Coagulation and Hemostasis

Coagulation
and
Hemostasis
Joy Loy, M.D.

MetroHealth Medical Center
December 2006
• Hemostatic process
• Coagulation cascade
• Fibrinolysis
• Laboratory studies
• Medications
• Coagulation disorders
Hemostasis
Purpose
 Ensure that coagulation mechanisms are
 activated when there is injury
 not unnecessarily activated
 Restore tissue blood flow after repair of
injury (fibrinolysis)
Hemostatic Process
3 main steps
 Primary hemostasis: local vasoconstriction &
platelet plug formation
 Coagulation cascade
 Fibrinolysis
Hemostatic Process
Platelet Plug Formation
• vascular injury
• release and binding of vWF to exposed
blood vessel collagen
• glycoprotein IB on platelet surface
membrane binds to vWF
• TxA2 → vasoconstriction & platelet adhesion
• platelet factor 3 (PF3) phospholipid layer
(procoagulant)
Platelet Activation & Aggregation
exposed endothelial surface
platelets exposed to collagen
“activated”
release contents of cytoplasmic granules
adenosine diphosphate (ADP) thromboxane (Tx
A2 )
accelerates platelet vasoconstriction

aggregation/activation ↑ ADP release from platelets
Hemostatic Process
Coagulation Cascade
 to stabilize and reinforce the weak platelet plug

 fibrinogen → fibrin
 3 main steps:
1. formation of prothrombin activator
2. conversion of prothrombin into thrombin
3. conversion of fibrinogen to fibrin

Coagulation Cascade
TF =tissue factor
PK = prekallikrein
HK=high molecular
kininogen
a = activated
Roberts HR, et al. Current Concepts for Hemostasis. Anesthesiology 2004;100:3. 722-30.
Coagulation Mechanism
 activation of clotting factors

 requires a phospholipid surface
 tissue factor (TF) extrinsic to the blood
 activated platelet (platelet factor 3 phospholipid)
intrinsic to blood
 vitamin-K dependent factors (II, VII, IX, X)
 formation of reaction complex
 labile factors : factors V and VIII
Factor VIII
 extrahepatic origin
 2 components (separate genetic control)
1. VIII R : Ag VIII antigen + vWF
2. VIII : C coagulant activity
*absence → hemophilia A
 von Willebrand factor (vWF)
• mediates adhesion of platelets to surface collagen
• carrier of VIII:C
• vWD: appears to have defect in primary hemostasis
& hemophilia A
Factor VIII
F VIII:C F VIII:vwF
hemophilia A decrease --------
vWD type 1 decrease decrease
vWD type 2 normal decrease

Coagulation Cascade
TF =tissue factor
PK = prekallikrein
HK=high molecular
kininogen
a = activated
Newer Concepts of Coagulation Reactions
2 main functions of tissue factor (TF)

1) to activate factor X to Xa
2) to activate factor IX to IXa
Control Mechanisms
APC: activated protein C

1) TF pathway inhibitor AT : antithrombin
GAG: glycoaminoglycans
2) Protein C system T : thrombin
PC : protein C
3) Antithrombin (e.g. AT III)
S : protein S
4) Glycoaminoglycans TF : tissue factor
TM : thrombomodulin
Antithrombin III (AT III)
 naturally-occuring anticoagulant
 binds to factors IXa, Xa, XIa, XIIa (slow)
 accelerated by heparin manyfold
Implication:
Heparin has almost NO anticoagulant
action without AT III

Coagulation Factors
FACTORS PLASMA t ½ FACTORS PLASMA t ½

(hrs) (hrs)
Fibrinogen (I) 72-120 XI 52
XII 60
Prothrombin (II) 60-70
Protein C 6
V 12-16
Protein S (total) 42
VII 3-6
VIII 8-12 Tissue factor --
IX 18-24 Thrombomodulin --
X 30-40 antithrombin 72
Roberts HR, et al. Current Concepts for Hemostasis. Anesthesiology 2004;100:3. 722-
30.
Fibrinolysis
 Plasminogen → plasmin
 Release of tPA by the endothelium
 Lysis of clot→ FDPs or FSPs
 Reopening of blood vessel

