1. Deep Vein Thrombosis & Malignancy Department of Radiation Oncology Presented by Dr. Muhammad Zubaer Hussain Deep Vein Thrombosis & Malignancy Department of Radiation Oncology Presented by Dr. Muhammad Zubaer Hussain

2. Incidence  About 600,000 hospitalizations per year occur for DVT in the United States.  100,000 to 300,000 VTE-related deaths occur annually in the United States.  Approximately 1 person in 20 develops a DVT in the course of his or her lifetime.

3. In-hospital VTE  In hospitalized patients, the incidence of venous thrombosis is considerably higher and varies from 20-70%.  The in-hospital case- fatality rate for VTE is 12% rising to 21% in elderly persons.  Venous thrombosis is second leading cause of death in cancer patients.

4. Lower Limb DVT  Although most DVT is occult and resolves spontaneously without complication,  It is the underlying source of 90% of acute PEs  PE occurs in approximately 10% of patients with acute DVT and can cause up to 10% of in hospital deaths.  Cause 25,000 deaths per year in the United States.

5. Upper Limb DVT  Asymmetry in the supraclavicular fossa or in the circumference of the upper arms.  A prominent superficial venous pattern may be evident on the anterior chest wall.

6. Lower Limb DVT Upper Limb DVT

7. Risk Factors  Age (In elderly persons, the incidence is increased 4-fold)  Immobilization longer than 3 days  Pregnancy and the postpartum period  Major surgery in previous 4 weeks  Plane/car trips (> 4 hours) in previous 4 wks  Cancer (30%)  Previous DVT

8. Risk Factors…Contd  Stroke ( DVT is found in 53% of paralyzed limbs, compared with only 7% on the nonaffected side.)  Acute myocardial infarction (AMI)  Congestive heart failure (CHF)  Sepsis  Nephrotic syndrome  Ulcerative colitis  Multiple trauma  CNS/spinal cord injury  Burns

9. Risk Factors  Homocystinuria  Polycythemia rubra vera  Thrombocytosis  Inherited disorders of coagulation  Drug abuse  Oral contraceptives

10. Malignancy & DVT  Malignancy is noted in as many as 30% of patients with venous thrombosis.  90% of cancer patients having some abnormal coagulation factors.  Chemotherapy may increase the risk of venous thrombosis by affecting the vascular endothelium, coagulation cascades, and tumor cell lysis.  The incidence has been shown to increase in those patients undergoing longer courses of therapy.

11. AETIOLOGY of DVT in CANCER PATIENTS  Hypercoagulable State  Increased plasma levels of Clotting factors  Cancer procoagulant  Tissue factor  Cytokines  Inrceased plasminogen activator  Surgical Intervertion  Chemotherapy  Prolonged Immobilization

12. TYPE of CANCERS with  DVT  Pancreas  Lung  Breast  GI tumor  Prostate  Multiple Myeloma  Lymphoma  Leaukaemia

13. Postoperative venous thrombosis  Varies depending on a multitude of patient factors, including the type of surgery undertaken.  Without prophylaxis, general surgery operations typically have an incidence of DVT around 20% in benign disease, whereas 36% in cancer patients.

14. DIAGNOSIS

15. Symptoms and Signs Lower limb DVT characteristically starts with  Pain (50%)  Swelling  An increase in temperature and  Dilatation of the superficial veins.  Often, however, there are only minimal S/S  Typically unilateral but may be bilateral ( when clot extends proximally into the inferior vena cava. ) ( Bilateral DVT is more commonly seen in patients with underlying malignancy )

16. Symptoms and Signs  Most specific symptom Leg pain - Occurs in 50% of patients but is nonspecific  Tenderness - Occurs in 75% of patients  Warmth or Erythema of the skin over the area of thrombosis

17. Symptoms and Signs …contd  Clinical symptoms of pulmonary embolism (PE) as the primary manifestation  Calf pain on dorsiflexion of the foot (Homans sign)  Variable discoloration of the lower extremity

