Hemostasis Flashcards
Platelets
150-400,000 per microliter of blood. 33% in spleen. life span 8-12 days
3 steps of primary hemostasis
Adhesion, Activation, Aggregation
Adhesion of Platelets
Factor needed: Von Willebrand’s Factor
surrounding endothelial cells synthesize and release VWF. VWF binds to the damaged endothelial wall and to GP1B receptor. GP1B receptor binds platelets.
Activation of Platelets
Factor needed: thrombin (factor II). Thrombin binds to activate platelets. Activation of platelets results in the production of thromboxane 2A and ADP.
Thrombin + Platelets –> Thromboxane A2 and ADP
thrombin + platelets = phospholipase with convert phospholipids into arachidonic acid which = prostaglandin G2. PGG2 is metabolized to PGH2 which converts to thromboxane A2 and ADP.
Aspirin effect on platelets
Irreversibly inhibits COX-1. for the life of the platelet 8-12 days. COX stops the conversion of arachidonic acid to PGG2 therefore inhibiting thromboxane A2 and ADP production.
NSAID effect on platelets
Reversibly inhibits COX 1, stop 24-48 hrs. COX stops the conversion of arachidonic acid to PGG2 therefore inhibiting thromboxane A2 and ADP production.
Aggregation of Platelets
Thromboxane A2 and ADP uncover fibrinogen receptors on the platelets to bind the platelets together. clot formation begins here but is still water soluble and friable
Secondary Hemostasis Steps
Production of fibrin. Extrinsic or intrinsic pathway to the final common pathway
Production of Fibrin
factor needed: factor XIII. crosslinks and weaves the platelets together. XIII is activated via either Extrinsic or Intrinsic pathway ending in the final common pathway.
Intrinsic Pathway
XII - XI - IX - VIII. damage occurs inside blood vessel.
Extrinsic
III - VII. damage occurs external to blood vessel.
Final Common Pathway
X - V - II - I - XIII
Coumadin
Acts on extrinsic and final common pathway. Prothrombin and INR.
Heparin
Forms complex with antithrombin III = 1000 fold increase
Acts on intrinsic and final common pathway
Inhibits IIa & Xa, depresses IX, XI, XII
rapid onset, 6 hr duration
Dose 5000 units for DVT
met: liver, elimination: reticuloendothelial system
Monitor PTT and ACT. Half life is 1.5hrs. Stop 6 hours prior to surgery.
Hemophilia A
Disorder of fibrin - factor VIII (intrinsic). sex linked genetic disorder. primarily affects males but carried by female.
TX: FFP or cryo – contains factor VIII
Preferred replacement is a factor VIII pooled plasma product
Hemophilia B
factor IX deficiency. Tx concentrated preparations of factor IX
Von Willebrands Disease
increased bleeding time with normal platelet count and clot retraction. insufficient synthesis of VWF. Treat with DDVAP which releases and stores endogenous VWF. second line is cryo or factor VIII concentrate.
Fibrinolysis
plasmin breaks down fibrin into fibrin split products
Plasminogen
Synthesized in the liver, circulates in the blood. during clot formation is incorporated into the growing thrombus. Plasminogen activates to plasmin
Plasminogen activators
tpa - tissue type plasminogen activator - produced by endothelial cells upa- urokinase type plasminogen activator streptokinase -produced by b hemolytic streptococci
Anti-fibrinolytics
Aprotinin, Epsilon aminocaproic acid (Amicar, EACA) and tranexamic acid
Aprotinin
inhibits plasmin = slowing of fibrin breakdown. Used during cardiac surgery to decrease intraop blood loss.
Epsilon aminocaproic acid (Amicar, EACA) & tranexamic acid
prevent the breakdown of fibrin by preventing displacement of the plasmin from the fibrin
May be beneficial in hemorrhage control.
DIC
from underlying disease (sepsis, hemolysis - massive transfusion, ischemia, brain trauma, hypotension/hypoperfusion, OB emergencies).
shock, ischemia, and infection are the most common in the surgical populations
Labs reflect consumption of factors and enhanced fibrinolysis. Decreased plts, fibrinogen, prothrombin, factors V, VIII, XIII. Increased fibrin degradation split products.
Liver Disease
most common cause of an isolated high PT.
Defects in coagulation.
1. formation of platelet plug - thrombocytopenia from hypersplenism and platelet dysfunction from increased fibrin degradation products.