Laboratory Monitoring
Prothrombin Time (PT)
 test of extrinsic pathway activity

 measures vitamin K - dependent factors activity
(factors II, VII, IX, X)
 thromboplastin + Ca+2 to plasma = clotting time
 normal values: 12-14 seconds
 International Normalized Ratio (INR)
▪ standardizes PT reporting
 normal values: 0.8 -1.2 seconds
Prothrombin Time (PT)
 monitors coumadin therapy
 most sensitive to alteration in F VII levels
 prolonged: 55 % ↓ of normal F VII activity
 antithrombotic activity: reduction of factor II
and factor X activity (after several days)

Activated Partial Prothrombin Time (aPTT)
 test for intrinsic and common pathways
 dependent on activity of all coagulation factors,
except VII and XIII
 normal values: 25 -35 seconds
 monitors heparin tx & screen for hemophilia

Activated Prothrombin Time (aPTT)
 prolonged: heparin, thrombin inhibitors,
fibrin degradation products (FDP)
 citrated plasma + surface activators +

phospholipid
 prolonged only if coagulation factors reduced

to < 30 % of normal
Activated Clotting Time (ACT)
 monitors heparin anticoagulation in the OR

(cardiac and vascular surgeries)
 normal values: 90 - 120 seconds

Thrombin Clotting Time (TCT)
 reflects abnormalities in fibrinogen → fibrin
 plasma + excessive amount of thrombin
 prolonged: heparin, thrombin inhibitors,
low fibrinogen, dysfibrinogenemia
 monitors hirudin, bivalirudin, LMWH tx

 INR & PT may be normal or ↑
 TCT prolonged with adequate therapeutic levels

Thromboelastography (TEG)
 continuous profiles during all phases of

clot formation
 provides more accurate picture of in vivo
coagulation process
 to evaluate:
• hypo / hypercoagulable state
• hemophilia
• dilutional coagulopathy
• rare coagulation disorders anticoagulation tx
• coagulation problems with liver transplantation
Thromboelastogram
(TEG)
Bleeding time
 monitors platelet function
 not specific indicator of platelet function
 not very reliable
 very operator - dependent
 variable from each institution

Bleeding time
 other factors: degree of venostasis, depth
and direction of incision
 no evidence as
• a predictor of risk of hemorrhage
• useful indicator of efficacy of antiplatelet therapy
 insensitive to mild platelet defects

Platelet Function Analyzer (PFA) - 100
 relatively new global test of platelet adhesion

and aggregation
 advantages
 noninvasive, simple, easy to perform
 very sensitive in detecting platelet defects
associated with vWD
 sensitive to dx of acquired platelet defects (ASA,
NSAID, dietary factors: excessive cocoa intake)
 monitors pro-hemostatic treatment

 DDAVP & platelet transfusions
PFA-100
Limitations
■ inflexibility
■ results should be interpreted in the context
of either a simultaneously or recently drawn
full blood count
■ platelet count < 80,000 or Hct < 30% will
prolonged CT even if no platelet abnormal

LABORATORY TEST NORMAL
COMPONENTS MEASURED VALUES
Bleeding time platelet function 3 - 10 mins

vascular integrity
PT 12 - 14 secs
I, II, V, VII, IX, X
PTT 24 - 35 secs
I, II, V, VIII, IX, X, XI, XII
12 - 20 secs
Thrombin time I, II
Implications for Therapy
 Congenital & acquired factor deficiencies

 history
 medications
 congenital factors: vWD, hemophilia, platelet disorders
 acquired disorders: multifactor-renal, hepatic, DIC
 Antiplatelet medications
 Anticoagulants
Drugs affecting Coagulation
HEMOSTATIC
PROCESS CLASS OF SPECIFIC
AFFECTED DRUGS DRUGS
1º platelet plug antiplatelet drugs reversible: NSAID
formation inhibition irreversible: ASA
coagulation cascade IV anticoagulants standard and LMW

heparins
oral anticoagulants warfarin
fibrinolysis fibrinolytic agents Streptokinase
Urokinase
t-PA
Prostaglandin Synthesis
arachidonic acid
cyclooxygenase
prostaglandin G2
peroxidase
prostaglandin H2
prostacyclin thromboxane
synthetase synthetase
prostacyclin thromboxane A2
PG F1a thromboxane B2
Mechanism of Action
ASPIRIN
arachidonic acid ASPIRIN

cyclooxygenase
prostaglandin G2
peroxidase
prostaglandin H2
Mechanism of Action
ASPIRIN and NSAIDS
arachidonic acid ASPIRIN

cyclooxygenase
prostaglandin G2 NSAIDS
peroxidase
prostaglandin H2
Antiplatelet Medications
SITE OF PLASMA META- Ø PRIOR ↑ PT / ANTI –
DRUG ACTION ROUTE t 1/2 BOLISM PROCEDURE DOTE
PTT
Aspirin COX 1 oral 20 min hepatic 7 days No/No none
and 2
Dipyrida- adenosine oral 40 min hepatic 24 hrs No/No none
mole
Clopidogrel ADP oral 7 hrs hepatic 5 days No/No none

