Antenatal management in fetal and neonatal alloimmune thrombocytopenia: a systematic review.

Several strategies can be used to manage fetal or neonatal alloimmune thrombocytopenia (FNAIT) in subsequent pregnancies. Serial fetal blood sampling (FBS) and intrauterine platelet transfusions (IUPT), as well as weekly maternal IV immunoglobulin infusion (IVIG), with or without additional corticosteroid therapy, are common options, but optimal management has not been determined. The aim of this systematic review was to assess antenatal treatment strategies for FNAIT. Four randomized controlled trials and 22 nonrandomized studies were included. Pooling of results was not possible due to considerable heterogeneity. Most studies found comparable outcomes regarding the occurrence of intracranial hemorrhage, regardless of the antenatal management strategy applied; FBS, IUPT, or IVIG with or without corticosteroids. There is no consistent evidence for the value of adding steroids to IVIG. FBS or IUPT resulted in a relatively high complication rate (consisting mainly of preterm emergency cesarean section) of 11% per treated pregnancy in all studies combined. Overall, noninvasive management in pregnant mothers who have had a previous neonate with FNAIT is effective without the relatively high rate of adverse outcomes seen with invasive strategies. This systematic review suggests that first-line antenatal management in FNAIT is weekly IVIG administration, with or without the addition of corticosteroids.

Maternal HPA-1a antibody level and its role in predicting the severity of Fetal/Neonatal Alloimmune Thrombocytopenia: a systematic review.

BACKGROUND AND OBJECTIVES: In Caucasians, fetal/neonatal alloimmune thrombocytopenia (FNAIT) is most commonly due to maternal HPA-1a antibodies. HPA-1a typing followed by screening for anti-HPA-1a antibodies in HPA-1bb women may identify first pregnancies at risk. Our goal was to review results from previous published studies to examine whether the maternal antibody level to HPA-1a could be used to identify high-risk pregnancies. MATERIALS AND METHODS: The studies included were categorized by recruitment strategies: screening of unselected pregnancies or samples analyzed from known or suspected FNAIT patients. RESULTS: Three prospective studies reported results from screening programmes, and 10 retrospective studies focused on suspected cases of FNAIT. In 8 studies samples for antibody measurement, performed by the monoclonal antibody immobilization of platelet antigen (MAIPA) assay, and samples for determining fetal/neonatal platelet count were collected simultaneously. In these 8 studies, the maternal antibody level correlated with the risk of severe thrombocytopenia. The prospective studies reported high negative predictive values (88-95%), which would allow for the use of maternal anti-HPA-1a antibody level as a predictive tool in a screening setting, in order to identify cases at low risk for FNAIT. However, due to low positive predictive values reported in prospective as well as retrospective studies (54-97%), the maternal antibody level is less suited for the final diagnosis and for guiding antenatal treatment. CONCLUSION: HPA-1a antibody level has the potential to predict the severity of FNAIT.

Red blood cell specifications for patients with hemoglobinopathies: a systematic review and guideline.

BACKGROUND: Red blood cell (RBC) transfusions remain essential in the treatment of patients with sickle cell disease (SCD) and ß-thalassemia. Alloimmunization, a well-documented complication of transfusion, increases the risk of delayed hemolytic transfusion reactions, complicates crossmatching and identifying compatible units, and delays provision of transfusions. Guidance is required to optimize the RBC product administered to these patients. STUDY DESIGN AND METHODS: An international, multidisciplinary team conducted a systematic review and developed, following the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology, recommendations to assist treating physicians and transfusion specialists in their decision to select RBCs for these patients. RESULTS: Eighteen studies (17 clinical studies and one cost-effectiveness study) were included in the systematic review. The overall quality of the studies was very low. In total, 3696 patients were included: 1680 with ß-thalassemia and 2016 with SCD. CONCLUSION: The panel recommends that ABO D CcEe K-matched RBCs are selected for individuals with SCD and ß-thalassemia, even in the absence of alloantibodies, to reduce the risk of alloimmunization. In patients with SCD and ß-thalassemia who have developed clinically significant alloantibodies, selection of RBCs antigen negative to the alloantibody is recommended, if feasible. In these patients, selection of more extended phenotype-matched RBCs will likely reduce the risk of further alloimmunization. However, given the limited availability of extended phenotype-matched units, attention should be given to ensure that a delay in transfusion does not adversely affect patient care.

Utility of cross-matched platelet transfusions in patients with hypoproliferative thrombocytopenia: a systematic review.

