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 Table of Contents  
Year : 2017  |  Volume : 8  |  Issue : 3  |  Page : 85-98

Implementation of international good clinical practice guidelines to improve care of patients with cancer-related venous thromboembolism

1 Department of Hematology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
2 Assistance Publique-Hôpitaux de Marseille, Hematology laboratory, La Timome University Hospital; Aix-Marseille University, INSERM UMRS 1076, VRCM, Marseille; Paris 7 -Diderot University, INSERM UMRS 960, Sorbonne Paris Cité, Paris, France
3 Assistance Publique-Hôpitaux de Paris, Saint-Louis Hospital, Internal, Medicine and Vascular Disease Unit; Paris 7 -Diderot University, INSERM U 796, Sorbonne Paris Cité, Paris, France
4 Assistance Publique-Hôpitaux de Paris, Saint-Louis Hospital, Groupe Francophone Thrombose et Cancer, Paris, France

Date of Web Publication18-Sep-2017

Correspondence Address:
Dominique Farge
Assistance Publique-Hôpitaux de Paris, Saint-Louis Hospital, Internal Medicine and Vascular Disease Unit, 1 avenue Claude Vellefaux, 75010 Paris
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/joah.joah_32_17

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Over the past 20 years, venous thromboembolism (VTE) has become the second cause of death in cancer patients, where it accounts for increased morbidity, mortality, and health-care costs. Incidental VTE is increasingly diagnosed on systematic computed tomography scan evaluations, raising new questions in daily oncology practice. The exact mechanisms underlying the increase in cancer-related VTE are not fully understood. Risk factors include patient-related, cancer-related, and treatment-related parameters which vary for a single patient throughout cancer disease and which require repeated individual risk assessments. Cumulative results from studies in cancer patients with versus without VTE suggest that anticoagulation therapy prevents morbidity and may reduce mortality. However, despite the availability of effective and safe therapeutic options, VTE is often underrecognized and sub-optimally managed. Clinical practice guidelines addressing the management of VTE in cancer patients are heterogeneous and require adequate educational and active implementation strategies. This review, resulting from an extensive literature search, aims to summarize the recently published evidence-based guidelines for treatment and prophylaxis of cancer-related VTE, as well as the place of new oral anticoagulants in the treatment strategies. Adherence to guidelines could substantially decrease the burden of VTE and increase survival in cancer patients.

Keywords: Anticoagulants, cancer, catheter-related thrombosis, clinical practice guidelines, venous thromboembolism

How to cite this article:
Qari R, Frere C, Farge D, El Ayoubi H. Implementation of international good clinical practice guidelines to improve care of patients with cancer-related venous thromboembolism. J Appl Hematol 2017;8:85-98

How to cite this URL:
Qari R, Frere C, Farge D, El Ayoubi H. Implementation of international good clinical practice guidelines to improve care of patients with cancer-related venous thromboembolism. J Appl Hematol [serial online] 2017 [cited 2023 Sep 30];8:85-98. Available from: https://www.jahjournal.org/text.asp?2017/8/3/85/214997

Dominique Farge, Hanadi El Ayoubi.
Contributed equally to the manuscript.

  Introduction Top

Venous thromboembolism (VTE) is an independent prognostic factor of mortality in cancer patients,[1] and its management remains a great challenge in oncology. Clinical practice guidelines (CPG) addressing the treatment and prophylaxis of cancer-associated VTE are heterogeneous and sub-optimally implemented worldwide.

With the objective to homogenize existing guidelines and enhance their dissemination, we performed an extensive literature analysis of the studies and guidelines published over the last decades and summarized the recommendations for management of VTE, including the role of direct oral anticoagulants (DOACs) in the treatment strategies. All recommendations were formulated according to an evidence-based medicine approach, using the grading system [Table 1].
Table 1: Grading of Recommendations Assessment Development and Evaluation scale*

