ABSTRACT

PURPOSE: Percutaneous hepatic perfusion (PHP) is a palliative intraarterial therapy for unresectable hepatic malignancies. During PHP, high-dose melphalan is infused via the hepatic artery to saturate tumor in the liver with the chemotherapeutic substance. The venous hepatic blood is filtered by an extracorporeal melphalan specific filtration system. Blood clotting in the extracorporeal filter system is prevented by administering unfractionated heparin (UFH) in high doses, which might be reversed with protamine sulfate after the procedure. Aim of this retrospective two-center-study was to analyze the potential effect of UFH reversal with protamine sulfate on complication rates following PHP.

MATERIALS AND METHODS: All patients receiving PHP treatment between 10/2014 and 04/2021 were classified according to their intraprocedural coagulation management: 92 patients/192 PHP received full UFH reversal with protamine (groupPROTAMINE); 13 patients/21 PHP in groupREDUCED_PROTAMINE received a reduced amount of protamine, and 28 patients/43 PHP did not receive UFH reversal with protamine (groupNO_PROTAMINE). Periinterventional clinical reports, findings and laboratory values were retrospectively evaluated. Complications and adverse events were classified according to Common Terminology Criteria for Adverse Events (CTCAEv5.0).

RESULTS: Thromboembolic events were recorded after 10 PHP procedures (5%) in groupPROTAMINE, six of which (3%) were major events (CTCAE grade 3-5). No (0%) thromboembolic events were recorded in groupREDUCED_PROTAMINE and groupNO_PROTAMINE. Hemorrhagic events were registered after 24 PHP (13%) in groupPROTAMINE, two of which (1%) were major (CTCAE grade 3-4). In groupREDUCED_PROTAMINE, only minor bleeding events were recorded, and one major hemorrhagic event was documented in groupNO_PROTAMINE (2%). There was a significant difference between the percentage of post-interventional thrombopenia in groupPROTAMINE (39%) and groupREDUCED_PROTAMINE (14%) versus groupNO_PROTAMINE (23%) (p=.00024). In groupPROTAMINE one patient suffered from a severe anaphylactic shock after the administration of protamine.

CONCLUSION: Our retrospective study implies that there might be a link between the practice of protamine sulfate administration to reverse the full hemodilutive effect of UFH after PHP and the post-interventional risk of thromboembolic events as well as clinically significant thrombopenia. Our data suggest that the standard use of protamine sulfate after PHP in low-risk patients without clinical signs of active bleeding should be critically re-evaluated.

PMID:37452405 | PMC:PMC10349410 | DOI:10.1186/s40644-023-00590-7

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PubMed articles on: Cancer & VTE/PE

Incidence of venous thromboembolism in patients with advanced stage ovarian cancer undergoing neoadjuvant chemotherapy: Is it time for thromboprophylaxis?

Gynecol Oncol. 2023 Jul 11;176:36-42. doi: 10.1016/j.ygyno.2023.06.577. Online ahead of print.

ABSTRACT

OBJECTIVES: Our objectives were to determine the incidence, timing, and risk factors for venous thromboembolisms (VTEs) in patients with advanced stage epithelial ovarian cancer (EOC) who received neoadjuvant chemotherapy (NACT). We explored the utilization of direct-acting oral anticoagulants (DOACs) for VTE treatment.

METHODS: This retrospective cohort study included patients with advanced stage EOC receiving NACT followed by interval cytoreductive surgery (ICS) at a single institution. Risk factors were compared between patients with versus without VTE between EOC diagnosis and 180 days after ICS. Bleeding complications were compared between patient who received a DOAC versus non-DOAC.

RESULTS: VTE cases occurred amongst 33 of the 154 (21.4%) patients with 4 (2.6%) concurrent with EOC diagnosis, 9 (5.8%) between EOC diagnosis and NACT start, 13 (8.4%) between NACT start and ICS, and 7 (4.5%) within 180 days after ICS. There were no statistically significant differences in risk factors assessed (age, body mass index, functional status, histology, Khorana score, and smoking history) between patients with versus without VTE. Eleven patients (33.3%) received a DOAC for VTE treatment. There were no significant differences in number of intraoperative blood transfusions (p = 0.38), blood loss (p = 0.95), or bleeding complications (p = 0.53) between patients treated with a DOAC versus a non-DOAC.

CONCLUSION: There is a high incidence of VTE events (21.4%) in patients with advanced stage EOC undergoing NACT. Two-thirds of the VTEs may have been prevented with thromboprophylaxis as they occurred between EOC diagnosis and ICS. These data support consideration of thromboprophylaxis in all patients with advanced stage EOC undergoing NACT.

