Platelet Increment Research Articles

Prevalence, Risk Factors, and Outcomes of Platelet Transfusion Refractoriness in Critically Ill Patients: A Retrospective Cohort Study

Background Refractoriness to platelet transfusion is an understudied phenomenon in critically ill patients. Our objective was to evaluate the prevalence, risk factors, and clinical outcomes of platelet refractoriness among patients in a tertiary-care intensive care unit (ICU). Methods A retrospective cohort study included all patients (age >14 years) who were admitted to a tertiary-care medical-surgical ICU between 2011 and 2016 and received ≥2 platelet transfusions during their ICU stay. We calculated platelet increment (PI) and corrected count increment (CCI). Results A total of 267 patients were enrolled in the study, collectively receiving 1357 transfusions with a median of 4.0 (interquartile range: 2.0, 6.0) transfusions per patient. The median pretransfusion platelet count was 31000.0 × 106/L (interquartile range: 16000.0, 50000.0). The median PI was 6000 × 106/L. The prevalence of platelet transfusion refractoriness was 54.8% based on PI < 10000 × 106/L and 57.0% based on CCI <5000. Patients admitted under hepatology/liver transplant had the highest rates of platelet refractoriness (69.6%), while those under general surgery had the lowest rate (43.2%). Younger age, nontrauma admission, and larger spleen size were associated with platelet refractoriness. Finally, refractoriness was associated with increased length of stay in the ICU (p = 0.02), but not with mortality. Conclusions Platelet transfusion refractoriness was highly (>50%) prevalent in ICU patients. However, it was not associated with increased mortality.

The Epidemiology of Platelet Transfusions: An Analysis of Platelet Use at 12 U.S. Hospitals

Background: Platelet transfusions in the United States are increasing in sharp contrast to the marked decrease in red cell and plasma use. Understanding the epidemiology and clinical practice for patients requiring platelet transfusions, particularly in the non-oncologic setting, is needed to identify clinical needs or significant change in practice. Such information can be used to focus the design of evidence based studies to assess platelet transfusion practice and efficacy to areas of high clinical need.Methods: Patient demographics, laboratory and clinical data were extracted from 2013 - 2015 from blood bank information systems and medical records from 12 REDS-III hospitals (both academic and community) located in four states across the U.S. A patient encounter was defined as any inpatient admission or outpatient visit documented with a unique visit date and discharge date. A transfusion episode was defined as all platelets transfused within an 8 hour interval beginning with the first platelet dose transfused within any encounter. Pre-platelet counts are defined as the nearest count up to 24 hours prior to the first transfusion for inpatients, and up to 48 hours before for outpatients. Post-platelet counts are defined as the first count up to 24 hours after completing the last transfusion for inpatients, and up to 48 hours after for outpatients.Results: A total of 122,298 platelet doses were issued for transfusion: 74,721 (61%) were apheresis platelets; 47,577 (39%) were pooled whole blood derived platelets; 103,759 (85%) were for inpatients, 18,539 (15%) were for outpatients. For inpatient transfusions 54% were issued to the General Ward, 29% to ICU, 12% to OR, 3% to ER. One platelet dose was issued per episode 78% of the time, 2 doses in 17%, 3 doses in 3%, and 4 doses in 1%. ABO donor-recipient identical platelets were transfused 37% of the time. For selected ABO mis-matched transfusions, type O platelets were given to non-type O patients 8%, and non-type O platelets to type O patients 19% of the time. Cardiovascular, Hematology-Oncology and Gastrointestinal were the most common broad diagnostic categories for encounters. The top three primary ICD 9-10 codes for each of these categories were: Cardiovascular: coronary atherosclerosis of the native coronary artery, aortic valve disorder and intracerebral hemorrhage; Hematology-Oncology: acute myeloid leukemia without achieving remission, neutropenia NOS, and multiple myeloma with achieving remission; Gastrointestinal: alcohol cirrhosis of the liver, cirrhosis of the liver NOS and hepatic encephalopathy.For inpatients a platelet count between >20,000/µL and 50,000/µL was the most common pre-transfusion count (28% of all episodes) with similar results for general ward (29%) and ICU patients (35%). In the ED and OR a platelet count >100,000/µL was most common - found in 38% and 37% of all episodes. For outpatient transfusions a count of >10,000/µL to 20,000/µL was most common (25%). For inpatients post-platelet count increment ranged from a median of 12,000/µL to 23,000/µL with progressively larger increments seen with progressively higher starting counts (Table 1). For outpatients post-platelet count increments ranged from 21,000/µL to 27,000/µL (Table 1).Conclusion: The REDS-III data base provides a wealth of information to assess platelet transfusion therapy in the U.S. Transfusion of more than 1 dose of platelets per episode is uncommon. Transfusion of ABO mismatched platelets is a common practice. Cardiovascular and Hematology -Oncology patients are prominent users of platelet products. General Ward and ICU dominate the location for platelet transfusion therapy and have similar transfusion practice patterns. The common pre-transfusion platelet count of 20,000-50,000/µL is surprising (as this exceeds evidence based recommendations for prophylactic transfusions in hematology-oncology patients) with reasons unclear. Platelet count increments were also surprisingly low. These findings, particularly the high pre-transfusion platelet count, the poor platelet increments and the high number ABO mis-matched transfusions, highlight differences in real world versus controlled studies and provide epidemiologic and laboratory data to develop future research to improve platelet transfusion practice. [Display omitted] DisclosuresNess:Terumo BCT: Consultancy.

