Vascular Complications in Patients with Hepatocellular Carcinoma Treated with Sorafenib

VEGF(R)-targeted therapies are associated with an increased risk of thromboembolism and bleeding, which might be pronounced in patients with increased cardiovascular risk. Nevertheless, sorafenib represents an important treatment option in patients with hepatocellular carcinoma (HCC). We retrospectively investigated the risk of arterial/venous thromboembolic and bleeding events in 252 patients treated with sorafenib for HCC between 05/2006 and 03/2020 at the Medical University of Vienna. Cardiovascular risk was assessed using Framingham score. Eight patients (3.2%) experienced 11 arterial/venous thromboembolic events. Only two patients (0.8%) developed arterial thromboembolism even though cardiovascular risk was low, intermediate, and high in 15 (8.7%), 104 (60%), and 54 (31.2%) of 173 assessable patients. Median overall survival (OS) was shorter in the high risk vs. low/intermediate risk group 7.4 (95% CI: 3.4–11.3) vs. 10.0 (95% CI: 6.8–13.2 months) and independently associated with OS in multivariable analysis HR: 1.53 (95% CI: 1.07–2.19; p = 0.019). Forty-eight (19%) patients experienced a bleeding, most commonly gastrointestinal bleeding (14%) followed by epistaxis (4.7%). Advanced liver dysfunction was not associated with an increased incidence of bleeding/venous thromboembolism. Sorafenib represents a safe treatment option even in patients with increased cardiovascular risk. Bleeding complications were comparable with previous reports, even though patients with more advanced liver disease were included.

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Extended thromboprophylaxis for medically ill patients with cancer: a systemic review and meta-analysis

Blood Advances ◽

10.1182/bloodadvances.2020004118 ◽

2021 ◽

Vol 5 (8) ◽

pp. 2055-2062

Author(s):

Soravis Osataphan ◽

Rushad Patell ◽

Thita Chiasakul ◽

Alok A. Khorana ◽

Jeffrey I. Zwicker

Keyword(s):

Meta Analysis ◽

Thromboembolic Events ◽

Medically Ill ◽

Patients With Cancer ◽

Randomized Controlled ◽

Increased Risk ◽

Venous Thromboembolic Events ◽

Venous Thromboembolic ◽

Extended Duration ◽

Medically Ill Patients

Abstract Hospitalized medically ill patients with cancer are at increased risk of both venous thromboembolism and bleeding. The safety and efficacy of extended thromboprophylaxis in patients with cancer are unclear. We conducted a systematic review and meta-analysis of the literature using of MEDLINE, EMBASE, and the Cochrane CENTRAL databases to identify cancer subgroups enrolled in randomized controlled trials evaluating extended thromboprophylaxis following hospitalization. The primary outcomes were symptomatic and incidental venous thromboembolic events and hemorrhage (major hemorrhage and clinically relevant nonmajor bleeding). Four randomized controlled trials reported the outcomes of extended thromboprophylaxis in 3655 medically ill patients with active or history of cancer. The rates of venous thromboembolic events were similar between the extended-duration and standard-duration groups (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.61-1.18; I2 = 0%). However, major and clinically relevant nonmajor bleeding occurred significantly more frequently in the extended-duration thromboprophylaxis group (OR, 2.10; 95% CI, 1.33-3.35; I2 = 8%). Extended thromboprophylaxis in hospitalized medically ill patients with cancer was not associated with a reduced rate of venous thromboembolic events but was associated with increased risk of hemorrhage. This study protocol was registered on PROSPERO as #CRD42020209333.

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The Efficacy of Dextran-40 as a Venous Thromboembolism Prophylaxis Strategy in Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

The American Surgeon ◽

10.1177/000313481708300212 ◽

2017 ◽

Vol 83 (2) ◽

pp. 134-140 ◽

Cited By ~ 4

Author(s):

Jason M. Foster ◽

Richard Sleightholm ◽

Duncan Watley ◽

Steven Wahlmeier ◽

Asish Patel

Keyword(s):

