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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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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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A scoping review of transition interventions for young adults with sickle cell disease
Viola A, Porter J, Shipman J, Brooks E, Valrie C
Pediatric blood & cancer. 2021;:e29135
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Abstract
Standardized programming for individuals with sickle cell disease (SCD) transitioning from pediatric to adult-centered care does not currently exist, resulting in high rates of mortality and morbidity. This scoping review examines and evaluates the current literature on SCD transition programs and interventions. Eligible studies described an existing program for individuals with SCD aged 12-29 years preparing to transition. The Evidence Project risk-of-bias tool was used to assess article quality. We identified 30 eligible articles, of which, only two were randomized controlled trials. Many studies have incomplete reports of feasibility information, such as completion rates, patient characteristics, and attrition; all studies were limited to a single institution; and most studies were rated high for risk of bias. Progress has been made in designing and gathering initial evaluation data for SCD transition programs; however, there is a need for higher quality studies, consistent assessment, and better dissemination of programs.
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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.
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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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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
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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Blood transfusion for preventing primary and secondary stroke in people with sickle cell disease
Estcourt LJ, Kohli R, Hopewell S, Trivella M, Wang WC
Cochrane Database Syst Rev. 2020;7:Cd003146
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Abstract
BACKGROUND Sickle cell disease is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. Sickle cell disease can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Stroke affects around 10% of children with sickle cell anaemia (HbSS). Chronic blood transfusions may reduce the risk of vaso-occlusion and stroke by diluting the proportion of sickled cells in the circulation. This is an update of a Cochrane Review first published in 2002, and last updated in 2017. OBJECTIVES To assess risks and benefits of chronic blood transfusion regimens in people with sickle cell disease for primary and secondary stroke prevention (excluding silent cerebral infarcts). SEARCH METHODS We searched for relevant trials in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to 8 October 2019. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register: 19 September 2019. SELECTION CRITERIA Randomised controlled trials comparing red blood cell transfusions as prophylaxis for stroke in people with sickle cell disease to alternative or standard treatment. There were no restrictions by outcomes examined, language or publication status. DATA COLLECTION AND ANALYSIS Two authors independently assessed trial eligibility and the risk of bias and extracted data. MAIN RESULTS We included five trials (660 participants) published between 1998 and 2016. Four of these trials were terminated early. The vast majority of participants had the haemoglobin (Hb)SS form of sickle cell disease. Three trials compared regular red cell transfusions to standard care in primary prevention of stroke: two in children with no previous long-term transfusions; and one in children and adolescents on long-term transfusion. Two trials compared the drug hydroxyurea (hydroxycarbamide) and phlebotomy to long-term transfusions and iron chelation therapy: one in primary prevention (children); and one in secondary prevention (children and adolescents). The quality of the evidence was very low to moderate across different outcomes according to GRADE methodology. This was due to the trials being at a high risk of bias due to lack of blinding, indirectness and imprecise outcome estimates. Red cell transfusions versus standard care Children with no previous long-term transfusions Long-term transfusions probably reduce