Clinical significance of platelet microparticles in autoimmune thrombocytopenias.

Platelet microparticles (PMPs) are vesicles derived from platelet membranes that are too small (less than 0.5 micron) to be detected in routine platelet counting. They arise in association with platelet activation and other unknown causes. Elevated PMPs have been observed in idiopathic thrombocytopenic purpura (ITP), a disorder in which autoantibody interacts with platelets and the opsonized platelets are destroyed by macrophages. However, the clinical significance of PMP has been unknown. Using flow cytometry, we examined PMP concentrations in 62 patients with ITP and in 33 normal control subjects to assess the clinical significance of PMP in ITP. When compared with PMP levels in control subjects, PMP levels were significantly higher (p less than 0.005) in patients with ITP, but considerable variation among individual patients was observed. Patients with platelet counts less than or equal to 60,000 were evaluated for correlation of PMP levels with manifestations of thrombocytopenias; patients without symptoms (free of petechiae or mucosal bleeding) are found to have significantly higher PMP levels (p less than 0.05) than patients with symptoms, suggesting hemostatic protection by PMP. Additionally, we identified a group of patients with ITP who experienced neurologic complications resembling transient cerebral ischemic attacks (TIAs): recurrent episodes of dizzy spells or weakness in mild cases, and coma, seizure, or progressive dementia in advanced cases. Small cerebral infarcts were demonstrated by computed axial tomography scan or magnetic resonance imaging in spite of severe thrombocytopenias. Patients with this syndrome are often found to have higher PMP levels (p less than 0.005) when compared with the group free of neurologic complications. It is concluded that PMPs play an important role in hemostasis in patients with thrombocytopenia, and that high concentrations of hemostatically active PMP can be thrombogenic in certain clinical settings. Quantitation and characterization of PMP is important in assessment and management of patients with thrombocytopenia.     

Effect of serum derived blocking factor (SDBF) on platelet associated-IgG

We analyzed the effect of an unknown factor, which derived from serum, on platelet associated IgG (PA-IgG) and we established the novel immunofluorescence method to measure the level of PA-IgG. Blood samples were obtained from 20 patients with idiopathic thrombocytopenic purpura (ITP). After the treatment of platelets with neuraminidase, the value of PA-IgG positive platelets (%PA-IgG) were significantly increased in patients with ITP, but not in controls. When the platelets pretreated with neuraminidase were incubated with human serum, %PA-IgG was remarkably decreased in ITP patients. In healthy individuals, when platelets bound to aggregated human IgG pretreated with human serum, the binding of FITC-conjugated anti-human IgG was inhibited. And the value of mouse anti-GP II b/III a monoclonal antibody positive platelets was decreased, when the platelets preincubated with mouse serum. The binding of FITC-conjugated anti-human IgG and anti-mouse IgG antibody was apparently inhibited by some unknown factor in serum. Our results showed that this substance had species specificity. We called this substance "Serum Derived Blocking Factor (SDBF)".     

Comparison of platelet immunity in patients with SLE and with ITP

Idiopathic thrombocytopenic purpura (ITP) is characterized by the development of a specific anti-platelet autoantibody immune response mediating the development of thrombocytopenia. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of a wide variety of autoantibodies. In 15-20% of SLE cases, patients develop thrombocytopenia which appears to be autoimmune in nature (SLE-TP). To better understand the pathogenesis of the thrombocytopenia associated with SLE, we investigated the overlapping platelet and cellular immune features between SLE and ITP. Thirty-one patients with SLE, eight with SLE-TP, and 17 with ITP, were studied and compared to 60 healthy controls. We evaluated platelet-associated IgG, platelet microparticles, reticulated platelets, platelet HLA-DR expression, in vivo cytokine levels, lymphocyte proliferation, and the T lymphocyte anti-platelet immune response in these patients. Patients with SLE-TP and those with ITP had increased platelet-associated IgG, an increased percentage of platelet microparticles, a higher percentage of reticulated platelets and larger platelets, suggesting antibody-mediated platelet destruction and increased platelet production. More than 50% of patients with ITP had increased HLA-DR on their platelet surface whereas subjects with SLE-TP did not. Analysis of serum cytokines demonstrated increased levels of IL-10, IL-15 and TNF-alpha in patients with SLE, but in those with ITP, only increased levels of IL-15 were seen, no increases in any of these cytokines were observed in patients with in SLE-TP. The ability of lymphocytes to proliferate in response to phorbol myristate acetate (PMA) stimulation was increased in SLE-TP, but was normal in both SLE and ITP. Lymphocytes from subjects with ITP displayed an increased ability to proliferate on exposure to platelets, in contrast, those with SLE-TP did not. While the number of subjects evaluated with SLE-TP was small, these data reveal a number of differences in the immunopathogenesis between SLE-TP and ITP.     

