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The influence of bleeding on trigger changes for platelet transfusion in patients with chemotherapy-induced thrombocytopenia
Abstract
Background:
For patients with thrombocytopenia without bleeding risk factors, a platelet transfusion trigger of 10 × 10(9) /L is recommended. No studies have evaluated the clinicians' decision-making process leading to trigger changes.
Study design and methods:
We report on the evaluation of trigger changes and the relation with bleeding. Eighty patients previously enrolled in the SPRINT trial represent the patient population for the current analysis.
Results:
Seventy-four patients had a starting trigger of 10 × 10(9) /L. Only a minority of patients treated with chemotherapy alone (3/12, 25%) and autologous transplant (6/15, 40%) had a change in their trigger in contrast to the majority of allogeneic transplant (37/47, 79%; p = 0.001 and p = 0.009, respectively, when compared to allogeneic transplant group). Bleeding was the main reason reported by clinicians for a trigger change, but the occurrence of significant bleeding (Grade 2-4) was similar in patients with or without a trigger change (51 and 54%, p = 1.00). Clinicians were influenced by the bleeding system: grade 1 mucocutaneous bleeding leading to a trigger change was overrepresented (71% of cases), as was grade 2 genitourinary bleeding not leading to a trigger change (57% of cases).
Conclusion:
A universal trigger of 10 × 10(9) /L may not be maintained in a diverse population of patients with their respective bleeding risk factors. Because the trigger is changed often, it may not be as effective as previously believed.
... Generally, chemotherapy is administered with caution at platelet counts < 100 × 10 9 /L, and the risk of spontaneous bleeding increases at platelet counts < 10 × 10 9 /L in hematologic malignancy patients 8 and potentially higher platelet thresholds < 20 × 10 9 /L in some solid tumor patients. 12,13 When maintaining the chemotherapy dose intensity is critical for response or survival, dose modifications are avoided, and when platelet counts fall below 10 × 10 9 /L or in cases of active bleeding, platelet transfusions are frequently utilized. 8 The most common clinical impact of CIT is on the ability to continue cancer therapy; however, other impacts include hospitalization for active bleeding and platelet transfusion, with its attendant risks. ...
Objectives
To estimate the risk of thrombocytopenia in various cancers and chemotherapy regimens.
Methods
Structured patient‐level data from the Flatiron Health Electronic Health Record database were used to identify adult patients who received chemotherapy for a solid tumor or hematologic malignancy from 2012 to 2017. Three‐month cumulative incidence of thrombocytopenia was assessed based on platelet counts, overall and by grade of thrombocytopenia. Co‐occurrence of anemia, neutropenia, and leukopenia was evaluated.
Results
Of 15 521 patients with solid tumors, 13% had thrombocytopenia within 3 months (platelet count <100×10⁹/L); 4% had grade 3 (25 to <50×10⁹/L), and 2% grade 4 (<25×10⁹/L) thrombocytopenia. Of 2537 patients with hematologic malignancies, 28% had any thrombocytopenia, 16% with grade 3 and 12% with grade 4. Among patients with thrombocytopenia, it occurred without another cytopenia in 18% of solid tumors and 7% of hematologic malignancies.
Conclusions
In a large, US‐representative sample of patients undergoing chemotherapy in clinical practice, thrombocytopenia incidence varied across tumor and regimen types. Despite recommendations to alter chemotherapy to avoid severe thrombocytopenia, 4% of patients with solid tumors and 16% with hematologic malignancies experienced grade 3 thrombocytopenia. Prediction and prevention of thrombocytopenia may help oncologists avoid dose modifications and its adverse effects on survival.
Background:
Chemotherapy-induced thrombocytopenia (CIT) is defined as a peripheral platelet count less than 100×109/L, with or without bleeding in cancer patients receiving myelosuppressive chemotherapy. CIT is a significant medical problem during chemotherapy, and it carries the risk of sub-optimal overall survival and bleeding. Alternative interventions to platelet transfusion are limited. Different stages of preclinical and clinical studies have examined the thrombopoietin receptor agonists (TPO-RAs) for CIT in patients with solid tumours.
Objectives:
To assess the effects of TPO-RAs to prevent and treat CIT in patients with solid tumours:(1) to prevent CIT in patients without thrombocytopenia before chemotherapy, (2) to prevent recurrence of CIT, and (3) to treat CIT in patients with thrombocytopenia during chemotherapy.
Search methods:
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, to 28 September 2017), MEDLINE (from 1950 to 28 September 2017), as well as online registers of ongoing trials (Clinical Trials, Chinese Clinical Trial Register, Australian New Zealand Clinical Trial Registry, WHO ICTRP Search Portal, International Standard Randomised Controlled Trial Number registry, GlaxoSmithKline Clinical Study Register, and Amgen Clinical Trials) and conference proceedings (American Society of Hematology, American Society of Clinical Oncology, European Hematology Association, European Society of Medical Oncology, and Conference Proceedings Citation Index-Science, from 2002 up to September 2017) for studies.
Selection criteria:
Randomised controlled trials (RCTs) comparing TPO-RAs alone, or in combination with other drugs, to placebo, no treatment, other drugs, or another TPO-RAs for CIT in patients with solid tumours.
Data collection and analysis:
Two review authors independently screened the results of the search strategies, extracted data, assessed risk of bias, and analysed data according to standard methodological methods expected by Cochrane.
