Anticoagulants & Procoagulants Class (3 per) PDF

12/2/24 Pharmacology of ANTICOAGULANTS & PROCOAGULANTS Kelly Elmore, DNP, APRN-CRNA Mary Baldwin University NAP Advanced Pharmacology for Anesthesiology Practice I 1 Physiology of Hemostasis A Quick Review of Coagulation 2 Overview Normal blood v...

12/2/24 Pharmacology of ANTICOAGULANTS & PROCOAGULANTS Kelly Elmore, DNP, APRN-CRNA Mary Baldwin University NAP Advanced Pharmacology for Anesthesiology Practice I 1 Physiology of Hemostasis A Quick Review of Coagulation 2 Overview Normal blood vessel Endothelial cells Nitric oxide Vasodilation _________________________________ Binds platelet receptors Cascade of reactions to prevent activation & aggregation 3 1  12/2/24 Overview Injured blood vessel Connective tissue & collagen exposed Platelets adhere & rupture ________________________________ Potent local vasoconstrictor Platelet plug, blood clot 4 Primary Hemostasis ADHESION ACTIVATION AGGREGATION 5 Platelet Plug: Adhesion Exposure of subendothelial collagen layer Endothelial cells synthesize & release Factor VIII = von Willebrand Factor Von Willebrand disease Increased bleeding time, despite normal PLT count and clot retraction ____________________________ releases endogenous stores of vWF ___________________________________________ (Factors I, VIII, XIII) 6 2  12/2/24 Platelet Plug: Adhesion h ttp s ://w w w.re s e a rc h g a te.n e t/fig u re /P la te le t-a d h e s io n -a n d -a g g re g a tio n -N o te s -A -P la te le ts -n o rm a lly -c irc u la te -th ro u g h -th e _ fig 1 _ 2 6 2 8 8 5 3 3 4 7 Platelet Plug: Activation Thrombin = activated Factor II (Factor IIa) binds thrombin receptor on PLT PLT ________________________________________ (activation) Mediator synthesis & release Thromboxane A2, adenosine diphosphate (ADP) Activates additional PLTs, promotes aggregation 8 Platelet Plug: Activation https://www.sciencedirect.com/science/article/abs/pii/S0049384818303050 9 3  12/2/24 Platelet Plug: Aggregation Thromboxane A2 uncovers fibrinogen receptors Fibrinogen binds, linking PLTs Water-soluble, friable PLT plug forms Temporary hemostasis Role of prostacyclin? 10 Platelet Plug: Aggregation h ttp s ://w w w.re s e a rc h g a te.n e t/fig u re /S te p s -in -p la te le t-a g g re g a tio n -a n d -ro le -o f-s e ro to n in -C o lla g e n -e xp o s e d -a fte r-e n d o th e liu m _ fig 1 _ 5 1 0 9 8 3 9 7 11 From PLT Plug… To Stable Clot h ttp s ://w w w.o s m o s is.o rg /le a rn /C o a g u la tio n _ % 2 8 s e c o n d a ry _ h e m o s ta s is % 2 9 12 4  12/2/24 Secondary Hemostasis Fibrin production Coagulation cascade: intrinsic, extrinsic, & final common pathway All clotting factors involved Fibrin fibers Woven net over platelet plug RBCs trapped Cross-linked and water insoluble Stable clot 13 h ttp s ://w w w.o s m o s is.o rg /a n s w e rs /c o a g u la tio n -c a s c a d e 14 Clotting Factors FACTOR NAM E SOURCE VITAM IN K DEPENDENT I Fibrinogen Liver No II Prothrombin/thrombin Liver Yes III Tissue factor/thromboplastin Vascular wall, injured cells --- IV Calcium Diet --- V Proaccelerin Liver No VII Proconvertin Liver Yes VIII:C Antihemophiliac Factor Liver No 15 5  12/2/24 Clotting Factors FACTOR NAM E SOURCE VITAM IN K DEPENDENT VIII:vWF von W illebrand Factor Vascular endothelial cells --- IX Christmas Factor Liver, tissues Yes X Stuart Prower Factor Liver Yes XI Plasma thromboplastin antecedent Liver No XII Hageman Factor Liver No XIII Fibrin-stabilizing Factor Liver No Protein C Liver Yes Protein S Liver Yes 16 3 Phase Cell-Based Coagulation Model INITIATION AMPLIFICATION PROPAGATION 17 Extrinsic Pathway: Initiation Low level initiation occurs in normal conditions Outside vascular compartment (= extrinsic) Tissue Factor pathway Tissue Factor (Thromboplastin or Factor III) Primary initiator of coagulation 18 6  12/2/24 Extrinsic Pathway: Initiation Extrinsic blood vessel damage à Thromboplastin (III) release Thromboplastin binds and activates factor VII Thromboplastin and activated factor VII (VIIa) forms a complex with calcium (factor IV) on the platelet surface This complex activates factor X (Xa) Small amounts of thrombin formed 19 Extrinsic (Tissue Factor) Pathway 20 Intrinsic Pathway: Amplification Intrinsic blood vessel damage à Factor XII activated (XIIa) Activates factor XI (XIa) Activates factor IX (IXa) Factor IXa forms complex with activated factor VIII:C and calcium (IV) on platelet surface This complex activates factor X (Xa) Thrombin is amplified by factors VII, IX, and XI 21 7  12/2/24 Intrinsic Pathway 22 Approaching the Final Common Pathway: Propagation Factor IXa generated by tissue factor/factor VIIa complex Also activated by factor XIa Factor IXa combines with its co-factor VIIIa on platelet surface Factor IXa responsible for activating factor X (Xa) 23 Final Common Pathway Activated factor Xa forms complex with activated factor Va and calcium (IV) on platelet surface This converts prothrombin (factor II) to thrombin (factor IIa) Thrombin converts fibrinogen (factor I) to fibrin (factor Ia) Presence of factor XIII causes covalent bonding à Fibrin cross-linking occurs, forming a clot ______________________________________________ = Stabilization 24 8  12/2/24 Final Common Pathway 25 Coagulation Testing A Quick Review of Laboratory Evaluation 26 27 9  12/2/24 Prothrombin Time (PT) Extrinsic pathway (& final common pathway) Detect & diagnose bleeding or excessive clotting disorders Monitor anticoagulant therapy Normal PT: 11 – 14 seconds Normal INR: 0.8 – 1.1 Prolonged PT Decreases in VII, V, X, prothrombin (II) _________________________________________________________________ (vitamin K antagonist) Hepatic dysfunction 28 Activated Partial Thromboplastin Time (aPTT) Intrinsic pathway (& final common pathway) Detect bleeding disorder, thrombotic episode Monitor anticoagulant therapy Normal aPTT: 25 – 35 seconds Prolonged PTT Hepatic dysfunction, leukemia Intrinsic coagulation factor or Vitamin K deficiencies ______________________________________________ therapy, other anticoagulants 29 30 10  12/2/24 Activated Clotting Time Intrinsic pathway (& final common pathway) Whole blood mixed with activator Activator speeds up clotting time to 70 – 150 seconds Monitors heparinization, protamine antagonization Prolonged by Hypothermia* Thrombocytopenia Contact activation inhibitors (aprotinin) Factor I, XII, VII deficiencies 31 Coagulation Tests Bleeding time: 3 – 10 minutes Platelet count: 150,000 – 400, 000 cells/mL Thrombin time: < 30 seconds Fibrinogen: > 150 mg/dL 32 Thromboelastography, Thromboelastometry Coagulation time: onset of clot Clot formation time (angle formation): rate of fibrin polymerization Maximum clot firmness: max clot strength Lysis time: diagnosis of premature clot lysis and hyperfibrinolysis 33 11  12/2/24 Thromboelastography 34 35 Pharmacology of Anticoagulants Drugs to Reduce Clotting 36 12  12/2/24 Indications Cardiovascular procedures Thrombus prophylaxis Cardiovascular disease Atrial fibrillation 37 Anticoagulants & Anesthesia Continuing vs holding anticoagulants Thromboembolic risk vs. bleeding risk? Comorbidities, type of surgery, etc. Determine timing of held anticoagulant Bridge therapy in place? Analgesics that interfere with PLT function 38 Heparin Unfractionated vs. fractionated heparin Naturally occurring glycosaminoglycan Released from _________________________________________ during injury/inflammation Unfractionated derived