|Year : 2022 | Volume
| Issue : 5 | Page : 359-363
Prognosis of patients with venous thromboembolism and cancer in India
Kereena Chukka, Pritee Sharma, G Satyendra Ramnadh, Vamsikrishna Yerramsetty, Fayazuddin Mohammad, Prem Chand Gupta, Gnaneswar Atturu
Department of Vascular and Endovascular Surgery, Care Outpatient Center, Hyderabad, Telangana, India
|Date of Submission||20-Sep-2022|
|Date of Acceptance||12-Oct-2022|
|Date of Web Publication||13-Jan-2023|
Dr. Kereena Chukka
Department of Vascular and Endovascular Surgery, Care Outpatient Center, Hyderabad, Telangana
Source of Support: None, Conflict of Interest: None
Introduction: Venous thromboembolism (VTE) is common in cancer patients and is considered one of the leading causes of death. Although activation of coagulation system is linked to tumor biology and considered as poor prognostic feature, there are several temporary/provoking factors such as perioperative period, immobilization, and debility that may cause VTE in these patients. It is not clear whether patients with such provoked VTE have different prognoses compared to patients without provoked VTE. Aim: To understand the overall prognosis of patients with cancer-associated thrombosis deep vein thrombosis (DVT) and whether there is a difference in survival between patients who underwent surgery (with or without chemotherapy) and patients who did not undergo surgery. Materials and Methods: This is a combined retrospective and prospective study. Electronic medical records of all patients who underwent VTE treatment between September 2014 and September 2019 were reviewed. Only patients who had DVT in the lower limb associated with malignancy were included in the study. Demographics, clinical, type, stage and type of cancer, and prophylactic treatment received and mortality data were collected. Results: Of 1364 patients treated for VTE, 86 patients (6.3%) had cancer-associated DVT. The mean age was 57 years (range 26–80 years) and 52 patients (60.46%) were female. The most common malignancies were cervix (15.11%), breast (12.79%), and colorectal (12.79%). Majority (68.60%) of the cancer patients were in the stages III and IV, other than having malignancy the most common risk factors were age, obesity, and postsurgery. Forty-three patients had surgery (with or without chemotherapy/radiotherapy). The left leg was commonly involved (53.48%) and the site of thrombus was in iliac (51.68%), femoral (16.85%), or popliteal veins (2.24%). All patients were initially started on low-molecular-weight heparin (LMWH) and then switched to Non-Vitamin K antagonist oral anticoagulants (NOAC) in 29 patients (33.72%) and VKA in 43 patients (50%). In seven patients, LMWH was continued (8.13%). Fifty-seven out of 86 patients (66.27%) were available for follow-up. Eighteen out of 57 patients (31.57%) were alive with an overall mortality of 59.64% and 1 year mortality of 37.5%. In patients who underwent surgery (with or without chemotherapy/radiotherapy), the overall mortality was 58.13% compared to 85.71% in patients who did not undergo surgery. Conclusion: VTE in cancer patients is not uncommon in India and is associated with high mortality. Patients with provoked DVT due to surgery (perioperative period) might have better survival compared to patients who did not undergo surgery.
Keywords: Cancer, deep vein thrombosis, prognosis, venous thromboembolism
|How to cite this article:|
Chukka K, Sharma P, Ramnadh G S, Yerramsetty V, Mohammad F, Gupta PC, Atturu G. Prognosis of patients with venous thromboembolism and cancer in India. Indian J Vasc Endovasc Surg 2022;9:359-63
|How to cite this URL:|
Chukka K, Sharma P, Ramnadh G S, Yerramsetty V, Mohammad F, Gupta PC, Atturu G. Prognosis of patients with venous thromboembolism and cancer in India. Indian J Vasc Endovasc Surg [serial online] 2022 [cited 2023 Jan 28];9:359-63. Available from: https://www.indjvascsurg.org/text.asp?2022/9/5/359/367725
| Introduction|| |
Venous thromboembolism (VTE) is associated with high morbidity and mortality rates. It is estimated that the incidence of VTE at 0.57–2.7 per 1000 population increasing to 7 per 1000 in the older age group above 70 years., Earlier studied from India reported the incidence to be 22 per 10,000, and in the latest study from Pawar et al. reported the incidence is 19.49 per 10,000 admissions. These rates increase by four- to seven-fold in patients with cancer making VTE the second leading cause of death in cancer patients.,,,,, VTE is a spectrum of disease in which clots develop in the venous bed and includes conditions such as pulmonary embolism (PE), deep vein thrombosis (DVT) in the upper extremities (axillary, subclavian, and/or jugular vein) or lower extremities (femoral, popliteal, superficial femoral and/or iliac veins)., Most of the cancer patients presented with bilateral DVT,, in another study, Imberti et al. reported that the rates of symptomatic bilateral lower limb DVT, iliocaval thrombosis, and upper limb DVT were higher in patients with cancer when compared with patients without cancer.