Continuous Platelet Transfusion As a Potential Desensitization Regimen in HLA Class I Alloimmune-Mediated Platelet Refractoriness

Background: The development of HLA antibodies is responsible for 4-8% of platelet transfusion refractoriness (PTR). The presence of HLA antibodies is a clinical complication that is generally managed by the selection of products that are negative for the antigens cognate to the patient's antibodies. Often, this selection is facilitated by targeted recruitment of donors with known HLA types. However, for very broadly HLA-alloimmunized patients, compatible products may be exceedingly scarce or completely unavailable, precluding the ability to consistently provide products the patient will likely increment to and benefit from. Here we describe a case of a patient with severe aplastic anemia (platelet count chronically <1 K/uL) and platelet transfusion refractoriness secondary to broad HLA-alloimmunization (98% PRA). HLA compatible products were unavailable due to the patient's rare HLA type and breadth of antibodies, and attempts at procuring compatible products via multiple national agency searches were unsuccessful. Thus, the patient could only be supplied with HLA incompatible products, which yielded insufficient post-transfusion platelet corrected-count increments (CCI). Her course was eventually complicated by multifocal intracranial hemorrhages, necessitating ICU admission with aggressive platelet transfusion support, immune-targeting therapy consisting of IVIg, and aminocaproic acid and recombinant activated factor VIIa.Methods: A continuous platelet infusion, or “platelet drip,” was employed in order to provide platelet transfusion support in the face of her severe thrombocytopenia with profound refractoriness. This consisted of consecutive transfusions of 4-6 equivalent unit apheresis platelet products (“doses”) transfused over 4 hours with a 15 minute post-transfusion CBC obtained from Q8 to Q12 hours to assess platelet increments. This ultimately resulted in 24-30 equivalent unit platelet product infusions/day.Results: Two days into the continuous platelet infusion, the patient began incrementing appropriately to occasional platelet products (CCI>>5) and, consequently, the infusions were able to sustain a platelet count >10K/uL, with a range of 20-70 K/uL, over the subsequent week. The improved counts, along with the patient's improved clinical condition and stable imaging findings showing resolving intracranial hemorrhages, allowed the transfusion support to be goal-directed targeting a prophylactic platelet threshhold of 10K/uL. Continued monitoring of the patient's CCIs enabled the identification of permissive antigens (i.e., allogeneic platelets with HLA antigens predicted to be incompatible with the patient's serum by solid-phase testing but were found to result in satisfactory increments); this knowledge allowed progressive widening of her permissive donor pool and enabled continued prophylactic support as needed. After three weeks the patient was able to be discharged from the ICU.Subsequent HLA class I antibody screens using flow-cytometry based single antigen bead (SAB) technology revealed progressive decrease in the patient's mean fluorescence intensity for most of her antibody specificities, with the majority of her class I A antibodies falling to undetectable or near-undetectable levels (while previously >5000 MFI). Simple regression analysis (RStudio 1.0.153, R version 3.4.1) was used to test to how level of exposure to individual HLA platelet antigens (as measured by the number of doses with a given antigen) affected subsequent MFI levels. The results of the regression indicate that pre MFI and exposure explain 70.6% of the variance (R2=0.706, F(2,78)=93.7, p=<2.2e-16). It was found that exposure is a significant predictor of decreased MFI (b=-107.20, p=0.01422). High initial MFI was strongly associated with high subsequent MFI (b=0.75, p= <2.2e-16).Conclusions: This data raises the possibility that large bolus platelet infusions could not only be of immediate therapeutic benefit in patients with HLA-alloimmune-mediated platelet refractoriness, but may also accelerate the evanescence of the responsible antibodies. Further research is warranted to explore this possibility, and to ascertain the potential magnitude of this effect in comparison to competing factors such as natural evanescence and/or B-cell immunosuppressive or immunomodulatory therapies. DisclosuresNo relevant conflicts of interest to declare.