Main results:
We identified six trials eligible for inclusion, of which two are ongoing, and one awaiting classification study. The three included trials were conducted at many different sites in Europe, America, and Asia. All of the three studies recruited adult and elder participants (no children were included) with solid tumours, and compared TPO-RAs with placebo. No studies compared TPO-RAs alone, or in combination with other drugs, to no treatment, or other drugs, or another TPO-RAs.We judged the overall risk of bias as high as we found a high risk for detection bias. We assessed the risk of bias arising from inadequate blinding of outcome assessors as high for number and severity of bleeding episodes (one of the primary outcomes).To prevent CIT: We included two trials (206 participants) comparing TPO-RAs (eltrombopag, multiple-dose oral administration with chemotherapy) with placebo. The use of TPO-RAs may make little or no difference to the all-cause mortality at 33 weeks of follow-up (RR 1.35, 95% CI 0.53 to 3.45; one trial, 26 participants; low quality of evidence). There is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one bleeding episode of any severity (RR 0.62, 95% CI 0.22 to 1.78; two trials, 206 participants; very low quality of evidence). There is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one severe/life-threatening bleeding episode (RR 0.36, 95% CI 0.06 to 2.06; two trials, 206 participants; very low quality of evidence). No studies were found that looked at overall survival (one of the primary outcomes), the number of treatment cycles with at least one bleeding episode, the number of days on which bleeding occurred, the amount of bleeding, or quality of life.To prevent recurrence of CIT: We included one trial (62 participants) comparing TPO-RAs (romiplostim, single-dose subcutaneous administration with chemotherapy) with placebo. There is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one bleeding episode of any severity (RR 2.80, 95% CI 0.17 to 47.53; one trial, 62 participants; very low quality of evidence). There is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one severe/life-threatening bleeding episode (no severe/life-threatening bleeding episodes; one trial, 62 participants; very low quality of evidence). No studies were found that looked at overall survival (one of the primary outcomes), the number of treatment cycles with at least one bleeding episode, the number of days on which bleeding occurred, the amount of bleeding, or quality of life. We found one ongoing study (expected recruitment 74 participants), it is planned to give TPO-RAs (romiplostim, subcutaneous administration with chemotherapy) to participants, but to date this trial has not reported any outcomes.To treat CIT: We found one ongoing study (expected recruitment 83 participants), which is planned to give TPO-RAs (eltrombopag, seven days orally) to participants when their platelet counts are less than 75×109/L during chemotherapy. This trial was originally planned to complete in March 2017, however, the completion date has passed and no results are reported.The one awaiting classification study included patients without thrombocytopenia before chemotherapy (to prevent CIT), patients with thrombocytopenia during chemotherapy (to prevent recurrence of CIT), and other patients during chemotherapy (uncertain whether CIT had happened). There was no evidence for a difference in the number of patients with at least one bleeding episode of any severity (RR 0.27, 95% CI 0.07 to 1.02; one trial, 75 participants). There was no evidence for a difference in the number of patients with at least one severe/life-threatening bleeding episode (RR 0.44, 95% CI 0.03 to 6.77; one trial, 75 participants). This study did not address overall survival or quality of life.
Authors' conclusions:
No certain conclusions can be drawn due to the lack of strong evidence in the review. The available weak evidence did not support the use of TPO-RAs for preventing CIT or preventing recurrence of CIT in patients with solid tumours. There was no evidence to support the use of TPO-RAs for treating CIT in patients with solid tumours.
Patients who are candidates for or are undergoing hematopoietic cell transplantation (HCT) have unique transfusion requirements. These are due to the need to minimize the likelihood of alloimmunization. An effective blood bank and transfusion medicine program are essential for a successful HCT program. This chapter talks focuses on red blood cells (RBCs), leukocyte-reduced red cells, washed red cells, and coagulation factor components, namely fresh frozen plasma (FFP) and cryoprecipitate and fibrinogen. Blood group compatibility of components used to replace coagulation factors and platelet components, and transfusion therapy for HCT donors, are also discussed. Transfusion-transmitted diseases include acquired immune deficiency syndrome (AIDS), hepatitis B virus (HBV), syphilis, human T-lymphotrophic virus-I (HTLV-I), and Epstein-Barr virus (EBV). Following transplantation, patient transfusion needs can be met effectively. The blood supply is safer than ever, and although some risks of infection remain, most patients can be supported safely and effectively.
This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effect of thrombopoietin receptor agonists (TPO-RAs) to prevent (Part 1) and treat (Part 2) chemotherapy-induced thrombocytopenia (CIT) in patients with solid tumours. © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
We conducted a trial of prophylactic platelet transfusions to evaluate the effect of platelet dose on bleeding in patients with hypoproliferative thrombocytopenia.
We randomly assigned hospitalized patients undergoing hematopoietic stem-cell transplantation or chemotherapy for hematologic cancers or solid tumors to receive prophylactic platelet transfusions at a low dose, a medium dose, or a high dose (1.1x10(11), 2.2x10(11), or 4.4x10(11) platelets per square meter of body-surface area, respectively), when morning platelet counts were 10,000 per cubic millimeter or lower. Clinical signs of bleeding were assessed daily. The primary end point was bleeding of grade 2 or higher (as defined on the basis of World Health Organization criteria).
In the 1272 patients who received at least one platelet transfusion, the primary end point was observed in 71%, 69%, and 70% of the patients in the low-dose group, the medium-dose group, and the high-dose group, respectively (differences were not significant). The incidences of higher grades of bleeding, and other adverse events, were similar among the three groups. The median number of platelets transfused was significantly lower in the low-dose group (9.25x10(11)) than in the medium-dose group (11.25x10(11)) or the high-dose group (19.63x10(11)) (P=0.002 for low vs. medium, P<0.001 for high vs. low and high vs. medium), but the median number of platelet transfusions given was significantly higher in the low-dose group (five, vs. three in the medium-dose and three in the high-dose group; P<0.001 for low vs. medium and low vs. high). Bleeding occurred on 25% of the study days on which morning platelet counts were 5000 per cubic millimeter or lower, as compared with 17% of study days on which platelet counts were 6000 to 80,000 per cubic millimeter (P<0.001).
Low doses of platelets administered as a prophylactic transfusion led to a decreased number of platelets transfused per patient but an increased number of transfusions given. At doses between 1.1x10(11) and 4.4x10(11) platelets per square meter, the number of platelets in the prophylactic transfusion had no effect on the incidence of bleeding. (ClinicalTrials.gov number, NCT00128713.)
The threshold for prophylactic platelet transfusions has been classically established at 20,000/microL. In 48 patients with de novo acute myeloblastic leukemia (AML) we analyzed the effect of reducing the threshold for prophylactic platelet transfusion from 20,000/microL (group A) to 10,000/microL (group B) after induction and consolidation chemotherapy.
Forty-eight adult patients with de novo AML diagnosed in a single institution in a nine year period were enrolled in the study. Between January 1989 and December 1993 the patients received prophylactic platelet transfusions when their platelet count was below 20,000/microL (group A), and from January 1994 to March 1998 prophylactic platelet transfusions were indicated below 10,000/microL or between 10,000/microL and 20,000/microL if there was any consumption factor.
The mean number (SD) of platelet transfusions during induction was 8.4 (5.3) in group A and 8.5 (5.5) in group B; and during consolidation 4.7 (3.4) in group A and 4.6 (3.8) in group B (p = n.s.). Excluding the cases with consumption factors from the analysis, group B patients required 34% fewer transfusions during induction and 15.5% fewer during consolidation (p = 0.04). There were no differences between groups regarding major bleeding episodes.
