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 <100, <50 and <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 >50-100 and >100x109/L respectively. Twenty-eight percent (69/249) bleeding events were associated with concomitant anticoagulation and/or antiplatelet therapy and importantly, platelets counts were >50x109/L and >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<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 >50X109/L. For all bleeding events that occurred while on anticoagulation and/or antiplatelet therapy, 83% events occurred with platelet counts >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.

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Burden of Cardiovascular Events and Bleeding Is High in Myelodysplastic Syndromes

Blood ◽

10.1182/blood-2020-143319 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 34-35

Author(s):

Rakchha Chhetri ◽

Oisin Friel ◽

Monika M Kutyna ◽

Kathleen Pao Lynn Cheok ◽

Li Yan A Wee ◽

...

Keyword(s):

Risk Factors ◽

Antiplatelet Therapy ◽

Myelodysplastic Syndromes ◽

Anticoagulation Therapy ◽

Bleeding Complications ◽

Severe Thrombocytopenia ◽

Bleeding Events ◽

Platelet Counts ◽

Risk Of Bleeding ◽

Rbc Transfusion

Background: Myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) patients are older and suffer with cardiovascular (CV) diseases. Management of these patients with antiplatelet and anticoagulation therapy is challenging as thrombocytopenia can increase the risk of bleeding. Aim: To assess burden and CV disease related mortality, review of anticoagulant /antiplatelet therapy and bleeding complications in MDS and oligoblastic AML patients. Methods: Electronic medical records of 910 MDS and oligoblastic AML patients enrolled in the South Australian MDS (SA-MDS) registry were reviewed. CV risk factors, CV and bleeding events requiring or occurring during hospitalisation, anticoagulation and/or antiplatelet therapy information were collected. Platelet counts of <100, <50 and <20 (x109/L) were defined as mild, moderate and severe thrombocytopenia respectively. Severity of bleeding events was classified using modified International Society of Thrombosis and Hemostasis (ISTH) classification. MDS patients require regular RBC transfusion, hence fall in hemoglobin ≥20 gm/L or ≥2 units of RBC transfusion were not used for defining major bleeding. Results: At the time of MDS diagnosis, 72% (658/910) and 42% (386/910) patients had ≥1 and ≥2 CV risk factors. Twenty-five percent patients required hospitalization for CV events prior to the MDS diagnosis and their median OS was significantly poor compared to patients who did not have CV events (Figure 1A). During median follow up of 28 months after MDS diagnosis, 27.5% (251/910) patients were admitted with or developed CV events during hospitalization. In a Cox-regression analysis age, absolute monocyte count, CV risk factors and prior CV events were independent predictors of CV events following MDS diagnosis (Figure 1B). The most frequent CV events were arrhythmia (137/399; 34%), congestive cardiac failure (129/399; 32%), and ischemic heart disease (94/399; 23%). Atrial fibrillation (AF) contributed towards 78% (108/137) of all arrhythmias. 