The first known case of vaccine‐induced thrombotic thrombocytopenia in Australia

The first known case of vaccine‐induced thrombotic thrombocytopenia in Australia

New design to remove leukocytes from platelet-rich plasma (PRP) based on cell dimension rather than density

Platelet-rich plasma (PRP) can stimulate the proliferation of stem cells and have a positive effect on tissue repair. Although many commercialized PRP preparation kits are already on the market, first-line clinical workers are still not satisfied with most of the PRP kits. The work of commercial PRP kits is based on the density of blood elements. However, the blood elements are very close in density which makes the separation challenging. Therefore, the mentioned commercialized kits are generally contaminated by leucocytes and erythrocyte. In this study, a home-designed PRP device was developed to use a separation membrane with adequate cut-off pore size of 5 μm, 3 μm and 2 μm for the groups of H5M, H3M, and H2M, respectively, to be placed in the middle of the centrifuge tube. The home-designed H2M showed a very promising results regardless of the final volume (1.82 ± 0.09 ml), platelet yield (8.39 ± 0.44%), Red Blood Cells (0%), White Blood Cells (0%), and Relative Concentration of Platelet Increment value (225.09%). Further, it showed a good result in cell viability and cytotoxicity and confirmed a good multilineage potentials. The concentration in PRP prepared by group H2M was relatively stable and far above average. All the fibrin fibers were linked together as bridging strands or strings and turned into an inter-connected porous structure for nutrients transportation and regenerative cell migration. We believe that the home-designed group H2M should have a great potential to develop into the final product to meet the requirements of first-line clinical workers.

Acquired Amegakaryocytic Thrombocytopenic Purpura Associated with a Paroxysmal Nocturnal Hemoglobinuria Clone: A Case Report and Review of the Literature

Background: Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare bone marrow disorder characterized by a marked reduction in megakaryocytes with otherwise normal hematopoiesis. Both humoral and cell-mediated suppression of megakaryocytopoeisis have been postulated as mechanisms causing AATP. Herein we report a case of a 67-year-old man diagnosed with AATP with a co-existent paroxysmal nocturnal hemoglobinuria (PNH) clone and review the literature on AATP, focusing on proposed etiologies for this rare condition. Case: A 67-year-old man presented to clinic with a 1-week history easy bruising, petechiae and a platelet count of 6 x 109/L. He had a history of left elbow bursitis caused by S. pyogenes, treated with antibiotics 6-months prior to his presentation. His CBC was normal at that time. On assessment, HIV, HBV, HCV, and H. pylori serologies were negative; CMV and EBV serologies were positive for IgG and negative for IgM. ANA and RF were negative, and vitamin B12 level was normal. There was no hepatosplenomegaly on ultrasound. Bone marrow aspirate and biopsy demonstrated a normocellular marrow with severe megakaryocytic hypoplasia. Cytogenetics demonstrated normal male karyotype with loss of Y chromosome in 9/20 metaphases. Flow cytometry revealed a population of 3.99% GPI-deficient neutrophils by FLAER assay. Molecular testing for myeloid mutations and T-cell gene rearrangement is pending. The patient was initially treated with corticosteroids and IVIG, and showed no response with persistent isolated thrombocytopenia. He was managed with platelet transfusions which resulted in a normal platelet increment of 35 x 109/L 1-hour post-transfusion. A diagnosis of AATP was established and he was admitted for immunosuppressive therapy (IST) with ATG and cyclosporine. Methods: We conducted a narrative review of the literature on AATP, searching MEDLINE and EMBASE for articles on AATP published in English between 1946 and 2020. Reference lists of selected articles were reviewed to identify additional cases. We extracted data on presentation, bone marrow findings (including cytogenetics, molecular genetics, and flow cytometry), treatment regimens and outcomes. Results: We identified 47 cases of adult patients with thrombocytopenia attributed to AATP reported in the literature (Table 1). Three main mechanisms were proposed: (i) cell-mediated autoimmunity, (ii) humoral autoimmunity, and (iii) intrinsic stem cell defect. All three mechanisms were supported by in vitro studies, which demonstrated suppression of colony forming unit-megakaryocytes (CFU-M) by patients' T-lymphocytes (Gerwitz et al. 1986; Colovic et al. 2004) and serum (Hoffman et al. 1982) found to contain IgG antibodies inhibiting CFU-M formation, as well as intrinsic defects in CFU-M progenitor proliferation. Few studies reported cytogenetic abnormalities and only one documented molecular genetic testing. Response to IST was reported in several cases, most commonly ATG and cyclosporine. Four recent cases demonstrated remission following treatment with TPO agonists eltrombopag and romiplostim. Six cases progressed to aplastic anemia and 4 to myelodysplastic syndrome (MDS). Flow cytometry results were not reported in the majority of cases, and only 1 case reported coexistence of a PNH clone, identified in a pregnant patient with AATP (Zimmerman et al. 2019). Discussion: AATP is defined as severe thrombocytopenia with bone marrow showing marked decrease or absence of megakaryocytes with preservation of other cell lineages. This broad definition encompasses a range of causes, and our review of the literature highlights the heterogenous nature of AATP which has several proposed mechanisms and a number of therapeutic options. The best evidence suggests that AATP is often secondary to T-cell-mediated suppression of megakaryocytopoeisis, which has been demonstrated by in vitro studies, and is supported in vivo by a case of AATP following PD-1 inhibition (Iyama et al. 2020), and frequent response of AATP to T-cell-directed IST. The co-existence of a PNH clone in our case lends further support to a T-cell-mediated autoimmune process, analogous to the mechanism described in aplastic anemia and hypoproliferative MDS. The application of molecular diagnostics may help to further elucidate the role of clonal hematopoiesis and intrinsic stem cell defects versus humoral and cell-mediated autoimmunity in AATP. Disclosures No relevant conflicts of interest to declare.

