BACKGROUND:There is an unmet need for improving platelet function testing methods in patients with low platelet count. Platelet aggregometry is recommended for platelet function testing; however, no specific guidelines on technical and performance aspects do hitherto exist for aggregometry in patients with low platelet counts. OBJECTIVES:The goal of this joint project between the International Society on Thrombosis and Haemostasis (ISTH) Scientific Standardization Committees on platelets in health and disease and immune-mediated platelet disorders is to provide an expert consensus on the use of aggregometry (light transmission and impedance based) for the evaluation of platelet function in patients with low platelet counts. METHODS:A literature review was performed to identify relevant questions and areas of uncertainty. An electronic expression of interest form was announced on the ISTH webpage, followed by a survey encompassing 38 questions regarding preanalytical, analytical, postanalytical, and performance aspects. Areas of disagreement or uncertainty were identified and formed the basis for 2 focus group discussions. RESULTS:Considerations relative to patient sample collection, preanalytical variables, sample type, platelet count cutoff, and potential specific modification of the standard aggregometry protocol are proposed based on the current practices, as identified in the literature and consensus of experts in the field. CONCLUSIONS:The proposed considerations would facilitate standardization of laboratory practices. Large multicenter studies are still needed to test some of the proposed technical considerations and compare the clinical utility of aggregometry with other methods such as flow cytometry assays for platelet function testing to identify platelet-associated defects and/or predict bleeding risk in patients with thrombocytopenia.

OBJECTIVES:To evaluate postoperative residual and reappearing heparin activity after low-dose, titration-guided protamine reversal following cardiopulmonary bypass (CPB) in elective coronary artery bypass grafting (CABG). DESIGN:Prospective, controlled clinical study. SETTING:Single-center university hospital. PARTICIPANTS:Forty adult patients undergoing elective CABG with CPB. INTERVENTIONS:Heparin and protamine dosing was guided by an automated titration system. MEASUREMENTS AND MAIN RESULTS:Blood samples were obtained before induction, at the end of CPB, before and after protamine administration, on intensive care unit (ICU) arrival, 3 hours after ICU arrival, and on postoperative day 1. Heparin activity was assessed by anti-factor Xa (anti-FXa), activated partial thromboplastin time (aPTT), and thrombin time (TT). Global coagulation was evaluated using endogenous thrombin potential (ETP). The mean protamine to heparin (P/H) ratio was 0.54 ± 0.14 mg/100 U. On ICU arrival (82 ± 23 minutes after protamine), anti-FXa activity was 0.14 ± 0.15 U/mL, with 60% of patients showing detectable levels. The P/H ratio correlated negatively with TT (r = -0.48, p = 0.004) and aPTT (r = -0.50, p = 0.0015) and positively with ETP (r = 0.41, p = 0.0012). Three hours after ICU arrival, anti-FXa activity increased to 0.18 ± 0.10 U/mL (98% detectable), independent of P/H ratio. No association was found between heparin activity and postoperative bleeding. CONCLUSIONS:Residual heparin activity was common after low-dose, titration-guided protamine reversal and related to P/H ratio on ICU arrival. Reappearing heparin activity occurred independently of protamine dosing and was not associated with bleeding.

Background The nitrate ester-bearing 6-piperazinyl-purine analogue MK128 is a Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor with cardioprotective, anti-inflammatory, and antiplatelet properties. However, structure-activity relationships of this compound class have not been systematically explored. This study aimed to elucidate the impact of spacer length on the antiplatelet activity of closely related piperazinyl-purine analogues and to identify the most active candidate for further evaluation. Methods Antiplatelet activity of piperazinyl-purine analogues bearing short (MK128), intermediate (MK176), and long (MK118) spacers was evaluated by lumi-aggregometry and flow cytometry in isolated platelets and whole blood. Platelets were activated by proteinase-activated receptor-1 agonist SFLLRN-OH or collagen. Binding interactions with ROCK1/ROCK2 were examined using SelectScreen™ Kinase Profiling, in silico docking, and molecular dynamics simulations. Results MK128 exhibited the strongest inhibition of platelet aggregation and secretion in isolated platelets and whole blood, and rapidly promoted disaggregation of preformed aggregates. The rank order of potency in whole blood was MK128>MK176>MK118. All analogues inhibited ROCK1 and ROCK2 in cell-free assays, while broader kinase profiling demonstrated high selectivity. Docking studies suggested stable bidentate interactions between the purine core and hinge region, whereas molecular dynamics simulations identified spacer length-dependent differences in nitrate ester tail interactions. Reduced spacer flexibility in MK128 enabled productive interactions with catalytically relevant residues, providing a mechanistic explanation for its superior functional activity. Conclusion Spacer length critically determines the antiplatelet effect of piperazinyl-purine analogues. The one-carbon spacer analogue MK128 demonstrated superior platelet and ROCK inhibition, making it a promising lead candidate for further evaluation in ischemic disease models.

