Management Of Platelet Refractoriness Research Articles

Platelet compatibility and platelet antibodies detection: A step towards resolving dilemma in management of platelet refractoriness in oncology patients

Background: Platelet refractoriness complicates the provision of platelet transfusions- a critical and essential part in management of thrombocytopenia in Oncology patients. Platelet refractoriness poses challenge due to alloimmunization to HLA (Class I) and human platelet antigens (HPAs) and is associated with adverse clinical outcomes and increases health care costs. Aim: A prospective, observational study was planned in medical oncology patients having thrombocytopenia to analyse result of platelet compatibility with post-transfusion platelet count increment and to ascertain presence of platelet antibodies as causative factor in platelet refractory patients. Methods: Eighty oncology patients having thrombocytopenia in a tertiary care centre; both solid organ and hematological malignancies, requiring platelet transfusion were included in this study. ABO-compatible, leucoreduced, random donor platelets with less than 72 hours storage and platelet cross matched were transfused. In case of platelet refractoriness and presence of platelet incompatibility, platelet antibody screening test was performed using SPRCA technique. A P-value

Platelet refractoriness--practical approaches and ongoing dilemmas in patient management.

Platelet refractoriness can represent a significant clinical problem that complicates the provision of platelet transfusions, is associated with adverse clinical outcomes and increases health care costs. Although it is most frequently due to non-immune platelet consumption, immunological factors are also often involved. Human leucocyte antigen (HLA) alloimmunization is the most important immune cause. Despite the fact that systematic reviews of the clinical studies evaluating different techniques for selecting HLA compatible platelets have not been powered to demonstrate improved clinical outcomes, platelet refractoriness is currently managed by the provision of HLA-matched or cross matched platelets. This review will address a practical approach to the diagnosis and management of platelet refractoriness while highlighting on-going dilemmas and knowledge gaps.

Platelet transfusion: basic aspects

Platelet transfusions have been shown to prevent major haemorrhage and improve survival in thrombocytopenic patients. Since then, advances in the preparation of platelet components, including the introduction of pathogen reduction techniques, have been achieved. The number of transfused platelet components is still growing owing to the increasing number of patients treated for haemato-oncological diseases. Additionally, indications have been extended, for example to patients with drug-induced platelet dysfunction. This review focuses on current platelet component production and storage techniques, including pathogen reduction, indications for platelet transfusion and safety issues including alloimmunisation and management of platelet refractoriness.

Survey of current practice for monitoring and management of platelet refractoriness in Italy

Platelet transfusion failure is a common phenomenon affecting from 7% to 34% of haematology–oncology patients. Monitoring the efficacy of platelet transfusion through the evaluation of a post-transfusion platelet count and clinical response represent an important guide for subsequent transfusions and for the detection of refractoriness. The aim of this survey was to investigate physicians’ attitudes and practices regarding the monitoring of platelet response and the management of platelet refractoriness. An e-mail based survey was conducted among the heads of blood banks with a hemapheresis ward in Italy.Heads of 64 centers out of the 122 initially identified (52%) completed the entire survey. Apheresis, buffy-coat pool, and platelet rich plasma represented an average of 46%, 38% and 17% of the total number of transfusions, respectively. In the prophylaxis of hemorrhagic episodes, most of the centers utilized as standard dose one unit of apheresis platelets (55.7%) and/or one unit of buffy-coat pool platelets (42.6%), while 11.4% of respondents used an average of 6 units of platelet rich plasma. In only 27.9% of the centers was the platelet dose established based on the body weight of the recipient. Only one-third of the centers evaluated the response to platelet transfusion in all patients, while the rate increased to 60% in onco-hematological patients. Among patients transfused on an outpatient basis, the rate dropped to 20%, and a platelet sample taken 10min after transfusion was generally used. The survey documented a substantial lack of interaction between the clinician requesting the transfusion and the one responsible for the preparation and delivery of the product, with both figures involved in the diagnosis of refractoriness in only one-third of the centers.In conclusion, despite being a frequent condition, platelet refractoriness is still managed with a high degree of heterogeneity and often overlooked. Better adherence to existing guidelines and standard operating procedures, as well as the involvement of transfusion centers in prospective evaluations can help reduce this variability and improve the outcome of transfused patients.

