1-4 Hemostasis, Surgical Bleeding and Transfusion

Surgery Hemostasis, Surgical Bleeding, and Transfusion

DR. Bibera July 5, 2012

BIOLOGY OF HOMEOSTASIS  

a complex process whose function is to limit blood loss from an injured vessel 4 major physiologic events o vascular constriction o platelet plug formation o fibrin formation o fibrinolysis

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Vascular Constriction is the initial response to vessel injury, more pronounced in vessels with medial smooth muscles dependent on local contraction of smooth muscle subsequently linked to platelet plug formation potent vasoconstrictors: vasoconstrictors: A2   (TXA2) is produced locally at o Thromboxane A2 the site of injury via the release of arachidonic acid from platelet membranes o Endothelinsynthesized Endothelinsynthesized by injured endothelium and serotonin (5-hydroxytryptamine) released during platelet aggregation Bradykinin  and Fibrinopeptides o Bradykinin and the extent of vasoconstriction varies with the degree of vessel injury Platelet Function platelets are anucleate fragments of megakaryocytes, normal circulating number of platelets ranges between 150,000 and 400,000/ L up to 30% may be sequestered in the spleen if not consumed in a clotting reaction, platelets are normally removed by the spleen and have an average life span of 7 to 10 days 10 days platelets play an integral role in hemostasis by forming a hemostatic plug and by contributing to thrombin formation injury to the intimal layer in the vascular wall exposes subendothelial collagen to which platelets adhere, which requires von Willebrand's factor (vWF) binds to glycoprotein I/IX/V on the platelet membrane

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after adhesion, platelets initiate a release reaction that recruits other platelets from the circulating blood to seal the disrupted vessel. Up to this point, this process is known as primary hemostasis platelet aggregation is reversible and is not associated with secretion o heparin does not interfere with this reaction (ADP)) and serotonin  serotonin  are o adenosine diphosphate (ADP the principal mediators in platelet aggregation

arachidonic acid released  converted by COX to prostaglandin G2 (PGG2) prostaglandin H2 (PGH2) converted to TXA2 effects:Arachidonic acid   shuttled to adjacent endothelial cells converted to prostacyclin (PGI2 ) vasodilation and acts to inhibit platelet aggregation

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platelet COX is o irreversibly inhibited by aspirin o reversibly blocked by NSAIDs o but is not affected by COX-2 inhibitor

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in the second wave of platelet aggregation, a release reaction occurs in which several substances, including ADP, Ca2+,serotonin, TXA2, and -granule proteins are discharged

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fibrinogen  is a required cofactor, acting as a bridge for the glycoprotein IIb/IIIa receptor on the activated platelets its release causes compaction of the plateletsinto a plug, a process that is irreversible thrombospondin , secreted by the granule, stabilizes fibrinogen binding to the activated platelet surface and strengthens the platelet-platelet interactions. platelet factor 4  4  (PF4), potent heparin antagonist, and thromboglobulin also are secreted during the release reaction

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the second wave of platelet aggregation is inhibited by aspirin and NSAIDs, by (cAMP), and by nit ric oxide

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alterations occur in the phospholipids of the platelet membrane that allow Ca2+ and clotting factors  bind to the platelet surface enzymatically active complexes

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the altered lipoprotein surface (sometimes referred to as platelet factor 3) catalyzes reactions that are involved in:

activation than is extrinsic (tissue factor-VIIa) complex, five to six orders of magnitude more effective than is factor IXa alone

- conversion of prothrombin to thrombin by

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activated factor X (Xa) in the presence of factor V and Ca2+ - is also involved in the reaction by which activated factor IX (IXa), factor VIII, and Ca2+ activate factor X

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Coagulation o

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the coagulation cascade has 2 intersecting pathways: o Intrinsic pathway - begins with factor XII and through a cascade of reactions activates factors XI, IX, and VII in sequence  fibrin clot formation, intrinsic to the circulating plasma and no surface is required to initiate the process o Extrinsic pathway - requires exposure of tissue factor on the surface of the injured vessel wall to initiate the cascade beginning with factor VII

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the prothrombinase is significantly more effective at catalyzing its substrate than is factor Xa alone once formed, thrombin leaves the membrane surface converts fibrinogen by two cleavage steps into fibrin and 2 small peptides termed fibrinopeptides A and B removal of fibrinopeptide A permits end-to-end polymerization of the fibrin cleavage of fibrinopeptide B allows side-to-side polymerization of the fibrin clot, facilitated by thrombin-activatable fibrinolysis inhibitor(TAFI)

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the coagulation system is exquisitely regulated. Feedback inhibition on the coagulation cascade deactivates the enzyme complexes leading to thrombin formation

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exists at upstream, intermediate, and downstream portions of the coagulation cascade to "turn off" thrombin formation once the procoagulantsequence is initially activated

the two arms of the coagulation cascade merge to a common pathway at factor X activation sequence of factors II (prothrombin) and I (fibrinogen) clot formation occurs after proteolytic conversion of fibrinogen to fibrin an elevated activated partial thromboplastin time(aPTT)  abnormal function Intrinsic pathway an elevated prothrombin time (PT) abnormal extrinsic pathway vitamin K deficiency and warfarin use affect factors II, VII, IX, and X fibrinogen levels of rotated through a 4.5-degree arc backwards and forwards o Normal clot goes through an acceleration and strengthening phase