Platelet antibodies in immune thrombocytopenia and related conditions

Abstract Platelet autoantibodies are a common finding in immune thrombocytopenia (ITP) and in rare cases of antibody-mediated platelet function (“acquired thrombasthenia”). In drug-induced immune thrombocytopenia, antibodies react with platelets only in the presence of the offending drug. Alloantibodies reacting with platelets are induced by transfusion of cellular blood products or during pregnancy. They are responsible for fetal/neonatal alloimmune thrombocytopenia (FNAIT), they are able to cause febrile, nonhemolytic transfusion reactions and they give rise to insufficient platelet increments following platelet transfusions. Two rare transfusion reactions: post-transfusion purpura (PTP) and passive alloimmune thrombocytopenia (PAT) are triggered by platelet alloantibodies. This review discusses the clinical value of tests for platelet antibodies in various clinical situations related to insufficient primary hemostasis.

Platelet Count Increment after Transfusion of Fresh and Stored Platelet Concentrates in Children with Acute Lymphoblastic Leukaemia

Background: Therapeutic platelet transfusion is necessary to prevent bleeding due to thrombocytopenia in childhood acute lymphoblastic leukaemia (ALL). Platelet concentrates may be transfused as fresh platelet concentrate immediately or with five days of storage after collection Objectives: To compare the platelet count increment between fresh and stored platelet concentrate transfusion in children with acute lymphoblastic leukaemia. Methodology: This observational study was carried out in the Department of Clinical Pathology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, in collaboration with the Department of Transfusion Medicine and Paediatric Haemato-Oncology, BSMMU, Dhaka. Seventy-two children diagnosed as acute lymphoblastic leukaemia were included in this study. ABO identical whole-blood derived platelet-rich-plasma platelet concentrates (PRP-PCs) were transfused within 24 hours of preparation or 1-5 days of storage. Effectiveness of platelet transfusion was carried out by measuring platelet count prior to transfusion, subsequently 1 hour and 24 hours of transfusion. Result: Post transfusion platelet count at 1 hour and 24 hours with fresh platelet concentrates (FPC) and stored platelet concentrates (SPC) were not statistically significant. Post transfusion platelet increment at 1 hour and 24 hours were also similar in both FPC and SPC. Corrected count increment (CCI) at 1 hour in FPC and SPC were 20.5±10.1 and 18.6 ±6.5 respectively and was statistically not significant (P: 0.168). CCI at 24 hours were 15.5±9.1 and 13±5.8 which were also statistically not significant. Percentage platelet recovery at 1 hour and 24 hours in both FPC and SPC were statistically not significant. But these values in SPC were consistently lower than that of FPC. All the values of FPC and SPC were well apart from the lower limit of CCI and percentage platelet recovery (PPR). It was also observed that 85.1% satisfactory platelet transfusion was achieved with FPC and rest of 14.9% was platelet refractory cases. In 79.5% cases satisfactory platelet transfusion were achieved with SPC and refractory cases were 20.5 %. Conclusion: One to five day’s stored PRP-PCs are as effective as fresh PRP-PCs to achieve satisfactory platelet increment.

A pilot trial of complement inhibition using eculizumab to overcome platelet transfusion refractoriness in human leukocyte antigen allo-immunized patients.

Heavily transfused patients frequently develop human leukocyte antigen (HLA) allo-immunization resulting in platelet transfusion refractoriness and a high risk for life-threatening thrombocytopenia. Data suggest complement activation leading to the destruction of platelets bound by HLA allo-antibodies may play a pathophysiologic role in platelet refractoriness. Here we conducted a pilot trial to investigate the use of eculizumab, a monoclonal antibody that binds and inhibits C5 complement, to treat platelet transfusion refractoriness in allo-immunized patients with severe thrombocytopenia. A single eculizumab infusion was administered to 10 eligible patients, with four (40%) patients overcoming platelet refractories assessed measuring the corrected platelet count increment (CCI) 10-60min and 18-24h post transfusion. Responding patients had a reduction in the requirement for subsequent platelet transfusions and had higher post-transfusion platelet increments for 14days following eculizumab administration. Remarkably, three of the four responders met CCI criteria for response despite receiving HLA-incompatible platelets. Our results suggest that eculizumab has the ability to overcome platelet transfusion refractoriness in patients with broad HLA allo-immunization. This study establishes proof of principle that complement inhibition can treat platelet transfusion refractoriness, laying the foundation for a large multicentre trial to assess the overall efficacy of this approach (ClinicalTrials.gov, identifier: NCT02298933).

