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Altered platelet function and circulation induced by amphotericin B in leukemic patients after platelet transfusion.

Four adults, recently diagnosed, acute leukemic patients received 40 separate platelet transfusion treatments before, during, and after intravenous administration of amphotericin B. Fourteen of these platelet transfusions were administered while the patients also received amphotericin B; 26 platelet transfusions were given before or after amphotericin B therapy. The mean platelet increment for platelet transfusions administered while the patients were untreated with amphotericin B was 58 +/- 6 per cent. While the same patients were being treated with amphotericin B, the mean platelet increment was significantly decreased to 29 +/- 8 per cent (t = 3.1; p less than 0.005). In addition, when the patients were not being given amphotericin B, a highly significant negative relationship (r = -0.77; p less than 0.001) between the values for bleeding time and venous platelet count was present. In contrast, during amphotericin B treatment there was no correlation between the patients' bleeding times and venous platelet counts. We propose that amphotericin B therapy has a direct toxic effect on the function and circulation of transfused platelets. These toxic effects are quickly corrected by discontinuing this antifungal antibiotic.

Adult↗

Platelet transfusion in the management of severe thrombocytopenia in neonatal intensive care unit patients.

Platelet transfusions are frequently given to neonatal intensive care unit (NICU) patients with severe thrombocytopenia (platelets less than 50 x 10(9) L(-1)) but no study has assessed whether this is clinically appropriate. To address this we conducted a retrospective review of platelet transfusion practice in patients developing severe thrombocytopenia over 3 years in a single NICU. Out of 901 admissions, 53 (6%) developed severe thrombocytopenia. Twenty-seven neonates received a total of 63 platelet transfusions, the main triggers being: platelet count less than 30 x 10(9) L(-1) (all patients), or less than 50 x 10(9) L(-1) in those with previous haemorrhage or clinical instability. No major haemorrhage occurred during severe thrombocytopenia either in neonates in whom platelet transfusions were withheld (26/53) or in neonates given platelets who survived to discharge (22/27). Five preterm neonates given platelets died but all had overwhelming sepsis or necrotizing enterocolitis and none died directly as a result of haemorrhage. Although the widely used liberal triggers for neonatal platelet transfusion highlighted in this review reflect available guidelines, and represent cautious ('safe') haemostatic practice, they are likely to result in unnecessary transfusion for a significant number of NICU patients. Improved practice requires definition of a safe lower limit for platelet count in stable neonates; effective platelet transfusion strategies for sick neonates; and improved therapies for conditions precipitating severe thrombocytopenia.

Disease Management↗

Influence of HLA-A2 on the effectiveness of platelet transfusions in alloimmunized thrombocytopenic patients.

Platelet transfusions from donors selectively mismatched for cross-reactive and certain non-cross-reactive HLA antigens were found to be more effective in HLA-A2 negative than in HLA-A2 positive, alloimmunized thrombocytopenic patients. The two groups of patients responded equally well to platelets matched for antigens of the HLA-A and B loci. Certain alloimmunized patients negative for HLA-A2 continued to respond satisfactorily to platelets selectively mismatched for non-cross-reactive HLA antigens as long as platelets containing HLA-A2 were avoided. The data indicate that platelet transfusion support can be provided within a broader range of donor-recipient HLA antigenic disparity to HLA-A2 negative alloimmunized patients than to those who are positive for this antigen.

Antibody Specificity↗

Alloimmunization following platelet transfusions in patients with acute nonlymphocytic leukemia.

Lymphocytotoxic (LCT) antibodies were measured in 20 adult patients with acute nonlymphocytic leukemia (ANLL) who received remission induction chemotherapy and multiple platelet transfusions. Nine (45%) became LCT positive and refractory to the platelet transfusions. This frequency of alloimmunization in ANLL patients was significantly lower than that in aplastic anemia patients (p less than 0.05). In one male with acute promyelocytic leukemia (APL), the LCT antibody disappeared during intensive chemotherapy and recovery of transfused platelets improved remarkably. The incidence of alloimmunization in the patients with APL appeared to be especially low. Six out of 9 LCT positive patients with ANLL became alloimmunized with less than 10 units of platelet transfusions. Three out of 11 LCT negative patients never became alloimmunized with more than 100 units. These facts indicated that there was no relationship between the number of platelet transfusions given and the development of alloimmunization. In addition, the remission rate also did not correlate with the development of alloimmunization.

Adolescent↗

The kinetics of HLA class I elution and the relevance for the use of HLA-eluted platelet transfusions.

