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1.
The Pitfalls of Global Hemostasis Assays in Myeloproliferative Neoplasms and Future Challenges
Tiu A, Chiasakul T, Kessler CM
Seminars in thrombosis and hemostasis. 2023
Abstract
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.
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Effect of Benson's relaxation technique versus music intervention on physiological parameters and stress of children with thalassemia during blood transfusions: A randomized controlled trial
Badr, E. A., Ibrahim, H., Saleh, S. E.
Journal of pediatric nursing. 2023
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Editor's Choice
Abstract
BACKGROUND Children with thalassemia are generally dependent on blood transfusions and face a lot of stress and alteration in their physiological parameters through the procedure. AIM: This study aimed to investigate the effect of Benson's relaxation technique versus music intervention on physiological parameters and stress of children with thalassemia during blood transfusions. DESIGN A randomized, controlled trial with three parallel groups. METHODS One hundred and twenty preschool-age children with thalassemia who underwent blood transfusions were randomly assigned to three groups. Children of the control group received only routine hospital care through blood transfusions. Music intervention group children listened to recorded Mozart's music and children of Benson's relaxation group received relaxation intervention before and during the blood transfusions. Outcome measures were physiological parameters and behavioral distress levels. SETTING Hematology outpatient clinic of the Children's University Hospital at El-Shatby in Alexandria from October 2022 to February 2023. RESULTS The mean total score of children's behavioral responses to stress before the blood transfusions procedure was 19.32 ± 4.08, 14.20 ± 0.93, and 16.92 ± 4.74 in the control, music, and Benson groups, respectively. Beyond that, there was a decline in their physiological parameters and behavioral stress response during and after procedure among groups of study (P = 0.005 & <0.001, respectively). CONCLUSION Music and Benson's relaxation interventions had a helpful effect on stabilizing the physiological parameters and reducing behavioral distress levels in children with thalassemia undergoing blood transfusions. PRACTICE IMPLICATIONS This study directs paediatric nurses to apply Benson's relaxation and music interventions for children with thalassemia to enhance their responses.
PICO Summary
Population
Preschool-age children with thalassemia who underwent blood transfusions (n= 120).
Intervention
Benson’s relaxation technique intervention (n= 40).
Comparison
Mozart's music intervention (n= 40); routine hospital care (n= 40).
Outcome
The mean total score of children's behavioral responses to stress before the blood transfusions procedure was 19.32 ± 4.08, 14.20 ± 0.93, and 16.92 ± 4.74 in the control, music, and Benson groups, respectively. Beyond that, there was a decline in their physiological parameters and behavioral stress response during and after procedure among groups of study.
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Patient-reported outcomes in autosomal inherited bleeding disorders: A systematic literature review
van Hoorn ES, Houwing ME, Al Arashi W, Leebeek FWG, Hazelzet JA, Gouw SC, Schutgens REG, Schols SEM, Lingsma HF, Cnossen MH
Haemophilia : the official journal of the World Federation of Hemophilia. 2022
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Abstract
AIM: Currently, it is unknown which patient-reported outcomes are important for patients with autosomal inherited bleeding disorders. Therefore, the purpose of this study is to systematically review the available literature assessing patient-reported outcomes and their measurement methods in autosomal inherited bleeding disorders. METHODS The Embase, Medline ALL, Web of Science Core Collection, Cochrane Central Register of Controlled Trails and Google Scholar databases were searched from inception until 14 August 2020. Studies on patient-reported outcomes in patients with von Willebrand disease, inherited platelet function disorders and coagulation factor deficiencies were included. RESULTS Twenty-one articles met the inclusion criteria. Three studies were assessed as having poor quality, and therefore a high risk of bias. Nineteen studies had fair quality rating. Different measurements methods were used, ranging from predefined to self-developed questionnaires. The majority of included studies focused on von Willebrand disease. Patients with von Willebrand disease reported lower health-related quality of life compared to the general population. Overall, this trend was especially visible in the following domains: vitality, physical and social functioning and pain. Women with inherited bleeding disorders scored lower on health-related quality of life compared to men, especially women with heavy menstrual bleeding. Patients with joint bleeds or heavy menstrual bleeding reported an increased level of pain. CONCLUSION Patients with autosomal inherited bleeding disorders report lower health related quality of life, especially those with joint bleeds or heavy menstrual bleeding. Numerous measurement methods are used in patients with autosomal inherited bleeding disorders, highlighting the need for studies using established, standardized measurement methods.
