Physiology and Biology of Hemostasis and Transfusion Wendi Rachman

Biology of HemostasisProcess to prevents or terminates blood loss4 major events:Vascular constriction Platelet plug formationFibrin formationFibrinolysis

Vascular ConstrictionInitial vascular response, before any platelet adherence Occurs even at capillary levelLinked to platelet plug formation- TXA2- endothelin- Serotonin, 5-HT- bradykinin & fibrinopeptidesAlso affected by the surrounding tissue pressure

Platelet Function 2 pathways:Forming hemostatic plugContributing to thrombin formation

Platelet FunctionNormally do not adhereForming a plug when vascular disruption occursAdhere to subendothelial collagen in 15 seconds Requires vWF that binds to GP I/IX/V on the platelet membraneAlso mediated by interaction between collagen and GP IaIIa on the platelet surface

Platelet FunctionExpand and develop pseudopodal and also recruits other platelets to aggregatesThis process is reversible and also known as primary hemostasisADP and serotonin are the principal mediators in this processPGI2, ASPIRIN, and NSAIDs act to inhibit this process.

Platelet FunctionANTITHROMBOTICAntiplatelet activitiesProstacyclin productionNitric oxide productionEcto-ADPasesAnticoagulan activitiesThrombomodulin protein CHeparan sulfate antithrombinFibrinolytic activationPlasminogen activator productiontPAuPAPROTHROMBOTICPlatelet-activating propertiesEndothelin productionvon Willebrand factor productionProcoagulant propertiesTissue factor productionBinding of clotting factorsFibrinolysis inhibitionPlasminogen activator inhibitor-1 productionEndothelial-mediated vasoconstrictionEndothelin productionEndothelial barrier function

Properties of the endothelium related to hemostasis and thrombosis

Platelet FunctionIn the second wave, platelet discharge ADP, Ca+ and granuleFibrinogen required as a bridge for the GP IIbIIIa receptor on the activated plateletsThe process made platelets compact to form amorphous plug, and no longer reversible

Platelet FunctionThrombospondin stabilizes fibrinogen binding to the activated platelet surface thrombo globulin and PF4 inhibit plasminogen activationThe second wave inhibit by NSAIDs, cAMP and nitric oxideThis process also allowed calcium and clotting factor to bind to the platelet surface

Coagulation2 pathways:Intrinsic (factor, XII, XI, IX, VIII)- requires no surface to initiate- prolongation aPTT is associated with abnormal function of this pathwayExtrinsic (factor VII, X, II, I)- requires exposure of tissue factor on the surface of the injured vessel to initiate- prolongation PT is associated with abnormality of this pathway

Coagulation

CoagulationVit K and warfarin use affect factor II, VII, IX, XPlatelet number or function can be insufficient to adequately support coagulation

FibrinolysisFibrin degraded by plasmin, a serine protease derived from the proenzyme plasminogenPlasminogen converted by plasminogen activators (e.g tPA, uPA)Plasmin cleaves fibrin and degrade fibrinogenSeveral characteristics of enzymatic reactions ensure that the process occurs at controlled rate and at the site of the clot

FibrinolysisPlasmin inhibit by 2 antiplasmin, a protein which is crosslinked with factor XIITAFI also inhibit fibrinolytic system by removes lysine residues, that are essential for binding plasminogen Clot lysis yields fibrin degradation products including E-nodules and D-dimers

Hemostatic DefectsCONGENITALCoagulation factor deficienciesHemophiliadeficiencies factor VIII (A), factor IX (B), factor XIsex linked recessive disordersvon Willebrands diseasedeficiency factor VIIIautosomal dominant disorders

Hemostatic DefectsACQUIREDPlatelet abnormalitiesITP, TTPAcquired hypofibrinogenemiaDefibrinogen syndromePrimary fibrinolysisMyeloproliperative disordersCoagulopathy of liver diseaseAcquired coagulation inhibitorsOther diseaseParaprotein disordersHypersplenism

DICSyndrome: Enhanced fibrin formingImpaired fibrin degradationLab : Prolonged PT, aPTT, Low platelet count, fibrin degradation result Th/ : Plasma and platelet concentrate Heparin and low molecular weight heparin

Anticoagulation and BleedingSpontaneous bleeding may be a complication of anticoagulant therapyIt may present only with ecchymoses or even GI tract bleeding.Surgical treatment can be undertaken without discontinuing the anticoagulant programLaboratory findingaPTT les than 1,3 control in a heparinized patientINR less than 1,5 in a patient on warfarinPatient who have been heparinized as treatment of DVT, can still be operated within several hours delay or for more rapid reversal, 1 mg of protamine sulfate for every 100 units heparin most recently administered

Anticoagulation and BleedingCardiopulmonary bypassoverheparinization, heparin rebound, inadequate protamine neutralization, protamine excess and thrombocytopenia all have been indicate as causes of excessive bleeding in patient undegoing cardiopulmonary bypass

