zhao mingyao bmc.zzu coagulation-anticoagulation balance & imbalance of haemostatic system...
TRANSCRIPT
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Zhao Mingyao
BMC.ZZU
Coagulation-anticoagulation balance & imbalance of haemostatic system
Chapter 9
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Section 1 Overview of haemostatic system
Thrombin
Fibrin Plasmin
FDP?
...
..
Coagulation and blood flowing
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TF
liverendothelium
TM
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Ⅷ 、Ⅸ、 Ca2+ + pltⅩ、Ⅴ、 Ca2+ + plt
Complex formation of clotting factors
Plt
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1.Prothrombin activator formation
2. Thrombin formation
3.Fibrin formation
3 steps of coagulation
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Section 2 Imbalance in haemostatic system
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Coagulation system
Extrinsic system
Intrinsic
system
Anticoagulation system
VEC
Microcirculation
TFPI, PC, PS, AT-III , Heparin
Coagulation statusChange
TF XIIa
other factor
fibrinolysis
balance & imbalance of Coagulation-anticoagulation
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Major types
1.Bleeding disorder:
inherited ~ & acquired ~
2.Thrombogenesis and thrombotic disorders
3.Blood vessel abnormity:
VEC, Factors activation
4.Fibrinolytic factors abnormity
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Twinkle Dwivedi‘s body ooze blood through her eyes, feet and even her head everyday
von Willebrand factor
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Section 3
Disseminated Intravascular Coagulation (DIC)
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Concept of DIC
Acquired blood coagulation disorder
= thrombosis + / or bleeding
•Coagulation is always the initial event
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Part 1 Etiology of ~
Acute ~ : infection ( G- & G+ ) 30%
obstetric accident 18%
serious trauma 10%
malignant tumor 9%
Amniotic fluid embolism; abruptio placentae Retained dead fetus Rheumatologic illness
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Part 2 Pathology of DIC
• Fibrin deposition, thrombosis
• Bleeding
• Edema
• Organ failure
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Part 3 Pathogenesis of DIC
1. Hypercoagulation ?
2. Consumptive hypocoagulayion ?
3. Secondary fibrinolysis ?
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1.TF release into blood and hyperexpression
• Septicemia • Injury• Obstetric accident• Tumor
TF - VIIaTF - VIIaCa2+
?
??
?
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2. VEC lesion
(1) TF (1) TF expression:
(2) TFPI↓: Degradation of TM/PC and HS/AT-III
system
(3) Fibrinolysis inhibited: t-PA ↓, PAI-1↑
(4) Plt adherence and aggregation: Collagen
exposure , though NO, PGI2 and ADP enzyme ↑
(5) XII activation: XII+HMWK+PK(prekallirein) +XI
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Impaired VEC + PltNormal VEC
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3.Entrance of procoagulant to blood
① Snake venom
② Metastatic tumor
③ Pathogenic microorganism
④ Foreign particles: amniotic fluid
⑤ Trypsin (proteolytic enzyme)
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4.blood cell damage
(1) RBC: TF, ADP
(2) WBC: leukemia, endotoxin,, IL-1, TNFa
(3) Plt:
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Part 4 Predisposing factors for DIC
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(1) Mononuclear phagocyte system dysfunction
GC and particles closing MPS
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巨噬细胞吞噬Macrophage
colibacillus
coccus
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iv ET iv ET18 ~ 24 Hr
Iv thorium dioxide iv ET
General Shwartzman Reaction GSR
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(2) Liver dysfunction
• Deactivation: IX, X, XI,
• Replenishing: plasminogen, α2-antiplasmin, AT-III, PC
• Release TF
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(3)Hypercoagulable state
• Pregnancy :
clotting factors ↑, plt ↑, but t-PA, u-PA, AT-III, PC ↓; TF rich in placenta
• Acidosis: heparin activity↓ CF activity ↑ Plt aggregation ↑
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Activity of TF
tissue activity of TF ( u/mg )
• Liver 10
• muscle 20
• Brain 50
• lung 50
• Placenta 2000
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(4) Microcirculation dysfunction
*Blood stagnation
*Plt aggregation *Acidosis: VEC damage
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Part 5 Clinical classification of ~
1.Acute ~ : several hrs ~ 1 or 2 d
2.Subacute ~: some days, malignancies, retained dead fetus
3.Chronic ~ : over months, connective tissue disorder SLE
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Part 6 Typical clinical manifestation of ~
Bleeding
Shock
MOF(MODS)
MHA
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1. 1. BleedingBleeding
(1)Consumption of coagulant and plt
(2)activation of fibrinolytic system
(3) formation of FDP
fibrin monomer to polymerize(Im)
thrombin (IIa)
pltsinhibit
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Patient with DIC bleed
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2.Organ dysfunction
• Thromboembolism ischemia
• Ischemia-reperfusion injury
• Inflammatory reaction out of control in body
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3.Shock3.Shock
• Bleeding
• Coronary thrombosis
• Vascular dilation
• Microcirculatory thrombosis
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4. 4. Microangiopathic Hemolytic Anemia
Schistocyte > 2%
RBC:* mechanic damaged* fragile
['ʃistəsait
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RBC hang on fibrin rope net ( screen electroscope L2000 , R5200 )
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Part 7Part 7 PPrinciples of prevention and treatment for DIC 1.Management of the underlying disorder
2.Improving the microcirculation
3.Reconstructing the balance of coagulation and fibrinolysis
heparin/AT-III/PC+low mol dextran
+dipyridamole+ PC+EACA /or streptokinase, urokinase
Epsilon-Aminocaproic Acid (EACA)
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Pathophysiological Basis of DIC diagnosis & Treatment
Diagnosis 1.Disease history 2.Clinic manifestation 3.Lab test 3+1
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Lab test 3+1
Screen test (3 items) 1.Plt: <100 000/mm3 ( 100 000 ~ 300 000)
2.Plasma fibrinogen count: <150 mg% (200~400)
3.PT: prolonged 3 sec (13~15 sec )
Confirm test 3P test 1.D-dimer or “3P ” positive
The plasma-protamine-paracoagulation-(3-P-) test
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Coagulation test
Ⅻ
Ⅺ
plt
ⅤCa2+Ⅹ
Ca2+
TF( )Ⅲ
ⅦCa2+
pltⅧ
Ⅸ
ⅡⅠ Ⅰm
Ca2+ⅠmⅠm
Ⅰm
ⅩIII
Inet
fibrin
plasmin
FDP
ACT
APTT
PT
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DIC Score Relates to Mortality Rate in Adults with Severe Sepsis
01020
3040506070
8090
100
0-2 3 4 5 6 7
DIC Score
28
Da
y %
Mo
rta
lity
Overt DICNo Overt DIC
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FbgIIa
D-dimer Test
XⅢa
PLn
FDP( D monomer)
A,B,C,X,Y,D,E
FDP( D dimer)
Second fibronolysis
A,B,C,X,Y,D,E
Fbn
FM
Primary fibronolysis
PLn
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Keep equilibrium anywhere and anytime
Zhao Mingyao