American Society Of Hematology Guidelines Research Articles

Indications for Platelet Transfusions: How Well Do Physicians Comply with Professional Guidelines

AbstractAbstract 4402 Background:Professional, evidence-based guidelines are developed to help physicians implement best practice care. Unfortunately, guidelines are not followed. Platelet transfusion guidelines have recently changed to a prophylactic transfusion threshold of 10, 000/μ L from the older threshold of 20,000/μ L. We conducted a retrospective analysis at a metropolitan teaching hospital to assess how well physicians comply with the new professional guidelines as well as the older, less stringent criteria to administer platelet transfusions. Methods:All patients admitted to the medical service who received platelet transfusions over a two month period in 2010 were reviewed. These patients represented the following services: ICU, general medicine, medical step down, interventional cardiology, CCU, and the cardiac step down unit. The indication selected in the computerized physician order entry (CPOE) system was compared to the clinical indication found in the patients' medical record. The medical record clinical indication was then evaluated against the American Society of Hematology (ASH) 2007 “Evidence-Based Platelet Transfusion Guidelines” (Slichter SJ. Hematology 2007): bleeding and platelets ≤50, 000/μ L, pre-invasive procedure and platelets ≤50, 000/μ L, prophylactic transfusion for platelets ≤10, 000/μ L and WHO bleeding grade ≥ 2. We also assessed how the patients' clinical indication met the older less stringent prophylactic threshold for platelet transfusion of ≤20, 000/μ L laid forth by the landmark study by Gaydos LA. et. al. (The quantitative relation between platelet count and hemorrhage in patients with acute leukemia. N Engl J Med 1962). Results:A total of 108 patients received platelet transfusions; 29 were medicine patients to tally 95 platelet transfusions. The most common patient clinical indication was “platelets ≤ 20, 000/μ L without bleeding” (27%), while the clinical indication was not specified in 16% of cases. The CPOE documented indication coincided with the patient's clinical indication from the medical record in 23% of cases. Sixty five percent of the time the patient's clinical indication failed to meet the currently accepted 2007 ASH guidelines and 36% of cases failed to meet the older less stringent guidelines. Conclusions:A majority of platelet transfusions did not meet the current professional guidelines for indication. Our pilot study suggests the need for more physician education regarding evidence-based guidelines for platelet transfusions, and in a larger context, initiatives to enhance compliance. We are currently developing an educational intervention and plan to reassess compliance with indications pre and post intervention. Disclosures:No relevant conflicts of interest to declare.

Incidence and Outcomes of Immune Thrombocytopenia (ITP) Following Hematopoietic Stem Cell Transplantation (HCT).

