Journal of Rawalpindi Medical College (JRMC); 2014;18(1):7-10 7 Original Article Levels of Natural Anticoagulants Protein C, Protein S and Antithrombin III in Patients with Solid Malignancies Samina T.Amanat,Masooma Raza, Huma Abdul Shakoor, Waqar Mehmood, Department of Pathology, Pakistan Atomic Energy Commission Hospital, Islamabad Abstract Background: To estimate plasma levels of natural anticoagulants, i.e., Protein C, Protein S and Antithrombin III in patients with solid malignancies Methods: A cross-sectional study was conducted wherein plasma levels of Protein C,S and Antithrombin III (AT III) in patients with solid malignancies were determined. The studied parameters included age, gender ,type of the tumor, stage of the cancer and plasma levels of protein C, S and antithrombin.A total of 91 samples from patients with solid tumors were selected using consecutive non-probability sampling method..Protein C,S and antithrombin levels in the plasma were determined using fully automated coagulation analyzer CA-500 (Sysmex Japan). Results: Total 91 patients fulfilled the inclusion criteria. The age range was 30 to 70 years. Mean age was 47.87±13.56 years . Out of the 91 patients, 43 (47.23%) were females and 48 (52.73%) were males, with a male to female ratio of1.1:1. Frequent malignancies noted in males were head and neck (10.98%), GIT (9 %), lymphoma (8.79%). In females breast cancer was the most common cancer accounting for 14.28 % followed by GIT (9.89 %), Head and neck (7.69 %) . Majority of the patients (67%) were in stage IV .Out of 91 patients, 58,2% and 4.4% were found Protein S and C deficient, respectively. AT III levels were above normal in majority (53.8%).With regards to stage of tumor decreased levels of these natural anticoagulants in stage I, II, III and IV were 2.19%, 3.29%, 6.59% and 48.35% respectively . Higher incidence of thrombophilia was noted in patients with Ca breast (20%) followed by tumors of G.I.T and tumours of head and neck due to low levels of Protein S . Conclusion: Increased frequency of thrombophilia is noted in patients with solid tumors (60%).Protein S deficiency is a major factor (92.7% of the total thrombophilic patients) leading to thrombophilic state in cancer population. Key Words: Thrombophilia ,Protein C, Protein S, Antithrombin, Solid tumors Introduction Malignancy is a hypercoagulable state. Majority of patients with solid tumors and leukemias may have subclinical hypercoagulable state with abnormalities of coagulation profiles only.Clinically apparent thromboembolism presents as arterial and venous thrombosis, migratory thrombophlebitis, thrombotic non bacterial endocarditis, thrombotic microangiopathy and/or, disseminated intravascular coagulation. 1 It has leading place among non cancer causes of death in patients with malignancy. Annual death rate for venous thromboembolism in population of cancer patients is 47 fold greater than the general population and the prevalence of unsuspected venous thrmboembolism is 6.3% in cancer patients. 2,3 Pathogenesis of thrombosis in cancer is multifactorial. 4 Deficiencies in Antithrombin III, protein C or protein S, the three core inhibitors of coagulation cascade, substantially increase the risk of venous thromboembolism. 5-11 Clotting activation also plays a role in tumor progression. 1,2 Incidence of thrombosis in malignancy is 15% but in certain tumors e.g pancreatic carcinoma it may be as high as 50%. 1 Thrombotic events can influence the morbidity and mortality of the underlying disease of the patient. Therefore, preventing these complications in cancer patients is a clinically relevant issue. The finding of a strong thrombophilia has several clinical consequences most important being the fact that it decreases the threshold to recommend prophylactic anticoagulation. Identification of several markers of acquired cancer related thrombophilia state is thus necessary to prevent thrombotic events by giving them long term or short term prophylactic anticoagulant therapy. Patients and Methods A total of 91 patients of age range 30 – 70 years affected by gastrointestinal, breast, gynecological and lung cancer of various stages diagnosed on histopathology reports/computed tomography scan or magnetic resonance imaging were included in the study. Patients with known inherited thrombophilia (i.e. Protein C, S deficiency, AT III deficiency, activated