(Plavix)
Ticlodipine ADP oral 4 days hepatic 10 days No/No none

(Ticlid)
Abciximab GPIIb-IIIa IV 30 min renal 72 hrs No/No none

(ReoPro)
Eptifibatide GPIIb-IIIa IV 2.5 hrs renal 24 hrs No/No none
Tiroban GPIIb-IIIa IV 2 hrs renal 24 hrs No/No hemo-

dialysis
Non-steroidal Anti-inflammatory Medications
SITE OF PLASMA META- Ø PRIOR ↑ PT / ANTI –
DRUG ACTION ROUTE t 1/2 BOLISM PROCEDURE DOTE
PTT
Piroxicam COX 1 & 2 oral 50 hrs hepatic 10 days No/No none
Indome – COX 1 & 2 oral/ 5 hrs hepatic 48 hrs No/No none
thacin supp
Ketorolac COX 1 & 2 oral / 5-7 hrs hepatic 48 hrs No/No none
IV
Ibuprofen COX 1 & 2 oral 2 hrs hepatic 24 hrs No/No none
naproxen COX 1 & 2 oral 13 hrs hepatic 48 hrs No/No none
Diclofenac COX 1 & 2 oral 2 hrs hepatic 24 hrs No/No none
Celecoxib COX 2 oral 10-17 hepatic none No/No none

hrs
Anticoagulants & Thrombolytics
DRUG SITE OF PLASMA EXCRE- Ø PRIOR ↑ PT / ANTI –

ACTION ROUTE t 1/2 TION PROCEDURE DOTE
PTT
Unfraction- IIa/Xa IV/SC 1.5 hrs hepatic 6 hrs No/ protamine
ated Yes
heparin
LMWHs Xa SC 4.5 hrs renal 12-24 hrs No/No protamine
IIIa (partial)
Strepto - plasmi – IV 23 mins hepatic 3 hrs Yes/ antifibri-
kinase nogen Yes nolytics
t-PA plasmi – IV <5 min hepatic 1 hr Yes/ antifibri-
nogen Yes nolytics
Oral vit-K dep. Oral 2-4days hepatic 2-4 days Yes/No Vit. K,
Anticoagu- factors rFVIIa
lants Plasma,
Prothrom.
complex
Roberts HR, et al. Current Concepts for Hemostasis. Anesthesiology 2004;100:3. 722-30. conc.
Other Anticoagulants
SITE PLASMA META- Ø PRIOR ↑ PT/ ANTI –
OF PROCEDURE PTT
DRUG ROUTE t 1/2 BOLISM DOTE
ACTION
Pentasac- Xa IV 14-17 renal 4 days No/No rFVIIa?
charide hrs
Bivalirudin IIa IV 25 min hepatic 2-3 hrs Yes/ None
Yes
Argatroban IIa IV 45 min hepatic 4-6hrs* Yes/ None
Yes
Hirudin IIa IV 1.5 hr renal 8 hrs* Yes/ PMMA
Yes dialysis
Activated Va/ IV 2 hrs hepatic 12 hrs No/Yes none
Protein C VIIIa
(APC)
Ximelagatran IIa IV 3 hrs renal 24 hrs Yes/ none
Yes
PMMA= polymethyl-methyl acrylate
*Argatroban &lepirudin may ↑ the normal PT 4-5 secs
Oral Anticoagulants
Warfarin
 inhibits synthesis of vitamin - k dependent
factors II, VII, IX, X and protein C & S
 reversal:
 stopping medication and waiting for ~4 days
for PT normalization
 vitamin K PO or IV (1-2mg)
 immediate: rFVIIa, FFP (1-2 units),
prothrombin complex concentrate
 check PT prior to surgery
Oral Anticoagulants
Warfarin
 biphasic effect on PT and INR
 initial ↑: ↓ F VII (shortest t ½) to 55 %
of normal
 subsequent ↑: ↓ F II and X – therapeutic
anticoagulant
 discontinuation
 return to normal: F VII followed by F II & X
 caution: INR =/< 1.4 no assurance of normal
coagulation
Unfractionated Heparin
 negatively charged, water - soluble
glycosaminoglycan
 extracted from porcine gut or bovine lung
 binds and ↑ anti - thrombin III (AT III) activity
to 1,000 fold →binds & inactivates factors IIa
and factor Xa
 degree of inhibition: F Xa = IIa
* LMWH inhibition of Xa > IIa
 lesser inhibition on F XIa, XIa and F XIIa
Low-dose or “minidose”
 5,000 U SC q 12 hrs for thromboprophylaxis