While thrombocytopenia is common following HCT, and has been associated with delayed engraftment, disease relapse, infections and drugs, autoantibody mediated ITP is rarely observed. In one series of non-Hodgkin's lymphoma patients, development of ITP following autologous HCT (autoHCT) was associated with long-term disease free survival (Hequet et al. Bone Marrow Transplant 2003; 32:89). Limited data is available on occurrence and prognosis of ITP following allogeneic HCT (alloHCT). Here we report the incidence and outcomes of ITP in 1700 adults who underwent autoHCT (n=749) and alloHCT (n=951) between January 1990 and December 2004. Of the alloHCT recipients, 531 patients received stem cells from a sibling donor (SD), 268 from an unrelated donor (URD), and in 147 patients umbilical cord blood (UCB) was used as the stem cell source. ITP was defined according to the American Society of Hematology guidelines for diagnosis of ITP (Ann Intern Med 1997; 126:319). In addition, a confirmatory bone marrow examination demonstrating adequate megakaryocyte numbers and morphology and absence of CMV viremia were required. Patients receiving interferon therapy around the time of ITP diagnosis were excluded. Recovery from ITP was defined as a sustained increase in platelet count to 140 x 109/liter (l). Ten patients (median age 37 years [range 25–51]), including 7 alloHCT and 3 autoHCT recipients developed ITP at a median 15 months (range 4–76) post transplant, with an overall cumulative incidence of 0.8% at 5 years (95% confidence interval [CI] 0.3–1.6%). Of the alloHCT recipients, four patients received one or two antigen mismatched UCB HCT, two received matched HCT from an URD and one a SD HCT. The overall cumulative incidence of ITP at 5 years was highest among UCB HCT recipients (3%; 95% CI 0–6%) as compared to SD (0.2%; 95%CI 0–0.5%) and URD (0.7%; 95% CI 0–1.7%) HCT recipients (p<0.01). Nine (7 alloHCT and 2 autoHCT) recipients were transplanted for hematologic malignancy and one autoHCT patient for metastatic breast cancer. Nine of ten patients received myeloablative conditioning regimen. Six of the seven alloHCT recipients received cyclosporin for graft versus host disease (GVHD) prophylaxis. ITP was severe, with a nadir platelet count of 10 x 109/l in all patients. Platelet antibodies were present in 50% (3 of 6) of patients tested. Nine of the ten patients were in complete remission from their underlying malignancy at the time of ITP diagnosis. ITP was steroid refractory in the majority of patients, and required multiple treatment modalities. All alloHCT recipients with ITP developed chronic GVHD and systemic viral infections. While nine patients recovered, one autoHCT recipient died of multi-organ hemorrhage at 76 months post HCT. At a median follow-up of 61 months, seven patients are still alive and disease free, while two additional patients died (one from relapsed acute myeloid leukemia 32 months and one from pulmonary Aspergillosis 154 months post HCT). In summary, we found ITP to be a rare complication of HCT, with the highest incidence in recipients of UCB HCT. While the majority of patients eventually recovered from ITP and achieved long-term overall survival, the illness was severe, associated with chronic GVHD and serious viral infections. Degree of antigenic disparity, immune dysregulation, development of autoimmunity and its contribution to maintenance of disease control after transplantation may be implicated in pathogenesis of ITP following HCT.

Immune thrombocytopenic purpura in pregnancy

This review assesses the need for revision of the present guidelines for immune thrombocytopenic purpura in pregnancy based on evidence-based data from published articles of relevance. The American Society of Hematology (ASH) and British Committee for Standards in Haematology (BCSH) guidelines indicate that at platelet counts below 70,000 or 80,000/microl, respectively, causes of thrombocytopenia other than gestational thrombocytopenia should be considered. The ASH guidelines indicate that for severe thrombocytopenia or thrombocytopenic bleeding in the third trimester, intravenous immunoglobulin is an appropriate first-line agent. No consensus was reached concerning the use of intravenous immunoglobulin or corticosteroids as first-line therapy at other gestational periods. Splenectomy is considered acceptable for patients with refractory immune thrombocytopenic purpura and severe thrombocytopenia with bleeding only in the second trimester. Laparoscopic splenectomy can be safely performed during pregnancy. The BCSH guidelines are consistent with contemporary practice in recommending that the mode of delivery of a pregnant patient with immune thrombocytopenic purpura should be determined based on maternal indications. Screening of articles published since the formulation of the BCSH guidelines in 2003 did not reveal new data that would lead to significant revisions in the guidelines. Though outdated in some aspects, the ASH and BCSH guidelines still provide a useful framework for management of pregnant patients with immune thrombocytopenic purpura.

Chronic Myeloid Leukemia (CML): A Model Disease for Utilizing Evidence Based Guidelines in a Decade of Progress.

