Random Donor Platelet Transfusions Research Articles

Maternal Immune Thrombocytopenic Purpura Leading to Severe Neonatal Autoimmune Thrombocytopenia: Report of Two Cases

Introduction: In neonatal intensive care units, neonatal thrombocytopenia is one of the common hematological abnormality seen. Neonatal autoimmune thrombocytopenia should be considered in any neonate who is born to a known case of immune thrombocytopenia purpura (ITP) mother, with early onset thrombocytopenia without any signs of sepsis. Neonatal ITP is a condition of autoantibody mediated platelet destruction. Case details: Two neonates with thrombocytopenia, born to mothers with ITP are described in this report. Lowest platelet count noted was 7000 cells/cmm in one of the neonate. Both neonates received intra venous immunoglobulin (IVIG) while one neonate had persistent and severe thrombocytopenia requiring multiple random donor platelet (RDP) transfusions followed by oral steroid as well. Conclusion: Neonatal thrombocytopenia associated with maternal ITP need close monitoring, early sampling and diagnosis to prevent any possible complications and warrant early initiation of treatment.

An Interesting Case of Hemophagocytic Lymphohistiocytosis Secondary to Systemic Lupus Erythematosus

ABSTRACT Hemophagocytic lymphohistiocytosis (HLH) is a reactive condition marked by cytopenias and clinical features of systemic inflammation related to macrophage activation. It may be familial and may present early in life or sporadic and may affect people of any age. HLH secondary to systemic lupus erythematosus (SLE) is a rare clinical entity with an estimated prevalence of 0.9–4.6%. A 19-year-old man with no significant past medical history presented with complaints of high-grade fever with chills and bleeding manifestations, such as hematemesis, hemoptysis, epistaxis, and petechial rash in both upper limbs and lower limbs. Laboratory investigations showed significant pancytopenia and raised plasma levels of ferritin, triglycerides, and soluble interleukin (IL)-2. Ultrasonography of the abdomen showed mild hepatomegaly. A bone marrow biopsy showed evidence of mild hemophagocytosis. Antinuclear antibody (ANA) by indirect immunofluorescence assay (IFA) and double-strand deoxyribonucleic acid (dsDNA) came positive, and a diagnosis of HLH secondary to SLE was made. The patient was treated symptomatically with PCV and random donor platelet (RDP) transfusions and definitively with steroid therapy. HLH provokes potential life-threatening systemic toxicity and organ failure. Thus, prompt recognition when a patient presents with unexplained fever, cytopenias, and hepatosplenomegaly is required for timely treatment to prevent end-organ irreversible damage.

Effectiveness of Random Donor Platelet (RDP) Transfusion Therapy in Acute Leukaemia Patients: A Retrospective Analysis

Introduction: In India, lympho-hematopoietic malignancies constitute 9.5% of all cancers in men and 5.5% in women. The incidence of ALL and AML are 35% and 15% of all hematological malignancies respectively. Acute leukemia patients require multiple transfusions for a prolonged period of time. Patients undergoing induction and/or consolidation chemotherapy for leukemia often require platelet transfusion at least every 3 days. Normal platelet survival is approximately 5-7 days. Long - term platelet supportive care may be complicated by the development of a state of refractoriness, resulting in inadequate recovery of platelets. Moreover, with the progress of medical technology, platelet transfusion therapy is gradually getting better in the treatment of leukemic patients.

Impact of dose and storage duration of platelet concentrates on platelet recovery between ABO identical and ABO non-identical random donor platelet transfusions in hemato-oncology patients

It is challenging to adopt a policy of ABO identical platelet transfusion in hemato-oncological patients because of the high demand. Moreover, there are no global standards for the management of ABO non-identical platelet transfusions due to limited evidence. The current study compared the impact of dose and storage duration of platelets on percent platelet recovery (PPR) at 1 h and 24 h between ABO identical and ABO non-identical platelet transfusions in hemato-oncological conditions. The other objectives were to assess the clinical efficacy and compare adverse reactions between the two groups. A total of 130 random donor platelet transfusion episodes (81 ABO identical and 49 ABO non-identical) were evaluated in 60 eligible patients with different malignant, as well as non-malignant, hematological conditions. All analysis was performed using two-sided tests, and p-values <0.05 were considered significant. The PPR at 1 h and 24 h was significantly higher in ABO identical platelet transfusion. Platelet recovery and survival were not affected by the gender, dose or storage duration of platelet concentrate. Aplastic anemia and myelodysplastic syndrome (MDS) disease conditions were observed to be independent risk predictors for 1-h post-transfusion refractoriness. ABO identical platelets have higher platelet recovery and survival. Both ABO identical and ABO non-identical platelet transfusions have similar efficacy in controlling bleeding episodes up to World Health Organization (WHO) grade two. Assessment of other factors, such as platelet functional properties in the donor, anti-HLA and anti-HPA antibodies, may be needed to better understand the platelet efficacy of platelet transfusions.