Venous Thromboembolism ◽

Intraperitoneal Chemotherapy ◽

Hyperthermic Intraperitoneal Chemotherapy ◽

Medical Center ◽

Bleeding Complications ◽

Bleeding Events ◽

Thromboembolism Prophylaxis ◽

Dextran 40 ◽

Perioperative Bleeding ◽

Increased Risk

The incidence of venous thromboembolism (VTE) in peritoneal malignancies can approach 30 to 50 per cent without prophylaxis. Prophylaxis in cytoreductive surgeries (CRS) presents a challenge to preoperative heparin-based therapy because of an increased risk of coagulopathy and potential for bleeding. Herein, we report the large series of CRS and hyperthermic intraperitoneal chemotherapy receiving dextran-40 prophylaxis. Retrospective chart review of peritoneal malignancies patients undergoing CRS at University of Nebraska Medical Center identified 69 individuals who received dextran-40 between 2010 and 2013. The incidences of VTEs, perioperative bleeding, complications, morbidity, and mortality were determined in-hospital and at 90 days. Of the 69 patients treated, the 30-day VTE rate was 8.7 per cent, and no pulmonary embolisms, bleeding, anaphylactoid reaction, or mortality were observed with dextran usage. The specific VTE events included three upper extremity and three lower extremity VTEs. No additional VTE events were identified between 30 and 90 days. In conclusion, dextran-40 prophylaxis was not associated with any perioperative bleeding events, and the observed incidence of VTE was comparable to reported heparin-based prophylaxis in CRS/hyperthermic intraperitoneal chemotherapy patients. This data supports further exploration of dextran-40 as a VTE prophylactic agent in complex surgical oncology cases.

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The Impact of COVID-19 Disease on Platelets and Coagulation

Pathobiology ◽

10.1159/000512007 ◽

2020 ◽

pp. 1-13 ◽

Cited By ~ 7

Author(s):

Geoffrey D. Wool ◽

Jonathan L. Miller

Keyword(s):

Degradation Products ◽

Severe Bleeding ◽

Bleeding Events ◽

Current State ◽

Venous Thromboembolic Events ◽

Venous Thromboembolic ◽

Intravascular Coagulopathy ◽

Vascular Beds ◽

The Impact ◽

D Dimer

Coronavirus disease 2019 (COVID-19) causes a spectrum of disease; some patients develop a severe proinflammatory state which can be associated with a unique coagulopathy and procoagulant endothelial phenotype. Initially, COVID-19 infection produces a prominent elevation of fibrinogen and D-dimer/fibrin(ogen) degradation products. This is associated with systemic hypercoagulability and frequent venous thromboembolic events. The degree of D-dimer elevation positively correlates with mortality in COVID-19 patients. COVID-19 also leads to arterial thrombotic events (including strokes and ischemic limbs) as well as microvascular thrombotic disorders (as frequently documented at autopsy in the pulmonary vascular beds). COVID-19 patients often have mild thrombocytopenia and appear to have increased platelet consumption, together with a corresponding increase in platelet production. Disseminated intravascular coagulopathy (DIC) and severe bleeding events are uncommon in COVID-19 patients. Here, we review the current state of knowledge of COVID-19 and hemostasis.

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Bleeding complications after systematic switch of routine thromboprophylaxis for major orthopaedic surgery

Thrombosis and Haemostasis ◽

10.1160/th08-01-0019 ◽

2008 ◽

Vol 99 (06) ◽

pp. 1049-1052 ◽

Cited By ~ 6

Author(s):

Urs Kistler ◽

Inès Quervain ◽

Urs Munzinger ◽

Nils Kucher

Keyword(s):

Postoperative Bleeding ◽

Bleeding Complications ◽

Thromboembolic Events ◽

Venous Thromboembolic Events ◽

Major Orthopedic Surgery ◽

Venous Thromboembolic ◽

Major Orthopaedic Surgery ◽

Orthopedic Patients ◽

Second Period ◽

Observation Period

SummaryThe rate of bleeding complications after major orthopedic surgery approximates 2%. It is unclear whether a systematic switch of routine thromboprophylaxis has an impact on the rate of postoperative bleeding complications. We analyzed prospectively recorded postoperative bleeding complications and symptomatic venous thromboembolic events in 8,176 consecutive orthopedic patients at the Schulthess Clinic Zurich during a systematic switch of thromboprophylaxis from nadroparin to enoxaparin in the year 2004. Overall, 3,893 patients received nadroparin in the first nine-month observation period before the switch and 4,283 patients received enoxaparin in the second nine-month observation period after the switch. Overall, 96 (2.5%) patients in the first period and 70 (1.6%) patients in the second period suffered a postoperative bleeding complication requiring surgical revision, puncture, or transfusion (p<0.01). Five objectively confirmed symptomatic venous thromboembolic events during hospitalization in the first period and three events in the second period were recorded. In conclusion, the switch of thromboprophylaxis in a large orthopedic clinic did not cause an increase of postoperative bleeding complications and therefore was accompanied by high patient safety.

