Management of Patients Refractory to Platelet Transfusion - Research Paper Example

Running head: REFRACTORINESS TO PLATELET TRANSFUSION Management of Patients Refractory to Platelet Transfusion 04 August 2011 Abstract How to manage patients refractory to platelet transfusion is a difficult question. Despite a wealth of literature, refractoriness to platelet transfusion remains a serious clinical challenge. This paper presents a brief discussion of patient refractoriness to platelet transfusion and the ways such patients should be managed. The paper relies on the current state of academic/ empirical studies related to the issue of refractoriness to platelet transfusion. Keywords: platelet transfusion, refractoriness, refractory, management. Management of Patients Refractory to Platelet Transfusion How to manage patients refractory to platelet transfusion is a continued debate. Much has been written and said about possible ways to resolve this clinical issue. Despite a wealth of literature on the topic, patient refractoriness to platelet transfusion remains a serious medical challenge. Patients refractory to platelet transfusion require special treatment and complex strategies to preserve and improve their health. It should be noted, that the current state of literature does not provide a single, universal response to the refractoriness problem. Different techniques of managing patients refractory to platelet transfusion have been used, at various degrees of success. Given the risks presented by refractoriness and high rates of platelet transfusion failures, there is the need for new clinical assessment protocols, which will assist in providing patients with adequate care, with little to no risks to their health. Refractoriness to Platelet Transfusion: What Is It? The past years were marked with increased attention to the problem of refractoriness to platelet transfusion in different groups of patients. That transfused platelets often fail to maintain and improve patient health beyond the post-transfusion redistribution phase remains a matter of serious professional concern (Friedberg et al, 1993). This is particularly the case of oncohematologic patients, who carry a disproportionate burden of refractoriness to platelet transfusion (Ferreira et al, 2011; Schiffer, 2001). Statistically, nearly 30% of oncohematologic patients are refractory to platelet transfusion, which makes it particularly difficult to improve their health (Ferreira et al, 2011). Generally, being refractory to platelet transfusion is essentially about having posttransfusion platelet count increments progressively decreased (Sandler, 1998). Diminished clinical responses to platelet transfusion is just another sign of refractoriness and a situation, which can become life-threatening, if platelet counts are lower than 10,000/μL (Sandler, 1998; Zeigler et al, 1987). The state of refractoriness in patients is usually determined by measuring “the corrected platelet count increment 1-hour after a platelet transfusion” (Sandler, 1998, p.2). Also, clinicians can easily define refractoriness by using uncorrected platelet transfusion count increments (Sandler, 1998). For example, a 75-kg patient receiving one unit of random donor platelet concentrate must experience an increase in platelet count equal to 5-6X109 (Sandler, 1998). Failure to achieve this result suggests the presence of refractoriness and requires developing other, unique methods of managing such patients. Refractoriness to Platelet Transfusion: Causes and Implications for Management The main causes of refractoriness to platelet transfusion are usually categorized as immune and non-immune. “Non-immune causes of refractoriness include but are not limited to fever, hypersplenism, infection, amphotericin B treatment, disseminated intravascular coagulation, and even venoclusive disease” (Sandler, 1998). These are the most usual predictors of low platelet count increments following platelet transfusion in patients, and it is no wonder that concerted effort are made to reduce the risks of failures in platelet transfusions as a result of non-immune health complexities. However, refractoriness to platelet transfusion can also result from various immune failures and controversies, of which the presence of platelet-reactive antibodies and the development of alloimmunization (Sandler, 1998). The latter is a frequent topic of discussion in academic circles (Rebulla, 2005). Nonetheless, these are non-immune factors that account for most cases of refractoriness to platelet transfusion (Rebulla, 2005). 80% of platelet transfusion refractoriness are due to non-immunologic factors, which may also include sepsis, bone marrow transplantation, splenomegaly, graft-versus-host disease, drug-induced thrombocytopenia, and hemorrhages (Ferreira et al, 2011). This information has far-reaching implications for managing patients with refractoriness to platelet transfusion: identifying non-immune factors should become the basic ingredient of patient assessment prior to and following the process of platelet transfusion. Managing Patients with Refractoriness to Platelet Transfusion Recent advances in hematology suggest that managing patients refractory to platelet transfusion is possible but not entirely effective. The rates of failure in platelet transfusion are still high. Management techniques for patients with refractoriness to platelet transfusion are numerous and used at various degrees of success. For many years, two most common approaches to managing patients refractory to platelet transfusion included (1) matching platelet concentrates based on the patients’ HLA phenotype or specificity, and (2) crossmatching of platelet concentrates (Engelfriet & Reesink, 1997). However, none of these methods is entirely satisfactory. In case of HLA-matched platelet concentrates, availability is one of the most serious problems (DeLoughery, 2009). These platelet concentrates fail in between 20 and 70 percent of refractory patients (DeLoughery, 2009). HLA-matched platelet transfusions have proved to be ineffective in 25% of patients with antiplatelet antibodies (DeLoughery, 2009). Likewise, crossmatching may not be available in timely fashion (DeLoughery, 2009). This is probably why clinicians propose other, more reliable ways to manage patients with refractoriness to platelet transfusions. Slitcher et al (2005) suggest that platelet refractoriness can be easily prevented by using ultraviolet B irradiation and leukocyte reduction. Both methods were rather effective in reducing the risks of platelet refractoriness in patients (Slitcher et al, 2005). Platelet “concentrates should be depleted of leukocytes by filtration” (Kooy et al, 1991). However, these methods can only be used to manage patients, whose refractoriness is caused by nonimmune factors (Slitcher et al, 2005). Therefore, the basic task is to assess the nonimmune risks of refractoriness in patients, which is possible by measuring the levels of HLA antibodies in patients (Sacher et al, 2003). Also, serial evaluations of lymphocytotoxic antibody levels can predict success or failure of platelet transfusion (Sacher et al, 2003). Apparently, the risks which refractoriness to platelet transfusion presents for patient health obligate clinicians to perform laboratory tests prior to initiating platelet transfusion activities. However, due to the lack of time, laboratory testing may not be available or appropriate. Even when the first attempt to transfuse platelet concentrates fails, medical professionals and clinicians still have a variety of options to improve the situation. First, cross-matching is a better alternative to HLA-matched platelet transfusion (Friedberg et al, 1993). The fact is that cross-matching entails using a broad range of antiplatelet antibody assays, which enhance compatibility of donors and recipients (Friedberg et al, 1993). However, more and more medical professional shift to using single-donor platelet concentrations; if that is the case, the use of IV IgG helps to achieve the desired platelet transfusion count and maintain these results over a long period of time (Zeigler et al, 1987). “rFVIIa support can become a reliable instrument of managing patients refractory to platelet transfusion; this is particularly the case of patients with Glanzmann’s thrombasthenia” (Franchini, 2009). Unfortunately, the utility of rFVIIa support in patients with other hematologic deficiencies is poorly understood. With all these methods at hand, clinicians face a difficult task of choosing the most appropriate ones. Also, there are risks that choosing the right method will require too much time, which can be extremely dangerous to patients in bleeding conditions. The main problem is not in that refractoriness to platelet transfusion is associated with numerous life risks but that there is still no single protocol for managing patients refractory to platelet transfusion. Patients in bleeding and oncohematologic conditions use a variety of medications, which can potentially reduce the efficacy of platelet transfusion (Ferreira et al, 2011). It is essential that the causes of refractoriness be identified and describe prior to the first platelet transfusion is attempted. Blood services need to (a) be informed about the frequency and risks of refractoriness to platelet transfusion; (b) develop laboratory and assessment measures to correctly identify the main predictors of refractoriness in different groups of patients; and (c) provide adequate medical support to zero the risks of undesirable hematologic events in these patients. Such protocols will help to standardize the main pre-transfusion procedures and improve the quality of hematologic and oncohematologic care provided. References DeLoughery, T.G. (2009). Management of acquired bleeding problems in cancer patients. Emergency Medicine Clinics of North America, 27, 423-444. Engelfriet, C.P. & Reesnik, H.W. (1997). Management of alloimmunized, refractory patients in need of platelet transfusions. Vox Sang, 73, 191-198. Ferreira, A.A., Zulli, R., Soares, S., Castro, V. & Moraes-Souza, H. (2011). Identification of platelet refractoriness in oncohematologic patients. Clinics, 66(1), 25-40. Franchini, M. (2009). The use of recombinant activated factor VII in platelet disorders: A critical review of the literature. Blood Transfusion, 7, 24-28. Friedberg, R.C., Donnelly, S.F., Boyd, J.C., Gray, L.S. & Mintz, P.D. (1993). Clinical and blood bank factors in the management of platelet refractoriness and alloimmunization. Blood, 81(12), 3428-3434. Kooy, M.M., Prooijen, H.C., Moes, M., Bosma-Stants, I. & Akkerman, J.W. (1991). Use of leukocyte-depleted platelet concentrates for the prevention of refractoriness and primary HLA alloimmunization: A prospective, randomized trial. Blood, 77, 201-205. Rebulla, P. (2005). A mini-review on platelet refractoriness. Haematologica, 90, 247-253. Sacher, R.A., Kickler, T.S., Schiffer, C.A., Sherman, L.A., Bracey, A.W. & Shulman, I.A. (2003). Management of patients refractory to platelet transfusion. Archives of Pathology and Laboratory Medicine, 127, 409-415. Sandler, S.G. (1998). Management of patients with hematologic malignancies and aplastic anemia who are refractory to platelet transfusions. Haemotologia, 29(1), 1-11. Schiffer, C.A. (2001). Management of patients refractory to platelet transfusion. Leukemia, 15, 683-685. 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