Coagulation-Anticoagulation Balance and Imbalance of Haemostatic SystemCoagulation-Anticoagulation Balance and Imbalance of Haemostatic System

Hemophilia A

Deficiencies in factor IX

Deficiency in vitamin K

von Willebrand disease

Antithrombin deficiency

VIII

Clinical Significances of HemostasisClinical Significances of Hemostasis

Bleeding Disorders

Thromboembolism

Role of Vitamin KRole of Vitamin K

Inactive prozymogen

Carboxylated prozymogens

Vitamin K-dependentcarboxylase

(Clotting factors II, VII, IX, X, protein C and S)

1. Concepts: Disseminated Intravascular Coagulation (DIC) , Shwartzman reaction

2. Conditions and predisposing factor

3. Mechanism of DIC

4. Clinical and laboratory findings

5. Prevention and treatment principle

ContentsContents

Disseminated Intravascular Coagulation (DIC)

Disseminated Intravascular Coagulation (DIC)

A disorder of widespread micro-vascular thrombosis caused by

activation of coagulation with or without bleeding caused by

secondary fibrinolytic activation.

DefinitionDefinition

Meningococcemia on the calves

Meningococcemia associated purpura

A 23-year woman, induced abortion, delivered one dead fetus.

Case PresentationCase Presentation

14 hrs after parturition, convulsion and obnubilation developed.

Large ecchymosis on extremities and abdomen.

After parturition, profluvium sanguis from vagina constantly.

BP: undetectable; platelet: 7,000; BT: 1 min; CT: 1min; PT: 18 sec; Fib:1.1g/L; 3P test (+)

Infections (most common): Acute DIC: Bacteria and their toxins, fungi, viruses, rickettsiae; Chronic DIC: Any chronic infection (eg, tuberculosis, abscesses, osteomyelitis)

Malignancy: Acute DIC: Acute promyelocytic leukemia, acute monocytic leukemia, disseminated prostatic carcinoma Chronic DIC: Lung, breast, gastrointestinal malignancy

Obstetrical complications: Acute DIC: Abruption placenta, abortions (especially therapeutic abortions), amniotic fluid embolism, hemorrhagic shock Chronic DIC: Dead fetus syndrome

Trauma: Acute DIC: Massive tissue destruction, brain damage

Vascular disease: Acute DIC: Brain infarction or hemorrhage Chronic DIC: Aortic aneurysm, giant hemangioma

Venoms: Acute DIC: Snake, spider (rare)

Others: Acute DIC: Heparin-induced thrombocytopenia with thrombosis (HITT), purpura in newborns (homozygous protein C deficiency)

Conditions Causing DIC SyndromesConditions Causing DIC Syndromes

DIC Predisposing FactorsDIC Predisposing Factors

Impaired clearance system: Liver, mononuclear phagocyte Shwartzman reaction;

Hypercoagulable state: e.g., pregnancy;

Disorder of microcirculation: e.g., giant hemangioma.

Excessive clotting

Infection

Cancer

Childbirth, dead fetus, or surgery

Severe head injuryPoisonous snake

Clotting factors and platelets are depleted

Excessive bleeding occurs

Endothelial damage; tissue damage; director activation of factor X, damage of blood cells

Hypercoagulable stage

Hypocoagulable stage

Secondary fibrinolytic stage

Roel of Endothelial CellRoel of Endothelial Cell

Scanning electron micrograph of moderately active plateletScanning electron micrograph of moderately active platelet

Pseudopods

Intrinsic Extrinsic

The “Cascade” theory of

Coagulation

The “Cascade” theory of

Coagulation

Anticoagulation SystemAnticoagulation System

Macrophage, endothelial cell, etc

Serine-containing enzyme inhibitors; Protein C system;

Tissue factor pathway inhibitor;Fibrinolytic system, etc

Molecules

Cells

Antithrombin III is the most important

a2-macroglobulinheparin cofactor II a1-antitrypsin

Controls at Thromblin LevelControls at Thromblin Level

Others:

Protein S

Activated Protein C

Degradation of Va, VIIIa

Protein C

Thrombin

Thrombomodulin

Resistance to activated protein C in patients with thromboembolism

tPA: tissue plasminogen activator; PAI-1: plasminogen activator inhibitor; AP: antiplasmin

VEC

Heparin+ATIII

TFPI

PC, PS, TM

FDPS

Plasmin

tPA,uPA

TFPI: tissue factor pathway inhibitor; PC: protein C; PS: protein S; TM: thrombodulin; ATIII: antithrombin III; tPA:tissue plasminogen activator; uPA:urokinase; FDPS: fibrin degradation products; plasminogen activator-inhibitors type 1 (PAI-1);VEC: vascular endothelial cell.

PAI

1. Bleeding at multiple sites (Ecchymoses of skin, mucous membranes; Visceral hemorrhage)

2. Organ dysfunction (Waterhouse-Friderichsen syndrome;

Sheehan’s syndrome)

3. Shock

4. Hemolytic anemia (microangiopathic hemolytic anemia)

Clinical findings

Clinical and Laboratory Findings in DICClinical and Laboratory Findings in DIC

Integumentary system: Widespread hemorrhage and vascular lesions, Oozing from puncture sites, incision, mucous membranes, irregular-shaped cyanotic patches

Central nervous system: Subarachnoid hemorrhage, altered state of consciousness

Gastrointestinal system: Occult bleeding to massive gastrointestinal bleeding; abdominal distention; malaise, weakness

Pulmanary system

Renal system: hematuria, oliguria, renal failure

1. Coagulation abnormalities: prolonged prothromb

in time, activated partial thromboplastin time, thr

ombin time; decreased fibrinogen levels; increas

ed levels of FDP (eg, “3P” test, D-dimer)

2. Platelet count decreased as a rule but may be fall

ing from a higher level yet still be normal

3. Schistocyte

Laboratory abnormalities

Plasma Protamin Paracoagulation Test (“3P”test)

ProtaminFDP+Fibrin

FDP+Protamin Fibrin Aggregation

Schistocyte

1. Avoid delay2. Treat vigorously

(eg, shock, sepsis, obstetrical problems)

Treat the underlying disease

Treatment PrinciplesTreatment Principles

      Blood components as needed

      Fresh frozen plasma

      Platelet transfusions  

      Anticoagulants after bleeding risk is corrected

Manage the DIC

SummarySummary

Thank youThank you