Our data show that the threshold for prophylactic platelet transfusion can be safely set at 10,000 microL during induction and consolidation chemotherapy for adult patients with de novo AML.
An optimal platelet-count threshold for prophylactic platelet transfusion in hematopoietic stem cell transplant (HSCT) recipients has yet to be determined. Between July 1997 and December 1999, we performed the first prospective randomized clinical trial addressing this issue in 159 HSCT recipients who received a prophylactic platelet transfusion when the morning platelet count fell below a 10,000/microL (10K) or 20,000/microL (20K) threshold. Subsequent prophylactic transfusions were administered according to a predetermined algorithm. The number of prophylactic and therapeutic transfusions and the incidence of minor and major bleeding were compared between the 2 groups. The groups were matched according to patient and transplantation characteristics. There were no significant differences in bleeding incidence or severity. Fourteen percent of patients in the 10K arm compared to 17% in the 20K arm had major bleeding events. Only 3 central nervous system bleeds occurred, 2 in the 10K group and 1 in the 20K group. No deaths were attributed to bleeding. An average of 11.4 days of bleeding occurred in both groups. An average of 10.4 platelet transfusions per patient were administered in the 10K group compared to 10.2 in the 20K group (P = .94). More transfusions were given above the assigned transfusion threshold in the 10K group than in the 20K group (4.3/patient versus 1.9/patient, respectively, P = .05). Safety measures incorporated into our study may have precluded demonstration of significant differences in platelet use between the groups. In conclusion, a platelet transfusion trigger of 10K was found to be safe; however, a decrease in platelet use was not achieved because of safety measures incorporated into our study design.
We report a transfusion trial of platelets photochemically treated for pathogen inactivation using the synthetic psoralen amotosalen HCl. Patients with thrombocytopenia were randomly assigned to receive either photochemically treated (PCT) or conventional (control) platelets for up to 28 days. The primary end point was the proportion of patients with World Health Organization (WHO) grade 2 bleeding during the period of platelet support. A total of 645 patients (318 PCT and 327 control) were evaluated. The primary end point, the incidence of grade 2 bleeding (58.5% PCT versus 57.5% control), and the secondary end point, the incidence of grade 3 or 4 bleeding (4.1% PCT versus 6.1% control), were equivalent between the 2 groups (P =.001 by noninferiority). The mean 1-hour posttransfusion platelet corrected count increment (CCI) (11.1 x 10(3) PCT versus 16.0 x 10(3) control), average number of days to next platelet transfusion (1.9 PCT versus 2.4 control), and number of platelet transfusions (8.4 PCT versus 6.2 control) were different (P <.001). Transfusion reactions were fewer following PCT platelets (3.0% PCT versus 4.4% control; P =.02). The incidence of grade 2 bleeding was equivalent for PCT and conventional platelets, although posttransfusion platelet count increments and days to next transfusion were decreased for PCT compared with conventional platelets.
Prophylactic platelet transfusions are considered as standard in most hematology centers, but there is a long-standing controversy as to whether standard prophylactic platelet transfusions are necessary or whether this strategy could be replaced by a therapeutic transfusion strategy. In 106 consecutive cases of patients receiving 140 autologous peripheral blood stem cell transplantations, we used a therapeutic platelet transfusion protocol when patients were in a clinically stable condition. Platelet transfusions were only used when relevant bleeding occurred (more than petechial). Median duration of thrombocytopenia <20 x 10(9)/l and <10 x 10(9)/l was 6 and 3 days, which resulted in a total of 989 and 508 days, respectively. In only 26 out of 140 transplants (19%), we observed clinically relevant bleeding of minor or moderate severity. No severe or life-threatening bleeding was registered. The median and mean number of single donor platelet transfusions was one per transplant (range 0-18). One-third of all transplants, and 47% after high-dose melphalan could be performed without any platelet transfusion. Compared with a historical control group, we could reduce the number of platelet transfusions by one half. This therapeutic platelet transfusion strategy can be performed safely resulting in a considerable reduction in prophylactic platelet transfusions.
Patients with acute myeloid leukemia are at risk of bleeding. The risk factors for different severities of bleeding are poorly studied.
Data from Rebulla et al. were analyzed in an exploratory analysis using multivariate Cox regression analyses for time-to-first bleed with time-depend- ent covariates reflecting measures of clinical and laboratory variables on the previous day. The relationships of the variables with three bleeding categories were studied: mild bleeding (WHO grades 1 and 2) clinically significant (bleeding grades 2, 3 and 4) and severe (bleeding grades 3 and 4).
Bleeding of any severity occurred in 149 (58.4%) of 255 patients. There were 743 days of bleeding over 7335 patient-days of observation. Risk factors for mild bleeding included increased body temperature and decreased platelet count; the risk was decreased with administration of antifungal medication or platelet transfusion on the previous day. Risk factors for clinically significant bleeding included grade 1 bleeding on the previous day, decreased platelet count and elevated body temperature. Decreased platelet count and mild bleeding on the previous day were risk factors for severe bleeding. Higher hemoglobin values were associated with a delay in the time-to-first clinically significant bleed.
These results support clinical guidelines for increasing the platelet transfusion threshold in the presence of fever and support the use of milder bleeding symptoms as an outcome in clinical trials. The suggestion that hemo- globin concentration maybe predictive of bleeding risk supports the hypothesis that this maybe a valuable intervention in anemic thrombocytopenic patients at high risk of bleeding.
We performed a multicenter randomized trial comparing the traditional prophylactic platelet transfusion strategy -arm P- (trigger: morning platelet count ≤ 10/nL) with an experimental therapeutic transfusion strategy -arm T- where patients (pts) received platelet transfusions only if they experienced clinically relevant bleeding (more than petechias or minimal mucosal bleeding). The morning platelet count was no trigger in arm T for transfusion as well as fever per se. Fever was no additional risk factor for bleeding in thrombocytopenic pts treated with our therapeutic transfusion strategy as published recently. (Wandt, H et al. Bone Marrow Transplant2006; 37:387–392) For safety reasons prophylactic transfusion was recommended in arm T, however, for pts with invasive aspergillosis, sepsis syndrome and unexpected headache. Randomisation was stratified according to age (<50 years), sex and center. Different diagnoses (multiple myeloma, non Hodgkin’s lymphoma, Hodgkin’s disease, acute leukemia) were well balanced between both arms. One hundred seventy one consecutive pts with a median of 56 years (19–68) who signed informed consent were included in the study. Primary objective was a reduction of platelet transfusions of 15–25%; secondary objectives were safety, duration of leuko- and thrombocytopenia, hospitalisation, and numbers of red blood cell transfusion. Red blood cells should be transfused when hemoglobin level dropped below 8 g/dL or as clinically indicated.
