Coagulation in cardiac anesthesia

Coagulation in cardiac anesthesia Dr k. fani

heparin PS protamine ATIII aprotinin PC warfarin TA LMWH EACA V XII X IX VIII TF VII XI plasmin cryo XIII PF3 prothrombin Ca kallikrein fibrinogen plt FFP

hemostasis Three major components of hemostasis: ,[object Object]

coagulaion cascade glycoprotein (secondary h.) Fibrinolyis: remains coagulation localized Ideal anticoagulation for CPB should be : ,[object Object]

Mechanisms of hemostasis Plasma coagulation pathway: ,[object Object]

vascular injury or disruption activate the extrinsic pathway. ,[object Object]

Extrinsic pathway Tissue factor initiates the extrinsic pathway, which proceeds quickly to the common pathway with the aid of factor VII and calcium.

Common pathway Beginning with the assisted activation of factor X, this pathway proceeds to convert prothrombin (factor II) to thrombin and fibrinogen (factor I) to fibrin monomer, which initiates the actual substance of the clot. Fibrin monomer then cross-links to form a more stable clot with the aid of calcium and factor XIII.

thrombin Thrombin is the most important enzyme in the pathway : 1- fibrinogen activation 2- positive feedback by activation cofactors V & VIII 3- accelerated cross linked fibrinogen by activation XIII 4- stronly stimulate plt adhesion & aggragation 5- facilitate clot resorption by release tPA 6- activate protein C & negative feedback by inactivating factors Va & VIIIa

Platelet activation thrombin is an especially potent platelet stimulator. Platelet activation -platelet aggregation - primary platelet plug. Fibrin clots and platelet plugs form simultaneously and mesh together. a. Von Willebrand factor (vWF) is essential to platelet adhesion, and fibrinogen to platelet aggregation. b. Products released from platelet storage granules (ADP, epinephrine, calcium, TXA2, factor V, and vWF) serve to perpetuate platelet activation and the plasma coagulation cascade.

fibrinolysis counterbalancing forces to discourage runaway clot formation and to dissolve clots include following: a. Proteins C and S, which inactivate factors Va and VIIIa b. Antithrombin III , which inhibits thrombin as well as factors XIa, IXa, XIIa, and Xa c. Tissue factor inhibitor, which inhibits the initiation of the extrinsic pathway d.tPA, which is released from endothelium and converts plasminogen to plasmin, which in turn breaks down fibrin. Plasminogen activator inhibitor 1 in turn inhibits tPA to prevent uncontrolled fibrinolysis.

Pediatric coagulation The newborn coagulation system is immature but contains all the elements for clotting. The levels of newborn clotting factors VII, IX, X, XI, and XII, prothrombin, prekallikrein, and high-molecular-weight kininogen are approximately 50% of adult levels . Levels of factors VIII, XIII, and V, fibrinogen, and von Willebrand factor (vWF) approach or exceed adult values . The newborn coagulation system matures to adult concentrations and function over 6 months. Levels of inhibitors of clotting—antithrombin (AT) and proteins C and S—at birth are 50% of adult values.

Newborn platelets are hyporeactive compared to adult platelets, yet newborns rarely manifest a bleeding tendency. Platelets achieve adult reactivity in only 10 to 14 days. Term and preterm infants form thrombin poorly. Overall clotting capacity is below that of adults because of reduced clotting factors and contact proteins .

EFFECT OF CPB ON COAGULATION CPB induce a whole body inflammatory response: ,[object Object]

release of inflammatory mediators

stimulation of the coagulation and fibrinolytic cascades(microvascularcoagulaion , platelet dysfunction, and enhanced fibrinolysis,[object Object]

CPB directly affects platelet function through the effects of hemodilution, hypothermia, and contact activation by bypass circuit materials. Platelets have receptors for several circulating ligands, such as fibrinogen, thrombin, and collagen .The components of the bypass circuit adsorb circulating proteins that can serve as foci for platelet attraction and adherence. These surface-bound platelets activate and release the contents of their cytoplasmic granules, which can then serve as localized sources of thrombin generation or embolize to initiate microvascularthrombosis.

