scholarly journals Platelet transfusion therapy. Optimal donor selection with a combination of lymphocytotoxicity and platelet fluorescence tests

Blood ◽  
1978 ◽  
Vol 51 (5) ◽  
pp. 781-788 ◽  
Author(s):  
A Brand ◽  
A van Leeuwen ◽  
JG Eernisse ◽  
JJ van Rood

Although the value of HLA matching for the selection of platelet donors for patients refractory to random platelets is beyond doubt, even perfectly matched combinations sometimes fail to give a satisfactory transfusion response. With HLA typing and negative lymphocytotoxicity crossmatches, 35% of the platelet transfusions administered to 15 patients gave disappointing results (29 of 82). Additional crossmatching with the newly developed platelet fluorescence test described in this paper reduced the unexpected transfusion failures to 7% (6 of 82). Five of these failures were observed in one patient. The target of the antibodies detected with this platelet fluorescence test is not yet fully specified. It seems probable that both HLA and platelet-specific non-HLA antibodies were detected. No correlation of the results of platelet transfusions with the presence or absence of leukoagglutinating antibodies was found.

Blood ◽  
1978 ◽  
Vol 51 (5) ◽  
pp. 781-788 ◽  
Author(s):  
A Brand ◽  
A van Leeuwen ◽  
JG Eernisse ◽  
JJ van Rood

Abstract Although the value of HLA matching for the selection of platelet donors for patients refractory to random platelets is beyond doubt, even perfectly matched combinations sometimes fail to give a satisfactory transfusion response. With HLA typing and negative lymphocytotoxicity crossmatches, 35% of the platelet transfusions administered to 15 patients gave disappointing results (29 of 82). Additional crossmatching with the newly developed platelet fluorescence test described in this paper reduced the unexpected transfusion failures to 7% (6 of 82). Five of these failures were observed in one patient. The target of the antibodies detected with this platelet fluorescence test is not yet fully specified. It seems probable that both HLA and platelet-specific non-HLA antibodies were detected. No correlation of the results of platelet transfusions with the presence or absence of leukoagglutinating antibodies was found.


Blood ◽  
1982 ◽  
Vol 59 (5) ◽  
pp. 971-975 ◽  
Author(s):  
MC McElligott ◽  
JE Menitove ◽  
RJ Duquesnoy ◽  
JB Hunter ◽  
RH Aster

Abstract Platelet transfusions from donors matched for cross-reactive antigens have been shown to be effective in providing hemostasis in alloimmunized thrombocytopenic patients. A significant number of these transfusions, however, fail to provide posttransfusion platelet recoveries. We investigated incompatibility in the Bw4/bw6 system as a possible explanation for these failures. The Bw4/Bw6 system is a biallelic antigen system closely associated with HLA-B. HLA-B locus antigens that are cross-reactive frequently differ in their Bw4/Bw6 specificity. Posttransfusion platelet recoveries from 21 alloimmunized thrombocytopenic patients homozygous for Bw4 or Bw6 and transfused with both Bw4/Bw6 compatible and incompatible platelets were analyzed. The mean 1-hr posttransfusion recovery was 84% following Bw4/Bw6-compatible platelets versus 52% with Bw4/Bw6-incompatible platelets (p less than 0.02). Twenty-four hours following transfusion, mean recoveries were 44% and 24%, respectively, (p less than 0.01). A subgroup of 8 patients (38%) was identified who had markedly lower responses following Bw4/Bw6- incompatible transfusions as compared to Bw4/Bw6-compatible transfusions (mean recoveries: 1 hr--compatible 100%, incompatible 27%, p less than 0.001; 24 hr--compatible 45%, incompatible 7%, p less than 0.01). These data suggest that the Bw4/Bw6 antigen system has clinical significance for some patients requiring platelet transfusion therapy and, when appropriate, should be considered in the selection of donors.


Blood ◽  
1982 ◽  
Vol 59 (5) ◽  
pp. 971-975 ◽  
Author(s):  
MC McElligott ◽  
JE Menitove ◽  
RJ Duquesnoy ◽  
JB Hunter ◽  
RH Aster