PMID:37442024 | DOI:10.1016/j.ygyno.2023.06.577

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PubMed articles on: Cancer & VTE/PE

Markers of right ventricular dysfunction predict 30-day adverse prognosis of pulmonary embolism on pulmonary computed tomographic angiography

Medicine (Baltimore). 2023 Jul 14;102(28):e34304. doi: 10.1097/MD.0000000000034304.

ABSTRACT

To investigate the value of parameters of the pulmonary artery and right ventricular function in predicting the 30-day poor prognosis of patients with acute pulmonary embolism (APE). The heart rate, respiratory rate, systolic blood pressure, Wells score for APE, history of recent operation or immobilization, history of cancer, respiratory failure, smoking were significantly (P < .05) different among the control, good prognosis, and poor prognosis groups. The maximal short diameter of the right and left ventricle (RVD/LVD) ratio (P < .001) and left pulmonary artery (LPA) (P = .01) were significantly different between the good and poor prognosis groups. Systolic blood pressure (odds ratio [OR]: 0.98, P = .045) and the RVD/LVD ratio (OR: 12.57, P = .02) were significant independent risk factors for poor prognosis. The risk for poor prognosis significantly increased when the RVD/LVD ratio was >1.11 (cutoff value) with the area under the curve (AUC) of 0.71 (95% confidence interval [CI]: 0.61-0.80, P < .001). LPA (OR: 9.12, P = .01) and RVD/LVD (OR: 4.62, P = .012) were the significant independent risk factors for poor prognosis in the central pulmonary embolism. The LPA of 2.1 cm had the highest predictive value for poor prognosis in the central APE (AUC: 0.68; sensitivity 84.6%; specificity 53.1%). The RVD/LVD ratio and systolic blood pressure are significant risk factors for short-term prognosis in patients with APE. When the LPA is >2.1 cm in the central APE or the RVD/LVD is >1.11, the risk of poor prognosis increases, which can be used as important indicators for predicting the prognosis of patients with APE. Two hundred forty-three APE patients and 61 patients without APE who underwent computed tomographic pulmonary angiography (CTPA) were retrospectively enrolled as the experimental and the control group, respectively. APE patients who were followed up at the 30-day time point were divided into the good prognosis (n = 195) and poor prognosis group (n = 32). The main pulmonary artery (MPA) to the aorta (AO) ratio, maximal diameter of the LPA and right pulmonary artery (RPA), ratio of the RVD/LVD and the height and volume of the pulmonary artery (PAh and PAV, respectively) were analyzed after indexing to the body surface area.

PMID:37443496 | PMC:PMC10344539 | DOI:10.1097/MD.0000000000034304

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PubMed articles on: Cancer & VTE/PE

Lung cancer presenting with acute myocardial infarction and pulmonary embolism within 1 month

SAGE Open Med Case Rep. 2023 Jul 6;11:2050313X231181979. doi: 10.1177/2050313X231181979. eCollection 2023.

ABSTRACT

Acute myocardial infarction and pulmonary embolism can have life-threatening consequences such as congestive heart and respiratory failure, respectively. Cancer patients are at great risk of both acute myocardial infarction and pulmonary embolism complications because the malignancy sparks the patient's blood hypercoagulable state. Nevertheless, the literature currently offers only a few reports on acute myocardial infarction associated with pulmonary embolism, and two of them occurred in the same cancer patient. Here, we present a case of a 60-year-old woman who had been diagnosed with lung cancer. She was admitted to the emergency department twice. She was diagnosed with acute myocardial infarction at her first admission, when she experienced sudden-onset chest pain. Electrocardiography showed ST-segment elevation in leads V1-V3 with inverted T wave and pathological Q wave, suggesting an acute myocardial infarction. Coronary angiography revealed a thrombus in the left anterior descending coronary artery, and thrombus aspiration was performed. After 1 month, she had an attack of pulmonary embolism with syncope upon the second admission. A computed tomographic pulmonary angiography showed branches of right and left pulmonary embolism. Anticoagulation and antiplatelet measures were taken. In this article, we discuss the relationship between cancer and thrombosis with a special focus on the conservative management strategy regarding anticoagulant and antiplatelet therapy in our case.

PMID:37434900 | PMC:PMC10331209 | DOI:10.1177/2050313X231181979

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PubMed articles on: Cancer & VTE/PE

Different kinds of oral contraceptive pills in polycystic ovary syndrome: a systematic review and meta-analysis

Eur J Endocrinol. 2023 Jul 20;189(1):S1-S16. doi: 10.1093/ejendo/lvad082.