Results: Platelet transfusions could be reduced significantly by 27% in arm T compared with arm P (p0.004). In arm T 46% of pts did not need any platelet transfusion and this was more than the double compared to arm P (0.001). Between younger and older pts there was no difference in numbers of platelet transfusions needed. Overall, adherence to the protocol was good. Since clinically relevant bleeding (more than petechias and minimal mucosal bleeding) was the trigger for platelet transfusion in arm T consequently more such hemorrhages occured in arm T (28.7% vs 9.5%). No life threatening or fatal bleeding was registered. Hemorrhages were mainly (21.8%) epistaxis or mucosal, 6.9% were minor bleedings (e.g. vaginal, hematochezia, hemoptysis, hematuria). One pt with sudden headache had a minor cerebral hemorrhage (subarachnoid) documented by ct-scan without any clinical sequelae. Days with hemorrhage overall were rare but significantly increased in arm T (0.69 vs 0.17 days per pt). Age was no risk factor for bleeding. As already expected by our former experience we could show that fever and infection were no additional risk factor for bleeding in arm T compared with arm P despite the very stringent platelet transfusion strategy in the experimental transfusion arm. In pts with multiple myeloma bleeding events were very rare compared to other diagnoses (p <0.0001). Numbers of red blood cell units were not significantly different between the two arms, as well as the duration of leukocytopenia and hospitalisation. In contrast duration of thrombocytopenia <20/nL was significantly longer in arm T (median 5 vs 3 days; p 0.004) as expected.
We conclude that our therapeutic platelet transfusion strategy is cost effective and safe in pts after autologous stem cell transplantation. Despite more minor hemorrhages in the experimental arm compared with the traditional prophylactic strategy all bleeding events could be safely controlled by consecutive platelet transfusion. Development of major bleeding could be prevented by the therapeutic transfusion strategy according to our protocol.
In 105 consecutive patients with de novo acute myeloid leukemia (French-American-British M3 excluded), we compared prospectively the risk of bleeding complications, the number of platelet and red blood cell transfusions administered, and the costs of transfusions using two different prophylactic platelet transfusion protocols. Two hundred sixteen cycles of induction or consolidation chemotherapy and 3,843 days of thrombocytopenia less than 25 × 109/L were evaluated. At the start of the study, each of the 17 participating centers decided whether they would use a 10 × 109/L prophylactic platelet transfusion trigger (group A/8 centers) or a 20 × 109/L trigger (group B/9 centers). Bleeding complications (World Health Organization grade 2-4) during treatment cycles were comparable in the two groups: 20 of 110 (18%) in group A and 18 of 106 (17%) in group B (P = .8). Serious bleeding events (grade 3-4) were generally not related to the patient's platelet count but were the consequence of local lesions and plasma coagulation factor deficiencies due to sepsis. Eighty-six percent of the serious bleeding episodes occurred during induction chemotherapy. No patient died of a bleeding complication. There were no significant differences in the number of red blood cell transfusions administered between the two groups, but there were significant differences in the number of platelet transfusions administered per treatment cycle: pooled random donor platelet concentrates averaged 15.4 versus 25.4 (P < .01) and apheresis platelets averaged 3.0 versus 4.8 (P < .05) for group A versus group B, respectively. This resulted in the cost of platelet therapy being one third lower in group A compared with group B without any associated increase in bleeding risk.
OBJECTIVE: To determine the most effective, evidence-based approach to the use of platelet transfusions in patients with cancer.
OUTCOMES: Outcomes of interest included prevention of morbidity and mortality from hemorrhage, effects on survival, quality of life, toxicity reduction, and cost-effectiveness.
EVIDENCE: A complete MedLine search was performed of the past 20 years of the medical literature. Keywords included platelet transfusion, alloimmunization, hemorrhage, threshold and thrombocytopenia. The search was broadened by articles from the bibliographies of selected articles.
VALUES: Levels of evidence and guideline grades were rated by a standard process. More weight was given to studies that tested a hypothesis directly related to one of the primary outcomes in a randomized design.
BENEFITS/HARMS/COST: The possible consequences of different approaches to the use of platelet transfusion were considered in evaluating a preference for one or another technique producing similar outcomes. Cost alone was not a determining factor.
RECOMMENDATIONS: Appendix A summarizes the recommendations concerning the choice of particular platelet preparations, the use of prophylactic platelet transfusions, indications for transfusion in selected clinical situations, and the diagnosis, prevention, and management of refractoriness to platelet transfusion.
VALIDATION: Five outside reviewers, the ASCO Health Services Research Committee, and the ASCO Board reviewed this document.
SPONSOR: American Society of Clinical Oncology
BACKGROUND: Prophylactic platelet transfusions are given to thrombocytopenic patients to prevent bleeding. The benefit of platelet transfusions has frequently been assessed by measuring the count increment; however, more recently, an assessment of bleeding has been used because it is a more clinically relevant outcome measure. The purpose of this study was to identify platelet transfusion trigger studies that used bleeding as an outcome measure, compare and contrast methods used to document bleeding and analyze bleeding outcomes, and identify and discuss methodologic issues to consider when bleeding is used as a study outcome.
STUDY DESIGN AND METHODS: A systematic search to identify platelet transfusion trigger studies was performed. Relevant articles were reviewed to identify how bleeding data was captured and analyzed, and methodologic considerations were identified.
RESULTS: Seven articles meeting the predefined entry criteria were identified. Methods used to document bleeding included chart review and clinical assessment. The frequency of assessment and the type of personnel performing the assessment were variable. Four approaches to analysis were identified: descriptive; comparison of the proportions of patients having at least one bleed; comparison of patient days with bleeding expressed as a proportion of the total days at risk of bleeding; and time-to-event (first bleed) analysis.
CONCLUSION: Methodologic issues for consideration when designing a clinical study with bleeding as the outcome measure included approaches to minimize bias in the documentation and classification of bleeding and selection of an analysis approach that is appropriate to the question being asked. The need for development of a valid and reliable bleeding scale was also identified.
In 105 consecutive patients with de novo acute myeloid leukemia (French-American-British M3 excluded), we compared prospectively the risk of bleeding complications, the number of platelet and red blood cell transfusions administered, and the costs of transfusions using two different prophylactic platelet transfusion protocols. Two hundred sixteen cycles of induction or consolidation chemotherapy and 3,843 days of thrombocytopenia less than 25 x 10(9)/L were evaluated. At the start of the study, each of the 17 participating centers decided whether they would use a 10 x 10(9)/L prophylactic platelet transfusion trigger (group A/8 centers) or a 20 x 10(9)/L trigger (group B/9 centers). Bleeding complications (World Health Organization grade 2-4) during treatment cycles were comparable in the two groups: 20 of 110 (18%) in group A and 18 of 106 (17%) in group B (P = .8). Serious bleeding events (grade 3-4) were generally not related to the patient's platelet count but were the consequence of local lesions and plasma coagulation factor deficiencies due to sepsis. Eighty-six percent of the serious bleeding episodes occurred during induction chemotherapy. No patient died of a bleeding complication. There were no significant differences in the number of red blood cell transfusions administered between the two groups, but there were significant differences in the number of platelet transfusions administered per treatment cycle: pooled random donor platelet concentrates averaged 15.4 versus 25.4 (P < .01) and apheresis platelets averaged 3.0 versus 4.8 (P < .05) for group A versus group B, respectively. This resulted in the cost of platelet therapy being one third lower in group A compared with group B without any associated increase in bleeding risk.
Although considerable advances have been made in many aspects of platelet transfusion therapy in the last 30 years, some areas continue to provoke debate, including the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding in patients with bone marrow failure. We have designed a randomized controlled trial to compare prophylactic platelet use with a threshold of a platelet count of 10 x 10(9)/L with no prophylaxis in adult thrombocytopenic patients with hematologic malignancies. The trial question is whether a no-prophylactic policy for the use of platelet transfusions in patients with hematologic malignancies is not inferior to a threshold prophylactic policy at 10 x 10(9)/L, for bleeding at World Health Organization (WHO) grade 2, 3, or 4, up to 30 days from randomization. The primary outcome measure is the proportion of patients who have a significant clinical bleed, defined as WHO grade 2 or higher up to 30 days from randomization. Subsidiary clinical outcome measures include time to first bleed and a descriptive analysis of all severe bleeds. A bleeding assessment form is completed daily for all study subjects until day 30 from randomization. Minor modifications were made to the definitions at WHO grades 1 and 2 for petechiae and duration of nose bleeds, after piloting of the bleeding assessment forms. This study has been designed as a 2-stage randomized trial with an interim analysis planned after a minimum of 100 patients had been randomized and had completed their period of observation. Patients have initially been enrolled through 3 United Kingdom hematology centers. The interim analysis has been completed, and the results have confirmed a final sample size of 600 patients. Recruitment is now being extended to other centers in United Kingdom and Australia. Local research nurses are not blinded to treatment allocation, but a number of measures to reduce risk of assessment bias include repeated education around standard operating procedures, common definitions, and duplication of assessments. The expected completion date for the 5-year study is December 2011.
The prescribing of inappropriate platelet (PLT) transfusions is always a significant problem. A computerized transfusion decision support system (CTDSS) has been used in Kaohsiung Medical University Hospital since September 2004. In this study, the physician compliance and appropriateness of PLT usage after using the CTDSS were investigated.
A total of 5887 PLT transfusion episodes between January and December 2008 were reviewed including the demographic data and the "true reason" for each transfusion practice. The pre- and posttransfusion PLT counts were retrieved. The physician compliance, the appropriateness of PLT usage, and the PLT increments after transfusion were investigated.
Physician compliance was 85.4%, and the appropriateness of PLT usage was 69.6%. The most commonly chosen indication from the CTDSS was "prophylactic use, PLT count ≤20×10(9) /L." The highest inappropriate order rate was from the emergency department. More than half of the inappropriate episodes were from the surgery unit. The inappropriate rates were significant in terms of both different order sources and functional units (p<0.0001). The posttransfusion PLT counts increased in two-thirds of the episodes, and most of them were with the pretransfusion PLT counts of less than 50×10(9) /L.
In Taiwan, the PLT concentration is too low-priced and this might cause the overuse of blood components. Under the global budget of National Health Insurance, preventing the overuse of blood components might serve as one of the mechanism to improve medical quality. The CTDSS should be more powerful and effective to intervene in the appropriateness of transfusion practice.
Early studies suggested that the risk of haemorrhagic complications become unacceptable when platelet counts drop below 20 x 10(9)/l. Because there are insufficient data to define 20 x 10(9)/l as the threshold for prophylactic platelet transfusions, the practicability of a more restrictive transfusion policy has been assessed prospectively in 102 consecutive patients being treated for acute leukaemia. Besides platelet count, the transfusion protocol took into consideration factors such as presence of bleeding, fever, coagulation disorders, and intention to do therapeutic procedures. 31 major bleeding episodes occurred on 1.9% of the study days when platelet counts were 10 x 10(9)/l or less and on 0.07% of study days when counts were 10-20 x 10(9)/l. The findings indicate that the threshold for prophylactic transfusions can safely be set at 5 x 10(9)/l in patients without fever or bleeding manifestations and at 10 x 10(9)/l in patients with such signs. For patients with coagulation disorders or anatomical lesions, or for those on heparin, the threshold should be at least 20 x 10(9)/l. Such a restrictive platelet transfusion policy, which is applicable not only to thrombocytopenia associated with acute leukaemia but also to other forms of hypoproliferative thrombocytopenia, reduces exposure of such patients to blood donors and results in substantial health-care savings.
On the initiative of the World Health Organization, two meetings on the Standardization of Reporting Results of Cancer Treatment have been held with representatives and members of several organizations. Recommendations have been developed for standardized approaches to the recording of baseline data relating to the patient, the tumor, laboratory and radiologic data, the reporting of treatment, grading of acute and subacute toxicity, reporting of response, recurrence and disease-free interval, and reporting results of therapy. These recommendations, already endorsed by a number of organizations, are proposed for international acceptance and use to make it possible for investigators to compare validly their results with those of others.