 peak action: 40 - 50 minutes
 duration 4 - 6 hrs
 low risk for hemorrhage during anesthesia
or surgery
 4 reported cases of SEH with CNB
Standard Dose
 regular doses for therapeutic anticoagulation
 high risk of bleeding during & after surgery
 stop at least 6 hrs before surgery

 restarted ~ 12 hrs postop if needed with close
monitoring
 immediate reversal: protamine

Low Molecular Weight Heparin (LMWH)
 4,000-6,500 daltons (vs. standard heparin 3,000
-30,000 daltons
 retains anti-Xa activity
 less anti -IIa than standard heparin
 enhances AT-III interaction with F IIa & F Xa
 degree of inhibition: F Xa > IIa

LMWH in the U.S.
LMWH TRADE MOLECULAR HALF - LIFE Anti Xa:
WEIGHT (minutes) Anti IIa
NAME
(daltons)
Dalteparin Fragmin 5,000 120 2:1
Enoxaparin Lovenox 4,500 150 2.7:1
Danaparoid Orgaran 6,500 1,100 20:1
Ardeparin Normiflo 6,000 200 2:1
Standard 14,000 60-90 1:1

Heparin
Standard Heparin vs. LMWH
PARAMETERS STANDARD HEPARIN LMWH
MOLECULAR WEIGHT 3, 000 - 30,000 daltons 4,000-6,500 daltons
BIOAVAILABILITY predictable
variable due to binding to
plasma protein &
macrophages
MONITORING PTT no need for monitoring
dose adjusted based on PTT no dose adjustments
HALF – LIFE 4-6 hrs

variable; dose-dependent
(30 min for 25 u/kg, 150
mins with 400 u/kg)
CLEARANCE hepatic renal

Standard Heparin vs. LMWH
PARAMETERS STANDARD HEPARIN LMWH
EFFECT ON Higher incidence of HIT Lower incidence of HIT

PLATELETS Inhibition of platelet function Less inhibition
Inhibits platelet-endothelium No interaction
interaction
RISK OF BLEEDING higher Lower
ANTI Xa: IIa 1:1 2:1

ACTIVITY
REVERSAL protamine Only anti-IIa (90%) but
not anti-Xa (60%) activity
reversed by protamine (1
mg/100 anti-Xa units
LMWH
COST inexpensive expensive
Recombinant Factor VIIa
(NovoSeven)
 FDA approved for use in hemophilia & patients
with inhibitors
 enhances the TF pathway
 binds loosely to platelets and directly activates F X

→ ↑ thrombin generation with F Va present
 never completely normalizes thrombin generation

but enhances hemostasis
 dose: 90-120 mcg/kg q 2 hrs x 1st 24 hrs

 variable individual thrombin- generating

capacity
 megadoses: 150-300 mcg/kg
 “off label” use (non - FDA approved)
 liver disease
 liver transplant
 trauma
 ICH
 platelet disorders
 common denominator: defective thrombin generation
 thrombocytopenia ▪ hypothermia
 ↓ plasma coagulation proteins ▪ hyperfibrinolysis
 dilutional coagulopathy
 prophylactic use reported for retropubic prostatectomy,
hepatectomy
 potential use: Jehovah’s witness