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Risk factors for bleeding in people living with Hemophilia A and B treated with regular prophylaxis: a systematic review of the literature
Germini F, Noronha N, Philip BA, Olasupo O, Pete D, Navarro T, Keepanasseril A, Matino D, de Wit K, Parpia S, et al
Journal of thrombosis and haemostasis : JTH. 2022
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Editor's Choice
Abstract
BACKGROUND Knowledge about the risk for bleeding in patients with hemophilia (PWH) would be relevant for patients, stakeholders, and policy makers. OBJECTIVES to perform a systematic review of the literature on risk assessment models (RAMs) and risk factors for bleeding in PWH on regular prophylaxis. METHODS We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews from inception through August 2019. In duplicate, reviewers screened the articles for inclusion, extracted data, and assessed the risk for bias using the QUIPS tool. A qualitative synthesis of the results was not performed due to high heterogeneity in risk factors, outcomes definition and measurement, and statistical analysis of the results. RESULTS From 1843 search results, 10 studies met the inclusion criteria. No RAM for the risk for bleeding in PWH was found. Most studies included only PWH A or both PWH A and B and were conducted in North America or Europe. Only one study had a low risk for bias in all the domains. Eight categories of risk factors were identified. The risk for bleeding was increased when factor levels were lower and in people with a significant history of bleeding or who engaged in physical activities involving contact. CONCLUSIONS Our findings suggest that plasma factor levels, history of bleeds, and physical activity should be considered for the derivation analysis when building a RAM for bleeding in PWH, and the role of other risk factors, including antithrombotic treatment and obesity, should be explored.
PICO Summary
Population
People living with haemophilia (PWH) A and B treated with regular prophylaxis (10 studies).
Intervention
Systematic review on risk assessment models and risk factors for bleeding.
Comparison
Outcome
No risk assessment model for the risk for bleeding was found. Most studies included only PWH A or both PWH A and B and were conducted in North America or Europe. Only one study had a low risk for bias in all the domains. Eight categories of risk factors were identified. The risk for bleeding was increased when factor levels were lower and in people with a significant history of bleeding or who engaged in physical activities involving contact.
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CREST: clinical bleeding and risk evaluation in hematology-oncology patients: a systematic review and meta-analysis of thromboelastography's role
Khoo CEH, Long MH, Shi L, Guo L, Hee HI
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. 2022
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Abstract
Thrombocytopenia and bleeding are common complications of hematologic malignancies. Often, prophylactic platelets are administered to minimize bleeding risk, based on total platelet count (TPC). However, TPC is a poor predictor, and does not provide rapid information. This review presents a novel prospective in the use of point-of-care viscoelastic studies to assess bleeding risk and guide transfusion therapy in a haematological oncological population, where its use can be extended to a ward level as a bedside test. Monitoring TEG maximum amplitude trends may be useful to guide transfusion protocols, especially for patients with total platelet counts ranging 30-100 × 109/l. Fibrinogen assessment in this group of patients may identify other blood components that require replacing to reduce bleeding risk. Normal maximum amplitude parameters for patients with low platelet counts can be a reassuring sign. This meta-analysis serves to remind the reader that absolute platelet quantity does not equate to the quality of clot formation.
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Estimating Bleeding Risk in Patients with Cancer-Associated Thrombosis: Evaluation of Existing Risk Scores and Development of a New Risk Score
de Winter MA, Dorresteijn JAN, Ageno W, Ay C, Beyer-Westendorf J, Coppens M, Klok FA, Moustafa F, Riva N, Ruiz Artacho PC, et al
Thrombosis and haemostasis. 2021
Abstract
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.