Click here to view

  Background Top

VTE is a significant cause of morbidity and mortality in patients with cancer.[1] The close relationship between cancer and thrombosis is known since 1865 when Armand Trousseau first described the clinical association between idiopathic VTE and occult malignancy. Cancer may affect all three components of the Virchow triad: venous stasis, blood components, and vessel damage, thereby inducing the alteration of normal blood flow and increasing the risk of thrombus formation.[2],[3] This hypercoagulable state associated with cancer results in a fourfold increase in thrombosis risk and a higher risk of mortality, irrespective of cancer stage,[4],[5] and chemotherapy elevates this risk even more. More importantly, we witnessed a steady increase in the incidence of cancer-associated thrombosis over the past decade,[6],[7] probably due to patient's increasing age, greater thrombogenicity of chemotherapy regimens, and better detection of incidental thrombosis. At present, VTE has become the second leading cause of death in cancer patients after metastasis [8] and represents an independent prognostic factor of death in patients with cancer.

Even though thromboembolic diseases are a rather common complication in oncology patients worldwide, there has been limited advancement in the management of cancer-associated thrombosis since the introduction of low-molecular-weight heparin (LMWH) for long-term therapy. In fact, treatment of VTE in the cancer population remains a great challenge.[9] Numerous published studies support the evidence of an inconsistent and inadequate implementation of existing CPG, which is likely a factor for the lack of consensus and the heterogeneity of management and prophylaxis strategies in clinical practice.[10],[11],[12],[13],[14],[15] Further, anticoagulant therapy remains a burden and is viewed as having a negative impact on patient's quality of life. It is associated with greater risks of VTE recurrence and major bleeding complications [16] and may limit the therapeutic options to treat underlying cancer.

Burden of cancer and venous thromboembolism in Saudi Arabia

Cancer is the third cause of death in Saudi Arabia (SAR) after cardiovascular diseases and communicable diseases and it represented 10% of the death rate in 2014 according to the WHO report.[17]

Clinical data from SAR related to VTE in cancer patients are scarce. In a retrospective study of 701 patients with solid tumors or lymphoma treated at a tertiary care center in Riyadh from 2004 to 2009, VTE was diagnosed in 6.7% with 79% of VTE patients having an advanced cancer stage.[18]

A retrospective review of 2286 patients treated in SAR for cancer between January 2013 and December 2014 revealed that VTE was diagnosed in 144 patients (6.3%) of total oncology center admissions. The mean age of the studied group was 53.2 years. Pulmonary embolism (PE) was documented in 39% while 61.8% had deep vein thrombosis (DVT). Fifty-two percent of the patients had distant metastasis. The mortality during the study period was about 31.8% in patients with VTE. The risk was higher in patients with advanced carcinoma stages, poor Eastern Cooperative Oncology Group performance status, and gastrointestinal adenocarcinoma.[19]

Recently, a single institute from SAR reported 132 (7.87%) VTE cases among 1678 cancer patients, with female to male ratio 1.3/1. Thirty-one patients (23.5%) were diagnosed with VTE and cancer simultaneously, 74 patients (56.1%) were on chemotherapy, and 28 patients (21.2%) were on best supportive care. VTE was symptomatic in 110 patients (83.3%) and asymptomatic in 22 patients (16.7%). Lower limbs were the most common site (42.4%), with the highest incidence in patients with advanced stages (93%). Forty-nine (37%) patients were receiving LMWH as prophylaxis. Median survival in months for patients with VTE prophylaxis versus without prophylaxis and asymptomatic versus symptomatic was 12.6 versus 6.3 (P = 0.12) and 9.8 versus 12.4 (P = 0.885), respectively.[20]

Such studies from the developing world highlighted the underutilization of thromboprophylaxis, the necessity of early detection and the need to adopt guidelines tailoring the regimen to the risk of developing thromboembolic complications in cancer patients.

