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The Cochrane Database of Systematic... 2000The development of Rh immunisation and its prophylactic use since the 1970s has meant that severe Rhesus D (RhD) alloimmunisation is now rarely seen. (Review)
Review
BACKGROUND
The development of Rh immunisation and its prophylactic use since the 1970s has meant that severe Rhesus D (RhD) alloimmunisation is now rarely seen.
OBJECTIVES
The objective of this systematic review was to assess the effects of giving anti-D to Rhesus negative women, with no anti-D antibodies, who had given birth to a Rhesus positive infant.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register, MEDLINE (from 1966 to January 1999) and reference lists of relevant articles. Date of last search of Cochrane Controlled Trials Register: January 1999.
SELECTION CRITERIA
Randomised trials in Rhesus negative women without antibodies who were given anti-D immunoglobulin postpartum compared with no treatment or placebo.
DATA COLLECTION AND ANALYSIS
Assessments of inclusion criteria, trial quality and data extraction were done by each author independently. Initial analyses included all trials. Other analyses assessed the effect of trial quality, ABO compatibility and dose.
MAIN RESULTS
Six eligible trials compared postpartum anti-D prophylaxis with no treatment or placebo. The trials involved over 10,000 women, but trial quality varied. Anti-D lowered the incidence of RhD alloimmunisation six months after birth (relative risk 0.04, 95% confidence interval 0.02 to 0.06), and in a subsequent pregnancy (relative risk 0.12, 95% confidence interval 0. 07 to 0.23). These benefits were seen regardless of the ABO status of the mother and baby and when anti-D was given within 72 hours of birth. Higher doses (up to 200 micro grams) were more effective than lower doses (up to 50 micro grams) in preventing RhD alloimmunisation in a subsequent pregnancy.
REVIEWER'S CONCLUSIONS
Anti-D, given within 72 hours after childbirth, reduces the risk of RhD alloimmunisation in Rhesus negative women who have given birth to a Rhesus positive infant. However the evidence on the optimal dose is limited.
Topics: Female; Humans; Postpartum Period; Rh Isoimmunization; Rho(D) Immune Globulin
PubMed: 10796089
DOI: 10.1002/14651858.CD000021 -
Transfusion Oct 2013HLA-matched platelets (PLTs) are widely used to transfuse patients but the effectiveness of HLA matching has not been well defined and the cost is approximately five... (Review)
Review
BACKGROUND
HLA-matched platelets (PLTs) are widely used to transfuse patients but the effectiveness of HLA matching has not been well defined and the cost is approximately five times the cost of preparing the random-donor PLTs. The objective of this systematic review was to determine whether HLA-matched PLTs lead to a reduction in mortality; reduction in frequency or severity of hemorrhage; reduction in HLA alloimmunization, refractoriness, or PLT utilization; or improvement in PLT count increment in patients with hypoproliferative thrombocytopenia.
STUDY DESIGN AND METHODS
We conducted a literature search of MEDLINE, Cochrane Controlled Register of Clinical Trials, EMBASE, and PubMed databases to April 2012.
RESULTS
A total of 788 citations were reviewed and 30 reports were included in the analysis. Most studies did not include technologies currently in use for HLA typing or detection of HLA antibodies as 75% were conducted before the year 2000. None of the studies were adequately powered to detect an effect on mortality or hemorrhage. HLA-matched PLTs did not reduce alloimmunization and refractoriness rates beyond that offered by leukoreduction, and utilization was not consistently improved. HLA-matched PLTs led to better 1-hour posttransfusion count increments and percentage of PLT recovery in refractory patients; however, the effect at 24 hours was inconsistent.
CONCLUSION
The correlation of the PLT increment with other clinical outcomes and the effect of leukoreduction on HLA-matched PLT transfusion could not be determined. Prospective studies utilizing current technology and examining clinical outcomes are necessary to demonstrate the effectiveness of HLA-matched PLT transfusion.
