Pathophysiology

Predisposing Factors
Age

Protein S deficiency occur in persons younger than

40-45 years.

Family history

Hereditary protein S deficiency is an autosomal

dominant trait.

Race

Current research indicates that protein S deficiency is

5-10 times higher in Japanese populations compared
with Caucasians.

Protein s levels decrease during pregnancy

Vitamin K
deficiency

Vitamin K is an essential factor to a hepatic gammaglutamyl carboxylase that adds a carboxyl group to
glutamic acid residues on factors II, VII, IX and X, as
well as Protein S, Protein C and Protein Z.

Liver disease

Clotting factors are produced by the liver

Precipitating Factors
Pregnancy

Symptomatology
Deep Vein
Thrombosis

Pulmonary
emboli

Deep vein thrombosis (DVT) is the formation of a

blood clot within a deep vein. It most commonly
affects leg veins, such as the femoral vein. Three
factors are important in the formation of a blood clot
within a deep veinthese are the rate of blood flow,
the thickness of the blood and qualities of the vessel
wall. Classical signs of DVT include swelling, pain
and redness of the affected area.

Pulmonary embolism (PE) is a blockage of the lung's

main artery or one of its branches by a substance
that has travelled from elsewhere in the body through
the bloodstream (embolism). PE results from a deep
vein thrombosis (commonly a blood clot in a leg) that
breaks off and migrates to the lung, a process
termed venous thromboembolism (VTE).

Predisposing
Factors:

Precipitating
Factors:

Decrease protein S

Decrease activated protein

Decrease in factor Va and factor VIIIa

degradation

Factor VIIIa will assist factor Xia to convert factor

X to factor Xa

Factor Va will assist factor Xa to

convert factor II to factor IIa

Factor IIa will convert factor I to

factor Ia

APC cannot inhibit PAI-1

PAI-1 inhibits tPA and uPA

Plasminogen-plasmin
conversion is inhibited

Fibrinolysis does not

occur

With the help of factor XIIIa it

stabilizes fibrin
Fibrin mesh is formed

The fibrin mesh attracts platelets and

phospholipids and forms a stable blood clot

Increase in blood clot formation in

the body
Blood clots in different parts of the circulatory
system and organs
Leading to thrombus or

If treated, this will result in a good

prognosis

If left untreated, there will be a bad

prognosis

Narrative:

Protein S is a vitamin K dependent glycoprotein. A naturally occurring anticoagulant in the body. Protein S is a co-factor for protein C to be activated protein C
(APC). APC, another anti-coagulant, has many functions, one of the functions is the
degradation of the clotting factor Va and factor VIIIa.
Factor VIIIa will assist factor IXa to convert factor X to factor Xa after that, factor
Va will assist factor Xa to convert factor II (prothrombin to factor IIa (thrombin), which
converts factor I (fibrinogen) to factor Ia (fibrin) leading to fibrin deposition and the
activation of platelets to form blood clots. Factor IIa (thrombin) also activates factor XIIIa
to stabilise the fibrin clot by cross-linking it, also factor IIa also activates factor V and
factor VIII in a positive feedback loop further amplifying the activation of the coagulation
cascade.
Activated protein C can also inactivate type I plasminogen activator inhibitor (PAI1), promoting fibrinolysis. PAI-1 inhibits tissue plasminogen activator (tPA) and
urokinase (uPA), the activators of plasminogen and hence fibrinolysis.
Without fibrinolysis, clots will form randomly in the body but with protein S
deficiency clots are commonly found in the lungs or in the lower extremeties.
The treatment would be heparin, an anticoagulant that prevents formation of
blood clots. Without treatment, it would lead to serious complications which can
inevitably lead to death.