COVID 19 vaccine induced thrombotic thrombocytopenia, cerebral venous thrombosis and neurogenic stunned myocardium.

To the Editor, Vaccine-induced thrombotic thrombocytopenia (VITT) manifesting as cerebral venous thrombosis (CVT) is rare but life-threatening complication after COVID-19 vaccination.[1] Neurogenic stunned myocardium (NSM) is a phenomenon of cardiac abnormalities occurring due to sympathetic storm after acute neurological injury.[2] This case reporting is done after obtaining written informed consent. We describe rare manifestation of VITT, CVT, and NSM after COVID-19 vaccination and its successful management. A 19-year-old lady presented with altered sensorium for 2 days. Prior to her current visit, she had low-grade fever for 2 days and holocranial headache with vomiting for one week after COVID-19 vaccination with COVAXIN® (Bharat Biotech). On examination, she was drowsy, obeying simple commands on repeated asking, aphasic, with motor power of 3/5. Her pupils were equal and reactive. Respiratory and cardiovascular system examination was normal. Brain computed tomography showed left temporo-parietal CVT with raised intracranial pressure (ICP), midline shift to right and left transverse sinus thrombosis [Figure 1]. Laboratory tests revealed thrombocytopenia (platelet count 43,000/μL), elevated D-dimer (7457 ng/mL), and prolonged prothrombin time (18.8s). VITT associated CVT was diagnosed. In view of neurological status and imaging findings, she underwent emergency temporo-parieto-occipital decompressive craniectomy. She received four units of random donor platelet transfusion and three units of fresh frozen plasma before and during surgery. She was shifted to neuro-intensive care unit for elective ventilation and further management. VITT was managed with Fondaparinux and therapeutic plasma exchange (TPE). On 2nd postoperative day (POD), she developed persistent hypotension with tachycardia resistant to fluid therapy, with abnormal arterial blood gas (PaO2 = 40.9 mmHg, PaCO2 = 25.7 mmHg, pH = 7.48, SaO2 = 80.9%). Hence, norepinephrine was started, positive end expiratory pressure (PEEP) and fraction of inspired oxygen (FiO2) increased to 8 cm water and 0.7, respectively. Following this, her heart rate was 112/min, blood pressure was 112/80 mmHg, electrocardiogram showed sinus tachycardia and oxygen saturation was 90%. The FiO2 was gradually reduced with improvement in oxygenation. Transthoracic echocardiography (TTE) showed left ventricular global hypokinesia with ejection fraction of 34%. She was diagnosed with acute left ventricular failure from NSM. Dobutamine and furosemide infusion with oral ivabradine resulted in improvement and cardiovascular medications were tapered and stopped on 9th POD and trachea was extubated on 10th POD. After 24h observation, she was shifted to ward and subsequently discharged home with improved neurological status. Follow up TTE at discharge showed normal cardiac contractility.Figure 1: Contrast computed tomography of the brain showing large temporo-parietal hematoma due to cerebral venous thrombosis with midline shift, mass effect, and significant cerebral edema with loss of gray-white differentiationVITT is characterized as vaccine-induced immune syndrome of severe thrombosis, antibodies to platelet factor 4–polyanion complexes and thrombocytopenia.[3] VITT begins 5-10 days after vaccination and is diagnosed between 5 to 30 days.[4] It is associated with CVT, splanchnic vein thrombosis, deep venous and arterial thrombosis with thrombocytopenia, and elevated D-dimer. Treatment includes non-heparin anticoagulants such as indirect Xa inhibitors (fondaparinux, danaparoid), oral anticoagulants or thrombin inhibitors (argatroban, bivalirudin), and intravenous immunoglobulin or TPE. NSM is reported after stroke, traumatic brain injury, and subarachnoid hemorrhage but not after CVT. Catecholamine excess, systemic inflammation, and neuroendocrine derangements contribute to occurrence of NSM.[5] It is likely that the NSM in our patient was due to interplay of acute increase in ICP (neurogenic) from VITT-associated malignant CVT and systemic vaccine-induced complication-associated stress on the myocardium. Treatment is supportive to improve myocardial function and prevents cardiovascular complications including sudden death.[5] Ivabradine reduces heart rate and improves cardiac failure while dobutamine improves hemodynamic instability associated with NSM.[5,6] To conclude, VITT-associated CVT leading to NSC is rare and challenging to identify and manage. Management goals include reduction of acute intracranial hypertension, restoration of platelet function, anti-coagulation, and supporting cardiac function. Patient consent form Yes. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