Venous thromboembolism is a major health issue in patients with cancer

Up to 20% of cancer patients present at least one VTE event, with DVT, PE, and catheter-related thrombosis (CRT) being the most common venous thrombotic complications.[11] Compared to noncancer patients, cancer patients have 4-fold–6-fold increased risk of VTE, 3-fold increased risk of recurrence of VTE, and 2-fold increased risk of postoperative VTE. The risk of VTE also varies according to the course of malignancy, from diagnosis through treatment, remission, metastasis, and end-of-life care.[12],[13]

The incidence of VTE in patients with cancer has increased in recent years.[17],[21] The observed worldwide increase in rates of VTE, particularly in treated patients (47% in chemotherapy treated patients versus 26% for those not receiving chemotherapy), might be explained in part by the use of newer chemotherapy agents.[21] Better performance of diagnostic technologies may also have played a role, with a trend, for example, of an increased likelihood of PE diagnosis in patients undergoing systematic staging computed tomographic (CT) scans and follow-up evaluations.[21]

Venous thromboembolism is one of the most common preventable causes of inpatient mortality

VTE events represent the second leading cause of death in cancer patients after metastasis [8] and are associated with poor prognosis, irrespective of cancer stage.[4],[5] When cancer is diagnosed at the same time or within a year after VTE, the risk of death at 1 year is three times greater than for cancer patients without VTE.[22] In hospitalized neutropenic patients with cancer, a VTE event increases the risk of death by 2 compared to those patients who do not have a VTE.[6]

Finally, patients who survive a thrombotic event are at risk for VTE recurrence and bleeding or may suffer from sequelae from the initial event, such as increased bleeding, postthrombotic syndrome, and pulmonary hypertension.[8],[23],[24] The cumulative risk for VTE recurrence reaches 30%, and the economic impact of VTE is significant.

These data highlight the need for optimal treatment and make prophylaxis critical in high-risk patients.[4],[5]

There are three overarching risk factors for venous thromboembolism

These correspond to hypercoagulability, venous stasis, and alteration of the vascular wall - known as the Virchow triad.[25]

Specific risk factors that can induce one or more of these states [25] may influence or increase the risk of VTE in a patient with cancer.[26],[27],[28] [Table 2] summarizes the risk factors for VTE in malignancy.
Table 2: Risk factors for venous thromboembolism in cancer

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In a German study [29] documenting cancer therapy and DVT risk factors of 507 patients with cancer, factors that were predictive of an increased risk of VTE included inpatient treatment (P< 0.0001), C-reactive protein (P< 0.001), chemotherapy (P = 0.0080), fever (P = 0.0093), prior DVT (P = 0.0275), and family history of DVT (P = 0.0598). Considering the number of risk factors, the predicted VTE risk increased with the number of factors in both outpatients (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.18–2.88, P = 0.0071) and inpatients (OR 2.34, 95% CI 1.63–3.36, P ≤ 0.0001). If all factors were absent, the predicted risk of VTE was 2.3% but rose to 72% if all risk factors were present.[29]

Finally, the long-term use of central venous catheters (CVC) in cancer patients represents an important risk factor for the onset of thrombotic events. Depending on the study, the demonstrated incidence of symptomatic VTE is 0.3%–28.3%.[30] PE is the manifestation of VTE in 15.9%–25.0% of CRT.[30]

Incidental venous thromboembolism, a rising question

Despite the availability of effective and safe therapeutic options, VTE is often underrecognized and physicians underestimate the increasing prevalence of VTE in patients with cancer: 50% of deceased cancer patients are found to have a VTE on autopsy,[31] but only up to 20% of patients with cancer are diagnosed with a VTE. In the past 10 years, a significant number of asymptomatic PEs were discovered during chest scans with multi-slice CT undertaken for another reason (e.g., cancer staging).[32],[33]

In a study by den Exter et al.[34] comparing cancer patients diagnosed with either symptomatic or incidental PE, they reported high rates of recurrent VTE, bleeding complications, and mortality in both groups; the 12-month cumulative incidence of recurrent VTE was 13.3% in patients incidentally diagnosed versus 16.9% of symptomatic patients (P = 0.77); the risk of major bleeding complications was similar for both the groups (12.5% for incidental vs. 8.6% for symptomatic patients, P = 0.5) as was the 12-month mortality risk (52.9% for incidental vs. 53.3% for symptomatic patients, P = 0.7).