Autoreactive T cells to platelet GPIIb-IIIa in immune thrombocytopenic purpura. Role in production of anti-platelet autoantibody.

T cell proliferative responses to platelet membrane GPIIb-IIIa were examined in 14 patients with chronic immune thrombocytopenic purpura (ITP), 7 systemic lupus erythematosus (SLE) patients with or without thrombocytopenia, and 10 healthy donors. Although peripheral blood T cells from all subjects failed to respond to the protein complex in its native state, reduced GPIIb-IIIa stimulated T cells from three ITP patients and one SLE patient with thrombocytopenia, and tryptic peptides of GPIIb-IIIa stimulated T cells from nearly all subjects. The specificity of the responses for GPIIb-IIIa was confirmed by activation of GPIIb-IIIa-primed T cells by a recombinant GPIIbalpha fragment in secondary cultures. Characterization of T cell response induced by modified GPIIb-IIIa showed that the response was restricted by HLA-DR, the responding T cells had a CD4(+) phenotype, and the proliferation was accelerated only in ITP patients, suggesting in vivo activation of these T cells. In vitro IgG anti-GPIIb-IIIa synthesis in PBMC cultures was induced by modified GPIIb-IIIa specifically in ITP patients with platelet-associated anti-GPIIb-IIIa antibody. Anti-GPIIb-IIIa antibody produced in supernatants was absorbed by incubation with normal platelets. In summary, CD4(+) and HLA-DR-restricted T cells to GPIIb-IIIa are involved in production of anti-platelet autoantibody in ITP patients and are related to the pathogenic process in chronic ITP.     

Platelet specific alloantigens.

The ability of platelets to aggregate and to form a platelet plug is central to the maintenance of normal hemostasis. When platelets have normal function, the severity of bleeding is related to the degree of thrombocytopenia. In patients with normal platelet production, the most common cause of thrombocytopenia is due to immune mechanisms that results in platelet injury and removal from the circulation. These mechanisms involve the binding of platelet-associated immunoglobulins and are classified as immune. Immune thrombocytopenias can be caused by autoantibodies (autoimmune thrombocytopenia), alloantibodies (isoimmune thrombocytopenia), or drug-induced immune complexes and conditions secondary to autoimmune disorders such as systemic lupus erythematosus. In this paper the focus is on alloimmune thrombocytopenias resulting from the formation of alloantibodies to platelet specific antigens. The clinical importance of the platelet alloantigens is due to their ability to elicit alloantibody production. Alloantigens, also referred to as isoantigens, are substances that induce the production of alloantibodies when they are infused into individuals of the same species who lack the specific alloantigen.     

Is the thrombopoietin assay useful for differential diagnosis of thrombocytopenia? Analysis of a cohort of 160 patients with thrombocytopenia and defined platelet life span

BACKGROUND: Thrombopoietin (TPO), the major hormone controlling platelet production, has been measured in thrombocytopenias with discordant results. The aim of our work was to assess the value of the TPO assay for differential diagnosis of thrombocytopenias in a large cohort of patients classified according to the results of their platelet isotopic study. METHODS: We measured TPO (R&D Systems) in serum of 160 thrombocytopenic patients referred to our department for platelet life span isotopic studies. We classified patients as follows: (a) idiopathic or autoimmune thrombocytopenia group (ITP; patients with increased platelet destruction and shortened platelet life span; n = 67); (b) pure genetic thrombocytopenia group (patients with decreased platelet production, normal platelet life span, and without bone marrow aplasia; n = 55); (c) bone marrow aplasia group (BM; patients with decreased platelet production, normal platelet life span, and bone marrow aplasia; n = 13). RESULTS: In patients with pure genetic thrombocytopenia, TPO (median, 55 ng/L) was not different from TPO in patients with ITP (median, 58 ng/L) or controls (n = 54; median, 51 ng/L). Only in patients with bone marrow aplasia was TPO significantly higher (median, 155 ng/L) and negatively correlated to the platelet count (r(2) = 0.5014). CONCLUSIONS: Although the median serum TPO is increased in thrombocytopenia with decreased platelet production from bone marrow aplasia, it does not differentiate patients with pure genetic thrombocytopenia from those with ITP.     