the incidence of clinical stroke in children with a higher risk of stroke (abnormal transcranial doppler velocities or previous history of silent cerebral infarct), risk ratio 0.12 (95% confidence interval 0.03 to 0.49) (two trials, 326 participants), moderate quality evidence. Long-term transfusions may: reduce the incidence of other sickle cell disease-related complications (acute chest syndrome, risk ratio 0.24 (95% confidence interval 0.12 to 0.48)) (two trials, 326 participants); increase quality of life (difference estimate -0.54, 95% confidence interval -0.92 to -0.17) (one trial, 166 participants); but make little or no difference to IQ scores (least square mean: 1.7, standard error 95% confidence interval -1.1 to 4.4) (one trial, 166 participants), low quality evidence. We are very uncertain whether long-term transfusions: reduce the risk of transient ischaemic attacks, Peto odds ratio 0.13 (95% confidence interval 0.01 to 2.11) (two trials, 323 participants); have any effect on all-cause mortality, no deaths reported (two trials, 326 participants); or increase the risk of alloimmunisation, risk ratio 3.16 (95% confidence interval 0.18 to 57.17) (one trial, 121 participants), very low quality evidence. Children and adolescents with previous long-term transfusions (one trial, 79 participants) We are very uncertain whether continuing long-term transfusions reduces the incidence of: stroke, risk ratio 0.22 (95% confidence interval 0.01 to 4.35); or all-cause mortality, Peto odds ratio 8.00 (95% confidence interval 0.16 to 404.12), very low quality evidence. Several review outcomes were only reported in one trial arm (sickle cell disease-related complications, alloimmunisation, transient ischaemic attacks). The trial did not report neurological impairment, or quality of life. Hydroxyurea and phlebotomy versus red cell transfusions and chelation Neither trial reported on neurological impairment, alloimmunisation, or quality of life. Primary prevention, children (one trial, 121 participants) Switching to hydroxyurea and phlebotomy may have little or no effect on liver iron concentrations, mean difference -1.80 mg Fe/g dry-weight liver (95% confidence interval -5.16 to 1.56), low quality evidence. We are very uncertain whether switching to hydroxyurea and phlebotomy has any effect on: risk of stroke (no strokes); all-cause mortality (no deaths); transient ischaemic attacks, risk ratio 1.02 (95% confidence interval 0.21 to 4.84); or other sickle cell disease-related complications (acute chest syndrome, risk ratio 2.03 (95% confidence interval 0.39 to 10.69)), very low quality evidence. Secondary prevention, children and adolescents (one trial, 133 participants) Switching to hydroxyurea and phlebotomy may: increase the risk of sickle cell disease-related serious adverse events, risk ratio 3.10 (95% confidence interval 1.42 to 6.75); but have little or no effect on median liver iron concentrations (hydroxyurea, 17.3 mg Fe/g dry-weight liver (interquartile range 10.0 to 30.6)); transfusion 17.3 mg Fe/g dry-weight liver (interquartile range 8.8 to 30.7), low quality evidence. We are very uncertain whether switching to hydroxyurea and phlebotomy: increases the risk of stroke, risk ratio 14.78 (95% confidence interval 0.86 to 253.66); or has any effect on all-cause mortality, Peto odds ratio 0.98 (95% confidence interval 0.06 to 15.92); or transient ischaemic attacks, risk ratio 0.66 (95% confidence interval 0.25 to 1.74), very low quality evidence. AUTHORS' CONCLUSIONS There is no evidence for managing adults, or children who do not have HbSS sickle cell disease. In children who are at higher risk of stroke and have not had previous long-term transfusions, there is moderate quality evidence that long-term red cell transfusions reduce the risk of stroke, and low quality evidence they also reduce the risk of other sickle cell disease-related complications. In primary and secondary prevention of stroke there is low quality evidence that switching to hydroxyurea with phlebotomy has little or no effect on the liver iron concentration. In secondary prevention of stroke there is low-quality evidence that switching to hydroxyurea with phlebotomy increases the risk of sickle cell disease-related events. All other evidence in this review is of very low quality.
PICO Summary
Population
Patients of all ages with sickle cell disease (SCD), (5 studies, n= 660).
Intervention
Red cell transfusions.
Comparison
Standard care, or hydroxyurea and phlebotomy.