Coagulation Disorders
Disorders of Hemostatic Mechanism
 Classification: depends on involvement of
 platelets and/or clotting factors
 and/or presence of inhibitors (such as FDP)
 Treatment
• transfusion of platelets and/or clotting factors
• pharmacologic agents affecting
 Platelets fx (DDAVP, antiplatelet drugs)
 Clotting factors (vit. K, coumadin, heparin)
 Inhibitors (antifibrinolytics, protamine, fibrinolytics)
Hereditary Platelet Disorder
von Willebrand Disease (vWD)
 most common congenital bleeding disorder

 quantitative or qualitative abn. of vWF
 Type 1: most common form
 partial quantitative deficiency of vWF
 autosomal dominant
 mucocutaneous bleeding
 hematology consult prior to surgery
 prolonged bleeding time, normal platelet
Hereditary Platelet Disorders
von Willebrand Disease (vWD)
Type 2: qualitative alterations in the vWF structure
& function
Type 3: least common and most severe

 Complete absence of vWF in plasma or storage organelle
 Autosomal recessive
 acquired vWD
 Lymphoproliferative disease ▪ cardiac/valvular disease
 Tumors ▪ medications (valproic acid)
 Autoimmune disease ▪ hypothyroidism
Hereditary Platelet Disorders
von Willebrand Disease
 Treatment: Desmopressin (DDAVP)
 synthetic analog of vasopressin
 ↑ both F VIII and vWF 3 - 5x in 30 mins
 preop prophylactic dose: 0.3 mcg/kg IV in 50

-100 ml NS infused 30-60 mins q 12-24 hrs PRN
 duration 8-10 hrs
 intranasal dose: 300 mcg – for home treatment,

not for preop prophylaxis
Hereditary Bleeding Disorders
von Willebrand Disease
 DDAVP
 vasomotor effect: flushing, ↑HR, headache
 SE: hyponatremia, seizures
 not for children < 3 yrs old
 unresponsive to DDAVP (15%)

 cryoprecipitate
 FFP
 factor VIII / vWF concentrate
Acquired Platelet Disorders
 Thrombocytopenia : platelets <150,000/mm3
 inadequate production by bone marrow
 splenic sequestration
 consumption coagulopathy
 dilutional thrombocytopenia
 immunogenic destruction
 Platelet dysfunction
 myeloproliferative and myelodysplastic syndromes
 renal failure, liver disease, DIC, CPB
 drugs: NSAIDS, ASA
* DDAVP: tx platelet dysfunction due to uremia, liver disease, and
patients on ASA for CABG
Hereditary Factor Deficiencies
Hemophilia
 x-linked recessive conditions (males only)
 type A : F VIII:C deficiency (Classical Hemophilia)
B : F IX deficiency (Christmas disease)

C : F XI deficiency
 unexplained bruising or bleeding in young males,
usually ~ 1 yr of age
 joint & muscle bleeding → arthropathy
Hereditary Factor Deficiencies
Hemophilia
■ screening: prolonged PTT
■ hemophilia A
mild
moderate
severe : life-threatening (CNS bleed)
 treatment
factor replacement
rFVIIa
Factor VIII Concentrate Necessary for Hemostasis
Factor VIII Concentrate

(% of normal)
Spontaneous hemorrhage 1-3 %
Moderate trauma 4-8 %
Hemarthrosis/deep skeletal 10-15 %

muscle hemorrhage
Major surgery > 30%
Acquired Factor Deficiencies
 Vitamin - K deficiency
malabsorption syndromes
pancreatic insufficiency
biliary obstruction
GI obstruction
 treatment: vitamin K
Platelet Dysfunction, Factor Deficiencies &
Presence of Inhibitors
 Liver disease
• synthesis of coagulation factors (except VIII),
anticoagulants, ATIII, protein C & S, plasminogen
• clearance of activated clotting factors, tPA, FDPs
 DIC
Hypercoagulable States
Factor V Leiden Mutation
 glutamine is substituted for arginine at
position 506→ resistant to inactivation by
protein C
 dx: genetic screening
 ↑ risk for DVT in lower extremities & brain
homozygous (20x) >heterozygous (7x)
 if asymptomatic: no anticoagulation
Hypercoagulable States
Factor V Leiden Mutation
 Treatment
▪ warfarin x 6 mos or until thrombosis
free for 2 mos
▪ LMWH x 2 wks after warfarin
then retested
▪ long term anticoagulation if persist
or recurrent thrombotic event
Idiopathic Thrombocytopenic Purpura
(ITP)
 more commonly found in children
 diagnosis of exclusion
 petechia <20,000x 109/l platelets
 bleeding <10,000x 109/l
 medical management
Blood Component Therapy
Platelet Transfusion
 1 unit ↑ platelets count 10,000 mm3
 adult dose: 1 unit/10 kg BW within 24 hrs
 indications (NIH)
▪ thrombocytopenia with clinical coagulopathy
10, 000 in ITP
20, 000 in bone marrow suppression
40,000 during massive transfusion
▪ platelet dysfunction even with platelets>100,000