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Bleeding Assessment Tools in the Diagnosis of von Willebrand Disease: Systematic Review & Meta-Analysis of Test Accuracy
Kalot MA, Husainat N, Tayiem S, El Alayli A, Dimassi AB, Diab O, Abughanimeh O, Madoukh B, Qureini A, Ameer B, et al
Blood advances. 2021
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Abstract
BACKGROUND Von Willebrand Disease (VWD) can be associated with significant morbidity. Patients with VWD can experience bruising, mucocutaneous bleeding, and bleeding after dental and surgical procedures. Early diagnosis and treatment are important to minimize the risk of these complications. Several bleeding assessment tools (BATs) have been used to quantify bleeding symptoms as a screening tool for VWD. OBJECTIVE We systematically reviewed diagnostic test accuracy results of bleeding assessment tools (BATs) to screen patients for VWD. METHODS We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. Two investigators screened and abstracted data. Risk of bias was assessed using QUADAS-2 and certainty of evidence using the GRADE framework. We pooled estimates of sensitivity and specificity. RESULTS The review included 7 cohort studies that evaluated the use of BATs to screen adult and pediatric patients for VWD. The pooled estimates for sensitivity and specificity were 75% (95% confidence interval [CI] 66%-83%) and 54% (29%-77%), respectively. Certainty of evidence varied from moderate to high. CONCLUSION This systematic review provides accuracy estimates for validated BATs as a screening modality for VWD. A BAT is a useful initial screening test to determine who needs specific blood testing. The pretest probability of VWD (often determined by the clinical setting/patient population), along with sensitivity and specificity estimates will influence patient management.
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Management of surgery, menorrhagia and child-birth for patients with unclassified bleeding disorders: a systematic review of cohort studies
Desborough MJR, Obaji S, Lowe GC, Doree C, Thomas W
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. 2021
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Editor's Choice
Abstract
Unclassified bleeding disorders account for 2.6% of all new bleeding disorder registrations in the UK. The management of the bleeding phenotype associated with these disorders is poorly described. Systematic review and meta-analysis to determine the bleeding rates associated with tranexamic acid, desmopressin, platelet transfusion, plasma transfusion and recombinant activated factor VII, for patients with unclassified bleeding disorders undergoing surgery, childbirth or with menorrhagia. We searched for randomized controlled trials in MEDLINE, Embase, The Cochrane Central Register of Controlled Trials, PubMed, ISI Web of Science and the Transfusion Evidence Library from inception to 24 February 2020. Wherever appropriate, data were pooled using the metaprop function of STATA. Two studies with 157 participants with unclassified bleeding disorders were identified. The pooled risk of minor bleeding for patients undergoing surgery treated with peri-operative tranexamic acid was 11% (95% confidence interval 3--20%; n = 52; I2 = 0%); the risk for desmopressin and tranexamic acid in combination was 3% (95% confidence interval 0--7%; n = 71; I2 = 0%). There were no instances of major bleeding. In one procedure, 1 of 71 (1.4%), treated with a combination of desmopressin and tranexamic acid, the patient had a line-related deep vein thrombosis. There were too few patients treated to prevent postpartum haemorrhage or for menorrhagia to draw conclusions. The GRADE quality of evidence was very low suggesting considerable uncertainty over the results. However, both tranexamic acid, and the combination of tranexamic and desmopressin have high rates of haemostatic efficacy and have few adverse events. PROTOCOL REGISTRATION PROSPERO CRD42020169727.
PICO Summary
Population
Patients with unclassified bleeding disorders undergoing surgery, childbirth or with menorrhagia (2 studies, n= 157).
Intervention
Systematic review and meta-analysis to determine the bleeding rates associated with tranexamic acid (TXA), desmopressin, platelet transfusion, plasma transfusion and recombinant activated factor VII.
Comparison
Outcome
The pooled risk of minor bleeding for patients undergoing surgery treated with peri-operative TXA was 11%; the risk for desmopressin and TXA in combination was 3%. There were no instances of major bleeding. There were too few patients treated to prevent postpartum haemorrhage or for menorrhagia. The GRADE quality of evidence was very low suggesting considerable uncertainty over the results. However, both TXA, and the combination of TXA and desmopressin have high rates of haemostatic efficacy and have few adverse events.