2. formation of fibrin clot on platelet surface. synthesis of all coag factors is decreased (EXCEPT VIII). increased fibrin split products interfere with fibrin polymerization
3. Fibrinolysis. increased lytic activity due to poor clearance of tpa.
Tx: replace clotting factors - cryo, FFP, vitamin K
Renal Failure
uremia is an anticoagulant. Platelet dysfunction -
adherence to subendothelial collagen & synthesis of thromboxane A2 is impaired.
• Lower concentration of ADP
• Platet transfusion is ineffective- transfused plts become abnormal
• Fibrinogen and other clotting factors are decreased, fibrinolytic system is impaired.
Tx: dialysis and increased hct. cryo and DDVP may help the bleeding.
Multiple Transfusions
transfused blood is deficient in clotting factors V & VIII and platelets. Diffuse bleeding during transfusion is usually from thrombocytopenia
o TX: platelets, FFP, cryo
Cryo is a primary source for I, VIII, XIII
Cryoprecipitate
Cryo is a primary source for I, VIII, XIII
ASA - acetylsalicyclic acid
anti-platelet, irreversible COX 1 inhibitor. half life 20 min. stop 7 days prior to surgery
Clopidogrel (Plavix)
ADP receptor antagonist - inhibits activation of GP2B receptors which bind platelets. Stop 5-7 days prior to surgery.
LMWH
anti-coagulant. antagonizes factor IIa & Xa (indirect). 4.5 hr half life. Monitor anti-factor Xa. Stop 12-24 hrs prior. Protamine is the reversal.
Warfarin
anti-coagulant.
Vitamin K epoxide reductase antagonist.
Half life 2-4 days.
stop 5 days before surgery
Monitor: PT
Reversal: Vit K, FFP, recombinant factor VII
Bleeding Time
3-7 min. Measures platelet function- adhesion & aggregation. Modest prolongations do not predict surgical bleeding. Altered by NSAIDs & Aspirin.
Platelet Count
150-400,000
Thrombocytopenia
Platelets < 100,000
Surgical Risk
platelets < 50,000
Spontaneous Bleeding
Platelets < 20,000
Prothrombin Time
PT 12-14s. Prolonged with extrinsic & common pathway disorders, altered by Coumadin derivatives
Activated partial thromboplastin time
aPTT 25-32s. Prolonged w intrinsic & common pathway disorders. altered by heparin & lovenox.
Thrombin Time
8-12s. common pathway. measures fibrinogen to fibrin action.
ACT
activated clotting time - 80-150s. guides anticoagulant dosing.
Fibrinogen
> 150mg/dL
Fibrinogen degredation products
<10mcg/ml. measures byproducts from clot dissolution
D-dimer
<500mg/ml - measures degradation products secondary to fibrinolysis
Antithrombin III
80-120%. decreased level may explain sub therapeutic heparin. is severely decreased in DIC.
Antithrombin neutralizes intrinsic & final common factors. inhibits II & X, depresses IX, XI, XII
Antithrombin deficiency: liver cirrhosis, nephrotic syndrome
tPA
fibrinolytic - plasminogen activator. half life is 23 minutes.
stop 3 hours prior to surgery.
monitor PT/PTT.
produced by endothelial cells
Tranexamic Acid - TXA
antifibrinolytic - synthetic reversible competitive inhibitor of the lysine receptor on plasminogen. binding to the receptor prevents plasmin from binding = stabilization of fibrin clot.
use: prevent bleeding/transfusion need
IV or PO
1g over 10 min, can do another within 8 hrs, MAX 2g
elimination: really unchanged
XXX in intracranial bleeding & thromboembolic
rapid infusion can cause hypotension
protamine
heparin reversal. forms inactive compound with heparin dose dep on heparin 1mg/100 units of heparin admin < 5mg/min 5 min onset 2 hr DOA = rebound bleeding M & E: reticuloendothelial system
Consideration: histamine release = hypotension, pulm HTN, circulatory collapse, facial flushing, bronchoconstriction
TEG
measures clot formation over time 1 - platelet reactions 2- coagulation 3 - fibrinolysis provide information of clot strength, platelet number & function, intrinsic defects, thrombin action, rate of fibrinolysis
Upa
Urokinase is the most widely used thrombolytic agent for intra-arterial infusion into the peripheral arterial system and grafts.