Given the prevalence of VTE and its associated morbidity, we propose herein to review and summarize the consensus of international CPG developed in 2013[13],[14] and updated in 2016[12] for optimal management of cancer-associated VTE, including guidance for the use direct oral anticoagulants [12] (DOACs). Implementation of these guidelines worldwide and among SAR physicians and health-care professionals with appropriate education strategy is necessary to underscore the gravity of VTE and the urgency for timely prophylaxis, effective treatment, and follow-up of VTE episodes in the cancer population.

  Therapy for Cancer-Related Thrombosis Top

The management of established VTE and implementation of specific prophylactic regimens in oncology have become an area of interest over the last 10 years because cancer patients often present with a variety of risk factors and comorbidities.

The evidence for superiority of LMWH over Vitamin K antagonists (VKAs) during at least 3 months of treatment for established cancer-associated VTE was first reported in the CANTHANOX study [35] and confirmed in subsequent studies,[36],[37],[38],[39] namely CLOT [36] and LITE [37] studies [Table 3]. Subsequently, several CPG have been elaborated in many countries to optimize the management of VTE, such as the Italian Association of Medical Oncology,[40] the American Society of Clinical Oncology,[26],[41] the French “Institut National du Cancer,”[11],[42] the American College of Chest Physicians (ACCP),[43],[44] the National Comprehensive Cancer Network,[45] and the European Society of Medical Oncology.[46],[47],[48]
Table 3: Studies evaluating low-molecular-weight heparin versus low-molecular-weight heparin + Vitamin K antagonist in early and long-term treatment of cancer-associated venous thromboembolism

Click here to view

Several difficulties may interfere with optimal implementation of these guidelines,[49],[50] including fear of bleeding, lack of multidisciplinary approach, and absence of consensus among various national and international guidelines, which have probably contributed to knowledge and practice gaps among physicians, and heterogeneous practices with inconsistent or inadequate management of VTE in oncology. This lead many organizations, such as the Joint Commission,[51] the Surgical Care Improvement Project,[52] and the ACCP, to provide strong incentives for improving VTE management practices supporting the implementation of a formal strategy based on multidisciplinary approach to formulate a VTE management and prophylaxis protocol [53] and track its implementation.[45] Many VTE risk-assessment tools were also formulated.[53]

Evidence-based recommendations for the management of established venous thromboembolism in cancer patients

Initial (0–10 days) treatment of established venous thromboembolism

The first 10 days of anticoagulation are a key to prevent the extension of VTE and onset of PE and VTE recurrence. No specific study has yet directly compared the use in oncology of unfractionated heparin (UFH), LMWH, or fondaparinux for the initial phase of VTE treatment. The short-term use of both UFH + VKA and LMWH + VKA was associated with high rate of relapse and major bleeding.[13],[54] Interestingly, indirect comparisons and several meta-analyses provided evidence that LMWH used during the first 10 days has the same efficacy than UFH, with a higher safety profile in terms of relapse, bleeding, risk of heparin-induced thrombocytopenia, and overall mortality.[13],[55] The MATISSE trial compared early treatment with fondaparinux versus UHF or LMWH followed by VKA and showed that rate of VTE recurrence was the lowest with LMWH followed by fondaparinux and then UFH, with similar risk of bleeding.[56] However, fondaparinux should be used with caution in cancer patients considering its long-half time, its contraindication in severe renal failure, and the absence of specific antidote for this drug.

Therefore, in the absence of contraindication, LMWH appears the anticoagulant of choice for initial treatment of VTE in oncology and is preferred in majority of guidelines [Grade 1B][13] [Table 4].
Table 4: Management of established venous thromboembolism in cancer patients

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Early maintenance and long-term treatment of venous thromboembolism

The superiority of early maintenance (10 days–3 months) and long-term treatment (beyond 3 months) with LMWH [Table 4] over short-term heparin followed by VKA is well documented.[35],[36],[37] In the CLOT study, the probability of recurrent VTE at 6 months was 17% in the VKA group and 9% in the dalteparin group (hazard ratio 0.48, P = 0.002).[36] Compared to VKA, LMWH used during at least 3–6 months significantly reduced the risk of VTE recurrence with the same safety profile [13],[58] and should be considered, in the absence of contraindications, as the standard of care for early maintenance and long-term treatment of VTE, as uniformly recommended in all clinical guidelines.[13]