巨核细胞与血小板参数在血小板减少性疾病中的应用

目的探讨巨核细胞与血小板(PLT)参数在血小板减少性疾病中的应用价值。方法对72例血小板减少症患者分组进行巨核细胞数及血小板4项参数[PLT、血小板体积(PCT)、血小板平均体积(MPV)、血小板体积分布宽度(PDW)]检测,并做比较。结果与正常对照组相比,PLT值特发性血小板减少性紫癫(ITP)组最低(P<0.01),脾亢组次之(P<0.01),PCT与PLT变化一致,各组PDW均增高(P<0.01),MPV以ITP组与免疫组显著增高(P<0.05);其他各组与ITP组相比,巨核细胞数、PLT值、PCT均有显著性差异(P<0.01),免疫组与ITP组相比MPV、PDW有显著性差异(P<0.05)。4组病例骨髓均表现为巨核细胞成熟障碍,ITP组巨核细胞总数及颗粒巨明显增多,巨幼细胞性贫血(MgA)组巨核细胞呈病态改变。结论观察血小板参数及巨核细胞的形态特征,对血小板减少性疾病诊断及鉴别诊断具有重要意义。     

Differences in platelet function in patients with acute myeloid leukemia and myelodysplasia compared to equally thrombocytopenic patients with immune thrombocytopenia

Summary. Background: Severe thrombocytopenia is a major risk factor for hemorrhage, but platelet function and bleeding risk at low platelet counts are poorly understood, because of the limitations of platelet function testing at very low platelet counts. Objectives: To examine and compare platelet function in severely thrombocytopenic patients with acute myeloid leukemia (AML) or myelodysplasia (MDS) with that in patients with immune thrombocytopenia (ITP). Methods: Whole blood flow cytometric measurement of platelet activation and platelet reactivity to agonists was correlated with the immature platelet fraction (IPF) and bleeding symptoms. Results: Patients with AML/MDS had smaller platelets, lower IPF and substantially lower platelet surface expression of activated glycoprotein (GP)IIb–IIIa and GPIb, both with and without addition of ex vivo ADP or thrombin receptor‐activating peptide, than patients with ITP. In both ITP and AML/MDS patients, increased platelet surface GPIb on circulating platelets and expression of activated GPIIb–IIIa and GPIb on ex vivo activated platelets correlated with a higher IPF. Whereas platelet reactivity was higher for AML/MDS patients with bleeding than for those with no bleeding, platelet reactivity was lower for ITP patients with bleeding than for those with no bleeding. Conclusions: AML/MDS patients have lower in vivo platelet activation and ex vivo platelet reactivity than patients with ITP. The proportion of newly produced platelets correlates with the expression of platelet surface markers of activation. These differences might contribute to differences in bleeding tendency between AML/MDS and ITP patients. This study is the first to define differences in platelet function between AML/MDS patients and ITP patients with equivalent degrees of thrombocytopenia.     

Platelet size distinguishes between inherited macrothrombocytopenias and immune thrombocytopenia

Summary. Background: Distinguishing inherited thrombocytopenias from immune thrombocytopenia (ITP) can be difficult, and patients are therefore at risk of misdiagnosis and inappropriate treatments. Although it is known that the most common inherited forms of thrombocytopenia are characterized by increased platelet size, the diagnostic power of this feature has never been investigated. Objectives: The aim of this study was to test the hypothesis that platelet size can be used to differentiate ITP from inherited macrothrombocytopenias. Patients/methods: We measured mean platelet volume (MPV) and mean platelet diameter (MPD), within 2 h of blood sampling, in 35 patients with inherited macrothrombocytopenias [15 MYH9‐related disease (MYH9‐RD), three biallelic and 17 monoallelic Bernard–Soulier syndrome (BSS)], and 56 with ITP. Using receiving operating characteristic analysis, we searched for the best cut‐off values to differentiate between these conditions. Results: As expected, platelets were larger in inherited macrothrombocytopenias than in ITP. An MPD larger than 3.3 μm differentiated MYH9‐RD and BSS from ITP with 0.89 sensitivity and 0.88 specificity, and an MPV larger than 12.4 fL had 0.83 sensitivity and 0.89 specificity. Combining MPD with MPV increased sensitivity and specificity to 0.97 and 0.89, respectively. Conclusion: Platelet size evaluation by both an appropriate cell counter and blood film examination is useful for differentiating inherited macrothrombocytopenias from ITP.     