The clinical characteristics of patients with acute leukemia or stem cell transplantation exhibiting immune based platelet refractoriness

BackgroundTo investigate the related factors influencing immune platelet transfusion refractoriness (PTR) in acute leukemia (AL) from induction to consolidation and compare management for immune PTR, so as to improve the Platelet increment in AL. MethodsThe primary analysis included 890 patients with AL, 225 of whom were the immune PTR (25 %).They are patients in our center from induction to consolidation or transplantation in the past 10 years. Flow cytometry, karyotype characteristics and other basic information were compared between the immune PTR vs control (no-PTR) groups. We analyzed the treatment outcomes of immune PTR including matched platelets, intravenous immunoglobulin (IVIG), increasing apheresis platelet does. Results: Immune PTR is more likely to occur in patients with poor prognosis in acute lymphoblastic leukemia (ALL) (P = 0.01).There is a relation between NPM1 mutation and occurrence of immune PTR (P = 0.029).The incidence of PTR at 35-59Y was higher than that at <35Y(OR = 0.68, 95 % CI = 0.48-0.96) and ≥60Y(OR = 0.49,95 % CI = 0.28-0.83), and the difference was statistically significant(P = 0.03, P = 0.01).The Platelet increment with 1 unit (u) was 47.12 %, 2 u increased to 71.14 %, and the matched 2 u (75.11 %) had the best effect. IVIG improved the Platelet increment, but there was no difference between 0.4 g/kg IVIG and 1 g/kg IVIG. Immune PTR is more likely to occur in the ages of 35–60 years. ConclusionThere are specific AL patient characteristics which predispose to the phenomenon of immune based PTR. Meanwhile, increasing the IVIG dose could not improve Platelet increment obviously.

Post-transfusion platelet responses in critically ill cancer patients with hypoproliferative thrombocytopenia.

Platelet transfusion is aimed at increasing platelet counts to prevent or treat bleeding. Critically ill cancer patients with hypoproliferative thrombocytopenia are high consumers of blood products. We herein described their post-transfusion platelet responses in the intensive care unit (ICU) and analyzed the determinants of poor post-transfusion increments. This was a single-center 9-year (2009-2017) retrospective observational study. Patients with malignancies and presumed or proven hypoproliferative thrombocytopenia who had received at least one platelet transfusion in the ICU were included. Poor post-transfusion platelet increments were defined as body surface-adjusted corrected count increment (CCI) <7, or alternatively as weight-adjusted platelet transfusion recovery (PTR) <0.2. Patients were deemed refractory to platelet transfusions when two consecutive ABO-compatible transfusions resulted in poor platelet increments. A total of 1470 platelet transfusions received by 326 patients were analyzed. Indications for platelet transfusions were distributed into prophylactic (44.5%), peri-procedural (18.1%) and therapeutic (37.4%). Regardless of indications, 54.6% and 55.4% of transfusion episodes were associated with a CCI <7 or a PTR <0.2. Factors independently associated with poor post-transfusion increments were lower body mass index, spleen enlargement, concurrent severity of clinical condition, fever ≥39°C, antibiotic therapy and increased storage duration of platelet concentrates. Eventually, 48 patients developed refractoriness to platelet transfusion, which was associated increased incidence of bleeding events. Platelet transfusions are often associated with poor increments in critically ill cancer patients with hypoproliferative thrombocytopenia. The findings suggest amenable interventions to improve the platelet transfusion practices in this setting.

The Burden of Clinically Significant Bleeding, Thrombocytopenia and Platelet Transfusions in Myelodysplastic Syndromes