A comparative study of the transfusion effect of single donor apheresis platelets versus random donor platelets in the management of severe dengue infection in children

Background: The national vector-borne diseases control programme (NVBDCP) dengue clinical care guidelines 2014 clearly specify the indications for platelet transfusion in dengue fever. The goal of the study was to see how successful guideline-driven platelet transfusion was, as well as whether single donor platelet (SDP) transfusion was superior to random donor platelet transfusion (RDP), which was widely thought but unproven.Methods: Two ml of the patient's blood were collected in EDTA tubes at two distinct times: once before the transfusion and the other 24 hours afterwards and the data were assessed using corrected count increments (CCI), percentage recovery (PR) and other criteria.Results: Platelet increments were substantially larger with SDP transfusions at 24 hours than with RDP transfusions (p&lt;0.01 for 24 hours post-transfusion period). However, in both groups, the corrected count increment and percentage recovery were nearly identical and the difference was statistically insignificant.Conclusions: Although post-transfusion increments were considerably higher in SDP patients than in RDP patients, the CCI and PR were similar in both groups of patients. When it comes to the number of donors exposed to patient and leukoreduction, SDP is superior to RDP in terms of logistics. However, in developing countries, SDP may be advised only in selected patients based on accessibility and affordability, due to their high cost and higher technical competence required.

Human leukocyte antigen (HLA)-incompatible mean fluorescence intensity-selected platelet products have corrected count increments similar to HLA antigen-matched platelets.

Donor specific antibody sum mean fluorescence intensity (MFI) values have been successfully used in transplant medicine to assess risk for organ rejection. However, little is known regarding whether MFI values could be similarly used to aid in platelet product selection. We have developed a novel protocol where MFI values are used to offer human leukocyte antigen (HLA)-incompatible platelet products when HLA antigen-matched products are not available. We aimed to evaluate the efficacy of this protocol. We performed a 4-year retrospective chart review for all patients who received at least one MFI-selected platelet product. A corrected count increment (CCI) was calculated for each transfusion event. A mixed effects model was used to investigate the association between CCIs for MFI-selected, HLA antigen matched, and random donor platelet transfusions. A random effects expectation-maximization regression tree was used to define the extent to which other patient variables, such as age, sex, and diagnosis impacted the CCI for each platelet transfusion. Twenty highly HLA alloimmunized patients received a total of 591 platelets. MFI-selected platelet (low MFI) transfusions had a significantly higher median CCI 0-6 hour post-transfusion (13,559, interquartile range [IQR]: 8275-18,736) compared to random donor platelets (2121, IQR: 0-10,368, p< 0.0001). There was no significant difference in median CCI between HLA antigen matched and MFI selected platelet transfusions (p= 0.2). Mixed effects and regression modeling revealed that MFI-selected platelet products had a significantly higher CCI than non-matched platelets, even when accounting for other significant patient variables. MFI-selected HLA-incompatible platelet products could provide a comparable alternative to traditional HLA antigen-matched platelet products.

The association of disease type, pre-transplant hemoglobin level and platelet count with transfusion requirement after autologous hematopoietic stem cell transplantation.