丁胺卡那霉素对EDTA依赖性凝集血小板的解离及其机制

目的研究丁胺卡那霉素对EDTA抗凝剂依赖的聚集血小板的解离作用和机制,为血常规标本中血小板凝聚提供可靠的解决方法。方法在EDTA依赖的假性血小板减少症(PTCP)患者的EDTA-K2抗凝血样本中,于不同时间段加入不同浓度丁胺卡那霉素进行凝集血小板的解离试验,通过血小板计数和涂片观察解离效果;用流式细胞仪检测血小板膜表面CD41、CD61、CD62p、PAC-1和IgG的表达百分率。结果抽血后1h内加入丁胺卡那霉素对血小板凝集的解离作用明显,血小板计数可恢复到即时检测的水平,血小板CD62p、PAC-1和IgG的表达量被显著抑制,而CD41和CD61未受明显影响。结论PTCP患者血常规样品抽血后1h内加入丁胺卡那霉素能有效解离凝集的血小板,作用机制可能与抑制患者血小板膜表面CD62p、PAC-1和IgG的表达有关;此法有助于解决EDTA所致的血小板计数的假性减少。     

Thrombocytopenia caused by platelet destruction,consumption or abnormal pooling

In this article, we refer to thrombocytopenia caused by increased destruction/consumption of platelets(immune thrombocytopenia and non-immune thrombocytopenia), abnormal pooling, and dilutional loss. The cause of idiopathic thrombocytopenic purpura (ITP) is a accelerated platelet destruction due to autoimmune mechanism. Differential diagnosis is important between ITP and other thrombocytopenic disorders, because the treatment and prognosis are distinct. Drug-induced thrombocytopenia is the most common among secondary autoimmune thrombocytopenia and clinically important. The immediate cessation of all suspect drugs is necessary when drug-induced thrombocytopenia is suspected. Thrombocytopenia of disseminated intravascular coagulation(DIC) and thrombotic microangiopathy(TMA) occur in diffuse intravascular coagulation and induce thrombocytopenia by the consumption of the platelet.     

SLFN14 mutations underlie thrombocytopenia with excessive bleeding and platelet secretion defects

Inherited thrombocytopenias are a group of disorders that are characterized by a low platelet count and are sometimes associated with excessive bleeding that ranges from mild to severe. We evaluated 36 unrelated patients and 17 family members displaying thrombocytopenia that were recruited to the UK Genotyping and Phenotyping of Platelets (GAPP) study. All patients had a history of excessive bleeding of unknown etiology. We performed platelet phenotyping and whole-exome sequencing (WES) on all patients and identified mutations in schlafen 14 (SLFN14) in 12 patients from 3 unrelated families. Patients harboring SLFN14 mutations displayed an analogous phenotype that consisted of moderate thrombocytopenia, enlarged platelets, decreased ATP secretion, and a dominant inheritance pattern. Three heterozygous missense mutations were identified in affected family members and predicted to encode substitutions (K218E, K219N, and V220D) within an ATPase-AAA-4, GTP/ATP-binding region of SLFN14. Endogenous SLFN14 expression was reduced in platelets from all patients, and mutant SLFN14 expression was markedly decreased compared with that of WT SLFN14 when overexpressed in transfected cells. Electron microscopy revealed a reduced number of dense granules in affected patients platelets, correlating with a decreased ATP secretion observed in lumiaggregometry studies. These results identify SLFN14 mutations as cause for an inherited thrombocytopenia with excessive bleeding, outlining a fundamental role for SLFN14 in platelet formation and function.     

血小板参数在血小板减少症鉴别诊断中的价值探讨

目的 探讨血小板参数在鉴别骨髓性和非骨髓性血小板减少症中的作用.方法 使用Cell-Dyn3700血细胞分析仪检测血小板减少症(TP)76例、特发性(免疫性、原发性)血小板减少性紫癜(ITP)66例、继发性血小板减少性紫癜(STP)8例、获得性纯巨核细胞再生障碍性血小板减少性紫癜(AATP)8例、造血干细胞疾病(HSCD)(急性白血病、再生障碍性贫血、骨髓增生异常综合征)140例、健康体检者100例(对照组)的血小板计数(PLT)、平均血小板体积(MPV)、血小板压积(PCT)、血小板分布宽度(PDW).结果 ①与对照组相比,HSCD患者的MPV显著减少,PDW明显增加;STP患者MPV、PDW显著增大.②AATP患者MPV正常,PDW增大.③ITP组和TP组与对照组的MPV、PCT、PDW差异有统计学意义(均P＜0.01).④HSCD组与对照组、ITP组和TP组比较,MPV、PCT和PDW差异有统计学意义(均P＜0.01).⑤骨髓性TP组与非骨髓性TP组比较,其MPV和PDW均有统计学意义(均P＜0.01).⑥当ITP患者治疗有效时,PLT升高,其MPV和PDW下降.结论 通过观察MPV和PDW数值的升降,特别是MPV的变化可初步判断血小板减少是由骨髓病变(MPV＜参考值)还是由骨髓外病症(MPV＞参考值)所引起.另外,当ITP患者治疗有效时,可用PDW和MPV较早地(比PLT提前5 d)观察到疗效.血小板参数的动态观察有助于ITP的鉴别诊断、病情判断及疗效观察.     