Aim: Although 40-65% of myelodysplastic syndromes (MDS) patients are thrombocytopenic and require platelet transfusions, there is limited literature on the risk factors predictive of bleeding and the burden of immune mediated platelet refractoriness (PLT-R). Objectives: To evaluate the prevalence of thrombocytopenia, incidence of bleeding events, platelet transfusion dependency (PLT-TD) and immune-mediated platelet refractoriness (PLT-R) in MDS patients. Methods: A retrospective analysis of 754 MDS patients enrolled in the South Australian MDS (SA-MDS) registry was performed. Platelet counts &amp;lt;100, &amp;lt;50 and &amp;lt;20 (x109/L) were used to define mild, moderate and severe thrombocytopenia respectively. The severity of bleeding events was classified according to the International Society of Thrombosis and Haemostasis (ISTH) classification. PLT-TD was defined as transfusion of at least one unit of platelets each month for four consecutive months. All other patients were classified as transfusion independent (PLT-TI). Immune mediated PLT-R was defined if a patient had HLA-class I or HPA antibodies, poor platelet increments and required HLA-matched platelets. Medication history with regards to anticoagulation and/or antiplatelet therapy was also collected. Results: At diagnosis, 332 (45%) patients had thrombocytopenia and 106 (14%) patients had moderate to severe thrombocytopenia. During the study period, 249 bleeding events were recorded in 162 (21%) patients with a cumulative incidence of 33% (Fig 1A). Of the 249 bleeding events, 85 (34%) were major and 164 (66%) were clinically relevant minor bleeding. Notably, 16, 90 and 5 bleeding events were intracranial, gastrointestinal, intraocular respectively. While 41% (96/235) bleeding events occurred in the setting of moderate to severe thrombocytopenia, 21% and 38% (Fig 1B) of bleeding events occurred at platelet counts of &amp;gt;50-100 and &amp;gt;100x109/L respectively. Twenty-eight percent (69/249) bleeding events were associated with concomitant anticoagulation and/or antiplatelet therapy and importantly, platelets counts were &amp;gt;50x109/L and &amp;gt;100 x109/L in 57 (83%) and 46 (67%) at the time of bleeding events, respectively. During the disease course, 393 (52%) patients required at least one unit of platelet transfusion. 106 (14%) patients were PLT-TD and had significantly poor overall survival (OS) compared to PLT-TI (26 vs 42 months, p&amp;lt;0.0001). In total, 30/393 (7%) required HLA-matched platelet transfusions. 20/30 (66%) of PLT-R patients were female receiving disease modifying therapy (DMT). This was substantiated by cox regression analysis, demonstrating that females (HR=5.32, p=0.0006), older age (HR=0.97, p=0.028) and haemoglobin (Hb) at diagnosis (HR=1.03, p=0.009) were independent risk factors for PLT-R. Importantly, 20/76 (25%) female patients receiving platelets and DMT developed immune mediated PLT-R requiring HLA matched platelets. Conclusions: In our cohort of MDS patients, cumulative incidence of bleeding is 33% and 59% of the bleeding events occurred at platelet counts &amp;gt;50X109/L. For all bleeding events that occurred while on anticoagulation and/or antiplatelet therapy, 83% events occurred with platelet counts &amp;gt;50 x 109/L. Therefore, guidelines for anticoagulation and/or antiplatelet therapy are required for MDS patients. We also showed that development of PLT-TD is associated with poor OS. Importantly, 1 in 4 female MDS patients receiving platelets and DMT required HLA-matched platelets. Platelet transfusions practices should be optimised for these high-risk groups. Disclosures No relevant conflicts of interest to declare.

Efficacy of cross-match compatible platelets in multi transfused haemato-oncology patients refractory to platelet transfusion

BackgroundPlatelet refractoriness, which leads to platelet transfusion failure resulting in significant morbidity and long hospital stay, is routinely not investigated. AimsTo determine the efficacy of cross-match compatible platelets in multi-transfused alloimmunized hemato-oncological patients refractory to platelet transfusion. Materials and method149 ABO compatible single donor apheresis platelet transfusions given to 38 alloimmunized refractory patients. Corrected Count Increment (CCI) <5000 (1 h) was taken to define refractoriness. Solid-phase red cell adherence assay was used to determine the alloimmunization status and platelet cross-matching. Post Transfusion Platelet Increment, CCI and the Percentage Platelet Recovery were used to monitor the effectiveness of platelet transfusion. ANOVA test followed by Post hoc test Tukey HSD used to compare group means and classified into three groups depending upon the cross-matching and compatibility status. Categorical data was analysed for various outcomes using Pearson's chi square test or Fischer exact test. ResultPatients showed statistically significant recovery in terms of PPI, CCI and PPR at 1 h post SDAP transfusions when they received cross-matched compatible platelets. The one-hour CCI was significantly higher for cross-match-compatible platelets (19173 ± 2692) than for incompatible (5888 ± 1526) and for uncross-matched (8140 ± 1480). Forty four (97.8%) of 45 cross-matched compatible platelet transfusion episodes showed a satisfactory response in terms of PPI and CCI values as compared to 50 % and 53.9% in uncross-matched group respectively (p < 0.0001). ConclusionPlatelet cross-matching is an effective intervention in the management of multi-transfused alloimmunized Haemato-oncological patients, refractory to platelet transfusion.

Frequency of Platelet Crossmatch Positivity and Predictive Value for Poor Platelet Increment Among Paediatric Oncohaematology Patients in India.

Immune platelet destruction is a significant cause for platelet refractoriness. The platelet crossmatch-a solid phase red cell adherence assay utilizes donor platelets and patient serum to assess compatibility and appears to be a feasible option in resource constrained settings. This study was done to evaluate the frequency of platelet crossmatch positivity among Paediatric Oncohaematology patients and also to assess whether a positive crossmatch is predictive of unsuccessful platelet transfusions in this group of patients. Paediatric Oncohaematology patients who received platelet transfusions between March 2013 and September 2013 were included in the study. The pre-transfusion patient sample and a segment from the transfused donor unit were used for performing the platelet crossmatch. A blood sample was collected one hour after the transfusion to assess post-transfusion platelet count. Corrected count increment (CCI) was calculated using the standard formula. CCI ≤ 7500/µL/m2/1011 was considered evidence of an unsuccessful transfusion. Seventy-three platelet crossmatches were performed for 69 patients, of which 30 patient samples (41%) showed crossmatch positivity. 25 (89.2%) of 28 unsuccessful transfusions showed crossmatch positivity, and 40 (88.9%) of 45 successful transfusions showed negative crossmatches (p = 0.03). Crossmatch positivity among transfusion dependent Paediatric Oncohaematology patients was as high as 42%, when ABO matched platelet units were allocated without further testing. Our results indicate that this test may be a reliable tool to select compatible platelet units and an effective intervention in the management of patients at risk of immune platelet refractoriness.

