Hyperfibrinolysis in Patients with Solid Malignant Neoplasms: A Systematic Review
Seminars in thrombosis and hemostasis. 2020
Solid malignant neoplasms have the capability of disturbing the fibrinolytic system, leading to primary hyperfibrinolysis, a paraneoplastic syndrome that potentially results in severe bleeding. Yet, the full extent of primary hyperfibrinolysis in solid malignant neoplasms is unknown. Thus, the purpose of this study was to systematically review the current literature regarding clinical manifestations, biochemical diagnosis, and treatment of primary hyperfibrinolysis in patients with solid malignant neoplasms. The review was performed in agreement with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases PubMed, Embase, Scopus, and Web of Science were searched on December 5, 2019, without time limits. Studies were included if they comprised at least one biochemical marker of fibrinolysis in addition to fibrinogen degradation products such as D-dimer, and furthermore included a correlation between biochemical marker and clinical outcome. In total, 12 studies were included. All studies were case reports including a total of 21 patients. Prostate cancer was the most frequently represented cancer type (76%), and the majority of cancer patients had metastatic disease (81%). Spontaneous bleeding was the clinical presentation in the majority of patients (76%), and the most frequently localization for the bleedings was subcutaneous. Antifibrinolytic agents were the most commonly used treatment and ceased bleedings in 80% of patients. Three patients died of uncontrolled bleedings. In conclusion, primary hyperfibrinolysis induced by solid malignant neoplasms is a rare but potentially life-threatening condition that should be considered, especially in patients with metastatic disease presenting with serious, spontaneous subcutaneous bleedings. A standardized diagnostic strategy is strongly needed.
Preoperative tranexamic acid does not reduce transfusion rates in major oncologic surgery: Results of a randomized, double-blind, and placebo-controlled trial
J Surg Oncol. 2020
BACKGROUND AND OBJECTIVES Allogeneic blood transfusions are associated with worse postoperative outcomes in oncologic surgery. The aim of this study was to introduce a preoperative intervention to reduce transfusion rates in this population. METHODS Adult patients undergoing major oncologic surgery in five categories with similar transfusion rates were recruited. Enrollees received a single preoperative intravenous dose of placebo or tranexamic acid (1000 mg). The primary outcome measure was perioperative transfusion rate. Secondary outcome measures included: estimated blood loss, thromboembolic events, morbidity, hospital length of stay, and readmission rate. RESULTS Seventy-six patients were enrolled, 39 in the tranexamic acid group and 37 in the placebo group, respectively. Demographics and surgery type were equivalent between groups. The transfusion rates were 8 out of 39 (20.5%) in the tranexamic acid group and 5 out of 37 (13.5%) in the placebo group, respectively (P = .418). Median estimated blood loss was 400 mL (interquartile range [IQR] = 150-600) in the tranexamic acid group compared with 300 mL (IQR = 150-800) in the placebo group (P = .983). There was one pulmonary embolism in each arm and no deep venous thrombosis (P > .999). CONCLUSION Preoperative administration of tranexamic acid at a 1000 mg intravenous dose does not decrease transfusion rates or estimated blood loss in patients undergoing major oncologic surgery.
Patients undergoing major oncologic surgery (n= 76).
Preoperative intravenous dose of tranexamic acid (n= 39).
Placebo (n= 37).
Transfusion rates were 8 out of 39 (20.5%) in the tranexamic acid group and 5 out of 37 (13.5%) in the placebo group. Median estimated blood loss was 400 mL (interquartile range [IQR] = 150-600) in the tranexamic acid group compared with 300 mL (IQR = 150-800) in the placebo group. There was one pulmonary embolism in each arm and no deep venous thrombosis.
