Volume 44, Issue 5 - Special Issue: Platelets — Updates for the Routine Laboratory; Issue Editors: Matthias Orth, Carl Thomas Nebe, Peter Schuff-Werner

Background The examination of a peripheral blood smear is mandatory in case of unexplained thrombocytopenia or thrombocytosis. First, the number of platelets should be estimated in order to confirm the platelet count determined by the haematology analyser, and to rule out causes of spuriously low or elevated platelet counts. Second, the size and morphological features of the platelets, which may provide information on the underlying cause of the low or enhanced platelet count, have to be assessed. Content This review summarizes the physiological and pathological features of platelet size and morphology, circulating megakaryocytes, micromegakaryocytes and megakaryoblasts, and provides an overview of current guidelines on the reporting of platelet morphology. Summary In the diagnostic work-up of a patient with thrombocytopenia, the size of the platelets is of diagnostic relevance. Thrombocytopenia with small platelets is suggestive of a defect in platelet production, whereas the presence of large platelets is more likely to be associated with enhanced platelet turnover or hereditary thrombocytopenias. Morphological platelet abnormalities may affect the granulation and the shape and are frequently associated with abnormalities of platelet size. Platelet anomalies can be found in various haematologic disorders, such as myelodysplastic syndromes, myeloproliferative neoplasms, acute megakaryoblastic leukaemia or hereditary thrombocytopenias.

Reticulated platelets are immature platelets freshly released from the bone marrow into the circulation and contain vestigial amounts of ribonucleic acid. Thus, they can serve as an indicator for the activity of thrombopoiesis. Despite the current lack of a standardized reference method, two types of hematology analyzers have incorporated a fully automated measurement of reticulated platelets. The “immature platelet fraction” (IPF; Sysmex XE-/XN-series) has some clinical utility in the differential diagnosis of thrombocytopenia. This is less clear for “reticulated platelets” (retPLT; Abbott CELL-DYN Sapphire/Alinity HQ). The usefulness of these parameters in the prediction of platelet recovery after chemotherapy or stem cell transplantation and as a decision aid for platelet transfusions has not been unequivocally confirmed. Recent findings have shown an association of reticulated platelets with an adverse risk in patients with coronary artery disease and stroke as well as resistance to anti-platelet therapy. Furthermore, a role of reticulated platelets for the prediction of sepsis was indicated. However, validation in larger prospective trials is necessary to establish the clinical benefit of reticulated platelets in these conditions. This review gives an overview of the available analytical methods and summarizes the current knowledge regarding the clinical application of reticulated platelets.

Platelets are the smallest and perhaps the most versatile components of human blood. Besides their role in coagulation and the maintenance of vascular integrity, they are involved in many physiological processes, ranging from immune response and leukocyte recruitment to the production of antimicrobial peptides and immune-suppressive factors like TGF-β. These versatile abilities make platelets interesting for researchers from different disciplines. However, beside profound investigation into platelets’ physiological role, there is a need for correct, standardized and thus reproducible quantification of platelet parameters. Mean platelet volume (MPV) is a widespread prognostic marker for several conditions, such as, acute coronary syndrome, chronic kidney disease and liver cirrhosis. Platelet activation is regarded as a marker for inflammatory processes, for example in autoimmune diseases such as type-1 diabetes, systemic lupus erythematosus and rheumatoid arthritis. The monitoring of platelet function is relevant for patients receiving antiplatelet medication. Platelet parameter measurement is affected by the choice of in vitro anticoagulant, the measurement technology and the time delay after sampling. This review focuses on the pre-analytical variability that arises as a result of the use of different in vitro anticoagulants and analyzer technologies when determining platelet parameters, since, even approximately 180 years after the discovery of platelets, there is still no standardized procedure.

Platelet autoantibodies are a common finding in immune thrombocytopenia (ITP) and in rare cases of antibody-mediated platelet function (“acquired thrombasthenia”). In drug-induced immune thrombocytopenia, antibodies react with platelets only in the presence of the offending drug. Alloantibodies reacting with platelets are induced by transfusion of cellular blood products or during pregnancy. They are responsible for fetal/neonatal alloimmune thrombocytopenia (FNAIT), they are able to cause febrile, nonhemolytic transfusion reactions and they give rise to insufficient platelet increments following platelet transfusions. Two rare transfusion reactions: post-transfusion purpura (PTP) and passive alloimmune thrombocytopenia (PAT) are triggered by platelet alloantibodies. This review discusses the clinical value of tests for platelet antibodies in various clinical situations related to insufficient primary hemostasis.

