______ are increasingly used in perioperative settings

Factor concentrates

Factor concentrates include (5)

Fibrinogen Prothrombin complex concentrates Hemophilia factors VIII and IX Factor XIII Recombinant Activated Factor VIIa

Aproptinin Epsilon aminocaproic acid Tranexemic acid

Antifibrinolytics

V2 agonist

Desompressin (DDAVP)

Specific single-protein activated factors that are considered bypassing agents to directly activate thrombin generation

Recombinant activated factor (s)

Recombinant activated factor (s) are currently approved for ________ with inhibitors and used off-label for _________ bleeding

hemophilia refractory

Unfractionated heparin (UFH) is an extract of _______ _____ or ______ ______, where heparin is stored in the mast cells

porcine intestine bovine lung

Unfractionated heparin (UFH) binds to __________

antithrombin (AT)

A unit of heparin is defined as the volume of heparin-containing solution that will prevent ___ mL of citrated sheep blood from clotting for ___ hour after the addition of ____mL of 1:100 _____ _______

1mL 1 hour 0.2 mL of 1:100 calcium chloride

Unfractionated heparin (UFH) metabolism

hepatic and reticuloendothelial

Unfractionated heparin (UFH) half life

0.5-2h

Unfractionated heparin (UFH) dose

2000-5000 units IV common, then titrated based on ACT Dose usually discussed with surgeon

Low-Molecular-Weight Heparins (LMWHs) are derived from standard commercial-grade _______ by chemical depolymerization to yield fragments with a mean molecular weight of _____ to ______ Da

Unfractionated heparin (UFH) 4,000 to 5,000 Da

The pharmacokinetics of enoxaparin and dalteparin between patients are more consistent than heparin because these drugs:

bind less avidly to proteins than heparin

Enoxaparin and dalteparin drug class

Low-Molecular-Weight Heparins (LMWHs)

Low-Molecular-Weight Heparins (LMWHs) Delay surgery for ___ hours after last dose in patients with normal renal function and longer with _______ ________

12 h renal dysfunction

________ does not neutralize Low-Molecular-Weight Heparins (LMWHs)

Protamine

Class of anticoagulants that high-risk surgery patients at risk for or history of HIT may receive

Direct thrombin inhibitors

Bivalirudin and argatroban drug class

Direct thrombin inhibitors

Bivalirudin MOA Bind in a ________ manner to _______ by interacting with both the _______ site and __________-binding site

bivalent thrombin catalytic fibrinogen

Bivalirudin metabolism

Plasma; CYP450

Bivalirudin half life

25 min

Bivalirudin dose

0.75mg/kg/dose (IV) x 1 then 1.75mg/kg/h for procedure duration

Argatroban metabolism

Hepatic

Argatroban half life

39-51 min

Argatroban dose

15-30mcg/kg/min (IV)

Bivalirudin and argatroban time to stop before surgery

4-6 h

Dabigatran etexilate time to stop before surgery

48 hours 72-96 h impaired renal function

Apixaban time to stop before surgery

Low risk bleeding: 1-2 days High risk bleeding: 2-3 days

Rivaroxaban time to stop before surgery

Low risk bleeding: 1-2 days High risk bleeding: 2-3 days

Heparin (UFH) time to stop before surgery

4-6 h may need to continue for cardiovascular surgery

Warfarin time to stop before surgery

5 days to allow INR <1.5 Bridge high risk patients with heparin

Current recommendations are to discontinue thienopyridines ___to___ days before elective surgery and to avoid ______ anesthesia until the effects of these drugs have dissipated

5 to 7

Thienopyridines are oral ___________agents

antiplatelet

Clopidogrel Prasugrel Ticagrelor Drug class

Thienopyridines platelet inhibitors

Clopidogrel, Prasugrel MOA: Selective, __________ binding to and inhibition of _______ receptor on platelets Both are ______ metabolized to active form

irreversible P2Y12 Prodrugs

Ticagrelor MOA Selective, __________ binding to and inhibition of _______ receptor on platelets It is a _______-acting agent (vs prodrug)

Reversible P2Y12 Direct

Aspirin in an _____________ and platelet _____________

acetylsalicylate inhibitor

Aspirin MOA

Cylooxygenase (COX) inhibition

Clopidogrel has a higher chance of causing _______ due to metabolism, while Prasugrel is more _______ and resistance is rare

resistance potent

Pharmacolologic thrombolysis is activated by drugs that act as __________ activators to convert the endogenous proenzyme __________ to the fibrinolytic enzyme ________ that lysis clot and other proteins

plasminogen plasminogen plasmin

The goal of thrombolytic therapy is to restore _____________

circulation

Tissue plasminogen activator (tPA) drug type

Fibrinolytic

Tissue plasminogen activator (tPA) is indicated for: (3)

Acute ischemic stroke Acute myocardial infarction Acute massive PE for lysis