Palliative interventions for controlling vaginal bleeding in advanced cervical cancer
The Cochrane database of systematic reviews. 2019;3:Cd011000
BACKGROUND This is an updated version of the original Cochrane review published in Issue 5, 2015.Cervical cancer is the fourth most common cancer among women worldwide, with estimated 569,847 new diagnoses and 311,365 deaths per year. However, incidence and stage at diagnosis vary greatly between geographic areas and are largely dependent on the availability of a robust population screening programme. For example, in Nigeria, advanced-stage disease at presentation is common (86% to 89.3% of new cases), whereas in the UK, only 21.9% of women present with International Federation of Gynaecology and Obstetrics (FIGO) stage II+ disease. Women with advanced cancer of the cervix often need palliation for distressing symptoms, such as vaginal bleeding. Vaginal bleeding can be life threatening in advanced disease, with an incidence ranging from 0.7% to 100%. Bleeding is the immediate cause of death in 6% of women with cervical cancer and its management often poses a challenge.Thus, vaginal bleeding remains a common consequence of advanced cervical cancer. Currently, there is no systematic review that addresses palliative interventions for controlling vaginal bleeding caused by advanced cervical cancer. A systematic evaluation of the available palliative interventions is needed to inform decision-making. OBJECTIVES To evaluate the efficacy and safety of tranexamic acid, vaginal packing (with or without formalin-soaked packs), interventional radiology or other interventions compared with radiotherapy for palliative treatment of vaginal bleeding in women with advanced cervical cancer. SEARCH METHODS The search for the original review was run in 23 March 2015, and subsequent searches for this update were run 21 March 2018. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 3) in the Cochrane Library; MEDLINE via Ovid to March week 2, 2018; and Embase via Ovid to March week 12, 2018. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of review articles, and contacted experts in the field. We handsearched citation lists of relevant studies. SELECTION CRITERIA We searched for randomised and non-randomised comparative studies that evaluated the efficacy and safety of tranexamic acid, vaginal packing (with or without formalin-soaked packs), interventional radiology or other interventions compared with radiotherapy techniques for palliative treatment of vaginal bleeding in women with advanced cervical cancer (with or without metastasis), irrespective of publication status, year of publication or language in the review. DATA COLLECTION AND ANALYSIS Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. We found no studies for inclusion and, therefore, we analysed no data. MAIN RESULTS The search strategy identified 1522 unique references of which we excluded 1330 on the basis of title and abstract. We retrieved the remaining 22 articles in full, but none satisfied the inclusion criteria. We identified only observational data from single-arm studies of women treated with formalin-soaked packs, interventional radiology or radiotherapy techniques for palliative control of vaginal bleeding in women with cervical cancer. AUTHORS' CONCLUSIONS Since the last version of this review we found no new studies. There is no evidence from controlled trials to support or refute the use of any of the proposed interventions compared with radiotherapy. Therefore, the choice of intervention will be based on local resources. Radiotherapy techniques for managing vaginal bleeding are not readily available in resource-poor settings, where advanced cases of cervical cancer are predominant. Thus, this systematic review identified the need for a randomised controlled trial assessing the benefits and risks of palliative treatments for vaginal bleeding in women with advanced cervical cancer.
Does tranexamic acid reduce blood loss during head and neck cancer surgery?
Indian Journal of Anaesthesia. 2016;60((1)):19-24.
BACKGROUND AND AIMS Transfusion of blood and blood products poses several hazards. Antifibrinolytic agents are used to reduce perioperative blood loss. We decided to assess the effect of tranexamic acid (TA) on blood loss and the need for transfusion in head and neck cancer surgery. METHODS After Institutional Review Board approval, 240 patients undergoing supramajor head and neck cancer surgeries were prospectively randomised to either TA (10 mg/kg) group or placebo (P) group. After induction, the drug was infused by the anaesthesiologist, who was blinded to allocation, over 20 min. The dose was repeated every 3 h. Perioperative (up to 24 h) blood loss, need for transfusion and fluid therapy was recorded. Thromboelastography (TEG) was performed at fixed intervals in the first 100 patients. Patients were watched for post-operative complications. RESULTS Two hundred and nineteen records were evaluable. We found no difference in intraoperative blood loss (TA - 750 [600-1000] ml vs. P - 780 [150-2600] ml, P = 0.22). Post-operative blood loss was significantly more in the placebo group at 24 h (P - 200 [120-250] ml vs. TA - 250 [50-1050] ml, P = 0.009), but this did not result in higher number of patients needing transfusions (TA - 22/108 and P - 27/111 patients, P = 0.51). TEG revealed faster clot formation and minimal fibrinolysis. Two patients died of causes unrelated to study drug. Incidence of wound complications and deep venous thrombosis was similar. CONCLUSION In head and neck cancer surgery, TA did not reduce intraoperative blood loss or need for transfusions. Perioperative TEG variables were similar. This may be attributed to pre-existing hypercoagulable state and minimal fibrinolysis in cancer patients.
