Platelet transfusion prophylaxis for patients with haematological malignancies: where to now?

National guidelines for platelet transfusion in many countries recommend that the general platelet transfusion trigger for prophylaxis is 10x10(9)/l. This annotation reviews the evidence for this threshold level and discusses other current unresolved issues relevant to platelet transfusion practice such as the optimal dose and the clinical benefit of a strategy for the prophylactic use of platelet transfusions when the platelet count falls below a given threshold.     

Platelet transfusion requirements of children with newly diagnosed lymphoblastic leukaemia.

The platelet transfusion requirements of 70 unselected children with lymphoblastic leukaemia were studied from the time of diagnosis to the achievement of complete remission, or to death if no remission was obtained. Platelets were not transfused unless clinically significant bleeding occurred in association with a platelet count of less than 20.0 x 10(9)/l, and on this basis only 31 transfusions were given to 11 (15%) patients for 17 episodes of apparent or presumed bleeding. No deaths occurred due to haemorrhage, and 67 (95%) patients achieved complete remission. These findings suggest that such children do not need prophylactic platelet transfusions, which are commonly given despite their inherent risks and sequelae.     

Thrombocytopenia Following Routine Blood Transfusion: Micro-Aggregate Blood Filters Prevent Worsening Thrombocytopenia in Patients with Low Platelet Counts

11 patients with anaemia and thrombocytopenia due to bone marrow failure each received 2 sets of red-cell transfusions. They were randomised to receive 1 blood transfusion through a standard 170-micron giving set filter and another through a 40 micron micro-aggregate filter. After transfusion, the mean fall in platelet count was 15 x 10(9)/l (41.7%) and 1.4 x 10(9)/l (4.6%), respectively (p less than 0.01). The results confirm the findings of a previous study which showed that micro-aggregate filters prevent a post-transfusional decrease in platelet counts. In addition, this new study shows that this is clinically relevant in patients who are thrombocytopenic at the time of their blood transfusion.     

Radiation recall following cisplatin chemotherapy

The decision to transfuse a neonate can be approached by addressing a series of questions that cover the cause of anaemia, alternatives to transfusion, the need for transfusion and the risks. Recent clinical trials of red cell transfusions have started to inform evidence‐based transfusion practice, but have raised uncertainties about neurological outcomes when policies advocating use of fewer red cell transfusions at lower haemoglobin concentration (Hb) thresholds were tested. Red cell transfusions should be considered when the Hb <120 g/l for premature neonates requiring mechanical ventilation support, with lower thresholds applying for oxygen‐dependent neonates not requiring ventilation or for late anaemia (Hb <70–100 g/l, depending on gestational and post‐natal age). There is no recent high quality evidence to inform thresholds for prophylactic platelet transfusions in stable non‐bleeding premature neonates with platelet count levels of 50 × 10⁹/l, although common practice has become more restrictive, using lower safe thresholds for platelet transfusion between 20 and 30 × 10⁹/l. A more appropriate transfusion strategy for fresh frozen plasma (FFP) in neonates is one that emphasizes the therapeutic use of FFP in the face of bleeding, rather than prophylactic use in stable non‐bleeding neonates who often have mild to moderate apparent abnormalities of standard coagulation tests, after allowing for appropriate reference ranges.     

Immunoplatelet counting: potential for reducing the use of platelet transfusions through more accurate platelet counting

Research is required to determine the optimal approach for prophylactic platelet transfusions in patients with haematological malignant disorders. It has been suggested that thresholds for prophylactic platelet transfusions of platelet counts below 10 x 109/l should be investigated, as these may be equivalent in clinical effectiveness and associated with lower costs and fewer complications. An important concern in such investigation is the accurate estimation of platelet counts below 10 x 109/l. This study aimed to further examine the potential reduction in platelet usage that could be made if a lowered platelet transfusion threshold of 5 x 109/l was used in conjunction with an immunoplatelet counting method. Clinical and laboratory data from 130 haematology patients were used. Standard platelet counting was performed using Bayer H3 and ABX Argos analysers. Immunoplatelet counting was performed by flow cytometry using anti-CD61. The potential for reducing platelet transfusions included consideration of clinical criteria that influence prophylactic platelet transfusion use. The results indicated that the use of an immunoplatelet count with a 5 x 109/l platelet transfusion threshold would potentially reduce the number of transfusions by 10.4% in comparison with a 10 x 109/l threshold and standard automated platelet counting with the ABX Argos analyser, and increase the number of transfusions by 5.4% in comparison with the same threshold using the Bayer H3 analyser. The immunoplatelet count may aid the clinical decision to transfuse platelets, but would not necessarily lead to a reduced use of platelet transfusions.     