Fibrinolytic activity is also increased by CPB. Contact activation of factor XII, prekallikrein, and high-molecular-weight kininogen leads to fibrinolytic activation through activation of endothelial cells to produce tissue plasminogen activator (t-PA) and lysis of fibrin strands and the fibrin precursor fibrinogen

Endothelial cells themselves are vulnerable to inflammatory activation by the effects of CPB. Endothelial cells, when exposed to hypoxia or inflammatory mediators during bypass, can induce a relatively prothrombotic state that leads to upregulation of tissue factor, accelerated platelet adhesion, and increased expression of leukocyte adhesion molecules

CPB in pediatric Many factors contribute to development of excessive bleeding in infants and children undergoing CPB, but EC plays a major role. The hemostatic derangement occurring as a result of CPB frequently is of greater severity in pediatric than adult patients, particularly in neonates and infants younger than 6 months . The infant's inflammatory response is profound because of the large discrepancy between the surface area of the oxygenator and that of the infant.

infants and children experience varying degrees of hemodilution as CPB is initiated. clotting factor levels decrease by 30% to 50% . Levels of factors VII and V, fibrinogen, and prothrombin decrease further during CPB; the levels of other clotting factors are unchanged Fibrinogen levels are especially susceptible to becoming very low, partially because preoperative levels are depressed secondary to poor liver perfusion and the resulting impaired synthesis.

Thrombocytopenia persist hours after CPB and is sever in infants younger than 1 year. Cyanotic are more affected because of decrease number of preoperative pltGPIb receptors Impaired plt function is major source of bleeding with CPB Hemodilution generally induces moderate thrombocytopenia that worsens as CPB progresses

Tests of hemostatic function With the exception of ACT,other are not used during CPB , because most of them will be abnormal as a result of hemodilution, anticoagulation, and sometimes hypothermia. routine preoperative hemostatic screening is not helpful in predicting patients who will bleed excessively during surgery. If the patient's clinical history (e.g., nosebleeds; prolonged bleeding with small cuts, dental work, or surgery; easy bruising; strong family history of pathologic bleeding) suggests the need for hemostatic screening. Similarly, when the patient is taking medications that alter hemostatic function, specific hemostatic function tests may be indicated.

Examples : (1) Heparin: aPTT or ACT (2) Low-molecular-weight heparin (LMWH): No test or anti-Xa heparin concentration (3) Warfarin:PT and/or INR 4) Platelet inhibitors including aspirin: No testing, bleeding time, or platelet function tests

CLOT Anticoagulants Monitor with PT Extrinsic Pathway Monitor with aPTT or ACT Intrinsic Pathway HEPARIN WARFARIN DXaI X Xa LMWH Common Pathway II IIa (thrombin) Hirudin & DTI Monitor with ?????

heparin its discovery by Jay McLean, MD, in 1915 mechanism underlying heparin's anticoagulant effect revolves around the heparin molecule's ability to bind simultaneously to antithrombin III (AT III) and thrombin. The binding process is mediated by a unique pentasaccharide sequence that binds to AT III . Thrombin is 10 times more sensitive to the inhibitory effects of heparin than factor Xa .

dosing of heparin for CPB is somewhat empirical. After a baseline activated clotting time (ACT) is measured (the normal range is 80 to 120 seconds), a dose of 300 to 400 U/kg is given in intravenous bolus form. Subsequent heparin dosing for extracorporeal circulation is targeted at maintaining ACT values greater than 480 seconds.

it is not a perfect anticoagulant. Intrinsic and extrinsic pathway coagulation occurs despite heparin administration, and platelets can still be activated by contact with the bypass circuitry and by heparin directly. Using ACT to monitor the efficacy of heparin is not an exact science. There is variability in patients’ anticoagulation response to a given dose of heparin. ACT values correlate poorly with actual heparin concentrations.

