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Management of fetal alloimmune thrombocytopenia by weekly in utero platelet transfusions.

Alloimmune neonatal thrombocytopenia (ANT) may cause intracranial haemorrhage in utero as well as at delivery. Recent management has concentrated on attempts to minimise fetal thrombocytopenia and prevent its complications. This report describes further experience with the use of repeated intravascular transfusions of compatible platelets in utero. The patient studied had already had one infant with intracranial haemorrhage due to ANT. In her next pregnancy, weekly intra-uterine platelet transfusions were given from 26 weeks, but intra-uterine death occurred at 30 weeks after the mother had a heavy fall. In her most recent pregnancy, weekly intravascular transfusions of platelets were given by cordocentesis from 29 to 34 weeks. The fetal platelet count was maintained above 30 X 10(9)/l for almost all of the last 6 weeks of pregnancy before delivery of a normal infant by Caesarean section at 35 weeks' gestation. This approach is effective in preventing severe fetal thrombocytopenia in the last trimester of pregnancy and is contrasted with alternative treatments of ANT. Further data are required to determine the efficacy and risks of these treatments.

Blood Transfusion, Intrauterine↗

Predictive value of lymphocytotoxic test and platelet aggregometry for the effect of transfused platelet concentrates.

Sera of patients with thrombocytopenic diathesis before platelet transfusion were evaluated using donor's platelets in the aggregometry test the donor's lymphocytes in the lymphocytotoxicity test. In most cases the results of both tests were in agreement, although sometimes, despite strongly positive results of LCTT, the Agr was negative. Both tests showed a similar value for the prediction of the effectiveness of platelet concentrates: Agr in 80% and LCTT in 71% of cases.

Blood Transfusion↗

Clinical aspects of platelet transfusions.

Refractoriness is the most important complication of platelet transfusion therapy, occurring in about 50% of patients receiving repeated transfusions. The major causes are HLA alloimmunization and non-immune platelet consumption associated with clinical factors such as septicaemia. DIC and splenomegaly. Initial management of alloimmunized patients who are refractory to platelet transfusions from random donors is the use of HLA-matched platelet transfusions, which improve responses to transfusions in about 65% of patients. It may be difficult to provide effective platelet transfusion support for alloimmunized patients not responding to HLA-matched transfusions. There has been much interest in methods for the prevention of HLA alloimmunization. Primary HLA alloimmunization is dependent on the presence of HLA class II antigen-bearing cells in transfusions; pure platelet transfusions are non-immunogenic as platelets only express HLA class I antigens. The use of leucocyte-depleted blood components in multitransfused patients has resulted in a reduction in HLA alloimmunization and platelet refractioness. Improvements in the techniques for leucocyte-depletion of red cell and platelet concentrates and the possibility of inactivation of HLA class II antigen-bearing cells by UV irradiation makes prevention of alloimmunization an attainable goal.

Blood Platelets↗

Factors affecting posttransfusion platelet increments, platelet refractoriness, and platelet transfusion intervals in thrombocytopenic patients.

A variety of patient and product-related factors influenced the outcome of 6379 transfusions given to 533 patients in the Trial to Reduce Alloimmunization to Platelets (TRAP). Responses measured were platelet increments, interval between platelet transfusions, and platelet refractoriness. Patient factors that improved platelet responses were splenectomy and increasing patient age. In contrast, at least 2 prior pregnancies, male gender, splenomegaly, bleeding, fever, infection, disseminated intravascular coagulation, increasing height and weight, lymphocytotoxic antibody positivity, an increasing number of platelet transfusions, or receiving heparin or amphotericin were associated with decreased posttransfusion platelet responses. Platelet factors that were associated with improved platelet responses were giving ABO-compatible platelets, platelets stored for 48 hours or less, and giving large doses of platelets while ultraviolet B (UV-B) or gamma irradiation decreased platelet responses. However, in alloimmunized lymphocytoxic antibody-positive patients, the immediate increment to UV-B-irradiated platelets was well maintained, whereas all other products showed substantial reductions. Refractoriness to platelet transfusions developed in 27% of the patients. Platelet refractoriness was associated with lymphocytotoxic antibody positivity, heparin administration, fever, bleeding, increasing number of platelet transfusions, increasing weight, at least 2 pregnancies, and male gender. The only factors that reduced platelet refractoriness rates were increasing the dose of platelets transfused or transfusing filtered apheresis platelets.

Blood Platelets↗

Autologous platelet transfusion in alloimmunized patients with acute leukemia.