Dasatinib is a second-generation tyrosine kinase inhibitor approved for therapeutic use in patients with Philadelphia-positive (Ph+) chronic myeloid leukemia. Dosing of dasatinib is limited by the potential for side effects, including pleural effusion and bleeding disorders. The propensity for bleeding problems is at least in part due to dasatinib inhibiting normal platelet functions. While dasatinib is effective in treating leukemia, the challenge in dosing is associated with a risk for emergence of the T315I mutation of BCR-ABL and potential tumor escape. Thus, the ability to combine dasatinib with other therapeutic agents is desirable and currently under investigation. We have developed an ex vivo test system using circulating fresh human whole blood, enabling direct study of the effects of various compounds on platelet aggregation and activation in a physiologically relevant environment. To see whether the clinical effects of dasatinib could be recapitulated in the test system, we incubated blood from healthy donors in the system with dasatinib prior to stimulation with Thrombin Receptor (PAR1) Activating Peptide 6 (TRAP-6). As predicted, dasatinib significantly inhibited TRAP-6-mediated platelet aggregation and activation as measured by whole blood free platelet counts, platelet expression of CD62P, and the formation of platelet-white blood cell conjugates. At the Cmax concentration, alemtuzumab (anti-CD52) results in antibody-dependent cellular cytotoxicity (ADCC) and release of large amounts of cytokines in the test system, mimicking clinical effects of the drug. We also see a drop in platelet count and platelet activation, correlating with acute effects of alemtuzumab observed in patients. Based on these observations, alemtuzumab was used in the system to investigate whether dasatinib could inhibit platelet activation by a therapeutic drug with known effects on platelets. Dasatinib significantly inhibited the drop in free platelet count and platelet activation seen in response to alemtuzumab. As dasatinib could potentially inhibit multiple signaling pathways, we also investigated whether it had effects on ADCC of CD52+ cell types (lymphocytes and monocytes) by alemtuzumab in the ex vivo system. The decreased lymphocyte and monocyte counts observed in alemtuzumab-treated samples were significantly increased by the addition of dasatinib, whereas non-CD52 expressing cells (such as neutrophils) were not affected. Taken together, the data suggest that the ex vivo test system can be used to investigate the effect of different therapeutic agents on platelet activation and that dasatinib at concentrations that inhibit platelet activation may also inhibit ADCC. Combination therapies involving dasatinib and antibodies with predicted ADCC-dependent effects may thus require further investigation prior to clinical use. Sakthi Srinivasan, Ali Zirakzadeh, Sofia Ramström, Erika A. Fletcher, Helena Harlin Laven. Inhibition of platelet activation and antibody-dependent cellular cytotoxicity by the tyrosine kinase inhibitor dasatinib in an ex vivo human whole blood system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6835.

Background Platelets contain many heterogeneous carbohydrates (glycans), often capped by sialic acid. The removal of sialic acid (desialylation) is important for platelet function and clearance, leading to novel diagnostic markers. Platelet desialylation can be easily measured using inexpensive, user-friendly lectins, and flow cytometry. Objectives Here, the Platelet Physiology Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis (ISTH) carried out a survey to assess current methods used for platelet desialylation. Based on the survey results, a consensus protocol was drafted and tested. Methods A survey/questionnaire was posted on the ISTH Platelet Physiology Standardization Committee pages. Washed platelets and diluted apheresis platelets were diluted to 50 and 200 × 106/mL ± CaCl2. Platelets were stained with a concentration range of either β-galactose binding fluoresceine-conjugated lectin Ricinus communis agglutinin 1 (RCA-1) or Erythrina cristagalli lectin (ECL). As positive controls, different recombinant sialidases were tested. Results The results of the survey (N = 20) showed that flow cytometry and RCA-1 are mostly used to assess platelet desialylation. Calcium did not significantly influence lectin binding, and optimal binding was achieved with ECL and RCA-1 at 2 and 5 μg/mL, respectively. The specificity of lectins varied, particularly after sialidase treatment, compared with cold-stored platelets. These findings contribute to the standardization of desialylation measurements, particularly in patient samples. Conclusion Our findings demonstrate that flow cytometry using RCA-1 and ECL is a robust method for quantifying platelet desialylation. The proposed standardized protocol addresses key preanalytical variables, enabling reproducible and accurate analysis of platelet glycosylation.