Several factors lead to increased risk of VTE in patients with cancer, including increased blood coagulability resulting from the release of inflammatory cytokines from cancer cells.,, Schmidt et al. in their case–control study reported that the incidence rate increases 3-fold within the 3 months after the infection. Other important independent risk factors such as congestive heart failure, renal disease, pulmonary disease,,,, and arterial thromboembolism are identified for the development of VTE in patients with cancer. Hospitalization, prolonged immobilization, and poor performance status are also considered as major risk factors.
Several studies evaluated the association between cancer type and the risk for developing VTE,, cancer-related (type and stage), and treatment-related (chemotherapy, radiation therapy, surgery, hormone therapy or immune checkpoint inhibitor, and placement of venous catheter)., Side effects of anticoagulation therapy in cancer patients are higher than the general population.
Identifying high-risk patients, understanding the severity by oncologist, and administering prophylactic measures can reduce the morbidity and mortality. There are limited data on the characteristics of DVT with cancer patients in the Indian population; thus, the relative VTE frequencies of cancer patients based on the type and risk factors are not yet understood. Therefore, in the present study, we aim to understand the overall prognosis of DVT with cancer patients and whether there is difference in survival between patients who underwent surgery (with or without chemotherapy) and patients who did not undergo surgery.
| Materials and Methods|| |
Electronic medical records (EMR) of all patients who underwent VTE treatment between September 2014 and September 2019 were reviewed. Patient demographic characteristics and health habits including age, address, gender, smoking, body mass index, significant comorbidities (diabetes, thyroidism, chronic kidney disease, hypertension, and cerebral accidents); clinical characteristics including involved limb, DVT location, anticoagulation treatment, history of immobilization, and any major surgeries done; and cancer type, stage and treatment received, radiological, and mortality data were collected. The data were collected using Google form and converted to excel sheet for analysis.
This is a combined retrospective and prospective study, do not need for ethical approval.
Inclusion and exclusion criteria
- Only adult patients (aged 18 and above) who had DVT in the lower limb associated with malignancy, were included in the study
- Patients with VTE at other sites were excluded from the study.
Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 23.0. (Armonk, NY): IBM Corp, categorical variables were reported as percentages and continuous variables as ranges and mean ± standard deviation.
| Results|| |
A total of 1364 patients were treated for VTE, out of which 86 patients (6.3%) had DVT with cancer. The demographic characteristics and health habits of the included patients are presented in [Table 1]. The mean age was 57 years (range 26–80 years) and 52 patients (60.46%) were female. Other than having malignancy, the most common other risk factors were older age (above 50 years of age; 75.58%), obesity (25.58%), multi-morbidities (26.74%) and postsurgery. Swelling and pain were the most common symptoms and Venous Doppler was commonly used for diagnosis.
|Table 1: Demographic characteristics and health habits of venous thromboembolism with cancer patients (n=86)|
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[Table 2] shows the clinical characteristics of DVT with cancer patients. The left leg was commonly involved (53.48%) and the site of thrombus was in iliac (51.68%), femoral (16.85%), or popliteal veins (2.24%). All patients were initially started on low-molecular-weight heparin (LMWH) and then switched to NOAC in 29 patients (33.72%) and VKA in 43 patients (50%). In seven patients, LMWH was continued (8.13%).