The threshold for prophylactic platelet transfusion remains controversial. Usually the decision is based on arbitrary numerical criteria. The classical 20 x 10(9)/l trigger could be safely reduced with considerable benefits. Few studies have evaluated the clinical impact of stringent policies. We have performed a retrospective analysis comparing major haemorrhages during hospitalization in 190 patients undergoing BMT in two different periods. In 87 patients transplanted from 1990 to 1991, the 20 x 10(9)/l trigger was used for prophylactic platelet transfusion. In 103 other patients transplanted from 1993 to 1994, we adopted a stringent prophylactic policy: < 10 x 10(9)/l for stable patients and < 20 x 10(9)/l when higher platelet consumption factors were present. In the stringent group, 12 patients presented 13 major haemorrhages and four died from haemorrhage. In the classical group 12 patients presented 14 major haemorrhages and three died from haemorrhage. Platelet consumption factors were present in 12 of 13 haemorrhages in the stringent group and in 12 of 14 in the classical group. By contrast, stable patients presented less haemorrhages (2/14 and 1/13, respectively). A statistically significant reduction in the use of platelet units was observed when comparing both groups: the median of platelet units administered in the first 100 days of transplant was 73 (3-943) and 54 (0-647) in the classical and in the stringent group, respectively (P < 0.01); and the median of platelet units received per day was 0.8 (0.03-30) and 0.5 (0-6.94) (P < 0.01). Our results emphasize the safety of a stringent prophylactic platelet transfusion policy after BMT, reducing the overall use of platelet transfusions. Further studies are necessary to confirm these results and to define optimal transfusion strategies.
We designed and conducted a randomized single-institution trial comparing two common prophylactic platelet transfusion thresholds in patients undergoing induction therapy for acute leukemia.
Seventy-eight patients undergoing induction therapy for acute leukemia were randomized to receive prophylactic apheresis platelet concentrates when the platelet count was either < or = 10,000/microL or < or = 20,000/microL.
There was no significant difference in the total number of bleeding episodes per patient with a median of four in the < or = 10,000/microL arm and two in the < or = 20,000/microL arm (25th to 75th percentiles of 2, 7 and 1, 5, respectively; P = .12). Patients randomized to the < or = 10,000/microL arm received more platelet transfusions for bleeding [one (0, 2) v zero (0, 0); P = .0003]. In contrast, patients on the < or = 20,000/microL arm received more platelet transfusions for prophylactic indications [10 (5, 14) v six (3, 8); P = 0.001], as would be expected, but less for bleeding. Nevertheless, the total number of platelet transfusions given to patients on the < or = 20,000/microL arm was higher and nearly significant [11 (6, 15) v seven (5, 11); P = .07]. There were no statistically significant differences between the groups with regard to RBC transfusion requirements, febrile days, days hospitalized, days thrombocytopenic, need for HLA-matched platelets, remission rate, or death during induction chemotherapy. No patient in either group died from hemorrhage or underwent major surgery for bleeding complications.
Giving prophylactic platelets at a threshold of < or = 10,000/microL compared with < or = 20,000/microL can decrease the total utilization of platelets with only a small adverse effect on bleeding, and no statistically significant effect on morbidity.
Prophylactic platelet transfusions are usually administered to patients receiving myelotoxic chemotherapy when their platelet count falls below 20,000 per cubic millimeter. Some observations suggest that lower platelet counts can be appropriate in patients in stable condition, but the safety of lower thresholds is uncertain.
We evaluated 255 adolescents and adults (age, 16 to 70 years) with newly diagnosed acute myeloid leukemia (but not acute promyelocytic leukemia), who were treated in 21 centers. One hundred thirty-five patients were randomly assigned to receive a transfusion when their platelet count fell below 10,000 per cubic millimeter (or 10,000 to 20,000 per cubic millimeter in those with a temperature above 38 degrees C, with active bleeding, or a need for invasive procedures), and 120 patients were assigned to receive a transfusion when their platelet count was less than 20,000 per cubic millimeter.
Patients in the group with a threshold of 10,000 platelets per cubic millimeter received 21.5 percent fewer platelet transfusions than the patients in the group with a threshold of 20,000 platelets per cubic millimeter (P=0.001). The numbers of red-cell units transfused were not significantly different between groups. Major bleeding (defined as any bleeding more than petechiae or mucosal or retinal bleeding) occurred in 21.5 and 20 percent of patients, respectively (P=0.41), and on 3.1 and 2.0 percent of the days of hospitalization. One episode of fatal cerebral hemorrhage occurred in the group with a threshold of 10,000 platelets per cubic millimeter; none occurred in the other group (P= 0.95). Actuarial estimates of survival during induction chemotherapy, actuarial estimates of the absence of major bleeding, and the length of hospital stay were not significantly different in the two groups.
The risk of major bleeding during induction chemotherapy in adolescents and adults with acute myeloid leukemia (except acute promyelocytic leukemia, which we did not study) was similar with platelet-transfusion thresholds of 20,000 per cubic millimeter and 10,000 per cubic millimeter (or 10,000 to 20,000 per cubic millimeter when body temperature exceeded 38 degrees C, there was active bleeding, or invasive procedures were needed). Use of the lower threshold reduced platelet use by 21.5 percent.
To determine the most effective, evidence-based approach to the use of platelet transfusions in patients with cancer.
Outcomes of interest included prevention of morbidity and mortality from hemorrhage, effects on survival, quality of life, toxicity reduction, and cost-effectiveness.
A complete MedLine search was performed of the past 20 years of the medical literature. Keywords included platelet transfusion, alloimmunization, hemorrhage, threshold and thrombocytopenia. The search was broadened by articles from the bibliographies of selected articles.
Levels of evidence and guideline grades were rated by a standard process. More weight was given to studies that tested a hypothesis directly related to one of the primary outcomes in a randomized design. BENEFITS/HARMS/COST: The possible consequences of different approaches to the use of platelet transfusion were considered in evaluating a preference for one or another technique producing similar outcomes. Cost alone was not a determining factor.
Appendix A summarizes the recommendations concerning the choice of particular platelet preparations, the use of prophylactic platelet transfusions, indications for transfusion in selected clinical situations, and the diagnosis, prevention, and management of refractoriness to platelet transfusion.
Five outside reviewers, the ASCO Health Services Research Committee, and the ASCO Board reviewed this document.