Topics: Histocompatibility Testing; Humans; Platelet Transfusion; Randomized Controlled Trials as Topic; Thrombocytopenia
PubMed: 23550773
DOI: 10.1111/trf.12175 -
The Cochrane Database of Systematic... Aug 2017Bleeding disorders are uncommon but may pose significant bleeding complications during pregnancy, labour and following delivery for both the woman and the foetus. While... (Review)
Review
BACKGROUND
Bleeding disorders are uncommon but may pose significant bleeding complications during pregnancy, labour and following delivery for both the woman and the foetus. While many bleeding disorders in women tend to improve in pregnancy, thus decreasing the haemorrhagic risk to the mother at the time of delivery, some do not correct or return quite quickly to their pre-pregnancy levels in the postpartum period. Therefore, specific measures to prevent maternal bleeding and foetal complications during childbirth, are required. The safest method of delivery to reduce morbidity and mortality in these women is controversial. This is an update of a previously published review.
OBJECTIVES
To assess the optimal mode of delivery in women with, or carriers of, bleeding disorders.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the Cochrane Pregnancy and Childbirth Group's Trials Register as well as trials registries and the reference lists of relevant articles and reviews.Date of last search of the Group's Trials Registers: 16 February 2017.
SELECTION CRITERIA
Randomised controlled trials and all types of controlled clinical trials investigating the optimal mode of delivery in women with, or carriers of, any type of bleeding disorder during pregnancy were eligible for the review.
DATA COLLECTION AND ANALYSIS
No trials matching the selection criteria were eligible for inclusion MAIN RESULTS: No results from randomised controlled trials were found.
AUTHORS' CONCLUSIONS
The review did not identify any randomised controlled trials investigating the safest mode of delivery and associated maternal and foetal complications during delivery in women with, or carriers of, a bleeding disorder. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials, case studies) to decide upon the optimal mode of delivery to ensure the safety of both mother and foetus.Given the ethical considerations, the rarity of the disorders and the low incidence of both maternal and foetal complications, future randomised controlled trials to find the optimal mode of delivery in this population are unlikely to be carried out. Other high quality controlled studies (such as risk allocation designs, sequential design, and parallel cohort design) are needed to investigate the risks and benefits of natural vaginal and caesarean section in this population or extrapolation from other clinical conditions that incur a haemorrhagic risk to the baby, such as platelet alloimmunisation.
Topics: Adult; Blood Coagulation Disorders; Cesarean Section; Delivery, Obstetric; Female; Fetus; Heterozygote; Humans; Pregnancy; Pregnancy Complications, Hematologic
PubMed: 28776324
DOI: 10.1002/14651858.CD011059.pub3 -
Journal For Immunotherapy of Cancer Apr 2019Checkpoint inhibitors (CPIs) have revolutionized the treatment of cancer, but their use remains limited by off-target inflammatory and immune-related adverse events....
BACKGROUND
Checkpoint inhibitors (CPIs) have revolutionized the treatment of cancer, but their use remains limited by off-target inflammatory and immune-related adverse events. Solid organ transplantation (SOT) recipients have been excluded from clinical trials owing to concerns about alloimmunity, organ rejection, and immunosuppressive therapy. Thus, we conducted a retrospective study and literature review to evaluate the safety of CPIs in patients with cancer and prior SOT.
METHODS
Data were collected from the medical records of patients with cancer and prior SOT who received CPIs at The University of Texas MD Anderson Cancer Center from January 1, 2004, through March 31, 2018. Additionally, we systematically reviewed five databases through April 2018 to identify studies reporting CPIs to treat cancer in SOT recipients. We evaluated the safety of CPIs in terms of alloimmunity, immune-related adverse events, and mortality. We also evaluated tumor response to CPIs.
RESULTS
Thirty-nine patients with allograft transplantation were identified. The median age was 63 years (range 14-79 years), 74% were male, 62% had metastatic melanoma, 77% received anti-PD-1 agents, and 59% had prior renal transplantation, 28% hepatic transplantation, and 13% cardiac transplantation. Median time to CPI initiation after SOT was 9 years (range 0.92-32 years). Allograft rejection occurred in 41% of patients (11/23 renal, 4/11 hepatic, and 1/5 cardiac transplantations), at similar rates for anti-CTLA-4 and anti-PD-1 therapy. The median time to rejection was 21 days (95% confidence interval 19.3-22.8 days). There were no associations between time since SOT and frequency, timing, or type of rejection. Overall, 31% of patients permanently discontinued CPIs because of allograft rejection. Graft loss occurred in 81%, and death was reported in 46%. Of the 12 patients with transplantation biopsies, nine (75%) had acute rejection, and five of these rejections were T cell-mediated. In melanoma patients, 36% responded to CPIs.