HLA-eluted platelet transfusions may be feasible for transfusion in HLA-alloimmunized refractory patients, but the reduction in HLA expression after elution is variable. Using different anti-HLA antibodies directed against the HLA class I complex, the heavy chain, beta 2-microglobulin (beta 2M) and the intracytoplasmatic part of the heavy chain, we investigated factors which influenced the HLA reduction by flow cytometry. Reduction of HLA expression by acid treatment resulted in an almost complete removal of HLA class I molecules from the site of the intracytoplasmatic part of the heavy chain. Re-expression of HLA heavy chain, beta 2M and some of the trimolecular complex (comprised by beta 2M, heavy chain and peptide) occurred within 4 h. This was presumably the result of adsorption from the supernatant (eluate or plasma). After immediate removal of the eluate and incubation in plasma-free supernatant no re-expression of HLA occurred after a 4 h interval.

Absorption↗

Refractoriness to platelet transfusion following partial hepatectomy for hepatocellular carcinoma: report of two cases.

Refractoriness to platelet transfusion indicates a condition in which an expected increase in platelet count is not attained after platelet transfusion. We report herein two cases of refractoriness to platelet transfusion that were caused by the presence of antibodies against the human leukocyte antigen following partial hepatectomy for hepatocellular carcinoma. Due to low postoperative platelet counts in the first case, the patient was transfused with 75 units of platelet concentrate for 3 days after surgery, but was unable to gain a significant increase in the platelet count because of platelet transfusion refractoriness due to anti-human leukocyte antigen antibodies. This case was not complicated and had a favorable clinical course. Despite being transfused with 60 units of platelet concentrate during the 2 days after surgery, the patient's platelet count in the second case did not increase because of the presence of anti-human leukocyte antigen antibodies. Bleeding from the cut surface of the liver into the intraperitoneal cavity was found on the second postoperative day because of a decrease in platelet count. On postoperative day 5, disseminated intravascular coagulation occurred. Perioperative refractoriness to platelet transfusion is an intractable complication since no efficient treatment is available. Preoperative examinations for anti-platelet antibodies should be performed in patients undergoing hepatectomy for hepatocellular carcinoma. This is especially true in cases of decreased platelet counts due to preceding liver cirrhosis and when the prediction for postoperative platelet transfusions is necessary.

Aged↗

Infectious complications after cardiac surgery: lack of association with fresh frozen plasma or platelet transfusions.

OBJECTIVE: The purpose of this study was to examine the effect of perioperative transfusion of platelets and fresh frozen plasma (FFP) on infection rates after cardiac surgery. DESIGN: Retrospective study comparing infection rates after cardiac surgery among patients receiving combinations of packed red blood cells (PRBCs), platelets, and FFP. SETTING: Tertiary care university teaching hospital. PARTICIPANTS: All elective primary coronary artery bypass (CABG) surgery patients from July 1995 to January 1998 before introduction of leukocyte-reduced blood products. INTERVENTIONS: Multivariate logistic and linear regression models were applied to identify clinical risk factors for postoperative infection and to determine the relationship between perioperative administration of PRBCs, platelets, and FFP with postoperative infection. MEASUREMENTS AND MAIN RESULTS: Transfusion of PRBCs, diabetes, age, preoperative hematocrit, and the duration of cardiopulmonary bypass were significantly associated with postoperative infection; platelet or FFP transfusion added no additional risk to PRBC transfusion alone. CONCLUSIONS: Infectious complications in a population of adult primary CABG surgery patients were not increased by transfusion of platelets or FFP. It is PRBC transfusion that confers an increased risk of postoperative infection in this population.

Bacterial Infections↗

Determination of an appropriate size of unrelated donor pool to be registered for HLA-matched platelet transfusion.

HLA-matched platelet transfusions from related or unrelated donors are effective in correcting bleeding tendencies of alloimmunized thrombocytopenic patients. To supply HLA-matched platelets, registration of unrelated HLA-typed donors and selection of compatible donors are necessary and practical considering HLA polymorphism. In this study, the frequencies of each possible HLA phenotype and of corresponding possible compatible donors were calculated with a computer from the table of frequencies of HLA-A and -B haplotypes. Appropriate sizes of such donor pools were theoretically evaluated in Japanese as well as in European Caucasoid and in North American Caucasoid populations. To enable more than 80 percent of patients to get more than five completely compatible donors, only 5000 donor candidates would be necessary for the Japanese population, whereas 18,000 and 25,000, respectively, would be required for European Caucasoid and North American Caucasoid populations.

Blood Donors↗

[Ineffective platelet transfusion in patients with hematology malignancy].