ABSTRACT

OBJECTIVE: To compare between different combined oral contraceptive pills (COCPs) as part of the update of the International Evidence-Based Guidelines on the Assessment and Management of polycystic ovary syndrome (PCOS).

DESIGN: A systematic review and meta-analysis was performed, Prospero CRD42022345640.

METHODS: MEDLINE, EMBASE, All EBM, CINAHL, and PsycINFO was searched on July, 8, 2022, for studies including women with PCOS, comparing 2 different COCPs in randomized controlled trials.

RESULTS: A total of 1660 studies were identified, and 19 randomized controlled trials (RCTs) were included.Fourth-generation COCP resulted in lower body mass index (BMI) (mean difference [MD] 1.17 kg/m2 [95% confidence interval {CI} 0.33; 2.02]) and testosterone (MD 0.60 nmol/L [95% CI 0.13; 1.07]) compared with third-generation agents, but no difference was seen in hirsutism.Ethinyl estradiol (EE)/cyproterone acetate (CPA) was better in reducing hirsutism as well as biochemical hyperandrogenism (testosterone [MD 0.38 nmol/L {95% CI 0.33-0.43}]) and BMI (MD 0.62 kg/m2 [95% CI 0.05-1.20]) compared with conventional COCPs.There was no difference in hirsutism between high and low EE doses. No evidence regarding natural estrogens in COCP was identified.

CONCLUSION: With current evidence, combined regimens containing an antiandrogen (EE/CPA) may be better compared with conventional COCPs in reducing hyperandrogenism, but EE/CPA will not be recommended as a first-line COCP treatment by the pending PCOS guideline update, due to higher venous thrombotic events (VTE) risk in the general population. Later-generation progestins offer theoretical benefits, but better evidence on clinical outcomes is needed in women with PCOS.

TRIAL REGISTRATION: The protocol for the systematic review was registered prospectively in Prospero, CRD42022345640.

PMID:37440702 | DOI:10.1093/ejendo/lvad082

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PubMed articles on: Cancer & VTE/PE

Direct oral anticoagulants (DOACs) use for prolonged venous thromboembolism prophylaxis following surgery for gynaecological malignancies in Australia and New Zealand - A clinician survey

Aust N Z J Obstet Gynaecol. 2023 Jul 11. doi: 10.1111/ajo.13737. Online ahead of print.

ABSTRACT

BACKGROUND: Current international guidelines recommend 28 days of enoxaparin as venous thromboembolism (VTE) prophylaxis after surgery for gynaecologic cancer. Direct oral anticoagulants (DOACs) have been investigated as an alternative to enoxaparin for post-operative VTE prophylaxis. High-quality evidence to demonstrate safety and efficacy is lacking.

AIMS: We aim to investigate the current practice regarding VTE prophylaxis among gynaecological oncologists in Australia and New Zealand following laparotomy for gynaecological malignancy, in particular the use of DOACs for VTE prophylaxis.

MATERIALS AND METHODS: Sixty-seven practising gynaecologic oncologists (GO) were identified through Royal Australia and New Zealand College of Obstetricians and Gynaecologists database and emailed online surveys that asked about VTE prophylaxis practice and views of DOACs in this setting. Data were then collected through Survey Monkey and evaluated.

RESULTS: The majority (77.1%) routinely prescribed 28 days of enoxaparin following laparotomy for gynaecological malignancies. In clinical circumstance such as laparoscopy for gynaecological malignancies and surgery for vulva malignancies, there was variation in thromboprophylaxis practices. No GO reported routine use of DOACs in any clinical circumstance. There were 56% of GOs who used a DOAC in their practice at some point. Barriers to routine use of DOACs in current practice included insufficient evidence (68%), issue with cost (40.4%) and concerns about safety (29.7%).

CONCLUSIONS: Enoxaparin prescribed for 28 days remains the current clinical practice in preventing VTE following laparotomy for gynaecological malignancy. The main barrier to routine DOAC use as post-operative thromboprophylaxis is a lack of evidence which reflects the need for a larger prospective study.

PMID:37434425 | DOI:10.1111/ajo.13737

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PubMed articles on: Cancer & VTE/PE

Rivaroxaban versus Apixaban for Treatment of Cancer-Associated Venous Thromboembolism in Patients at Lower Risk of Bleeding

TH Open. 2023 Jul 10;7(3):e206-e216. doi: 10.1055/s-0043-1770783. eCollection 2023 Jul.