18. Well’s Score Clinical characteristicScore Active cancer (patient receiving treatment for cancer within the previous 6 months or currently receiving palliative treatment) 1 Paralysis, paresis or recent plaster immobilisation of the lower extremities 1 Recently bedridden for 3 days or more, or major surgery within the previous 4 weeks 1 Localised tenderness along the distribution of the deep venous system 1 Entire leg swollen 1 Calf swelling at least 3 cm larger than that on the asymptomatic side (measured 10 cm below the tibial tuberosity) 1 Pitting oedema confined to the symptomatic leg 1 Collateral superficial veins (non-varicose) 1 Alternative diagnosis at least as likely as DVT -2

19. Well’s Score…contd Clinical probability Total score DVT low probability< 1 DVT moderate probability1-2 DVT high probability> 2

20. DIFFERENTIAL DIAGNOSES Table 262-2 Differential Diagnosis Ruptured Baker's cyst Cellulitis Postphlebitic syndrome/venous insufficiency

21. Symptoms and Signs …contd  Baker's cysts usually occur in patients with rheumatoid arthritis.  Cellulitis is usually distinguished by  Marked skin erythema and temperature which is localised within a well-demarcated area of the leg and may be associated with an obvious source of entry of infection  Fever and chills  Postphlebitic syndrome.  Leg is diffusely edematous  skin ulceration, especially in the medial malleolus of the leg

22. INVESTIGATIONS

23.  D-dimer  Compression USG (sensitivity is ~99.5%)  Venogram

24. Investigations of Suspected DVT

25. D-dimer  D-dimer is a useful "rule out" test.  Sensitivity >80% for DVT and >95% for PE.  Levels increase in patients with  MI  Pneumonia  Sepsis

26. USG of Rt. Popliteal Vein

27. COMPLICATIONS VTE can cause  death from PE or, among survivors  Ch. thromboemboli c Pulmonary HTN  Postphlebitic/Post thrombotic/C hronic venous insufficiency ± Ulceration

28. Management Prophylactic management: Non Pharmacological:  Early mobilization of all patients  Intermittent pneumatic compression  Mechanical foot pumps  Graduated compression stockings.

29. Prophylactic management (Contd) Pharmacological: (Moderate to High risk of DVT)  Low molecular weight heparins (eg. Enoxaparin)  Unfractionated heparin  Fondaparinux  Apixaban  Dabigatran  Rivaroxaban  Warfarin  Aspirin

30. Prophylactic management (Contd) Pharmacological:  Enoxaparin 40mg sc once daily  Fondaparinux 2.5 mg sc once daily  Apixaban PO ( Showing promising result in clinical trial)  Warfarin 10 mg on the first and second days, with 5 mg on the third day; subsequent doses are titrated against the INR.

31. Moderate risk of DVT:  Major surgery Or,  Major medical illness, e.g.  Heart failure  Myocardial infarction with complications  Sepsis  Active malignancy  Stroke and other conditions leading to lower limb paralysis

32. High risk of DVT:  Major abdominal or pelvic surgery for malignancy for malignancy or or with history of DVT with history of DVT or or known thrombophilia known thrombophilia  Major hip or knee surgery  Neurosurgery

33. Management of Established DVT  General management:  Elevation of limb  Analgesia  Anticoagulant: ( mainstay of treatment)  Inferior Vena Caval (IVC) Filters  CI to anticoagulation and  Recurrent venous thrombosis despite intensive anticoagulation.

34. Management of Established DVT  Anticoagulant: Low molecular weight heparin(LMWH): 1mg/kg sc 12 hrly or, Unfractionated heparin 5000 U iv loading  continuous inf 20U/kg/hr 5000 U iv loading  continuous inf 20U/kg/hr Parenteral anticoagulation should be continued for a minimum of 5 days Warfarin: 10 mg on the first and second days, with 5 mg on the third day; subsequent doses are titrated against the INR.