ORIGINAL ARTICLE Year : 2022  |  Volume : 9  |  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 Submission20-Sep-2022Date of Acceptance12-Oct-2022Date of Web Publication13-Jan-2023

Correspondence Address:
Dr. Kereena Chukka
Department of Vascular and Endovascular Surgery, Care Outpatient Center, Hyderabad, Telangana
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/ijves.ijves_68_22

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 14];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.[1],[2] Earlier studied from India reported the incidence to be 22 per 10,000,[3] and in the latest study from Pawar et al. reported the incidence is 19.49 per 10,000 admissions.[4] These rates increase by four- to seven-fold in patients with cancer making VTE the second leading cause of death in cancer patients.[5],[6],[7],[8],[9],[10] 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).[11],[12] Most of the cancer patients presented with bilateral DVT,[13],[14] in another study, Imberti et al.[15] 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,[16] including increased blood coagulability resulting from the release of inflammatory cytokines from cancer cells.[17],[18],[19] Schmidt et al.[20] 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,[21] renal disease,[22] pulmonary disease,[23],[24],[25],[26] and arterial thromboembolism[27] 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.[28]

Several studies evaluated the association between cancer type and the risk for developing VTE,[29],[30] cancer-related (type and stage), and treatment-related (chemotherapy, radiation therapy, surgery, hormone therapy or immune checkpoint inhibitor, and placement of venous catheter).[31],[32] 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.

Ethics

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 studyPatients with VTE at other sites were excluded from the study.

Statistical analysis

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.[33] 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.[34],[35],[36] Appropriate prophylactic anticoagulation therapy in cancer patients can reduce the thrombotic events, clinical hypercoagulable state, and worse prognosis.[37],[38]

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.[39],[40],[41],[42] The changing patient baseline characteristics with increasing proportion of older patients with cancer may further increase the incidence of CAT.[43],[44] Active cancer is one of the important predictors for DVT recurrence,[44] 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.[34],[45]

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,[46] 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.[47] 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

Nil.

Conflicts of interest

There are no conflicts of interest.

 

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  [Table 1], [Table 2], [Table 3], [Table 4]