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Zhao Mingyao
BMC.ZZU
Coagulation-anticoagulation balance & imbalance of haemostatic system
Chapter 9
Section 1 Overview of haemostatic system
Thrombin
Fibrin Plasmin
FDP?
...
..
Coagulation and blood flowing
Clot formation (electron microscope)
TF
liverendothelium
TM
Ⅷ 、Ⅸ、 Ca2+ + pltⅩ、Ⅴ、 Ca2+ + plt
Complex formation of clotting factors
Plt
1.Prothrombin activator formation
2. Thrombin formation
3.Fibrin formation
3 steps of coagulation
Section 2 Imbalance in haemostatic system
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
Major types
1.Bleeding disorder:
inherited ~ & acquired ~
2.Thrombogenesis and thrombotic disorders
3.Blood vessel abnormity:
VEC, Factors activation
4.Fibrinolytic factors abnormity
Twinkle Dwivedi‘s body ooze blood through her eyes, feet and even her head everyday
von Willebrand factor
Section 3
Disseminated Intravascular Coagulation (DIC)
Concept of DIC
Acquired blood coagulation disorder
= thrombosis + / or bleeding
•Coagulation is always the initial event
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
Part 2 Pathology of DIC
• Fibrin deposition, thrombosis
• Bleeding
• Edema
• Organ failure
Part 3 Pathogenesis of DIC
1. Hypercoagulation ?
2. Consumptive hypocoagulayion ?
3. Secondary fibrinolysis ?
1.TF release into blood and hyperexpression
• Septicemia • Injury• Obstetric accident• Tumor
TF - VIIaTF - VIIaCa2+
?
??
?
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
Impaired VEC + PltNormal VEC
3.Entrance of procoagulant to blood
① Snake venom
② Metastatic tumor
③ Pathogenic microorganism
④ Foreign particles: amniotic fluid
⑤ Trypsin (proteolytic enzyme)
4.blood cell damage
(1) RBC: TF, ADP
(2) WBC: leukemia, endotoxin,, IL-1, TNFa
(3) Plt:
Part 4 Predisposing factors for DIC
(1) Mononuclear phagocyte system dysfunction
GC and particles closing MPS
巨噬细胞吞噬Macrophage
colibacillus
coccus
iv ET iv ET18 ~ 24 Hr
Iv thorium dioxide iv ET
General Shwartzman Reaction GSR
(2) Liver dysfunction
• Deactivation: IX, X, XI,
• Replenishing: plasminogen, α2-antiplasmin, AT-III, PC
• Release TF
(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 ↑
Activity of TF
tissue activity of TF ( u/mg )
• Liver 10
• muscle 20
• Brain 50
• lung 50
• Placenta 2000
(4) Microcirculation dysfunction
*Blood stagnation
*Plt aggregation *Acidosis: VEC damage
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
Part 6 Typical clinical manifestation of ~
Bleeding
Shock
MOF(MODS)
MHA
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
Patient with DIC bleed
2.Organ dysfunction
• Thromboembolism ischemia
• Ischemia-reperfusion injury
• Inflammatory reaction out of control in body
3.Shock3.Shock
• Bleeding
• Coronary thrombosis
• Vascular dilation
• Microcirculatory thrombosis
4. 4. Microangiopathic Hemolytic Anemia
Schistocyte > 2%
RBC:* mechanic damaged* fragile
['ʃistəsait
RBC hang on fibrin rope net ( screen electroscope L2000 , R5200 )
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)
Pathophysiological Basis of DIC diagnosis & Treatment
Diagnosis 1.Disease history 2.Clinic manifestation 3.Lab test 3+1
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
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
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
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
Keep equilibrium anywhere and anytime
Zhao Mingyao