|Table 2: Clinical characteristics of venous thromboembolism with cancer patients (n=86)|
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[Table 3] shows the cancer stage, treatment received in patients with cancer-associated thrombosis (CAT). Majority (68.60%) of the cancer patients were in the Stage III and 43 patients had surgery (with or without chemotherapy/radiotherapy). [Table 4] shows the type of cancer and mortality rate among CAT patients. The most common malignancies were cervix (15.11%), breast (12.79%), colorectal (12.79%), and lung (10.46%). Fifty-seven out of 86 patients (66.27%) were available for follow-up. Eighteen out of 57 patients (31.57%) were alive with an overall mortality of 59.64% and 1-year mortality of 37.5%. In patients who underwent surgery (with or without chemotherapy/radiotherapy), the overall mortality was 58.13% compared to 85.71% in patients who did not undergo surgery.
|Table 3: Cancer stage and type of treatment received in venous thromboembolism patients with cancer|
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|Table 4: Cancer types, and mortality rate among venous thromboembolism with cancer patients (n=86)|
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| Discussion|| |
Cancer and the occurrence of VTE were strongly associated. Studies have shown that the incidence of DVT was significantly lower among Asian DVT with cancer patients when compared to the western population incidence reports. Among all first VTE events, the proportion of CAT was higher in this study than that reported by Western studies.,, Appropriate prophylactic anticoagulation therapy in cancer patients can reduce the thrombotic events, clinical hypercoagulable state, and worse prognosis.,
In the present study, out of 1364 patients treated for VTE, 86 patients (6.3%) had cancer-associated DVT. The mean age was 57 years (range 26–80 years) and 52 patients (60.46%) were females and Obesity (25.58%). Advanced age and obesity are associated with an increased risk for DVT with cancer patients in some clinical settings.,,, The changing patient baseline characteristics with increasing proportion of older patients with cancer may further increase the incidence of CAT., Active cancer is one of the important predictors for DVT recurrence, to predict the risk of DVT and its recurrence in cancer patients, clinicians must consider existing cancer conditions including site, stage, and treatment type. Patient-related factors including age, previous history of DVT, comorbidities, and immobilization also plays an important role in the development of DVT.,
In the present study, high-risk predictors for DVT among cancer patients are females, cancer type (cervix, breast, colorectal, and lung), stages III and IV. Improvements in prognosis and quality of life of these patients can be achieved through anticoagulant prophylaxis aimed at preventing DVT incidents. DVT with cancer patients is treated with both LMWH and VKA. In the present study, all patients were initially started on LMWH and then switched to NOAC in 29 patients (33.72%) and VKA in 43 patients (50%). Based on the meta-analysis study, LMWH is recommended for the treatment than VKA. However, because of the heterogeneous of cancer biology, types, and stages, further studies are needed to better understand the clinical spectrum of DVT patients with cancer. In the present study, medical comorbidities (26.74%) were identified as one of the important risk factors for the patients with CAT.
Mortality was significantly higher in cancer patients who developed VTE as compared to those who did not. In the present study, we did not compare the duration of the survival between patients with or without cancer. Eighteen out of 57 patients (31.57%) were alive with an overall mortality of 59.64% and 1 year mortality of 37.5%. The results indicated that the risk of death increased in the first 6 months after the diagnosis of VTE.
Limitations of the study
Although we collected a retrospective and prospective data through EMR and telephonic follow-up for all possible cases of VTE in our hospital, we cannot claim complete case ascertainment of index DVT with cancer events, detailed anticoagulation management after hospital discharge, recurrence, or major bleeding. Therefore, we cannot comment on the impact of use or nonuse of anticoagulation.
| Conclusion|| |
VTE in cancer patients is not uncommon in India and is associated with high morbidity mortality. Patients with provoked DVT due to surgery (perioperative period) might have better survival compared to patients who did not undergo surgery. Early identification and treatment could help in reducing the morbidity and mortality in this high-risk group. Future prospective studies with larger number cohorts will lead to a better understanding of clinical spectrum among these patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Raskob GE, Angchaisuksiri P, Blanco AN, Buller H, Gallus A, Hunt BJ, et al
. Thrombosis: A major contributor to global disease burden. Arterioscler Thromb Vasc Biol 2014;34:2363-71.
Bell EJ, Lutsey PL, Basu S, Cushman M, Heckbert SR, Lloyd-Jones DM, et al
. Lifetime risk of venous thromboembolism in two cohort studies. Am J Med 2016;129:26.e19-26.
Lee AD, Stephen E, Agarwal S, Premkumar P. Venous thrombo-embolism in India. Eur J Vasc Endovasc Surg 2009;37:482-5.
