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
Fibrinolysis = lysis of the fibrin clot
Plasminogen Plasmin degrades fibrin, Factor V and VIII
Binds and inhibits thrombin and factors IX, X, XI
Protein C
Breakdown of the clot permits restoration of blood flow and fibrin clot in vessel
wall may be replaced with collagen
Antithrombin III
Plasminogenplasmin 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
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 ADPstimulated 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?