Venous Thromboembolism In 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venous ultrasonography with compressibility and flow Indirect CT Venography MRI CTA for PE Invasive venography may be outdated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, MD www.syriaoncology.com