CONCLUSIONS
SOT recipients had a high allograft rejection rate that was observed shortly after CPI initiation, with high mortality rates. Further studies are needed to optimize the anticancer treatment approach in these patients.
Topics: Adolescent; Adult; Aged; Antineoplastic Agents, Immunological; CTLA-4 Antigen; Female; Follow-Up Studies; Graft Rejection; Humans; Immunosuppressive Agents; Male; Middle Aged; Neoplasms; Organ Transplantation; Programmed Cell Death 1 Receptor; Retrospective Studies; Risk Assessment; Transplantation, Homologous; Treatment Outcome; Young Adult
PubMed: 30992053
DOI: 10.1186/s40425-019-0585-1 -
The Cochrane Database of Systematic... 2000A woman may develop Rh-negative antibodies during her first pregnancy when her fetus is Rh-positive. Antibodies develop most frequently after the 28th week of gestation. (Review)
Review
BACKGROUND
A woman may develop Rh-negative antibodies during her first pregnancy when her fetus is Rh-positive. Antibodies develop most frequently after the 28th week of gestation.
OBJECTIVES
The objective of this review was to asses the effects of giving antenatal anti-D immunoglobulin at 28 weeks or more of pregnancy on the incidence of RhD alloimmunisation when given to Rhesus negative mothers without anti-D antibodies.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group trials register, Cochrane Controlled Trials Register, and bibliographies. Date of last search: December 1998.
SELECTION CRITERIA
Randomised trials in Rhesus negative women without anti-D antibodies given anti-D after 28 weeks of pregnancy, compared with no treatment or placebo.
DATA COLLECTION AND ANALYSIS
Data were extracted by one reviewer and double entered.
MAIN RESULTS
Two eligible trials, which involved over 4500 women, compared anti-D prophylaxis with no treatment. Although the data suggested, when women receive anti-D at 28 and 34 weeks gestation, a reduced incidence of immunisation during pregnancy (0R O.44, 95% CI 0.18-1.12), after the birth of a Rhesus positive infant (OR 0.44, 95% CI 0.18-1.12), and within 12 months after birth of a Rhesus positive infant (OR 0.44, 95% CI 0.19-1.01), none of these differences were statistically significant. In the trial, which used the larger dose of anti-D (100ug; 500IU), there was a clear reduction in the incidence of immunisation at 2-12 months following birth in women who had received Anti-D at 28 and 34 weeks (OR 0.22 95% CI 0.05-0.88). No data were available for the risk of RhD alloimmunisation in a subsequent pregnancy. No differences were observed in the incidence of neonatal jaundice.
REVIEWER'S CONCLUSIONS
The risk of RhD alloimmunisation during or immediately after a first pregnancy is about 1.5%. Administration of 100ug (500IU) anti-D at 28 weeks and 34 weeks gestation to women in their first pregnancy can reduce this risk to about 0.2% without, to date, any adverse effects. Although such a policy is unlikely to confer benefit or improve outcome in the present pregnancy, fewer women will have Rhesus D antibodies in their next pregnancy. Adoption of such a policy will need to consider the costs of prophylaxis against the costs of care for women who become sensitised and their affected infants, and local adequacy of supply of anti-D gammaglobulin.
Topics: Female; Humans; Pregnancy; Pregnancy Trimester, Third; Rh Isoimmunization; Rho(D) Immune Globulin
PubMed: 10796088
DOI: 10.1002/14651858.CD000020 -
European Journal of Obstetrics,... May 2024Umbilical Artery Thrombosis (UAT) is an extremely rare complication of pregnancy strongly associated with severe fetal distress and death. The pathogenesis is still... (Review)
Review
Umbilical Artery Thrombosis (UAT) is an extremely rare complication of pregnancy strongly associated with severe fetal distress and death. The pathogenesis is still unclear but it is often associated with anatomical cord abnormalities that leads to blood stasis and thrombosis formation. Other possible risk factors are maternal thrombophilia, autoimmune disease, gestational diabetes, hypertension disorders of pregnancy and Rh-alloimmunization. The most common clinical symptom is the reduction of fetal movements. The diagnosis is histopathological, but it can be suspected by clinical and prenatal ultrasound findings. Generally, the first choice therapy is the immediate delivery with cesarean section. This study reported a case of a spontaneous intrauterine UAT in a low-risk pregnancy and a systematic review of the literature on clinical, ultrasound and histopathological findings of UAT, in order to help clinicians in the diagnostic process and management of this rare complication.