BACKGROUND: Multiply transfused hypoproliferative thrombocytopenic (HT) patients with alloimmune transfusion refractoriness require specially selected platelets (PLTs). Cross-matching apheresis PLTs is a popular support option, avoiding requirements for large panels of typed donors for HLA-based selection. We undertook a systematic review of the utility of various cross-matching techniques on mortality reduction, prevention of hemorrhage, alloimmunization and refractoriness, and improvement in PLT utilization or count increments. STUDY DESIGN AND METHODS: A systematic review to December 2012 was conducted of MEDLINE, EMBASE, and Cochrane databases along with a bibliographic search of pertinent references. RESULTS: Of 146 retrieved citations, 20 met inclusion criteria. Eleven more were chosen from bibliographies, describing 29 unique cohorts. All but five enrolled transfusion-refractory, predominantly alloimmunized patients. Cross-match impact on mortality and hemorrhage could not be assessed from these studies. Two studies demonstrated durable corrected count increments and/or breadth of alloimmunization throughout cross-match support; none addressed development or persistence of refractoriness. In alloimmunized refractory patients and nonrefractory cohorts with greater than 25% alloimmunization, higher increments were seen with cross-match-compatible PLTs than incompatible or un-cross-matched units. In two nonrefractory, nonalloimmunized cohorts, the lack of utility of cross-match was reflected by test sensitivity of less than 20%. Comparison of cross-matched PLT success with that of HLA-identical units revealed inferior success rates for the former in one study and equivalent rates in another. No trend was observed regarding relative utility of the various commonly employed techniques. CONCLUSION: Cross-matched PLTs are useful in increasing PLT counts in alloimmunized, transfusion-refractory HT patients, but data about their impact on hemorrhage and mortality are lacking.

Efficacy of HLA-matched platelet transfusions for patients with hypoproliferative thrombocytopenia: a systematic 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.

Postnatal intervention for the treatment of FNAIT: a systematic review.

OBJECTIVE: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is associated with life-threatening bleeding. This systematic review of postnatal management of FNAIT examined transfusion of human platelet antigen (HPA) selected or unselected platelets, and/or IVIg on platelet increments, hemorrhage and mortality. STUDY DESIGN: MEDLINE, EMBASE and Cochrane searches were conducted until 11 May 2018. RESULT: Of 754 neonates, 382 received platelet transfusions (51%). HPA-selected platelets resulted in higher platelet increments and longer response times than HPA-unselected platelets. However, unselected platelets generally led to sufficient platelet increments to 30 × 109/L, a level above which intracranial hemorrhage or other life-threatening bleeding rarely occurred. Platelet increments were not improved with the addition of IVIg to platelet transfusion. CONCLUSION: Overall, HPA-selected platelet transfusions were more effective than HPA-unselected platelets but unselected platelets were often effective enough to achieve clinical goals. Available studies do not clearly demonstrate a benefit for addition of IVIg to platelet transfusion.

Quality of Evidence-Based Guidelines for Transfusion of Red Blood Cells and Plasma: A Systematic Review.

Many transfusion guidelines are available, but little appraisal of their quality has been undertaken. The quality of guidelines may potentially influence adoption. Our aim was to determine the quality of evidence-based transfusion guidelines (EBG) for red cells and plasma, using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument, and assess duplication and consistency of recommendations. MEDLINE and EMBASE were systematically searched for EBG from 2005 to June 3, 2016. Citations were reviewed for inclusion in duplicate. A guideline was included if it had a specified clinical question, described a systematic search strategy, included critical appraisal of the literature and a description of how recommendations were developed. Four to six physicians used AGREE II to appraise each guideline. Median and scaled scores were calculated, with each item scored on a scale of one to seven, seven representing the highest score. Of 6174 citations, 30 guidelines met inclusion criteria. Twenty six guidelines had recommendations for red cells and 18 included recommendations for plasma use. The median score, the scaled score and the interquartile range of the scaled score were: scope and purpose: median score 5, scaled score 60%, IQR (49-74%); stakeholder involvement 4, 43%, (33-49%); rigor of development 4, 41%, (19-59%); clarity of presentation 5, 69%, (52-81%); applicability 1, 16%, (9-23%); editorial independence 3, 43%, (20-58%). Sixteen guidelines were evaluated to have a scaled domain score of 50% or less. Variations in recommendations were found for the use of hemoglobin triggers for red cell transfusion in patients with acute coronary syndromes and for plasma use for patients with bleeding. Our findings document, limited rigor in guideline development and duplication and inconsistencies in recommendations for the same topic. The process of developing guidelines for red cells and plasma transfusion can be enhanced to improve implementation.

Guidance on platelet transfusion for patients with hypoproliferative thrombocytopenia.