Background:Autologous hematopoietic stem cell transplantation (auto-HSCT) has become an effective treatment for a wide range of hematologic and non-hematologic diseases. Patients undergoing HSCT might require multiple platelets and red blood cell (RBC) transfusions during aplasia phase until engraftment, which could profoundly affect patients’ conditions. Identification of risk factors associated with blood product requirements could help in decreasing transfusion-related complications. We evaluated the association of disease type, pre-transplant hemoglobin level, and pre-transplant platelet count with RBC/platelet transfusion requirement after auto-HSCT.Methods:In this retrospective study, 324 patients diagnosed with multiple myeloma (MM), Hodgkin disease (HD), and non-Hodgkin lymphoma (NHL) and underwent auto-HSCT were included. The associations of disease type, pre-transplant hemoglobin level, and platelet count with post-transplant packed cell and single-/random-donor platelet transfusions were evaluated.Results:Our study results illustrated that the higher pre-transplant hemoglobin level significantly decreased the post-HSCT requirement for packed cell (IRR=0.81, [CI: 9.73-0.90], P=0.0001), while the pre-transplant platelet showed no significant relationship with platelet requirement after HSCT. HD was associated with increment in packed cell (IRR=2.04, [CI: 1.35-3.08], P=0.001) and single donor platelet (IRR=1.39, [CI: 1.09-1.78], P=0.008) requirement after transplant. The trends showed that a higher platelet level led to a lower need for platelet transfusion.Conclusion:Pre-transplant hemoglobin level could be valuable markers for predicting post-HSCT RBC requirements and might be beneficial for better management of transfusion requirements to minimize the transfusion-related complications. Patients with HD seem to be more prone to blood product requirements post-transplant.

Outcome of Fludarabine-Based Conditioning in High-Risk Aplastic Anemia Patients Undergoing Matched Related Donor Transplantation: A Single-Center Study from Pakistan.

Despite excellent transplant outcomes of aplastic anemia (AA) in developed countries, management in developing countries is challenging because of delay in the diagnosis, use of family donors for transfusions, and higher infection risk pretransplant. These factors can lead to allo-immunization, increased risk of graft failure, graft-versus-host disease (GVHD), and transplant-related mortality, leading to unfavorable outcomes. Conventional cyclophosphamide (Cy) and antithymocyte globulin (ATG) are associated with inferior overall survival in such high-risk patients. We conducted single-center retrospective analysis of high-risk AA patients (N = 147) enrolled consecutively and undergoing matched related donor transplant from March 2002 through October 2018. We included high-risk AA patients receiving fludarabine (Flu)-based conditioning. Median patient age was 20 years (range, 3 to 52). The median time from diagnosis to transplant was 11 months (range, 3 to 63). High-risk features included age ≥ 20 years in 55.8% of patients (n = 82), disease duration more than 3 months in 95 % (n = 140), RBC concentrates transfusions > 20 in 79.6% (n = 117), random donor platelet transfusion > 50 in 64.6% of patients (n = 95), and second hematopoietic stem cell transplant (HSCT) in 7.4% (11). We divided patients into 2 groups based on different conditioning regimens. Flu group 1 (Flu1) received Flu 120 to 150 mg/m2, Cy 120 to 200 mg/kg, and ATG 20 mg/kg, and Flu group 2 (Flu2) was given Flu 150 mg/m2, Cy 300 mg/m2, and ATG 20 mg/kg. Bone marrow stem cells were used as graft source in 97% of patients (n = 144) (alone in 52% and with peripheral blood stem cells in 45%). Cyclosporine alone was used for GVHD prophylaxis in 75% (n = 110) and cyclosporine plus methotrexate in 25% (n = 37). Median total nucleated cell dose was 5 × 108/kg. Median days for neutrophil engraftment was 13 (range, 10 to 20) and platelet engraftment 20 (range, 14 to 43). Day 100 mortality was 7.5% (n = 11). Sustained successful engraftment was achieved in 87.8% of patients (n = 129). Most graft failures (40%) occurred in Flu2 conditioning (P = .000) and in patients with >2 risk factors (P = .000). Overall incidence of acute and chronic GVHD was 11.6% (n = 17) and 12.9% (n = 19), respectively, in Flu1 and Flu2 groups. Overall survival (OS), disease-free survival (DFS), and GVHD-free relapse-free survival (GRFS) was 83.7%, 78.2%, and 70.7%, respectively. A trend toward improved OS was observed in patients receiving Flu1 conditioning but was statistically nonsignificant (P = .256), whereas DFS and GRFS were significantly better in Flu1 versus Flu2 (P = .004 and .001, respectively). When stratified per number of risk factors (age > 20, RBC concentrate > 20 or platelet > 50 random, duration > 3 months, previous HSCT), OS and DFS decreased significantly with increasing number of risk factors (P = .000 and .001, respectively). Patients are able to tolerate Flu-based conditioning well with lower rates of rejection and excellent long-term survival in high-risk AA patients. Cyclosporine alone as GVHD prophylaxis and marrow source stem cells as graft source are preferable options. Use of Flu plus low-dose Cy conditioning is associated with inferior survival outcomes. A randomized trial of Flu-based versus conventional Cy-containing conditioning would be helpful in establishing a standard of care conditioning regimen in high-risk AA patients.