Outcome
Red cell transfusions versus standard care: long term transfusions probably reduce the incidence of clinical stroke in children with a higher risk of stroke (abnormal transcranial doppler velocities or previous history of silent cerebral infarct). Long-term transfusions may: reduce the incidence of other sickle cell disease-related complications but make little or no difference to IQ scores. We are very uncertain whether long-term transfusions reduce the risk of transient ischaemic attacks, have any effect on all-cause mortality, or increase the risk of alloimmunisation. Hydroxyurea and phlebotomy versus red cell transfusions and chelation: Neither trial reported on neurological impairment, alloimmunisation, or quality of life. Switching to hydroxyurea and phlebotomy may have little or no effect on liver iron concentrations. We are very uncertain whether switching to hydroxyurea and phlebotomy has any effect on: risk of stroke, transient ischaemic attacks or other sickle cell disease-related complications. Switching to hydroxyurea and phlebotomy may: increase the risk of sickle cell disease-related serious adverse events, but have little or no effect on median liver iron. We are very uncertain whether switching to hydroxyurea and phlebotomy: increases the risk of stroke, or has any effect on all-cause mortality, or transient ischaemic attacks.
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Quality assessment of evidence-based clinical practice guidelines for the management of pregnant women with sickle cell disease using the AGREE II instrument: a systematic review
Amer YS, Sabr Y, ElGohary GM, Altaki AM, Khojah OT, El-Malky A, Alzahrani MF
BMC pregnancy and childbirth. 2020;20(1):595
Abstract
BACKGROUND The management of pregnant women with sickle cell disease (SCD) poses a major challenge for maternal healthcare services owing to the potential for complications associated with morbidity and mortality. Trustworthy evidence-based clinical practice guidelines (CPGs) have a major impact on the positive outcomes of appropriate healthcare. The objective of this study was to critically appraise the quality of recent CPGs for SCD in pregnant women. METHODS Clinical questions were identified and the relevant CPG and bibliographic databases were searched and screened for eligible CPGs. Each CPG was appraised by four independent appraisers using the AGREE II Instrument. Inter-rater analysis was conducted. RESULTS Four eligible CPGs were appraised: American College of Obstetricians and Gynecologists (ACOG), National Heart, Lung, and Blood Institute (NHLBI), National Institute of Health and Care Excellence (NICE), and Royal College of Obstetricians and Gynaecologists (RCOG). Among them, the overall assessments of three CPGs (NICE, RCOG, NHLBI) scored greater than 70%; these findings were consistent with the high scores in the six domains of AGREE II, including:[1] scope and purpose,[2] stakeholder involvement,[3] rigor of development,[4] clarity of presentation,[5] applicability, and [6] editorial independence domains. Domain [3] scored (90%, 73%, 71%), domain [5] (90%, 46%, 47%), and domain [6] (71%, 77%, 52%) for NICE, RCOG, and NHLBI, respectively. Overall, the clinical recommendations were not significantly different between the included CPGs. CONCLUSIONS Three evidence-based CPGs presented superior methodological quality. NICE demonstrated the highest quality followed by RCOG and NHLBI and all three CPGs were recommended for use in practice.
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Prevalence of neonatal hyperbilirubinaemia and its association with glucose-6-phosphate dehydrogenase deficiency and blood-type incompatibility in sub-Saharan Africa: a systematic review and meta-analysis
Aynalem YA, Mulu GB, Akalu TY, Shiferaw WS
BMJ paediatrics open. 2020;4(1):e000750
Abstract
BACKGROUND Hyperbilirubinaemia is a silent cause of newborn disease and death worldwide. However, studies of the disease in sub-Saharan Africa are highly variable with respect to its prevalence. Hence, this study aimed to estimate the overall magnitude of neonatal hyperbilirubinaemia and its association with glucose-6-phosphate dehydrogenase (G6PD) deficiency and blood-type incompatibility in sub-Saharan Africa. METHODS PubMed, Scopus, Google Scholar and the Cochrane Review were systematically searched online to retrieve hyperbilirubinaemia-related articles. All observational studies reported the prevalence of hyperbilirubinaemia in sub-Saharan Africa were included for analysis and excluded if the study failed to determine the desired outcome. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Heterogeneity across the included studies was evaluated using the inconsistency index (I(2)). Subgroup and meta- regression analysis were also done. Publication bias was examined by funnel plot and the Egger's regression test. The random-effect model was fitted to estimate the pooled prevalence of neonatal hyperbilirubinaemia. The meta-analysis was performed using the STATA V.14 software. RESULTS A total of 30 486 studies were collected from the different databases and 10 articles were included for the final analysis. The overall magnitude of neonatal hyperbilirubinaemia was 28.08% (95% CI20.23 to 35.94, I(2)=83.2) in sub-Saharan Africa. Neonates with G6PD deficiency (OR 2.42, 95% CI 1.64 to 3.56, I(2)=37%) and neonates that had a blood type that was incompatible with their mother's (OR 3.3, (95% CI 1.96 to 5.72, I(2)=84%) were more likely to develop hyperbilirubinaemia. CONCLUSION The failure to prevent and screen G6PD deficiency and blood-type incompatibility with their mother's results in high burden of neonatal hyperbilirubinaemia in sub-Saharan Africa. Therefore, early identification and care strategies should be developed to the affected neonates with G6PD deficiency and blood-type incompatibility with their mother's to address long-term medical and scholastic damages among those exposed to hyperbilirubinaemia.