Characterization of antibodies directed against platelet cryptantigens detected during the immunological study of 356 consecutive patients with presumed autoimmune thrombocytopenia (AITP)

SUMMARY. Cryptic antigens are detected by anti-bodies present in a wide spectrum of patients with or without thrombocytopenia, and even in healthy individuals. They are produced for unknown reasons and do not react with antigens of native platelets, but only with altered platelets. Cryptantigen antibodies may not only result in spuriously low platelet counts, but also in 'falsely' positive tests for platelet antibodies. We report our experience in the characterization of the different types of antibodies directed against cryptantigens of platelets: EDTA-dependent antibodies, PFA-dependent antibodies, EDTA-PFA-dependent antibodies and cold agglutinins. These antibodies were detected in the course of the serological study of 37 patients from a group of 356 (10%) whose blood was sent to our laboratory for platelet antibody testing. Pseudothrombocytopenia was diagnosed in 24 cases. Twenty-one of these showed EDTA-dependent or EDTA-PFA-dependent platelet agglutination and three were due to the presence of cold agglutinins. In 13 patients the thrombocytopenia was genuine. Eleven of these presented EDTA-dependent or EDTA-PFA-dependent antibodies in their serum and in the two remaining cases PFA-dependent antibodies were found. Cryptantigen antibodies were also detected in 9 out of 228 (4%) blood donors who were used as healthy controls in the platelet immunofluorescence test. In the light of the results obtained we put forward some guidelines to detect the presence of these antibodies and establish an accurate serological and clinical diagnosis of the autoimmune thrombocytopenias.     

Protein C inhibitor and serum amyloid A in immune thrombocytopaenic purpura

In immune thrombocytopaenic purpura (ITP), phagocytic cells prematurely destroy platelets opsonized by anti-platelet auto-antibodies, while residual platelets rescued from these autoimmune attacks are hyperfunctioning. The exact pathobiological basis of this phenomenon is unknown. Protein C inhibitor (PCI), a platelet alpha-granule pro-coagulant molecule, is released on activation of platelets. Serum amyloid A (SAA; an acute phase protein), however, inhibits platelet aggregation and modulates platelet adhesion. We aimed to assess circulating soluble plasma PCI and SAA concentrations in 17 patients with newly diagnosed ITP and ten healthy volunteers. Plasma PCI concentrations tended to be higher in ITP patients, despite absolute thrombocytopaenia, than in normal controls. SAA levels were significantly higher in ITP patients compared with the control group. We conclude that secretion of the alpha-granule PCI content of platelets could result from platelet activation, and that PCI may be the link between platelet microparticles and haemostatically active ITP platelets. Increased concentrations of SAA and PCI may interfere with the disordered and compensatory pro-coagulant mechanisms of ITP.     

Plasma thrombospondin in immune thrombocytopenic purpura

Patients with immune thrombocytopenic purpura (ITP) rarely suffer life-threatening haemorrhages despite significant thrombocytopenia, probably because large numbers of hyperfunctioning platelets are present. Thrombospondin is a platelet alpha-granule protein and its plasma level may reflect platelet activation. We assessed circulating thrombospondin levels in 12 newly diagnosed ITP patients (one man; 11 women, aged 36 +/- 16 years) before they were treated for ITP. Twelve healthy people (four men; eight women, aged 31 +/- 11 years) acted as controls. Plasma thrombospondin concentrations were measured using enzyme-linked immunoassays. Thrombospondin concentrations tended to be higher, despite thrombocytopenia, in ITP patients (158.8 +/- 28.2 ng/ml) compared with controls (120.7 +/- 18.2 ng/ml). The difference was not statistically significant, but the relatively high circulating thrombospondin concentrations we observed suggest that residual platelets could be activated in ITP, thus indicating a more benign clinical course compared with aplastic thrombocytopenia.     