ABSTRACT

This retrospective study, utilizing U.S. electronic health record (EHR) data from January 2013 to December 2020, sought to assess whether rivaroxaban and apixaban had similar effectiveness and safety in the treatment of cancer-associated venous thromboembolism (VTE) in patients with a cancer type not associated with a high risk of bleeding. We included adults diagnosed with active cancer, excluding esophageal, gastric, unresected colorectal, bladder, noncerebral central nervous system cancers and leukemia, who experienced VTE and received a therapeutic VTE dose of rivaroxaban or apixaban on day 7 post-VTE, and were active in the EHR ≥12 months prior to the VTE. Primary outcome was the composite of recurrent VTE or any bleed resulting in hospitalization at 3 months. Secondary outcomes included recurrent VTE, any bleed resulting in hospitalization, any critical organ bleed, and composites of these outcomes at 3 and 6 months. Inverse probability of treatment-weighted Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). We included 1,344 apixaban and 1,093 rivaroxaban patients. At 3 months, rivaroxaban was found to have similar hazard to apixaban for developing recurrent VTE or any bleed resulting in hospitalization (HR: 0.87; 95% CI: 0.60-1.27). No differences were observed between cohorts for this outcome at 6 months (HR: 1.00; 95% CI: 0.71-1.40) or for any other outcome at 3 or 6 months. In conclusion, patients receiving rivaroxaban or apixaban showed similar risks of the composite of recurrent VTE or any bleed resulting in hospitalization in patients with cancer-associated VTE. This study was registered at www.clinicaltrials.gov as #NCT05461807. Key PointsRivaroxaban and apixaban have similar effectiveness and safety for treatment of cancer-associated VTE through 6 months.Clinicians should therefore consider patient preference and adherence when choosing the optimal anticoagulant.

PMID:37435565 | PMC:PMC10332896 | DOI:10.1055/s-0043-1770783

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PubMed articles on: Cancer & VTE/PE

Intravenous tranexamic acid is associated with an increased risk of pulmonary embolism following sarcoma resection

J Surg Oncol. 2023 Jul 10. doi: 10.1002/jso.27391. Online ahead of print.

ABSTRACT

INTRODUCTION: Tranexamic acid (TXA) is an antifibrinolytic drug that has been shown to reduce blood loss following surgery. The use of TXA during orthopedic procedures has gained widespread acceptance, with multiple clinical studies demonstrating no increase in thrombotic complications. While TXA has been shown to be safe and effective for several orthopedic procedures, its use in orthopedic sarcoma surgery is not well established. Cancer-associated thrombosis remains a significant cause of morbidity and mortality in patients with sarcoma. It is unknown if intraoperative TXA use will increase the risk of developing a postoperative thrombotic complication in this population. This study aimed to compare the risk of postoperative thrombotic complications in patients who received TXA during sarcoma resection to patients who did not receive TXA.

METHODS: A retrospective review was performed of 1099 patients who underwent resection of a soft tissue or bone sarcoma at our institution between 2010 and 2021. Baseline demographics and postoperative outcomes were compared between patients who did and did not receive intraoperative TXA. We evaluated 90-day complication rates, including: deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI), cerebrovascular accident (CVA), and mortality.

RESULTS: TXA was used more commonly for bone tumors (p < 0.001), tumors located in the pelvis (p = 0.004), and larger tumors (p < 0.001). Patients who received intraoperative TXA were associated with a significant increase in developing a postoperative DVT (odds ratio [OR]: 2.22, p = 0.036) and PE (OR: 4.62, p < 0.001), but had no increase in CVA, MI, or mortality (all p > 0.05) within 90 days of surgery, following univariate analysis. Multivariable analysis confirmed that TXA was independently associated with developing a postoperative PE (OR: 10.64, 95% confidence interval: 2.23-50.86, p = 0.003). We found no association with DVT, MI, CVA, or mortality within 90 days postoperatively, following intraoperative TXA use.

CONCLUSION: Our results demonstrate a higher associated risk of PE following TXA use in sarcoma surgery and caution is warranted with TXA use in this patient population.

PMID:37428014 | DOI:10.1002/jso.27391

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PubMed articles on: Cancer & VTE/PE

COMPASS-CAT versus Khorana risk assessment model for predicting venous thromboembolic events in patients with non-small cell lung cancer on active treatment with chemotherapy and/or immunotherapy, the CK-RAM study

J Thromb Thrombolysis. 2023 Jul 11. doi: 10.1007/s11239-023-02860-4. Online ahead of print.