Does the preoperative administration of tranexamic acid reduce perioperative blood loss and transfusion requirements after head neck cancer surgery? A randomized, controlled trial
Albang Maqalat Wa Abhat Fi Altahdir Waalinas. 2015;9((3)):384-90.
BACKGROUND Head and neck cancer (HNC) surgery is associated with high intraoperative blood loss which may require urgent blood transfusion. Many strategies have been recommended to decrease the need for allogenic transfusion. Use of perioperative tranexamic acid (TA) has a promising role. AIMS This study was to evaluate the effectiveness of single preoperative bolus dose of TA on blood loss prevention and red blood cell transfusion in patients undergoing HNC surgery. STUDY DESIGN A prospective, double-blind, and randomized controlled study. MATERIALS AND METHODS From 2007 July to 2010 January; 80 patients, aged (35-55), of American Society of Anesthesiologists II-III scheduled for unilateral HNC surgeries were randomly received either TA (Group T) in a dose of 20 mg/kg diluted to 25 cc with normal saline or an equivalent volume of normal saline (Group C) in a tertiary care hospital. Hemoglobin (Hb) concentration, platelet count, packed cell volume, fibrinogen level, D-dimer level were measured pre- and post-operatively. RESULTS Saline (C) Group required more blood, colloid, crystalloid for blood loss. In Group T, 32 patients did not require transfusion of any blood products compared to five patients in Group C (P < 0.0001) and only eight units of blood was transfused in Group T, whereas a total of 42 units of blood was transfused in Group C. Even after numerous transfusions, Hb% after 6 h and 24 h in Group C were significantly low in comparison with Group T (P < 0.05). CONCLUSION Thus, TA significantly reduces blood loss and chances of colloid, blood, and crystalloid transfusion caused by HNC surgery.
Single-dose tranexamic acid in advanced ovarian cancer surgery reduces blood loss and transfusions: double-blind placebo-controlled randomized multicenter study
Acta Obstetricia et Gynecologica Scandinavica. 2014;93((4):):335-44.
OBJECTIVE To determine whether single-dose tranexamic acid given intravenously immediately before surgery for presumed advanced ovarian cancer reduces perioperative blood loss and blood transfusions. DESIGN A randomized double-blind, placebo-controlled multicenter study. SETTING Two university hospitals and two central hospitals in the southeast health region of Sweden. POPULATION One hundred women with presumed advanced ovarian cancer scheduled for radical debulking surgery between March 2008 and May 2012 who complied with inclusion/exclusion criteria were randomized; 50 were allocated to receive tranexamic acid and 50 to receive placebo. Analysis was performed according to intention-to-treat principles. METHODS The volume of tranexamic acid (15 mg/kg body weight, 100 mg/mL tranexamic acid) or the same volume of placebo (0.9% NaCl) was added to a 100-mL saline solution plastic bag. The study medication was given immediately before the start of surgery. Data were analyzed by means of non-parametric statistics and multivariate models adjusted for confounding factors. MAIN OUTCOME MEASURES Blood loss and red blood cell transfusions. RESULTS The total blood loss volume and transfusion rate were significantly lower in the tranexamic acid group compared with the placebo group. Median total blood loss was 520 and 730 mL, respectively (p = 0.03). Fifteen (30%) and 22 (44%), respectively received transfusions (odds ratio 0.44; upper 95% CI 0.97; p = 0.02). CONCLUSION A single dose of tranexamic acid given immediately before surgery reduces blood loss and transfusion rates significantly in advanced ovarian cancer surgery. Tranexamic acid may be recommended as standard prophylactic treatment in advanced ovarian cancer surgery. 2014 Nordic Federation of Societies of Obstetrics and Gynecology.
A possible association between aprotinin and improved survival after radical surgery for mesothelioma
BACKGROUND Aprotinin has been used to decrease blood loss with complicated cardiac surgery but has not been investigated in extrapleural pneumonectomy, an operation that does not use cardiopulmonary bypass. In this prospective, randomized, placebo-controlled, double-blind trial, the authors investigated whether aprotinin decreased blood loss in patients who underwent this operation. METHODS After appropriate statistical design and institutional review board approval, eligible patients who were scheduled for extrapleural pneumonectomy were randomized to receive either aprotinin or placebo during the operation. Blood loss and survival data were obtained from electronic medical records and surgical databases. RESULTS Of 20 patients who were enrolled, 16 patients met criteria for blood loss analysis. Four patients were excluded from the blood loss analysis: Three patients were inoperable because of tumor spread and underwent limited surgery, and 1 patient died intraoperatively because of acute, massive hemorrhage. The mean blood loss was 769 mL with aprotinin versus 1832 mL with placebo (P = . 05; Wilcoxon test). All 20 patients were included in survival analyses. All 9 patients who received placebo died. In contrast, 7 of 11 patients who received aprotinin remained alive at the time of the current report. Kaplan-Meier survival curves differed significantly between the 2 groups (P = . 0004). A Bayesian multivariate survival analysis of 18 patients who had complete data available on 8 prognostic variables indicated a posterior probability of . 99 that aprotinin was beneficial. CONCLUSIONS Aprotinin decreased blood loss. After accounting for covariate effects, there was a significant comparative benefit with aprotinin in postoperative survival. This finding was unexpected and could not be considered conclusive because of the small size of the current study. A confirmatory study may be warranted.
Perioperative and postoperative tranexamic acid reduces the local wound complication rate after surgery for breast cancer
British Journal of Surgery. 1994;81((6):):856-9.
A randomized double-blind trial has shown that, in 160 women with breast cancer undergoing lumpectomy or mastectomy with axillary clearance, perioperative and postoperative administration of tranexamic acid 1 g three times daily resulted in a significant reduction in the mean postoperative drainage volume compared with patients given placebo (283 versus 432 ml, P < 0.001). The frequency of postoperative seroma formation was also decreased by tranexamic acid administration (27 versus 37 per cent, P = 0.2). Haematoma formation was infrequent in both groups and was not altered by administration of tranexamic acid. No infectious complications occurred. Age over 60 years was a significant risk factor for overall wound complications but tumour size and regional lymph node metastases were not. Tranexamic acid may be used to reduce the frequency of postoperative wound complications following surgery for breast cancer.
The hemostatic effect of tranexamic acid in conisatio colli uteri
Acta Obstetricia et Gynecologica Scandinavica. 1984;63((1):):81-4.
To evaluate the inhibitory effect of tranexamic acid (AMCA) on increased fibrinolyctical activity in connection with conisatio colli uteri we have carried out a randomized, double-blind study with patients operated upon partly with an open method of operation (80 patients) and partly with modified Sturmdorff sutures (150 patients). In connection with the open method the frequency of late bleeding decreased from 17.5% to 2.5%, which is significant. The corresponding decrease in connection with the other method was from 10.7% to 4.1%. This material was not sufficiently large to verify significance. The side effects of the prophylactic treatment with AMCA were few. The study indicates that AMCA affords good protection against late bleeding in conisatio colli uteri.
Use of an antifibrinolytic agent (tranexamic acid) and lateral sutures with laser conization of the cervix
Obstetrics & Gynecology. 1984;64((4):):573-6.
One hundred forty patients who underwent laser conization and 220 patients who underwent laser miniconizations were prospectively randomized into two study groups. One treatment group was given antifibrinolytic therapy in the form of tranexamic acid (Cyklokapron, KabiVitrum, Sweden) intraoperatively and for 14 days postoperatively. The other group did not receive antifibrinolytic therapy. In the group of 68 patients with laser conizations who were given antifibrinolytic therapy, no postoperative hemorrhages occurred, whereas there were eight such hemorrhages in 72 conizations (11%) in the untreated patients. This difference is statistically significant (P = .004, Fisher exact test for two proportions). Also, for laser miniconization, the frequency of postoperative hemorrhage was almost halved, from 9.1% in 110 patients not receiving antifibrinolytic therapy to 5.5% in the 110 treated patients. The use of lateral cervical sutures did not reduce the frequency of postoperative hemorrhage at laser conization in the present study.