Menoufia Medical Journal

ORIGINAL ARTICLE
Year
: 2019  |  Volume : 32  |  Issue : 4  |  Page : 1328--1332

Recent trends in the management of deep vein thrombosis in cancer patients


Nehad A Zaid1, Mahmoud S Abd El-Haleem1, Ali M. S El-Sayed Shaat2,  
1 General and Vascular Surgery Department, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt
2 General and Vascular Surgery Department, Ahmed Maher Teaching Hospital, Cairo, Egypt

Correspondence Address:
Ali M. S El-Sayed Shaat
General and Vascular Surgery Department, Ahmed Maher Teaching Hospital, Cairo
Egypt

Abstract

Objective To focus on the recent trends in the management of deep vein thrombosis (DVT) in malignancy as well as its fatal complications. Background DVT is usually silent in nature in most of the hospitalized patients and is usually presented by nonspecific symptoms and signs. Patients and methods A prospective study was carried out on 60 patients at Ahmed Maher Teaching Hospital between 2017 and 2018. The patients were divided into two groups: the first group composed of 30 cancer patients on whom prophylactic measures against venous thromboembolism was applied for 8 months and the second group composed of 30 cancer patients with a history of DVT and who had undergone management and follow-up for 3–6 months. Full history, routine, physical examination, routine investigations, and coagulation profile were done. Results The mean age of the prevention group was 54.87 ± 11.34 and 59.10 ± 12.50 in the management group. The incidence of DVT was 16.7%. In the management group, the rate of resolution of DVT without complications after being treated with low molecular weight heparin (LMWH) for 6 months was 66. The rate of cases developed pulmonary embolism from the management group was 10%. The rate of deaths due to DVT and its complications was 3.3%. Conclusion LMWH prophylaxis in patients undergoing cancer-related surgery has proved to be effective and safe in reducing the risk of an acute event. Thromboprophylaxis with LMWH, unfractionated heparin, and mechanical methods should be considered for all patients with a malignancy who undergo surgery.



How to cite this article:
Zaid NA, Abd El-Haleem MS, El-Sayed Shaat AM. Recent trends in the management of deep vein thrombosis in cancer patients.Menoufia Med J 2019;32:1328-1332


How to cite this URL:
Zaid NA, Abd El-Haleem MS, El-Sayed Shaat AM. Recent trends in the management of deep vein thrombosis in cancer patients. Menoufia Med J [serial online] 2019 [cited 2020 May 31 ];32:1328-1332
Available from: http://www.mmj.eg.net/text.asp?2019/32/4/1328/274273


Full Text



 Introduction



The complications of deep vein thrombosis (DVT) are one of the most common causes of hospital death, ~300 000 die per year in the USA from pulmonary embolism (PE), the majority of which results from DVT [1]. Understanding the underlying epidemiology, pathophysiology, and natural history in DVT is essential in guiding appropriate prophylaxis, diagnosis, and treatment. DVT is usually silent in nature in most of the hospitalized patients and is usually presented by nonspecific symptoms and signs [2]. In 1856, a German pathologist (Rudolf Virchow) postulated the interplay of three processes resulting in venous thrombosis known as Virchow's triad; this triad is a description for the components of the risk factors of DVT, which include abnormalities of thrombosis, abnormalities of blood flow, and abnormalities in the vessel wall [3]. Malignancy is considered one of the most important risk factors of the DVT and that is what we are targeting in this research. Patients with cancer are at an increased risk of venous thromboembolism (VTE). Approximately 15% of malignancies are complicated by VTE with higher prevalence in autopsy studies [2]. Several structured scoring systems have been developed and introduced; the most widely used and well-studied is the Wells score. It utilizes information from medical history and physical examination and consists of nine items that initially categorized patients into 'likely' and 'unlikely' patients to develop DVT [4]. Thrombogenic mechanisms associated with cancer may be heterogeneous, but likely involve substances that directly or indirectly activate coagulation. About 90% of patients with cancer have abnormal coagulation parameters including increased coagulation factors, fibrinogen, and thrombocytosis. The levels of coagulation inhibitors, antithrombin, and protein C and protein S may be reduced in malignancy [5]. Clinical trials have shown that thromboprophylaxis reduces the incidence of DVT in cancer patients. We are aiming for prevention, early diagnosis, and treatment of DVT [6]. Diagnosis of DVT is very challenging as the limb that appears clinically normal may have a life-threatening clot. On the other hand, the limb with typical symptoms and signs of DVT may prove to be normal. Diagnosis is by clinical assessment, imaging, and by biological tests [7]. There are two methods of prophylaxis: the first one is nonpharmacological by elastic stocking, good hydration, postoperative early ambulation, and active leg exercises, and the second method is pharmacological like heparin, low molecular weight heparin (LMWH), oral anticoagulant or vitamin K antagonist and new oral anticoagulant. Treatment of DVT include general measures like bed rest and limb elevation, use of unfractionated heparin, LMWH, oral anticoagulants, new oral anticoagulants, thrombolytic agents, or surgical treatment [8]. The aim of this study was to focus on the recent trends in the management (diagnosis and treatment) of DVT in malignancy as well as its fatal complications.