Legal Briefs: In Utero Cerebral Hemorrhage and Alloimmune Thrombocytopenia: Was It Preventable?

A 3,425-g, 39-week-gestation male infant was born to a 24-year-old gravida 1 para 0 woman via cesarean section because of a nonreassuring fetal heart rate tracing. Apgar scores were 9 and 9 at 1 and 5 minutes, respectively. He was admitted to the normal newborn nursery, where the nurse noted that he had generalized petechiae. The complete blood cell count was normal, except for a platelet count of 7 × 103/μL (7 × 109/L). He was admitted to the NICU at 27 hours of age for evaluation and care. He was alert and active, with normal blood pressure and vital signs. The neonatologist ruled out autoimmune thromobocytopenia after determining that the mother's platelet count was normal. He asked the obstetrician to order an antiplatelet antibody test on the mother to determine if alloimmune thrombocytopenia was the diagnosis. Intravenous immunoglobulin (IVIG) was given, as well as 2 random donor platelet transfusions, which moderately elevated the platelet count. Because a heart murmur was noted, cardiac ultrasonography was performed, which showed the infant to have a hypoplastic right ventricle, tricuspid atresia, a ventricular septal defect, and a patent foramen ovale. Prostaglandins were started and the infant was sent to a referral center, where a balloon septostomy was performed. The neonatologist at the referral hospital requested a hematology consultation and ordered a platelet antibody test; however, because it was the weekend, the test was deferred until the following Monday. By Monday, the platelet count was normal, and the hematologist wrote a note that alloimmune thrombocytopenia was probably not the cause and the test was never performed. The parents were told that the low platelet count was idiopathic, and because it resolved, nothing further needed to be done. The complex cardiac defect was subsequently repaired, with excellent results. The mother shared …

The utility of thromboelastometry in prophylactic platelet transfusion for hematological malignancies

There is still debate on how platelet transfusions should be used to prevent severe bleeding. The aim of our study is to assess the clinical efficacy of thromboelastometry in reducing number of prophylactic platelet transfusions in patients with hematological malignancies. One hundred hematological malignancy patients were included in the study. Six units random donor platelets (RDPs) was given to the first group, three units RDPs was given to the second group, one unit single donor platelets (SDPs) was given to the third group, and 1/2 unit SDPs was given to the fourth group. Before and 15 minutes after transfusion, rotation thromboelastometry (ROTEM) was performed (Pentapharm GmbH, Munich, Germany). ROTEM(®) parameters did not show any statistical difference between 'low dose' and 'high dose' random or single donor platelet transfusions. Therefore, low dose platelet transfusion can be considered because of its reduced adverse transfusion reactions and economic burden.