39% of AF occurred in the setting of infections and 12% patients died during the same hospitalization or were palliated. 89% of AF patients had a CHADS2VASc2 score ≥2, however only 30% (20/65) and 24% (16/65) events with available information were treated with anticoagulation and antiplatelet therapy respectively. While 60% (39/65) AF events did not receive antiplatelet or anticoagulation therapies. Four AF patients developed ischemic stroke following MDS diagnosis and five patients had stroke before MDS diagnosis and were subsequently diagnosed with AF. Importantly, 36% (34/94) AF patients developed 45 bleeding events. The frequency of bleeding events was not significantly different between patients treated with anticoagulation/antiplatelet therapy versus who were not treated (13.8% vs. 13.6%). Although, cumulative incidence of bleeding and CV events was similar at 29% and 28% at five-years (Figure 1C-D), only some patients had both events. Of the 387 patients, 39% (n= 152) and 39% (n=153) patients required hospitalization only for CV or bleeding events, while only 21% (82/387) required hospitalization for both bleeding and CV events. Identifying these three groups early is crucial to optimize their outcome. Of the 387 bleeding events, 88 (24%) were major and 296 (76%) were clinically relevant minor bleeding. Notably, 127, 47 and 15 bleeding events were gastrointestinal, intracranial and intraocular respectively. While 50% bleeding events occurred in the setting of moderate to severe thrombocytopenia, 19% and 31% of bleeding events occurred at platelet counts of >50-100 and >100x109/L respectively (Figure 1E). Details of anticoagulation/antiplatelet therapy were available for 66% (161/243) of bleeding events. Importantly, 76% of bleeding events occurred without anticoagulation and antiplatelet therapy, while 10% and 13% bleeding occurred while on anticoagulation therapy and antiplatelet therapy respectively. Conclusions: Our analysis demonstrates a significant burden of CV and bleeding in MDS. Only 23% of all bleeding events occurred while on anticoagulation therapy and some patients with recurrent CV events did not require hospitalization for bleeding. However, large numbers of CV events are sub-optimally managed due to perceived excess risk of bleeding. Therefore, guidelines for anticoagulation and/or antiplatelet therapy are required for MDS patients. Disclosures Hiwase: Novartis Australia: Research Funding.

