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Summary. 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 × 109/l for stable patients and < 20 × 109/l in the presence of major bleeding or additional risk factors. A trigger of < 50 × 109/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 × 109/l and 2·3% (50/2147) of the study days when platelet counts were 10–20 × 109/l. In patients with platelets > 20 × 109/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 ≥ 10 × 109/l. There was a 36% reduction in platelet units transfused compared with retrospective data when an arbitrary transfusion trigger of 20 × 109/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 × 109/l in the absence of fresh bleeding and sepsis (> 38°C) is safe and has a significant impact on overall hospital transfusion costs.
The pioneering use of platelet transfusions during the 1960s enabled the introduction of more aggressive chemotherapy regimens, which were associated with improved clinical efficacy.
The relationship between haemorrhage and patient platelet count was defined by a landmark study (Gaydos et al, 1962). Subsequently, it was considered that the risk of haemorrhagic complications was unacceptable when the platelet count was reduced to below 20 × 109/l. This was ata time when there was still widespread administration ofaspirin to patients with acute leukaemia.
During the 1980s, however, increasing evidence emerged to suggest that such high thresholds for prophylactic platelet transfusion were, in fact, harmful to patients, and in 1987 the National Institutes of Health (NIH) formally questioned the validity of the 20 × 109/l trigger (NIH, 1987; Beutler, 1993).
In the last 10 years, significantly lower thresholds have been accepted for prophylactic platelet transfusions. Studies by Gmur et al (1991), Gil Fernandez et al (1996) and Rebulla et al (1997) have all indicated that the classical trigger of 20 × 109/l could be safely reduced in certain, well-defined patient groups with possible economic benefits and reduced transfusion requirements for patients. Other studies have investigated the effects of changing platelet dose in order to reduce the costs of platelet transfusions; Ackerman et al (2000) suggested that efforts to use lower-dose single-donor platelets result in an increase in patient transfusion requirements with a corresponding overall increase in overall hospital transfusion costs.
Despite these studies, indications for the transfusion of platelets have remained controversial, and in many cases continue to be based on arbitrary and poorly justified numerical criteria (Patten, 1992). This practice has the potential for unnecessary exposure to the infectious and immunological risks of transfusion.
In December 1997, there was cautious agreement in the Royal College of Physicians Consensus Conference statement on platelet transfusion that a platelet threshold of 10 × 109/l is as safe as higher levels in managing patients without additional risk factors (Contreras, 1998). However, the UK demand for platelet transfusions has remained relatively static over the last 5 years and this suggests that many centres have not changed their platelet transfusion practice.
Given the widespread, considerable variations in clinical practice, there remains a need to develop prospective studies that evaluate the impact of changing platelet transfusion policies for all haematological patients. We therefore decided to evaluate our prophylactic platelet transfusion practice by defining new protocols and policies that altered the platelet transfusion threshold from 20 × 109/l to 10 × 109/l.
In total, 98 patients receiving intensive chemotherapy for haematological malignancies were evaluated over a 3 month period. We performed a non-randomised prospective analysis of the frequency of bleeding events and measured the effects on blood product usage. We compared the use of blood products during this period with data from the preceding 9 month period.
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Despite several reports indicating the safety of reducing transfusion triggers for prophylactic platelet transfusions, optimal transfusion strategies for supporting patients undergoing treatment for haematological malignancy have still yet to be defined. To date, few studies have set out to analyse the criteria for prophylactic platelet transfusion methodically and to evaluate the pharmoeconomic impact of such policies.
Gmur et al (1991) reported results on the safety of introducing a stringent prophylactic platelet transfusion policy in leukaemia patients during induction chemotherapy. In this study, a threshold of 5 × 109/l was shown to be safe for this group of patients in the absence of fresh bleeding or fever (> 38°C). Gil Fernandez et al(1996) reported the clinical results from 190 patients undergoing bone marrow transplantation, where there was a reduction in the transfusion trigger from 20 to < 10 × 109/l. In this study, no significant differences were reported in the relative risk of death from haemorrhage or bleeding between the classical threshold group and the stringent threshold group.
Despite these studies, a survey by the American Association of Blood Banks (AABB) of practices at 630 hospitals involved in the care of onco-haematology patients continued to demonstrate widely varying practice (Pisciotto et al, 1995). Sixty percent of hospitals continued to set thresholds for prophylactic transfusion at 20 × 109/l and 20% higher than 20 × 109/l.
In 1997, results from a multicentre randomised clinical trial by Rebulla et al (1997) further supported the safety of decreasing the classical platelet transfusion threshold. This study of 255 patients undergoing induction chemotherapy for acute myeloid leukaemia demonstrated a 21% reduction in platelet use, following a reduction in the platelet transfusion threshold to 10 × 109/l.
In our study, a threshold of < 10 × 109/l was adopted for all patients undergoing intensive chemotherapy who were not actively bleeding or septic with acceptable relative risk levels of bleeding. Other studies have shown that a reduction in the traditional threshold is safe without increasing the bleeding risk but only in certain well-defined patient groups and settings.
Our results concur with previously published data that a transfusion trigger of < 10 × 109/l in the absence of fresh bleeding and sepsis (> 38°C) is safe. However, the presence of additional risk factors significantly increases the bleeding risk.
There were 44 major haemorrhagic episodes associated with these additional risk factors, 14 of these complications occurred at platelet counts of 10–20 × 109/l. Four patients presented with DIC. Platelet counts were generally maintained above 50 × 109/l in the presence of major bleeding and while clotting times remained abnormal (prothrombin time > 17secs and activated partial thromboplastin time > 34 s), to minimize the risk of major bleeding complications. Despite this, there were 18 major bleeding episodes associated with these patients.
We also found a high incidence of haematuria during our study period, primarily in four patients with platelet counts above 10 × 109/l. This was largely attributable to HC and accounted for 40·2% of all the episodes of haematuria recorded during the study (54/134).
Overall, 36% of major haemorrhagic episodes (72/117) were associated with DIC and HC alone, and all of these complications occurred at platelet counts of ≥ 10 × 109/l. We have since instituted a higher trigger point of > 20 × 109/l in patients with additional risk factors, to reduce the incidence of major bleeding complications.
We demonstrated a significant reduction in platelet usage in comparison with a previous 9 month period. If this reduction was sustained over the next financial year, this would represent health-care savings of £ 181 322 with the potential for reinvestment in patient care (Table VIII). We also established a reduction in red cell usage of 15%. This is difficult to explain but this is probably due to the heightened awareness of appropriate blood product usage as a consequence of the audit. If these reductions in red cell usage were sustained, projected savings would exceed £ 250 000 over the next financial year.
Table VIII. Blood product costs.
|Blood product||Prior to changes (annual cost) (£)||Post changes (projected annual cost) (£)||Projected savings (£)|
|RBC cost||292 380||244 860||47 520|
|Platelet cost||502 619||321 297||181 322|
|CMV-testing supplement (RBC)||798||668||129|
|CMV-testing supplement (Plt)||3873||2475||1397|
|HLA-testing supplement (Plt)||48 382||30 928||17 454|
|Total||848 054·01||600 230·47||247 823·54|
In summary, our findings indicate that our threshold of 10 × 109/l for prophylactic platelet transfusions is safe in all patients being treated for haematological malignancy who are not actively bleeding or septic. Where additional risk factors are present, the threshold should be > 20 × 109/l and in the presence of major bleeding complications platelet counts should be maintained > 50 × 109/l. In addition to achieving substantial health care savings, a more restrictive transfusion policy will also reduce the risk of transfusion-associated immunological complications with the potential to improve patient outcome.