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MANAGEMENT OF
THROMBOSIS IN CANCER
Anticoagulant and Laboratory Tests
Usi Sukorini
INTRODUCTION
Timp JF, Braekkan SK, Versteeg HH, Cannegieter SC. Epidemiology of cancer-associated venous thrombosis. Blood.
2013;122:1712–23
Cancer Virchow’s triad
Direct mechanisms involved in
cancer‐associated thrombosis.
Razak et al., Cancer-Associated Thrombosis: An Overview of Mechanisms, Risk Factors, and Treatment Cancers 2018, 10, 380;
doi:10.3390/cancers10100380
Indirect mechanisms promoting thrombosis
in cancer
Razak et al., Cancer-Associated Thrombosis: An Overview of Mechanisms, Risk Factors, and Treatment Cancers 2018, 10,
380; doi:10.3390/cancers10100380
Unique Challenges in Cancer-associated
Thrombosis
Indirect: Fondaparinux
Unfractionated FXa Direct: Rivaroxaban
Heparin (UFH) inhibitors Apixaban
Edoxaban
Low-Molecular-
Weight Direct
Heparin Thrombin Hirudin
(LMWH) Inhibitors Dabigatran
(DTI)
Vitamin K
Antagonists
Laboratory monitoring for anticoagulants
No Anticoagulants Tests
1 Vitamin K antagonists PT (less sensitive)
INR
2 UFH, LMWH APTT (less sensitive)
Chromogenic anti FXa assay
3 FXa inhibitor APTT
(Rivaroxaban, Apixaban, Edoxaban) Chromogenic anti FXa assay
4 Direct Thrombin Inhibitor (DTI): APTT, TT
(Hirudin, Dabigatran etexilate) Diluted thrombin time (dTT)
Ecarin clotting time (ECT)
Ecarin chromogenic assay (ECA)
Chromogenic anti IIa assay
• Traditional oral anticoagulant (warfarin)
• Vitamin K dependent, interfere with normal synthesis of factors
II, VII, IX and X, and protein C and S
• Warfarin cause incomplete coagulation due to lacking calcium
binding site and cannot form enzyme substrate complexes
• The onset of action: 8 – 12 hours, maximum effect: 36 hours
• Duration of action:
72 hours
ISI
PT patient (sec)
INR =
mean normal PT (sec)
Therapeutic INR range recommended for standard
oral anticoagulant therapy (VKA)
INR Indication
• optimal level for anticoagulant therapy
• post myocardial infarction therapy & prophylaxis
• atrial fibrillation
2–3
• treatment of VTE, PE
• prevention of systemic embolism
• tissue heart valves
• high risk of clot formation
2.5 – 3.5 • mechanical prosthetic heart valves
• recurrence embolism
Ikeda & Tachibana, 2016. Clinical implication of monitoring rivaroxaban and apixaban by using anti-factor Xa assay in patients with non-valvular atrial
fibrillation, Journal of Arrhythmia 32: 42–50
Direct Oral Anticoagulant
(DOACs)/
New Oral Anticoagulant (NOACs)
Usi Sukorini
Direct oral anticoagulants
• Rivaroxaban • Dabigatran
• Apixaban
• Edoxaban
in Debate
Rivaroxaban
Apixaban
Ieko et al. Journal of Intensive Care (2016) 4:19 Edoxaban Dabigatran
Direct oral anticoagulants
http://www.islh.org/speaker-portal/files/handouts/HANDOUT-34-1525520837.pdf
Expected plasma concentration of dabigatran or
rivaroxaban after treatment
Tripodi, The laboratory and the direct oral anticoagulants, Blood, 2013;121(20):4032-4035
Timing of Testing
Drugs Cpeak (hours) Ctrough (hours)
Dabigatran 2 or 3 12
RIvaroxaban 2 or 3 24
Rivaroxaban
• PT & APTT :
• Available, easy, little expertise
• Prolong PT & APTT:
• linearly and dose-dependently to the [rivaroxaban]
• responsiveness is adequate
• Standardization: concern
• PT more sensitive than APTT, but not specific
• PT is not sensitive to dabigatran
Tripodi A, 2013. The Laboratory and the New Oral Anticoagulants, Clinical Chemistry 59:2
FXa inhibitor: Global assays
Tripodi A, 2013. The Laboratory and the New Oral Anticoagulants, Clinical Chemistry 59:2
Anti-FXa chromogenic assay: rivaroxaban measurement
Tripodi A, 2013. The Laboratory and the New Oral Anticoagulants, Clinical Chemistry 59:2
Chromogenic Anti-FXa assay: FXa inhibitor measurement
Ikeda & Tachibana, 2016. Clinical implication of monitoring rivaroxaban and apixaban by using anti-factor Xa assay in patients with non-valvular atrial
fibrillation, Journal of Arrhythmia 32: 42–50
Anti-FXa clotting-based assay
Douxfils et al, 2018. Laboratory testing in patients treated with direct oral anticoagulants: a practical guide for clinicians, Journal of Thrombosis and Haemostasis, 16:
Thrombin Time (TT) & Dabigatran
Tripodi A., 2013. The Laboratory and the New Oral Anticoagulants, Clinical Chemistry 59:2
Ecarin Chromogenic Assay (ECA)
• Clot formation is obtained by a venom extract (ecarin) from the snake Echis
carinatus.
• Ecarin converts FII into meizothrombin, which is then measured with a specific
synthetic chromogenic substrate
http://www.viapath.co.uk/news-and-press/measurement-of-direct-oral-anticoagulants
Tripodi A., 2013. The Laboratory and the New Oral Anticoagulants, Clinical Chemistry 59:2
Ecarin Chromogenic Assay (ECA)
Rivaroxaban Dabigatran
• Screening: • Screening:
• PT • APTT or TT
• Quantification: • Quantification:
• Anti-Fxa assay • dTT or ECT
Tripodi A., 2013. The Laboratory and the New Oral Anticoagulants, Clinical Chemistry 59:2
Absorption and metabolism of the different
new anticoagulant drugs
http://www.islh.org/speaker-portal/files/handouts/HANDOUT-34-1525520837.pdf
Other laboratory tests