European Journal of Internal Medicine 25 (2014) e37
Contents lists available at ScienceDirect
European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim
Letter to the Editor What is the evidence for platelet transfusion thresholds? Keywords: Bleeding Platelets Transfusions
Physicians are reasonably familiar with the different thresholds which are recommended for considering platelet transfusions in patients at risk (more commonly) or actively bleeding. However, in most of these situations, the threshold set is based purely on expert opinion. In the current evidence-based world, this is not entirely acceptable, but nevertheless followed on the basis that there is no solid evidence available and needs to be based on retrospective analysis [1]. What is also not known in these clinical scenarios is whether the platelet transfusions are clearly responsible for improving the patient outcome or harmful consequences would have resulted, if the transfusions were not undertaken in the first place. From a clinical point of view, in this regard, it is important that the attending physician does not base the decision to transfuse platelets based on just the platelet count and disregard several other factors. Haemostasis is a complex interplay of various components of the circulatory system including the vascular endothelium, von Willebrand factor, coagulation factors, and platelets but also the red cells, and the leucocytes. Isolated drop in platelet count by itself is not translatable to a high bleeding risk, when the rest of the parameters are completely normal. This is very evident in patients with immune thrombocytopenia or ITP where even very low platelet counts do not cause bleeding in an otherwise well individual. For a perfect haemostasis, it is the platelet function rather than platelet number that matters most. What would be ideal here, in addition to the clinical findings, are some laboratory measures to predict platelet function. It has long been considered that the reason for ITP patients to be less haemorrhagic is the predominance of younger and more active platelets. This is reflected in the laboratory results as an increase in immature platelet fraction (IPF) and a high IPF percentage has been suggested to be indicative of consumptive (eg; ITP) or recovering (eg; post stem cell transplant) thrombocytopenic disorders in contrast to a low IPF percentage in under-production thrombocytopenia (marrow disorders) [2]. Since IPF can be obtained rapidly as part of the results of the complete blood count by automation, it should become a standard parameter in evaluating the bleeding risk in thrombocytopenic patient. Although, IPF is not validated for use in patients with moderate thrombocytopenia, who may need to undergo invasive procedures, its potential cannot be underestimated. Tremendous progress has been made in recent years with global coagulation tests in reducing blood component transfusion in different settings. Attempts have commenced to use these tests to include assessment of platelet function, although the recent Chest guidelines on perioperative antithrombotic therapy guidelines concluded ‘additional studies are needed, especially in patients having non-cardiac surgery,
before these assays can be considered for use in clinical practice’ [3]. So what is required is well-planned, prospective trials taking into consideration both clinical information and laboratory methods like the global tests to determine platelet function. This approach has dramatically decreased prophylactic platelet transfusion usage in liver transplant patients and is a good lesson to follow [4]. In the case of liver disease in the non-transplant setting, debate has arisen in relation to the need for administration of platelets especially since there is a rebalanced haemostatic state in both the primary and secondary haemostatic pathways [5]. Recent study from Tripodi et al. has also shown that infusing one standard adult platelet dose secures only a small increase in platelet count without normalizing thrombin generation and thromboelastometry tests [6]. However, single dose platelet transfusion remains a common practice in this setting. In this context, it needs to be stressed that it is not yet clear whether more platelet transfusions are necessary for haemostasis in patients with liver disease. In summary, currently there is no evidence basis for the different platelet thresholds recommended for transfusions in clinical practice. Collaborative and urgent efforts are required to determine platelet function before considering platelet transfusion thus promoting evidencebased rather than expert-opinion based policy.
Conflict of interests None of the authors have any actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations within three years of beginning the submitted work that could inappropriately influence, or be perceived to influence, their work.
References [1] Tosetto A, Balduini CL, Cattaneo M, et al. Management of bleeding and of invasive procedures in patients with platelet disorders and/or thrombocytopenia: guidelines of the SISET. Thromb Res 2009;124:e13–8. [2] Briggs C, Kunka S, Hart D, et al. Assessment of immature platelet fraction (IPF) in peripheral thrombocytopenia. Br J Haematol 2004;126:93–9. [3] Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy: antithrombotic therapy and prevention of thrombosis, 9th edition. Chest 2012;141:e326S–50S. [4] Pereboom IT, Lisman T, Porte RJ. Platelets in liver transplantation: friend or foe? Liver Transpl 2008;14:923–31. [5] Tripodi A, Mannucci PM. Mechanisms of disease. The coagulopathy of chronic liver disease. New Engl J Med 2011;365:147–56. [6] Tripodi A, Primignani M, Chantarangkul V, et al. Global hemostasis tests in patients with cirrhosis before and after prophylactic platelet transfusion. Liver Int 2013;33:362–7.
Jecko Thachil Department of Haematology, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL, United Kingdom Tel.: +44 161 276 4812; fax: +44 161 276 8085. E-mail address: [email protected].