from porcine intestine, bovine lung Uses DVT, PE, arterial thromboembolism ACS, MI, UA Perioperative anticoagulation, extra-corporeal circulation, hemodialysis 39 13  12/2/24 h ttp s ://w w w.o s m o s is.o rg /le a rn /A n tic o a g u la n ts :_ H e p a rin 40 Heparin Mechanism of action Reversibly binds antithrombin III Increases its activity 1,000 - 10,000 times Inhibits Thrombin*, Factor Xa* Factors XIIa, XIa, and IXa Inhibits PLT activation by fibrin h ttp s ://w w w.re s e a rc h g a te.n e t/fig u re /M e c h a n is m -o f-a c tio n -o f-u n fra c tio n a te d -a n d -lo w -m o le c u la r-w e ig h t-h e p a rin _ fig 1 _ 2 5 6 2 8 9 9 9 2 41 Heparin Pharmacokinetics IV (therapeutic) onset immediate SC (prophylactic) onset 1 – 2 hrs Effectiveness related to antithrombin III activity, protein binding, individual response ______________________________________________*** and protein binding may cause heparin resistance 42 14  12/2/24 Heparin Pregnancy Lower plasma levels Reduced efficacy Monitor Xa levels Does not cross placenta No available data on birth defect, miscarriage risk Peds Use preservative free 43 Unfractionated Heparin: Sites of Action h ttp s ://w w w.s c ie n c e d ire c t.c o m /s c ie n c e /a rtic le /a b s /p ii/S 1 0 8 4 2 0 8 X 0 6 0 0 0 2 0 6 44 Heparin & Anesthetic Considerations Review medications, labs Neuraxial anesthesia Recommended > 4 hrs interruption (therapeutic) Avoided in coagulopathy Increased bleeding risk in bloody or difficult neuraxial procedures No contraindication to regional anesthesia with low-dose Monitor for _________________________________________________ deficit Reversal required? 45 15  12/2/24 Heparin: Laboratory Evaluation Activated Partial Activated Clotting Time (ACT) Thromboplastin Time (aPTT) Heparin blocks classical intrinsic and Heparin blocks classical intrinsic and final common pathways final common pathways Prolongs ACT Prolongs PTT Goal > 350 – 400 seconds Goal range 1.5 – 2.5x normal 46 Heparin-Induced Thrombocytopenia (HIT) Formation of heparin-dependent antibodies to platelet factor IV Platelet activation + aggregation Arterial and venous thrombosis Preformed antibodies may cause subsequent allergic reaction to heparin Severe thrombocytopenia: 50% decrease or < 100,000 May occur within hours of heparin exposure Severe reaction within 4-5 days 47 Low-Molecular-Weight Heparin Greater inhibition of factor Xa than thrombin (IIa) Less protein binding – greater predictability in dose-response curve 100% bioavailability Peak 2 – 4 hrs (SC) Renal clearance Monitor factor Xa levels for therapeutic effect 48 16  12/2/24 Low-Molecular-Weight Heparin Indications Thromboembolic prophylaxis Treatment of DVT/PE, MI Bridge therapy Protamine Does not neutralize LMWH Unpredictable response to protamine 49 LMWH & Anesthetic Considerations Held for 12 hrs prior to surgery Risk of spinal, epidural hematoma Delay PNB/neuraxial 10 – 12 hrs following prophylactic Delay PNB/neuraxial 24 hrs following therapeutic Consult ASRA guidelines 50 Warfarin Vitamin K antagonist Vit K epoxide reductase converts vit K-dependent coagulation proteins to active form Inhibits synthesis of Factors.. II (prothrombin) VII IX X h ttp s ://w w w.m d p i.c o m /2 0 7 3 -4 4 0 9 /1 0 /4 /7 7 3 51 17  12/2/24 Warfarin Sites of Action h ttp s ://w w w.s c ie n c e d ire c t.c o m /s c ie n c e /a rtic le /a b s /p ii/S 1 0 8 4 2 0 8 X 0 6 0 0 0 2 0 6 52 Warfarin Coumarin derivative Oral anticoagulant (100% bioavailability) Delayed onset: 8 – 12 hrs Delayed peak: 36 – 72 hrs Dose: 2 – 10 mg (variable) Crosses __________________________________________________* Hepatic metabolism; biliary, renal excretion 53 Warfarin Laboratory Evaluation Prothrombin