Changing profile of Plasmodium vivax malaria

Background: Malaria, endemic in India, tends to be a major contributor to morbidity and mortality globally. Of the various species, Plasmodium Falciparum is associated with serious prognosis,(morbidity and mortality) in a sizeable number of patients. Chloroquine resistance was an important clinical issue; the current issue is that of an apparently changing scenario with rising number of P.Vivax malaria cases, associated with severity of complications. The observational study is aimed to find out whether there is change in P.Vivax malaria features and how it influences management. Methods & Materials: An observational study conducted at a teaching hospital in centralmetropolitanMumbai, India during the monsoon months (June-October 2013). Febrile patients admitted from the medical outdoor and emergency service form the basis of this study. Patients with moderate to severe degree fever, with chills, localized and generalized body ache, varying degrees of weakness/fatigue and malaise/lethargy, vomiting suspected clinically to be suffering from malaria were tested by peripheral smear examination/malaria specific Antigen. Other investigations included total and differential count, liver function testsmainly Serum Bilirubin, Transaminases, renal function tests (Serum Creatinine). Haemodynamic Instability (hypotension), thrombocytopenia withmanifest bleeding, affected renal function singly and in combination were the differentiating criteria towards critical care. Results: A total of 41 cases (29M, 12 F) of malaria were diagnosed39 were P.vivax and 2 were mixed malaria. As many as 32 patients were found to be thrombocytopenic (platelet count <1.5 lakhs), the range being from 12,000 to 1.4 lakhs/cumm. Seven patients (17%) presented with hypotension and required ICU monitoring. 14 patients (34%) had deranged liver function test mostly in the form of transaminitis and 3 cases with renal insufficiency.3 patient presentedwith bleeding. 7 patients required platelet transfusion (4 units each of Random Donor Platelet transfusion) and 1 patient required platelet transfusion twice. Patients who tested positive for Dengue Antigen fared poorly. Fluctuating and decreasing platelet countwithout bleeding contributed to prolongation of hospital stay. Conclusion: P.falciparum has been considered malignant malaria, P.vivax malaria particularly with thrombocytopenia has increased in incidence and is not considered benign any longer.

The Mean Fluorescence Intensities of Anti-HLA Antibodies Detected Using Micro-Bead Flow Cytometry Predict the Risk of Platelet Transfusion Refractoriness.

Abstract Abstract 2285 Background: HLA allo-immunized patients often receive matched platelets only after demonstrating platelet transfusion refractoriness (PTR). If further risk stratification was possible, high risk patients could be considered for pre-emptive HLA-matched platelets, cryopreserved autologous platelets, or possibly thrombopoietin analogues. Micro-bead flow cytometry is widely used to detect anti-HLA antibodies, and mean fluorescence intensities (MFI) obtained from these assays correlate with antibody titers. We asked whether MFIs could be used to stratify the risk of PTR among allo-immunized patients. Study design: We retrospectively identified 387 patients who received an autologous stem cell transplant or induction therapy for acute leukemia, between January 2005 and March 2012. All patients had a serum sample taken for HLA antibody assay within 6 weeks of commencing cellular blood product transfusions. No patient was scheduled to receive prophylactic HLA matched platelets. The primary endpoint was the development of PTR. To minimize the influence of sensitization occurring after screening, only outcomes during the first 2 weeks from commencing cellular blood product transfusions were considered. PTR was defined as having received ≥ 2 consecutive RDPLT transfusions associated with an 18–24h corrected count increment of &lt; 2.5 at 18 – 24 hours. Antibody testing was performed using a micro-bead flow cytometry assay (Lifecodes LifeScreen Deluxe, with positive results confirmed by Lifecodes Class I ID assay, Gen-Probe Transplant Diagnostics, Stamford, CT) either during the treatment period, or on serum samples stored at −30°C. Mean fluorescence intensities (MFI) were acquired using a Luminex 100 analyzer (Luminex Corporation, Austin, TX), and analyzed using Lifecodes Quicktype v2.5.5 (Gen-Probe Transplant Diagnostics, Stamford, CT). We defined the predictor variable avgMFI to be the average MFI of the 7 individual beads in the assay, weighted by whether the presence of antibodies was confirmed or not: where w = 1 if the presence of antibodies is confirmed, and 0 otherwise; and subscript i refers to the ith class I bead. Results: Antibodies were detected in 57 (14.7%) patients of whom 45 (78.9%) were female. A total of 1443 random donor platelet (RDPLT) transfusions (mean platelet count 2.4×1011/unit) were studied. Sixty six (17%) patients developed PTR, of whom 28 had detectable antibodies; 29 of 321 patients who did not develop PTR also tested positive. Among antibody positive patients, median avgMFI for refractory patients was 4589 versus 349 for patients who were not, Wilcoxon rank sum test P&lt; 0.0001. (Figure 1). The area under the receiver operating characteristic curve for avgMFI as a predictor of PTR was 0.8633 (95% confidence interval: 0.7664 – 0.9602). Higher avgMFIs also correlated with a broader range of target antigens, likely due to increasingly avid binding to cross-reactive epitopes. (Spearman's r = 0.7736 for correlation between avgMFI and panel reactive antibody percentages (cPRA), calculated in reference to the general American population, and used here as a surrogate for the range of antibody specificities). cPRA was &gt;80% in 25/27 patients with avgMFI&gt;1000, suggesting poor ability to discriminate among patients with moderate to high antibody titers, and was not an independent predictor of PTR. Hence, while the increased probability of encountering a cognate antigen on a RDPLT may partly explain the correlation between avgMFI and PTR, the avidity of binding, represented in vitro by the MFIs, appears to be a more significant determinant of risk. In conclusion, we provide evidence for the concept that PTR risk due to HLA allo-immunization is usefully predicted by the MFIs of antibodies detected using micro-bead flow cytometry. Our model allows cut-offs for identifying high risk patients to be based on the degree of risk acceptable in a given clinical situation. This should enable hematology units to develop risk-adapted strategies for supporting allo-immunized thrombocytopenic patients. Disclosures: No relevant conflicts of interest to declare.

