Coagulation Disorder

Luciana
 Introduction

Coagulation disorders result from a decreased of platelets,

decreased function of platelets, coagulation factor deficiency,
or enhanced fibrinolyric activity
Maintenance of blood flow involve 4 major components :
The vessel wall
Platelets
The coagulation system
The fibrinolytic system
 Coagulation could be initiated via either the intrinsic or
the extrinsic pathway
The extrinsic pathway is initiated by exposure of tissue
during trauma
The intrinsic pathway is initiated when circulating factor
XII contacts with the subenothelial membrane
Coagulation Factors

The coagulation factor can be divided into three groups

on the basis of biochemical properties :
Vit K-dependent factors : ( II, VII, IX and X )
Contact activation factors ( XI and XII, prekallikrein, high-
molecular-weight kininogen )
Thrombin-sensitive factors ( V, VIII, XIII, and fibrinogen )
Vessel Wall And Platelets

Blood vessel walls and activated platelets play central

roles in primary hemostasis
Damage to a vessel wall initiates vasoconstriction and
exposure of collagen and tissue factor to blood
Platelet function in response to vascular injury includes 4
phases :
a. Adhesion
b. Secretion
c. Aggregation
d. Elaboration of procoagulant activity
 Platelets release granular contents, such as ADP and
thromboxane A2, which lead to platelet aggregation
Activated coagulation factors are generated at the site
of bleeding on the activated platelets to form fibrin
Factor XIIIa cross-links the fibrin and stabilizes the fibrin
clot
 Unbound factors : Iia, Ixa, Xa, Xia and XII a are inactivated by
antithrombin when they migrate to the endothelial cell
surface
Thrombomodulin binds thrombin and activates protein C.
Activated protein C and its cofactor, protein S, are vit K-
dependent proteins that inactivate factor Va and VIIIa on the
endothelial surface
Tissue Factor Pathway

Tissue factor is a membrane protein found in organs and

surrounding vasculature
Coagulation is initiated when factor VIIa binds to
exposed TF
The factor VIIa-TF complex activates factors IX and X
Activated platelets form complexes with factor IXa-
factor VIIIa and factor Xa-factor Va
Thrombin activates platelets and catalyza the
conversion of fibrinogen to fibrin
Fibrinolysis

The coagulation system regulates fibrin formation

The fibrinolytic system removes fibrin deposits and
prevents unnecessary fibrin clots
Plasminogen is the primary compound of the fibrinolytic
enzyme system
Plasminogen activators ( tissue plasminogen activator
and urokinase plasminogen activator ) are released in
response :
 Ischemia
Physical exercise
Activators convert plasminogen to plasmin in the
presence of fibrin
Plasmin digests fibrin, dissolves the clot, and releases a
number of fibrin degradation products ( FDPs )
Plasminogen activator inhibitor type 1 ( PAI-1 ) blocks the
plasminogen activators, whereas to prevent systemic
fibrinolysis
Laboratory finding
Congenital Coagulation Disorder

Hemophilia :
Hemophilia is a bleeding disorder that results from a
congenital deficiency in a plasma coagulation protein.
Hemophilia A is caused by a deficiency of factor VIII
and hemophilia is caused by a deficiency of faxtor IX
Patients with hemophilia usually present with clinical
manifestation after age 1 year and increase the risk of
bleeding
Clinical Presentation Of Hemophilia

Signs and symptoms :

Hematuria
Muscle hemorrhage
Swelling
Oral bleeding
ICH
Excessive bleeding with surgery
Laboratory Testing

Prolonged aPTT
Decreased factor VIII of factor IX level
Normal PT
Normal platelet count
Normal von Willebrand factor antigen and activity
Normal bleeding time
Treatment of Hemophilia A

Recombinant Factor VIII

From cultured Chinese hamster ovary cells
Plasma-Derived Factor VIII products :
From the plasma of thousands donors and potentially
transmit infection
Factor VIII concentrates can be slassified according to
their level purity :
Cryoprecipitate : low purity product
Contains : von Willebrand factor, fibrinogen, and factor
XIII
 Intermediate-purity products : have a specific activity of
factor VIII of 5 units/mg of protein
High-purity products : have 2000 units/mg of protein
Ultrahigh-purity plasma : have 3000 units/mg of protein

