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:
– About 18% occur in malignancy patients
– 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
– 15% will have symptomatic VTE
– As many as 30- 50% have VTE at autopsy
• Compared to patients without malignancy:
– Higher risk of first and recurrent VTE (about 7- fold
increased )
– 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 ( CONT…)
TREATMENT RELATED FACTOR
Pharmacologic therapy
Chemotherapeutic agent
14. Pathogenesis of Thrombosis in malignancy
patient
1.
Stasis
A Modification of Virchow’s Triad
– Prolonged bed rest
– Extrinsic compression of blood vessels by tumor
2. Vascular Injury
– Direct invasion by tumor
– Prolonged use of central venous catheters
– Endothelial damage by chemotherapy drugs
– Effect of tumor cytokines on vascular endothelium
3. Hypercoagulability
– Tumor-associated procoagulants & cytokines (tissue
factor, CP, TNF , IL-1 , VEGF, etc.)
– Impaired endothelial cell defense mechanisms (APC
resistance; deficiencies of AT, Protein C and S)
– Enhanced selectin/integrin-mediated, adhesive
interactions between tumor cells,vascular endothelial
cells, platelets & host macrophages
15. VTE: PATHOPHYSIOLOGY Cont…….
The PRINCIPAL prothrombotic properties
of tumor cell :
Capacity of tumor cell to interact w/ host
blood cells; endothelial, leukocytes &
platelet.
Capacity 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 :
Patient receiving highly thrombotic
antiangiogenic therapy (i.e., thalidomide/
lenalidomide in combination w/ high dose
dexamethasone
Myeloma patients w/ 2 or more
individual or myeloma risk factors
21. Ambulatory Patient (Cont….)
Modality for prophylaxis:
Low dose warfarin (1mg
for 6 weeks ) adjusted to INR
1,3-1,9
Enoxaparin 1mg/kg SC
every 24 hour for at least 3
months.
Apixaban
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 ( cont…)
pharmacological
• Modality prophylaxis for malignancy
patient w/ surgery is not
significantly different w/ medical in
patient w/ chemotherapy
27. VTE PREVENTION
SECONDARY PREVENTION
Warfarin
●Difficulty maintaining tight therapeutic
control, due to anorexia, vomiting, drug
interactions
●Frequent interruptions for
thrombocytopenia & procedures
●Difficulty in venous access for
monitoring
● Increased risk of both recurrence &
bleeding
Low molecular weight heparin
34. PROGNOSIS
►Survival after VTE is lower than expected in
malignancy patients.
►VTE : 2nd most common cause of death in
hospitalized patients w/ malignancy(tied
with infection)
►Survival among active cancer patients with
VTE differs by gender.
36. SUMMARY
►VTE : 2nd most common cause of death
in hospitalized malignancy patient
► Risk factors for VTE in the setting of
malignancy have been well characterized:
solid tumors, chemotherapy, surgery,
thrombocytopenia
► Long-term secondary prevention w/ LMWH
has been shown to produce better outcomes
than warfarin
► malignancy patients are under-prophylaxed
for VTE
37. SUMMARY (Cont….)
Effective VTE prophylaxis in malignancy
patients usually requires anticoagulation
w/ LMWH but when bleeding risk is too
high, use mechanical measures.
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.