CPB drugs (ASA, etc)
uremia thrombasthenia
Transfusion of FFP
1) replacement of isolated factor deficiency
2) reversal of coumadin
3) antitrombin III deficiency
4) treatment of immunodeficiencies
5) treatment of TTP
6) massive blood transfusion

Cryoprecipitate
 contains significant levels of factor VIIIC,

factor VIII: vwF, XIII, fibrinogen
 indications:
1) hemophilia
2) von Willebrand disease
3) fibrinogen deficiencies
4) uremic platelet dysfunction
References
 Roberts HR, Monroe DM, Escobar MA. Current Concepts of Hemostasis.

Anesthesiology 2004; 100:722-30.
 De Souza GJ. Anticoagulation and Central Neuraxial Anesthesia. Progress in
Anesthesiology. 2000;vol XIV, Chap 9: 132-148.
 Petrovich, CT. An approach to the patient who may have a bleeding
disorder. 2005 ASA nnual Meeting Refresher Course Lectures. Atlanta, GA.
2006;241:1-6.
 Kelly RE, Yao FF. Hemophilia and Coagulation Disorders. Yao & Artusio’s
Problem Oriented Anesthesiology 4th Ed. Lippincott Williams & Wilkins.
1998. Chapter 40, pp 763-774.
 Fleisher LA. Evidence-based Practice of Anesthesiology. Saunders. 2004.
 Stoelting RK,Dierdorf, SF. Coagulation Disorders. Anesthesia and Co-existing
diseases 3rd Ed. Churchill Livingston. 1993. Chapter 25, p 407-426.

Coagulation and Hemostasis

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Coagulation and Hemostasis

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Coagulation

Joy Loy, M.D.

 Ensure that coagulation mechanisms are

 activated when there is injury

 not unnecessarily activated

 Restore tissue blood flow after repair of

 Primary hemostasis: local vasoconstriction &

platelet plug formation

exposed endothelial surface

platelets exposed to collagen

release contents of cytoplasmic granules

adenosine diphosphate (ADP) thromboxane (Tx

accelerates platelet vasoconstriction

 to stabilize and reinforce the weak platelet plug

2. conversion of prothrombin into thrombin

3. conversion of fibrinogen to fibrin

 activation of clotting factors

hemophilia A decrease --------

vWD type 1 decrease decrease

vWD type 2 normal decrease

2 main functions of tissue factor (TF)

APC: activated protein C

Heparin has almost NO anticoagulant

action without AT III

FACTORS PLASMA t ½ FACTORS PLASMA t ½

Fibrinogen (I) 72-120 XI 52

VIII 8-12 Tissue factor --

 Release of tPA by the endothelium

 Lysis of clot→ FDPs or FSPs

 Reopening of blood vessel

 test of extrinsic pathway activity

 monitors coumadin therapy

 most sensitive to alteration in F VII levels

 prolonged: 55 % ↓ of normal F VII activity

 antithrombotic activity: reduction of factor II

and factor X activity (after several days)

 test for intrinsic and common pathways

 dependent on activity of all coagulation factors,

except VII and XIII

 normal values: 25 -35 seconds

 monitors heparin tx & screen for hemophilia

 prolonged: heparin, thrombin inhibitors,

fibrin degradation products (FDP)

 citrated plasma + surface activators +

 prolonged only if coagulation factors reduced

 monitors heparin anticoagulation in the OR

 normal values: 90 - 120 seconds

 reflects abnormalities in fibrinogen → fibrin

 plasma + excessive amount of thrombin

 prolonged: heparin, thrombin inhibitors,

low fibrinogen, dysfibrinogenemia

 monitors hirudin, bivalirudin, LMWH tx

 TCT prolonged with adequate therapeutic levels

 continuous profiles during all phases of

 monitors platelet function

 not specific indicator of platelet function

 not very reliable

 very operator - dependent

 variable from each institution

 other factors: degree of venostasis, depth

and direction of incision

• useful indicator of efficacy of antiplatelet therapy

 insensitive to mild platelet defects