BACKGROUND AND OBJECTIVES:The Nordic region includes Denmark, Finland, Iceland, Norway and Sweden, with a population of >27.5 million. Blood services are managed differently in each country. Current data on platelet concentrate (PC) production methods and capacity are important for developing efficiency and cross-border preparedness. MATERIALS AND METHODS:Retrospective data for 2018-2022 were collected through an online survey sent to all blood centres producing platelets in the region. Questions focused on collection procedures (aphaeresis [AP] or whole blood [WB]-derived pools), use of bacterial culture screening (BCS) or pathogen reduction (PR), shelf-life, transfusion practices and quality control. RESULTS:A total of 43 blood centres provided data (83% response), including complete national coverage for Sweden, Finland and Iceland. Between 2018 and 2022, 632,596 PCs were produced at participating centres. Annual PC production was stable over the period. Most PCs were WB pools (77%). Automated separation to produce interim platelet unit (IPU) pools was performed at 19 centres. PR and BCS were used in 17 and 23 centres, respectively. Shelf-life ranged from 5 days (no safety measure) to 7 days (PR or BCS). The number of PCs transfused in the region declined by ~5% from 2018 to 2022. CONCLUSION:Platelet production methods, including safety measures to prevent bacterial contamination, varied widely in the Nordic region. Harmonization, including the use of PR or BCS with 7-day storage, may contribute to resilient platelet supplies in the region.

Background Given the role of platelets in coronary artery disease (CAD), assessment of a soluble platelet-activation marker may be useful to improve thrombotic risk stratification. Objectives This study aimed to perform a meta-analysis investigating the association between levels of 14 such markers associated with CAD. Methods PubMed, Web of Science, and Excerpta Medica dataBASE (EMBASE) were searched until November 2024. The primary end point was the difference in levels of 11-dehydro-thromboxane B2, 2,3-dinor-thromboxane B2, β-thromboglobulin, soluble CD40L (sCD40L), glycocalicin, glycoprotein (GP)V, GPVI, matrix metalloproteinase (MMP)-9 and MMP-2, platelet factor (PF)4, soluble (s) P-selectin, SCUBE1, serotonin and thrombospondin (TSP)-1 between patients with CAD and healthy subjects (HSs) in plasma and/or serum. When possible, patients with CAD were stratified into acute coronary syndrome (ACS) and chronic coronary disease. Standardized mean difference (SMD) was calculated. Results Due to heterogeneity in the assessed studies, meta-analysis was performed for sCD40L, soluble GPV, MMP-9, PF4, sP-selectin, SCUBE1, and TSP-1. All markers but TSP-1 were significantly elevated in patients with CAD compared with HSs. Differences in sCD40L and SCUBE1 were statistically significant only when studies that assessed plasma were combined with those that assessed serum. When compared with HSs, the differences were bigger in patients with ACS than patients with chronic coronary disease for MMP-9 (SMD, 2.49 vs 0.49), PF4 (SMD, 2.01 vs 0.96), and sP-selectin (SMD, 1.81 vs 0.63). Publication bias was identified for sCD40L and, in ACS, for sP-selectin and PF4. Conclusion The increased levels of sCD40L, soluble GPV, MMP-9, PF4, sP-selectin, and SCUBE1 in patients with CAD compared with HSs provide a rationale for designing new studies to address the potential of such molecules as biomarkers for thrombotic risk stratification.

Over the past 3 decades, omics technologies have revolutionized our understanding of platelet molecular content and organization, enabling the systematic analyses of platelet physiology. Among these approaches, proteomics has been especially significant in discovering as well as validating molecular mechanisms of platelet function in health and disease. However, several conceptual and practical challenges continue to limit the full utility of platelet proteomics tools and data. Methodological and analytical inconsistencies remain a key concern, with biological and technical variables exerting substantial influence on study outcomes and interpretation. These issues are compounded by the rapid pace of proteomics tool development and dataset collection, outstripping efforts to standardize best practices and ensure consensus, as platelet proteomics consolidates itself as a tool for research even outside the thrombosis and hemostasis field.In this communication from the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee, we highlight recent advances in platelet proteomics studies, and we identify where collective efforts can strengthen experimental design, execution, and analysis. As a practical recommendation, we encourage platelet biologists to recognize current discrepancies and advance efforts to standardize and customize methods and reporting practices, including blood collection, platelet isolation, data acquisition, and data interpretation. By aligning protocols and ensuring detailed reporting, the field can more effectively integrate proteomics findings and accelerate our understanding of platelet biology.

