hemostasis
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Hemostasis. Shaina Eckhouse 10/12/2010. Objectives. Biology of Hemostasis Congenital Hemostasis Defects Aquired Hemostasis Defects Hypercoagulable States Venous thromboembolism Transfusion Evaluation of the Surgical Patient at Hemostatic Risk. Name that Movie. - PowerPoint PPT PresentationTRANSCRIPT
Hemostasis
Shaina Eckhouse10/12/2010
Objectives
Biology of Hemostasis
Congenital Hemostasis Defects
Aquired Hemostasis Defects
Hypercoagulable States
Venous thromboembolism
Transfusion
Evaluation of the Surgical Patient at Hemostatic Risk
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Biology of Hemostasis
Complex process that prevents or terminates blood loss from a disrupted intravascular space
Major physiologic events Vascular constriction Platelet plug formation Fibrin formation fibrinolysis
Biology of Hemostasis
Vascular Constriction Initial vascular response to injury Vasoconstriction linked to platelet plug
formation TXA2 ET 5-HT Bradykinin & Fibrinopeptides
Biology of Hemostasis
Platelet Function 150-400K circulating platelets ~30% sequestered in the spleen Thrombopeptin, IL-1, IL-6 mediate platelet
production
Biology of Hemostasis
Platelets play an integral role in: Formation of a
hemostatic plug Contributes to thrombin
formation
Biology of Hemostasis
VC + platelet plug formation = PRIMARY HEMOSTASIS Reversible Not associated with secretion
Biology of Hemostasis
Biology of Hemostasis
Intrinsic Pathway All the components
leading to the fibrin clot formation are intrinsic to the circulating plasma
Elevated PTT associated with an abnormality in the intrinsic clotting pathway
Biology of Hemostasis
Extrinsic Pathway Requires exposure of
tissue factor on the surface of the injured vessel wall
Starts with Factor VII
Abnormality of the extrinsic pathway is associated with an elevated PT
Biology of Hemostasis
Biology of Hemostasis
Fibrinolysis = lysis of the fibrin clot Plasminogen Plasmin degrades fibrin, Factor V and VIII
Plasminogenplasmin by several activators—tPA, (kalikrein increases release of tPA), uPA, factor XII
Plasminogen levels rise due to exercise, venous occlusion, and anoxia Breakdown of the clot permits restoration of blood flow and fibrin clot in
vessel wall may be replaced with collagen
Antithrombin III Binds and inhibits thrombin and factors IX, X, XI
Protein C Vitamin K-dependent Degrades fibrinogen and factors V and VIII
Protein S Vitamin K-dependent Protein C cofactor
Biology of Hemostasis
How do SCDs work?
The squeeze stimulates the release of tPA from the endothelial cells of vessels. Induction of fibrinolysis. (tPA is selective for fibrin-bound plasminogen
and converts to plasmin; therefore, fibrinolysis occurs mostly at the site of clot formation.)
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Congenital Hemostatic Defects
Coagulation Factor Deficiencies Hemophilia
Factor VIII deficiency = Hemophilia A Sex-linked recessive Both prolonged aPTT and PT Need level to be 100% pre-op and 30% post-op Crosses placenta Hemophiliac Joint
No aspiration; ice; ROM exercises, factor VIII concentrate or cryoprecipitate
Factor IX deficiency = Hemophilia B/Christmas Disease Sex-linked recessive Need level 50% pre-operatively Prolonged aPTT and normal PT Tx-factor IX concentrate or cryoprecipitate
Congenital Hemostatic Defects
von Willibrand’s Disease MOST COMMON congenital bleeding disorder Low levels of vWFvariable decrease in Factor VIII due to
loss of the carrier protein vWF is necessary for normal platelet aggregation;
therefore deficiency presents in a similar fashion to platelet disorders
Prolonged bleeding time, possible abnormal PTT, normal PT
Types- I-partial quantitative deficiency (AD) II-qualitative defect (AD) III-total deficiency (AR)
Tx—intermediate purity factor VIII or DDAVP (Type I or II only)
Congenital Hemostatic Defects
Platelet disorders Glanzmann’s thrombocytopenia—deficiency in
GIIbIIIa receptor of platelets; therefore, platelets cannot bind to each other Tx-platelets
Bernard Soulier—Gp1b receptor deficiency; therefore, platelets cannot bind collagen via vWF Tx-platelets
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Acquired Hemostatic Defects
Anticoagulation Heparin—potentiates ATIII action
Reversed with administration of protamine (1mg protamine for every 100u heparin received)
Follow aPTTwant 1.5-2.5x upper limit of nl (60-90) Does not cross placental barrier
Lovenox—potentiates ATIII and inhibits both thrombin and Factor Xa “more reliable therapeutic anticoagulation can be achieved” Drug effect can be determined by anti-Xa assay No definitive reversal
Warfarin (Coumadin) Inhibits Vitamin K synthesis Reversed by FFP or Vitamin K administration Follow INR/PT
Acquired Hemostatic Defects
Why do we bridge with heparin or Lovenox when initially starting Coumadin?
