PATHOPHYSIOLOGY OF THROMBOCYTOPENIA AND RESULTANT CLINICAL INDICATIONS FOR PLATELET TRANSFUSION

1987 ◽  
Author(s):  
Sherrill J Slichter

Careful evaluation of platelet survival data in normal individuals and patients with thrombocytopeniasecondary to marrow aplasia has demonstrated that platelets are lost from circulation by two mechanisms a fixed fraction of platelets, amounting to approxi mately 7,100 platelets/ul/day, are lost randomly while the remaining platelets are removed by senescent mechanisms. At platelet counts of <100,000/ul, platelet survival becomes progressively shorter as the fixed platelet loss becomes a proportionately greater fraction of the circulating platelets. Thus, there is a direct relationship between platelet count and platelet survival in thrombocytopenic patients. Therefore, when judging the effectiveness of platelet therapy in thrombocytopenic patients, the influence of platelet count on platelet survival must be considered. As yet, there have been no studies to determine if there are ways to interrupt this fixed platelet loss? whether such therapy might improve platelet support in thrombocyotpenic patients by prolonging platelet survival? or, alternatively, whether such therapy might enhance the bleeding risk if random platelet removal is related to physiologic platelet-endothelial cell interactions.Besides taking into account the effect of thrombocytopenia on the expected response to platelet transfusions, the risk of alloimmunization with platelet transfusion therapy requires a careful assessment of the indications for platelet transfusions for each patient.Based on 51Cr-labeled stool blood loss measurements, we have determined that the bleeding risk is minimal at platelet counts above 10,000 platelets/ul.Only when the platelet count falls to a lower level of 5,000/ul is GI bleeding significantly increased. However, there are certain medications that may enhance the bleeding risk and require platelet transfusions to be given at higher platelet counts.In those patients who are thrombocytopenic, not because of failure of marrow platelet production, but rather because of accelerated platelet removal, indications for platelet transfusions must be adjusted to meet the particular problem. For example, for patients with autoimmune thrombocytopenic purpura, platelet transfusions are rarely indicated (one exception being intracerebral bleeding) because of the rapid rate of platelet removal and because the patients are usually releasing young hyperfunctional platelets from the bone marrow reducing the hemorrhagic risk at any given platelet count. In some patients with consumptive coagulopathies, even though platelet removal is rapid, platelets may have to be provided until specific therapy resolves the underlying disease process causing the platelet consumption. For these patients, increased levels of fibrinogen/fibrin degregation products, as well as various medications they maybe receiving, may produce platelet dysfunction necessitating platelet transfusions at higher platelet levels. Finally, massive transfusion patients may develop a dilution thrombocytopenia requiring platelet transfusions.

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2096-2096
Author(s):  
Eric Mou ◽  
Colin Murphy ◽  
Jason Hom ◽  
Lisa Shieh ◽  
Neil Shah

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.


1994 ◽  
Vol 12 (11) ◽  
pp. 2317-2320 ◽  
Author(s):  
G L Goldberg ◽  
D G Gibbon ◽  
H O Smith ◽  
C DeVictoria ◽  
C D Runowicz ◽  
...  

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.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4740-4740
Author(s):  
Shannon Nixon ◽  
Dawn Maze ◽  
Eshetu G Atenafu ◽  
Danielle Brandys ◽  
Cindy Susan Murray ◽  
...  