0953-6205/$ – see front matter © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ejim.2013.12.006
Contents lists available at ScienceDirect
European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim
Letter to the Editor What is the evidence for platelet transfusion thresholds? Keywords: Bleeding Platelets Transfusions
Physicians are reasonably familiar with the different thresholds which are recommended for considering platelet transfusions in patients at risk (more commonly) or actively bleeding. However, in most of these situations, the threshold set is based purely on expert opinion. In the current evidence-based world, this is not entirely acceptable, but nevertheless followed on the basis that there is no solid evidence available and needs to be based on retrospective analysis [1]. What is also not known in these clinical scenarios is whether the platelet transfusions are clearly responsible for improving the patient outcome or harmful consequences would have resulted, if the transfusions were not undertaken in the first place. From a clinical point of view, in this regard, it is important that the attending physician does not base the decision to transfuse platelets based on just the platelet count and disregard several other factors. Haemostasis is a complex interplay of various components of the circulatory system including the vascular endothelium, von Willebrand factor, coagulation factors, and platelets but also the red cells, and the leucocytes. Isolated drop in platelet count by itself is not translatable to a high bleeding risk, when the rest of the parameters are completely normal. This is very evident in patients with immune thrombocytopenia or ITP where even very low platelet counts do not cause bleeding in an otherwise well individual. For a perfect haemostasis, it is the platelet function rather than platelet number that matters most. What would be ideal here, in addition to the clinical findings, are some laboratory measures to predict platelet function. It has long been considered that the reason for ITP patients to be less haemorrhagic is the predominance of younger and more active platelets. This is reflected in the laboratory results as an increase in immature platelet fraction (IPF) and a high IPF percentage has been suggested to be indicative of consumptive (eg; ITP) or recovering (eg; post stem cell transplant) thrombocytopenic disorders in contrast to a low IPF percentage in under-production thrombocytopenia (marrow disorders) [2]. Since IPF can be obtained rapidly as part of the results of the complete blood count by automation, it should become a standard parameter in evaluating the bleeding risk in thrombocytopenic patient. Although, IPF is not validated for use in patients with moderate thrombocytopenia, who may need to undergo invasive procedures, its potential cannot be underestimated. Tremendous progress has been made in recent years with global coagulation tests in reducing blood component transfusion in different settings. Attempts have commenced to use these tests to include assessment of platelet function, although the recent Chest guidelines on perioperative antithrombotic therapy guidelines concluded ‘additional studies are needed, especially in patients having non-cardiac surgery,
before these assays can be considered for use in clinical practice’ [3]. So what is required is well-planned, prospective trials taking into consideration both clinical information and laboratory methods like the global tests to determine platelet function. This approach has dramatically decreased prophylactic platelet transfusion usage in liver transplant patients and is a good lesson to follow [4]. In the case of liver disease in the non-transplant setting, debate has arisen in relation to the need for administration of platelets especially since there is a rebalanced haemostatic state in both the primary and secondary haemostatic pathways [5]. Recent study from Tripodi et al. has also shown that infusing one standard adult platelet dose secures only a small increase in platelet count without normalizing thrombin generation and thromboelastometry tests [6]. However, single dose platelet transfusion remains a common practice in this setting. In this context, it needs to be stressed that it is not yet clear whether more platelet transfusions are necessary for haemostasis in patients with liver disease. In summary, currently there is no evidence basis for the different platelet thresholds recommended for transfusions in clinical practice. Collaborative and urgent efforts are required to determine platelet function before considering platelet transfusion thus promoting evidencebased rather than expert-opinion based policy.
Conflict of interests None of the authors have any actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations within three years of beginning the submitted work that could inappropriately influence, or be perceived to influence, their work.
References [1] Tosetto A, Balduini CL, Cattaneo M, et al. Management of bleeding and of invasive procedures in patients with platelet disorders and/or thrombocytopenia: guidelines of the SISET. Thromb Res 2009;124:e13–8. [2] Briggs C, Kunka S, Hart D, et al. Assessment of immature platelet fraction (IPF) in peripheral thrombocytopenia. Br J Haematol 2004;126:93–9. [3] Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy: antithrombotic therapy and prevention of thrombosis, 9th edition. Chest 2012;141:e326S–50S. [4] Pereboom IT, Lisman T, Porte RJ. Platelets in liver transplantation: friend or foe? Liver Transpl 2008;14:923–31. [5] Tripodi A, Mannucci PM. Mechanisms of disease. The coagulopathy of chronic liver disease. New Engl J Med 2011;365:147–56. [6] Tripodi A, Primignani M, Chantarangkul V, et al. Global hemostasis tests in patients with cirrhosis before and after prophylactic platelet transfusion. Liver Int 2013;33:362–7.
Jecko Thachil Department of Haematology, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL, United Kingdom Tel.: +44 161 276 4812; fax: +44 161 276 8085. E-mail address: [email protected].
0953-6205/$ – see front matter © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ejim.2013.12.006
