The Pitfalls of Global Hemostasis Assays in Myeloproliferative Neoplasms and Future Challenges
Seminars in thrombosis and hemostasis. 2023
Venous and arterial thromboembolism are major complications of myeloproliferative neoplasms (MPNs), comprising polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Global hemostasis assays, including thrombin generation assay (TGA), rotational thromboelastometry (ROTEM), and thromboelastography (TEG), have been proposed as biomarkers to assess the hypercoagulability and thrombotic risk stratification in MPNs. We performed a systematic literature review on the parameters of TGA, ROTEM, and TEG and their association with thrombotic events and treatment strategies in MPNs. Thirty-two studies (all cross-sectional) were included, which collectively enrolled 1,062 controls and 1,608 MPN patients. Among the 13 studies that reported arterial or venous thrombosis, the overall thrombosis rate was 13.8% with 6 splanchnic thromboses reported. Out of the 27 TGA studies, there was substantial heterogeneity in plasma preparation and trigger reagents employed in laboratory assays. There was a trend toward increased peak height among all MPN cohorts versus controls and higher endogenous thrombin potential (ETP) between ET patients versus controls. There was an overall trend toward lower ETP between PV and PMF patients versus. controls. There were no substantial differences in ETP between JAK2-positive versus JAK2-negative MPNs, prior history versus negative history of thrombotic events, and among different treatment strategies. Of the three ROTEM studies, there was a trend toward higher maximum clot firmness and shorter clot formation times for all MPNs versus controls. The three TEG studies had mixed results. We conclude that the ability of parameters from global hemostasis assays to predict for hypercoagulability events in MPN patients is inconsistent and inconclusive. Further prospective longitudinal studies are needed to validate these biomarker tools so that thrombotic potential could be utilized as a primary endpoint of such studies.
Estimating Bleeding Risk in Patients with Cancer-Associated Thrombosis: Evaluation of Existing Risk Scores and Development of a New Risk Score
Thrombosis and haemostasis. 2021
BACKGROUND Bleeding risk is highly relevant for treatment decisions in cancer-associated thrombosis (CAT). Several risk scores exist, but have never been validated in patients with CAT and are not recommended for practice. OBJECTIVES To compare methods of estimating clinically relevant (major and clinically relevant nonmajor) bleeding risk in patients with CAT: (1) existing risk scores for bleeding in venous thromboembolism, (2) pragmatic classification based on cancer type, and (3) new prediction model. METHODS In a posthoc analysis of the Hokusai VTE Cancer study, a randomized trial comparing edoxaban with dalteparin for treatment of CAT, seven bleeding risk scores were externally validated (ACCP-VTE, HAS-BLED, Hokusai, Kuijer, Martinez, RIETE, and VTE-BLEED). The predictive performance of these scores was compared with a pragmatic classification based on cancer type (gastrointestinal; genitourinary; other) and a newly derived competing risk-adjusted prediction model based on clinical predictors for clinically relevant bleeding within 6 months after CAT diagnosis with nonbleeding-related mortality as the competing event ("CAT-BLEED"). RESULTS Data of 1,046 patients (149 events) were analyzed. Predictive performance of existing risk scores was poor to moderate (C-statistics: 0.50-0.57; poor calibration). Internal validation of the pragmatic classification and "CAT-BLEED" showed moderate performance (respective C-statistics: 0.61; 95% confidence interval [CI]: 0.56-0.66, and 0.63; 95% CI 0.58-0.68; good calibration). CONCLUSION Existing risk scores for bleeding perform poorly after CAT. Pragmatic classification based on cancer type provides marginally better estimates of clinically relevant bleeding risk. Further improvement may be achieved with "CAT-BLEED," but this requires external validation in practice-based settings and with other DOACs and its clinical usefulness is yet to be demonstrated.
Prognostic Value of Bleeding in Gastrointestinal Stromal Tumors: A Meta-Analysis
Technology in cancer research & treatment. 2021;20:15330338211034259
BACKGROUND Gastrointestinal bleeding is the most common clinical manifestation of gastrointestinal stromal tumor. It is of great significance to the prognosis of patients. But the results are controversial. The purpose of this study was to evaluate the relationship between gastrointestinal bleeding and clinical prognosis in patients with GIST. METHODS A systematic literature search was performed in Pumbed, Cochrane Library, EMBASE, ClinicalTrials.gov, CNKI, VIP and wanfang databases with the pattern of unlimited languages. 12 studies with 2781 individuals were included in the final analysis. The overall survival (OS), recurrence-free survival/disease-free survival (RFS/DFS) and related factors affecting bleeding in patients with gastrointestinal stromal tumor (GIST) were extracted. Hazard ratio (HR) and 95% confidence interval (CI) were used for in the meta-analysis. RESULTS A total of 12 articles were included in the study, including 2781 patients with GIST, including 845 patients with gastrointestinal bleeding. The OS of GIST patients with gastrointestinal bleeding was significantly worse (HR = 2.54, 95% CI = 1.13-5.73, P = 0.025). But there was no significant difference in RFS between gastrointestinal bleeding patients and non-bleeding patients (HR = 1.35, 95% CI = 0.70-2.61, P = 0.371). Further analysis of the related factors of GI bleeding in GIST patients was observed, besides the aging factor (HR = 1.02, 95% CI = 0.69-1.50, P = 0.929), Small intestinal stromal tumor (HR = 0.56, 95% CI = 0.41-0.76, P < 0.001), tumor diameter ≥ 5 cm (HR = 2.09, 95% CI = 1.20-3.63, P = 0.009), Mitotic index ≥ 5/50 HPF (HR = 1.66, 95% CI = 1.11-2.49, P = 0.014) and tumor rupture (HR = 2.04, 95% CI = 1.0-3.82, P = 0.026) all increased the risk of GI bleeding in patients with GIST. CONCLUSIONS The OS of GIST patients with GI bleeding was worse than non-GI bleeding, but had no significant effect on RFS. Nevertheless the aging factor, the location of GIST in the small intestine, tumor diameter ≥ 5 cm, Mitotic index ≥ 5/50 HPF and tumor rupture all increased the risk of GI bleeding in patients with GIST.