The frequency of bleeding complications in patients with haematological malignancy following the introduction of a stringent prophylactic platelet transfusion policy

Indications for platelet transfusion remain controversial and are frequently based on arbitrary numerical criteria. In October 2000, we introduced a stringent prophylactic-platelet transfusion policy < 10 x 109/l for stable patients and < 20 x 10(9)/l in the presence of major bleeding or additional risk factors. A trigger of < 50 x 10(9)/l was introduced for patients undergoing invasive procedures. A prospective analysis was performed measuring the frequency of minor and major bleeding events, morbidity, mortality and duration of pancytopenia. Blood product usage was assessed and health care savings measured. A total of 98 patients were evaluated on 2147 patient study days and 271 bleeding episodes were recorded. Major bleeding occurred on 1.39% (30/2147) of the study days when platelet counts were < 10 x 10(9)/l and 2.3% (50/2147) of the study days when platelet counts were 10-20 x 10(9)/l. In patients with platelets > 20 x 10(9)/l, there were 117 major bleeding episodes observed on 5.4% of the study days. In patients with no identified additional risk factors present, major haemorrhages were recorded in 0.51% (11/2147) of the study days in patients with platelet counts > or = 10 x 10(9)/l . There was a 36% reduction in platelet units transfused compared with retrospective data when an arbitrary transfusion trigger of 20 x 10(9)/l was in place (P = < 0.02). Of note, a 16% reduction in red cell transfusions was recorded. These data confirm that the introduction of a transfusion trigger of < 10 x 10(9)/l in the absence of fresh bleeding and sepsis (> 38 degrees C) is safe and has a significant impact on overall hospital transfusion costs.     

Efficacy of prophylactic transfusions using single donor apheresis platelets versus pooled platelet concentrates in AML/MDS patients receiving allogeneic hematopoietic stem cell transplantation

Superiority of single-donor apheresis platelets (SDAP) over pooled platelet concentrates (PPC) transfusions is largely assumed, but unproven. We hypothesized that prophylactic SDAP and PPC transfusions are clinically equivalent after allogeneic hematopoietic stem cell transplants (HSCT). We studied all transfusions administered to 33 patients with AML/MDS during the first 100 days after busulfan-based, myeloablative HSCT. All donor-recipient pairs were ABO identical. Transfusion threshold was a platelet count < or =15 x 10(9)/l. The corrected increment (CCI) was used for all comparisons. Median time to platelet engraftment was 13 days (n=30). PPC transfusions (n=105) were ABO compatible, while 10% of 41 SDAP were not (P=0.006). Median post-transfusion platelet count was 51K/microl (5-118K) after SDAP and 36K/microl (3-115K) after PPC (P=0.0004). Median CCI was 14.178 (SDAP) versus 7.793 (PPC) (P=0.0001). Median time to another transfusion was 3 days (SDAP) and 2 days (PPC; P=0.3). In the week following any given transfusion, the median number of new transfusions was similar (n=2), as well as the need of further transfusion (16 versus 24%, P=0.2). A total of 17% of SDAP and 30% of PPC transfusions were labeled 'ineffective' (P=0.1). There were two non-lethal hemorrhage episodes (6%). SDAP transfusions produced better platelet counts, but SDAP and PPC were equally effective in preventing hemorrhage.     

Current practice and future directions for optimization of platelet transfusions in patients with severe therapy-induced cytopenia

Platelet transfusions are mainly used for patients with thrombocytopenia due to bone marrow failure, especially cancer patients developing severe chemotherapy-induced thrombocytopenia (e.g. patients with acute leukemia or other hematologic malignancies). A prophylactic transfusion strategy is now generally accepted in developed countries. Some clinical data, however, support the use of a therapeutic transfusion strategy at least for certain subsets of these patients. Several methodological approaches can then be used to evaluate the outcome of platelet transfusions, including peripheral blood platelet increments and bleeding assessments. Several factors will influence the efficiency of platelet transfusions; fever and ongoing hemorrhage are among the most important patient-dependent factors, but the number and quality of the transfused platelets are also important. The quality of transfused platelets can be evaluated by analyzing platelet activation, metabolism or senescence/apoptosis. Only evaluation of metabolism is included in international guidelines, but high-throughput methods for evaluation of activation and senescence/apoptosis are available and should be incorporated into routine clinical practice if future studies demonstrate that they reflect clinically relevant platelet characteristics. Finally, platelet transfusions have additional biological effects that may cause immunomodulation or altered angioregulation; at present it is not known whether these effects will influence the long-time prognosis of cancer patients. Thus, several questions with regard to the optimal use of platelet transfusions in cancer patients still need to be answered.     