Protein C and S are inhibited before factors II, VII, IX and X which makes the patient relatively hypercoaguable for 5-7 days
Acquired Hemostatic Defects
Antiplatelet Medications Asprin—Platelet cyclooxygenase is irreversibly
inhibited ; decreases TXA2 which promotes platelet aggregation
Plavix (Clopidogrel)—ADP receptor antagonist Pentoxifylline—inhibits platelet aggregation and
decreases viscosity of blood; used in treatment of peripheral arterial disease
Acquired Hemostatic Defects
Heparin Induced Thrombocytopenia 2/2 antiplatelet Ab (IgG) that results in platelet
destruction Platelet count falls to <100K or by <50% in 5-7
days if first exposure or in 1-2 days if re-exposure
High incidence of platelet aggregation and thrombosis (white clot)
If suspected— STOP heparin Start alternate anticoagulation (lepirudin or
argatroban)
Acquired Hemostatic Defects
Disseminated Intravascular Coagulation Systemic process producing both thrombosis and
hemorrhage Exposure of blood to procoagulants Formation of fibrin in the circulation Fibrinolysis Depletion of clotting factors end-organ damage
Dx= decreased platelets, prolonged PT and aPTT, low fibrinogen, high fibrin split products, high D-dimer
Treat the underlying disease (sepsis, trauma, burns, malignancy)
Acquired Hemostatic Defects
Thrombocytopenia MOST COMMON abnormality of hemostasis Variety of etiologies (ITP, TTP, HUS, SLE,
lymphoma, secondary hypersplenism, portal HTN, uremia…)
In setting of massive transfusion—exchange of 1L of blood volume (~11units) decreases platelet count from 250K to 80K. Associated impaired ADP-stimulated aggregation if >10units of blood transfused.
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Hypercoagulable States
Factor V Leiden Deficiency MOST COMMON congenital hypercoagulable
disorder AD Leiden variant of Factor V cannot be inactivated
by Protein C Increased risk for DVT, spontaneous abortion Tx = heparin or warfarin
Hypercoagulable States
AT-III deficiency Spontaneous venous thrombosis Heparin does not work on these patients unless
pretreated by FFP Tx: AT-III concentrated
Antiphospholipid Antibody Syndrome Presence of lupus anticoagulant that bind to
phospholipids and proteins on the cell membrane an interfere with clotting; HOWEVER, associated with thrombosis and habitual abortions (prolonged PTT in the face of a hypercoagulable state)
Tx: Heparin, coumadin
Hypercoagulable States
Amicar Aminocaproic acid Inhibits fibrinolysis by inhibiting plasmin Indications: DIC, persistent bleeding following
CPB, thrombolytic overdose
Aprotinin Inhibits fibrinolysis by inhibiting activation of
plasminogen to plasmin
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Venous thromboembolism
DVT and PE Virchow’s triad = stasis, endothelial injury,
hypercoagulability Treatment for DVT
1st= warfarin x 6months 2nd= warfarin x 1year 3rd or significant PE = lifetime warfarin
Greenfield filters For patients with contraindications to anticoagulation Documented PE while on anticoagulation Free-floating iliofemoral clot IVC or femoral DVT Patients who have undergone previous pulmonary
embolectomy PE most commonly caused by DVT in iliofemoral region
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Transfusion
PRBCs 1unit=~250mL Storage life ~35days 1unit increases Hgb by 1 and Hct by 3 Fever without hemolysis is the most common
transfusion reaction (1 in 6,000) Usually recipient antibody reaction against WBCs in
donor blood Acute Hemolytic reactions occur 1 in 35,000
Caused by ABO incompatibility or Ab mediated usually from human error (Ab in recipient binding to surface Ag on donor RBC)
Sx=hypotension, fever, dyspnea, chest pain, low back pain
Tx=fluids, diuretics, HCO3, histamine blockers, pressors
Transfusion
Platelets 50-100 billion in 50mL plasma Can be stored for ~7 days (viability declines after 3
days) Each platelet concentration should raise circulating
platelets by >5,000 (4-6 pack of platelets shound increase platelets by 20-30K)
Febrile nonhemolytic reactions more common than with PRBCs (incidence is ~30%)
Antiplatelet antibodies develop in 20% of patients after 10-20 transfusions
Indictions in active bleeding: plt<50K or plt<100K in setting of ICH; trauma victims who have received multiple transfusion
Contraindicated in HIT and TTP
Transfusion
FFP ~250 mL collected from 1 unit whole blood by
apheresis Stored between -18 and -30 degree C and is good
for 1 year Dose is ~10-15mL/kg Contains all coagulation factors, protein C, protein
S, and AT-III (only blood product with factor V) Indications-warfarin overdose, liver failure,
dilutional coagulopathy associated with massive transfusion
Highest risk of TRALI—important to distinguish from volume overload. Tx=supportive
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Evaluation of the Surgical Patient at Hemostatic Risk
Preoperative Assessment History
Bruises without apparent injury Prolonged bleeding after injury PMHx—liver disease, congenital or acquired bleeding
disorders Medications
Labs—CBC, Coagulation panel, T&S or T&C
Intraoperative and Postoperative Ineffective local hemostasis Complications of blood transfusion Consumptive coagulopathy Fibrinolysis
Questions?