time (PT) Sensitive to prothrombin, factors VII and X International normalized ratio (INR) Anticoagulation target value of 2.0 – 3.0 Dose response changes may occur d/t dietary changes, poor compliance, liver disease 54 18  12/2/24 Warfarin Indications Venous thromboembolism prophylaxis Prevention of systemic emboli & stroke Valve replacement Atrial fibrillation Hypercoagulable patients 55 Warfarin & Anesthetic Considerations Evaluate INR 3 – 5 days preoperative discontinuation Reversal ___________________________________________________________________ (emergent) Vitamin K O ral preferred, m ore predictable response IV for severe episodes, slow adm inistration to avoid anaphylaxis Reversal not im m ediate (up to 24 hrs) Prothrombin complex concentrate (immediate reversal) 56 57 19  12/2/24 Fondaparinux (Arixtra) Synthetic anticoagulant Inhibits factor ____________________________ (indirectly) Administered subcutaneously Indications DVT/PE prevention Alternative to heparin in HIT Held 2+ days prior to surgery 58 Direct Thrombin Inhibitors (Parenteral) Bivalirudin Argatroban High affinity, specificity for binding Less affinity, specificity for binding thrombin thrombin Interventional cardiology, high-risk HIT Interventional cardiology, high-risk HIT Monitor ACT Monitor aPTT, ACT Hold 4 – 6 hrs before surgery Hold 4 – 6 hrs before surgery 59 Direct Thrombin Inhibitors (PO) Dabigatran Etexilate (Pradaxa) Indications Stroke, embolism risk in aFib DVT/PE treatment, prevention Monitor _____________________________________________* or aPTT Consider risk:benefit in perioperative period (minimal data on recommendations) 60 20  12/2/24 Direct Factor Xa Inhibitors Rivaroxaban (Xarelto) Apixaban Inhibits free, clot-bound, and Inhibits free, clot-bound, and prothrombinase complex bound Xa prothrombinase complex bound Xa Reduced stroke risk in aFib Reduced stroke risk in aFib DVT/PE prophylaxis, treatment DVT/PE prophylaxis, treatment Hold 1-2 days before surgery (3 days Hold 3-5 days before regional/neuraxial recommended for regional) 61 Coagulation Cascade Revisited 62 Aspirin Acetylsalicylic acid, non-steroidal anti-inflammatory drug _________________________________________________________ Indications Atherosclerotic vascular disease Coronary artery disease Reduce occlusive vascular events Pain, fever, inflammation 63 21  12/2/24 Aspirin Mechanism of action Irreversible acetylation of cyclooxygenase Inhibits both isozyme forms (COX-1 > COX-2) Cyclooxygenase produces pro-inflammatory prostaglandins and pro- clotting thromboxanes Prevents formation of thromboxane A2 Lasts for life of PLT: _______________________________________________ 64 o rth o b u lle ts /p h o to s /illu s tra tio n -s h o w s -th e -m e c h a n is m -o f-a c tio n -o f-a s p irin /1 0 1 6 2 3 1 7 0 5 1 0 5 5 4 6 8 / 65 Clopidogrel (Plavix) Prodrug (active metabolite) Mechanism of action Irreversible binding to P2Y12 receptor _____________________________________________ for PLT activation and aggregation Indications Dual antiplatelet therapy with ASA in ACS, PCI Plavix resistance is a risk 66 22  12/2/24 h ttp s ://w w w.re s e a rc h g a te.n e t/fig u re /M e c h a n is m -o f-a c tio n -c lo p id o g re l-T h e -a c tiv e -m e ta b o lite -s e le c tiv e ly -in h ib its -A D P -b in d in g _ fig 2 _ 4 2 6 4 0 0 0 8 67 Clopidogrel & Anesthetic Considerations Discontinue 5 – 7 days before surgery, regional anesthesia Elective, high-risk surgery preferably delayed 1 year after PCI with DES + Plavix therapy 1 month after BMS May be instructed to _________________________________________ 68 Cangrelor ___________________________________________________ P2Y 12 Inhibitor FDA – adjunct to PCI to decrease risk of: MI