Pawar P, Ayyappan MK, Jagan J, Rajendra N, Mathur K, Raju R. Analysis of patients with venous thromboembolism in a multi-specialty tertiary hospital in South India. Indian J Vasc Endovasc Surg 2020;7:29-33. [Full text]
Khalil J, Bensaid B, Elkacemi H, Afif M, Bensaid Y, Kebdani T, et al
. Venous thromboembolism in cancer patients: An underestimated major health problem. World J Surg Oncol 2015;13:204.
Sørensen HT, Mellemkjaer L, Olsen JH, Baron JA. Prognosis of cancers associated with venous thromboembolism. N Engl J Med 2000;343:1846-50.
Chew HK, Wun T, Harvey D, Zhou H, White RH. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med 2006;166:458-64.
Blom JW, Doggen CJ, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 2005;293:715-22.
Walker AJ, Card TR, West J, Crooks C, Grainge MJ. Incidence of venous thromboembolism in patients with cancer – A cohort study using linked United Kingdom databases. Eur J Cancer 2013;49:1404-13.
Khorana AA. Venous thromboembolism and prognosis in cancer. Thromb Res 2010;125:490-3.
Bartholomew JR. Update on the management of venous thromboembolism. Cleve Clin J Med 2017;84:39-46.
Bura A, Cailleux N, Bienvenu B, Léger P, Bissery A, Boccalon H, et al
. Incidence and prognosis of cancer associated with bilateral venous thrombosis: A prospective study of 103 patients. J Thromb Haemost 2004;2:441-4.
Seinturier C, Bosson JL, Colonna M, Imbert B, Carpentier PH. Site and clinical outcome of deep vein thrombosis of the lower limbs: An epidemiological study. J Thromb Haemost 2005;3:1362-7.
Imberti D, Agnelli G, Ageno W, Moia M, Palareti G, Pistelli R, et al.
Clinical characteristics and management of cancer-associated acute venous thromboembolism: Findings from the MASTER Registry. Haematologica 2008;93:273-8.
Hisada Y, Mackman N. Cancer-associated pathways and biomarkers of venous thrombosis. Blood 2017;130:1499-506.
Falanga A, Russo L, Milesi V, Vignoli A. Mechanisms and risk factors of thrombosis in cancer. Crit Rev Oncol Hematol 2017;118:79-83.
Ikushima S, Ono R, Fukuda K, Sakayori M, Awano N, Kondo K. Trousseau's syndrome: Cancer-associated thrombosis. Jpn J Clin Oncol 2016;46:204-8.
Ay C, Pabinger I, Cohen AT. Cancer-associated venous thromboembolism: Burden, mechanisms, and management. Thromb Haemost 2017;117:219-30.
Schmidt M, Horvath-Puho E, Thomsen RW, Smeeth L, Sørensen HT. Acute infections and venous thromboembolism. J Intern Med 2012;271:608-18.
Tang L, Wu YY, Lip GY, Yin P, Hu Y. Heart failure and risk of venous thromboembolism: A systematic review and meta-analysis. Lancet Haematol 2016;3:e30-44.
Lu HY, Liao KM. Increased risk of deep vein thrombosis in end-stage renal disease patients. BMC Nephrol 2018;19:204.
Børvik T, Brækkan SK, Enga K, Schirmer H, Brodin EE, Melbye H, et al
. COPD and risk of venous thromboembolism and mortality in a general population. Eur Respir J 2016;47:473-81.
Kim V, Goel N, Gangar J, Zhao H, Ciccolella DE, Silverman EK, et al
. Risk factors for venous thromboembolism in chronic obstructive pulmonary disease. Chronic Obstr Pulm Dis 2014;1:239-49.
Piazza G, Goldhaber SZ, Kroll A, Goldberg RJ, Emery C, Spencer FA. Venous thromboembolism in patients with chronic obstructive pulmonary disease. Am J Med 2012;125:1010-8.
Bertoletti L, Quenet S, Laporte S, Sahuquillo JC, Conget F, Pedrajas JM, et al
. Pulmonary embolism and 3-month outcomes in 4036 patients with venous thromboembolism and chronic obstructive pulmonary disease: Data from the RIETE registry. Respir Res 2013;14:75.