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Diagnostic yield of capsule endoscopy for small bowel arteriovenous malformations in patients with hereditary hemorrhagic telangiectasia: a systematic review and meta-analysis
Singh K, Zubair A, Prindle A, Nadeem AJ, Khan G
Endoscopy international open. 2019;7(2):E282-e289
Abstract
Background and study aims Small bowel arteriovenous malformations (AVMs) pose a bleeding risk and have traditionally been diagnosed by invasive enteroscopic procedures in patients with hereditary hemorrhagic telangiectasia (HHT). Capsule endoscopy (CE) is emerging as a safe and non-invasive alternative for small intestinal evaluation, but its diagnostic yield and utility in diagnosing small bowel AVMs in HHT patients are understudied. The aim of this study was to meta-analyze the utility of CE for diagnosing AVMs in HHT patients. Methods A meta-analysis and systematic review of the literature on CE in HHT patients identified in the PubMed, EMBASE, Scopus, and Cochrane databases from inception to March 2018 were conducted. Summary effects were estimated using a random effects model. Results After applying exclusion criteria, five studies (n = 124 patients) were eligible for meta-analysis. The pooled diagnostic yield for visualization of small bowel AVMs by CE was 77.0 % (95 % CI 65.8 - 85.4 %, P < 0.001). Conclusions CE has a good diagnostic yield for small bowel AVMs in HHT. It can be regarded as a sufficient, noninvasive diagnostic modality for identifying small bowel AVMs in HHT patients.
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Fetal thrombocytopenia in pregnancies complicated by fetal anemia due to red-cell alloimmunization: cohort study and meta-analysis
Rosenbloom JI, Bruno AM, Conner SN, Tuuli MG, Simon LE, Macones GA, Cahill AG
Journal of perinatology : official journal of the California Perinatal Association. 2019
Abstract
OBJECTIVE To estimate the prevalence and characteristics of fetal thrombocytopenia at the time of percutaneous umbilical cord sampling (PUBS) in pregnancies complicated by alloimmunization and to conduct a systematic review on fetal thrombocytopenia in these pregnancies. STUDY DESIGN Retrospective cohort study of all patients undergoing PUBS at our institution from 2000-2017. Clinical data, including fetal platelet counts, were abstracted from the medical record and analyzed with routine statistical procedures. A systematic review and meta-analysis were also conducted according to standard procedures. RESULT At first procedure, prior to any transfusion, 13/36 fetuses (36%) had thrombocytopenia: 11/36 (31%) had moderate thrombocytopenia and 2/36 (6%) had severe thrombocytopenia (14 patients had no platelet count at first procedure). The systematic review identified six studies, and the prevalence of fetal thrombocytopenia at the time of PUBS for alloimmunization was 18% (95% confidence interval 11%, 26%). CONCLUSION Thrombocytopenia is common and underappreciated in fetuses undergoing PUBS for alloimmunization.