Abstract Background: Intracranial hemorrhage (ICH) is a common complication in acute leukemia that is associated with significant morbidity and mortality. While evidence supports prophylactic platelet transfusions at a threshold < 10 x 109/L to reduce the risk of bleeding in acute leukemia, there is little data to guide platelet transfusion practice in patients following ICH. The objectives of this study were to characterize the clinical features and outcomes of acute leukemia patients with ICH and to understand current platelet transfusion practice following ICH. Methods: This was a retrospective study conducted at a large, quaternary, academic cancer centre. We included all adult patients with a diagnosis of acute leukemia who had a documented ICH at our centre between January 1, 2009 and December 31, 2016. We assessed demographics, medications, infection and bleeding history in the week preceding ICH, characteristics of ICH including site of bleed, acute management, transfusion practice in the first 90 days, and clinical outcomes. Radiologic scans were re-assessed by neuroradiology to determine if the ICH was stable or if new or progressive bleeding had developed. Transfusion practice following the ICH was compared between the two groups with longitudinal data analysis using platelet counts as outcome. Kaplan-Meier product limit method was used to estimate overall survival (OS) rates as well as to obtain median survival; log-rank test was used to compare OS among those without new or progressive ICH vs. those with progression. Results: During the study period, of 2576 patients diagnosed with acute leukemia, 101 suffered from ICH and were included in the study. Most patients (94) had AML, of which 9 had APL, 6 had ALL, and 1 had MPAL. At the time of ICH, 61 patients were newly diagnosed or receiving induction chemotherapy, 33 had relapsed disease and 7 were in complete remission. Spontaneous ICH occurred in 76 patients. Within the week preceding ICH, 7 patients were on medications known to increase bleeding risk and 39 were on tranexamic acid. Sixty-four patients had clinical evidence of bleeding elsewhere and 22 had evidence of infection. On the day of ICH, the median platelet count was 16 x 109/L (range 0- 433 x109/L). Thirty-one patients had a platelet count < 10 x 109/L and 10 of these patients received a platelet transfusion prior to the bleed. Seventy patients had a platelet count ≥10 x109/L and 17 of these received a platelet transfusion prior to the bleed. Six patients (6%) exhibited evidence of platelet transfusion refractoriness. In the 90 days following ICH, 21% of platelet transfusions were given for a platelet count < 10 x 109/L, 55% were given with a platelet count between 10-29 x109/L, and 24% were given with a platelet count ≥ 30 x 109/L. New or progressive ICH occurred in 28 patients. The median platelet transfusion threshold was 19 x 109/L (range 0-114 x 109/L) for those without new or progressive ICH and 21 x 109/L (range 0-93 x 109/L) for those with progression (p=0.04; Figure 1). Of the 101 study patients, 79 have died. Median OS was 5.6 months for those without new or progressive ICH and 2.9 months for those with progression (p=0.002) (Figure 2). Cause of death was attributed to non-ICH causes in the majority of patients 65/79 (82%). Conclusions: In this retrospective study, we evaluated the outcomes of 101 patients with acute leukemia and ICH. At the time of the bleed, the majority of patients had active disease and more than two thirds had platelet counts of 10 x 109/L or higher. During 90 days of follow-up, nearly one third of patients developed new or progressive ICH. Platelet transfusion practice was variable and the median threshold was, in fact, higher in those who subsequently developed new or progressive bleeding. The reasons for this were unclear from our chart review, but we hypothesize that these patients may have had additional risk factors, e.g. fever, infection. The outcomes of patients with acute leukemia and ICH are poor. Factors other than platelet transfusion threshold likely contribute to secondary ICH events and the overall poor prognosis. Disclosures Maze: Novartis: Consultancy, Honoraria.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1141-1141 ◽  
Author(s):  
Shuoyan Ning ◽  
Brent Kerbel ◽  
Jeannie Callum ◽  
Yulia Lin