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Severe Thrombocytopenia Does Not Increase Bleeding Complications in Patients Undergoing Bronchoscopy

Blood ◽

10.1182/blood.v124.21.4293.4293 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4293-4293

Author(s):

Lakshminarayanan Nandagopal ◽

Muthu Veeraputhiran ◽

Tania Jain ◽

Ayman Soubani ◽

Charles A. Schiffer

Keyword(s):

Platelet Count ◽

Renal Dysfunction ◽

Platelet Transfusion ◽

Conflicts Of Interest ◽

Bleeding Complications ◽

British Thoracic Society ◽

Severe Thrombocytopenia ◽

Platelet Counts ◽

Number Of Patients ◽

Platelet Transfusions

Abstract Introduction Prophylactic platelet transfusions are often performed prior to bronchoscopy or broncho-alveolar lavage (BAL) to prevent bleeding in thrombocytopenic patients. There is a paucity of data to validate this approach, with a platelet transfusion threshold of <50,000/mm3 largely based on expert opinion. We conducted a retrospective study on the incidence of bleeding complications in thrombocytopenic patients undergoing bronchoscopy. Methods We identified 150 consecutive patients with platelet counts <100,000/mm3 who underwent bronchoscopy and/or BAL from January 2009 to May 2014 at our institution. Bronchoscopies performed in patients with frank hemoptysis and trans-bronchial lung biopsy procedures were excluded. Patient characteristics, underlying diagnosis, platelet count prior to bronchoscopy, administration of platelet transfusions and bronchoscopy details were recorded. Factors affecting bleeding risk including presence of renal dysfunction (defined as BUN >30 and/or Cr>2.0) and coagulation studies (PT, PTT, INR) were identified. The British Thoracic Society guidelines1 were used to categorize bleeding as a result of bronchoscopy. Data were analyzed using descriptive statistics. Results The median age was 59 years (range 27-90), with two-thirds of patients (63%) being male. One hundred and seventeen (78%) patients had underlying malignancy and 55 (37%) had thrombocytopenia related to malignancy. Fellows and residents under the supervision of a bronchoscopy certified attending performed all but 4 of the bronchoscopies. Infection (40%) was the primary indication for bronchoscopy with BAL performed in 127 (85%) patients. Fifty-eight of 89 (65%) patients with baseline platelet counts <50,000/mm3 received prophylactic transfusions compared to 8% of those with platelet counts >50,000/mm3. The platelet count did not rise to >50,000//mm3 in many transfused patients. Seventy patients (47%) had counts <50,000/mm3 and eighty patients (53%) had counts >50,000/mm3 at the time of bronchoscopy. 49% were receiving immunosuppressive medications, 45% had renal dysfunction and 8% had INR >1.5. Bloody lavage that resolved spontaneously without continuous suctioning (Grade 0) was observed in 9 (6%) patients. Bleeding that required continuous suctioning but then resolved spontaneously (Grade 1) was noted in 1 patient with a platelet count of 61,000/mm3. Of 10 total bleeding events, 7 occurred in patients who were intubated. Two additional patients with platelet counts of 30,000/mm3 and 53,000/mm3 had diffuse alveolar hemorrhage, which was present before bronchoscopy. “Old” blood and blood clots were observed in 6 patients. Discussion The low incidence of bleeding complications from bronchoscopy +/- BAL even in patients with platelet counts <30,000/mm3 (3 episodes in 31 patients, all grade 0) demonstrates that bronchoscopy can be safely done in severely thrombocytopenic patients. Adopting a lower threshold for prophylactic transfusions could save a considerable number of platelet units and translate into significant cost savings and decreased risk of transfusion-related complications. Table 1 Platelet count, transfusion history and bleeding complications during bronchoscopy Platelet count at the time of bronchoscopy Number (n) and percentage (%) of patients who underwent bronchoscopy Number of patients who received prior platelet transfusion Bleeding during bronchoscopy n % 0-15,000/mm3 9 6% (9/150) 5 Grade 0=1 pt 16-29 22 15% 16 Grade 0=2 pts 30-39 17 11% 9 Grade 0=1 pt 40-49 22 15% 9 Grade 0=3 pts 50-75 44 29% 14 Grade 1=1 pt 76-100 36 24% 10 Grade 0=2 pts Total 150 63 Grade 0=9 pts, Grade 1=1 pt. 1.Du Rand IA, Blaikley J, Booton R, et al. British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults: accredited by NICE. Thorax. 2013:68 Suppl 1:i1-i44 Disclosures No relevant conflicts of interest to declare.