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Neonatal Uterine Bleedings: An Ignored Sign but a Possible Cause of Early-Onset Endometriosis - A Systematic Review
Dekker J, Hooijer I, Ket JCF, Vejnović A, Benagiano G, Brosens I, Mijatovic V
Biomedicine hub. 2021;6(1):6-16
Abstract
OBJECTIVE Based on the hypothesis that neonatal uterine bleedings (NUB), occurring mostly in the first week after birth, could represent a pathogenetic mechanism for early-onset endometriosis, this systematic review (SR) was undertaken to evaluate the prevalence and screening strategies used to assess and quantify NUB. DESIGN Both a SR and a sample literature search in PubMed and Embase were conducted to gather information on NUB prevalence and screening techniques. This was performed by an information specialist. Only full-text articles regarding the assessment of NUB in neonates in the first 2 weeks after birth were included. No limit on language or publication data was used. MATERIALS AND METHODS The SR was registered in PROSPERO (CRD42019138121). Data was first assessed for eligibility on title and abstract by 2 blinded review authors. Any disagreements were discussed with a third reviewer if necessary. Subsequently, full-text articles were read and assessed for quality using the Cochrane Collaboration Handbook. RESULTS Out of 1,988 articles in the systematic search, 10 relevant articles were selected, of which 8 were identified through the systematic search and 2 were found through other sources. The sample search of 4,445 articles did not bring up relevant articles. Results were not comparable due to the heterogeneity of screening techniques, although data showed consensus. The prevalence of visible bleeding ranged from 3.3 to 53.8% and the prevalence of occult bleeding from 25.4 to 96.7%. The occurrence was the highest between the 3rd and 7th day postpartum (PP) and the bleeding lasted for 3-4 days on average. Various screening techniques for detecting NUB were found in the literature, including the use of hemoglobin detection devices (such as Hemastix) in the vaginal vestibulum, comparison of diapers with stains of known volume, colposcopy, and ultrasonography. CONCLUSION The reported prevalence of NUB varies considerably, with a consistent occurrence between the 3rd and the 7th day PP. Literature to assess NUB is dated. The techniques are poorly described and heterogeneous. Future research should focus on prospective cohort studies in order to attempt to correlate NUB cases to (early-onset) endometriosis.
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Evidence-based interventions implemented in low-and middle-income countries for sickle cell disease management: A systematic review of randomized controlled trials
Gyamfi J, Ojo T, Epou S, Diawara A, Dike L, Adenikinju D, Enechukwu S, Vieira D, Nnodu O, Ogedegbe G, et al
PloS one. 2021;16(2):e0246700
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Editor's Choice
Abstract
BACKGROUND Despite ~90% of sickle cell disease (SCD) occurring in low-and middle-income countries (LMICs), the vast majority of people are not receiving evidence-based interventions (EBIs) to reduce SCD-related adverse outcomes and mortality, and data on implementation research outcomes (IROs) and SCD is limited. This study aims to synthesize available data on EBIs for SCD and assess IROs. METHODS We conducted a systematic review of RCTs reporting on EBIs for SCD management implemented in LMICs. We identified articles from PubMed/Medline, Global Health, PubMed Central, Embase, Web of Science medical subject heading (MeSH and Emtree) and keywords, published from inception through February 23, 2020, and conducted an updated search through December 24, 2020. We provide intervention characteristics for each study, EBI impact on SCD, and evidence of reporting on IROs. MAIN RESULTS 29 RCTs were analyzed. EBIs identified included disease modifying agents, supportive care agents/analgesics, anti-malarials, systemic treatments, patient/ provider education, and nutritional supplements. Studies using disease modifying agents, nutritional supplements, and anti-malarials reported improvements in pain crisis, hospitalization, children's growth and reduction in severity and prevalence of malaria. Two studies reported on the sustainability of supplementary arginine, citrulline, and daily chloroquine and hydroxyurea for SCD patients. Only 13 studies (44.8%) provided descriptions that captured at least three of the eight IROs. There was limited reporting of acceptability, feasibility, fidelity, cost and sustainability. CONCLUSION EBIs are effective for SCD management in LMICs; however, measurement of IROs is scarce. Future research should focus on penetration of EBIs to inform evidence-based practice and sustainability in the context of LMICs. CLINICAL TRIAL REGISTRATION This review is registered in PROSPERO #CRD42020167289.
PICO Summary
Population
Children and adults with sickle cell disease (SCD) in 14 low- and middle-income countries, (30 studies).
Intervention
Evidence-based interventions including: disease modifying agents, supportive care agents/analgesics, anti-malarials, systemic treatments (e.g., red blood cell transfusions), patient/provider education, and nutritional supplements.
Comparison
Placebo or comparator intervention
Outcome
Studies using disease modifying agents, nutritional supplements, and anti-malarials reported improvements in pain crisis, hospitalization, children's growth and reduction in severity and prevalence of malaria. Two studies reported on the sustainability of supplementary arginine, citrulline, and daily chloroquine and hydroxyurea for SCD patients. Only 13 studies (44.8%) provided descriptions that captured at least three of the eight implementation research outcomes. There was limited reporting of acceptability, feasibility, fidelity, cost and sustainability.