Local HemostasisMechanical proceduresthe oldest method is digital pressure, than develop to hemostatgenerally ligature or a hemoclip replaces hemostat as permanent method on effecting hemostasis of a single disrupt vessel1st century Aulus Cornelius Celsus devise the use of ligature1552 Pare rediscovered the principle of ligature1800 Philip Sying Phsick employ absorbable suture1858 Simpson introduce fine wire suture, 1881 Lister used catgut1900 Halsted indicated the advantages of non absorbable silk1911 Cushing use silver clips to effect hemostasis in areas that are hard to reachRecently introduced Harmonic scalpel, an instrument that cuts and coagulates tissue via vibration at 55 kHz

Local HemostasisThermal AgentsHeat achieves hemostasis by denaturation of protein that result in coagulation of large are of tissueThe electrocautery can be AC or DCLocal cooling has been applied to control bleeding from the eroded mucosa of the eophagus and stomach, direct cooling with iced saline is effective but may provoke hypothermiaCryogenic procedure, at tempertures of -20 C, tissue, capillaries and arterioles undergo necrosis Chemical AgentsEpinephrine1911 Cushing use skeletal muscle, shortly thereafter hemostatic fibrin was introducedGelatin, oxydized cellulose, oxydized regenerated cellulose and micronized collagen are the most widely used

TransfusionBackgound1667 Jean-Baptiste Denis and Emmerez transfused sheep blood into 15 y.o boys1668 transfusion in humans were forbidden unless approved by a Faculty of Medicine in Paris1900 Landsteiner introduce the ABO concept1939 Levine and Stetson found Rh group

Replacement Therapy

Typing and CrossmatchingBlood typing established by he antigen on the surface of the RBC, wherethere A, B, A and B, or none.Crossmatching between the donors red blood cells and the recipients sera is perform to establish the serologic compatibility

Replacement Therapy

Replacement Blood typeFresh whole bloodblood that administered within 24hrBanked whole bloodrarely indicated, because after 24hr of storage there are some changes in blood components, pH, ions

Replacement Therapy

Packed red cellsproduct of choice for most clinical situations, removing most of supernatant plasma and reduce potassium, sodium, lactic acid and citrateWashed red cellsis the standard red cells product in most western nationsLeukocyte reduction reduce non hemolytic transfusion reactionsPlatelet concentratesshould be used within 120hr of donation

Replacement Therapy

Frozen plasmaprepared from freshly donated bloodsource of Vit K, factor II,IX,XIDextrancombination of serum albumin and lactated Rigers solutionmax 1L/dConcentrates and DNA recombinant technologyanti hemophilic concentrates (factor VIII, factor IX) and albuminPolyHeme human polymerized hemoglobin

Indications of Replacement TherapyGENERAL INDICATIONSImprovement in Oxygen-Carrying Capacity1988 National Institutes of Health Consensus Report Hb less than 10 g/dl or Ht less than 30%Volume replacementin patient with normal preoperative value:Blood loss up to 20% replaced with crystalloidBlood loss up to 50% replaced with crystalloid and PRCBlood loss above 50% receive same components plus FFP

Methods of AdministrationRoutine administrationusually 5ml/min for 1st min then 10-20ml/minOther methodsintramedullary or intraperitoneally

ComplicationsHEMOLYTIC REACTIONSincompatibility of ABO and Rh groupsthe most common symptoms are heat and pain along the entrance vein, flushing face, pain in the lumbar region, and constricting chest painStop immediately, insert Foley catheter, urine alkalinizing, diureticsIf oliguria or anuria occur, treat like renal failure

ComplicationsALLERGIC AND FEBRILEMay occur after administration of any blood product Antihistamines, epinephrine, or steroidsBACTERIAL SEPSISContaminated blood or blood bagStop immediately, blood culture, O2and antibioticsEMBOLISMSUPERFISCIAL THROMBOPHLEBITIS OVERTRANSFUSION AND PULMONARY EDEMAAvoidable by measuring CVPSymptom are arise in venous pressure, dyspnea, couhg, rale at the lung basesStop immediately, diuretics, placing the patient in sitting position, intensive pulmonary support, sometimes intubationTRANSMISSION OF DISEASE

Evaluation of the Surgical Patient as a Hemostatic RiskPREOPERATIVEPatients historyProlonged bleeding or swelling after biting the li or tongueBruises without apparent injuryProlonged bleeding after dental extractionExcessive menstrual bleedingBleeding problems associated with major or minor operativesMedical problems receiving a physicians attention within the past 5 yearMedications including aspirin or remedies for headache taken within past 10 daysA relative wit a bleeding problemLaboratory findings (PT, aPTT, INR, Platelet count)

Evaluation of the Surgical Patient as a Hemostatic RiskEVALUATION OF EXCESSIVE INTRAOPERATIVE OR POST OPERATIVE BLEEDINGMaybe the result of the following factors:Ineffective local hemostasisComplications of blood transfusionA previously undetected hemostatic defectConsumptive coagulopathy Fibrinolysis