Seventy-eight transfusions of autologous platelets were given to eight alloimmunized patients receiving curative chemotherapy for acute leukemia. Platelets were collected at regeneration of hematopoiesis after a chemotherapy cycle, cryopreserved with 5% dimethylsulfoxide in liquid nitrogen, and retransfused during bone marrow aplasia following the next treatment cycle. The in vitro platelet recovery after freezing, thawing, and washing was 85 +/- 4%. The in vivo corrected count increment 1 h after autologous platelet transfusions was 11 +/- 5 x 10(9)/l. With the exception of moderate urticaria and slight nausea each after one transfusion, no immediate or chronic side effects occurred. The bleeding time was shortened and hemorrhage during bone marrow aplasia was prevented in all alloimmunized patients by autologous platelet transfusions.

Acute Disease↗

The value of alloantibody detection in predicting response to HLA-matched platelet transfusions.

Alloantibody tests demonstrate immunological causes of insufficient increments in random platelet transfusions. The value of a positive or negative test result in predicting the outcome of human leucocyte antigen (HLA)-matched transfusions in patients refractory to leucodepleted random platelet transfusions has not been assessed. We retrospectively evaluated the outcome of the first HLA-matched platelet transfusion in 72 patients with haematological diseases in two ways: first, the strategy according to which the patient was selected for HLA-matched platelet transfusions was analysed. The strategies were: (i) results of alloantibody tests were not available, (ii) a positive alloantibody test, (iii) a negative alloantibody test. Secondly, the outcome of the first HLA-matched transfusion was investigated relative to the results of alloantibody tests, irrespective of the decision strategy. No significant association was found between the decision strategy and the outcome of the first HLA-matched platelet transfusion. Positive alloantibody tests, however, predicted a better outcome of the first HLA-matched platelet transfusion (P = 0.04 and P = 0.03 after 1 and 16 h respectively). In patients refractory to random platelet transfusions, positive alloantibody tests predicted a better outcome of HLA-matched platelet transfusions. Patients with negative alloantibody tests, however, may benefit from HLA-matched platelet transfusions.

Female↗

Effect of pre-incubation at 37 degrees C of platelet concentrates on the post-transfusion platelet adhesion capacity to collagen and fibrinogen.

The effect of warming (37 degrees C) of stored platelet concentrates (PC) on the post-transfusion platelet function as measured by the adhesion capacity in a rectangular perfusion system under flow conditions was analyzed in 22 patients undergoing transfusion for stable thrombocytopenia. Nine patients received a PC stored at 22 degrees C and incubated at 37 degrees C for 1 h before transfusion, 10 patients received a non-warmed PC, 3 patients received both a pre-warmed and a non-warmed PC. In the PC the platelet adhesion capacity to collagen was higher in the pre-warmed PC than in the non-warmed PC (33 +/- 5.9% coverage vs. 22 +/- 4.7% coverage, respectively, in a selected group with the same platelet concentration). The adhesion capacity to collagen of the platelets in the patient's blood, measured 10 min after transfusion, had increased considerably in both patient groups and 4 h later the adhesion capacity in both patient groups was similar to that of the pre-warmed PC before transfusion. We conclude that though pre-warming of stored PC had a beneficial effect on the adhesion capacity to collagen of the platelets in the PC, the clinical significance is questionable because already 10 min after transfusion the adhesion capacity to collagen of stored non-warmed platelets had improved to the level of the pre-warmed platelets and 4 h after transfusion this improvement was still present.

Adult↗

Clinical aspects of platelet transfusion.

Several clinical complications of platelet transfusions relate to contaminating donor leucocytes, and a number of strategies have been devised to leucodeplete platelet products before transfusion. Both alloimmunization to class I human leucocyte antigens (HLA), which causes febrile transfusion reactions and refractoriness to transfused platelets, and transmission of cytomegalovirus have been shown to be reduced by 3-log10 leucodepletion by filtration. Lesser degree of leucodepletion, e.g. by platelet preparation from buffy coats, will control febrile transfusion reactions, but will not reliably prevent other complications. The clinical implications and cost-effectiveness of different strategies of platelet production remain a matter of debate.

Blood Component Transfusion↗

Single-donor platelets reduce the risk of septic platelet transfusion reactions.