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Thrombopoietin (TPO)-Receptor Agonists In Myelodysplastic Syndromes (MDS): A Systematic Review and Meta-Analysis

Blood ◽

10.1182/blood.v122.21.2806.2806 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2806-2806 ◽

Cited By ~ 4

Author(s):

Anca Prica ◽

Michelle Sholzberg ◽

Rena Buckstein

Keyword(s):

Systematic Review ◽

High Risk ◽

Myelodysplastic Syndromes ◽

Platelet Transfusion ◽

Meta Analysis ◽

Outcome Data ◽

Controlled Trials ◽

Bleeding Events ◽

Receptor Agonists ◽

Platelet Transfusions

Abstract Background Thrombocytopenia is a common (40-65%) manifestation of MDS. The incidence of bleeding ranges from 3% to 56% encompassing minor bleeds such as petechiae and gingival bleeding, and more serious bleeds (18%), such as gastrointestinal (GI, 6-7%) and intracranial (3-5%) bleeding. Lenalidomide and azacitidine are not specifically used or approved for the treatment of thrombocytopenia in MDS and while effective in some patients, may in fact engender a thrombocytopenia that is dose limiting. The interaction between thrombopoietin (TPO) and its receptor c-Mpl is essential for platelet production. Romiplostim and Eltrombopag are two TPO-receptor agonists presently approved by the FDA. They have been tested in MDS, with some evidence of benefit, but there are safety concerns regarding progression to acute myeloid leukemia (AML). Purpose To determine the safety, as well as the clinical outcomes of adding a TPO-receptor agonist to standard treatment in patients with myelodysplastic syndromes. Methods A systematic literature search strategy was conducted up to February 2013, using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, as well as conference proceedings. All randomized controlled trials (RCTs) that enrolled adult patients with myelodysplastic syndromes were included if the RCT compared a TPO-R agonist (Romiplostim or Eltrombopag) to placebo or no treatment. A meta-analysis of the effects was performed. Pooled treatment effects were calculated as risk ratios (RR) for binary data, using a random effects model. Bleeding and platelet transfusion rates were also reported as exposure-adjusted rates per patient-month, as it was felt to be a meaningful time period for this disease. The exposure adjusted rate was defined as the number of events per person-time at risk and captures the total cumulative bleeding events (even multiple events within the same patient). Months of person time were defined as months from first dose date to study end date. Results Four RCTs met all inclusion criteria, and a total of 358 patients were included in the systematic review. 2 studies included only lower risk MDS patients (IPSS low/int-1) and 2 studies included lower and higher risk patients (IPSS low/int-1 and int-2). Romiplostim was compared to placebo in all 4 trials, but each trial had a different backbone for MDS therapy (lenalidomide, azacitidine, decitabine and just placebo). Two trials compared 2 dosing regimens to placebo (500ug weekly and 750ug weekly) and 2 trials used the higher dosing of 750ug weekly. Three studies of eltrombopag vs. placebo are ongoing, and results were not available for inclusion. Relative risk (RR) of bleeding with romiplostim vs. placebo was 0.84 (95% CI: 0.57-1.24; I2:12%). Exposure-adjusted bleeding rate per patient month was significantly less with romiplostim vs. placebo at 0.92 (95% CI: 0.86-0.99; I2:0%). Only one study reported severe grade 3-4 bleeding events, and the rates were very low, at 1/27 in the intervention arms (4%) and 2/13 (13%) in the control group, giving a favourable RR of 0.24, but very wide 95% CI of 0.02 to 2.42. The exposure-adjusted platelet transfusion rate per patient month was also significantly less with romiplostim at 0.69 (95% CI: 0.53-0.88; I2:34%). The RR of AML progression with romiplostim vs. placebo was 1.36 (95% CI: 0.54-3.40; I2:0%), however the AML progression outcome data were felt to be at high risk of bias because of the early termination of one trial. Mortality was reported as a proportion of deaths during the study period for all 4 trials, giving a RR with romiplostim of 0.90 (95% CI: 0.54-1.50; I2: 30%). Conclusions Romiplostim is promising in its ability to decrease patient-important outcomes: cumulative bleeding events and the need for platelet transfusions. However, most of those bleeding events were likely grade 2, which are not necessarily clinically important, and platelet transfusion reduction may not be as relevant for those practicing therapeutic (not prophylactic) platelet transfusions. Although the risk of AML progression was not increased, the outcome data were felt to be at high risk for bias, and thus this safety concern cannot be ignored. Therefore, romiplostim cannot yet be routinely recommended. Results of ongoing eltrombopag studies are awaited. Disclosures: No relevant conflicts of interest to declare.

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Use of an Antifibrinolytic Agent and Vitamin K As Alternative to Platelet Transfusions in Autologous Hematopoietic Cell Transplantation

Blood ◽

10.1182/blood-2021-149823 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2916-2916

Author(s):

Patricia Locantore-Ford ◽

Ronak Mistry ◽

Evani Patel ◽

Sarah Chen ◽

Robert C Goodacre

Keyword(s):

Vitamin K ◽

Platelet Transfusion ◽

Aminocaproic Acid ◽

Vitamin K Deficiency ◽

Bleeding Events ◽

Antifibrinolytic Agents ◽

Platelet Counts ◽

K Deficiency ◽

Autologous Hct ◽

Platelet Transfusions

Abstract Background Managing thrombocytopenia with a prophylactic strategy was previously recommended for patients with impaired bone marrow function, hematological malignancies, and recipients of HCT when platelet counts declined to under 10,000/uL. However, the updated 2018 ASCO guidelines now suggest a place for a therapeutic i.e., after a bleeding event rather than a prophylactic platelet transfusion strategy for patients with hematologic malignancies undergoing autologous HCT. Studies show a lack of significant difference between trial groups in hemostatic outcomes, such as the number of WHO grade 2-4 bleeds, and number of days with bleeding events. Platelet transfusions increase risks of infectious and non-infectious complications as well as inducing a platelet refractory state. Our Transfusion Free Medicine Program has now performed over 200 autologous hematopoietic stem cell transplants (HCT) in Jehovah's Witnesses who due to religious convictions, do not accept red cell or platelet transfusions. Vitamin K is a fat-soluble vitamin that is required for normal blood clotting. Autologous HCT patients are at risk for vitamin K deficiency from multiple reasons including malnutrition, frequent use of antibiotics, chemotherapy induced gastrointestinal toxicity leading to malabsorption and colitis. The prothrombin test lacks the sensitivity and specificity to detect mild deficiency. A mild vitamin K deficiency may be underdiagnosed in our transplant patients adding to bleeding risk. With the effective use of antifibrinolytic agents and Vitamin K as an alternative to platelet transfusions we believe this may enhance hemostasis and prove a valuable adjunct to a therapeutic approach. Methods Patients in our study were those who were of the Jehovah's Witness faith undergoing autologous HCT for Multiple Myeloma and Lymphoma. Patients received aminocaproic acid as an alternative to platelet transfusion to enhance hemostasis at a dose of 1 g every 4 hours or prophylactically for platelet counts less than 30,000 /uL. Titration to 4 g every 4 hours intravenously was required for platelet counts less than 10,000/ul or clinical bleeding. Vitamin K 10 mg orally or subcutaneous was also started at this time. Results Table 1 illustrates the low number of bleeding events especially grade 3 or 4 that occurred. There were no Grade 3 or 4 bleeding events in patients with platelet counts above 5000/uL. No patient had residual long term effects nor was there an increase in thromboembolic events. Conclusions These data add to the body of literature supporting a therapeutic platelet transfusion strategy in an experienced center for autologous HCT patients and challenges the prophylactic platelet count of 10,000 /uL suggesting instead 5000/uL. The safety and efficacy of antifibrinolytic agents and Vitamin K as an alternative to platelet transfusions to enhance hemostasis in autologous stem cell transplant patients may prove beneficial not only in JW patients but also in those transplant centers wishing to offer a therapeutic platelet transfusion approach and as a strategy to manage platelet refractoriness. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Aminocaproic Acid is an antifibrinolytic agent approved for treatment of bleeding in surgical patients and hematological bleeding disorders. Vitamin K is approved for use in reversal of anticoagulation from Warfarin, vitamin K deficiency without liver disease and in the newborn.

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Characteristics and Financial Impact of Potentially Inappropriate Platelet Transfusion in the Inpatient Hospital Setting

Blood ◽

10.1182/blood-2019-125949 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2096-2096

Author(s):

Eric Mou ◽

Colin Murphy ◽

Jason Hom ◽

Lisa Shieh ◽

Neil Shah

Keyword(s):