Topics: Pregnancy; Humans; Female; Umbilical Arteries; Cesarean Section; Pregnancy Complications; Prenatal Diagnosis; Thrombosis; Ultrasonography, Prenatal
PubMed: 38394717
DOI: 10.1016/j.ejogrb.2024.02.016 -
The Cochrane Database of Systematic... Sep 2012Red-cell alloimmunisation can occur when there are incompatibilities between a woman's blood type and that of her unborn baby. This can cause the baby to become anaemic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Red-cell alloimmunisation can occur when there are incompatibilities between a woman's blood type and that of her unborn baby. This can cause the baby to become anaemic (low red blood cell count), which may require treatment during the pregnancy by blood transfusion while the baby remains within the uterus (called an intrauterine blood transfusion).
OBJECTIVES
To compare, using the best available evidence, the benefits and harms of different techniques of intrauterine fetal blood transfusion for women with red-cell alloimmunisation.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (13 June 2012).
SELECTION CRITERIA
We considered randomised controlled trials comparing different techniques of intrauterine fetal blood transfusion (either alone or in combination with another technique) for inclusion.
DATA COLLECTION AND ANALYSIS
Two authors evaluated trials under consideration for appropriateness for inclusion and methodological quality, without consideration of their results according to the prestated eligibility criteria. We planned to use a fixed-effect meta-analysis for combining study data if we judged the trials to be sufficiently similar. We planned to investigate statistical heterogeneity using the I² statistic; if this indicated a high degree of statistical heterogeneity, we planned to use a random-effects model.
MAIN RESULTS
Our search strategy identified four reports of three studies for consideration, of which two met the inclusion criteria, involving 44 women. We identified a single trial comparing the use of intrauterine fetal blood transfusion and intravenous immunoglobulin versus intrauterine fetal blood transfusion alone, and a single trial comparing the use of atracurium and pancuronium. There were no statistically significant differences identified for any of the reported outcomes.
AUTHORS' CONCLUSIONS
There is little available high quality information from randomised controlled trials to inform the optimal procedural technique when performing fetal intrauterine fetal blood transfusions for women with an anaemic fetus due to red cell alloimmunisation. Further research evaluating the benefits and harms associated with different techniques is required.
Topics: Atracurium; Blood Transfusion, Intrauterine; Erythrocyte Transfusion; Female; Humans; Immunoglobulins, Intravenous; Neuromuscular Depolarizing Agents; Pancuronium; Pregnancy; Randomized Controlled Trials as Topic; Rh Isoimmunization; Treatment Outcome
PubMed: 22972102
DOI: 10.1002/14651858.CD007096.pub3 -
Hematology (Amsterdam, Netherlands) Dec 2019Investigate globally, current treatment patterns, benefit-risk assessments, humanistic, societal and economic burden of platelet transfusion (PT). Publications from...
Investigate globally, current treatment patterns, benefit-risk assessments, humanistic, societal and economic burden of platelet transfusion (PT). Publications from 1998 to June 27, 2018 were identified, based on databases searches including MEDLINE®; Embase and Cochrane Database of Systematic Reviews. Data from studies meeting pre-specified criteria were extracted and validated by independent reviewers. Data were obtained for efficacy and safety from randomized controlled trials (RCTs); data for epidemiology, treatment patterns, effectiveness, safety, humanistic and societal burden from real-world evidence (RWE) studies; and economic data from both. A total of 3425 abstracts, 194 publications (190 studies) were included. PT use varied widely, from 0%-100% of TCP patients; 1.7%-24.5% in large studies (>1000 patients). Most were used prophylactically rather than therapeutically. 5 of 43 RCTs compared prophylactic PT with no intervention, with mixed results. In RWE studies PT generally increased platelet count (PC). This increase varied by patient characteristics and hence did not always translate into a clinically significant reduction in bleeding risk. Safety concerns included infection risk, alloimmunization and refractoriness with associated cost burden. In RCTs and RWE studies there was significant heterogeneity in study design and outcome measures. In RWE studies, patients receiving PT may have been at higher risk than those not receiving PT creating potential bias. There were limited data on humanistic and societal burden. Although PTs are used widely for increasing PC in TCP, it is important to understand the limitations of PTs, and to explore the use of alternative treatment options where available.