Patients with hypoproliferative thrombocytopenia are at an increased risk for hemorrhage and alloimmunization to platelets. Updated guidance for optimizing platelet transfusion therapy is needed as data from recent pivotal trials have the potential to change practice. This guideline, developed by a large international panel using a systematic search strategy and standardized methods to develop recommendations, incorporates recent trials not available when previous guidelines were developed. We found that prophylactic platelet transfusion for platelet counts less than or equal to 10 × 10(9)/L is the optimal approach to decrease the risk of hemorrhage for patients requiring chemotherapy or undergoing allogeneic or autologous transplantation. A low dose of platelets (1.41 × 10(11)/m2) is hemostatically as effective as higher dose of platelets but requires more frequent platelet transfusions suggesting that low-dose platelets may be used in hospitalized patients. For outpatients, a median dose (2.4 × 10(11)/m2) may be more cost-effective to prevent clinic visits only to receive a transfusion. In terms of platelet products, whole blood-derived platelet concentrates can be used interchangeably with apheresis platelets, and ABO-compatible platelet should be given to improve platelet increments and decrease the rate of refractoriness to platelet transfusion. For RhD-negative female children or women of child-bearing potential who have received RhD-positive platelets, Rh immunoglobulin should probably be given to prevent immunization to the RhD antigen. Providing platelet support for the alloimmunized refractory patients with ABO-matched and HLA-selected or crossmatched products is of some benefit, yet the degree of benefit needs to be assessed in the era of leukoreduction.

Red blood cell specifications for patients with hemoglobinopathies: a systematic review and guideline

BACKGROUND Red blood cell (RBC) transfusions remain essential in the treatment of patients with sickle cell disease (SCD) and ß­thalassemia. Alloimmunization, a well­documented complication of transfusion, increases the risk of delayed hemolytic transfusion reactions, complicates crossmatching and identifying compatible units, and delays provision of transfusions. Guidance is required to optimize the RBC product administered to these patients. STUDY DESIGN AND METHODS An international, multidisciplinary team conducted a systematic review and developed, following the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology, recommendations to assist treating physicians and transfusion specialists in their decision to select RBCs for these patients. RESULTS Eighteen studies (17 clinical studies and one cost­effectiveness study) were included in the systematic review. The overall quality of the studies was very low. In total, 3696 patients were included: 1680 with ß­thalassemia and 2016 with SCD. CONCLUSION The panel recommends that ABO D CcEe K­matched RBCs are selected for individuals with SCD and ß­thalassemia, even in the absence of alloantibodies, to reduce the risk of alloimmunization. In patients with SCD and ß­thalassemia who have developed clinically significant alloantibodies, selection of RBCs antigen negative to the alloantibody is recommended, if feasible. In these patients, selection of more extended phenotype­matched RBCs will likely reduce the risk of further alloimmunization. However, given the limited availability of extended phenotype­matched units, attention should be given to ensure that a delay in transfusion does not adversely affect patient care.

Specimen handling and tissue preaparation in pre-analytical phase of HER2 testing at tertiary referral hospitals of Metro Manila

INTRODUCTION: HER2 test result depends on a good quality histological section of the breast specimen. Laboratories that process specimens using sophisticated and molecular testing should receive suitable specimen for more accurate results and less waste of expensive resources.METHODS: A questionnaire based on the ASCO-CAP Guidelines for HER2 testing was developed and administered to pathologists from the local laboratories of Metro Manila-Philippines tertiary referral hospitals. Questionnaire responses were analyzed using descriptive statistics.RESULTS: Most laboratories did quality control/quality assessment monitoring for the pre-analytic, analytic,post-analytic and turn¬around time phases. Many transported their specimens from the operating room to the laboratoryCONCLUSION: Even in standardized procedures, small variations in sample processing for IHC and FISH can still occur. Inexperienced laboratories will have greater problems interpreting HER2 status results. Laboratories should look into their system in handling specimens for an accurate HER2 testing towards quality assurance.

Understanding current attitudes in HER2 testing for breast cancer at tertiary referral hospitals of Metro Manila, Philippines