Platelet transfusions from donors matched for cross-reactive antigens have been shown to be effective in providing hemostasis in alloimmunized thrombocytopenic patients. A significant number of these transfusions, however, fail to provide posttransfusion platelet recoveries. We investigated incompatibility in the Bw4/bw6 system as a possible explanation for these failures. The Bw4/Bw6 system is a biallelic antigen system closely associated with HLA-B. HLA-B locus antigens that are cross-reactive frequently differ in their Bw4/Bw6 specificity. Posttransfusion platelet recoveries from 21 alloimmunized thrombocytopenic patients homozygous for Bw4 or Bw6 and transfused with both Bw4/Bw6 compatible and incompatible platelets were analyzed. The mean 1-hr posttransfusion recovery was 84% following Bw4/Bw6-compatible platelets versus 52% with Bw4/Bw6-incompatible platelets (p less than 0.02). Twenty-four hours following transfusion, mean recoveries were 44% and 24%, respectively, (p less than 0.01). A subgroup of 8 patients (38%) was identified who had markedly lower responses following Bw4/Bw6- incompatible transfusions as compared to Bw4/Bw6-compatible transfusions (mean recoveries: 1 hr--compatible 100%, incompatible 27%, p less than 0.001; 24 hr--compatible 45%, incompatible 7%, p less than 0.01). These data suggest that the Bw4/Bw6 antigen system has clinical significance for some patients requiring platelet transfusion therapy and, when appropriate, should be considered in the selection of donors.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3366-3366
Author(s):  
Christopher J Sharpe ◽  
Robert S Liwski ◽  
Stephen Couban ◽  
Irene Sadek ◽  
Eiad B Kahwash

Abstract Abstract 3366 Background: Refractoriness to platelet transfusion is a common clinical problem occurring in up to 34% of hematology/oncology patients (Hod and Schwartz 2008). While often non-immunologic in etiology, alloimmunization to human leukocyte antigens (HLA) or human platelet antigens (HPA) may contribute to this phenomenon. If patients are refractory to pooled, random donor platelets, most institutions have an explicit algorithm which facilitates a supply of single-donor (SD) apheresis and/or HLA-matched platelets. At our institution, platelet refractoriness is defined as a platelet count rise of <10×109/L measured within 24 hours post-transfusion of ABO-matched single-donor platelets on at least two occasions. In this circumstance, HLA matched platelets have been provided regardless of the HLA/HPA alloimmunization status. The goal of this study was to measure the HLA- and HPA-alloimmunization rates in adult patients at our institution who were refractory to single donor platelet transfusions. Methods: All patients at our centre who were refractory to single donor platelet transfusion between January 2006 and June 2011 were included. Patients were tested for the presence of HLA and HPA antibodies at the Canadian Blood Services Platelet Immunology Laboratory. HLA typing was performed by molecular SSO/SSP method and antibody identification was achieved using Luminex single antigen assay following an initial screening test. HPA antibody determination was performed by ELISA. For patients with HLA antibodies, panel reactive antibody (PRA), which estimates the percentage of potential reactivity against donors in the population, was calculated using cPRA software from the Organ Procurement Transplantation Network (OPTN). Results: Thirty-three patients (18 male and 15 female) were tested for HLA and HPA antibodies in the setting of platelet transfusion refractoriness. All patients received multiple blood transfusions prior to becoming refractory to platelets. Most patients (85%; 28/33) had a hematologic malignancy (leukemia (19), lymphoma (5), myelodysplastic syndrome (2), myelofibrosis (1), and amyloidosis (1)) while five patients had non-malignant hematological disorders (aplastic anemia (3), antiphospholipid syndrome (1), and congenital pancytopenia (1)). No HPA antibodies were identified in any patient. HLA antibodies were found in 42% of patients (14/33) and was different according to gender: 22% for males (4/18) vs 67% for females (10/15). Males (n=4) were found to be mildly to moderately sensitized to HLA with an average PRA of 33% (range 11–62%). Nine out of 10 females were highly sensitized to HLA with PRA values between 95 and 100%. There was no association between the presence of HLA antibodies and either patient diagnosis or a history of allogeneic stem cell transplantation. Conclusion: We have demonstrated a relatively high rate of HLA alloimmunization (42%) among patients refractory to single donor platelets compared to previously published reports. This may be due to differences in testing methodology and/or stringency of the definition of platelet transfusion refractoriness. Similar to other studies, we found no significant contribution of HPA antibodies to platelet refractoriness in our patient population. Patient diagnosis and/or history of allogeneic stem cell transplantation did not appear to influence the rate of HLA alloimmunization. Importantly, we found that the majority of refractory patients with HLA-antibodies and high level of HLA sensitization (PRA ≥ 95%) were female (64%; 9/14), implicating pregnancy as a possible contributor to immunologically-based platelet transfusion refractoriness. The finding of high PRA values (≥ 60%) in the majority of HLA-sensitized patients (71%, 10/14) argues against the utility of platelet crossmatching for identification of HLA compatible platelets. In addition, the marked differences in the incidence and the extent of HLA sensitization between male and female patients suggests that gender should be added as an important factor in HLA-matching algorithms for the purposes of platelet transfusion support in refractory patients to optimize the use of HLA-matched platelet donors. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
1987 ◽  
Vol 69 (5) ◽  
pp. 1425-1430
Author(s):  
JG McFarland ◽  
RH Aster

Four platelet compatibility assays were performed on serum and platelet or lymphocyte samples from 38 closely HLA-matched donor/recipient pairs involved in 55 single-donor platelet transfusions. The 22 patients studied were refractory to transfusions of pooled random-donor platelets. Of the four assays (platelet suspension immunofluorescence, PSIFT; 51Cr release; microlymphocytotoxicity; and a monoclonal anti-IgG assay, MAIA), the MAIA was most predictive of platelet transfusion outcome (predictability, 74% for one-hour posttransfusion platelet recovery and 76% for 24-hour recovery). The only other assay to reach statistical significance was the PSIFT (63% predictability for one-hour posttransfusion recovery). The degree of HLA compatibility between donor and recipient (exact matches v those utilizing cross-reactive associations) was unrelated to the ability of the MAIA to predict transfusion results. The MAIA may be capable of differentiating HLA antibodies, ABO antibodies, and platelet-specific antibodies responsible for failure of HLA-matched and selectively mismatched single-donor platelet transfusions.


Blood ◽  
1989 ◽  
Vol 74 (3) ◽  
pp. 1172-1176 ◽  
Author(s):  
CA Schiffer ◽  
B O'Connell ◽  
EJ Lee

There can be wide variation in the expression of the HLA B12 antigen and its “splits,” B44 and 45, on the platelets and lymphocytes from the same individual. One hundred sixty-two single donor platelet transfusions mismatched only for this antigen group were administered to 54 alloimmunized patients who were refractory to random donor platelets. Satisfactory increments (one-hour post-transfusion corrected- count increment [CCI] greater than 7,500) were seen following 111/162 transfusions (69%). In 31 patients (57%), all transfusions (n = 85) produced CCI greater than 7,500, and 76% of patients received some transfusions that were satisfactory. Of note is that ten patients had excellent increments despite either preformed lymphocytotoxic antibody against the mismatched antigen or positive lymphocytotoxic cross- matches with the donor. In contrast, poor increments were seen in ten recipients under similar circumstances, implying disparities in antigen expression on the platelets and lymphocytes of different donors. There was no obvious pattern of other donor HLA antigens which could be correlated with these differences. The HLA B12 antigen group is relatively common (found in approximately 25% of the population), and these data indicate that selective mismatching for these antigens can be an effective donor-selection strategy to increase the number of donors for alloimmunized recipients.


Blood ◽  
1995 ◽  
Vol 85 (3) ◽  
pp. 824-828 ◽  
Author(s):  
K Sintnicolaas ◽  
M van Marwijk Kooij ◽  
HC van Prooijen ◽  
BA van Dijk ◽  
WL van Putten ◽  
...  

We studied the value of leukocyte depletion of platelet transfusions for the prevention of secondary human leukocyte antigen (HLA)- alloimmunization in patients with a high-risk of prior immunization induced by pregnancies. Seventy-five female patients with hematologic malignancies (mostly acute leukemia) and a history of pregnancy were randomized to receive either standard random single-donor platelet transfusions (mean leukocytes, 430 x 10(6) per transfusion) or leukocyte-depleted random single-donor platelet transfusions. Leukocyte depletion to less than 5 x 10(6) leukocytes per platelet transfusion (mean leukocytes, 2 x 10(6) per transfusion) was achieved by filtration. Of the 62 evaluable patients, refractoriness to random donor platelets occurred in 41% (14 of 34) of the patients in the standard group and in 29% (8 of 28) of the patients in the filtered group (P = .52); anti-HLA antibodies developed in 43% (9 of 21) of individuals in the standard group and 44% (11 of 25) of cases in the filtered group. The time toward refractoriness and development of anti- HLA antibodies was similar for both groups. We conclude that leukocyte depletion of random single-donor platelet products to less than 5 x 10(6) per transfusion does not reduce the incidence of refractoriness to random donor platelet transfusion because of boostering of anti-HLA antibodies.