Factor VIII Concentrate Replacement

 The half life of factor VIII ranges from 8 to 15 hours
It is generally to administer half of the initial dose every 12 hours
A single treatment adequate for minor bleeding, such as : oral
bleeding
Administration of factor VIII concentrate via continuous infusion has
been shown to be safe and effective
A potential side effect with continuous infusion is thrombophlebitis
at the delivery side
Treatment of Hemophilia B

Recombinant Factor IX
Blood and plasma products are not used to produce recombinant
factor IX or to stabilize the final product
The half life of recombinant factor IX is similar to that of the plasma-
derived products, recovery is 30% lower
Recombinant factor IX is considered the treatment of choice for
hemophilia B
Plasma-Derived Factor IX Products

High purity factor IX concentrates have excellent

efficacy in the treatment of bleeding episodes and in
the control of bleeding
Von WilleBrand Disease

Von Willebrand disease has an autosomal inheritance pattern

Von Willebrand factor is important for both primary and secondary
hemostasis
In response to vascular injury, it promotes platelet adhesion by
interacting with the glycoprotein Ib receptor on platelets
It can facilitate platelet aggregation by binding to the platelet
glycoprotein Iib/IIIa receptor
A deficiency of Von willebrand factor reduces the half life of factor
VIII and decreases plasma factor VIII levels
Classification of von Willebrand Disease
 Type I von Willebrand disease :
The most common congenital bleeding disorder
Bleeding symptoms are very mild to moderate
Type 2 von Willebrand disease :
Bleeding manifestation may be more severe than type 1 disease
Type 3 von Willebrand disease :
Factor VIII levels are very low
Clinical Presentation of Von Willebrand Disease

Some patients are symptomatic

Mucocutaneous bleeding : epistaxis, gingival bleeding,
menorrhagia
Easy bruising
Postoperative bleeding
Treatment

The goal of systemic therapy is correction of platelet adhesion and

coagulation defects by stimulating the relesase of endogenous von
Willebrand factor
Acquired Coagulation Disorders

Disseminated Intravascular Coagulation

Systemic process with the potential for causing thrombosis and
hemorrhage
Clinical Presentation Of DIC

Signs and symptoms :

Bleeding, thrombosis
Petechiae and purpura
Peripheral cyanosis
Laboratory tests :
Elevated D-dimer
Decreased fibrinogen
Thrombocytopenia
Decreased proteins C and S
 Elevated prothrombin fragments 1 and 2
Evidence of end-organ dysfunction or failure
Conditions Associated with DIC
Treatment of DIC

The efficacy of fresh-frozen plasma or platelet transfusion has not

been proven for patients who are bleeding or require invasive
procedure
Fresh-frozen plasma replaces clotting factors, fibrinogen, protein S,
protein C and antithrombin
Heparin use in patients with DIC may prevent the formation of new
blood clots. The most common complication of heparin therapy is
bleeding
Monitoring of heparin therapy is difficult because the aPTT is
elevated before initiation of heparin therapy , following D-dimer
and fibrinogen levels is best
Critically ill patients may develop Vit K deficiency
 Vitamin K Deficiency
Vitamin K is a cofactor for activation of factors II, VII, IX and X
Vitamin K is required -carboxylation of these clotting factors
Vitamin K is necessary for the active forms of protein C and S
Vitamin K deficiency causes a bleeding as a result of marked
deficiency of factors II, VII, IX and X
Treatment of Vitamin K Deficiency

Phytonadione is used to treat Vit K deficiency

Vitamin K can be administered orally, IM, SC or IV.
Patients with life-threatening bleeding should receive fresh-frozen
plasma as a source of vitamin K-dependent factors
 Coagulopathy And Liver Disease
Bleeding disorders can be associated with acute or chronic liver
disease
The liver synthesizes the blood coagulation factors and inhibitors of
coagulaton ( antithrombin and proteins C and S )
All clotting factors except factor VIII are decreased in liver failure
Platelet count and function are dcreased in patients with liver
disease
The development of DIC may worsen the coagulopathy
Treatment of Coagulopathy and Liver Disease

Treatment of the coagulopathy associated with liver disease is

recommended for correction of coagulation parameters ( PT and
aPTT ) prior to an invasive procedure
Bleeding in associated with a coagulopathy, replacement therapy
with platelets and fresh-frozen plasma may decrease bleeding