Postoperative bleeding in essential thrombocytosis patients with colorectal cancer: Case report and literature review
International journal of surgery case reports. 2021;86:106374
INTRODUCTION AND IMPORTANCE Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by increased platelet count and a high risk of bleeding or thrombotic events due to platelet dysfunction. Patients with ET are treated according to their risk of complications with cytoreductive or anti-aggregant treatment. Neither guidelines for oncologic patients nor perioperative management of patients with ET have been determined. CASE PRESENTATION A 41-year-old female patient with ET who had alternating constipation and diarrhea was referred after a screening colonoscopy diagnosing a locally advanced rectosigmoid junction colon adenocarcinoma with liver metastases. Systemic preoperative chemotherapy was indicated. The patient underwent laparoscopic low anterior resection plus volume-preserving right lobectomy of the liver. Postoperative bleeding of the internal iliac artery (IIA) associated with hematoma at the lower pelvic cavity was diagnosed and treated by interventional radiology; the patient was discharged without other complications 16 days after surgery. CLINICAL DISCUSSION ET has been related to the development of hematologic complications or second non-hematologic malignancies. A systematic review was conducted to seek guidance for the management of such patients in the perioperative period. Special perioperative care must be taken, and complications management should avoid further hemorrhages or cloth formation. CONCLUSION Under oncologic and hematological guidance, minimally invasive surgery and non-invasive management of complications are advised in the lack of published perioperative management guidelines of ET patients with colorectal cancer.
The risk factors for delayed bleeding after endoscopic resection of colorectal tumors: a meta-analysis
Expert Rev Gastroenterol Hepatol. 2020
INTRODUCTION The most common complication of post-colorectal endoscopic resection is delayed bleeding. The assessment of risk factors for delayed bleeding provide important and useful information in standard clinical operations. The risk factors have been previously reported, however they remain inconsistent across different studies. AREAS COVERED In this meta-analysis the patient conditions, lesion-related factors, and operation-related factors were compared between delayed bleeding and no bleeding. PubMed, Cochrane, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang Database were searched to identify eligible studies. Pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated along with heterogeneity. EXPERT OPINION This study is the first meta-analysis to investigate risk factors for colorectal delayed bleeding. We found several risk factors contributing to this condition: colorectal tumors located in the proximal colon, a history of antithrombotic drug use, high-grade intraepithelial neoplasia or early cancer, piecemeal resection, intraoperative hemorrhage, no clip placement, and severe submucosal fibrosis. Despite our findings, we also conclude that more high-quality, large-scale clinical randomized controlled studies are needed due to limited retrospective studies at present. Future therapeutic colonoscopies should focus on precise diagnosis, treatment safety, and management during the perioperative period.
The effects of infusion methods on platelet count, morphology, and corrected count increment in children with cancer: in vitro and in vivo studies
Oncology Nursing Forum. 1994;21((10):):1669-73.
PURPOSE/OBJECTIVES To determine whether infusion method influences the quality of platelets transfused. DESIGN Linked in vitro and in vivo study. Quasi-experimental design for in vitro and cross-over design with balanced randomization for in vivo. SETTING Pediatric cancer center in the midsouthern United States. SAMPLE Pheresed/pooled platelet units in vitro (n = 12). In vivo convenience sample of 26 children, ages 2-19 years, with cancer and thrombocytopenia who required platelet transfusion. METHODS Two infusion pumps (IMED 980 and Gemini, IMED Corp., San Diego, CA) versus gravity flow for in vitro platelet infusion. Gemini infusion pump versus gravity flow for in vivo platelet transfusion. MAIN OUTCOME MEASURES Platelet count, morphology score, and corrected count increment. FINDINGS No significant differences noted in platelet count or morphology score among or across the three infusion methods in vitro. No significant differences noted between the two infusion methods in platelet count or corrected count increment in vivo. CONCLUSIONS Although limited to a specific patient population, setting, and infusion device, findings revealed that the pump was clinically acceptable because it did not negatively affect platelet recovery. Replication of this study with other infusion devices is recommended. IMPLICATIONS FOR NURSING PRACTICE Study findings validate the current nursing procedure for the administration of platelets at the study setting. Use of infusion pumps for platelet transfusions is time-efficient and energy-efficient for nurses because the pumps offer a well-controlled infusion rate, accurate volume measurement, and an alarm system for monitoring the infusion.