Blood ◽  
1987 ◽  
Vol 70 (1) ◽  
pp. 23-30 ◽  
Author(s):  
JM Heal ◽  
N Blumberg ◽  
D Masel

Refractoriness occurs in many patients receiving multiple platelet transfusions. We used a sensitive ELISA assay to assess the utility of crossmatching HLA-A,B matched single donor platelets in 51 consecutive, typical refractory patients. Of the 222 transfusions evaluated at 1 to 4 hours posttransfusion, only 17 of 54 (31%) with positive crossmatches had corrected platelet count increments of greater than or equal to 7,500/microL. In contrast, 95 of 168 (57%) of those with negative crossmatches had such increments (P less than .001). Regardless of the results of the crossmatch, HLA-A,B, and ABO matching had independent influences on transfusion outcome. The median corrected 1- to 4-hour increment for crossmatch negative transfusions was 13,300/microL for A/BU grade matches, 9,700 for BX, and 7,800 for C. Increments were 10,000/microL for ABO-identical transfusions and 5,900 for transfusions of platelets ABO incompatible with the recipient's plasma antibodies. When the donor platelets were ABO compatible, but the donor plasma contained ABO antibodies to the recipient's platelets, the increment was intermediate (8,200/microL). The most important factor in predicting platelet survival was the crossmatch, followed by HLA-A,B and ABO, each having independent predictive value. These data demonstrate that the predictive value of a negative crossmatch may be considerably less than that reported in previous studies with stable, less ill patients. In typical refractory patients, there appear to be mechanisms of platelet destruction that are related to HLA-A,B and ABO but are not detected with current crossmatch methods. We hypothesize that soluble plasma HLA-A,B and ABO antigens contribute to the destruction of donor and sometimes recipient platelets by an immune complex or other “innocent bystander” mechanism. With our crossmatching technique, HLA-A,B and ABO match grades remain relevant to platelet transfusion therapy in some refractory patients.


Blood ◽  
1987 ◽  
Vol 70 (1) ◽  
pp. 23-30 ◽  
Author(s):  
JM Heal ◽  
N Blumberg ◽  
D Masel

Abstract Refractoriness occurs in many patients receiving multiple platelet transfusions. We used a sensitive ELISA assay to assess the utility of crossmatching HLA-A,B matched single donor platelets in 51 consecutive, typical refractory patients. Of the 222 transfusions evaluated at 1 to 4 hours posttransfusion, only 17 of 54 (31%) with positive crossmatches had corrected platelet count increments of greater than or equal to 7,500/microL. In contrast, 95 of 168 (57%) of those with negative crossmatches had such increments (P less than .001). Regardless of the results of the crossmatch, HLA-A,B, and ABO matching had independent influences on transfusion outcome. The median corrected 1- to 4-hour increment for crossmatch negative transfusions was 13,300/microL for A/BU grade matches, 9,700 for BX, and 7,800 for C. Increments were 10,000/microL for ABO-identical transfusions and 5,900 for transfusions of platelets ABO incompatible with the recipient's plasma antibodies. When the donor platelets were ABO compatible, but the donor plasma contained ABO antibodies to the recipient's platelets, the increment was intermediate (8,200/microL). The most important factor in predicting platelet survival was the crossmatch, followed by HLA-A,B and ABO, each having independent predictive value. These data demonstrate that the predictive value of a negative crossmatch may be considerably less than that reported in previous studies with stable, less ill patients. In typical refractory patients, there appear to be mechanisms of platelet destruction that are related to HLA-A,B and ABO but are not detected with current crossmatch methods. We hypothesize that soluble plasma HLA-A,B and ABO antigens contribute to the destruction of donor and sometimes recipient platelets by an immune complex or other “innocent bystander” mechanism. With our crossmatching technique, HLA-A,B and ABO match grades remain relevant to platelet transfusion therapy in some refractory patients.


Blood ◽  
1987 ◽  
Vol 69 (5) ◽  
pp. 1425-1430 ◽  
Author(s):  
JG McFarland ◽  
RH Aster

Abstract Four platelet compatibility assays were performed on serum and platelet or lymphocyte samples from 38 closely HLA-matched donor/recipient pairs involved in 55 single-donor platelet transfusions. The 22 patients studied were refractory to transfusions of pooled random-donor platelets. Of the four assays (platelet suspension immunofluorescence, PSIFT; 51Cr release; microlymphocytotoxicity; and a monoclonal anti-IgG assay, MAIA), the MAIA was most predictive of platelet transfusion outcome (predictability, 74% for one-hour posttransfusion platelet recovery and 76% for 24-hour recovery). The only other assay to reach statistical significance was the PSIFT (63% predictability for one-hour posttransfusion recovery). The degree of HLA compatibility between donor and recipient (exact matches v those utilizing cross-reactive associations) was unrelated to the ability of the MAIA to predict transfusion results. The MAIA may be capable of differentiating HLA antibodies, ABO antibodies, and platelet-specific antibodies responsible for failure of HLA-matched and selectively mismatched single-donor platelet transfusions.


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