Treatment duration

No study has yet prospectively addressed the optimal length of anticoagulation in cancer patients with established VTE. Most of the guidelines recommend a minimal treatment duration of 3 months, underlying that daily subcutaneous injection may represent a burden for patients, but that patients were treated for 6 months in the two largest studies in this setting [Grade 1A].[35],[36],[37],[41],[45],[57] After 3–6 months, termination or continuation of anticoagulation (LMWH or VKA) should be based on individual evaluation of the benefit–risk ratio, tolerability, patient's preference, and cancer activity (best clinical practice).[12],[13]

Extended anticoagulation beyond 6 months

It is usually proposed for cancer patients with a high risk of recurrence and a low bleeding risk and those with active malignancy.[59] The presence of residual VTE on ultrasound-Doppler or the D-dimers levels is insufficient to guide the clinician decision to maintain anticoagulation after 3 months.[13]

Special indications


The use of thrombolysis in cancer patients with VTE was addressed in one single retrospective study that showed the feasibility of this approach.[60] In the absence of evidence, thrombolysis should only be considered on a case-by-case basis, after thorough evaluation of the risk-benefit ratio, especially the bleeding risk.[12],[13]

Vena cava filters

Insertion of vena cava filters (VCFs) is associated with complications, namely inferior vena cava (IVC) penetration or perforation, filter embolization or fracture, and IVC thrombosis. Specific data in cancer patients are limited.[67],[68] In an RIETE registry prospective cohort study of patients with acute VTE, VCF filter insertion was associated with a lower risk of PE-related death (1.7% vs. 4.9%, P = 0.03) but a higher risk of recurrent VTE (6.1% vs. 0.6%, P < 0.001).[69] Therefore, a thorough case-by-case analysis after evaluation of the benefit–risk ratio is required.[12],[13] Currently, most guidelines recommended the insertion of VCF only in patients with contraindications for anticoagulant treatments or with recurrent VTE under optimal anticoagulation.[12],[13]

Specific cases

Recommendations for the management of VTE in cancer patients with challenging situations/brain tumor,[70],[71],[72],[73],[74] renal failure,[13] thrombocytopenia,[75] bleeding,[54],[76] and pregnancy [13] are summarized in [Table 5].
Table 5: Management of special situations with venous thromboembolism in cancer patients

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Treatment of recurrent venous thromboembolism in cancer patients under anticoagulant

Data to determine the best management of recurrent VTE in cancer patients under optimal therapy are scarce. The current recommendations support considering three options according to individual preferences: (1) switch from VKA to LMWH when treated with VKA, (2) increase in LMWH dose when treated with LMWH, or (3) VCF insertion.[13] The first two options were analyzed in a single small retrospective study [66] (n = 70 patients) which found no difference in terms of efficacy between the two arms. The insertion of a VCF is another therapeutic option despite the absence of evidence to support its use in cancer patients.[54]

Evidence-based recommendations for prophylaxis of venous thromboembolism in cancer patients

VTE is potentially preventable with the use of thromboprophylaxis in appropriate patients. For medically ill patients without contraindications to anticoagulant therapy, several regimens were demonstrated to be effective and well tolerated. However, prophylaxis continues to be insufficiently used in hospitalized medical patients [10] and particularly in cancer patients who represent an added major therapeutic challenge. The implementation of specific prophylactic regimens in onco-hematology has become an area of interest,[51],[52],[53],[77],[78] and several studies have illustrated the underuse of prophylaxis in oncology settings,[10],[79],[80] probably secondary to the fear of anticoagulants adverse effects. In a Canadian multicenter hospital audit, patients admitted for cancer were significantly less likely to receive prophylaxis than other medical patients (OR: 0.40; 95%CI: 0.24–0.68; P = 0.0007).[81]