Platelet transfusion is a topic of common interest for many specialists involved in patient care, from laboratory staff to clinical physicians. Various aspects make this type of transfusion different from those of other blood components. In this review, the challenges in platelet transfusion practice that are relevant for laboratory colleagues will be discussed, highlighting how the biochemical and structural characteristics of these blood elements directly affect their function and consequently the clinical outcome. More than 1,300 platelet concentrates are transfused in Germany every day, and several types are offered by their respective manufacturers. We describe the technological advances in platelet concentrate production, with a focus on how the storage conditions of platelets can be improved. Laboratory quality assessment procedures for a safe transfusion are discussed in detail. For this purpose, we will refer to the Hemotherapy Directives ( Richtlinie Hämotherapie ) of the German Medical Association.

Anticoagulation with ethylenediaminetetraacetic acid (EDTA) is a necessary pre-requisite for automated blood cell counting. With a prevalence of 0.01–1%, EDTA anticoagulation is accompanied by time- and temperature-dependent in vitro aggregation of platelets, resulting in false low counts. To avoid wrong clinical conclusions, spontaneous anticoagulant-induced platelet agglutination should therefore be recognized during analysis. This might be a challenge for the routine laboratory. The actual knowledge of this rare but clinically important laboratory artefact will be summarized and reviewed in the following, based on our own experiences and the available literature. This includes pathophysiological and epidemiological aspects, valuable information regarding the detection and prevention of a PTCP, and the possibilities for determination of the correct platelet count.

The mean platelet volume (MPV) is an easy, rapid and inexpensive laboratory parameter which basically mirrors platelet size. Due to the essential role of platelets in hemostasis, many studies have assessed the MPV value in patients with arterial and venous thrombotic disorders. These have then been summarized in some interesting meta-analyses and recent studies that will be discussed in this narrative review. Taken together, the currently available evidence suggests that the MPV may be substantially increased in concomitance with acute episodes of coronary artery disease, venous thromboembolism, portal vein thrombosis, stroke, erectile dysfunction and preeclampsia. In many of these conditions, an increased MPV value may also be associated with unfavorable outcomes. Despite these convincing findings, some important technical issues should be considered for improving the clinical usefulness of this measure. These essentially include anticoagulant, timing of sample collection, the sample storage conditions, the influence of the analytical techniques, the approaches used for its calculation, the accurate definition of reference ranges and diagnostic cut-offs, as well as the current lack of standardization, which makes data obtained with different techniques/analyzers poorly comparable. Provided that the impact of these variables can be abated or minimized, the MPV can gain a valuable role in the laboratory workout of many arterial and venous thrombotic disorders.

Objectives Gestational thrombocytopenia (GT) is the most common cause of thrombocytopenia during pregnancy. However, the occurrence and severity of thrombocytopenia throughout pregnancy in Chinese women are not fully defined. Methods We analyzed platelet counts in Chinese women who received prenatal care and/or delivered at the First Affiliated Hospital with Nanjing Medical University between January 2, 2018 and July 19, 2018 in China. These platelet counts were compared with those of nonpregnant women in the same study period. Results The platelet counts of all women continued to decrease significantly each trimester (p < 0.0001). The mean platelet counts of the 818 women who had pregnancy-related complications were lower than those of the 796 women who had uncomplicated pregnancies during the third trimester (p = 0.047). At the time of delivery, platelet counts less than 150 × 10 9 /L were more common in women with pregnancy-related complications than in women with uncomplicated pregnancy (26.7% vs. 19.7%, p = 0.03). Conclusions Platelet counts decrease throughout pregnancy in Chinese women and platelet counts less than 150 × 10 9 /L were more common in women with pregnancy-related complications than in women with uncomplicated pregnancy. The pregnant women should be paid more attention for thrombocytopenia to avoid the occurrence of bleeding events.