The importance of evidence-based guidelines (EBG), including CML, has been long recognized and supported by the American Society of Hematology (ASH). The extraordinary progress in treating CML with imatinib is well known, yet there remains need for alternative treatment for imatinib (IM) resistant disease. This mandated an up-to-date evaluation of current treatment results and methods for quantifying treatment effects. The European LeukemiaNet therefore assembled 19 experts from 9 countries in Europe, the USA, and Australia to recommend new guidelines for evaluating the treatment of CML. Eight members of the current committee were also members of the prior ASH committee of 1998. We also examined progress in evidence-based CML trials since the last (1998) ASH guidelines publication. A computerized Medline search of relevant literature since 1998 was conducted together with pertinent abstracts presented in 2004 and 2005 at ASH, ASCO, and European and International Society meetings. The new major conclusions are: the initial treatment recommended for nearly all CML patients is IM 400mg/d (for very young patients with an appropriate HLA match, allo HSCT may be considered). Failure is defined as no hematologic response (HR) at 3 mos, incomplete HR, or no cytogenetic response (CgR) at 6 mos, less than partial CgR at 12 mos (Ph>35%), less than complete CgR at 18 mos, and loss of HR or CgR or the appearance of IM resistant BCR-ABL mutations with a major increase of the IC50 to IM. Suboptimal response is defined as incomplete HR at 3 mos, less than partial CgR at 6 mos, less than complete CgR at 12 mos, less than major molecular response (MMolR) at 18 mos, loss of MMolR, BCR-ABL mutations with a minor increase of IC50 to IM, or additional chromosome abnormalities. In this event, a dose increase of IM, allo HSCT, dasatinib, or investigational agents are recommended. The importance of regular molecular monitoring for BCR-ABL transcripts is stressed. We compared the data of the EBG of 1998 with those of 2006. Older data (1998) often did not include relevant information such as age, physical findings, duration of follow up, and long-term survival. In general, sample sizes were small, and treatment protocols were not adhered to systematically. External review committees did not exist and committee members felt personally challenged if their opinions, not evidence-based, disagreed with the majority. Based on evidence, an overall superiority of allo HSCT compared to interferon-based regimens could not be demonstrated. Studies of the past 8 years have substantially corrected the deficiencies of the past. Shared decision-making between patient and physician remains critical. The current guidelines represent an important achievement of the European LeukemiaNet, reflect improved scientific quality of CML trials, and are a splendid example of international cooperation.

Treatment of Immune Thrombocytopenic Purpura in Children

Treatment of immune thrombocytopenic purpura (ITP), the most common bleeding disorder of childhood, is a controversial subject for most practitioners. Diagnosis and management of ITP has historically been based primarily on expert opinion rather than on evidence. Due to a paucity of carefully conducted clinical trials in children, the management of ITP varies widely, ranging from observation only, to aggressive management with intravenous immunoglobulin (IVIG), intravenous anti-D rhesus (Rh)0 immunoglobulin (IV RhIG), corticosteroids, and splenectomy. To address the controversies, the American Society of Hematology (ASH) and the British Society for Hematology (BSH) have developed ITP practice guidelines. These guidelines, based on expert opinion, differ in their recommendations for treatment. The ASH guidelines favor therapy based on a low platelet count, and the more current BSH guidelines recommend a more conservative 'wait and watch' approach. In addition to treating children with severe bleeding symptoms, there is a tendency (not evidence based) to treat early in order to prevent a life-threatening bleeding episode, including intracerebral hemorrhage. Corticosteroids are a highly effective therapy, inexpensive, and can usually increase the platelet count within hours to days. However, chronic or prolonged use is associated with toxicity. In the US, based on the knowledge of known toxicities of corticosteroids, as well as the efficacy of alternative treatments (IV RhIG, IVIG), many pediatricians prefer to treat with IVIG and IV RhIG, reserving corticosteroid treatment for serious bleeding or refractory disease. However, in the UK, for the most part, corticosteroids are used as first-line therapy in children with ITP. Splenectomy is rarely indicated in children except for those with life-threatening bleeding and chronic, severe ITP with impairment of quality of life. For children who develop chronic or refractory ITP, immunosuppressive drugs and/or chemotherapy agents may offer some promise. However, the long-term effects of these drugs in children are unknown and they should not be considered unless there is unequivocal evidence that the patient is refractory to IV RhIG, IVIG, and corticosteroids. To date, virtually all of the randomized clinical trials conducted in children with ITP have focused on platelet counts as the sole outcome measure. Only carefully designed, multicenter, randomized clinical trials comparing the effects of different treatment modalities in terms of bleeding, quality of life, adverse effects, and treatment-related costs will be able to address the controversies surrounding childhood ITP treatment and allow management of this condition to be based on scientific data rather than treatment philosophy.