Heparin Structure Heparin resides physiologically in mast cells, and it is commercially derived most often from the lungs of cattle (bovine lung heparin) or the intestines of pigs (porcine mucosal heparin). Commercial preparations used for CPB typically include a range of molecular weights from 3,000 to 40,000 Da, with a mean molecular weight of approximately 15,000 Da. Each molecule is a heavily sulfated glycosaminoglycan polymer, so heparin is a strong biologic acid that is negatively charged at physiologic pH.

Heparin Action This binding potentiates the action of ATIII more than 1,000-fold heparin inhibit thrombin and factor Xa most importantly, but also factors IXa, XIa, and XIIa. Inhibition of thrombin requires simultaneous binding of heparin to both ATIII and thrombin, whereas inhibition of factor Xa requires only that heparin bind to ATIII. The former reaction limits thrombin inhibition to longer saccharide chains (18 or more saccharide units); shorter chains can selectively inhibit Xa. (LMWH) Because thrombin inhibition appears pivotal for CPB anticoagulation and because LMWH and heparinoids have a long half life and are poorly neutralized by protamine, LMWH is inadvisable as a CPB anticoagulant. Heparin binds and activates cofactor II, a non-ATIII-dependent thrombin inhibitor.

Heparin potency USP defines 1 unit of activity as the amount of heparin that maintains the fluidity of 1 mL of citrated sheep plasma for 1 hour after recalcification. The most common concentration is 100 units/mg (1,000 units/mL) .

Pharmacokinetics of heparin After central venous administration, heparin's effect peaks within 1 minute . Heparin's large molecular size and its polarity restrict it to the intravascular space and endothelial cells. Heparin is eliminated by the kidneys or by metabolism in the reticuloendothelial system. heparin's elimination time is dose dependent. At lower doses, such as 100 to 150 USP units/kg, elimination half-time is approximately 1 hour. At CPB doses of 300 to 400 USP units/kg, elimination half-time is 2 or more hours; anticoagulation might persist for 4 to 6 hours in the absence of neutralization by protamine. Hypothermia and probably CPB itself prolong elimination.

Side effects Heparin's actions on the hemostatic system extend beyond its primary anticoagulant mechanism to include activation of tPA, platelet activation, and enhancement of tissue factor pathway inhibitor. a. Lipoprotein lipase activation influences plasma lipid concentrations, which indirectly affects the plasma concentrations of lipid-soluble drugs. b. Heparin boluses decrease systemic vascular resistance. Typically this effect is small (10% to 20%), but rarely it can be more impressive and may merit treatment with a vasopressor or calcium chloride. c. Anaphylaxis rarely occurs. d. Heparin-induced thrombocytopenia (HIT)

Heparin dose The most common initial dose for CPB is 300 USP units (U)/kg. Some centers choose 400 U/kg or base the initial dose on a bedside ex vivo heparin dose-response titration. there is seldom reason to exceed an initial dose of 35,000 to 40,000 units, even in patients weighing more than 100 kg, as lean body mass tends to peak at 90 kg for females and 110 kg for males. Heparin dosing for OPCAB: doses range from 100 to 300 units/kg, but most centers use 100 to 150 units/kg and set minimum acceptable ACT values at 200 to 300 seconds. A priming volume of 1,500 mL should contain at least 5,000 units of heparin. CPB priming solutions commonly contain 5,000 to 10,000 units of heparin.

MONITORING OF ANTICOAGULATION Whole blood is added to a tube containing a contact-phase activator, celite or kaolin, and a small iron cylinder. The sample is warmed to 37°C, and the tube is rotated. Clot formation is detected by retracting the iron cylinder, which disrupts a magnetic field.