 Patients and Methods



A prospective study was carried out on 60 patients at Ahmed Maher Teaching Hospital between August 2017 and August 2018. All studied patients were divided into two groups: group I: the first group is composed of 30 cancer patients on whom prophylactic measures against VTE will be applied for 8 months.

Inclusion criteria

Active cancer patients

Patients on treatment for cancer, patients received treatment for cancer within previous 6 months, and patients receiving palliative treatment were excluded.

Motivation and acceptance to follow instructions, medications, and data collection.

Exclusion criteria

Patients having DVT (and/or PE), active internal bleeding, recent cerebrovascular accident, recent major surgery, recent serious gastrointestinal bleeding, recent serious trauma, severe uncontrolled hypertension, pregnancy and puerperium, and patient refusal to participate in the study were excluded.

Group II: the second group is composed of 30 cancer patients who already have DVT and will undergo management and follow-up for 3–6 months.

Inclusion criteria

Active cancer patients (patient on treatment for cancer, patient received treatment for cancer within previous 6 months, patient receiving palliative treatment) and patients having DVT (and/or) PE, motivation, and acceptance to follow instructions, medications, and data collection are included.

Exclusion criteria

Patients excluded were those with high-risk of bleeding (peptic ulcer, esophageal varices, history of hemorrhagic strokes), active internal bleeding, recent cerebrovascular accident, allergy to thrombolytic agents, recent major surgery, recent serious gastrointestinal bleeding, recent serious trauma, severe uncontrolled hypertension, pregnancy, and puerperium, and those who refused to participate in the study.

Ethical consideration

The study was approved by the Ethics Committee of Menoufia Faculty of Medicine and an informed consent was obtained from all patient's guardian before the study was started.

Method of sampling

Sample size was calculated using computer sample block randomization type. Samples were obtained during routine investigations. A 5 ml sample of venous blood was drained by sterile syringes, and was put in a tube containing dipotassium EDTA reagent; the sample was shaken gently and analyzed by Medonic 20 (IndiaMART, New Delhi, India ).

All cases were subjected to the following: full history in detail, including age, obesity, prolonged bed rest, smoking, previous documented DVT, present illness and history of chemotherapy, stressing on history of recent leg swelling and/or aching pain. Special attention to past history of recent operations, hip trauma, cerebrovascular accidents, and coronary attacks was done to exclude patients unfit for thrombolytic therapy. Clinical examination: general examination included recording of vital signs (pulse, blood pressure, temperature, and respiratory rate) in every patient. The patients were also examined for signs of PE (chest pain, cyanosis, tachycardia, and tachypnea). Abdominal examination was performed to exclude masses compressing large (iliac) veins. Local examination: individual signs and symptoms are of relatively little value in the diagnosis of DVT, the lower limb is inspected for any swelling, collateral superficial (nonvaricose) veins, color changes either whitish or bluish, and for signs of superficial thrombophlebitis.

Investigations

Routine investigations

Duplex study of the venous system of the suspected limb was performed to confirm the diagnosis and define the extent and level of DVT. d-Dimer is the best recognized biomarker for the initial assessment of suspected VTE. A combination of clinical risk stratification and a d-dimer test can exclude VTE in more than 25% of patients presenting with symptoms suggestive of VTE without the need for additional investigations. Complete blood count included platelet count and hemoglobin level using the Sysmex KX-21 automatized hematology analyzer (Sysmex corporation, Japan). Coagulation profile included prothrombin time and activated partial thromboplastin time. Prophylaxis: The first group received drugs as LMWH or heparin as prophylaxis for 1 week starting 12 h before the operation and for at least 10 days postoperatively and for up to 4 weeks after major abdominal or pelvic surgery. Also, mechanical thromoprophylactic measures were applied. Treatment: The second group was treated either with LMWH for at least 6 months and treatment could be extended up to 1 year in patients with high-risk factors for recurrence or patients who show recurrence despite anticoagulation or with initial anticoagulant with LMWH for 10 days, with early initiation of a vitamin K antagonist such as warfarin for 6 months up to 1 year.

Statistical analysis

The results were tabulated and statistically analyzed by using a personal computer using Microsoft Excel 2016 and SPSS version 21 (SPSS Inc., Chicago, Illinois, USA). Statistical analysis was done using: descriptive statistics, for example, percentage, mean and SD. A value of P less than 0.05 was considered statistically significant.