Genome-wide platelet transcriptomics is increasingly used to uncover new aspects of platelet biology and as a diagnostic and prognostic tool. Nevertheless, platelet isolation methods for transcriptomic studies are not standardized, introducing challenges for cross-study comparisons, data integration, and replication. In this prospective multicenter study, called "Standardizing Platelet Transcriptomics for Discovery, Diagnostics, and Therapeutics in the Thrombosis and Hemostasis Community (STRIDE)" by the International Society on Thrombosis and Haemostasis Scientific and Standardization Committees, we assessed how 3 of the most commonly used platelet isolation protocols influence metrics from next-generation bulk RNA sequencing and functional assays. Compared with washing alone, more stringent removal of leukocytes by anti-CD45 beads or PALL filters resulted in a sufficient quantity of RNA for next-generation sequencing and similar quality of RNA sequencing metrics. Importantly, stringent removal of leukocytes resulted in the lower relative expression of known leukocyte-specific genes and the higher relative expression of known platelet-specific genes. The results were consistent across enrolling sites, suggesting that the techniques are transferrable and reproducible. Moreover, all 3 isolation techniques did not influence basal platelet reactivity, but agonist-induced integrin αIIbβ3 activation is reduced by anti-CD45 bead isolation compared with washing alone. In conclusion, the isolation technique chosen influences genome-wide transcriptional and functional assays in platelets. These results should help the research community make informed choices about platelet isolation techniques in their own platelet studies.

OBJECTIVES:Previous studies have described impaired platelet function after cardiopulmonary bypass (CPB). Whether this is still valid in contemporary cardiac surgery is unclear. This study aimed to quantify changes in function and number of platelets during CPB in a present-day cardiac surgery cohort.DESIGN:Prospective, controlled clinical study.SETTING:A single-center university hospital.PARTICIPANTS:Thirty-nine patients scheduled for coronary artery bypass graft surgery with CPB.INTERVENTIONS:Platelet function and numbers were measured at 6 timepoints in 39 patients during and after coronary artery bypass graft surgery; at baseline before anesthesia, at the end of CPB, after protamine administration, at intensive care unit (ICU) arrival, 3 hours after ICU arrival, and on the morning after surgery.MEASUREMENTS AND MAIN RESULTS:Platelet function was assessed with impedance aggregometry and flow cytometry. Platelet numbers are expressed as actual concentration and as numbers corrected for dilution using hemoglobin as a reference marker. There was no consistent impairment of platelet function during CPB with either impedance aggregometry or flow cytometry. After protamine administration, a decrease in platelet function was seen with impedance aggregometry and for some markers of activation with flow cytometry. Platelet function was restored 3 hours after arrival in the ICU. During CPB (85.0 ± 21 min), the number of circulating platelets corrected for dilution increased from 1.73 ± 0.42 × 109/g to 1.91 ± 0.51 × 109/g (p < 0.001).CONCLUSIONS:During cardiac surgery with moderate CPB times, platelet function was not impaired, and no consumption of circulating platelets could be detected. Administration of protamine transiently affected platelet function.

Platelets are transfused to patients to prevent bleeding. Since both preparation and storage can impact the hemostatic functions of platelets, we studied platelet concentrates (PCs) with different initial composition in regard to platelet fragmentation and its impact on storage-induced changes in activation potential. Ten whole blood derived PCs were assessed over 7 storage days. Using flow cytometry, platelet (CD41+) subpopulations were characterized for activation potential using activation markers (PAC-1, P-selectin, and LAMP-1), phosphatidylserine (Annexin V), and mitochondrial integrity (DiIC1(5)). Aggregation response, coagulation, and soluble activation markers (cytokines and sGPVI) were also measured. Of the CD41+ events, the PCs contained a median of 82% normal-sized platelets, 10% small platelets, and 8% fragments. The small platelets exhibited procoagulant hallmarks (increased P-selectin and Annexin V and reduced DiIC1(5)). Normal-sized platelets responded to activation, whereas activation potential was decreased for small and abolished for fragments. Five PCs contained a high proportion of small platelets and fragments (median of 28% of CD41+ events), which was significantly higher than the other five PCs (median of 9%). A high proportion of small platelets and fragments was associated with procoagulant hallmarks and decreased activation potential, but, although diminished, they still retained some activation potential throughout 7 days storage.