Abstract Introduction: Lumbar puncture (LP) is a frequently performed diagnostic and therapeutic intervention in adult oncology patients. While thrombocytopenia is common in this patient population, the minimum "safe" platelet count required for LPs is unknown. Recent guidelines from the AABB (American Association of Blood Banks) recommend a pre-procedure platelet count of 50 x 109/L. However this recommendation is largely based on expert opinion, and there remains a paucity of studies in the adult oncology literature to address this important question. Methods: We retrospectively reviewed all oncology patients ≥18 years who underwent 1 or more LPs over a 2 year period at a single tertiary care institution to determine 1) the range of platelet counts at which LPs are performed; 2) the rate of traumatic taps; and 3) the rate of hemorrhagic complications. Laboratory, clinical, and transfusion information were extracted through the Laboratory Information System, chart review, and blood bank database, respectively. Thrombocytopenia was defined as a platelet count of < 150 x 109/L. Pre-LP platelet counts were those collected ≤24 hours from, and closest to the time of the LP. The following bleeding risk factors were documented: end stage renal disease; platelet dysfunction; von Willebrand disease; hemophilia. Anticoagulation, anti-platelet, and non-steroidal inflammatory use was also recorded, with accuracy limited by the study's retrospective nature. All patients with coagulopathy were excluded (INR ≥ 1.5, aPTT ≥ 40, fibrinogen ≤ 1.0). Traumatic tap was defined as 500 or more red blood cells per high-power field in the cerebrospinal fluid. A follow up of 1 week after LP was used to capture any hemorrhagic complications. Results: From January 2013 to December 2014, 135 oncology patients underwent 369 LPs; 64 (47.4%) patients were female, and the mean age was 59 years (range 20-87). 119 (88.1%) patients had a primary hematological diagnosis. 113 (30.6%) LPs were performed in thrombocytopenic patients. 28 (7.6%) procedures had a pre-procedure platelet count of ≤ 50 x 109/L, with 18 receiving a single platelet transfusion on the day of the LP. Of these 18 transfusions, only 1 had a post-transfusion platelet count available prior to LP with no improvement in platelet count (33 x 109/L). 15 transfusions had post-LP platelet counts within 24 hours of the transfusion (8 below 50 x 109/L with lowest 14 x 109/L), 1 had post-LP platelet count within 24-48 hours (54 x 109/L) and 1 did not have a post-transfusion platelet count. Traumatic taps occurred in 17 (15.0%) LPs in patient with thrombocytopenia, compared to 26 (11.0%) LPs in patients with a normal platelet count (fisher's exact test P=0.39). There was 1 traumatic tap in a patient with a pre-LP platelet count of ≤ 50 x 109/L; however, this patient received a pre-LP platelet transfusion for a platelet count of 42 x 109/L and had a post-LP platelet count of 66 x 109/L. Presence of bleeding risk factors did not increase the risk of a traumatic tap (present in 48.8% of traumatic taps vs. 88.3% of non-traumatic taps). There were no hemorrhagic complications. Conclusion: Among this cohort of adult oncology patients undergoing diagnostic and therapeutic LPs, there were no hemorrhagic complications. There was no significant increase in traumatic taps in patients with thrombocytopenia or bleeding risk factors. While platelet transfusions were frequently administered for patients with a platelet count of ≤ 50 x 109/L, post-transfusion platelet counts were infrequently assessed prior to the procedure. Our findings question whether a platelet transfusion threshold of 50 x 109/L is necessary for lumbar puncture.Table 1.Platelet Count Pre-LP(x109/L)Number of LPsNumber of Traumatic TapsNumber of Hemorrhagic Complications0-90N/AN/A10-2030021-5070051-1003380101-1495270> 150242270Unknown1400< 50 x 109/L and received platelet transfusion on day of LP181*0Total369430*There was one traumatic tap in a patient with a platelet count of 42 x 109/L who received a platelet transfusion pre-LP. The post transfusion platelet count was 66 x 109/L. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4293-4293
Author(s):  
Lakshminarayanan Nandagopal ◽  
Muthu Veeraputhiran ◽  
Tania Jain ◽  
Ayman Soubani ◽  
Charles A. Schiffer

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.


Blood ◽  
1987 ◽  
Vol 70 (1) ◽  
pp. 23-30 ◽  
Author(s):  
JM Heal ◽  
N Blumberg ◽  
D Masel

Refractoriness occurs in many patients receiving multiple platelet transfusions. We used a sensitive ELISA assay to assess the utility of crossmatching HLA-A,B matched single donor platelets in 51 consecutive, typical refractory patients. Of the 222 transfusions evaluated at 1 to 4 hours posttransfusion, only 17 of 54 (31%) with positive crossmatches had corrected platelet count increments of greater than or equal to 7,500/microL. In contrast, 95 of 168 (57%) of those with negative crossmatches had such increments (P less than .001). Regardless of the results of the crossmatch, HLA-A,B, and ABO matching had independent influences on transfusion outcome. The median corrected 1- to 4-hour increment for crossmatch negative transfusions was 13,300/microL for A/BU grade matches, 9,700 for BX, and 7,800 for C. Increments were 10,000/microL for ABO-identical transfusions and 5,900 for transfusions of platelets ABO incompatible with the recipient's plasma antibodies. When the donor platelets were ABO compatible, but the donor plasma contained ABO antibodies to the recipient's platelets, the increment was intermediate (8,200/microL). The most important factor in predicting platelet survival was the crossmatch, followed by HLA-A,B and ABO, each having independent predictive value. These data demonstrate that the predictive value of a negative crossmatch may be considerably less than that reported in previous studies with stable, less ill patients. In typical refractory patients, there appear to be mechanisms of platelet destruction that are related to HLA-A,B and ABO but are not detected with current crossmatch methods. We hypothesize that soluble plasma HLA-A,B and ABO antigens contribute to the destruction of donor and sometimes recipient platelets by an immune complex or other “innocent bystander” mechanism. With our crossmatching technique, HLA-A,B and ABO match grades remain relevant to platelet transfusion therapy in some refractory patients.


Blood ◽  
1987 ◽  
Vol 70 (1) ◽  
pp. 23-30 ◽  
Author(s):  
JM Heal ◽  
N Blumberg ◽  
D Masel

Abstract Refractoriness occurs in many patients receiving multiple platelet transfusions. We used a sensitive ELISA assay to assess the utility of crossmatching HLA-A,B matched single donor platelets in 51 consecutive, typical refractory patients. Of the 222 transfusions evaluated at 1 to 4 hours posttransfusion, only 17 of 54 (31%) with positive crossmatches had corrected platelet count increments of greater than or equal to 7,500/microL. In contrast, 95 of 168 (57%) of those with negative crossmatches had such increments (P less than .001). Regardless of the results of the crossmatch, HLA-A,B, and ABO matching had independent influences on transfusion outcome. The median corrected 1- to 4-hour increment for crossmatch negative transfusions was 13,300/microL for A/BU grade matches, 9,700 for BX, and 7,800 for C. Increments were 10,000/microL for ABO-identical transfusions and 5,900 for transfusions of platelets ABO incompatible with the recipient's plasma antibodies. When the donor platelets were ABO compatible, but the donor plasma contained ABO antibodies to the recipient's platelets, the increment was intermediate (8,200/microL). The most important factor in predicting platelet survival was the crossmatch, followed by HLA-A,B and ABO, each having independent predictive value. These data demonstrate that the predictive value of a negative crossmatch may be considerably less than that reported in previous studies with stable, less ill patients. In typical refractory patients, there appear to be mechanisms of platelet destruction that are related to HLA-A,B and ABO but are not detected with current crossmatch methods. We hypothesize that soluble plasma HLA-A,B and ABO antigens contribute to the destruction of donor and sometimes recipient platelets by an immune complex or other “innocent bystander” mechanism. With our crossmatching technique, HLA-A,B and ABO match grades remain relevant to platelet transfusion therapy in some refractory patients.


Blood ◽  
2001 ◽  
Vol 98 (5) ◽  
pp. 1346-1351 ◽  
Author(s):  
Lawrence T. Goodnough ◽  
David J. Kuter ◽  
Jeffrey McCullough ◽  
Sherrill J. Slichter ◽  
John DiPersio ◽  
...  