Hemodilution: Prolongs the ACT in the presence of heparin Hypothermia: Prolongs the ACT Thrombocytopenia: Prolongs the ACT Platelet inhibitors: Prolongs the ACT Platelet lysis: Shortens the ACT Aprotinin: Prolongs the ACT with celite activator Surgical stress : Shortens the ACT

ACT in pediatric ACT more questionable for pediatric than adult under CPB. Heparin concentration – based heparin dosing have recently been recommended in infants and children. In CHD (infancy to 14 years)amount of heparin for ACT 480 is higher in infants(579+_220u/kg) and preschool(477+_159u/kg) than school aged and adult(300u/kg) Age related AT concentration differences and volume of distribution. Initial heparin doses between 300-450u/kg Recommendation for heparin concentration : 1.3 – 3.5u/cc Fixed dose:1-1.3 mg protamin per 100 u of heparin.(?)

The high-dose thrombin time (HiTT) correlates well with the heparin concentration, both before and during CPB.Unlikethe ACT, HiTT is not affected by hemodilution and hyperthermia; in addition, it is a more specific test of heparin's effect on thrombin, and it appears to possess less artifactualvariability.Aprotininand preoperative heparin infusions do not affect HiTT values

ANTITHROMBIN III DEFICIENCY/ HEPARIN RESISTANCE Heparin resistance has been defined as an ACT of less than 480 seconds after 500 U/kg of heparin is administered intravenously. Others have defined heparin resistance as an ACT of less than 400 seconds at any time during the course of CPB and heparin administration. A more accurate term to describe the clinical findings is “altered heparin responsiveness. altered heparin responsiveness was found in approximately 40% of the patients who had received preoperative heparin therapy.

Heparin resistance Causes: hypercoagulable state(ATIII deficiency(<60%) , arteriosclerotic d., septicemia, pregnancy, HIT, thrombocytosis>300000),drugs (heparin, TNG),protein binding(acid glycoprotein, histidine rich glycoprotein, Ig),other(neonates,elderly) Clinical approach: supplemental ATIII if more than 600 u/kg for target ACT FFP:2-4 u for adults,ATIII concentrate 1000 u

HEPARIN REBOUND Heparin rebound is clinical bleeding that occurs within approximately 1 hour of protamine neutralization. It is accompanied by coagulation test results indicating residual heparinization, such as aPTT and TT and increased anti–factor Xa activity. Mechanisms of heparin rebound include slow dissociation of protein-bound heparin after protamine clearance, more rapid clearance of protamine than heparin, lymphatic return of extracellular sequestered heparin, or clearance of an unknown heparin antagonist. Heparin rebound is treated with supplemental protamine.

HIT Incidence: 5-28% Cause: proaggregatory effect on PLT, HIT type1:rapid onset(2-5days)mild decrease in PLT, HIT type2: more severe,after more than 5 days,immunemediated,whiteclot,,morbid &fatal, thrombosis 20%, mortality40% Diagnosis:heparin induced serotonin release assay(gold standard),heparin induced platelet activity assay,enzyme linked immunosorbent assay(specific for heparin/PF4 complex) Treatement:changing tissue source,LMWH,heparinoids,ancrod,plasmapheresis, heparin with PLT inhibitor, thrombin inhibitor, heparin discontinuation

Heparin-induced thrombocytopenia (HIT) is an immune-mediated prothromboticdisorder that occurs in patients exposed to heparin. Antibodies form against the protein platelet factor 4 (PF4) when PF4 has formed a complex with heparin. Although PF4 is found in only trace amounts in human plasma and is stored in platelet granules, the presence of heparin increases plasma concentrations of PF4 15- to 30-fold by displacing bound PF4 on endothelial cell surfaces making it available to bind with heparin. Binding of the resulting PF4-heparin complex to platelets leads to immunologically mediated platelet activation.

The hallmark of findings in patients with HIT is a decrease in the platelet count to less than 100,000 or to less than 50% of the baseline count. The incidence of seroconversion after bypass and heparin exposure is quite high (20% to 50%).However, the reported prevalence of HIT after CPB is only 1% to 3%.