Arterial thrombosis (AT) originates through platelet-mediated thrombus formation in the blood vessel and can lead to heart attack, stroke, and peripheral vascular diseases. Restricting the thrombus growth and its simultaneous monitoring by visualisation is an unmet clinical need for a better AT prognosis. As a proof-of-concept, we have engineered a nanoparticle-based theranostic (combined therapy and monitoring) platform that has the potential to monitor and restrain the growth of a thrombus concurrently. The theranostic nanotool is fabricated using biocompatible super-paramagnetic iron oxide nanoparticles (SPIONs) as a core module tethered with the anti-platelet agent Abciximab (ReoPro) on its surface. Our in vitro feasibility results indicate that ReoPro-conjugated SPIONS (Tx@ReoPro) can effectively prevent thrombus growth by inhibiting fibrinogen receptors (GPIIbIIIa) on the platelet surface, and simultaneously, it can also be visible through non-invasive magnetic resonance imaging (MRI) for potential reporting of the real-time thrombus status.

Background: Procoagulant platelets are a subpopulation of highly activated platelets that promote coagulation through surface-exposed, negatively charged phospholipids, especially phosphatidylserine. Procoagulant platelets are important for clot stabilization during hemostasis, and an increased number of these platelets is associated with thrombotic risk. There is a need for harmonization in this area since many of the markers and methods used to assess procoagulant platelets are not specific when used in isolation but are also associated with platelet apoptosis.Objectives: We initiated this project to identify a minimum set of markers and/or methods that can detect and distinguish procoagulant platelets from apoptotic platelets.Methods: The study design involved a primary panel with 27 international experts who participated in an online survey and moderated virtual focus group meetings. Primary and secondary panel members were then invited to provide input on themes and statements generated from the focus groups.Results: This led to a recommendation to use flow cytometry and a combination of the following 3 surface markers to differentiate procoagulant platelets from apoptotic platelets: P-selectin (CD62P), phosphatidylserine (recognized by annexin V), and the platelet-specific receptor GPIX (CD42a) or & alpha;IIb integrin (CD41, GPIIb).Conclusion: Procoagulant platelets are expected to be positive for all 3 markers, while apoptotic platelets are positive for annexin V and the platelet-specific surface receptor(s) but negative for P-selectin.

BACKGROUND:Platelet count alone does not reliably predict bleeding risk, suggesting platelet function is important to monitor in patients with thrombocytopenia. There is still an unmet need for improved platelet function diagnostics in patients with low platelet count in many clinical situations. Flow cytometry is a promising tool allowing reliable platelet function study in this setting.OBJECTIVES:The goal of this joint project between the International Society on Thrombosis and Haemostasis (ISTH) Scientific Standardization Committee (SSC) Subcommittees on Platelet Physiology and Platelet Immunology is to provide expert consensus guidance on the use of flow cytometry for the evaluation of platelet function, particularly activation, in patients with low platelet counts.METHODS:A literature review was performed to identify relevant questions and areas of interest. An electronic expression of interest form was thereafter announced on the ISTH webpage, followed by a survey encompassing 37 issues regarding preanalytical, analytical, postanalytical, and performance aspects. Areas of disagreement or uncertainty were identified and formed the basis for 2 focus group discussions.RESULTS:Consensus recommendations relative to patient sample collection, preanalytical variables, sample type, platelet-count cutoff, any potential specific modification of the standard flow cytometry protocol, and results expression and reporting are proposed based on the current practices of experts in the field as well as on literature review.CONCLUSION:The proposed consensus recommendations would allow standardization of protocols in upcoming clinical studies. The clinical utility of platelet function testing using flow cytometry to predict bleeding risk still needs rigorous multicenter outcome studies in patients with thrombocytopenia.

The soluble tumor necrosis factor receptors (sTNFR1 and sTNFR2) are suggested to play dual roles on physiological and pathophysiological actions of TNF-α. The aim of this study was to investigate the dynamic changes of these biomarkers in patients with ST-segment elevation myocardial infarction (STEMI). Blood was collected from 165 STEMI patients at admission, 1–3 days and 3 months after percutaneous coronary intervention (PCI) and from 40 healthy blood donors. sTNFR1 and sTNFR2 were measured with ELISA. The plasma levels of both sTNFR1 and sTNFR2 were significantly higher than in healthy donors at all three time points. We found no significant differences in sTNFR1 or sTNFR2 when comparing patients with patent versus occluded culprit vessels, or between patients having a thrombus aspiration or not. