1. Venous Thromboembolism
In Cancer Patients
VTE
Nabeel Rajeh, MD

2. VTE in Cancer patients First described by Trousseau 1865
Hypercoagulability related to cancer
Procoagulant, vessel wall damage, stasis and immobilization, chemotherapy, surgery, radiation,
Underlying intrinsic hypercoagulability
Factor V leiden, antiphospholipid syndrome
2-6 fold increase in risk of death

6. Venous thrombosis in cancer patients FRONTLINE survey
first comprehensive global survey of thrombosis and cancer
3,891 completed responses were analyzed
Brain and pancreatic tumors were a high risk for VTE
50% surgeons used thromboprophylaxis routinely
5% oncologists used thromboprophylaxis routinely
Low molecular weight heparin (LMWH) was the most popular Aspirin for prophylaxis used in 20%
LMWH use by as initial treatment for VTE as outpatient followed by VKA
The results of the FRONTLINE survey demonstrate a need for guidelines to direct clinical practice in line with evidence-based data concerning cancer and VTE

7. Risk may be 1-35%

12. Predictors of VTE in Cancer
Anemia , Leukocytosis, Thrombocytosis
History of VTE
Hospitalization
Infections
Immobilization
D-Dimer and P- Selectin

13. Predictors of VTE in Cancer
Adenoca compared to squamous cell ca
Solid tumors as well as liquid tumors
Certain treatment
Thalidomid, lenalidomide, doxorubicin, tamoxifen, oral contraceptive, Dexamethasone erythropoietin, Bevacizumab

14. Why Cancer Patient
Patient with solid tumor and distant metastases has 20 fold increase VTE
VTE second leading cause of cancer deaths
Risk of bleeding is 13% compared with 4% in none cancer
Significant early mortality if VTE

15. Diagnosis of VTE Clinical prediction of risk Symptoms and signs
D-Dimer testing to diagnose VTE is not recommended
Duplex venous ultrasonography with compressibility and flow
Indirect CT Venography
MRI
CTA for PE
Invasive venography may be outdated

16. Superficial Vein Thrombosis
Clinical diagnosis
Must rule out DVT
Trouseau Syndrome migratory SVT require UFH, or LMWH
Treatment with 4 weeks LMWH if central catheter related
NSAID

17. LMWH Dalteparin, Enoxaparin, Tinzaparin All inhibit Xa
Therapeutically equivalent and Interchangeable
RCT Tinzaparin compared to Dalteparin prove equality
Immediate therapy and prophylaxis is FDA
Continuation therapy require dose reduction?
Concern in renal, obese, elderly, HIT,

18. Fondaparinux Specific Xa inhibitor No cross reaction with HIT
Value in renal failure, obese, underweight, elderly is questionable
Dosing once daily

19. Unfractionated Heparin
Do we remember!
SQ prophylaxis may be better than LMWH
Bid or tid dosing
Treatment based on weight 80u/kg/h
Can be used with renal failure (liver metabolism)
Risk of HIT
Resistance

20. Warfarin The advisable chronic therapy
Concomitant with UFH or LMWH for 5 days
PT INR monitoring
Labile INR result
Resistance to therapeutic INR (genetically interaction and none compliance)

23. Inpatient Prophylactic therapy
To all patients hospitalized with active cancer
Or suspicious cancer
Encourage ambulation although it is not enough prophylaxis
LMWH, UFH, Fondaparinux are effective
Low dose warfarin and adjusted to INR1.5-2 for port catheter or chemotherapy catheter are not recommended
May extend for 4 week post discharge in very high risk patient

25. Prophylaxis
SHOULD AMBULATORY PATIENTS WITH CANCER RECEIVE ANTICOAGULATION FOR VTE PROPHYLAXIS DURING SYSTEMIC CHEMOTHERAPY
Not at this time

26. Treatment of VTE Immediate LMWH, UFH, Fondaparinux for 5-10 days
Followed by LMWH for 6 m in patient with active cancer
LMWH beyond 6 m is not recommended
Warfarin with close monitoring
Meta-analysis LMWH reduce 3 m mortality comapred to UFH
Recurrence VTE and major bleeding are higher with chronic warfarin compared to LMWH

27. WHAT IS THE BEST TREATMENT FOR PATIENTS WITH CANCER WITH ESTABLISHED VTE TO PREVENT RECURRENT VTE?
LMWH is the preferred approach for the initial 5 to 10 days of anticoagulant treatment of the cancer patient with established VTE.
LMWH given for at least 6 months is also the preferred approach for long-term anticoagulant therapy. Vitamin K antagonists with a targeted INR of 2 to 3 are acceptable for long-term therapy when LMWH is not available

34. SHOULD PATIENTS WITH CANCER RECEIVE ANTICOAGULANTS IN THE ABSENCE OF ESTABLISHED VTE TO IMPROVE SURVIVAL?
Anticoagulants are not recommended to improve survival in patients with cancer without VTE.

38. Heparin Induced Thrombocytopenia

39. HIT Thrombocytopenia Timeing, Thrombosis, oThers
PF4/antibodies detection and serotonin release assay
Stop warfarin stop heparin no platelets
Direct thrombin inhibitors lepirudin argatroban
Fondaparinux

42. Thank You
Nabeel Rajeh, MD