Thrombosis and cancer Dr Galila Zaher Consultant Hematologist MRCPath Oct 2003
Venous thrombosis and cancer are two way clinical association. • Pathgenisis of thrombosis is different . • The frequency is greater. • The management required is more complex.
Pathogenesis • Tumor cells express pro-coagulant TF. • TF :receptor &cofactor for FVIIa. • TF expressed in pancreatic adeno-carcemona. • TF: correlates with the degree of differentiation . • TF: associated with switch in angiogenic balance & up regulation of vascular endothelial growth factor . • TF-VII up-regulates palsminogen activator receptor promoting tumor cell invasion. • FXa :over expression of the angiogenesis. • Thrombin binding to its receptors upregulates TF expression.
VTE and occult cancer • Idiopathic VTE have an increased incidence of subsequently developed cancer . • The standardized incidence ratio for cancer in patients with VTE is 4.4. • The SIRs are highest in the first 6m & drop to 1 beyond 12m. • The cumulative probability of cancer over 6Y FU in idiopathic VTE is 17% Vs 5% in secondary VTE.
Extensive Investigations for underlying cancer • The potential benefit of screening must be weighed against potential harms. • Procedure related morbidity. • The psychological burden of false positive test. • The cost of screening. • Small randomized trail :no statistically significant difference in cancer related mortality . • It is premature to recommend extensive screening in patients who present with idiopathic VTE.
Prevention of thrombosis • Surgical prophylaxis: meta-analysis of trials comparing LMWH &UFH in high –risk surgery included cancer patients : • Evidence that once daily LMWH is as safe &effective as UFH. • Incidence of venographic DVT can be reduced with extended out of hospital prophylaxis. • Extended prophylaxis in cancer surgery there is a significant reduction in DVT from 12% with placebo Vs 4% with extended prophylaxis .”Enoxacan II”
Prevention of thrombosis • Medical cancer patients: • Fewer data are available on prophylaxis in ambulatory cancer patients. • PMH of VTE with breast cancer ,aromatase inhibitor has much lower risk of thrombosis than tamoxifen . • Low dose warfarin for the prevention of thrombo-embolism in cancer patients. ” Levine”
Prevention of thrombosis • Central vein catheter thrombosis: • Small trials Low dose warfarin or LMWH : demonstrated significant reduction in catheter thrombosis. Randomized trials :no difference . • Routine prophylaxis is not practiced .
Treatment of VTE • Difficult : • Increased risk of recurrence(27%/y Vs 9) . • Increased anticoagulant induced bleeding x6. • Both occur predominantly during the first month of anticoagulation • Increased mortality compared to cancer without VTE.
Initial Treatment of DVT • Meta-analysis:LMWH is as safe & more effective than UFH . • 20% were cancer patients. • it is reasonable to generalize the resuls to cancer patients. • LMWH :SC ,no need for monitoring improve the quality of life. • Home treatment :comparable. • LMWH at home in cancer patient is recommended positive impact on the quality of life. • Compliance ,reliability &good support system.
Initial Treatment of PE • Few trials comparing LMWH&UFH.
Case Presentation • 24 Dec: 199846 Years old Egyptian patientE.R. admission.Bilateral leg pain.Red discoloration.
Risk factor • No surgery, No immobilizationNo bedridden, No trauma. • FH : diabetics mother. • HT: On Renetic- Adalat . • No symptoms of PE. • Non-smoker Teacher
Upon Examination • Leg Swollen. • Lf : 45cm Rt : 38 cm • Warm tender. • Heart rate 70/m RR 20/m BP-145/90
Investigations • Duplex U/S. Sub acute thrombosis involving DVT Superficial Femoral vein – popliteal veinAnterior & post tibial veins.
Management • Standard Heparin started 24/12/02 • 5000 IVI. • 1.5 x APTT control : 26/12. • Thrombophilia Screen :26/1201. • LFT , U&E Normal . • Hepatitis Screen Negative
Follow up OAC for 6m. • Thrombophilia Screen :Unprovoked DVT, Obesity. • Off Wanferin x 6 w • PC ,PS ,AT,APCR,ACA IgG - IgM :Negative ANA , DNA CRP, Rhd Factor :Neg. • LA. Screen & Confirmatory + ve
April 2001 • Abd US : Rt upper pole renal mass. • CT & biopsy are recommendedCortical lesion confined to the organ • Renal cell adeno-carcinoma.
APL SECONARY TO CANCER • Lupus type anticoagulant in a patient with renal cell carcinoma • An autoimmune paraneoplastic syndrome.J Urol 2002 May;167(5):2129 Ather MH, Mithani S, Bhutto S, Adil S. • woman with pulmonary embolism and positive lupus anticoagulant before the diagnosis of renal cell carcinoma. J Urol 1994 Sep;152(3):941-2 Papagiannis A, Cooper A, Banks J.
ovarian cancer. • APS before ovarian endometrial adenocarcinoma. • widespread thromboembolism . • No respond to anticoagulant treatment. • The paraneoplastic nature is suggested by the disappearance of both thromboembolism and APL only after surgical removal of the cancer.
CLL& Lung cancer • Autoimmune complications of CLL: • APL (LA,ACA). • Anti-factor VIII inhibitors. Ann Ital Med Int 1999 Jan-Mar;14(1):46-50 • The lung cancer may trigger catastrophic APS. • Occlusion of the superior mesenteric artery. Nippon Geka Gakkai Zasshi 1999 Feb;100(2):228-30