Determinants of donor platelet variability when testing for heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia is a common immune-mediated drug reaction that can be complicated by life-threatening arterial thrombosis. The diagnosis can be confirmed by demonstrating heparin-dependent release of radiolabeled serotonin from washed normal platelets in the presence of patient serum. However, certain serum samples from these patients produce 14C-serotonin release from some but not other normal donor platelets. We investigated this problem of donor platelet variability by studying the reactivities of 10 serum samples from patients with heparin-induced thrombocytopenia with platelets from 10 normal donors (100 serum and platelet combinations). We observed a marked variability in reactivity for patient serum and platelets from normal donors; this initially appeared random. However, closer examination indicated that the reactivities varied hierarchically. Because heparin-induced thrombocytopenia is caused by binding of heparin-dependent IgG to platelet Fc receptors, we examined whether platelet Fc receptor number or function explained the variability in platelet reactivity. We observed that platelet Fc receptor function, as measured by platelet release associated with heat-aggregated IgG, was highly correlated with platelet reactivity to heparin-induced thrombocytopenia serum samples. No significant correlation, however, was found between Fc receptor number and platelet response. Reaction of murine monoclonal antibodies that activate human platelets by means of the platelet Fc receptors was not predictive of platelet reactivity to heparin-induced thrombocytopenia serum.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reticulated platelet counts correlate with treatment response in patients with idiopathic thrombocytopenic purpura and help identify the complex causes of thrombocytopenia in patients after allogeneic hematopoietic stem cell transplantation

BACKGROUND: In thrombocytopenic conditions of unknown origin, quantification of reticulated platelets (RP) in the peripheral blood by flow cytometry has been shown to differentiate increased platelet (Plt) turnover from insufficient Plt production. METHODS: We used a whole blood flow cytometry method combining thiazole orange and anti-CD41a-staining to assess RP in 71 healthy subjects, six with thrombocytopenic myelodysplastic syndrome (MDS), nine with liver cirrhosis, 14 patients with idiopathic thrombocytopenic purpura (ITP), and 12 patients who had undergone hematopoietic stem cell transplantation (HSCT). RESULTS: Patients with MDS had normal, patients with liver cirrhosis had slightly elevated RP counts compared to healthy subjects. ITP patients had elevated RP counts, and RP >15% were associated with treatment response (P = 0.015). In 7/10 patients after HSCT, an increase of RP preceded Plt recovery, whereas in patients with secondary thrombocytopenia after normal regeneration, the assessment of RP allowed the differentiation between conditions with high Plt turnover, such as GvHD and microangiopathy, indicated by high RP counts, and graft failure, indicated by low RP counts. CONCLUSIONS: Our data provide the rationale for prospective studies on the diagnostic and prognostic value of RP counts in larger patient populations with ITP and after HSCT.     

Viability and function of platelet concentrates stored in CPD-adenine (CPDA-1)

The effective use of CPDA-1 as an anticoagulant in routine blood banking practice requires demonstration that platelet concentrates prepared in this solution meet both in vitro quality control standards and maintain posttransfusion viability and function after storage. In this study of 138 units of CPDA-1 platelet concentrates, the average platelet count was 8.0 +/− 0.2 × 10(10) with 81 per cent of the units having greater than 5.5 × 10(10) platelets. The mean poststorage pH was 6.68 +/− 0.03 and only four of the units had a pH of less than 6.0 (3%). Residual plasma volume averaged 75 +/− 1 ml. Platelet viability was determined in 16 normal volunteers by measuring survival of 51Cr- labeled autologous platelets after storage for 72 hours at 22 +/− 2 C. Platelet recovery averaged 50 +/− 4 per cent, while survival was 7.3 +/− 0.4 days for the 15 units with a pH above 6.0. Measurements of posttransfusion platelet viability and function were made in 12 paients with thrombocytopenia secondary to marrow failure. Their mean pretransfusion platelet count was 17,000 +/− 2,000/microliter, and their standardized template bleeding times were all greater than 30 minutes. Platelet recovery averaged 44 +/− 5 per cent and survival 3.3 +/− 0.5 days. In seven of the patients with the best posttransfusion increments, bleeding time was improved. Five patients with poor posttranfusion platelet increments showed no improvement in bleeding time with CPDA-1; two of these patients were also transfused with CPD platelets and had no response. Our studies indicate that platelet concentrates prepared in CPDA-1 meet in vitro quality control standards and after transfusion, maintain viability and function comparable to that of CPD collected platelets.