The description of corrected count increment on one hour and 24 hours after platelet apheresis transfusion in Sanglah General Hospital Denpasar

Introduction: Evaluating the response after platelet transfusion is vital to measure the success rate of the therapy and plan the subsequent management of patients. The evaluation can be done by calculating the corrected count increment (CCI) at 1 hour and 24 hours after transfusion. The purpose of this study was to determine the therapeutic response to apheresis platelet transfusion by measuring the CCI at 1 hour and 24 hours after transfusion.Methods: This study was a cross-sectional descriptive study of patients who received apheresis platelet transfusions. In total, 35 samples were examined for platelet counts before and after transfusion. The CCI was measured at 1 hour and 24 hours after transfusion. Descriptive statistical analysis was performed to calculate the percentage and mean count.Result: The mean count of transfused platelets was 2.7 × 10¹¹ / unit. The mean platelet count before transfusion was 18.5 × 10³ / μL. The mean platelet increment at 1 hour was 25.4 10³ / μL and 24 hours was 22.6 × 10³ / μL. The mean CCI ± SD at 1 hour and 24 hours was 15,036.63 ± 13,709.73 and 13,625.60 ± 13,580 respectively. A total of 63% of samples reached the target CCI at the 1-hour measurement, while the remaining 37% did not. Meanwhile, 60% of the samples reached the CCI target at the 24-hour measurement, while 40% did not.Conclusion: The response to apheresis platelet transfusion by measuring the CCI reached the target in 63% of patients at 1 hour after transfusion and 60% of patients at 24 hours after transfusion.

Platelet increment is not associated with endothelial damage in haematological patients: a prospective observational study

The aim of this study was to investigate if thrombocytopenic haematology patients show signs of endothelial damage when transfused with platelets and if that damage correlates with platelet increment measured with corrected count increment (CCI). Endothelial damage secondary to radiation or chemotherapy may lead to consumption of transfused platelets but research in this field is scarce. Patients were divided into four groups: Group 1: Acute leukaemia; Group 2: Autologous stem cell transplantation (SCT); Group 3: Allogenic SCT; and Group 4: patients receiving platelets prior to interventions. Blood was sampled before (baseline) and immediately after (0 h) transfusion and then at 1, 4, 8, 16 and 24 h after transfusion. The biomarkers syndecan-1, soluble thrombomodulin (sTM) and vascular endothelial growth factor (VEGF) were analysed. The plasma concentration differences between baseline and later sampling times were referred to as delta (Δ). Fifty-four platelet transfusion events were studied. All biomarkers were within the normal ranges both before and after the transfusions. The Δsyndecan-1 increased at 0 h (p = .02), but there was no significant correlation between Δsyndecan-1 and CCI. There was no change in any of the other biomarkers after transfusion compared to before. There were no differences between the groups and no correlations were found between CCI and C-reactive protein, Δsyndecan-1, ΔsTM or ΔVEGF. There were no signs of endothelial damage before or after platelet transfusions. A transient significant change in syndecan-1 immediately after platelet transfusion did not influence platelet count or platelet CCI.Trial registration: ClinicalTrials.gov identifier: NCT02601131.

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

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. MEDLINE, EMBASE and Cochrane searches were conducted until 11 May 2018. 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. 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.

Platelet refractoriness

Platelet transfusion support is extensively required for hemato-oncology patients who are multiply transfused. Platelet refractoriness can represent a significant clinical condition that complicates the platelet transfusion support in such patients. It remains a challenge associated with an increased bleeding risk, longer hospital stays, and increased morbidity and mortality. Causes for refractoriness are broadly divided into nonimmune and immune causes. Approximately two-thirds of refractory episodes are due to nonimmune factors while one-third are due to immune factors. Common formulae to assess platelet refractoriness include corrected count increment (CCI), posttransfusion platelet increment, and percentage platelet recovery. Measurement of CCI is one of the best parameters to differentiate between immune and nonimmune causes. In nonimmune factors which are associated with increased platelet consumption, treating the underlying cause and increasing the frequency of transfusion should be considered. However, in immune factors which are due to increased destruction of platelets owing to alloimmunization, other strategies such as ABO-identical/ABO-compatible fresh platelets, human leukocyte antigen-matched platelets, and crossmatched platelet transfusions should be considered. The newer approach includes epitope-matched platelet transfusion which is still in amateur stage. The strategies in the prevention of alloimmunization include leukoreduction of blood components, reducing donor exposure by providing single-donor platelets, and providing ABO-compatible platelets from the beginning of the treatment. This review will address the causes of platelet refractoriness and practical approach to the diagnosis, management, and its prevention.