American Society of Clinical Oncology
The 20 x 10(9) /L threshold for prophylactic platelet transfusion may be unnecessarily high. Few prospective studies, however, in which other trigger values were tested have been published. In this study all hospitalized, thrombocytopenic adult hematology-oncology patients in our institution were prospectively evaluated daily for hemorrhage and platelet transfusion during a one year period; no patients were excluded for bleeding or infectious problems. By design, during the initial six-months (baseline period), the prophylactic platelet transfusion trigger was 20 x 10(9) /L; for the second six-months (study period) this threshold was changed to 10 x 10(9) /L. Patients studied during the two periods did not differ significantly in age, gender, diagnosis, blood or marrow transplant status, and duration of neutropenia. Compliance with the thresholds was 95.6% (baseline period) and 93.5% (study period). For patients with platelet counts under 20 x 10(9) /L, the mean use of platelet transfusions per patient per day was significantly lower in the study period (4.47) than in the baseline period (6.48; p<0.001). Both mean prophylactic (1.54/patient-day) and therapeutic (2.93/patient-day) platelet transfusions were reduced in the study period compared with the baseline period (2.26 and 4.22/patient-day, respectively). Hemorrhage was slightly reduced in the study period compared with the baseline period: major hemorrhage, 15.2% vs. 18.4% (p=0.014); minor hemorrhage, 63.6% vs. 70.1% (p<0.001). Thus, hemorrhage was not increased with the lower trigger level. A 10 x 10(9) /L prophylactic platelet transfusion threshold value is safe and effective.
Platelet transfusion therapy is an integral part of modern oncological practice and is used to treat hemorrhage associated with thrombocytopenia. More commonly, platelets are transfused to prevent hemorrhage in thrombocytopenic patients. Conventional wisdom has suggested a threshold for prophylactic transfusion of <20x10(9)/l. Many studies now support the safety of more conservative transfusion regimes that reduce patient exposure to donors and conserve precious resources, without an increase in risk of hemorrhage. This review presents the data to support the use of a prophylactic transfusion threshold of <10x10(9)/l in patients without risk factors for hemorrhage and who have ready access to emergent medical care.
HEMORRHAGE is a frequent and often major complication in patients with acute leukemia. In addition to thrombocytopenia and its resulting coagulation defects disturbances of the hemostatic mechanism have been described in such patients.1 These include qualitative platelet defects2 3 4 and the presence of a fibrinolytic system and hypofibrinogenemia.5 , 6 Fever, which is presumably due to bacterial infection, has been found to be related to bleeding in patients with acute leukemia.6 , 7 This may result from the anticoagulant effect of bacterial polysaccharide demonstrated in vitro.8 Capillary damage resulting from lysins,9 anoxemia or leukemic infiltration has been postulated.10 Although any or all of these disturbances . . .
Platelets are lost from circulation by 2 mechanisms: senescence and random loss. Approximately 7.1 x 10(3) platelets/microL/d are postulated to be randomly used in maintaining vascular integrity. Thus, in clinically stable patients, major bleeding is unusual unless the platelet count is </=5 x 10(3)/microL. Risk factors for bleeding at higher platelet counts are disseminated intravascular coagulation with contributory clotting factor deficiencies, structural lesions with loss of vascular integrity, and refractoriness to platelet transfusions. Several large studies have documented the safety of lowering the prophylactic platelet transfusion trigger from the previously used 20 x 10(3)/microL to 10 x 10(3)/microL. A few studies have even suggested that a 5 x 10(3)/microL trigger is acceptable. Based on these results, the next step of giving just therapeutic platelet transfusions is being evaluated. In a large retrospective study, the most significant predictor of bleeding was not the patient's platelet count but a history of bleeding in the prior 5 days. These data suggest that attention should be focused on providing aggressive platelet therapy for active bleeding rather than transfusing platelets prophylactically. Therapeutic platelet transfusions have been documented to control bleeding, and mortality rates are not increased when comparing patients receiving therapeutic to that seen in patients receiving prophylactic platelet transfusions.
This review was undertaken to determine the best use of platelet transfusion for the prevention of bleeding (prophylactic platelet transfusion) in patients who have haematological malignancies and are receiving intensive chemotherapy or stem cell transplantation. The review aimed to look at two main topics. One, what is the evidence to indicate if platelet transfusions should be given to prevent bleeding as compared to a strategy aimed at transfusion when bleeding occurs? Second, if platelet transfusions are given to prevent bleeding, when should they be given, for example, at what level of platelet count when measured in a blood sample? The reviewers found that there is uncertainty about the practice of prophylactic transfusion therapy. New studies may be needed to better answer these two questions, particularly in view of concerns about the safety and cost of blood and the scenario that blood products, including platelets, could become an increasingly scarce resource in the future.
The aim of prophylactic platelet transfusions in haemato-oncologic patients with thrombocytopenia is to prevent bleeding. Currently, a platelet transfusion trigger of 10 x 10(9) L(- 1) is considered to be safe. Transfusion compliance with this trigger can save costs. To investigate the compliance with this trigger of 10 x 10(9) L(- 1), we have evaluated 1447 platelet transfusions given during a period of 1 year to haematological patients. In half of the transfusions, there had been compliance with the trigger of 10 x 10(9) L(- 1). About three-quarters of all platelet transfusions were given at platelet counts < or =20 x 10(9) L(- 1). Transfusions at levels >20 x 10(9) L(- 1) were usually performed because of bleeding, scheduled interventions or concurrent anticoagulant therapy. We conclude that compliance with the prophylactic platelet transfusion trigger of 10 x 10(9) L(- 1) was about 50%; however, deviation from the trigger was partly explained by risk factors that justify a higher transfusion trigger.
The impact of lowering the platelet (PLT) count threshold for prophylactic PLT transfusion on bleeding and PLT use in allogeneic hematopoietic progenitor cell (HPC) transplant recipients is a matter of debate.
In 166 patients, randomly assigned to receive prophylactic PLT transfusion at a trigger level less than 10 x 10(9) PLTs per L (T10; n = 79) or less than 30 x 10(9) per L (T30; n = 87), the number of PLT and red blood cell (RBC) transfusions given and the number of hemorrhagic events (WHO Grades 2-4) were recorded.
No significant differences were found between the two groups regarding the clinical outcome variables (i.e., bacteremia, engraftment, graft-vs.-host disease [GVHD], hospital stay, death, and survival) or in the median total number of RBC transfusions given. The incidence, in Group T10 18 percent (14/79) and in Group T30 15 percent (13/87), as well as the type of bleeding were comparable. No deaths were attributed to hemorrhages. The number of PLT units transfused, however, was significantly lower in Group T10 (median, 4; range, 0-32), than in Group T30 (median, 10; range, 0-48; p < 0.001). Apart from the trigger level, the day of engraftment, the presence of acute GVHD, or bacteremia also affected the number of PLT transfusions.
A prophylactic PLT transfusion trigger level of less than 10 x 10(9) PLTs per L instead of less than 30 x 10(9) PLTs per L in allogeneic HPC transplant recipients was found to be safe and resulted in a decreased use of PLTs.