Repeat revascularization Stent thrombosis Short-acting intravenous form Half-life: 3 – 6 min. PLT recovery: 30 – 60 min. 69 23  12/2/24 Platelet Glycoprotein IIb/IIIa Antagonists Abciximab, tirofiban, eptifibatide Reduce thrombus formation Acute coronary syndrome Angioplasty failure Stent thrombosis 70 GP IIb/IIIa Antagonists Mechanism: Bind or competitively inhibit the fibrinogen receptor Block binding of fibrinogen to GP IIb/IIIa receptors Block PLT aggregation Im a g e : D.J. S c h n e id e r v ia h ttp s ://w w w.re s e a rc h g a te.n e t/fig u re /M e c h a n is m -o f-a c tio n -o f-a n tip la te t-th e ra p y -c o m m o n ly -u s e d -in -p e rc u ta n e o u s -c o ro n a ry _ fig 6 _ 5 1 6 3 7 6 3 2 71 GP IIb/IIIa Antagonists & Anesthetic Considerations Bridge therapy Reports of use as bridge following discontinuation of Plavix preoperatively Tirofiban: 50% platelet function recovery, 4 hours after d/c May reduce risk of stent thrombosis, adverse CV events Evidence for recommendation is low (preferable in high risk?) Discontinuation Most sources: _________________________________ before surgery Im a g e : D.J. S c h n e id e r v ia h ttp s ://w w w.re s e a rc h g a te.n e t/fig u re /M e c h a n is m -o f-a c tio n -o f-a n tip la te t-th e ra p y -c o m m o n ly -u s e d -in -p e rc u ta n e o u s -c o ro n a ry _ fig 6 _ 5 1 6 3 7 6 3 2 72 24  12/2/24 Thrombolytic Agents Plasminogen activators Convert plasminogen to plasmin (fibrinolytic enzyme) Clot lysis Indications Restore circulation through occluded vessel (PE, ischemic CVA, AMI, etc.) Streptokinase, urokinase, tissue plasminogen activator (tPA) 73 Thrombolytic Agents Side effects, risks _____________________________________________________________ Hemorrhage in trauma, surgery, invasive procedures Angioedema Anesthetic management Contraindicated within minimum of 2 days neuraxial/regional, surgery Assessments every 2 hrs for neurological deficits 74 MemoryMaster Knowledge Check What are the options for coumadin reversal? What is the onset of action of heparin? Valley Anesthesia.(2023). Memory Master: Questions and answers for the student nurse anesthetist (33rd ed.). pp.99-101 75 25  12/2/24 MemoryMaster Knowledge Check What is the most common cause of heparin resistance? How can this be treated? Where do coumarin-like drugs work (organ)? How long should therapeutic dose LMWH be held before surgery? Valley Anesthesia.(2023). Memory Master: Questions and answers for the student nurse anesthetist (33rd ed.). pp.99-101 76 Physiology of Anticoagulation A Quick Review 77 Anti-coagulation Pathway: Antithrombin III Activated antithrombin III binds: Factor IIa (thrombin)* Factor Xa* Partial inhibition – factors IX, XI, XII Forms complexes Removes clotting factors from circulation Intrinsic & final common pathway (neutralizes) 78 26  12/2/24 Antithrombin III Synthesized by the liver Required co-factor for heparin Unresponsive to heparin – suspect ATIII deficiency Acquired ATIII deficiency Cirrhosis Nephrotic syndrome 79 Anti-Coagulation Pathway: Plasmin Plasminogen (inactive form of plasmin) Synthesized in liver Circulates in blood vessels Mixes into thrombus during formation 80 Anti-Coagulation Pathway: Plasmin Tissue-type plasminogen activator (tPA) Synthesized by _______________________________________________ Released into circulation, stimulated by thrombin + venous stasis Joins fibrin in thrombus, binding strongly Converts plasminogen to plasmin 81 27  12/2/24 Anti-Coagulation Pathway: Plasmin Urokinase-type plasminogen activator (uPA) Small amounts in circulation Low affinity for binding fibrin Converts plasminogen into plasmin Streptokinase Another plasminogen activator Low affinity for fibrin 82 Plasmin