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Homocysteine and thrombosis: from basic science to clinical evidence

Thrombosis and Haemostasis ◽

10.1160/th05-05-0313 ◽

2005 ◽

Vol 94 (11) ◽

pp. 907-915 ◽

Cited By ~ 49

Author(s):

Jan Brożek ◽

Andrzej Szczeklik ◽

Anetta Undas

Keyword(s):

Molecular Mechanisms ◽

Platelet Reactivity ◽

Current Evidence ◽

Factor V ◽

Dna Hypomethylation ◽

Homocysteine Concentration ◽

Increased Risk ◽

Venous Thromboembolic Events ◽

Venous Thromboembolic ◽

Artery Disease

SummaryHomocysteine is a sulfhydryl-containing amino acid formed during the metabolism of methionine. Rapidly accumulating evidence links elevated homocysteine levels to thrombosis via several mechanisms such as increased tissue factor expression, attenuated anticoagulant processes, enhanced platelet reactivity, increased thrombin generation, augmented factor V activity, impaired fibrinolytic potential, and vascular injury, including endothelial dysfunction. Molecular mechanisms underlying prothrombotic actions of homocysteine are incompletely understood and involve oxidative stress, DNA hypomethylation, and proinflammatory effects. Current evidence from retrospective and prospective studies supports the concept that higher total plasma homocysteine concentration is associated with increased risk of coronary artery disease, stroke, and venous thromboembolism. Hyperhomocysteinemia is currently considered a relatively weak prothrombotic factor. It is still unclear whether administration of vitamins, that reduce homocysteine levels acting as cofactors of the enzymes involved in the methionine metabolism, may decrease the risk of arterial and/or venous thromboembolic events. Ongoing clinical trials might help clarify this issue.

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Is prolonged immobilization a risk factor for symptomatic venous thromboembolism in elderly bedridden patients?

Thrombosis and Haemostasis ◽

10.1160/th03-07-0481 ◽

2004 ◽

Vol 91 (03) ◽

pp. 538-543 ◽

Cited By ~ 37

Author(s):

Ora Paltiel ◽

Michael Bursztyn ◽

Moshe Gatt

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Early Period ◽

Thromboembolic Events ◽

Historical Cohort ◽

Increased Risk ◽

Venous Thromboembolic Events ◽

Venous Thromboembolic ◽

Prolonged Immobilization ◽

The Impact

SummaryProlonged immobilization and advanced age are considered to be important risk factors for venous thromboembolism (VTE). Nevertheless, the need for VTE prophylaxis in long-term bedridden patients is not known. To assess whether very prolonged immobilization (i.e. over three months) carries an increased risk for clinically apparent VTE, we performed a historical-cohort study of nursing home residents during a ten-year period. Data concerning patient’s mobility and incidence of overt deep vein thrombosis or pulmonary embolism were registered. The mean resident age was 85 ± 8.4 years. Eighteen mobile and eight immobile patients were diagnosed with clinically significant thromboembolic events, during 1137 and 573 patient-years of follow up, respectively. The incidence of venous thromboembolic events was similar in both chronically immobilized and mobile patient groups, 13.9 and 15.8 per thousand patient years, respectively (p = 0.77). The rate ratio for having a VTE event in the immobilized patient group as compared with the mobile group was 0.88 (95% Confidence Interval (CI) 0.33 to 2.13). When taking into account baseline characteristics, risk factors and death rates by various causes, no differences were found between the two groups. In conclusion, chronically immobile bedridden patients are no more prone to clinically overt venous thromboembolic events than institutionalized mobile patients. Until further studies are performed concerning the impact of very prolonged immobilization on the risk of VTE, there is no evidence to support primary prevention after the first three months of immobilization. Evidence for efficacy or cost effectiveness beyond this early period is not available.

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Risk of venous thromboembolism in cancer patients treated with cisplatin: A systematic review and meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e21016 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e21016-e21016

Author(s):

Sonia Maria Seng ◽

Ziyue Liu ◽

Sophia Chiu ◽

Tracey Proverbs-Singh ◽

Guru Sonpavde ◽

...

