Thrombosis and cancer Dr Galila Zaher Consultant Hematologist

Thrombosis and cancer Dr Galila Zaher Consultant Hematologist MRCPath Oct 2003

Venous thrombosis and cancer are two way clinical association. Ø Pathgenisis of thrombosis is different. Ø The frequency is greater. Ø The management required is more complex.

Pathogenesis l l l l 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 l l 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 6 m & drop to 1 beyond 12 m. The cumulative probability of cancer over 6 Y FU in idiopathic VTE is 17% Vs 5% in secondary VTE.

Extensive Investigations for underlying cancer l l l 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 l l 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: l Fewer data are available on prophylaxis in ambulatory cancer patients. l PMH of VTE with breast cancer , aromatase inhibitor has much lower risk of thrombosis than tamoxifen. l Low dose warfarin for the prevention of thrombo-embolism in cancer patients. ” Levine” l

Prevention of thrombosis Central vein catheter thrombosis: l Small trials Low dose warfarin or LMWH : demonstrated significant reduction in catheter thrombosis. Randomized trials : no difference. l Routine prophylaxis is not practiced. l

Treatment of VTE Difficult : l Increased risk of recurrence(27%/y Vs 9). l Increased anticoagulant induced bleeding x 6. l Both occur predominantly during the first month of anticoagulation l Increased mortality compared to cancer without VTE. l

Initial Treatment of DVT l l l l 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 l Few trials comparing LMWH&UFH.

Case Presentation l 24 Dec: 1998 46 Years old Egyptian patient E. R. admission. Bilateral leg pain. Red discoloration.

Risk factor l l l No surgery, No immobilization No bedridden, No trauma. FH : diabetics mother. HT: On Renetic- Adalat. No symptoms of PE. Non-smoker Teacher

Upon Examination l l Leg Swollen. Lf : 45 cm Rt : 38 cm Warm tender. Heart rate 70/m RR 20/m BP-145/90

Investigations l Duplex U/S. Sub acute thrombosis involving DVT Superficial Femoral vein – popliteal vein Anterior & post tibial veins.

Management l l l 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 6 m. l Thrombophilia Screen : Unprovoked DVT, Obesity. l Off Wanferin x 6 w l PC , PS , AT, APCR, ACA Ig. G - Ig. M : Negative ANA , DNA CRP, Rhd Factor : Neg. l LA. Screen & Confirmatory + ve

April 2001 Abd US : Rt upper pole renal mass. l CT & biopsy are recommended Cortical lesion confined to the organ l Renal cell adeno-carcinoma. l

APL SECONARY TO CANCER l l 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. l 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. l l 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 l Autoimmune complications of CLL: APL (LA, ACA). l Anti-factor VIII inhibitors. l Ann Ital Med Int 1999 Jan-Mar; 14(1): 46 -50 l l The lung cancer may trigger catastrophic APS. Occlusion of the superior mesenteric artery. Nippon Geka Gakkai Zasshi 1999 Feb; 100(2): 228 -30