Breaks down fibrin = fibrinolysis Fibrin degradation products = fibrin split products Maintains vascular patency Endothelial cells regulate coagulation + anti-coagulation 83 h ttp s ://w w w.c e ll.c o m /tre n d s /b io c h e m ic a l- s c ie n c e s /fu llte xt/S 0 9 6 8 -0 0 0 4 % 2 8 9 9 % 2 9 0 1 5 2 1 -2 ?c o d e = c e ll- s ite 84 28  12/2/24 Anti-Coagulation Pathway: Protein C Protein C Activated by thrombin-thrombomodulin complex Bound thrombin has no procoagulant property Regulates anti-coagulation Anti-inflammatory properties Binds Protein S 85 Anti-Coagulation Pathway: Protein S Protein S Binds factors Va and VIIIa (co-factors for thrombin) Compromises complex formation 86 Pharmacology of Procoagulants Drugs to Reduce Bleeding 87 29  12/2/24 Antifibrinolytics & Anesthesia Increasing prophylactic use Reduce bleeding, need for allogeneic blood transfusion Cardiac surgery w/CPB Major ______________________________________________ Hepatic surgery Major trauma 88 Epsilon Aminocaproic Acid (EACA, Amicar) Synthetic anti-fibrinolytic Enhances formation of stable clots Competitive inhibition of plasminogen to plasmin Reduction in need for _____________________________________________ Cardiac surgery (US) Safety concerns (Europe; limited conclusive data) 89 Tranexamic Acid (TXA) Synthetic anti-fibrinolytic Enhances formation of stable clot Reduces need for RBC transfusion Competitive inhibition of plasminogen to plasmin High dose direct inhibition of plasmin Cardiac, orthopedic, trauma surgery, obstetrics 90 30  12/2/24 Tranexamic Acid (TXA) 10x more potent than EACA Parenteral, topical, oral Similar efficacy Topical à local effects with minimal systemic Safety concerns (limited conclusive data) Seizure risk (dose-related?) GABA receptor blockade in frontal cortex 91 92 Aprotinin Anti-fibrinolytic Inhibits plasmin Reduces bleeding and need for transfusion US manufacturer removal related to safety concerns May be used in high risk, special treatment protocols Increased risk of thrombus formation, ________________________________ 93 31  12/2/24 Antifibrinolytic Adverse Effects Thrombus Unclear risks associated with TXA, EACA High risk with ______________________________________________ Limited evidence of thrombosis in higher risk patients Coronary graft occlusion VTE/PE 94 Antifibrinolytic Adverse Effects Contraindications Known hypercoagulable conditions Vascular anastomosis DIC _____________________________________ (high dose TXA) Renal dysfunction (EACA) 95 Antifibrinolytic Adverse Effects Wrong site administration Multiple case reports Unintentional intrathecal TXA Attributed to similar ampule appearance Symptoms Back, leg pain Myoclonus, seizures HTN, tachycardia, VF Mortality 50% 96 32  12/2/24 Protamine Polypeptide base Inactivates acidic heparin molecules Acid-base neutralization Does not work on low-molecular weight heparin Inhibits platelets, serine proteases involved in coagulation Reticuloendothelial clearance within 20 minutes 97 98 Protamine Administration Considerations Dose: 1 mg protamine inactivates 100 units heparin Risk for ____________________________________ 2-3 hrs after dose Risk for coagulopathy, PLT dysfunction with excess dosing Administer slowly 99 33  12/2/24 Protamine Side Effects Hypotension* Anaphylaxis Acute pulmonary vasoconstriction Right ventricular failure Increased risk in patients using NPH insulin 100 Desmopressin (DDAVP) Analogue of vasopressin Releases endogenous stores of von Willebrand Factor (VIII:vWF) from endothelial cells h ttp s ://o n lin e lib ra ry.w ile y.c o m /d o i/1 0.1 1 1 1 /e jh.1 3 9 3 0 101 Desmopressin (DDAVP) Treatment for vW disease Shortens bleeding time, PTT 0.3 mcg/kg IV infusion over 15 – 30 minutes