The efficiency of transfusing high doses of platelets in hematologic patients with thrombocytopenia: results of a prospective, randomized, open, blinded end point (PROBE) study

We performed a prospective, randomized, open, blinded end point (PROBE) study to assess the efficiency of transfusing high doses of platelets in patients with thrombocytopenia, either acute leukemia (AL) or those undergoing autologous hematopoietic stem cell transplantation (AT). Patients were randomly assigned to receive transfusions with a target dose of 0.5 x 10(11)/10 kg (arm A) or 1 x 10(11)/10 kg (arm B). A total of 101 patients were included, of whom 96 were given at least one transfusion. The median time between the first transfusion and when the platelet count reached at least 20 x 10(9)/L increased from 63 hours to 95 hours in the arm B group (P = .001), and the median number of transfusions was lower in this group (2; P = .037). The total number of transfused platelets did not differ between groups (14.9 x 10(11) for arm A versus 18.5 x 10(11) for arm B; P = .156). In such patients, a prophylactic strategy of high doses of platelets could improve platelet transfusion efficiency.     

An audit of the use of platelet concentrates in the prophylaxis of thrombocytopenic haemorrhage in a large haematology unit.

Platelet transfusions are valuable in the prevention of thrombocytopenic bleeding in patients undergoing chemotherapy for haematological malignancies. The commonly used threshold platelet count for transfusion of 20 x 10(9)/l was established in the 1960s when the clinical situation was very different from today. Review of the use of platelet concentrates in a large haematology unit showed lack of adherence to this threshold with the use of platelet transfusions at higher platelet counts. Major bleeding episodes occurred at counts above the threshold when additional clinical factors were operating. A lower threshold was therefore recommended and instituted. This resulted in a 20% reduction in the use of platelet concentrates with no increase in major bleeding episodes.     

Assessment of thrombocytopenic disorders using the Platelet Function Analyzer (PFA-100)

The Platelet Function Analyzer (PFA-100) was used to measure platelet function in paediatric patients with destructive versus underproduction thrombocytopenia. Closure time (CT) and total volume (TV) measurements with standard 150 microm apertures discriminated between patients with similar platelet counts from 30 to 150 x 10(9)/l. However, at platelet counts < 30 x 10(9)/l, a 100-microm aperture (experimental) gave the best assessment of platelet function. TV results could be analysed even when CTs were indeterminate. Further investigations are warranted to more fully understand the relationships among platelet function as measured by the PFA-100 in standard/experimental modes, bleeding and transfusion outcome in thrombocytopenia.     

Acute bleeding and thrombocytopenia after bone marrow transplantation

The relationship between hemorrhage and low platelet count was first established in patients with acute leukemia, and has been widely applied to thrombocytopenic patients, including BMT patients. Yet, the role of thrombocytopenia in bleeding post BMT has not been systematically studied. We evaluated the risk of bleeding and outcome associated with thrombocytopenia in BMT patients who had prophylactic platelet transfusions at a trigger of 20 x 10(9)/l. Thrombocytopenia was investigated in 321 patients with moderate or severe bleeding (BLD), and in a matched comparison group of 287 patients who did not bleed (NBLD). Profound thrombocytopenia (< or = 10 x 10(9)/l) was found in 8.6% of the BLD patients during the week before the bleeding onset, significantly more frequent than in NBLD patients (2.1% to 4%, P < 0.02), during weeks 2 to 6 post BMT (the period when 75% of the bleeding initiated). On the first day of bleeding, platelet counts < or = 10 x 10(9)/l were found in 13.5%, 11-20 x 10(9)/l in 20.4%, and > 20 x 10(9)/l in 66.1% of all episodes. Overall survival in BLD patients was not associated with the severity of thrombocytopenia before bleeding onset. Severity of thrombocytopenia was significantly associated with reduced survival in NBLD patients. We concluded that bleeding post BMT was significantly associated with thrombocytopenia, but the attributable risk of bleeding from profound thrombocytopenia was not large. Thrombocytopenia may be an important clinical sign in NBLD patients, and should be further explored in relation to acute toxicities other than bleeding.     

