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