Download Cancer and Thrombosis Friday September 30, 2011 Kelly Cheung, BSc, BSP

Cancer and Thrombosis
Friday September 30, 2011
Kelly Cheung, BSc, BSP
Learning Objectives
1. Recognize the association and risk
factors between cancer and venous
thromboembolism
2. Identify anti-cancer therapies that are
associated with an increased risk of
thrombosis
3. Review guidelines/recommendations for
the use of VTE prophylaxis in cancer
patients
Risk Factors for VTE in Cancer
Patient factors
– Age
– Race
– Elevated biomarkers
– Performance status
– Comorbidities: heart failure, respiratory
failure, obesity, diabetes, previous VTE,
infection, familial and/or acquired
hypercoagulability
J Clin Oncol 25:5490-5505, Hematology 2010:144-149
Risk Factors for VTE in Cancer
(cont’d)
Cancer-related factors
– Primary site of cancer – GI, brain, lung,
gynecologic, renal, hematologic
– First 3-6 months after diagnosis
– Metastatic and/or bulky disease
J Clin Oncol 25:5490-5505
Risk Factors for VTE in Cancer
(cont’d)
Treatment-related factors
– Surgery
– Hospitalization
– Chemotherapy
– Hormonal therapy
– Antiangiogenic therapy
– Erythropoesis-stimulating agents
– Central venous catheters
J Clin Oncol 25:5490-5505
Virchow’s Triad in Cancer
Venous stasis
– Prolonged bed rest/immobility
– Compression of blood vessels by tumour
Vascular damage
– Direct invasion by tumour
– Central Venous Catheters
– Chemotherapy drugs
– Tumour cytokines
J Clin Oncol 25:5490-5505
Virchow’s Triad in Cancer (cont’d)
Hypercoagulability
– Procoagulant effects
– Fibrinolytic activity
– Tumour cytokines
– Impaired endothelial cell defense
mechanisms
– Tumour cell/host cell interactions
– Prothrombotic effects of cancer therapy and
supportive therapy
Winter et al. Hematological Oncology 2006;24:126-133
Anti-cancer therapies associated
with increased risk of thrombosis
Antiangiogenic agents (thalidomide
and lenalidomide) and their
combinations
VEGF inhibitors (bevacizumab)
SERMs (tamoxifen, raloxifene)
Supportive Therapies: erythropoietin,
growth factors and hormones
Guidelines for VTE Prophylaxis - IMIDs
Risk Group
High
Clinical Factors
♦
IMID and previous personal history of
VTE
♦ IMIDs plus other therapy (high dose
dexamethasone, doxorubicin or multiagent
chemotherapy)
Intermediate •
♦
IMID and any 2 VTE risk factors such
as:
o
Strong family history of VTE
or known thrombophilia
o
Obesity
o
Prolonged immobilization
o
Indwelling catheters
o
Additional medication with
VTE risk (estrogens, EPO)
o
Additional comorbidities that
can additionally increase the risk
(nephrotic syndrome, aggressive
disease)
Recommendation
♦
Prophylactic dose of
LWMH
♦ Warfarin adjusted for
INR 2-3
•
Prophylactic dose of
LMWH or adjusted
warfarin for INR 2-3 if
bleeding risk is low
•
If risk of bleeding is high
(prior uncontrolled bleed,
platelet count <80x10 9/L
or difficult to control
warfarin) then reasonable to
offer ECASA 81mg OD
IMID therapy is the only VTE risk
♦
factor
IMID = immunomodulatory drug (thalidomide or lenalidomide)
Low
ECASA 81mg OD
Taken from CCMB Evidence-Based Recommendations for the Management of Multiple Myeloma, July 2011
update. Table prepared by Dr. Vi Dao
Guidelines for VTE Prophylaxis IMIDs
High risk patients: warfarin (target INR 23) or prophylactic LMWH for at least 4-6
months. May continue for the entire
duration of treatment or can consider
switching to ASA
Low risk patients: ECASA 81mg OD is
favoured
Intermediate risk: prophylactic LMWH or
warfarin (target INR 2-3) is preferred
unless high bleeding risk
CCMB Evidence-Based Recommendations for the Management of Multiple
Myeloma, July 2011 update. Section prepared by Dr. Vi Dao.
Guidelines for VTE Prophylaxis –
Other Therapies
Bevacizumab is associated with increased
risk of VTE; however, also associated with
increased risk of bleeding
– No routine VTE prophylaxis recommended
Routine prophylaxis not recommended for
patients with CVC
Current guidelines do not recommend
routine VTE prophylaxis in ambulatory
patients with cancer
Conclusions
The potential causes of VTE in cancer are
multifactorial
In the ambulatory setting, only patients receiving
thalidomide/lenalidomide treatment require VTE
prophylaxis
– Choice of prophylactic agent depends on patient
factors
Further studies are required to determine if
routine prophylaxis would be of benefit and for
which patient subgroups