HLAMatchmaker-driven analysis of responses to HLA-typed platelet transfusions in alloimmunized thrombocytopenic patients

This study describes a novel application of HLAMatchmaker to determine platelet compatibility in 16 alloimmunized patients with aplastic anemia refractory to random donor platelet transfusions. HLAMatchmaker is a software algorithm that predicts HLA compatibility by identifying immunogenic epitopes represented by amino acid triplets in antibody-accessible regions of human leukocyte antigen (HLA) molecules and determines the number of triplet mismatches (TMMs) and highly immunogenic triplet mismatches (HIMMs). Corrected count increments (CCIs) and molecular HLA typing were available for 523 transfusions. Conventional compatibility assessment based on cross-reactive group (CREG) determination was not predictive of transfusion outcome. Low HIMMs and TMMs numbers were associated with a higher likelihood of satisfactory (CCIs > or = 8) compared with unsatisfactory (CCIs < 8) outcomes (median HIMMs = 4 vs 6, p2 value < .001; median TMMs = 11 vs 13, p2 value < .001). Although receiver operator characteristic curves revealed that HIMMs or TMMs number are not powerful predictors of individual transfusion outcome, a threshold of at least 3 HIMMs or at least 9 TMMs appeared to be associated with successful transfusions. Triplet-matched transfusions were successful, regardless of CREG matching. Our data validate HLAMatchmaker for platelet transfusions and demonstrate its potential to refine and expand donor selection for HLA-alloimmunized patients.

Platelet transfusion refractoriness caused by a mismatch in HLA-C antigens.

HLA-C antigens have been thought to be of little significance in determining the efficacy of platelet transfusions. However, six alloimmunized patients were encountered who were refractory to platelet transfusions because of anti-HLA-Cw3, -Cw3, -Cw7, or -Cw8. Between 1995 and the present, 88 patients with hematologic malignancies became refractory to random-donor platelet transfusions due to HLA antibodies. HLA-A- and HLA-B-compatible platelet transfusions were successful in boosting platelet levels with 82 of the patients. This study concerns the remaining six HLA-immunized patients who were refractory to HLA-A- and HLA-B-compatible platelet transfusions. The response to the platelet transfusions was assessed by calculating both 1- and 24-hour posttransfusion CCIs for each transfusion. The average CCI(1 hour) and CCI(24 hours) in all patients were 20.0 and 12.8 for HLA-A-, HLA-B-, and HLA-C-compatible transfusions and were 1.4 and 1.2 for HLA-A- and HLA-B-compatible but HLA-C-incompatible transfusions, respectively (p < 0.001). These findings clearly indicate that matching of the HLA-C antigens is also required in some alloimmunized patients to obtain the effectiveness of platelet transfusions.

Bleeding risk and platelet transfusion refractoriness in patients with acute myelogenous leukemia who undergo autologous stem cell transplantation.