Our 1100-bed referral hospital uses approximately 12,000 units of random-donor platelets (PLTs) and 1,900 units of single-donor apheresis PLTs per year with a mean of 23 percent outdating. An analysis of patterns of utilization has been undertaken to evaluate practice.
Over a 9-month period, data were collected on a total of 1682 transfusion episodes in 464 patients. When the pretransfusion count was greater than 10 x 10(9) per L an attempt was made to identify the specific indications for PLT transfusions such as bleeding.
The majority (78%) of PLTs were transfused when the counts were above 10 x 10(9) per L. The mean pretransfusion counts for different services were: bone marrow transplant (BMT) 17.4 x 10(9) per L, hematology-oncology 14.6 x 10(9) per L, the Heart Institute 3 x 10(9) per L, and other services 36 x 10(9) per L. The percentage of transfusions given to patients with a count greater than 10 x 10(9) per L varied by service with 79 percent in BMT, 60 percent in hematology and oncology, 98 percent at the Heart Institute, and 81 percent in other services. Routine monitoring of counts shows a mean increment of 10.2 x 10(9) per L per transfusion. One hour posttransfusion counts, 24-hour posttransfustion counts, and documentation of clinical justification for transfusions was often not available.
The data show that most patients who receive PLTs have pretransfusion counts of more than 10 x 10(9) per L and more than one-third have pretransfusion counts of greater than 20 x 10(9) per L. The medical literature supports prophylactic PLT transfusion based solely on the count when the PLT number is 10 x 10(9) per L or less. Above this level additional justification is needed although there are different points of view concerning the appropriate triggers. Our data suggest that there is a need for clear hospital transfusion guidelines and ongoing monitoring of PLT use.
Prophylactic platelet (PLT) transfusion practices have become more conservative as studies support a threshold for transfusions at 10 x 10(9) per L. This change in practice may reduce our use of PLT transfusions.
Data were prospectively collected to assess the impact at one academic hospital when the transition from a 20 x 10(9) to a 10 x 10(9) per L threshold prophylactic transfusion was made.
A total of 503 patients received 7401 PLT transfusions. Seventy-four percent of the transfusions were prophylactic. During the first phase of the study, only 53 percent of transfusions were given at a pretransfusion PLT count of less than 20 x 10(9) per L and 20 percent less than 10 x 10(9) per L. In the second phase of the study when the transfusion trigger was 10 x 10(9) per L, 28 percent of transfusions were given at this level.
Many prophylactic PLT transfusions were given at PLT counts higher than the recommended trigger. Although the new transfusion guidelines altered transfusion practice, only a minor change in overall PLT usage was observed. Other changes in transfusion practices, such as dose per transfusion or sampling interval, will be required before significant reduction in the costs and hazards of prophylactic PLT transfusions can be realized.
Prophylactic platelet (PLT) transfusions are given as a standard care in patients with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT). This retrospective analysis evaluates utilization of blood transfusions, risk of bleeding, and survival in 480 HSCT patients at 10 x 10(9) and 20 x 10(9) per L prophylactic trigger levels.
A total of 224 patients received prophylactic PLT transfusions at 20 x 10(9) per L threshold (1997-1998, SP1); 256 patients had prophylaxis at 10 x 10(9) per L (1999-2001, SP2). Bleeding scores were assigned daily.
A slight reduction in PLT transfusions per patient in SP2 compared with SP1 was not statistically significant (odds ratio, 0.82; 95% confidence interval, 0.51-1.33; p = 0.416), yet a significantly higher proportion of patients in SP2 had PLT counts less than or equal to 10 x 10(9) per L compared to SP1 (p < 0.001). In patients who bled, however, there was no excess exposure to low PLT counts before bleeding started. A substantial number of patients who bled received PLT transfusions above the goal before bleeding started (82.9% in SP2, 41.5% in SP1) because of medical complications that associated with increased risk of bleeding. Bleeding incidence was similar in both study periods (21.9% in SP1, 16.4% in SP2; p = 0.526). Bleeding was significantly associated with reduced survival in both study periods.
Patients who bled were usually placed on a higher threshold before the onset of their major bleeding event and were not exposed to additional risk of bleeding from thrombocytopenia. Similarity in bleeding incidence between study periods appears to associate with adjustments to high-risk conditions and may not reflect consequences of the lower transfusion threshold.
A trigger of 10 x 10(9) per L for prophylactic platelet (PLT) transfusions is generally recommended for stable thrombocytopenic patients who receive chemotherapy, based on studies showing similar incidence, severity, and fatality of bleeding compared with the 20 x 10(9) per L trigger. The outcome of thrombocytopenic nonbleeding patients has not been well described. This retrospective analysis evaluates thrombocytopenia and survival of 381 hematopoietic stem cell transplant (HSCT) patients without clinically significant bleeding, with 10 x 10(9) and 20 x 10(9) per L prophylactic triggers.
A total of 170 patients who received prophylactic PLT transfusions at 20 x 10(9) per L (1997-1998, SP1) and 211 patients who had prophylaxis at 10 x 10(9) per L (1999-2001, SP2) were identified as nonbleeding patients. PLT counts and clinical complications were assessed within 100 days from HSCT.
PLT counts less than or equal to 10 x 10(9) per L were found in 69.2 percent of patients in SP2 and 38.3 percent in SP1 (p < 0.001). Profound thrombocytopenia (4+ PLT counts <or=10 x 10(9)/L) was found in 19.0 percent of patients in SP2 and 7.0 percent in SP1 (p = 0.001). Patients with profound thrombocytopenia had significantly increased early mortality (odds ratio [OR], 3.18; 95% confidence interval [CI], 1.25-8.07) and significantly reduced overall survival (hazard ratio [HR], 1.95; 95% CI, 1.28-2.97) compared to patients with 0 to 3 PLT counts less than or equal to 10 x 10(9) per L. The association of profound thrombocytopenia with early mortality was more notable in SP2.
The 10 x 10(9) per L transfusion trigger is associated with significantly greater exposure to low PLT counts. Nonbleeding patients with profound thrombocytopenia were at significantly greater risk of dying compared with nonthrombocytopenic patients. These results suggest that safety of the 10 x 10(9) per L trigger should be more thoroughly evaluated.
Time to rethink clini-2007
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Reporting results of cancer treatment
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Blood transfusion task force. Guidelines for the use of platelet transfusions
- British Committee for Standards in Haematology