Transcript Hemostasis

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
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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
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Fibrinolysis = lysis of the fibrin clot
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Plasminogen Plasmin degrades fibrin, Factor V and VIII
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Binds and inhibits thrombin and factors IX, X, XI
Protein C
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Breakdown of the clot permits restoration of blood flow and fibrin clot in vessel
wall may be replaced with collagen
Antithrombin III
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Plasminogenplasmin by several activators—tPA, (kalikrein increases release of tPA),
uPA, factor XII
Plasminogen levels rise due to exercise, venous occlusion, and anoxia
Vitamin K-dependent
Degrades fibrinogen and factors V and VIII
Protein S
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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
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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 vWFvariable 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
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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
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Reversed with administration of protamine (1mg protamine for
every 100u heparin received)
Follow aPTTwant 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
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“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
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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 ADPstimulated aggregation if >10units of blood
transfused.
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Hypercoagulable States
 Factor V Leiden Deficiency
 MOST COMMON congenital hypercoagulable
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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
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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
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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
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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?