BACKGROUND: Septic platelet transfusion reactions (SPTRs) are the most common, serious risk of transfusion. Because SPTRs result from donor skin flora or asymptomatic bacteremia, the use of single-donor platelets (SDPs) has been proposed to reduce the risk of SPTRs from the risks with pools of platelet concentrates (PCs). STUDY DESIGN AND METHODS: Beginning in 1986, all febrile transfusion reactions were evaluated by culture of the platelet bag. Confirmed SPTRs were identified by isolation of the same bacteria from the bag and the patient's blood or by positive Gram's stain of the bag that confirmed a positive platelet culture. In 1987, a program to minimize PC use in favor of SDP use was initiated as a means of reducing SPTRs. RESULTS: In 12 years, the use of SDPs increased from 51.7 percent to 99.4 percent of all platelet transfusions at one institution. SPTRs fell from three events in 1 year to the current rate of one event per year. The incidence of SPTRs decreased from 1 in 4,818 transfusions to 1 in 15,098 transfusions. The rate of SPTRs due to PCs was 5.39 times higher than that of SPTRs due to SDPs (95% CI, 1.89,12.9). CONCLUSION: The use of SDPs is a simple means of reducing SPTRs. Other measures such as sterilization will be required to eliminate all SPTRs.

Adult↗

Novel methodology for assessment of prophylactic platelet transfusion therapy by measuring increased thrombus formation and thrombin generation.

Currently, patients developing severe thrombocytopenia during chemotherapy treatment are prophylactically transfused with platelets. We developed two platelet function tests to report the improved haemostasis in the transfused patients, which were capable of detecting aberrant responsiveness of the platelets after transfusion. First, in a whole-blood flow test, platelet adhesion and thrombus formation were determined under high-shear flow conditions. Second, the procoagulant function of platelets was assayed in platelet-rich plasma by measurement of thrombin generation. Experimental conditions were established, where flow-induced adhesion and thrombin generation test parameters increased semi-linearly with the platelet concentration, and informed on the activation properties of platelets. The transfusion effects were evaluated for 38 thrombocytopenic patients, who were transfused with platelets stored in plasma or in synthetic medium (platelet additive solution II). In most but not all patients, transfusion resulted in increased adhesion and thrombus formation, as well as in improved platelet-dependent coagulation. Taken together, the increase in platelet count after transfusion explained 57% of the overall improvement in platelet function. In acute graft-versus-host disease, thrombus formation was normal, while platelet-dependent coagulation was higher than expected. We conclude that assessment of flow-induced adhesion and thrombin generation in acquired thrombocytopenia adequately determines the improved haemostatic activity by transfused platelets.

Acute Disease↗

Functional capacity of transfused platelets estimated by the Thrombostat 4000/2.

Post-transfusion platelet increment is a useful test for the evaluation of transfusion efficacy. It does not, however, give information about the in vivo platelet function. We have evaluated the in vitro bleeding time (IVBT) using the Thrombostat 4000/2 with ADP as activating agent in 60 platelet transfusions given to 17 chemotherapy-induced severely thrombocytopenic patients. Determinations were performed before and after transfusion of platelet concentrates (PC) prepared from buffy coat. Both fresh and stored platelets resulted in significant reductions of the IVBT already 10 minutes after completed platelet transfusion. In the majority of patients there was a correspondence between IVBT and platelet increment. However, in 30% of the cases there was no improvement of the IVBT despite an increase of the platelet count. Fresh PCs were more effective than stored. The IVBT seems to represent a clear-cut improvement in the possibilities for evaluating and monitoring the effect of platelet transfusion.

Adolescent↗

Current issues with platelet transfusion in patients with cancer.

For the past 30 years, platelet transfusions have been used in the treatment of thrombocytopenia caused by decreased production, inadequate function, or increased destruction of platelets. The number of platelet transfusions has increased more than transfusions of other blood components, shifting from whole blood use for the platelet source to plateletpheresis. Hematology/oncology patients are among the largest group receiving platelet transfusions, primarily because the more aggressive chemotherapies produce more acute and prolonged thrombocytopenia. While platelet transfusions often rescue patients with very low platelet levels, they are associated with the risk of viral and bacterial infections, as well as alloimmunization. Platelet donor recruitment can also be difficult, and platelet transfusion can be very expensive depending on the source of platelets. As a result, prophylactic transfusions are less likely to be administered at higher platelet counts, reducing platelet use and cost of platelet transfusions. However, cancer patients receiving intensive chemotherapy or myeloablative regimens require multiple platelet transfusions. For these patients, alternate strategies are needed so that platelet transfusions can be significantly reduced or eliminated.

Antineoplastic Combined Chemotherapy Protocols↗

Febrile reactions to platelet transfusion: the effect of increased interleukin 6 levels in concentrates prepared by the platelet-rich plasma method.