Surgical cancer patients

Cancer patients undergoing surgery have an increased risk of VTE as compared to those without cancer.[82] Therefore, VTE prophylaxis after surgery is warranted. The risk is increased according to the type of surgery, with laparotomy, laparoscopy, thoracotomy, and brain surgery being considered at highest risk of VTE.[13],[82] Both LMWH and UFH have been demonstrated to be superior to placebo or no prophylaxis in the prevention of postsurgical VTE in cancer patients and have shown the same efficacy in several meta-analyses.[55],[83],[84],[85],[86] To date, there are no sufficient data to conclude on the superiority of one type of LMWH over another one nor to support fondaparinux as an alternative to LMWH.[12],[13] The optimal duration of VTE prophylaxis after surgery remains unknown, but two studies [87],[88] suggest that extended prophylaxis should be considered in surgical cancer patients with additional risk factors for VTE and in the absence of bleeding risk. The use of external compression devices (ECDs) as postsurgical prophylaxis appeared to be superior to no prophylaxis but inferior to LMWH.[89],[90],[91],[92]

Of note, neurosurgery for malignant brain tumor may be associated with increased risk of intracranial bleeding, but prophylaxis after surgery with LMWH, UFH, and ECD was shown to be superior to no prophylaxis despite an increased risk of minor bleeding, but with no increase in intracranial or major bleeding.

Summary of recommendations in surgical cancer patients is summarized in [Table 6].
Table 6: Thromboprophylaxis in surgical cancer patients

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Medical cancer patients

Hospitalized cancer patients

No randomized controlled study has evaluated the benefit–risk ratio of thromboprophylaxis in medically hospitalized cancer patients, and recommendations related to primary VTE prophylaxis have been extrapolated to cancer patients. In this setting, prophylaxis with UFH, LMWH, or fondaparinux was shown to be similarly effective, with a nonsignificant trend toward an increased bleeding risk (except for enoxaparin 40 mg and fondaparinux). No study reported a difference in efficacy between cancer and noncancer patients.[12],[13] All guidelines recommend the use of usual prophylactic doses of LMWH for cancer patients requiring hospitalization for acute medical illness or with a lower mobility in the absence of bleeding or contraindication to anticoagulation.[13],[41],[45],[49]

Ambulatory patients treated with chemotherapy

VTE occurs frequently in outpatients receiving chemotherapy, and the trials of primary prophylaxis of VTE in medical ambulatory cancer patients under chemotherapy show a benefit from prophylaxis with LMWH.[93],[94] Better risk stratification is necessary to identify the subgroup of patients who should benefit from thromboprophylaxis because of a VTE risk much higher than the bleeding risk. The Khorana score was specifically designed to stratify the risk in cancer patients receiving chemotherapy.[27]

The current evidence suggests that primary prophylaxis with LMWH in ambulatory patients treated with chemotherapy decreases the rate of VTE in those with locally advanced or metastatic pancreatic [95],[96],[97] or locally advanced or metastatic lung cancers [98],[99] without excess of bleeding [Table 7].
Table 7: Prophylaxis of venous thromboembolism in medical cancer patients

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However, primary prophylaxis with LMWH might be dangerous for patients with a brain tumor [101] because of increased intracranial bleeding.

Patients treated with thalidomide or lenalidomide in combination with chemotherapy or dexamethasone

These patients experiment high rates of venous thromboembolism. Studies comparing the use of low-dose aspirin, VKA at low or therapeutic doses, or LMWH at prophylactic doses have shown similar effects with regard to preventing VTE;[100],[102] however, the efficacy of these regimens remains unclear [Grade 2C] due to lack of randomized studies versus placebo or of an observation group. A risk assessment model for the management of VTE in multiple myeloma patients has been proposed by the International Myeloma Working Group but requires to be further validated.[48]

Patients with acute lymphocytic leukemia treated with L-asparaginase

Two small studies [103],[104] did not allow to conclude about the efficacy of antithrombin III (ATIII) or ATIII + LMWH due to the small number of patients. Patients with acute lymphocytic leukemia receiving L-asparaginase may be considered for VTE prophylaxis, depending on local policy and individual patient characteristics (platelet count, kidney function, fibrinogen, and ATIII levels) [Table 7] (best clinical practice).[13]