Acute bleeding complications in patients after bone marrow transplantation

Acute bleeding is a frequent complication that commonly associates with increased morbidity after bone marrow transplantation. Except for diffuse alveolar hemorrhage and cerebral hemorrhage, bleeding is infrequently recorded as a direct cause of death. Yet outcome analyses showed that bleeding from any reviewed site was associated with reduced survival. Reduced survival was correlated with bleeding intensity and the number of bleeding sites. These data point to the need to monitor all manifestations of bleeding, as bleeding may identify patients at risk for bone marrow transplantation toxicity. Until recently, prophylactic platelet transfusions were commonly given at a trigger of 20 x 10(9)/L. Whereas bleeding is more likely to occur when platelet counts drop to low levels, most bleeding episodes were recorded with platelet counts greater than 20 x 10(9)/L, suggesting causes other than profound thrombocytopenia in the pathogenesis of bleeding. Given that a trigger of 10 x 10(9)/L has become accepted for prophylactic platelet transfusions, care should be taken to ensure that parameters other than the incidence of bleeding have not been adversely affected.     

Survey on the threshold for platelet transfusions

We carried out a survey on platelet transfusions performed in nine general hospitals. We evaluated 303 adults who received a total of 24455 units over 1864 platelet transfusions. The underlying diseases were hematologic disorders with chemotherapy (59.7%), hematologic disorders without chemotherapy (15.5%), hematopoietic stem cell transplantation (18.5%), and others (2.0%). The patient platelet count before transfusion (platelet trigger value) was measured in only 77.1%. The platelet trigger value differed greatly between the hospitals, with an average of 2.2 x 10(4)/microl, a minimum of 1.3 x 10(4)/microl, and maximum of 3.2 x 10(4)/microl. Only 55.3% of the platelet transfusions carried out complied with the Platelet Transfusion Guideline published by the Ministry of Health, Labour and Welfare. The hospitals surveyed could be divided into those who gave mainly around 10 units and those who gave over 10 units. The total dose of platelets transfused was more in the hospitals that used mainly 15 or more unit-PCs than in the hospitals that used mainly 10 unit-PCs. These results indicate that platelet transfusion may be greatly reduced by complying with the 2 x 10(4)/microl of platelet transfusion threshold and by selecting less than 10 units of PC per transfusion.     

The impact of platelet transfusion characteristics on posttransfusion platelet increments and clinical bleeding in patients with hypoproliferative thrombocytopenia

Platelet characteristics, such as platelet dose, platelet source (apheresis vs pooled), platelet donor-recipient ABO compatibility, and duration of platelet storage, can affect posttransfusion platelet increments, but it is unclear whether these factors impact platelet transfusion efficacy on clinical bleeding. We performed secondary analyses of platelet transfusions given in the prospective randomized Platelet Dose Study, which included 1272 platelet-transfused hematology-oncology patients who received 6031 prophylactic platelet transfusions. The primary outcome of these analyses was time from first transfusion to first World Health Organization ≥ grade 2 bleeding. Platelet transfusion increments were assessed at 0.25 to 4 hours and 16 to 32 hours after platelet transfusion. There were 778 patients evaluable for analysis of time to bleeding. Adjusted models showed that randomized dose strategy, platelet source, ABO compatibility, and duration of storage did not predict this outcome. Platelet increments were generally higher for transfusions of apheresis platelets, ABO-identical platelets, and platelets stored 3 days versus 4 to 5 days. Thus, although platelet source, ABO compatibility, and duration of storage exert a modest impact on both absolute and corrected posttransfusion platelet increments, they have no measurable impact on prevention of clinical bleeding. This trial was registered at www.clinicaltrials.gov as #NCT00128713.     

The rational use of platelet transfusions in children

Platelet transfusions are undoubtedly effective in securing hemostasis in bleeding children with absent or nonfunctioning platelets. They are, however, abused in some circumstances and are not without risk. The use of platelet transfusions to prevent rather than to treat bleeding in children with malignant disease has increased several times over the last two decades. When joining in this widespread practice, physicians should be aware that there is a relatively unimpressive evidence base supporting it and also that for patients with uncomplicated myelo-suppression the most persuasive studies suggest that a threshold platelet count of 10 x 10(9)/L is no less effective than the more customary 20 x 10(9)/L is. Still lower thresholds await evaluation. For children with nonmalignant conditions the use of platelet transfusions should be carefully evaluated on a case-by-case basis, but they should normally be avoided in the absence of clinically important bleeding. Neonates with thrombocytopenia, particularly those with immune disease due to a maternal alloantibody, are considered an exception to this generalization. The serious hazards of platelet transfusions include alloimmunization and the induction of refractoriness, graft-versus-host (GVH) disease, and the transmission of infection, all of which can be life threatening. Less risky alternative therapeutic approaches may become more widely available in the future, including recombinant thrombopoietin and lyophilized heat-treated platelet membrane preparations.     