BACKGROUND: A relation between febrile reactions to platelet transfusion and high cytokine levels in platelet concentrates (PCs) was found previously. The levels of cytokines such as interleukin (IL)-6 are related to the while cell content of the PC during storage. Therefore, early removal of white cells should prevent reactions. STUDY DESIGN AND METHODS: This prospective study was set up to compare methods for the preparation of random PCs, the platelet-rich plasma method (PRP-PCs), which results in a high white cell content, and the buffy coat method (BC-PCs), which results in a low white cell content, with regard to the frequency and severity of reactions to platelet transfusion and the IL-6 level of the PC. IL-6 was chosen because it is the major mediator of the acute-phase response. White cells were reduced in all PCs before transfusion. RESULTS: Platelet transfusions (n = 584) in 64 patients were studied. An overall reaction frequency of 7.2 percent was observed. Transfusion reactions were seen predominantly in patients who received PRP-PCs (PRP-PCs: 9.3% vs. BC-PCs: 2.7%, p = 0.007). Allergic reactions were limited to transfusions of PRP-PCs. The following PRP-PC characteristics were significantly correlated with febrile transfusion reactions: IL-6 level (p < 0.0001), initial white cell count (p = 0.001), and storage time (p = 0.02). In this group, reactions were less frequent in patients receiving pretransfusion medication (p < 0.001). In the PRP-PC group, IL-6 content (p = 0.01) and initial white cell count (p = 0.04) were also significantly correlated with allergic reactions, which indicated that these or associated factors might have an effect on the outcome of this type of reaction. CONCLUSION: Febrile reactions are highly correlated with IL-6 levels in PCs. The low white cell content of BC-PCs is associated with undetectable IL-6 levels and a reduced frequency of febrile as well as allergic reactions in recipients. The BC method is the preferable one for the production of random-donor PCs.

Acute-Phase Reaction↗

Guidelines for platelet transfusions. British Committee for Standards in Haematology, Working Party of the Blood Transfusion Task Force.

Recommendations for the optimal transfusion support of patients likely to receive repeated platelet transfusions. 1. Determine policy for prophylactic platelet support, and select the platelet count below which platelet transfusions will be used. 2. Consider using leucocyte depletion of red cell and platelet concentrates to prevent HLA alloimmunization from the outset. 3. Type patients for HLA-A and B antigens at an early stage. 4. Use random donor platelet concentrates for initial platelet support (either single or multiple donor, depending on availability). 5. If refractoriness occurs, determine whether clinical factors, which may be associated with non-immune consumption of platelets, are present and test the patient's serum for HLA antibodies. 6. Use HLA-matched platelet transfusions if HLA alloimmunization is the most likely cause of refractoriness. 7. If there is no improvement with HLA-matched transfusions, platelet crossmatching may identify the cause of the problem and help with the selection of compatible donors. 8. Discontinue prophylactic platelet support if a compatible donor cannot be found. Use platelet transfusions from random donors to control bleeding and increase the dose, if necessary.

Blood Coagulation Disorders↗

A prospective randomized trial of HLA-matched versus mismatched single-donor platelet transfusions in cancer patients.

The use of histocompatability antigen (HLA)-matched platelets has been advocated for the support of thrombocytopenic cancer patients. We randomized 78 newly diagnosed cancer patients prospectively (before thrombocytopenia) to receive either HLA-matched or mismatched single-donor platelet transfusions. Three hundred forty-one platelet transfusions were given for 80 separate episodes of therapy-induced thrombocytopenia in 33 patients. Forty-five patients receiving intensive chemotherapy did not develop significant (less than 20,000 platelets/mm3) thrombocytopenia and did not receive a platelet transfusion. No marked difference was observed between the matched and mismatched groups in regard to number of total platelet transfusions per patient (median, 3 vs. 5, respectively; P = 0.076), number of platelet transfusions per episode (median, 3.0 vs. 3.5, respectively; P = 0.28), or days between transfusions (median, 2 vs. 2, respectively, P greater than 0.4). Bleeding episodes, although rare, tended to be of increased severity in the mismatched group. Febrile patients receiving mismatched platelets tended to have a lower posttransfusion increment increase than their nonfebrile counterparts (P = 0.068), although a similar trend could not be demonstrated between febrile and nonfebrile patients who received matched platelets (P = 0.22). Patients treated as outpatients had significantly higher posttransfusion increments than when transfused as inpatients when they were given mismatched platelets (P less than 0.0005). Development of antiplatelet antibody did not appear to affect response to platelet transfusions. Only one patient developed sustained high-level antibody titers. In patients where thrombocytopenia was significant, the transfusion of HLA-matched platelets did not appear to offer a significant advantage. However, HLA-matched platelet transfusions tended to be associated with higher posttransfusion increments in febrile patients and a trend toward fewer severe bleeding episodes. A multi-institution trial containing a large number of patients is needed to evaluate trends observed in this study.