Many patients receiving dose-intensive chemotherapy acquire thrombocytopenia and need platelet transfusions. A study was conducted to determine whether platelets harvested from healthy donors treated with thrombopoietin could provide larger increases in platelet counts and thereby delay time to next platelet transfusion compared to routinely available platelets given to thrombocytopenic patients. Community platelet donors received either 1 or 3 μg/kg pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) or placebo and then donated platelets 10 to 15 days later. One hundred sixty-six of these platelet concentrates were then transfused to 120 patients with platelets counts 25 × 109/L or lower. Pretransfusion platelet counts (11 × 109/L) were similar for recipients of placebo-derived and PEG-rHuMGDF–derived platelets. Early after transfusion, the median platelet count increment was higher in patients receiving PEG-rHuMGDF–derived platelets: 19 (range, −12-66) × 109/L, 41 (range, 5-133) × 109/L, and 82 (range, −4-188) × 109/L for placebo-, 1-μg/kg–, and 3-μ/kg–derived platelets, respectively. This difference was maintained 18 to 24 hours after transfusion. Transfusion-free intervals were 1.72, 2.64, and 3.80 days for the recipients of the placebo-, 1-μg/kg–, and 3-μ/kg–derived platelets, respectively. The rate of transfusion-related adverse events was not different in recipients of placebo-derived and PEG-rHuMGDF–derived platelets. Therefore, when transfused into patients with thrombocytopenia, platelets collected from healthy donors undergoing thrombopoietin therapy were safe and resulted in significantly greater platelet count increments and longer transfusion-free intervals than platelets obtained from donors treated with placebo.


Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 707-707
Author(s):  
Suzanne F Fustolo-Gunnink ◽  
K Fijnvandraat ◽  
I M Ree ◽  
C Caram-Deelder ◽  
P Andriessen ◽  
...  

Abstract Introduction Limited evidence supports the widely used practice of administering platelet transfusions to prevent major bleeding in preterm thrombocytopenic neonates. Only 1 randomized controlled trial addressed this issue, but used thresholds higher than those currently used in clinical practice. In order to assess the impact of platelet transfusions on bleeding risk, the primary objective of this study was to develop a prediction model for bleeding. Platelet transfusion was included as variable in this model. In these secondary analyses, we further explored the impact of platelet transfusions on bleeding risk. Materials and methods In this multicenter cohort study, neonates with a gestational age (GA) &lt;34 weeks at birth, admitted to a neonatal intensive care unit (NICU) who developed a platelet count &lt;50x109/L were included. The main study endpoint was major bleeding, defined as intraventricular hemorrhage (IVH) grade 3, IVH with parenchymal involvement, other types of intracranial hemorrhage visible on ultrasound scans, pulmonary hemorrhage or any other type of bleeding requiring immediate interventions. The prediction model was developed using landmarking, in which multiple cox models at regular time-points were combined into 1 supermodel. To further explore the impact of platelet transfusions on bleeding risk, we performed 3 sensitivity analyses by selecting specific transfusions (instead of all transfusions). Sensitivity analysis 1 : transfusions according to protocol, defined as transfusions for platelet counts &gt;20x109/L only allowed in case of GA&lt;32 weeks and &lt;1500 grams and presence of NEC, sepsis, or treatment with mechanical ventilation, or in case of invasive procedures. Sensitivity analysis 2: transfusions with fair increments, defined as platelet count ≥50x109/L within 24 hours. Sensitivity analysis 3: transfusion dose 11 ml/kg or higher. Results A total of 640 neonates were included with a median gestational age of 28 weeks. 70 neonates developed a major bleed. IUGR, postnatal age, platelet count and mechanical ventilation were independent predictors of bleeding. The model allowed calculation of two bleeding risks for individual neonates: one in case of platelet transfusion and one in case of no platelet transfusion. 1361 platelet transfusions were administered to 449 of 640 (70%) neonates, of which 87 were hyperconcentrates. The hazard ratio for transfusion in the original model was 1.0, indicating no predictive power. Sensitivity analysis 1: 704 (52%) transfusions were given according to protocol. When selecting these transfusions, the hazard ratio for transfusion changed from 1.0 to 0.5, but the p-value remained &gt; 0.05.Sensitivity analysis 2: 764 (56%) of transfusions resulted in a count &gt;50x109/L within 24 hours. When selecting these transfusions, the hazard ratio for transfusion changed from 1.0 to 0.25, but the p-value remained &gt;0.05. 115 (8%) transfusions did not have a follow up platelet count within 24 hours. Sensitivity analysis 3: of the non-hyperconcentrated platelet transfusions, 517 of 1274 (41%) transfusions were ≥ 11 ml/kg. When selecting these transfusions, the hazard ratio for transfusion changed from 1.0 to 0.1, with a p-value of 0.05. Conclusion With this tool, absolute risk of bleeding in individual preterm thrombocytopenic neonates can be calculated. Additionally, risk of bleeding can be assessed for 2 scenarios: with and without platelet transfusion. This can help clinicians in deciding whether or not to transfuse a patient. In the primary model, platelet transfusion was not a predictor for bleeding risk. However, the findings of the sensitivity analyses suggest that transfusions with a dose &gt; 11ml/kg may have a more profound effect on bleeding risk. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4826-4826 ◽  
Author(s):  
Deniz Goren Sahin ◽  
Olga M. Akay ◽  
Mustafa Karagulle ◽  
Eren Gunduz ◽  
Zafer Gulbas