A restrictive platelet transfusion policy allowing long-term support of outpatients with severe aplastic anemia

The threshold for prophylactic platelet transfusions in patients with hypoplastic thrombopenia generally recommended in the standard literature is 20,000 platelets/microL. A more restrictive transfusion policy may be indicated in patients with chronic severe aplastic anemia (SAA) in need of long-term platelet support. We evaluated the feasibility and safety of a policy with low thresholds for prophylactic transfusions (相似文献   

Hematopoietic stem cell allografts using a non-myeloablative conditioning regimen can be safely performed on an outpatient basis: report of four cases

Using a non-myeloablative, immunosuppressive, fludarabine-based conditioning regimen, we performed allogeneic peripheral blood stem cell transplants totally on an outpatient basis in four patients (two with chronic myelogenous leukemia, one with acute myelogenous leukemia and one with thalassemia major). The median granulocyte recovery time to 0.5 x 109/l was 10 days and the lowest absolute neutrophil count was 0.064 x 109/l; only one patient developed thrombocytopenia below 20 x 109/l. No patient required red blood cell transfusions and one was given a single prophylactic platelet transfusion. All patients are alive at 210-390 (median 285) days and have definite evidence of chimerism; one developed biopsy-proven GVHD on day 50, with a limited cutaneous rash. The procedure is less costly than its counterpart using myeloablative conditioning regimens and may represent another approach in the management of patients requiring an allogeneic stem cell transplant. Bone Marrow Transplantation (2000) 25, 131-133.     

Accuracy of platelet counting haematology analysers in severe thrombocytopenia and potential impact on platelet transfusion

Although haematology analysers provide reliable full blood counts, they are known to be inaccurate at enumerating platelets in severe thrombocytopenia. If the thresholds for platelet transfusion, currently set at 10 x 10(9)/l, are to be further reduced, it is vital that the limitations of current analysers are fully understood. The aim of this large multicentre study was to determine the accuracy of haematology analysers in current routine practice for platelet counts below 20 x 10(9)/l. Platelet counts estimated by analysers using optical, impedance and immunological methods were compared with the International Reference Method for platelet counting. The results demonstrated variation in platelet counting between different analysers and even the same type of analyser at different sites. Optical methods for platelet counting on the XE 2100, Advia 120, Cell-Dyn 4000 and H3* were not superior to impedance methods on the XE 2100, LH750 and Pentra analysers. All analysers except one overestimated the platelet count, which would result in under transfusion of platelets. This study highlights the inaccuracies of haematology analysers in platelet counting in severe thrombocytopenia. It re-emphasizes the need for external quality control to improve analyser calibration for samples with low platelet counts, and suggests that the optimal thresholds for prophylactic platelet transfusions should be re-evaluated.     

An audit of platelet transfusion within the Wellington Cancer Centre

Aim: An audit of platelet transfusion was performed to assess adherence to local prophylactic policy and to assess if therapeutic transfusions were administered in line with international recommendations. Methods: A prospective audit of platelet transfusion therapy was conducted at the Wellington Cancer Centre in patients with hypoproliferative thrombocytopenia over a 3‐month period from 26 January 2008 to 30 April 2008. There were 398 episodes of evaluable clinical decision activity generated through either platelet counts <50 × 10⁹/L or platelet transfusion events. Each episode was assessed and defined as either adhering to or breaching the local prophylactic platelet transfusion policy. Results: Thrombocytopenia and/or platelet transfusion occurred in 63 patients aged 16–84 years with either a haematological or solid organ malignancy. Decisions to withhold prophylactic platelet transfusion in thrombocytopenic patients adhered to policy for 99% of platelet counts <50 × 10⁹/L. Where transfusions were administered, 77% were prophylactic and 23% were for therapeutic indications. Prophylactic transfusions adhered to policy for 72% of platelet counts <50 × 10⁹/L. Adherence to prophylactic transfusion policy for febrile patients with a threshold of ≤15 × 10⁹/L was 84%, compared to 63% for stable afebrile patients with a threshold of ≤10 × 10⁹/L. Where policy was breached, in 80% of cases the platelet count had not reached the prophylactic transfusion threshold. Of the clinical decisions leading to therapeutic transfusions, 67% were deemed appropriate and predominantly a single adult therapeutic dose of platelets was administered. Where multiple doses of platelets were transfused, 86% of these transfusion events either breached policy or were deemed suboptimal management. Conclusion: The audit demonstrated a high rate of adherence to local transfusion policy. Where policy was breached, predominantly a transfusion had occurred prior to a platelet count reaching the pre‐defined trigger. The use of multiple dose platelet transfusions was almost never appropriate. Educating staff in the use of a stringent transfusion policy may lead to reductions in platelet product use.