CLINICAL UTILITY OF D-DIMER

16 Agustus 2017
Yogyakarta

Usi Sukorini, Departemen Patologi Klinik & Kedokteran

Laboratorium FK UGM
 What is D-dimer?
▪ D-dimer is a specific degradation product of cross-linked fibrin
by plasmin  D-dimer is a marker of fibrinolysis
▪ D-dimer is a protein that is released into the circulation during
the process of fibrin clot breakdown
▪ D-dimer in elevated levels are seen in many conditions such as
DIC, DVT, PE, pregnancy, post-surgery, neoplasm, etc.
▪ Hence, D-dimer is not a specific marker for any condition
▪ It is a marker of coagulation activation and active fibrinolysis
INTRODUCTION
Fibrinolysis

Crosslinked fibrin

D-dimer
D-dimer
 Clinical aspects

D-dimer measurement has been validated in the following:

• The exclusion of venous thromboembolism (VTE) in certain
patient populations:
• Deep vein thrombosis (DVT)
• Pulmonary embolism (PE)
• Prediction of recurrent VTE and risk stratification of patients
for VTE recurrence
• Diagnosis and monitoring of disseminated intravascular
coagulation (DIC)
Performance of D-dimer assay

Best marker for exclusion of DVT/PE

Conditions associated w/ high levels of D-dimer

Pathological Non-Pathological
• Acute coronary syndromes • Age (healthy elderly people)
• Acute upper gastrointestinal haemorrhage • Cigarette smoking
• Aortic dissection • Functional impairment
• Arterial or venous thromboembolism • Post-operatively
• Atrial fibrillation • Pregnancy
• Consumptive coagulopathy (DIC) • Race (e.g. African Americans)
• Infection
• Malignancy
• Pre-eclampsia
• Stroke
• Superficial thrombophlebitis
• Trauma
Venous thromboembolism (VTE)

Venous thromboembolism (VTE) is the

formation of blood clots in the vein (legs,
pelvis or upper extremities)
When a clot forms in a deep vein 
usually in the leg, it is called a deep vein
thrombosis or DVT

If that clot breaks loose and travels to the

lungs, it is called a pulmonary embolism or
PE
Development of PE

A life threatening
disease  FATAL !
Pathophysiology of DVT

Wolberg et al., 2012

 Predisposing factors for VTE

Acquired Inherited

• Obesity • Deficiency
• Major surgery • Antithrombin
• Malignancy • Protein C
• Increasing age • Protein S
• Prolonged immobility • Mutation
• Previous VTE • FV Leiden
• Anti-phospholipid syndrome • Prothrombin G20210A
• Others (i.e. oral contraceptive pills, • Others:
etc.) • Dysfibrinogenemia
 Diagnosis of DVT

▪ Efficient and cost effective diagnosis of VTE is

facilitated by combining:
• Medical history, family history
• sign & symptom, & physical examination
• Pre-test probability models
• D-dimer testing
• Selective use of confirmatory imaging: USG Doppler
vascular
 Sign & Symptom oF DVT

The clot(s) can cause partial or

complete blocking of circulation in
the vein
pain, swelling, tenderness, discoloration,
or redness of the affected area, pitting
Pretest (Clinical) Probability
Sequelae: POST THROMBOTIC SYNDROME
(PTS)

 Severe post-thrombotic syndrome of

both lower legs (left > right) with
blue-red discoloration of the skin,
swelling, and hyperpigmentation
 Laboratory findings in DVT/PE

Fibrinogen: PT, APTT:

normal or normal or
increase shortened (coagulopathy consumption (-)

D-dimer: hypercoagulable
increase • Platelet count:
normal or
increase
FVIII/FIX: • thrombopathy
increase consumption (-)

Thrombophilia markers
Thrombosis in cancer
 D-DIMER IN PREGNANCY

1. Hedengran et al., 2016. Large D-Dimer Fluctuation in Normal Pregnancy: A Longitudinal Cohort Study of 4,117 Samples from 714 Healthy Danish Woman,
Obstetric and Gynecology International, Volume 2016, Article ID 3561675, t pages, http://dx.doi.org/10.1155/2016/3561675
 D-DIMER IN PREGNANCY

1. Hedengran et al., 2016. Large D-Dimer Fluctuation in Normal Pregnancy: A Longitudinal Cohort Study of 4,117 Samples from 714 Healthy Danish Woman,
Obstetric and Gynecology International, Volume 2016, Article ID 3561675, t pages, http://dx.doi.org/10.1155/2016/3561675
D-dimer in Pregnancy
 Disseminated Intravascular
Coagulation (DIC)
▪ Disseminated intravascular coagulation is
characterized by:
▪ systemic activation of blood coagulation
▪  which results in generation and deposition of fibrin
▪  leading to microvascular thrombi in various organs
▪  contributing to multiple organ dysfunction syndrome
(MODS)
▪ >> microtrombi  hyperfibrinolysis  D-dimer >>

▪ Thrombopathy & coagulopathy consumption 

Pathophysiology of dIC
Characteristic of DIC phenotypes
Pathogenesis DIC in Sepsis
Laboratory findings in DIC

• Platelet count: decrease

(thrombopathy consumption)
• PT & APTT: >>
(coagulopathy consumption)
• Fibrinogen level <
• D-dimer: >>
DIC score
 DIC in APL
• Hb : low
• WBC : increase
(promyelocyte >>)
• Platelet count : low
• PT & APTT : >>
• Fibrinogen : low
• D-dimer : increase

Wang ZY and Chen Z., Acute promyelocytic leukemia: from highly fatal to highly curable, Blood. 2008;111:2505-2515
 DIC in APL

Avvisati, 2012. Coagulopathy in APL: a step forward?,

Blood, Vo. 120, no. 1
Fibrinolytic Activation in APL
 D-dimer levels as a determinant
of recurrence risk

• Current evidence suggests that quantitative D-dimer assays

measured at the end of wafarin therapy and then one month
after its discontinuation can help determine the recurrence risk.

• Warfarin reduces thrombin generation in vivo, resulting in

decreased D-dimer levels.
• A negative D-dimer test was associated with lower annual risk
of recurrence than a positive D-dimer test

• D-dimer therefore appears to be a useful biomarker in

evaluating recurrence risk.
 KESIMPULAN

Aplikasi klinis D-dimer :

• Penanda fibrinolisis
• Eksklusi DVT/PE
• Penanda DIC
• Perlu dipertimbangkan pada kehamilan dan orang
tua
• Pemantauan rekurensi DVT/PE
• Penanda prognosis pada kanker
• Diagnosis  patient-based oriented
THANK YOU