Management of Patients Refractory to Platelet Transfusion

This article discusses the causes and management of platelet refractoriness. Improvements in the quality of platelets and leukoreduction have reduced the morbidity and mortality related to alloimmunization and refractoriness of patients to platelet transfusion. Alloimmunization can be distinguished from other causes of poor post-transfusion platelet increments by the measurement of platelet alloantibodies. Options for managing platelet refractoriness caused by alloimmunization include platelet transfusion from human leukocyte antigen-matched or donor-recipient cross-matched platelets. Prevention strategies include efforts to limit recipients' exposure to human leukocyte antigen specificities by using single-donor platelets, filtration to reduce the number of human leukocyte antigen-bearing leukocytes, and pretransfusion ultraviolet B irradiation to decrease their immunogenicity. For appropriate management of patients refractory to platelets, close cooperation and good communication are necessary between clinicians and blood centers.

The evaluation and management of platelet refractoriness and alloimmunization

T HE ARREST of hemorrhage associated with an increase in the patient's platelet count after blood transfusion was first reported by Duke in 1910.' It was not until the 1960s that clinical studies showed that therapeutic platelet transfusions decreased fatal hemorrhagic complications in thrombocytopenic patients2 and that prophylactic platelet transfusions reduced episodes of bleeding.3 More recent reports have suggested that a threshold of I O,OOO/~ for prophylactic platelet transfusion is equivalent to 20,OOO/~ in the absence of additional complicating clinical factors such as platelet dysfunction, associated coagulopathy, or primary defects of vascular integrity.4.5 The hemostatic benefit of platelet transfusion is presumably mediated through an increase in the posttransfusion platelet count above a target level, and clai!s that platelet transfusion may be beneficial even in the absence of such an increase are not commonly accepted.

Clinical and Blood Bank Factors in the Management of Platelet Refractoriness and Alloimmunization

AbstractNumerous independent and interdependent factors are involved in the posttransfusion platelet response. Factors such as ABO match and platelet age are related to circumstances potentially under the control of the blood bank physician and therefore may permit circumvention by an active transfusion service. On the other hand, factors such as fever or sepsis may be unavoidable, being related more to the individual patient or clinical condition. To evaluate which factors could be circumvented, we prospectively followed the 1-hour corrected count increments (CCIs) for 962 single-donor apheresis platelet transfusions to 71 refractory hematologic oncology inpatients, with concomitant recording of implicated factors. Stepwise regression analysis allowed for determination of which concurrent and confounding clinical-, patient-, and blood bank-related factors significantly affected the CCIs. Although many implicated factors proved to be independently associated with an increased or decreased CCI, we found that no single variable consistently explained the CCI variation across the patient population. Each patient appeared sensitive to one or a few particular factors, but because of marked intraindividual variation, it was not possible to identify a priori which factors were important for a given patient. The single exception was a solid-phase red blood cell adherence assay used to cross-match platelets, but only for alloimmunized patients. We also evaluated the utility of requesting FILA-matched platelets from the local suppliers and maintained a clear distinction between platelets simply ordered as HLA matched and actually H LA-identical platelets. Accounting for the confounding clinical-, patient-, and blood bank—related factors, the cross-match assay was a better predictor of an adequate CCI than ordering platelets as FILA matched.