Therapy for acute myelogenous leukemia can be complicated by alloimmunization to histocompatibility antigens (HLA), with resultant refractoriness to platelet transfusions. Autologous peripheral blood or bone marrow stem cell transplantation (referred here collectively as 'autoBMT') is emerging as a standard consolidative strategy in acute myelogenous leukemia (AML). We had noted life-threatening bleeding associated with platelet transfusion refractoriness following autoBMT; we therefore retrospectively analyzed 39 AML patients for this complication following BMT. All patients received high-dose chemoradiotherapy, followed by infusion of allogeneic sibling donor (n = 12, alloBMT) or autologous (n = 27, autoBMT) stem cells. HLA alloimmunization was assessed if patients were suspected of immune refractoriness to random donor platelet transfusions. Within 100 days of stem cell infusion, one of three alloBMT and six of 12 autoBMT recipients tested were HLA alloimmunized (not statistically significant, NS). Five of six HLA alloimmunized autoBMT patients experienced delayed bleeding, which contributed to their demise while still in remission (P < 0.001). Increased platelet requirements in HLA alloimmunized autoBMT recipients were observed between days 61 and 100 post-BMT, at a median of 211 platelet transfusions vs 0 in non-alloimmunized autoBMT patients (P < 0.01) and 17 in alloBMT patients. Our data suggest that platelet transfusion refractoriness, when associated with HLA alloimmunization, is a risk factor for increased platelet transfusion requirements, delayed bleeding, and poor outcome following autoBMT for AML.

Leukocyte-reduced blood transfusions: perioperative indications, adverse effects, and cost analysis.

Leukocyte-reduced blood transfusions: perioperative indications, adverse effects, and cost analysis.

The utility of ≤3‐day‐old whole‐blood platelets in reducing the incidence of febrile nonhemolytic transfusion reactions

Febrile nonhemolytic transfusion reactions (FNHTRs) to platelet transfusions have been linked to the presence of cytokines in supernatant plasma. Cytokine concentration is directly related to WBC content and storage time. This study evaluated the effect of limiting the storage time of random-donor platelet concentrates on the FNHTR rate. FNHTR rates were calculated retrospectively for single-donor apheresis platelet (SDP) and pooled random-donor platelet (PP) transfusions given during three consecutive 5-month study periods (November 1995 to February 1997) to patients on a single hematology/oncology/bone marrow transplant unit. Transfusion practice policies were: Baseline Period, SDPs preferred; Study Period A, PPs preferred; and Study Period B, < or =3-day-old PPs preferred. FNHTR rates were calculated from physicians' interpretations of reported reactions and the total number of SDP and PP transfusions in each period. SDPs were collected on two cell separators. All platelet components were filtered at issue in the laboratory by WBC-reduction filters. FNHTR rates for PP transfusions were: baseline, 11.1 percent (3/27); Study Period A, 4.6 percent (22/481); and Study Period B, 1.1 percent (3/282). The rates for SDP transfusions were 0. 15 percent (1/650), 0.75 percent (2/267), and 0.36 percent (1/273), respectively. The FNHTR rate for < or =3-day-old PPs was significantly less than the rate for older PPs (p = 0.0086 for Study Period A vs. Study Period B), and was not significantly different than that for SDPs (p = 0.33 for PPs vs. SDPs in Study Period B). Limiting transfusion of PPs to those stored </=3 days is an effective strategy in reducing the rate of FNHTR and results in an FNHTR rate comparable to that seen with SDPs.

Meta-analysis of randomized controlled trials of the efficacy of white cell reduction in preventing HLA-alloimmunization and refractoriness to random-donor platelet transfusions.

Meta-analysis of randomized controlled trials of the efficacy of white cell reduction in preventing HLA-alloimmunization and refractoriness to random-donor platelet transfusions.

Neonatal Alloimmune Thrombocytopenia due to Anti‐HPA‐1b (PLA2) (Zwb)

Abstract Background: Neonatal alloimmune thrombocytopenia is a rare condition due to passively acquired maternal antibodies directed against paternal platelet antigens inherited by the infant. Only 5 cases have been reported due to antibodies against HPA‐lb (PLA2) (Zwb). Case Report: We report a case of neonatal alloimmune thrombocytopenia due to anti‐HPA‐lb in the second pregnancy of a 26‐year‐old Caucasian female. The male infant was treated with a 5‐day course of intravenous immunoglobulin without complications. We report the HLA phenotype of the infant's mother and summarize the previous case reports due to anti‐HPA‐lb. Conclusion: Based on this case and a review of the literature, intravenous immunoglobulin as well as random donor exchange transfusion and random donor platelet transfusions are effective in the treatment of neonatal alloimmune thrombocytopenia due to anti‐HPA‐lb. Obvious associations between HLA alleles and sensitization to HPA‐lb have not been elucidated.