 Results



Results showed that out of the 30 patients of the prevention group included in this study, eight (26.7%) of were women and 22 (73.3%) were men. The age of the patients ranged between 33 and 82 years with a mean age of the patients being 53 years. Six (20%) patients had a special habit of smoking, in the treatment group they were seven (23.3%), there were nine (30%) patients who had a history of obesity, while in the treatment group, there were five (16.7%). There were three (10%) patients with a history of arterial embolism in the form of ischemic heart disease. There were three (10%) patients with a history of previous DVT. The most common malignancies to develop DVT were malignancies of the pancreas, colon and the stomach [Table 1]. In cancer patients undergoing surgery without thromboprophylaxis, the rates of DVT and fatal PE ranges from 15 to 30 and 0.2 to 0.9%, respectively. The incidence of DVT in this study was 16.7% and the incidence of fatal PE was 0% [Table 2]. Out of the 30 patients of the treatment group included in this study 12 (40%) were women and 18 (60%) were men. The age of the patients ranged between 33 and 82 years with a mean age of the patients being 59 years. Seven (23.3%) had a special habit of smoking. Five (16.7%) patients had a history of obesity. There were three (10%) patients with a history of arterial embolism in the form of ischemic heart disease. Six (20%) patients had a history of DVT [Table 3]. Regarding the management group in the present study, the rate of resolution of DVT without complications after being treated with LMWH for 6 months was 66.7%; the rate of cases who developed PE from the management group was 10%. The rate of deaths due to DVT and its complications was 3.3% [Table 4].{Table 1}{Table 2}{Table 3}{Table 4}

 Discussion



In the current study, eight (26.7%) patients of the prevention group were women and 22 (73.3%) were men. Their age ranged from 33 to 82 years with a mean age of 53 years, whereas 12 (40%) patients of the treatment group were women and 18 (60%) were men. Their age ranged from 33 and 82 years with a mean age of 59 years. These results agree with a study done by Giorgio et al. [9], in which 74 patients were included, 41 (55.4%) of them were men and 33 (44.6%) were women with a mean age of 63.6 years. In another study conducted by Kroger et al. [10] there were 507 surgical cancer patients (53% male and 47% females with mean age 68 years). In the present study, six (20%) patients of the prevention group had a special habit of smoking, in the treatment group they were seven (23.3%). Also nine (30%) patients of the prevention group had a history of obesity, while in the treatment group, there were five (16.7%) similar to the study done by David et al. [11] in which the percentage of obesity of cancer patients undergoing surgery was 35.4%. In the present study, three (10%) patients of the prevention group as well as the treatment group had a history of arterial embolism in the form of ischemic heart disease, which agrees with a study done by Alok et al. [12] where the rate of the patients with a positive history of IHD were 17.4%. In the current study, three (10%) patients of the prevention group gave a history of DVT, while in the treatment group there were six (20%), which disagrees with the results of the study by Kroger et al. [10] with a history of DVT in 33% of the patients. Regarding the base data of the present study, it agrees with the results by Hotoleanu and Aurel [13] in which there were 181 surgical patients, 120 (66.8%) patients were men and 61 (33.2%) were women with a mean age of 58.57. Also, patients who had a smoking habit were 81 (44.6%) patients and patients with a history of DVT were 30% of the included patients in the study. In this study, the most common malignancies to develop DVT were malignancies of the pancreas, colon and the stomach, which agrees with a study done by Qureshi et al. [14] where the most common malignancies to develop DVT were brain tumors, pancreatic, stomach, uterine, and lung carcinomas. Another study done by Falanga et al. [15] showed that pancreatic cancer is considered to be on the top of solid tumors with a high-risk of VTE. Diagnosis of patients with acute DVT was achieved after subjecting the patients to detailed history taking, general examination, local examination of the suspected lower limb, and investigations that involved routine laboratory work and duplex study of the venous system. Leefmans and Czeredarczuk [16] suggested the same diagnostic criteria. In cancer patients undergoing surgery without thromboprophylaxis, the rates of DVT and fatal PE ranges from 15 to 30 and 0.2 to 0.9%, respectively. The clinical value of thromboprophylaxis has been confirmed by a meta-analysis of randomized trials in which the prophylactic regimens was compared with no prophylaxis. The frequency of DVT was significantly reduced by thromoprophylactic measures from 22 to 9% and fatal PE from 0.8 to 0.3% [17]. The incidence of DVT in this study was 16.7% and the incidence of fatal PE was 0%. These results resemble the data published by Agnelli and Becattini [17]. Another study made by Niklus et al. [18] has shown that the incidence of DVT among cancer patients, who used a preoperative thromboprophylactic regimen, postsurgery was12.4% which agrees with the current study. Regarding the management group in the present study, the rate of resolution of DVT without complications after being treated with LMWH for 6 months was 66.7%, while in a study done by Maxwell and Bennett [2] 87% of patients experienced complete or partial resolution of the signs and symptoms of DVT. In the current study, the rate of cases developed PE from the management group was 10%, which is not far from a study done by Maxwell and Bennett [2], where pulmonary embolus occurred in 4% of the patients. In the current study, 3.3% of the management group died from DVT and its complications was 3.3%, while in a study done by Maxwell and Bennett [2], death due to DVT was also relatively uncommon (2%).

 Conclusion



LMWH prophylaxis in patients undergoing cancer-related surgery has proved to be effective and safe in reducing the risk of an acute event. The author recommends the use of thromboprophylaxis with LMWH, unfractionated heparin, and mechanical methods for all patients with a malignancy who undergo surgery and the use of LMWH in the treatment of cancer patients with DVT.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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