Eliasson A, Bergqvist D, Björck M, Acosta S, Sternby NH, Ogren M. Incidence and risk of venous thromboembolism in patients with verified arterial thrombosis: A population study based on 23,796 consecutive autopsies. J Thromb Haemost 2006;4:1897-902.
Flinterman LE, van Hylckama Vlieg A, Rosendaal FR, Cannegieter SC. Body height, mobility, and risk of first and recurrent venous thrombosis. J Thromb Haemost 2015;13:548-54.
Khorana AA, Dalal M, Lin J, Connolly GC. Incidence and predictors of venous thromboembolism (VTE) among ambulatory high-risk cancer patients undergoing chemotherapy in the United States. Cancer 2013;119:648-55.
Ogren M, Bergqvist D, Wåhlander K, Eriksson H, Sternby NH. Trousseau's syndrome – What is the evidence? A population-based autopsy study. Thromb Haemost 2006;95:541-5.
Streiff MB, Holmstrom B, Angelini D, Ashrani A, Elshoury A, Fanikos J, et al.
Cancer-associated venous thromboembolic disease, version 2.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2021;19:1181-201.
Fernandes CJ, Morinaga LT, Alves JL Jr., Castro MA, Calderaro D, Jardim CV, et al
. Cancer-associated thrombosis: The when, how and why. Eur Respir Rev 2019;28:180119.
Prandoni P, Piccioli A, Girolami A. Cancer and venous thromboembolism: An overview. Haematologica 1999;84:437-45.
Timp JF, Braekkan SK, Versteeg HH, Cannegieter SC. Epidemiology of cancer-associated venous thrombosis. Blood 2013;122:1712-23.
Noboa S, Mottier D, Oger E, EPI-GETBO Study Group. Estimation of a potentially preventable fraction of venous thromboembolism: A community-based prospective study. J Thromb Haemost 2006;4:2720-2.
Kok VC. Bidirectional risk between venous thromboembolism and cancer in East Asian patients: Synthesis of evidence from recent population-based epidemiological studies. Cancer Manag Res 2017;9:751-9.
Yu Y, Lv Q, Zhang B, Lan F, Dai Y. Adjuvant therapy with heparin in patients with lung cancer without indication for anticoagulants: A systematic review of the literature with meta-analysis. J Cancer Res Ther 2016;12:37-42.
Liu ZL, Wang Q, Wang M, Wang B, Huang LN. Low molecular weight heparin in treating patients with lung cancer received chemotherapy: A meta-analysis. J Cancer Res Ther 2018;14:S437-43.
Khorana AA, Francis CW, Culakova E, Fisher RI, Kuderer NM, Lyman GH. Thromboembolism in hospitalized neutropenic cancer patients. J Clin Oncol 2006;24:484-90.
Agnelli G, Bolis G, Capussotti L, Scarpa RM, Tonelli F, Bonizzoni E, et al
. A clinical outcome-based prospective study on venous thromboembolism after cancer surgery: The @RISTOS project. Ann Surg 2006;243:89-95.
Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008;111:4902-7.
Connolly GC, Khorana AA. Emerging risk stratification approaches to cancer-associated thrombosis: Risk factors, biomarkers and a risk score. Thromb Res 2010;125 Suppl 2:S1-7.
Louzada ML, Carrier M, Lazo-Langner A, Dao V, Kovacs MJ, Ramsay TO, et al
. Development of a clinical prediction rule for risk stratification of recurrent venous thromboembolism in patients with cancer-associated venous thromboembolism. Circulation 2012;126:448-54.
Chee CE, Ashrani AA, Marks RS, Petterson TM, Bailey KR, Melton LJ 3rd
, et al
. Predictors of venous thromboembolism recurrence and bleeding among active cancer patients: A population-based cohort study. Blood 2014;123:3972-8.
Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients. Cancer 2007;110:2339-46.
Louzada ML, Majeed H, Wells PS. Efficacy of low- molecular- weight- heparin versus vitamin K antagonists for long term treatment of cancer-associated venous thromboembolism in adults: A systematic review of randomized controlled trials. Thromb Res 2009;123:837-44.
Amer MH. Cancer-associated thrombosis: Clinical presentation and survival. Cancer Manag Res 2013;5:165-78.
[Table 1], [Table 2], [Table 3], [Table 4]