Topics: Humans; Platelet Transfusion; Thrombocytopenia
PubMed: 31581933
DOI: 10.1080/16078454.2019.1662200 -
BJOG : An International Journal of... Oct 2010Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a potentially devastating disease, which may lead to intracranial haemorrhage (ICH), with neurological... (Review)
Review
BACKGROUND
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a potentially devastating disease, which may lead to intracranial haemorrhage (ICH), with neurological damage as a consequence. In the absence of screening, FNAIT is only diagnosed after bleeding symptoms, with preventive options limited to a next pregnancy.
OBJECTIVES
To estimate the population incidence of FNAIT and its consequences to prepare for study design of a screening programme.
SEARCH STRATEGY
An electronic literature search using MEDLINE, EMBASE and Cochrane database, and references of retrieved articles. No language restrictions were applied.
SELECTION CRITERIA
Prospective studies on screening for human platelet antigen 1a (HPA-1a) alloimmunisation in low-risk pregnant women.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed studies for inclusion and extracted data. Main outcome data were prevalence of HPA-1a negativity, HPA-1a immunisation, platelet count at birth and perinatal ICH. We aimed to compare outcome with and without intervention.
MAIN RESULTS
HPA-1a alloimmunisation occurred in 294/3028 (9.7%) pregnancies at risk. Severe FNAIT occurred in 71/227 (31%) immunised pregnancies, with perinatal ICH in 7/71 (10%). True natural history data were not found because interventions were performed in most screen-positive women.
AUTHORS' CONCLUSIONS
Screening for HPA-1a alloimmunisation detects about two cases in 1000 pregnancies. The calculated risk for perinatal ICH of 10% in pregnancies with severe FNAIT is an underestimation because studies without interventions were lacking. Screening of all pregnancies together with effective antenatal treatment such as intravenous immunoglobulin may reduce the mortality and morbidity associated with FNAIT.
Topics: Antigens, Human Platelet; Female; HLA-DR Antigens; HLA-DRB3 Chains; Humans; Infant Mortality; Infant, Newborn; Integrin beta3; Perinatal Mortality; Pregnancy; Pregnancy Outcome; Pregnancy, High-Risk; Prenatal Diagnosis; Prospective Studies; Thrombocytopenia, Neonatal Alloimmune
PubMed: 20618318
DOI: 10.1111/j.1471-0528.2010.02657.x -
Journal of Clinical Medicine Jan 2021Congenital factor (F) VII deficiency is a rare coagulation factor deficiency with an estimated incidence of 1 per 500,000 individuals. Patients with severe FVII... (Review)
Review
BACKGROUND
Congenital factor (F) VII deficiency is a rare coagulation factor deficiency with an estimated incidence of 1 per 500,000 individuals. Patients with severe FVII deficiency present a broad range of clinical presentations. Alloimmunization against exogenous FVII, as the main challenge of replacement therapy, is an extremely rare phenomenon that is accompanied by a high rate of life-threatening bleeding, that renders replacement therapy less effective. Due to the importance of the issue, we performed a systematic literature review in order to assess incidence, molecular basis, clinical presentations, and therapeutic challenge and management of inhibitor in congenital FVII deficiency. Strategy of search: This systematic review was performed in accordance with PRISMA guidelines. We performed an English-language literature review in the PubMed, EMBASE, Scopus, and Google Scholar databases, using the following keywords: "factor VII inhibitor", "factor VII inhibitors", "FVII inhibitors", "congenital FVII deficiency", "recombinant factor VII", "anti rFVIIa", "replacement therapy", and "alloantibody".
RESULTS
Out of 380 patients in the 13 studies, 27 had inhibitor against FVII; 18 were male, 7 were female, while the sex of 2 was not stated. The majority (92%) developed a high-titer inhibitor (Bethesda Unit > 5). All patients had severe FVII deficiency (FVII:C < 10%), and the majority received recombinant FVII prior to inhibitor development (N: 24, 89%). Among ten patients with a detected mutation, three subjects had a common non-sense (30%), and two had a deletion (20%).
CONCLUSIONS
Inhibitor development is a relatively rare phenomenon seen only in severe FVII deficiency, where it is associated with severe and life-threatening presentations, treatment challenge, and economic burden on the patients and their families.
PubMed: 33435610
DOI: 10.3390/jcm10020211