Challenging cases

For cases with severe renal failure, thrombocytopenia, and pregnancy, recommendations are based on best clinical practice and a balance between the bleeding risk and VTE risk [Table 5]. In pregnant patients with cancer, a standard thromboprophylaxis is recommended.[13]

Evidence-based recommendation for the treatment and prophylaxis of central venous catheter-related thrombosis in cancer patients

Treatment of symptomatic catheter-related thrombosis in cancer patients

CVCs are increasingly used in cancer patients. CRT is an important complication and may become symptomatic in approximately 5% of patients.[61] To date, published studies [62] provided insufficient data to determine the efficacy and safety of LMWH or VKA or thrombolytics [64],[65] for treating CRT. One study did not support the withdrawal of a noninfected, functioning, and well-positioned CVC.[63] The risk of recurrence is high. Whether the CVC is kept or removed, no standard is established yet for the duration of anticoagulation.[14] Therefore, for the treatment of symptomatic CRT in cancer patients, anticoagulation is recommended for a minimum of 3 months.[14] Both LMWHs and VKAs can be used in the absence of direct comparison of the two anticoagulants in this setting.

Prophylaxis of catheter-related thrombosis

Routine prophylaxis using anticoagulant is not recommended in patients with CVC [12],[53] [Grade 1A].

Guidance for the use of direct oral anticoagulants in cancer patients

The potential benefit of DOACs as part of cancer-related VTE therapy has not been specifically evaluated to date, and many ongoing trials study their use in cancer patients. However, important limitations for their use in cancer should be taken into consideration including an unpredictable absorption in the specific cancer population, a higher risk of bleeding, unknown interactions with anticancer drugs, and no currently available antidote. Today, DOACs are not recommended routinely for the prevention of VTE in cancer patients [12] (best practice). Results of ongoing studies are required to determine the potential role of DOACs in this setting, their efficacy, and their safety.

The use of DOACs in early maintenance and long-term therapy can be considered for stable patients off systemic anticancer therapy and when VKA is acceptable but not available (best practice): In a meta-analysis with documented cancer subgroups (1132 cancer patients), VTE recurrence was 3.4% with a DOAC versus 5.9% with a VKA, with no difference in rates of major and minor bleeding between treatment groups.[12]

  Conclusion Top

In daily oncology practice, cancer-related VTE remains a major concern, being the second-leading cause of death in cancer patients after metastasis. However, clinicians still underestimate the risk and the increasing prevalence of VTE in this population. Although adequate anticoagulation has been demonstrated efficacious and relatively safe for prophylaxis and treatment of VTE in cancer patients, with prolonged use of LMWH as therapeutic option in most of the cases, there is still large heterogeneity worldwide in the clinical knowledge and implementation of the CPG. In addition, many clinicians are reluctant to modify their practice or still have doubt on the tolerability and acceptance of long-term daily subcutaneous treatment [58] recommended as standard therapy. Tolerance and cost-effectiveness of long-term use of LMWH may account for large heterogeneity in daily clinical practice, and the implementation of specific recommendations for cancer patients is still low.

Due to the patient burden and related costs, cancer-associated VTE represents a major public health problem. SAR and other countries worldwide need to implement specific strategies in their health care plan to assess the burden of the VTE in their cancer population and to improve adherence to international CPG among physicians and health-care professionals. This can be achieved with adequate education strategy that highlights the gravity of VTE in cancer patients and the urgency for timely prophylaxis and effective treatment in established VTE and that supports the creation of multidisciplinary approach to formulate VTE management protocols and track their implementation. A minimum standard clinical data set may be used to collect data and create a VTE registry that will help the clinical team to build a comprehensive picture of VTE incidence, treatment, outcomes, and recurrence. Risk factors can be identified using adequate risk assessment models, which may greatly contribute to target prophylaxis for high-risk patients and thus preventing possible future complications. Clinical tools, based on the 2016 international guidelines which are available as web and mobile (iOS App Store or Google Play) applications with decision-tree algorithm, may also be used to assist clinicians in adopting optimal treatment strategies.(www.itaccme.com/app).

Adherence to the international guidelines and expert opinion could substantially decrease the burden of VTE, enhance quality of life, and increase survival in cancer patients.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]


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