Clinically, HIT is categorized into type I (platelet counts >100,000) and type II (platelet counts <100,000), and it is sometimes accompanied by clinical thrombosis. It is preferred, when possible, to defer surgery until antibody titers have become undetectable or only weakly positive. If surgical postponement is not practical, other therapeutic options must be considered. Lepirudinand argatroban are approved by FDA for use in patients with HIT-related thrombosis. Bivalirudinhas been approved by the FDA for use in percutaneous interventions. no drug other than heparin has FDA approval for specific use as an anticoagulant in patients during CPB

Alternatives to unfractionated heparin LMWH:half life at least twice,protamin neutralized only factor IIa , Heparinoids: dermatan sulfate, danaparoid(heparine sulfate80%,dermatan sulfate20%,chondroitin sulfate) Hirudin: salivary gland of medicinal leech,independent of ATIII &inhibit clot bound thrombin,inhibit thrombin activation of protein C, a small molecule, kidney elimination,half life 40 min., Bivalirudin: inhibit thrombin by binding simultaneously to its active catalytic site, half life 24 min.,elimination by proteolysis&renal Argatroban: direct thrombin inhibitor Ancrod: from malayan pit viper venom,lysesfibrinogen,long half time

PROTAMINE from fish sperm Protamine, which has been in clinical use about as long as heparin, remains the heparin reversal agent of choice in cardiac surgery. The protamine dose required to reverse heparin is somewhat controversial. The amount quoted in most cardiac anesthesia texts is 1 to 1.3 mg of protamine for every 100 units of heparin.

The question to be answered revolves around which end point one uses in the protamine calculation: the total amount of heparin used for the procedure or the amount present in the patient at the time of reversal. In current practice, dosing usually follows one of the following protocols:

1. Protamine is administered according to the total amount of heparin given for the procedure, specifically, 1 to 1.3 mg protamine per 100 units of heparin. This method may result in luxuriant protamine doses, which reduces any theoretical or real risks of heparin rebound but may put the patient at higher risk for the anticoagulant effect of protamine.

2. Another practice involves the use of calculated heparin concentrations . The amount of protamine used in this method is based on the circulating concentration of heparin in the patient at the time of reversal. Because theoretically there is no excess protamine, these patients might be at risk for heparin rebound and could require additional protamine.

PROTAMINE REACTIONS Adverse reactions from mild hypotension to more profound and hemodynamically significant reactions (1) isolated hypotension, with normal to low filling pressure and normal airway pressure (2) hypotension accompanied by elevated PA pressure, evidence of bronchoconstriction with elevated airway pressure, evidence of acute RV failure . The first manifestation is usually mild and responds to volume infusion, slowing of protamine infusion, and gentle titration of vasoactive medications. The second can be profound and could result in global cardiovascular collapse or necessitate a return to CPB because of intractable RV failure.

Risk factors Prior reaction to protamine 189-fold Allergy to true (vertebrate) fish 24.5-fold Exposure to NPH insulin 8.2-fold Allergy to any drug 3-fold Prior exposure to protamine No increase!

1. Hypotension from rapid administration. over 3 or fewer minutes decreases both systemic and pulmonary arterial pressures as well as venous return 2. Anaphylactoid reactions. true allergy to protamine is uncommon. 3. Pulmonary vasoconstriction. Occasionally increases pulmonary arterial pressure, resulting in right ventricular (RV) failure, decreased cardiac output, and systemic hypotension. 4. Antihemostatic effects. activates thrombin receptors on platelets, causing partial activation and subsequent impairment of platelet aggregation. Transient thrombocytopenia also occurs in the first hour after a full neutralizing dose of protamine. Inhibition of plasma coagulation can also occur.

Treatment of adverse protamine reactions a. Normal or low pulmonary artery pressures suggest either rapid administration or an anaphylactoid reaction. Rapid fluid administration , large doses of epinephrine, and possibly other vasoactive compounds and inhaled bronchodilators ,systemic steroids. b. High pulmonary artery pressures suggest a pulmonary vasoconstriction reaction. Inotropes with pulmonary dilating properties, such as isoproterenol or milrinone, Nitric oxide may also be useful. With extreme hemodynamic deterioration, reinstitution of CPB may be necessary. In this case, give a fullheparin dose . Occasionally heparin alone will correct the pulmonary hypertension (presumably by breaking up large heparin-protamine complexes,) such that CPB no longer becomes necessary.

Prevention of protamine adverse responses administer slowly (min. duration 3 minutes, target of 10 minutes ). peripheral vein infusion offers no benefit over central venous . High-risk subgroups. Only patients with a prior history of an adverse response to protamine warrant special treatment. Prior protamine reaction. 1 mg in 100 mL and administer over 10 minutes. If no adverse response occurs, administer the fully neutralizing dose . Skin tests provide little predictive value and frequently are falsely positive. immunologic tests for allergy, such as the RAST and the ELISA, also demonstrate many false-positive results.

Alternatives to protamine 1. Allow heparin's effect to dissipate. 2. Platelet concentrates. PF4 combines with and neutralizes heparin. 3. Hexadimethrine. This synthetic polycation, with renal toxicity, can avoid true allergic reactions to protamine. 4. Methylene blue. Even large doses do not effectively restore the ACT. 5. Investigational substances. Heparinase I, Lactoferrin,. 6.alternatives to heparin

1. Anticoagulant therapy. Warfarin should be discontinue 3 to 5 days before the anticipated cardiac surgery. Generally an INR value less than 2 is considered an acceptable recovery of vitamin K-dependent clotting factors. If anticoagulation is so vitally important that it must be maintained until the time of surgery, an intravenous infusion of heparin may be started preoperatively. Heparin may be discontinued a few hours before surgery or continued into the operative period. Enoxaparin, an LMWH, has been associated with increased transfusion rates and surgical re-exploration. LMWH may also decrease heparin responsiveness.Although LMWH is a weaker anticoagulant overall than heparin is, it has greater antithrombotic activity.

2. Antiplatelet therapy a. Aspirin. a propensity for increased bleeding postoperatively; however, the benefits of aspirin therapy, weighed against a potential for bleeding, often leads to preoperative continuation of aspirin therapy. b. Glycoprotein IIb/IIIa (GPIIb-IIIa) inhibitors. GPIIb-IIIa inhibitors inhibit platelet aggregation and have been increasingly used during interventional cardiology procedures. there is strong potential for hemorrhagic complications if these patients present for emergent cardiac surgery especially within 12 hours of drug use. Currently the three intravenous GPIIb-IIIa inhibitors in clinical use are abciximab, tirofiban, and eptifibatide.

c. ADP receptor inhibitors. ticlopidine and clopidogrel noncompetitively antagonize at a platelet ADP receptor to induce profound and rapid platelet disaggregation. Clopidogrel use in conjunction with percutaneous coronary intervention or in acute coronary syndromes reduces the occurrence of adverse ischemic events . Antiplatelet activity is permanent for the life span of the platelet . clopidogrel pretreatment is associated with more bleeding than in nonexposed patients

Pharmacologic & protective prophylaxis Platelet protection: anti fibrinolytic agents coated surfaces:attenuate inflammatory response anti platelet agents;

Anti fibrinolytic agents a- synthetic anti fibrinolytic agents: EACA & TA act as lysine analogues that bind to plasmin & plasminogen, TA is more potent than EACA. FDP inhibit plt function thus plasmin inhibition protect plts. benefits are most obvious when used prophylactically. EACA dose: 50mg/kg and then 20-25 mg/kg/h. TA dose range: 10-20 mg/kg bolus,1-2mg/kg/h , 5g bolus to 15 g Pharmacologic & protective prophylaxis

Pharmacologic & protective prophylaxisAntifibrinolytic agents b-aprotinin: HMW proteinase inhibitor of bovine origin that inhibit plasmin, kallikrein, and other serine proteases. like EACA & TA reduce perioperative blood loss but have post operative renal dysfunction, full hammersmith dose:10000kiu test dose 5 min. later 2million kiu bolus, 2 million add to pump prime , 500000kiu/h infusion

Accurate heparin & protamin dosing giving heparin just enough to maintain a threshold minimum acceptable ACT. Some postulate higher concentration blunt consumptive coagulopathy in microvascular Lower protamine dose associated with reduce bleeding