Keyword(s):

Relative Risk ◽

Solid Tumors ◽

Meta Analysis ◽

Systemic Review ◽

Advanced Solid Tumors ◽

Thromboembolic Events ◽

Patients With Cancer ◽

Increased Risk ◽

Venous Thromboembolic Events ◽

Venous Thromboembolic

e21016 Background: Several reports suggest that cisplatin is associated with an increased risk of thromboembolism (TE). However, patients with solid tumors have multiple risk factors for TE and the excess risk of venous thromboembolic events (VTEs) with cisplatin-based chemotherapy as compared with non-cisplatin-based chemotherapy has not been well described. We performed a systemic review and meta-analysis of randomized controlled trials (RCTs) evaluating the incidence and risk of VTE associated with cisplatin-based chemotherapy. Methods: PubMed was searched for articles published from January 1, 1990 until December 31, 2010.The primary aim was to evaluate the association between treatment with cisplatin and VTEs in patients with cancer. Clinical trials that met the following criteria were included in the meta-analysis: (1) prospective randomized phase 2 and 3 trials of patients with cancer; (2) randomization to treatment with cisplatin versus a non-cisplatin containing chemotherapy regimen (3) available data on venous thromboembolic events. Data on all grade venous thromboembolic events was extracted. Study quality was calculated utilizing Jadad scores. Incidence rates, relative risks, and 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup analyses included the impact of publication year, tumor type, and cisplatin dose. Results: A total of 8216 patients with a variety of advanced solid tumors from 38 RCTs were included for analysis. Among patients treated with cisplatin-based chemotherapy, the summary incidence of VTE was 1.64% (95% CI, 1.06–2.25). Patients treated with cisplatin-based chemotherapy had a significantly increased risk of VTE with a relative risk of 1.65 (95% CI, 1.25–2.18; P = .01) compared with controls. Exploratory subgroup analysis revealed the highest relative risk of VTE in patients receiving a weekly equivalent cisplatin dose >30 mg/m2 (2.64; 95% CI, 1.18–5.77; P = .02) and in studies reported during 2000-2010 (1.70; 95% CI, 1.27–2.28; P = .01). Conclusions: Cisplatin chemotherapy is associated with a significant increase in the risk of VTE in patients with advanced solid tumors compared with non-cisplatin chemotherapy.

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Modified Khorana risk score for prediction of venous thromboembolic events in cancer patients receiving chemotherapy: An Australian single institution experience.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e20610 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e20610-e20610

Author(s):

Wolfgang H Heller ◽

Alhossain A Khalafallah ◽

Rebecca Yuan Li ◽

Anurag Arora ◽

Maimoona Latif ◽

...

Keyword(s):

Platelet Count ◽

Cancer Patients ◽

White Cell Count ◽

Thromboembolic Events ◽

Cancer Subtypes ◽

Increased Risk ◽

Venous Thromboembolic Events ◽

Venous Thromboembolic ◽

Breast And Prostate Cancer ◽

Chemotherapy Patients

e20610 Background: Venous thromboembolic events (VTEs) are a common complication in cancer. The Khorana Score (KS) is widely used for the prediction of VTEs in malignancy. The KS is composed of 5 items: cancer entity, platelet count >350/nL, white cell count (WCC) >11/nL, Hb <100 g/L and body mass index ≥35 (BMI). Scores are grouped into 3 categories indicating the VTE-risk (0=low, 1-2= intermediate, 3 or more points= high-risk). Methods: All ambulatory cancer patients at our institution starting chemotherapy from January 2010 to December 2011 were included. We applied the KS and then modified by adding further cancer subtypes and metastatic status. Results: In 658 of 766 chemotherapy patients, all the data were available for calculating the KS, of whom 52 had a VTE. In multivariate analysis, associations between KS and VTE were found (P≤0.05) in pancreas (p<0.001), lung (p=0.002), stomach (p=0.008), gynaecological cancers (p=0.037), and BMI ≥35 (p=0.004), but not found in lymphoma (p=0.14), high platelet count (p=0.6) and high WCC (p=0.8), or low Hb (p=0.53). There was an increased risk for VTE in some cancers not included in the KS: breast (p=0.01), colorectal (CRC)(p<0.001), prostate (p=0.003) and oesophageal cancer (p= 0.041). The original KS score did not significantly predict VTEs. When adding cases of neoadjuvant/adjuvant (n/a) and/or metastatic (met) CRC, breast, and prostate cancer, significant associations were found, as shown in the Table. Conclusions: The original KS showed only a weak association with VTE occurrence. However, the association was improved by including other cancer entities and / or metastatic status. Major differences between our and other cohorts, such as different proportions of cancer entities and general referral patterns, could explain the discrepancies with other studies. [Table: see text]

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Incidence of venous thromboembolic events following major pelvic and abdominal surgery for cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.478 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 478-478

Author(s):

Pablo Emilio Serrano Aybar ◽

Kavita Dhamanaskar ◽

Laurie Elit ◽

Sameer Parpia ◽

Lori-Ann Linkins ◽

...