Platelet Count ◽

Patient Care ◽

Platelet Transfusion ◽

Bypass Surgery ◽

Hospital Setting ◽

Financial Impact ◽

Platelet Counts ◽

Cardiac Bypass ◽

Platelet Defects ◽

Platelet Transfusions

Introduction Platelets are transfused prophylactically to prevent hemorrhage in a variety of patient populations. However, guidelines indicate that prophylactic platelet transfusions in patients with platelet counts above 50k/uL are usually not indicated, with notable exceptions including those undergoing neurological or cardiac bypass surgery. Common minor procedures such as paracentesis, central line placement, and lumbar puncture have been safely performed at platelet counts below 50k/uL. Despite this evidence, our institution incurred approximately 10 million dollars (USD) in direct platelet costs in 2017, with nearly 40% of platelet transfusions are occurring when the patient's platelet count exceeded 50k/uL. Given the significant financial impact of, and potential adverse effects associated with inappropriate platelet transfusion, we implemented a best practice advisory (BPA) in our electronic medical record (EMR) in order to better characterize patterns of platelet transfusion orders in patients with platelet counts >50k/uL. Methods An EMR-embedded BPA was activated in the inpatient hospital setting of a large, tertiary care academic medical center on May 1, 2019, and triggered whenever a platelet transfusion order was placed on an admitted patient whose most recent documented platelet count was >50k/ul. To inform the comparative impact of BPA alerts on provider behavior, alerts were randomized at the patient level to trigger either in standard or silent fashion. For standard alerts, the BPA appeared on-screen, informing the provider that their platelet transfusion order was potentially inappropriate and citing supportive evidence. Providers had the option of following or overriding the alert (Figure 1). In case of alert override, a pre-specified or free text justification was requested. Pre-specified options included upcoming neurosurgery, cardiac bypass surgery, known qualitative platelet defects, or patients taking antiplatelet drugs. Charge data were based on charges for platelet transfusion orders as listed in the hospital charge master. Results From May 1, 2019 to July 30, 2019, the alert fired 181 times (Figure 2). Alerts were silently triggered in 64 (35%) cases. Of the 117 active alerts, 23 (20%) were followed and 94 (80%) were overridden. The most common reasons for alert override included prophylactic transfusions ahead of non-cardiac and non-neurosurgical operations (18%), upcoming cardiac bypass surgery (18%), qualitative platelet defects (12%), active central nervous system (CNS) bleeding (12%), and active non-CNS bleeding (7%). The estimated cost savings associated with followed alerts was $18,170 USD. Discussion Our BPA was effective in reducing instances of platelet transfusion orders by 20% over a three-month period, translating to an estimated annual savings of nearly $70,000 USD in hospital charges. Conversely, the 80% alert override rate indicates that platelet transfusion in patients with platelet counts >50k/uL remains common, occurring in a variety of contexts. Potentially appropriate reasons for platelet transfusions included orders in the setting of cardiovascular bypass surgery, active CNS bleeding, or qualitative platelet defects, representing circumstances in which platelet thresholds are often set higher than 50k/uL. Alternatively, 25% of alert overrides occurred in potentially inappropriate contexts, including patients undergoing non-cardiovascular/non-neurosurgical procedures and patients with non-CNS active bleeding, settings where routinely targeting a platelet threshold >50k/uL is not supported by evidence. As a result of our study's randomized design, future directions include comparative analyses between patient care encounters in which alerts were silently versus visibly triggered, allowing for rigorous determination as to whether providers' interaction with our BPA influences subsequent rates of potentially inappropriate platelet utilization as compared to a control group. Overall, our findings show that platelets are frequently ordered in potentially inappropriate settings, and that reducing these orders imparts significant financial savings. These results provide an impetus for interventions directed at educating providers on appropriate platelet ordering practices, in order to further reduce unnecessary expenditures and optimize patient care. Disclosures No relevant conflicts of interest to declare.

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The burden of immune‐mediated refractoriness to platelet transfusions in myelodysplastic syndromes

Transfusion ◽

10.1111/trf.16029 ◽

2020 ◽

Vol 60 (10) ◽

pp. 2192-2198

Author(s):

Kathleen P. L. Cheok ◽

Rakchha Chhetri ◽

Li Yan A. Wee ◽

Oisin Friel ◽

Anh Pham ◽

...

Keyword(s):

Myelodysplastic Syndromes ◽

Immune Mediated ◽

Platelet Transfusions

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A Restrictive Platelet Transfusion Policy Allowing Long-Term Support of Outpatients With Severe Aplastic Anemia

Blood ◽

10.1182/blood.v93.9.3124 ◽

1999 ◽

Vol 93 (9) ◽

pp. 3124-3126 ◽

Cited By ~ 68

Author(s):

Markus Sagmeister ◽

Lic Oec ◽

Jürg Gmür

Keyword(s):