Inhibition of inflammation Coated surfaces: attenuate inflammatory response to CPB Steroids: methyl prednisolone 500-1000 mg Aprotinin: kallikrein inhibition MUF: dramatic reducing in post operative morbidity& improving organ function in pediatric. Complement inhibitors: exprimental agents

Adults: received 68% PC,32%FFP,22% plt Pediatric: 98% PC,58%FFP,54% plt CHD is a strong risk factor for bleeding due to factor reduction , chronic congestion, plt dysfunction and reduction Bleeding is worse in cyanotic(?) Plt abnormality In number and function attributed in cyanotic CHD Direct relation between severity of polycythemia and thrombocytopenia 25% cyanotics have plt count<100000

Coagulation testes are not recommended unless a preexisting coagulation disorder is known. Age inversely related to blood loss ,neonates have greatest and above 5 years least postoperative blood loss Minimal core temperature Weight: <8kg have more blood loss(98% compare with 75%) Complexity of surgery, duration of circulatory arrest and CPB, previous sternotomy

Blood conservation technique 1-Preautologous blood donation 2-acute normovolemichemodilution 3-fresh whole blood 4-antifibrinolytic therapy 5-desmopressin acetate(arginine vasopressin) 6-recombinant factor VII 7-topical hemostatic agents 8-cell salvage 9-ultrafiltration

Preoperative Autologous Blood Donation unavoidable waste and costs have lessened its popularity. The technique is unsuitable for infants and problematic for children. Difficulties with PAD include procurement of blood from children with poor venous access, storage of donated blood, and the volume of blood that must be withdrawn to successfully reduce transfusions.

Acute NormovolemicHemodilution ANH is unsuitable for infants, but it can be performed in small children by withdrawing 20 mL/kg of blood after induction of anesthesia . Subsequently, the blood remains in the operating room at ambient temperature and is reinfused after protamine administration. The fluid chosen to maintain euvolemia during blood withdrawal : Albumin,Crystalloid , low-molecular-weight hetastarch

Fresh Whole Blood Use of fresh whole blood, unavailable in most institutions, reduces blood loss and transfusion requirements to the greatest degree in neonates undergoing complex surgical procedures; children older than 2 years undergoing complex operations receive little benefit. Platelet count generally increases with fresh whole blood similar to the administration of 4 to 6 units of platelet concentrates.

Antifibrinolytic Therapy from 1990s. aprotinin (APN), tranexamic acid (TA), and ε-aminocaproic acid (EACA). EACA is a synthetic lysine analog that competitively inhibits plasmin. A 150 mg/kg bolus and 30 mg/kg/hour continuous infusion of EACA significantly reduced intraoperative blood loss by 30% but not 24-hour losses.

Tranexamic acid, a synthetic lysine analog ten times more potent than EACA, is a competitive inhibitor of plasmin. A dose consisting of a 100 mg/kg bolus, 100 mg/kg prime, and 10 mg/kg/hour infusion of TA was given to infants and children

Aprotinin, a serine protease inhibitor, not only inhibits plasmin as EACA and TA but has anticoagulant and antiinflammatory properties and ability to preserve platelets. Complications with APN are not as well established in children as in adults. Thrombosis and anaphylaxis occur infrequently and unpredictably in infants and children , but they can be fatal. occurrence of renal failure exist. The cost of APN compared to other antifibrinolytic

Desmopressin a vasopressin analog that increases circulating levels of factor VIII and vWF. And reduces platelet dysfunction . Presently, DDAVP is not recommended as a prophylactic agent to reduce bleeding in infants or children, but it may be useful if administered in conjunction with a thromboelastogram (TEG)-defined coagulopathy.

Recombinant Factor Vlla produced by hamster kidney cell . rFVII is administered at a dose of 60 to 90 µg/kg. It has been used extensively in patients with hemophilia but infrequently in cardiac surgery, especially pediatric patients.

Coagulation in cardiac anesthesia

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