Introduction Prophylactic thrombocyte transfusion is being used to reduce increased bleeding risk after chemotherapy treatment for leukemia or malignancy. This transfusion is frequently applied when thrombocyte count is below <10.000/uL or between 10.000 and 20.000/uL. However, it was shown that thrombocyte count alone is not enough for determining bleeding risk. Moreover, given the fact that thrombocyte transfusions have inherent risks and economic burden, new laboratory approaches such as thromboelastography can be considered to determine bleeding risk in these patients. Thromboelastography is a new alternative method to conventional coagulation tests, which gives information about hemostatic system by evaluating clot’s visco-elastic and mechanical features. The aim of our study to establish a transfusion algorithm by thromboelastographic follow-up of prophylactic thrombocyte transfusion. Methods Eighty patients who have been diagnosed as acute leukemia were randomized into 4 groups. Six units random thrombocyte was given to the first group, three units random thrombocyte was given to the second group, one unit apheresis was given to the third group, and ½ unit apheresis was given to the fourth group. Before and 15 minutes after transfusion, peripheral blood was taken and CBC and rotation thromboelastograpy (ROTEM) was performed by standard device (Pentapharm GmbH, Munich, Germany). Clotting time (CT), clot formation time (CFT), and maximum clot firmness (MCF) were evaluated by 2 methods, in-TEM and ex-TEM. Patients were followed up during study by using clinical bleeding signs based on WHO bleeding grade. Patients who used medications that can affect thrombocyte functions within the last 14 days and patients who have systemic disorders (renal, hepatic, endocrinological) or hemostatic disorders were not included in this study. Variance analysis was used in order to find out statistical differences. P<0.05 was considered statistically significant. Results When platelet counts and ROTEM results were analyzed for each parameter before platelet transfusion, there were no statistically significant differences among groups. We analyzed the differences of platelet counts and thromboelastographic parameters before and after prophylactic platelet transfusion and we didn’t see any statistically significant differences between groups. Clinical bleeding signs were not correlated with platelet count in any groups. Conclusion Six units random, three units random, complete apheresis or half apheresis prophylactic platelet transfusion does not cause any significant changes in platelet count, ROTEM parameters and clinical bleeding signs. Therefore, low dose platelet transfusion can be considered because of its lower economic burden. Moreover, further studies are needed to evaluate the potential of ROTEM as an independent factor for transfusion indication. Disclosures: No relevant conflicts of interest to declare.


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