Clinical Aplication of Fibrinogen

and D-DIMER
Fibrinogen is a 45 nm-long plasma glycoprotein with a
molecular weight of 340 KDa
 Fibrinogen is synthetized in liver
plasma concentration 150-400 mg/dl
Half life 4 days
 Aα, Bβ, γ chains
are encoded by a 3 gene cluster
on the long arm on human chromosome
4
 Fibrinogen synthesis is regulated at the
transcriptional and translational levels
 Inducible upregulation in response to
inflammatory events.
Factor I Fibrinogen
Factor II Prothrombin
Factor III Tissue thrombo
plastin Factor IX Christmas factor
Factor IV Calsium ion Factor X Stuart Prower factor
Factor XI Antihemophilic C
Factor V Proaccelerin
Factor XII Hageman factor
Factor VII Proconvertin
Factor VIII Anti hemophilic f.
Factor XIII Fibrin stabilizing f.
Prekallikrein Fletcher factor
HMW kininogen Fitzgerald factor.
 HEMOSTASI
S
A body mechanism

platelet Coagulation
To keep the fluidity of blood factors

To prevent spontaneous bleeding

To stop traumatic bleeding hemostasis

vascular
 Vascular injury

Vaso constriction Platelet adherent Tissue thromboplastin

Factor XII

Coagulation cascade
platelet aggregation
Semi permeable platelet plug

Fibrin

Non permeable platelet plug

 D- DIMER

 D-dimer is a soluble fibrin degradation product

deriving from the plasmin-mediated degradation

of cross-linked fibrin.

 D-dimer can hence be considered a biomarker of

activation of coagulation and fibrinolysis

Fibrigenolysis

Fibrinolysis
Fibrinogen levels are reduced in : Fibrinogen levels are increasced in :

 D.I.C  pregnancy

 Liver disease  Oral contraceptive

 Massive transfusion  post menopausal

 Inherited defisiencies  acute phase reactan

 Folowing thrombolytic therapy  disseminated malignancy

 Primary hyperfibrinolysis
Paul,circ
ulation
DISSEMINATED INTRAVASCULAR COAGULATION
(D.I.C)
 DISSEMINATED INTRAVASCULAR COAGULATION
(D.I.C)

D.I.C has been defined by Interrnational Society on Thrombosis

and Haemostasis (ISTH) :
 An aquired syndrome
 Characterized by the intravascular activation
 Arising from different causes
 Cause damage to the microvasculare, which if sufficiently
severe, can produce organ dysfunction
 D.I.C. is marked by both
Thrombotic and hemorrhagic phenotype
Clinical criteria
bleeding
thrombosis
or both
typically with progressive organ dysfunction
an underlying illness or process that may cause tissue damage,
cell death, or production/release Tissue factor
 Underlying condition
(sepsis, trauma etc)

cytokines
TF mediated
PAI-1 mediated
Activation of Depression of inhibition of
coagulation Inhibitory systems fibrinolysis

Fibrin formation Inadequate

Fibrin removal

Fibrin deposition

Organ failure
 Sytemic activation of coagulation

Intravascular Depletion of platelet and

deposition of fibrin coagulation factors

Thrombosis of small and mild Bleeding

size vessels

Organ failure
LAB
 coagulation activation
 fibrinolytic activation
 inhibitor consumption
 end organ failure
Laboratory parameters
 Coagulation activation

 prothrombin fragment 1+2

 fibrinopeptide A

 fibrinopeptide B

 thrombin-antithrombin complex (TAT)

 D-dimer
Laboratory parameters
 fibrinolytic activation

 D-dimer

 FDP

 plasmin

 plasmin-antiplasmin complex (PAP)

Laboratory parameters
 inhibitor consumption

 AT (III)

 a2- antiplasmin

 heparin cofactor II

 protein C atau S
Laboratory parameters
 end organ failure

 LDH
 Creatinine
 pH

 paO2
DIAGNOSTIC :
SCORING
SYSTEM
 Fase I : compensated
 asimptomatic
 Lab

PT, APTT , TT N
Platelet count N
F1+2 , TAT
AT agak
Soluble fibrin monomer : 
 Fase II : decompensated
 Bleeding, organ failure
 Lab :
PT, APTT >
TT N
Platelet count, fibrinogen, antithrombin
F1+2 , TAT , D-dimer
 Soluble fibrin monomer : positif
 Fase III: full-blown DIC
 Bleeding, multi-organ failure
 labor :
PT, APTT , TT >>
Platelet count
Fibrinogen, antitrombin
F1+2, TAT, dan FDP (D-dimer)
Soluble fibrin monomer
 Venous thromboembolism (VTE)

Definition :
• Venous thromboembolism (VTE) results from the
presence of a clot in the venous circulation
(lower or upper extremity veins in particular)
• and/or by embolization of parts of the clot into the
pulmonary circulation
Consequently,
 Two clinical manifestation :
- deep vein thrombosis (DVT)
- pulmonary embolism (PE)
LIVER
DISEASE
 The role of liver in hemostasis
Inhibitors of
Coagulation
Clotting factors system

Thrombopoietin

Plasminogen and
antiplasmin
Clearance mechanism
(act. clotting factors and
plasminogen activators)
Pathogenesis of hemostatic problems

 Impaired synthesis of clotting factors

 Thrombocytopenia
 Platelet function defects
 Disseminated intravascular coagulation
 Systemic fibrinolysis
 Dysfibrinogenemia
 Vitamin K deficiency
Impaired synthesis of clotting factors
 F VII and F V are sensitive indicators.
 PT : sensitive marker of impaired synthetic function
 Fibrinogen: acute phase reactant
 Hypofibrinogenemia : unusual in liver disease (end-stage liver failure,
DIC, acute fulminant hepatitis)
The cause of DIC in liver diseases

Hypothesis :
 release of procoagulant from necrotic liver cells
 TF expression induced by viral infection
 impaired clearance of activated clotting factors
 decreased of antithrombin, protein C, and protein S
 Advanced liver disease : low grade DIC
 IncreasedD dimer, TAT complexes, prothrombin
fragment 1.2
 For diagnosis of DIC: D dimer (cut off 500 ng/ml)
sensitivity 85%, specificity 97% and positive
predictive value 96%
 Increased D dimer was found in 59,48% of patients
with liver cirrhosis
 The cause of DIC is not completely understood
Clinical application for fibrinogen

 Investigation of abnormal coagulation tests (e.g. PT / PTT)

 Investigation of unexplained bleeding

 Investigation of suspected inherited or acquired disorders of fibrinogen

(afibrinogenemia, hypofibrinogenemia and dysfibrinogenemia)

 Evaluation of DIC

 Establishment and monitoring of thrombolytic therapy

 Assessment of cardiovascular risk

Clinical application for D-Dimer

 Excluding venous thromboembolism in patient with low clinical

probability for venous thromboembolism
 Estabilishing the risk of recurrent thrombosis
 Diagnosis and management of disseminater intravascular coagulation
 Predicting and monitoring thrombotic complication in patients with
severe infections and sepsis
 Detection of thrombotic risk in malignancies
 Vaso-occlusive crisis in sickle desease
Thank you