Dave.Linelle.Deane.Mhe.Te.Paul

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fiber strands that interact with activated platelets attach to the surface of the cuvette and the suspended piston clot forming in the cuvette transmits its movement onto the suspended piston Weak clot stretches and therefore delays the arc movement of the piston, which is graphically expressed as a narrow thromboelastogram Strong clot will move the piston simultaneously and proportionally to the cuvette's movements, creating a thick thromboelastogram strength of a clot is graphically represented over time as a characteristic cigar-shaped figure

k- measure of the time from the beginning of clot formation until the amplitude of the TEG tracing reaches 20 mm and represents the dynamics of clot formation alpha angle - angle between the line in the middle of the TEG(r) tracing and the line tangential to the developing body of the TEG(r) tracing. The alpha angle represents the acceleration (kinetics) of fibrin buildup and cross-linking MA -maximum amplitude and reflects the strength of the clot, which is dependent on the number and function of platelets and the clot's interaction with fibrin MA60 -  rate of amplitude reduction 60 minutes after MA and represents the stability of the clot EVALUATION OF HEMOSTATIC RISK IN THE SURGICAL PATIENT

Preoperative Evaluation of Hemostasis Several hematologic disorders may have an impact on the outcome of surgery. pre-existing anemia and oral anticoagulation therapy-common clinical situations faced by the surgeon Assessment of bleeding risk should also be considered in patients with li ver or renal dysfunction When feasible, diagnostic evaluation of the patient with previously unrecognized anemia should be carried out before surgery, because certain types of anemia (particularly sickle cell disease and immune hemolytic anemias) may have implications for perioperative management Hemoglobin levels below 7 or 8 g/dL appear to be associated with significantly more perioperative complications than higher levels Determination of the need for preoperative transfusion in an individual patient must consider factors other than the absolute hemoglobin level, including o presence of cardiopulmonary disease type of surgery o likelihood of surgical blood loss o Many patients have anemia postoperatively secondary to blood loss and hemodilution and do not necessarily require transfusion directed bleeding history- most important component of the bleeding risk assessment provide meaningful clues to the presence o of a bleeding tendency 

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Patients who are reliable historians and who reveal no suggestion of abnormal bleeding on directed bleeding history and physical examination are at very low risk for having an occult bleeding disorder Laboratory tests of hemostatic o parameters is not required When the directed bleeding history is unreliable or incomplete or when abnormal bleeding i s suggested formal evaluation of hemostasis should o be performed before surgery PT, the aPTT, and the platelet  count EVALUATION OF EXCESSIVE INTRAOPERATIVE OR POSTOPERATIVE BLEEDING

Excessive bleeding during or after a surgical procedure may be the result of o ineffective hemostasis o blood transfusion o undetected hemostatic defect o consumptive coagulopathy o fibrinolysis Excessive bleeding from the operative field unassociated with bleeding from other sites usually suggests inadequate mechanical hemostasis Massive blood transfusion-well-known cause of thrombocytopenia Bleeding after massive transfusion can occur due to o Hypothermia o dilutional coagulopathy o platelet dysfunction, o fibrinolysis o hypofibrinogenemia Another cause of hemostatic failure related to the administration of blood is hemolytic transfusion reaction diffuse bleeding -first sign of a transfusion reaction o release of ADP from hemolyzed red blood cells-> diffuse platelet aggregation->after which the platelet clumps are removed out of the circulation->bleeding Transfusion purpura occurs when the donor platelets are of the uncommon Pl(A1) group uncommon cause of thrombocytopenia and o an associated bleeding after transfusion The platelets sensitize the recipient, who makes antibody -> antibody then destroys the recipient's own platelets-> thrombocytopenia and bleeding may continue for several weeks. This uncommon cause of thrombocytopenia should be considered if bleeding follows transfusion by 5 or 6 days. Platelet transfusions are of little help in the management of this syndrome, because the new donor platelets usually are subject to the binding of antigen and damage from the antibody Corticosteroids may be of some help in reducing the bleeding tendency. Posttransfusion purpura is self-limited, and the passage of several weeks inevitably leads to subsidence of the problem. DIC is characterized by systemic activation of the blood coagulation system-> results in the generation and deposition of fibrin ->leading to microvascular thrombi in various organs -> contributing to the development of multiorgan failure Consumption and subsequent exhaustion of coagulation proteins and platelets due to the ongoing activation of the coagulation system may induce severe bleeding complications

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Severe hemorrhagic disorders due to thrombocytopenia have occurred as a result of gramnegative sepsis pathogenesis of endotoxin-induced o thrombocytopemia- related to lability of factor V Defibrination and hemostatic failure also may occur with meningococcemia, Clostridium perfringens sepsis, and staphylococcal sepsis Hemolysis appears to be one mechanism in o sepsis leading to defibrination

From omgfacts.com: 

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Dave.Linelle.Deane.Mhe.Te.Paul

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