Venous ThromboembolismIn Cancer Patients
VTE
Nabeel Rajeh, MD
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
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
Risk may be 1-35%
PREDICTORS OF VTE IN CANCER
• Anemia , Leukocytosis, Thrombocytosis
• History of VTE
• Hospitalization
• Infections
• Immobilization
• D-Dimer and P- Selectin
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
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
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• Invasive venography may be outdated
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
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,
FONDAPARINUX
• Specific Xa inhibitor
• No cross reaction with HIT
• Value in renal failure, obese, underweight, elderly is questionable
• Dosing once daily
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
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)
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
PROPHYLAXIS
• SHOULD AMBULATORY PATIENTS WITH CANCER RECEIVE ANTICOAGULATION FOR VTE PROPHYLAXIS DURING SYSTEMIC CHEMOTHERAPY
• Not at this time
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
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
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.
HEPARIN INDUCED THROMBOCYTOPENIA
HIT
• Thrombocytopenia Timeing, Thrombosis, oThers
• PF4/antibodies detection and serotonin release assay
• Stop warfarin stop heparin no platelets
• Direct thrombin inhibitors lepirudin argatroban
• Fondaparinux
Thank You
Nabeel Rajeh, MDwww.syriaoncology.com