Aplastic Anemia ◽

Platelet Transfusion ◽

Severe Aplastic Anemia ◽

Bleeding Complications ◽

Outpatient Basis ◽

Platelet Counts ◽

The Mean ◽

Restrictive Policy ◽

Platelet Transfusions

Abstract The threshold for prophylactic platelet transfusions in patients with hypoplastic thrombopenia generally recommended in the standard literature is 20,000 platelets/μL. A more restrictive transfusion policy may be indicated in patients with chronic severe aplastic anemia (SAA) in need of long-term platelet support. We evaluated the feasibility and safety of a policy with low thresholds for prophylactic transfusions (≤5,000 platelets/μL in stable patients; 6,000 to 10,000 platelets/μL in cases with fever and/or hemorrhagic signs) combined with progressive lengthening of transfusion intervals (up to at least 7 days irrespective of the interim course of platelet counts). The study was based on a retrospective analysis of a total of 18,706 patient days with platelet counts ≤10,000/μL in patients with chronic SAA treated (for more than 3 months) on an outpatient basis. Altogether, 1,135 platelet transfusions were given, 88% at counts ≤10,000/μL and 57% at counts ≤5,000/μL. The mean transfusion interval was 10 days. During the period of observation, three major nonlethal bleeding complications occurred, which could be well controlled. We conclude that the restrictive policy with low transfusion thresholds and prolonged transfusion intervals proved feasible and safe in chronic SAA patients.

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A Risk Model for Thrombocytopenia Requiring Platelet Transfusion After Cytotoxic Chemotherapy

Blood ◽

10.1182/blood.v92.2.405 ◽

1998 ◽

Vol 92 (2) ◽

pp. 405-410 ◽

Cited By ~ 93

Author(s):

J.Y. Blay ◽

A. Le Cesne ◽

C. Mermet ◽

C. Maugard ◽

A. Ravaud ◽

...

Keyword(s):

Risk Factors ◽

Platelet Count ◽

High Risk ◽

Risk Model ◽

Univariate Analysis ◽

Cytotoxic Chemotherapy ◽

Phase Iii ◽

Severe Thrombocytopenia ◽

Increased Risk ◽

Platelet Transfusions

Abstract Severe thrombocytopenia is a rare but life-threatening side effect of cytotoxic chemotherapy for which risk factors are not well known. Our objective was to delineate a risk model for chemotherapy-induced thrombocytopenia requiring platelet transfusions in cancer patients. Univariate and multivariate analysis of risk factors for chemotherapy-induced thrombocytopenia requiring platelet transfusions were performed on the cohort of the 1,051 patients (CLB 1996) treated with chemotherapy in the Department of Medicine of the Centre Léon Bérard (CLB) in 1996. In univariate analysis, performance status (PS) greater than 1, platelet count less than 150,000/μL at day 1 (d1) before the initiation of chemotherapy, d1 lymphocyte count ≤700/μL, d1 polymorphonuclear leukocyte count less than 1,500/μL, and the type of chemotherapy (high risk v others) were significantly associated (P < .01) with an increased risk of severe thrombocytopenia requiring platelet transfusions. Using logistic regression, d1 platelet count less than 150,000/μL (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.9 to 9.6), d1 lymphocyte counts ≤700/μL (OR, 3.37; 95% CI, 1.77 to 6.4), the type of chemotherapy (OR, 3.38; 95% CI, 1.77 to 6.4), and PS greater than 1 (OR, 2.23; 95% CI, 1.22 to 4.1) were identified as independent risk factors for platelet transfusions. The observed incidences of platelet transfusions were 45%, 13%, 7%, and 1.5% for patients with ≥3, 2, 1, or 0 risk factors, respectively. This model was then tested in 3 groups of patients treated with chemotherapy used as validation samples: (1) the series of 340 patients treated in the CLB in the first 6 months of 1997, (2) the prospective multicentric cohort of 321 patients of the ELYPSE 1 study, and (3) the series of 149 patients with non-Hodgkin's lymphoma treated in the CLB within prospective phase III trials (1987 to 1995). In these 3 groups, the observed incidences of platelet transfusions in the above-defined risk groups did not differ significantly (P > .1) from those calculated in the model. This risk index could be useful to identify patients at high risk for chemotherapy-induced thrombocytopenia requiring platelet transfusions.

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Clinical impact of chemotherapy-induced thrombocytopenia in patients with gynecologic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.11.2317 ◽

1994 ◽

Vol 12 (11) ◽

pp. 2317-2320 ◽

Cited By ~ 25

Author(s):

G L Goldberg ◽

D G Gibbon ◽

H O Smith ◽

C DeVictoria ◽

C D Runowicz ◽

...