OBJECTIVE: To explore the relationship between the effects of platelet transfusion and histocompatibility antigen (HLA). METHODS: The relationship between the corrected count increment (CCI) of platelet with lymphocytotoxicity test (LCT) and human histocompatibity antigen system-I subtype (HLA-I) in 126 hospitalized patients who accepted platelet transfusion. RESULTS: Ineffective platelet transfusion was strongly related to LCT positive and LCT intensity (P < 0.01). The HLA A2 gene frequency was 0.91. The frequency was much higher than that of health human being (0.54). CONCLUSION: Positive LCT was mainly immune factor for ineffective platelet transfusion. CCI and LCT should be the routine test for platelet patients. It may improve the effects of platelet transfusion.

Adolescent↗

Epidemiologic and outcome studies of patients who received platelet transfusions in the neonatal intensive care unit.

STUDY DESIGN: We conducted a historic cohort study of neonates who received platelet transfusions at the National Institute of Perinatology, Mexico City, from January 1997 to May 2000. We obtained descriptive and outcome data, and assessed demographic and laboratory means of predicting "good candidates" for a future recombinant thrombopoietin (rTpo) trial. RESULTS: A minority of the transfused patients (11.4%) received only one transfusion; the majority (88.6%) received multiple transfusions. Neonates who received one or more platelet transfusions were more likely to die (24.5% mortality) than neonates who received no platelet transfusions (3.7% mortality). Regression analyses indicated that the presence of liver disease was the best predictor of a "good candidate" for rTpo administration. CONCLUSION: The majority of neonates in our institution who receive platelet transfusions receive multiple, not single, transfusions. Receiving any platelet transfusion is a marker for high risk of death. Neonates with liver disease who receive platelet transfusions might be a reasonable group for a phase I rTpo trial.

Cohort Studies↗

[Efficacy of leukocyte-depleted platelet concentrates for prevention of HLA-alloimmunization in patients with frequent platelet transfusions: a prospective multi-institutional study using a polyester platelet filter].

A prospective multi-institutional study was conducted to assess the efficacy of leukocyte-depleted platelet concentrates, prepared by a method using a newly developed polyester filter, in the prevention of HLA-alloimmunization in patients with hematological disorders. Patients who were expected frequent platelet transfusions, were assigned into two groups, receiving either standard platelet concentrates (control group) or leukocyte-depleted platelet concentrates prepared through a polyester platelet filter, Sepacell-PL (filtered group). All patients received leukocyte-depleted red cell products. Of III patients enrolled, 72 were evaluable, 23 in the control and 49 in the filtered group. Both groups were comparable according to age, sex ratio, underlying disorders, previous exposure to alloantigens by transfusion and/or pregnancy. There was no statistically significant difference in the number and duration of transfusion in the two groups. There were significant differences in HLA-alloimmunization rate (9 cases out of 23, 39% in the control group versus 4 cases out of 49, 8% in the filtered group; p less than 0.01) and refractoriness to platelet transfusion from random donors (6 cases out of 23, 26% in the control group versus 2 cases out of 49, 4% in the filtered group; p less than 0.05). These results indicated that leukocyte-depleted platelet concentrates prepared through the polyester platelet filter are beneficial to reduce HLA-alloimmunization in patients with frequent platelet transfusions.

Adolescent↗

Platelet transfusion therapy in acute leukemia: lack of effect of splenomegaly on transfusion requirements and risk of hemorrhage.

Platelet transfusions are an important supportive measure during treatment for acute nonlymphocytic leukemia (ANLL). The presence of splenomegaly may produce decreased posttransfusion platelet increments leading some to recommend an increased dose of platelets per transfusion in this situation. Forty-nine newly diagnosed patients with ANLL were evaluated during 1980 and 1981, and 24% had palpable splenomegaly. Although treated with usual doses of platelets per transfusion, there was no detectable statistical increase in transfusion requirement or incidence of hemorrhage in patients with splenomegaly. Experimental evidence indicates that the splenic platelet pool enlarges with splenomegaly, but the life span of circulating platelets is not significantly changed. Furthermore, the splenic platelet pool is in dynamic equilibrium with the circulating platelet pool thus allowing these platelets to participate in hemostasis. Although posttransfusion increment in platelet count may be less, it appears that platelet transfusion therapy need not be altered solely because of splenomegaly.

Acute Disease↗

The value of platelet transfusions as preparation for kidney transplantation.

