Fibrinolysis

Fibrin Degradation Product

D-dimer
DIC
Protein C
Protein S

Ma.LourdesN.Cabrera,RMT,AMT,IMT
M.S.MICROBIOLOGY
USTGraduateSchool
 Fibrinolysis

• Is the process wherein a fibrin clot ,the product of coagulation

, is broken down.

• Its main enzyme plasmin cuts the fibrin mesh at various

places , leading into the production of circulating fragments
that are cleared by other proteases or by the kidney or liver.
PHYSIOLOGY
 Measurement
 Thrombin clotting time- prolonged in a person that has active fibrinolysis
 Specific FDP – D-dimer – can be measured by Ag-Ab technology

 Euglobulin lysis time ( ELT) assay- used in testing overall fibrinolysis

-the ELT measures fibrinolysis by clotting the euglobin fraction from
citrate plasma and then measuring the time for clot breakdown .A
shortened lysis time indicates hyperfibrinolytic stage and bleeding risk.
 Pharmacology

 Antifibrinolytic drugs

A. aminocaproic acid
B. tranexamic acid

 are used as inhibitors of fibrinolysis

 DISSEMINATEDINTRAVASCULARCOAGULATION(DIC)

 Alsoknownasconsumptivecoagulopathy
 Is a pathological activation of coagulation(blood
clotting) mechanism that happens in variety of
diseases.
 It leads to the formation of small blood clots inside
the blood vessels throughout the body
CAUSES:
DIC occurs in the ff conditions:
 Cancerofthelungs,pancreas,prostrateandstomach
 Obstetrics:abruptioplacenta,retaineddeadfetus,pre-eclampsia,amnioticfluid
embolism
 Massivetissueinjury:trauma,burns,extensivesurgery
 Infections:gramnegative sepsis,malaria,histoplasmosis,aspergillosis
 Misc:Liverdse,snakebite,shock,heatstroke,vasculitis
Signs & Symptoms
 Theaffectedpersonisoftenacutelyillandshockedwithwidespreadhaemorrhage
(commonbleedingsitesarethemouth,noseandvenipuncturesites)extensive
bruising,renalfailure.andgangrene

 TheonsetofDICcanbefulminant,asinendotoxicshockoramnioticfluidembolismand
maybechronicincasesofcarcinomatosisorretentionofdeadfetus
 Diagnosis
• Dxisusuallysuggestedbythefollowingconditions:
A. severe cases with haemorrhage
- the PT and APTT are usually prolonged and fibrinogen level markedly
reduced.
- high levels of FDP including d-dimer
- severe thrombocytopenia
-blood film may show fragmented rbc
( schistocytes)
B. Mild cases without bleeding
- there is increased synthesis of coagulation factors and plts
-PT, APTT, and platelets count are normal
- FDP’s are raised
 Treatment
 Platelets maybetransfused ifcountsarelessthan5,000-10,000/mm3andmassive
hemorrhageisoccuring

 Freshfrozenplasma-toreplenishcoagulationfactorsandanti-thromboticfactors

 Infusionwith antithrombin

 Drotrecoginalfa (Xigris)-isarecombinantactiveCproduct
D-dimer
 Is a fibrin degradation product
 A small protein fragment present in the blood after a blood clot is
degraded by fibrinolysis.
 D-dimer concentration blood test will help diagnose a.DVT(deep venous
thrombosis) b.PE(pulmonary embolism)
 And also aid in the diagnosis of DIC (dessiminated intravascular
coagulation)

 They are the breakdown of fibrin mesh that has been stabilized by Factor
XIII
 was originally developed in dx of DIC and turn out to be useful in
thromboembolic process
 Types of Assays of D –dimer

 ELISA ( eg. Vidas)

 Latex Turbidimetric Assays( automated immunoassay eg.Roche
Tinaquant,MDA D dimer)
 Enhanced Microlatex
 Latex enhanced photometric
 Whole Blood Aggltn(eg SimpleRed)
 Rapid Lateral Flow (eg. Clearview Simplify)
 Reference Range
- 0-300ng/ml= normal range
- > 300-500ng/ml = considered (+)
 Test Properties

 Variouskitshave93-95%sensitivityand50%specificity

 False(+)readingscanbedueto
liverdse,highRF,inflammation, malignancy,trauma,pregnancyandrecentsurgery

 False(-) canoccurifsampleistakentooearlyafterthrombusformationordelayedtesting
 FDP-FibrinDegradationProducts

 Are substances leftbehind when clot dissolves in the blood

Alternative Names:
 FSP-fibrin split products
 FBP-fibrin breakdown products
 How to prepare for the tests

 Stoptakingdrugsbeforethetest

 Certaindrugslikebarbiturates,heparin,streptokinaseandurokinase
becausethesedrugsmayelevateFDPmeasurements.
 What abnormal results mean

 IncreaseFDPsmayindicate primary or
secondaryfibrinolysis (clotdissolvingactivity)fromsuchconditions:
 Abruptioplacentae,burns,DIC
 Congenitalheartdisease,hypoxia,infections
 Intrauterinefetaldeath,leukemia
 Liverdisease,preeclamsia,septicemia
 Transplantrejections,renaldisease
 Transfusionreactions
 Why the test is performed?