Keyword(s):

Platelet Count ◽

Major Bleeding ◽

Gynecologic Cancer ◽

Minor Bleeding ◽

Clinical Effects ◽

Bleeding Events ◽

Transfusion Therapy ◽

Platelet Counts ◽

Major Bleeding Events ◽

Platelet Transfusions

PURPOSE AND METHODS This retrospective analysis of 501 patients with gynecologic cancer treated with chemotherapy evaluates the relationship between platelet count and clinical bleeding, as well as the clinical effects of platelet transfusion therapy. Thrombocytopenic patients were divided into six groups according to platelet counts, and major or minor bleeding manifestations were documented. Thrombocytopenia was defined as a platelet count less than 100,000/microL. RESULTS Thrombocytopenia occurred in 182 (36.3%) patients over 808 of 1,546 chemotherapy cycles (52%). No intracranial or life-threatening bleeding occurred in any patient. The majority of patients (139 [76.4%]) had no clinical bleeding. Minor bleeding, such as purpura, occurred in 34 patients (18.7%) and 44 cycles (5.4%). Major bleeding occurred in nine patients (4.9%) and 10 cycles (1.3%). Five major bleeding events occurred in 49 patients with platelet counts between 0 and 10,000/microL. Forty-three of these patients received platelet transfusions. Thirty-eight of 43 transfused patients (88.3%) had no bleeding. Of the remaining five patients, two were transfused prophylactically with no effect. Three major bleeding events occurred in patients with platelet counts that ranged from 11,000 to 20,000/microL, but these were due to chronic instrumentation or trauma. In patients with platelet counts more than 20,000/microL, major bleeding occurred only from necrotic metastatic lesions. Random-donor platelet transfusions provided inconsistent increments in platelet counts. Overall, 27.5% of patients achieved the expected increase in platelet number based on units of platelet concentrate transfused. The use of single-donor or human leukocyte antigen (HLA)-matched platelets did not provide greater increments in those patients who were refractory to random-donor platelets. CONCLUSION Platelet counts > or = 10,000/microL are not associated with spontaneous major bleeding. Prophylactic platelet transfusions in patients with gynecologic malignancies and chemotherapy-induced thrombocytopenia should be limited to those with platelet counts < or = 10,000/microL, provided they are not bleeding and have no major anatomic or pathophysiologic precursors of bleeding.

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How well do platelets prevent bleeding?

Hematology ◽

10.1182/hematology.2020000136 ◽

2020 ◽

Vol 2020 (1) ◽

pp. 518-522

Author(s):

Darrell J. Triulzi

Keyword(s):

Platelet Transfusion ◽

Anticoagulation Therapy ◽

Outpatient Setting ◽

Severe Thrombocytopenia ◽

Transfusion Threshold ◽

Spontaneous Bleeding ◽

Risk Of Bleeding ◽

Increased Risk ◽

High Incidence ◽

Platelet Transfusions

Abstract Prophylactic platelet transfusions are used to reduce the risk of spontaneous bleeding in patients with treatment- or disease-related severe thrombocytopenia. A prophylactic platelet-transfusion threshold of <10 × 103/µL has been shown to be safe in stable hematology/oncology patients. A higher threshold and/or larger or more frequent platelet doses may be appropriate for patients with clinical features associated with an increased risk of bleeding such as high fevers, sepsis, disseminated intravascular coagulation, anticoagulation therapy, or splenomegaly. Unique factors in the outpatient setting may support the use of a higher platelet-transfusion threshold and/or dose of platelets. A prophylactic platelet-transfusion strategy has been shown to be associated with a lower risk of bleeding compared with no prophylaxis in adult patients receiving chemotherapy but not for autologous transplant recipients. Despite the use of prophylactic platelet transfusions, a high incidence (50% to 70%) of spontaneous bleeding remains. Using a higher threshold or larger doses of platelets does not change this risk. New approaches to reduce the risk of spontaneous bleeding, including antifibrinolytic therapy, are currently under study.

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