3. Thrombosis is a general term for
the formation or presence of a
thrombus (a clot of coagulated
blood) in a blood vessel
Thrombus can develop in
vein,artery,heart &
microcirculation
Thrombosis is much more
prevalent in patients
w/malignancy & predominantly
of the venous circulation
7. VTE and malignancy : Epidemiology
⢠Of all cases of VTE:
â About 18% occur in malignancy patients
â About 10-17% patients ,in which no underlying cause
of VTE, will go on to have the diagnosis of a new
malignancy within two years
⢠Of all patients w/ malignancy
â 15% will have symptomatic VTE
â As many as 30- 50% have VTE at autopsy
⢠Compared to patients without malignancy:
â Higher risk of first and recurrent VTE (about 7- fold
increased )
â In certain malignancy risk for VTE increased 28-fold
8. VTE AND RISK FACTOR
PATIENT RELATED FACTOR
Age,sex,ethnicity,comorbid condition &
prothrombotic mutation
TUMOR RELATED FACTOR
type, site, stage & duration of malignancy
9. VTE AND RISK FACTOR ( CONTâŚ)
TREATMENT RELATED FACTOR
ďś Pharmacologic therapy
ď§ Chemotherapeutic agent
ďś
14. Pathogenesis of Thrombosis in malignancy
patient
1.
Stasis
A Modification of Virchowâs Triad
â Prolonged bed rest
â Extrinsic compression of blood vessels by tumor
2. Vascular Injury
â Direct invasion by tumor
â Prolonged use of central venous catheters
â Endothelial damage by chemotherapy drugs
â Effect of tumor cytokines on vascular endothelium
3. Hypercoagulability
â Tumor-associated procoagulants & cytokines (tissue
factor, CP, TNF , IL-1 , VEGF, etc.)
â Impaired endothelial cell defense mechanisms (APC
resistance; deficiencies of AT, Protein C and S)
â Enhanced selectin/integrin-mediated, adhesive
interactions between tumor cells,vascular endothelial
cells, platelets & host macrophages
15. VTE: PATHOPHYSIOLOGY ContâŚâŚ.
ďś The PRINCIPAL prothrombotic properties
of tumor cell :
ďśCapacity of tumor cell to interact w/ host
blood cells; endothelial, leukocytes &
platelet.
ďśCapacity of tumor cell to produce & release
its own procoagulant & fibrinolytic activities,
beside proinflammatory cytokines
19. VTE : PREVENTION
PRIMARY PREVENTION
AMBULATORY PATIENT W/ CHEMOTHERAPY
MEDICAL INPATIENT W/ CHEMOTHERAPY
MALIGNANCY PATIENT W/ SURGERY
20. ⢠Ambulatory Patient with Chemotherapy
NCCN Recommended VTE prophylaxis in
high risk setting :
ďśPatient receiving highly thrombotic
antiangiogenic therapy (i.e., thalidomide/
lenalidomide in combination w/ high dose
dexamethasone
ďśMyeloma patients w/ 2 or more
individual or myeloma risk factors
21. Ambulatory Patient (ContâŚ.)
Modality for prophylaxis:
ďą Low dose warfarin (1mg
for 6 weeks ) adjusted to INR
1,3-1,9
ďąEnoxaparin 1mg/kg SC
every 24 hour for at least 3
months.
ďąApixaban
22. VTE : PREVENTION
PRIMARY PREVENTION
AMBULATORY PATIENT W/ CHEMOTHERAPY
MEDICAL INPATIENT W/ CHEMOTHERAPY
CANCER SURGERY PATIENT
23. Medical Inpatient with chemotherapy
NCCN recommended :
⢠Enoxaparin, 40 mg sc daily
⢠Tinzaparin, 4500 units (fixed dose) sc daily or
75 units/kg sc daily
⢠Dalteparin, 5000 units sc daily
⢠Fondaparinux ; 2.5 mg sc daily
⢠Unfractionated heparin:5000 units sc 3 times
daily
⢠Warfarin (adjusted to INR 2-3)
24. VTE : PREVENTION
PRIMARY PREVENTION
AMBULATORY PATIENT W/ CHEMOTHERAPY
MEDICAL NPATIENT W/ CHEMOTHERAPY
MALIGNANCY PATIENT W/ SURGERY
26. Malignanct inpatient w/ surgery ( contâŚ)
pharmacological
⢠Modality prophylaxis for malignancy
patient w/ surgery is not
significantly different w/ medical in
patient w/ chemotherapy
27. VTE PREVENTION
SECONDARY PREVENTION
ďśWarfarin
âDifficulty maintaining tight therapeutic
control, due to anorexia, vomiting, drug
interactions
âFrequent interruptions for
thrombocytopenia & procedures
âDifficulty in venous access for
monitoring
â Increased risk of both recurrence &
bleeding
ďśLow molecular weight heparin
34. PROGNOSIS
âşSurvival after VTE is lower than expected in
malignancy patients.
âşVTE : 2nd most common cause of death in
hospitalized patients w/ malignancy(tied
with infection)
âşSurvival among active cancer patients with
VTE differs by gender.
36. SUMMARY
âşVTE : 2nd most common cause of death
in hospitalized malignancy patient
âş Risk factors for VTE in the setting of
malignancy have been well characterized:
solid tumors, chemotherapy, surgery,
thrombocytopenia
âş Long-term secondary prevention w/ LMWH
has been shown to produce better outcomes
than warfarin
âş malignancy patients are under-prophylaxed
for VTE
37. SUMMARY (ContâŚ.)
ď§ Effective VTE prophylaxis in malignancy
patients usually requires anticoagulation
w/ LMWH but when bleeding risk is too
high, use mechanical measures.
ď§ VTE prophylaxis in malignancy patients is
under-utilized & requires increased
vigilance and prophylaxis-focused
intervention
43. Trombosis lebih sering pada vena dibanding
arteri because:
⢠Aliran darah pada vena lebih lambat
dibandingkan arteri.
⢠Trombus pada arteri : trombus putih karena
terdiri dari trombin bersifat lebih kuat tidak
mudah lepas,pada vena trombus merah
terbentuk dari fibrin mudah lepas menjadi
emboli.
44. ⢠APC resistance = Activated Protein C resisten
adalah kegagalan protein C aktiv merubah FVa
menjadi FV,sehingga FVa menjadi bertumpuk
yang memudahkan trombosis.