Platelet adhesion increased within 30 minutes Duration 4 – 6 hours Risk hypotension (rapid administration), hyponatremia (peds) 102 34  12/2/24 Fibrinogen (Factor I) Stable clot formation Enzyme substrate for thrombin, Factor XIIIa, plasmin Binds platelet receptors (GP IIb/IIIa) responsible for aggregation Fibrinogen loss Hemorrhage or ______________________________________ Decreases clot stability 103 Fibrinogen (Factor I) Normal level: 200 - 400 mg/dL Typical replacement recommendation at levels below 100 - 150 mg/dL Low levels may increase PT, PTT Treatment Cryoprecipitate: 1 unit/10 kg increases by 50 - 70 mg/dL Fibrinogen concentrate 104 Recombinant Proteins Recombinant activated factor VIIa (rFVIIa) Bleeding management in hemophilia Life-threatening hemorrhage, cardiac surgery (off-label) Forms complex with tissue factor à ____________________________ May normalize PT/INR without correcting coagulation defect 105 35  12/2/24 h ttp s ://w w w.n a tu re.c o m /a rtic le s /1 7 0 5 6 7 0 106 Recombinant Proteins Factor XIII, recombinant factor XIII Final common pathway stabilization of fibrin clot Reduction in postoperative hemorrhage, transfusion requirements Prothrombin complex concentrates Factors II, VII, IX, X Bleeding management in hemophilia B Warfarin reversal, increased INR with life-threatening bleeding 107 MemoryMaster Knowledge Check What is the cause of protamine-induced hypotension or allergic reaction? What factor does DDAVP stimulate the release of and where? Is protamine an acid or base? Valley Anesthesia.(2023). Memory Master: Questions and answers for the student nurse anesthetist (33rd ed.). pp.99-101 108 36  12/2/24 Topical Hemostatic Agents Vessel embolization Absorbable agents Gelatin sponges (ie, Gelfoam) – increase contact activation to create clot Surgicel, Oxycel, Avitene, CoSeal, BioGlue Topical thrombin Human derived recommended for clinical use (vs. bovine) 109 Topical Hemostatic Agents Fibrin sealants Biologic glue (fibrin tissue adhesives) Combine thrombin and fibrinogen Tisseal, Crosseal, FloSeal Many topical agents should not be used near nerves or in confined spaces 110 Review! 111 37  12/2/24 Let’s Review When the endothelial lining of the blood vessel is damaged, platelets adhere to the subendothelial collagen. What substance anchors platelets to subendothelial collagen? 112 Let’s Review What clotting factor activates the platelet at the site of injury? What two substances, released from the activated platelet, stimulates platelet aggregation? 113 Let’s Review Which factor is the primary initiator of the coagulation cascade? Which factor is responsible for cross-linking the fibrin clot? 114 38  12/2/24 Let’s Review Cryoprecipitate is most rich in what 3 coagulation factors? a) I, VIII, XIII b) II, VII, X c) I, VII, X d) II, X, XI 115 Let’s Review Antithrombin III primarily neutralizes which pathways and strongly inhibits which two coagulation factors? a) Extrinsic, final common; II, XIII b) Intrinsic, final common; VIII, XIII c) Intrinsic, final common; II, X d) Intrinsic, extrinsic; VII, X 116 Let’s Review How does heparin work? How does coumadin work? 117 39  12/2/24 Let’s Review What agents inhibit platelet aggregation by impairing cyclo-oxygenase? Formation of which other platelet aggregator is blocked? 118 Let’s Review Which anti-platelet agent prevents ADP-induced platelet aggregation? a) Aspirin b) Ibuprofen c) Ketorolac d) Clopidogrel 119 Let’s Review Your patient with von Willebrand’s disease has not responded to desmopressin (DDAVP). What will you try next? a) Fresh frozen plasma b) Cryoprecipitate c) Amicar d) Plasmin 120 40  12/2/24 Let’s Review How does protamine work? How does tranexamic acid work? 121 QUESTIONS? 122 41