5.1....coagulation anticoagulation balance

Coagulation-anticoagulation balance & imbalance of haemostatic system

Hemostasis and Blood Coagulation

( DIC )

The term hemostasis means prevention of blood loss.

Whenever a vessel is ruptured, hemostasis is achieved by several mechanisms:

(1)vascular constriction,

(2) formation of a platelet plug,

(3) formation of a blood clot as a result of blood coagulation, and

(4) eventual growth of fibrous tissue into the blood clot to close the hole in the vessel permanently.

Coagulation cascade

The coagulation cascade is classically divided into three pathways.

The tissue factor and contact activation pathways both activate the "final common pathway" of factor X, thrombin and fibrin.

The coagulation cascade

Disseminated Intravascular Coagulation ( DIC )

Concept of DIC Acquired blood coagulation disorder= Thrombosis + / or Bleeding

• Coagulation is always the initial event

Etiology

Acute ~ : infection ( G- & G+ )

obstetric accident

serious trauma

malignant tumor

Pathology of DIC

Fibrin deposition, thrombosis

Bleeding

Edema

Organ failure

Pathogenesis of DIC

Over activation of TF.

Over activation of factor XII

Decrease Fibrinolytic activity.

Decrease anticoagulative property ( Protein C etc.)

Mechanism

1.TF release into blood and hyperexpression.

Septicemia

Injury

Obstetric accident

2. VEC lesion

TFTF Expression

TFPI↓: Degradation of Protein C and Antithrombin-III system

Fibrinolysis inhibited: Tissue Plasminogen Activator (t-PA)↓, PAI-1↑

Platelet adherence and aggregation: Collagen exposure , though NO,PGI2 and ADP enzyme ↑

XII activation.

3. Entrance of procoagulant to blood

① Snake venom② Metastatic tumor③ Pathogenic microorganism④ Foreign particles: amniotic fluid

Tumors and traumatized or necrotic tissue release Tissue factor into the circulation.

Endotoxin from gram-negative bacteria activates several steps in the coagulation cascade.

In addition to a direct effect on the activation of Hageman factor (factor XII), endotoxin induces the expression of tissue factor on the surface of monocytes and endothelial cells.

These activated cell surfaces then accelerate coagulation reactions.

4. Blood cell damage

RBC: Haemolysis usually a result of incompatible transfusion trigger the coagulation activation.

WBC: leukemia, endotoxin, IL-1, TNFa

Platelet: Endotoxin, immune complex, directly damage platelet promote their adhesion, release, as well as aggregation.

Platelet adhere to exposed ECM via vWF and are activated, release ADP , TXA2 lead to further platelet aggregation, which form platelet plug.

Aggregated platelets (white) surrounded by red blood cells                                                     

Predisposing factors for DIC

(1) Mononuclear phagocyte system dysfunction :

MPS plays a important role in protection from DIC.

The phagocyte can remove Endotoxin, Thrombin, Fibrinogen and FDP.

Thus, their function of clearance will be blocked while the cells are dysfunctional.

(2) Liver dysfunction.

(3)Microcirculation dysfunction:*Blood stagnation *Plt aggregation *Acidosis: VEC damage

(4)Hypercoagulable state :

Pregnancy : clotting factors ↑, plt ↑, but t-PA, AT-III, PC ↓; TF rich in placenta.

Typical clinical manifestation of DIC

Bleeding

Shock

MOF(MODS)

HEMOLYTIC ANAEMIAA

1. Bleeding

(1)Consumption of coagulant and platelet.

(2)Activation of fibrinolytic system.

Patient with DIC bleed

2.Organ dysfunction

Thromboembolism ischemia Thromboembolism ischemia

Ischemia-reperfusion injuryIschemia-reperfusion injury

3.shock

Bleeding

Coronary thrombosis

Vascular dilation

Microcirculatory thrombosis

Pathophysiological Basis of DIC diagnosis & Treatment

Diagnosis

1.Disease history 2.Clinic manifestation 3.Lab test 3+1

Diagnosis of DIC

Presence of disease associated with DIC

Appropriate clinical setting Clinical evidence of thrombosis, hemorrhage or

both.

Laboratory studies

no single test is accurate

Lab test

Screen test (3 items)

Platelet: <100 000/mm3 ( 100 000 ~ 300 000)

plasma fibrinogen count: <150 mg% (200~400)

PT: prolonged 3 sec (13~15 sec )

Confirm test ?? ??3P test

1. D-dimer or “3P ” positive

Principles of prevention and treatment for DIC

1.Management of the underlying disorder

2.Improving the microcirculation

3.Reconstructing the balance of coagulation and fibrinolysis

The End