Clinical and blood bank factors in the management of platelet refractoriness and alloimmunization

Numerous independent and interdependent factors are involved in the posttransfusion platelet response. Factors such as ABO match and platelet age are related to circumstances potentially under the control of the blood bank physician and therefore may permit circumvention by an active transfusion service. On the other hand, factors such as fever or sepsis may be unavoidable, being related more to the individual patient or clinical condition. To evaluate which factors could be circumvented, we prospectively followed the 1-hour corrected count increments (CCIs) for 962 single-donor apheresis platelet transfusions to 71 refractory hematologic oncology inpatients, with concomitant recording of implicated factors. Stepwise regression analysis allowed for determination of which concurrent and confounding clinical-, patient-, and blood bank-related factors significantly affected the CCIs. Although many implicated factors proved to be independently associated with an increased or decreased CCI, we found that no single variable consistently explained the CCI variation across the patient population. Each patient appeared sensitive to one or a few particular factors, but because of marked intraindividual variation, it was not possible to identify a priori which factors were important for a given patient. The single exception was a solid-phase red blood cell adherence assay used to cross-match platelets, but only for alloimmunized patients. We also evaluated the utility of requesting HLA- matched platelets from the local suppliers and maintained a clear distinction between platelets simply ordered as HLA matched and actually HLA-identical platelets. Accounting for the confounding clinical-, patient-, and blood bank-related factors, the cross-match assay was a better predictor of an adequate CCI than ordering platelets as HLA matched.

Platelet Transfusion Therapy

This article reviews appropriate platelet support of those patients who are chronically thrombocytopenic because of decreased platelet production, including those receiving chemotherapy or radiation treatments and those undergoing bone marrow transplants. The platelet products available for transfusion and the indications for platelet transfusions are discussed. Expected responses to platelet transfusions are reviewed as well as the prevention of platelet alloimmunization. Finally, a discussion of the mechanisms and management of platelet refractoriness is included.

High-Dose Intravenous Gamma Globulin Improves Responses to Single-Donor Platelets in Patients Refractory to Platelet Transfusion

Abstract Ten patients, with bone marrow failure or malignant disorders, became refractory to platelet transfusions using random, as well as partial or fully HLA-matched, single-donor platelets. To determine its effect on platelet refractoriness, intravenous gamma globulin (IV IgG) was administered at 400 or 800 mg/kg/d for five days, and postinfusion platelet responses were monitored. Platelet transfusion responses following intravenous gamma globulin (IV IgG) were graded as follows: Excellent, 48-hour posttransfusion count greater than 50,000/microL; good, 48-hour count greater than 20,000 but less than 50,000/microL; Fair, increased increment, 48-hour count less than 20,000; and failed, no increased increment. Six of ten patients (60%) had improved responses to selected single-donor platelets (two were excellent, three were good, and one was fair). The time to achieve a platelet transfusion count greater than 25,000/microL ranged from one to nine days of IgG therapy. One individual had sustained benefit (greater than 1 year); the remaining responses persisted for 6 to 8 weeks. These results suggest that IV IgG may be useful in the management of platelet refractoriness, especially in patients receiving single-donor platelets.

High-dose intravenous gamma globulin improves responses to single-donor platelets in patients refractory to platelet transfusion

Ten patients, with bone marrow failure or malignant disorders, became refractory to platelet transfusions using random, as well as partial or fully HLA-matched, single-donor platelets. To determine its effect on platelet refractoriness, intravenous gamma globulin (IV IgG) was administered at 400 or 800 mg/kg/d for five days, and postinfusion platelet responses were monitored. Platelet transfusion responses following intravenous gamma globulin (IV IgG) were graded as follows: Excellent, 48-hour posttransfusion count greater than 50,000/microL; good, 48-hour count greater than 20,000 but less than 50,000/microL; Fair, increased increment, 48-hour count less than 20,000; and failed, no increased increment. Six of ten patients (60%) had improved responses to selected single-donor platelets (two were excellent, three were good, and one was fair). The time to achieve a platelet transfusion count greater than 25,000/microL ranged from one to nine days of IgG therapy. One individual had sustained benefit (greater than 1 year); the remaining responses persisted for 6 to 8 weeks. These results suggest that IV IgG may be useful in the management of platelet refractoriness, especially in patients receiving single-donor platelets.