Keyword(s):

Hospital Discharge ◽

Multivariable Analysis ◽

Pelvic Surgery ◽

Negative Events ◽

Thromboembolic Events ◽

Vte Prophylaxis ◽

Venous Thromboembolic Events ◽

Venous Thromboembolic ◽

Extended Duration ◽

Screening Ultrasound

478 Background: The recommendation to administer extended-duration (28 days) venous thromboembolic events (VTE) prophylaxis with low molecular weight heparin in patients undergoing abdominal and pelvic surgery for cancer has not been widely implemented mainly because most studies focus on asymptomatic events with unknown clinical significance. The objective of this study was to determine the post-hospital discharge VTE incidence in these patients who do not receive post-hospital discharge prophylaxis. Methods: Prospective cohort study of patients undergoing abdominal and pelvic operations for cancer within the gastrointestinal tract, hepatobiliary (HPB) system or gynecological organs, with surgery lasting > 1 hour, post-operative stay < 28 days, and not undergoing anticoagulant therapy. Patients were evaluated at 1, 3 and 6 months from index operation for the presence of VTE by means of a screening ultrasound at 28 days and a questionnaire at each follow-up. The proportion with 95% confidence interval (CI) of VTE was calculated. Multivariable logistical regression was performed. Results: Of 284 patients, there were 79 (28%) colorectal, 97 (35%) HPB and 100 (35%) gynecology. All patients received pre- and post-operative in-patient prophylaxis. The proportion of VTE at 6 months was 7%, 95% CI 4.4-10.7 (20 events). Most events occurred between 3-6 months, 4.6%, 95% CI 2.46 – 7.7. Only one event occurred at one month after surgery (0.35%, 95% CI 0.06-1.97). 50% of the cohort had screening ultrasound, all of which were negative. Events were evenly distributed according to the type of surgery. The proportion of patients who died was 6.6%, 95% CI 3.5 – 9.4 (17 patients, 2 of which had a VTE-related death). In the multivariable analysis, post-operative chemotherapy was significantly associated with VTE, odds ratio (OR) 2.74, 95% CI 1.07-6.99. Caprini score was also associated with VTE but was not significant when included in the multivariable analysis, OR 1.19, 95% CI 0.99-1.42. Conclusions: Incidence of VTE following abdominal cancer surgery is low. Most events occur between 3-6 months from surgery. Post-operative chemotherapy is significantly associated with post-hospital discharge VTE.

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Calculation of HAS-BLED Score Is Useful for Early Identification of Venous Thromboembolism Patients at High Risk for Major Bleeding Events: A Prospective Outpatients Cohort Study

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0037-1607433 ◽

2017 ◽

Vol 44 (04) ◽

pp. 348-352 ◽

Cited By ~ 4

Author(s):

Reinhard Raggam ◽

Franz Hafner ◽

Alexander Avian ◽

Gerald Hackl ◽

Gerhard Cvirn ◽

...

Keyword(s):

Venous Thromboembolism ◽

Major Bleeding ◽

Odds Ratio ◽

Bleeding Complications ◽

Minor Bleeding ◽

Prospective Evaluation ◽

Bleeding Events ◽

Increased Risk ◽

Major Bleeding Events

AbstractThe aim of this study was prospective evaluation of the performance of the HAS-BLED score in predicting major bleeding complications in a real-world outpatient cohort, during long-term anticoagulation for venous thromboembolism (VTE), treated with a broad spectrum of anticoagulants. We analyzed 111 outpatients objectively diagnosed with VTE and treated long-term with various anticoagulants. Patients were grouped in three cohorts based on the anticoagulant regimen. Calculation of the HAS-BLED score and documentation of bleeding events were performed every 6 months for 1 year. Patients with a HAS-BLED score ≥ 3 had an increased risk for major bleeding events (odds ratio [OR]: 13.05, 95% confidence interval [CI]: 0.96–692.58, p = 0.028) and a trend to higher risk for minor bleeding events as well (OR: 2.25, 95% CI: 0.87–5.85, p = 0.091) when compared with patients with a HAS-BLED score < 3.This indicates that a HAS-BLED score ≥ 3 allows for identification of patients with VTE on long-term anticoagulation at an increased risk for major bleeding events, irrespective of the anticoagulant agent used.

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