INTRODUCTION: The difficulty of obtaining accurate and reproducible assessment of HER2 status in the Philippines, despite the predictive value of the test for HER2 positive breast cancer patients, may be sufficiently addressed if an effective multidisciplinary approach to HER2 testing is carried out. This may be accomplished by identifying disparities and similarities in HER2 testing for breast cancer.METHODS: This is a cross-sectional study which included medical oncologists who had used trastuzumab for HER2-positive patients. Surgeons, who belonged to the same tertiary hospital as the medical oncologists were also interviewed. The survey questionnaires were administered via face-to-face, mail, or fax. Responses were kept confidential. Questionnaire responses were analysed using summary statistics.RESULTS: There were 35 medical oncologists and 37 surgeons - 93% stated that all women diagnosed with breast cancer should be tested for HER2 at the point of diagnosis; 61% stated that the greatest barrier to initiating HER2 testing was inadequate patient funds. 57% medical oncologists and 65% surgeons believed that HER2 testing for all breast cancer patients at the point of clinical diagnosis was being observed at their hospital. 69% stated that medical oncologists or surgeons should request for HER2 test whoever saw the patients first; 59% stated that whoever saw the patient first provide the patient information about HER2 testing whereas 28% stated it is the medical oncologist who should provide information about HER2 testing. 47% medical oncologist and 63% surgeons stated that surgeons should arrange for breast tissue sample collection; 27% medical oncologists and 20% surgeons stated that pathologists should do this.CONCLUSION: Medical oncologists and surgeons were similar in the opinion that all women diagnosed with breast cancer should be tested for HER2 at the point of diagnosis, financial capability was the greatest barrier for initiating HER2 testing, and whoever saw the patient first should provide patient education. There was disparity on who should request and who should arrange for tissue collection.

Satisfaction in HER2 testing among medical oncologists- Aiming for multidisciplinary HER2 testing in the Philippines

INTRODUCTION: A multidisciplinary approach is essential to optimize patient care. In the practice of oncology, surgeons, medical oncologists, and pathologists are essential for the histology-based diagnosis of cancer patients. In breast cancer, hormone receptor and HER2 positivity are both predictive and prognostic, and so testing for these has been strongly recommended for every newly diagnosed breast cancer patient. A unique but meaningful information that can be provided by medical oncologists, as customers, is their satisfaction to the services (e.g. HER2 testing) and product (e.g. reports) of the pathology laboratory. Any quality initiative effort to improve HER2 testing can also be extended to hormone receptor (ER/PR) testing. This study measures the general satisfaction of medical oncologists practicing in Metro Manila with local HER2 testing services and reports.METHODS: This cross-sectional study had survey questionnaires distributed to medical oncologists practicing in Metro Manila chosen on the basis of their considerable experience with requesting HER2tests and with the use of anti-HER2 therapy in their management of breast carcinoma patients. Demographics, practice information, rating of satisfaction per laboratory service category, and a checklist of elements of IHC/FISH reports were collected.RESULTS: 32 medical oncologists participated in the survey, most of whom were from tertiary hospitals. Breast carcinoma cases make up around 26-50% of cancer cases in their practice. More than half request HER2 testing for their breast cancer patients. Medical oncologists are generally satisfied with the services for IHC and FISH HER2 testing (composite scores >2) provided by the laboratories. Overall, medical oncologists were very satisfied with diagnostic accuracy and completeness of relevant information in the report. Laboratory services were mostly rated good, with the exception of pathologists' responsiveness to problems and notification of equivocal results. For both IHC and FISH, patient/physician identification, date of service, specimen identification/ site/ type, results, and interpretation were reported to be included in the reports. However, time to/duration of/ type of fixation, method and image analysis method, antibody clone/ vendor, and comment that an FDA-approved method was used, were reported missing by the many.CONCLUSION: For both IHC and FISH, overall satisfaction was found to be moderately directly correlated with diagnostic accuracy. In a country like the Philippines where quality initiatives of laboratories may still be far from ideal, medical oncologists can demand inclusion of their preferences into assessments processes by laboratories and correct assumptions of laboratory managers as to what element of the services and products they value most. Measurement of customer satisfaction can be integrated into the quality assurance programs of laboratories and corresponding hospitals.  

Chromosomal aberrations among Filipino health workers at the chemotherapy oncology wards/clinics of a tertiary government hospital

INTRODUCTION: Chromosomal mutations are casual events in neoplasia development. Biomarker cytogenetic assays can determine exposure to mutagenic agents in occupational settings. This study assessed early biological marker chromosomal aberrations among health workers in the chemotheraphy oncology wards/ clinics, exploring its association to the subjects' occupational, environmental and baseline profile.METHODS: This was an IRB approved cross-sectional exploratory study among hospital personnel working in the chemotherapy oncology facility of a tertiary government hospital, who underwent structured interview and blood extraction for cytogenetic assay after informed consent. Study funds only permitted assay of 44 specimens of 144 planned sample size, hence, Stata 6.0 only analyzed data from 44 subjects.RESULTS: All 44 subjects had varying exposure to chemotherapy drug infusions. Of these, 79% had 1.0 breaks per cell (hypersensitive). Predominantly chromatid breaks (CTB), chromatid gaps (CTG), sister chromatid exhanges (SCE) were seen. No significant association was shown between mutagenic sensitivity and baseline characteristics, but with small sample size.CONCLUSION: 21% borderline to hypersensitive mutagenic sensitivity among oncology workers at the tertiary government hospital is relatively significant, despite small sample size, connoting a must preventive promotive practice of chemotherapy administration in the workplace.