Anti-HLA antibodies with complementary and synergistic interaction geometries promote classical complement activation on platelets.

High titers of HLA antibodies are associated with platelet refractoriness, causing poor platelet increments after transfusions in a subset of patients with HLA antibodies. Currently, we do not know the biological mechanisms that explain the variability in clinical responses in HLA alloimmunized patients receiving platelet transfusions. Previously we showed that a subset of anti-HLA IgG-antibodies induces FcγRIIa-dependent platelet activation and enhanced phagocytosis. Here, we investigated whether anti-HLA IgG can induce complement activation on platelets. We found that a subset of anti-HLA IgG induced complement activation via the classical pathway, causing C4b and C3b deposition and formation of the membrane-attack complex. This resulted in permeabilization of platelet membranes and increased calcium influx. Complement activation also caused enhanced α-granule release, as measured by CD62P surface exposure. Blocking studies revealed that platelet activation was caused by FcγRIIa-dependent signaling as well as HLA antibody induced complement activation. Synergistic complement activation employing combinations of monoclonal IgGs suggested that assembly of oligomeric IgG complexes strongly promoted complement activation through binding of IgGs to different antigenic determinants on HLA. In agreement with this, we observed that preventing anti-HLA-IgG hexamer formation using an IgG-Fc:Fc blocking peptide, completely inhibited C3b and C4b deposition. Our results show that HLA antibodies can induce complement activation on platelets including membrane attack complex formation, pore formation and calcium influx. We propose that these events can contribute to fast platelet clearance in vivo in patients refractory to platelet transfusions with HLA alloantibodies, who may benefit from functional-platelet matching and treatment with complement inhibitors.

REFRACTORINESS TO DONOR PLATELETS TRANSFUSION IN PATIENTS WITH APLASTIC ANEMIA AND HEMOBLASTOSIS

Refractoriness to transfusions of platelet concentrates (PC) adversely affects the conduct of complex therapy in hematological patients. Individual selection of platelets is recommended for such patients. In cases of high degree of alloimmunization with the formation of polyspecific antibodies, when individual selection is difficult, procedures plasmapheresis (PPs) is included in the treatment program.Aims: to evaluate the effectiveness of PC transfusions by individual selection in patients refractory to transfusions and the use of PPs as a second line therapy in combination with individual platelet selection.Materials and methods: from September 2015 to December 2017, 91 patients with refractory to PC transfusions from 1263 patients who received PC transfusion were observed in the center’s clinics. The median age was 43 (18–71) years. M/F – 38/53. Patients: 20 – aplastic anemia (AA), 17 – myelodysplastic syndrome (MDS), 45 – acute myeloid leukemia (AML), 9 – acute lymphoblastic leukemia (ALL). All patients underwent PC transfusion by individual selection (HLA/HPA) Immucor’s Capture-P solid phase technology. In 28 (30 %) of 91 patients, due to the inability to select, there was a need for PP as a second line therapy. Patients: AA – 4 (20 %); MDS – 8 (47 %); AML – 12 (26 %); ALL– 4 (44 %). The median age was 48 (23–71) years. M/F – 8/20. From 2 to 15 procedures were performed (on average – 6) for each patient. All patients received PC transfusions by individual selection by cross-matching immediately after the PP procedure. The efficacy of PC transfusions was assessed by Absolute Platelet Increment (API) and Corrected Count Increment (CCI), relief of hemorrhagic syndrome.Results: in 26 of 28 refractory to PC transfusions patients, in the absence of compatible donor platelets, carrying out PPs in combination with subsequent individual platelet selection promoted relief of hemorrhagic syndrome, increase in API from 3.3 × 109/L at 29.5 × 109/L and CCI from 1.3 to 10.7. Against the background of PPs, combined with individual selection, the degree of alloimmunization (the percentage of incompatible pairs) decreased on average: AA (n = 4) – from 91.7 to 50.2 %; MDS (n = 8) – from 89.6 to 31.6 %; AML (n = 12) – 86.0 to 40.5 % and ALL (n = 4) – from 91.7 to 37.7 %. In 2 patients with a high degree of alloimmunization and after carrying out PPs, it was not possible to select compatible platelets, PC transfusions were ineffective (API = 5 × 109/L, CCI = 1), and hemorrhagic syndrome was not completely managed, but its severity was reduced.Conclusions. With the development of refractoriness to PC transfusions and the ineffectiveness of individual platelet selection, PPs should be used as the second line of therapy, which, combined with individual selection, increases the likelihood of compatible donor-recipient pairs and increases the clinical efficacy of PC transfusions. When PPs is ineffective in combination with individual selection, it is necessary to exclude the syndrome of increased consumption and other mechanisms of refractoriness.