Adolescent↗

A prospective study of symptomatic bacteremia following platelet transfusion and of its management.

BACKGROUND: The danger of bacteremia due to contaminated platelets is not well known. There are also no established guidelines for the management of febrile reactions after platelet transfusion. STUDY DESIGN AND METHODS: To determine the risk of symptomatic bacteremia after platelet transfusion, 3584 platelet transfusions given to 161 patients after bone marrow transplantation were prospectively studied. Platelet bags were routinely refrigerated for 24 hours after transfusion. Septic work-up was initiated for a temperature rise of more than 2 degrees C above the pretransfusion value within 24 hours of platelet transfusion or a temperature rise of more than 1 degree C that was associated with chills and rigor. Diagnosis of bacteremia after platelet transfusion was made only when the pairs of isolates from the blood and the platelet bags were identical with respect to their biochemical profile, antibiotic sensitivity, serotyping, or ribotyping. RESULTS: Thirty-seven febrile reactions, as defined above, occurred. Bacteremia subsequent to platelet transfusion was diagnosed in 10 cases. There was a 27-percent chance (95% CI, 15-43%) that these febrile reactions represented bacteremia that resulted from platelet transfusion. For a subgroup of 19 patients with a temperature rise of more than 2 degrees C, the risk of bacteremia was 42 percent (95% CI, 23-64%). Septic shock occurred in 4 of the 10 bacteremic patients. A rapid diagnosis was possible because the involved bacteria were demonstrated by direct Gram stain of the samples taken from the platelet bags of all 10 patients. CONCLUSION: Significant febrile reactions after platelet transfusion are highly likely to be indicative of bacteremia. Routine retention of platelet bags for subsequent microbiologic study was useful in the investigation of these febrile reactions. Empiric antibiotic therapy is indicated.

Bacteremia↗

Platelet transfusion. Current techniques, remaining problems, and future prospects.

The use of platelet transfusions to stop or to prevent bleeding in patients with thrombocytopenia or platelet dysfunction has accelerated in the past decade. Platelet counts and bleeding times, performed in conjunction with careful clinical evaluation of the patient, are appropriate guides in assessing the need for platelet transfusion. Complications of platelet transfusions are similar to those of red cell transfusions, with some additional concerns. Pooled random donor or single-donor apheresis concentrates, either randomly or selectively matched, are the major platelet products available. In most cases, transfusion requirements can be satisfied by use of random donor units. Proper evaluation of the effectiveness of transfused platelets is essential in determining the dose and frequency of future platelet transfusions. Refractoriness to random donor platelets eventually occurs in many recipients. This is most commonly associated with alloimmunization to histocompatibility antigens, but other platelet alloantigens may play a role. Many in vitro tests for platelet antibodies have been developed, and the clinical utility of these assays in selecting compatible platelets is now under evaluation. Strategies and different approaches to the management of thrombocytopenic patients with hypoplastic bone marrow states are also reviewed.

Bleeding Time↗

Alloimmune refractoriness to platelet transfusions.

Patients who are transfused on multiple occasions with red cells or platelets may develop platelet-reactive alloantibodies and experience decreased clinical responsiveness to platelet transfusion. This situation, conventionally described as "refractoriness to platelet transfusions," is defined by an unsatisfactory low post-transfusion platelet count increment. If antibodies to HLAs are detected, improved clinical outcomes may result from transfusions of HLA-matched or donor-recipient cross-matched platelets. Because refractoriness is an expected, frequently occurring phenomenon, prevention of HLA alloimmunization is an important management strategy. Prevention strategies include efforts to decrease the number of transfusions, filtration of cellular components to reduce the number of HLA-bearing leukocytes, or pretransfusion ultraviolet B irradiation of cellular components to decrease their immunogenicity. Other investigational approaches include reducing the expression of HLAs on transfused platelets, inducing a transient reticuloendothelial system blockade by infusions of specialized immunoglobulin products, or transfusing semisynthetic platelet substitutes (thromboerythrocytes, thrombospheres) or modified platelets (infusible platelet membranes, lyophilized platelets).

Biological Products↗