PREVENTION OF BLOOD CLOTTING IN

NOMAL VASCULAR SYSTEM

INTRAVASCULAR
ANTICOAGULANTS

ENDOTHELIAL SURFACE FACTORS

Smoothness of endothelial cell surface
Glycocalyx layer on endothelial surface
Thrombomodulin (bound to endothelial
surface)
Activation of Protein C by thrombinthrombomodulin complex

FIBRIN & ANTITHROMBIN

Both have antithrombin effect
Remove thrombin from blood
Antithrombin (antithrombin-heparin cofactor)
90% thrombin is adsorbed in fibrin
10% combines with antithrombin

HEPARIN
Negatively charged molecule
Chemically a conjugated polysaccharide
Effectiveness

when combines with antithrombin

Also removes activated factors X,X,X ,X

Produced by mast cells & basophils

LYSIS OF BLOOD CLOTS

PLASMIN
OR

FIBRINOLYSIN

profibrinolysin

fibrinolysin

Plasmin digests following:

Fibrin fibers
Fibrinogen
Factor V
Factor V
Factor X
Prothrombin

CONDITIONS THAT CAUSE

EXCESSIVE BLEEDING IN HUMANS

1. Vitamin K deficiency
2. Hemophilias
3. Thrombocytopenia

VITAMIN K DEFICIENCY
Production by gut flora
Absorption affected by antibiotics, GIT & bile
disorders
Special consideration: Infants & neonates
Essential for some clotting factors
synthesized by liver
Glutamic acid residues in clotting factor
precursors & formation of -carboxyglutamate

vitamin K epoxide
reductase complex 1 (VKOR
c1)

Reduced vitamin K is a cofactor

required for the carboxylation
of the vitamin K-dependent
coagulation proteins

HEMOPHILIA
Bleeding disease
Hemophilia A or classic hemophilia
Hemophilia B or Christmas disease
Flip top mutation in genes on X chromosome
Genetic transmission
vWD disease or pseudohemophilia

vWD disease

X-LINKED RECESSIVE DISORDERS

Caused by mutations in genes on the X
chromosome
Males are more frequently affected than
females, and the chance of passing on the
disorder differs between men and women
Families with an X-linked recessive disorder
often have affected males, but rarely affected
females

THROMBOCYTOPENIA
Quantitative decrease in platelets
Platelets and primary haemostasis
50,000 / L leads to bleeding
10,000 / L is usually fatal
Purpuras
Treatment options:
Whole blood transfusion
Spleenectomy
Steroids
Immunosuppressants

THROMBOCYTOPENIA
SYMPTOMS

Bruising
Bleeding
Clotting failure
Petechiae (reddish
purple spots)
Bleeding into skin
Purpura
Oral bleeding
Nosebleeds
Enlarged spleen

Vaginal bleeding
Excessive bleeding
after surgery
Excessive postpartum
bleeding
Gastrointestinal
bleeding
Blood in stool
Black stools
Blood in urine

THROMBO-EMBOLIC
CONDITIONS IN HUMANS

THROMBUS: abnormal clot in an intact vessel

3 major types:

1.
2.
3.

Arterial
Venous
Mural

CAUSES OF THROMBO-EMBOLIC
CONDITIONS
Virchows triad
ENDOTHELIAL
INJURY

THROMBUS

ABNORMAL BLOOD FLOW

(STASIS)

HYPERCOAGUBILITY

EMBOLUS
A detached intravascular solid, liquid or
gaseous mass that is carried by the blood to
a site distant from its point of origin
Usually thrombotic
Other forms include fat, air or nitrogen
bubbles, bone particles, foreign objects e.g.,
bullet pieces

FEMORAL VENOUS
THROMBOSIS
&
MASSIVE PULMONARY
EMBOLISM

QUESTIONS?