• The test is done to see if your clot dissolving

( fibrinolytic) system is working properly

• Reference Range
-less than 10 mcg/ml
 Protein C and Protein S

 Are normally present in small quantities in the blood

 They work together to inhibit excessive blood clotting
 Protein C and protein S can be inherited or acquired
 Both protein are produced in the liver and are Vit K dependent

 Two types of Protein C deficiencies

a. Type I is related to quantity
b. Type 2 to abnormal function
 Protein S
 Has 2 forms a) free b) bound

 Only free protein S is available to combine with protein C

 There are 3 types of protein S deficiencies
a)type I deficiency is due to insufficient quantity.
b) type 2 to abnormal function
c) type 3 to a shift from free protein s to bound(or total) protein S
 INHERITED MUTATIONS IN THE GENES THAT PRODUCE PROTEIN C AND
PROTEIN S ARE RELATIVELY RARE, THEY CAN RESULT IN:

 A decreased level of Protein C and Protein S being produced

 An abnormal Protein C or S that cannot bind properly to the other to form

a functional activated Protein C complex

 An abnormal protein which can bind and form a complex, but the complex
is not capable of degrading factors VIIIa and Va normally.
JOURNALS
 The value of D-dimer in the detection of early deep-vein
thrombosis after total knee arthroplasty in Asian
patients: a cohort study

 Background and purpose

 The relationship of D-dimer and deep-vein thrombosis (DVT) after

total knee arthroplasty (TKA) remains controversial.
 The purpose of this study was to assess the value of D-dimer in
the detection of early DVT after TKA.
 Methods

 ThemeasurementsofplasmaD-dimerlevelwereobtained
preoperativelyandatday7postoperativelyin78patientsundergoing
TKA.
 Ascendingvenographywasperformedin7to10daysaftersurgery.
 TheplasmaD-dimerlevelswerecorrelatedstatisticallywiththe
venographicDVT.
 Results

 Venographic DVT was identified in 40% of patients.

 High plasma D-dimer level >2.0 μg/ml was found in 68% of
patients with DVT and 45% without DVT
(P < 0.05)
 Therefore, high D-dimer level greater than 2.0 μg/ml showed
68% sensitivity, 55% specificity, 60% accuracy, 50% positive
predictive rate and 72% negative predictive rate in the
detection of early DVT after TKA.
 Conclusion

 High plasma D-dimer level is a moderately sensitive, but less

specific marker in the detection of early of DVT after TKA.
 Measurement of serum D-dimer alone is not accurate enough to
detect DVT after TKA.
 Venography is recommended in patients with elevated D-dimer
and clinically suspected but asymptomatic DVT after TKA.
 D-Dimer Predicts Early Clinical Progression in Ischemic Stroke
From the University Section of Clinical Gerontology and Vascular Medicine, Royal Infirmary, Glasgow, UK.

 Background and Purpose

 Plasma D-dimer levels, measured using a research laboratory
assay, independently predict progressing ischemic stroke.
 the authors wished to confirm these findings using
commercially available assays and to provide data to allow
the design of intervention studies.
 Methods

 they studied 219 consecutive acute ischemic stroke

admissions of whom 54 (25%) met criteria for
progressing stroke.
 Results
There were strong correlations between D-dimer results as measured
by the Biopool AB, MDA and VIDAS assays; correlation coefficients
r=0.91 to 0.94; all P<0.001.

 In binary logistic regression analyses, D-dimer, as measured by the 3

different assays, was an independent predictor of progressing stroke
(odds ratios, 1.87 to 2.45; all P<0.001)

This confirms the results of our original analysis (Biopool AB) using 2
commercial D-dimer assays, demonstrating the potential usefulness of
D-dimer in providing early prognostic information after ischemic stroke
in different clinical settings.
 Conclusions
 Ischemic stroke patients at high risk of early progression can
be identified using commercial D-dimer measurements.
 This could allow selection of high-risk patients for inclusion in
randomized trials of early antithrombotic treatments.
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