The role of platelet transfusion as a preparative method for kidney transplantation is still a matter of debate. Two groups of 28 male patients transplanted between 1983 and 1988, paired for age, date of transplant, absence of anti-HLA antibody and immunosuppressive therapy have been compared. Group I was given 5 purified platelet transfusions at 1-week intervals before transplantation. Each transfusion contained 7.6 x 10(6) platelets contaminated by less than 1 leukocyte in 10(5) platelets. Group II received from 3 to 5 whole blood transfusions. In all cases it was a first transplant from cadaveric donors and previously untransfused patients before entering the protocol. No patient in group I developed cytotoxic antibodies. Acute tubular necrosis occurred with the same incidence in group I and in group II but was more severe and longer in group I, requiring hemodialysis in 62.5% and only 22% in group II. ATN was significantly associated with graft loss in group I (P less than 0.05). The total number of rejections and the number of patients undergoing rejection were not significantly different in both groups. However, the intensity of rejection was significantly higher in group I with 41% (21/51) of severe or irreversible rejections versus 9/46 (19.5%) in group II (P less than 0.05). The first rejection occurred significantly earlier in group I than in group II since 75% of the first rejection episodes occurred in the first 10 days versus 38% in group II (P less than 0.02) with a mean delay of 12.8 +/- 3.2 and 19.10 +/- 3.3 days, respectively. Although platelet transfusions are devoid of leukocytes the incidence of CMV infection was not significantly different in both groups: 57% in group I and 68% in group II. Purified platelet transfusions did not induce humoral immunization but lack of sensitization does not imply indefinite graft prolongation. Because platelets do not carry class II antigens, purified platelets transfusions represent a useful model to analyze the role of class I antigens alone in the induction of unresponsiveness in organ transplantation.

Adult↗

Genetic and structural characterization of an amino acid dimorphism in glycoprotein Ib alpha involved in platelet transfusion refractoriness.

The platelet-specific alloantigen, Siba, located within the alpha-subunit of the glycoprotein (GP) Ib-IX membrane receptor, has been found to be involved in the pathogenesis of platelet transfusion refractoriness. We have identified the existence of a naturally occurring threonine/methionine dimorphism at position 145 of the GPIb alpha sequence, and determined that the Siba antigen corresponds to the molecule containing methionine145. The diallelic codons can be detected by restriction enzyme analysis of amplified genomic DNA fragments from the GPIb alpha gene. Evaluation of 61 healthy blood donors showed that the allele frequencies are 89% and 11% for the threonine145 and methionine145 codons, respectively. A positive correlation exists between platelet reactivity with the anti-Siba antibody and the presence of a methionine145-encoding allele. Moreover, recombinant expression of two soluble GPIb alpha fragments differing only at residue 145, provided definitive evidence that the human anti-Siba antibody reacts only with the molecule containing methionine145. These results explain the structural basis of the Siba human alloantigen system and define screening methodologies useful in transfusion medicine to match donor and recipient platelets accordingly.

Amino Acids↗

High dose intravenous gammaglobulin and platelet transfusions in leukaemic HLA-immunized patients.

3 aplastic patients with acute leukaemia, strongly HLA-immunized and refractory to platelet transfusions, received polyvalent gammaglobulin i.v. infusions (0.4 g/kg/d for 5 or 6 d) in association with daily random platelet transfusions. Platelet recovery was obtained in 2 patients. The 3rd patient did not show any significant rise in platelet count. The ability of gammaglobulin to prolong the life-span of incompatible transfused platelets could facilitate the management of HLA-immunized patients.

Adult↗

Platelet transfusions: the problem of refractoriness.

Refractoriness is a complication of multiple platelet transfusions in 30-70% of patients with bone marrow failure. The major causes are HLA alloimmunisation and non-immune platelet consumption; the latter is usually found in patients with DIC, septicaemia or splenomegaly. Initial management of alloimmunised patients who are refractory to platelet transfusions from random donors is the use of HLA-matched platelet donors; this results in improved responses to platelet transfusions in about 65% of these patients. Platelet crossmatching may reveal the presence of platelet-specific antibodies in some patients who are refractory to platelet transfusions from HLA-matched donors and may assist in the selection of compatible platelet donors. The identification of compatible donors is not possible in all refractory patients; alternative approaches such as plasma exchange and high dose intravenous gammaglobulin have been used in such patients with variable results. Insights into the mechanism of HLA alloimmunisation have suggested methods for its prevention. Primary HLA alloimmunisation is dependent on the presence in transfusions of contaminating cells bearing HLA class II antigens; pure platelet concentrates are non-immunogenic as platelets only express HLA class I antigens. Studies using leucocyte-poor blood components for multitransfused patients have demonstrated a reduction in HLA alloimmunisation from about 50-20% and a decrease in the incidence of refractoriness. Improvements in the techniques for leucocyte depletion of red cell and platelet concentrates and the possibility of inactivation of the HLA class II antigen-bearing cells by UV irradiation might make prevention of alloimmunisation an attainable goal in the near future.

Blood Platelets↗