Platelet function tests, independent of platelet count, are associated with bleeding severity in ITP

Frelinger, Andrew L.; Grace, Rachael F.; Gerrits, Anja J.; Berny‐Lang, Michelle A.; Brown, Travis; Carmichael, Sabrina L.; Neufeld, Ellis J.; Michelson, Alan D.

doi:10.1182/blood-2015-02-628461

Cited by 132 publications

(135 citation statements)

References 28 publications

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“…2 Recently, pediatric ITP patients with lower agonist inducible platelet activity were shown to have more severe bleeding than pediatric ITP patients with higher platelet activity and this association persisted after correction for platelet counts. 3 It is, however, unclear whether this observation also holds for adult ITP patients and how platelet activity in ITP patients compares to healthy controls.…”

Section: Introductionmentioning

confidence: 99%

Platelet function in adult ITP patients can be either increased or decreased, compared to healthy controls, and is associated with bleeding risk

et al. 2016

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Objectives: To test whether, together with platelet count, platelet activity could be an important predictor of bleeding risk in immune thrombocytopenia (ITP) patients.Methods: Platelet activity was tested by flow cytometric measurement of agonist induced P-selectin expression and compared between 23 adult ITP patients and 22 healthy volunteers. Results: Platelet activity could be either increased or decreased in ITP patients, compared to healthy volunteers. In the lowest platelet count category, normal to low platelet activity was associated with the biggest increase in bleeding risk. Risk difference 80% (95% confidence interval: 45-115%) for <32 × 10 9 platelets/L. For higher platelet counts, there was no association of platelet activity with bleeding risk. Discussion: Increased platelet activity was associated with decreased bleeding risk, but only in patients with low platelet counts. Conclusion: Platelet activity can be a predictor of bleeding risk in ITP patients with low platelet counts.

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Section: Introductionmentioning

confidence: 99%

Platelet function in adult ITP patients can be either increased or decreased, compared to healthy controls, and is associated with bleeding risk

et al. 2016

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“…Assessment of P-selectin exposure and GPIIbIIIa activation by flow cytometry is an accepted approach for quantifying platelet activation, and this approach has been used to characterize platelet activation in patients with thrombocytopenia [8, 17]. Interpretation of the results of such studies is, however, hampered by failure to include controls with similarly low numbers of normally functioning platelets.…”

Section: Resultsmentioning

confidence: 99%

“…Platelet dysfunction likely contributes to bleeding in thrombocytopenic patients [7, 8]. Assessment of platelet function in patients with thrombocytopenia may help to identify patients who are at risk for bleeding and therefore requires a prophylactic platelet transfusion.…”

Section: Introductionmentioning

confidence: 99%

“…It can be used to evaluate resting and agonist-stimulated platelets by measuring physical characteristics such as size and granularity and surface expression of integrins, granule contents, and bound ligands [15, 16]. Flow cytometry has been used to investigate platelet activation in patients with idiopathic thrombocytopenia purpura (ITP) and chemotherapy-induced thrombocytopenia [8, 17]. However, the ability of flow cytometry to measure platelet function irrespective of platelet count has not been thoroughly tested.…”

Section: Introductionmentioning

confidence: 99%

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A whole blood model of thrombocytopenia that controls platelet count and hematocrit

Bercovitz¹,

Brenner

Newman

2016

Ann Hematol

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In patients with thrombocytopenia, it can be difficult to predict a patient’s bleeding risk based on platelet count alone. Platelet reactivity may provide additional information; however, current clinical assays cannot reliably assess platelet function in the setting of thrombocytopenia. New methods to study platelet reactivity in thrombocytopenic samples are needed. In this study, we sought to develop a laboratory model of thrombocytopenia using blood from healthy subjects that preserves the whole blood environment and reproducibly produces samples with a specific platelet count and hematocrit. We compared the activation state of unstimulated and agonist-stimulated platelets in thrombocytopenic samples derived from this method with normocytic controls. Whole blood was diluted with autologous red blood cell concentrate and platelet-poor plasma, which were obtained via centrifugation, in specific ratios to attain a final sample with a predetermined platelet count and hematocrit. P-selectin exposure and GPIIbIIIa activation in unstimulated platelets and platelets stimulated with collagen-related peptide (CRP) or adenosine diphosphate (ADP) in thrombocytopenic samples and the normocytic control from which they were derived were quantified by flow cytometry. Our methodology reliably produced thrombocytopenic samples with a platelet count ≤50,000/µL and an accurately and precisely controlled hematocrit. P-selectin exposure and GPIIbIIIa activation on unstimulated platelets or on ADP- or CRP-stimulated platelets did not differ in thrombocytopenic samples compared to normocytic controls. We describe a new method for creating thrombocytopenic blood that can be used to better understand the contributions of platelet number and function to hemostasis.

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“…Thrombocytopenia, particularly at markedly low levels, may raise concerns of increased bleeding risk. However, it is increasingly observed that platelet count in isolation is an imprecise predictor of bleeding as patients with similarly low platelet count can demonstrate differing tendencies in bleeding . The recent platelet dose (PLADO) trial found that bleeding occurred over a wide range of platelet counts and that prophylactic platelet transfusion did not prevent bleeding.…”

Section: Introductionmentioning

confidence: 99%

A comparison of global coagulation assays between normal controls and patients with thrombocytopenia

Lim

Leung

Manitta

et al. 2018

Int J Lab Hematology

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Introduction Some patients with thrombocytopenia may be at risk of bleeding although quantitative platelet count is not always a sufficient predictive factor. Global coagulation assays such as thromboelastography (TEG®), calibrated automated thrombogram (CAT) and overall haemostatic potential (OHP) may provide a better assessment of an individual's haemostatic profile. Methods Blood samples were collected from thrombocytopenic patients. TEG® was performed on citrated whole blood, while CAT and OHP were performed on platelet‐poor plasma. Results were compared to our previously collected normal controls. Results Fifty‐eight participants (24 immune thrombocytopenia, 34 chemotherapy/malignancy‐related) with mean age of 57.5 years were recruited. Compared to normal controls, thrombocytopenic participants had comparable maximum amplitude but reduced clot lysis (0.0% vs 0.6%; P < 0.001) on TEG® with reduced endogenous thrombin potential on CAT (1252.2 vs 1353.0 nmol/L/min; P = 0.040). No differences were seen in the OHP parameters. TEG® showed significant difference between marked and mild thrombocytopenia groups with minimal differences seen on CAT and OHP. Those with marked thrombocytopenia showed reduced maximum amplitude (47.2 vs 57.8 mm; P = 0.002) as expected while participants with mild thrombocytopenia (platelet count 100‐150 × 109/L) paradoxically demonstrated increased maximum amplitude (66.4 vs 57.8 mm; P < 0.001). Conclusion Global coagulation assays, particularly TEG®, can detect subtle differences in coagulation in thrombocytopenic patients. While patients with marked thrombocytopenia showed reduced maximum amplitude, patients with mild thrombocytopenia appear to paradoxically show increased maximum amplitude, suggesting compensatory activity within the coagulation pathway which may in part explain why not all thrombocytopenic patients have bleeding complications.

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Platelet function tests, independent of platelet count, are associated with bleeding severity in ITP

Cited by 132 publications

References 28 publications

Platelet function in adult ITP patients can be either increased or decreased, compared to healthy controls, and is associated with bleeding risk

Platelet function in adult ITP patients can be either increased or decreased, compared to healthy controls, and is associated with bleeding risk

A whole blood model of thrombocytopenia that controls platelet count and hematocrit

A comparison of global coagulation assays between normal controls and patients with thrombocytopenia

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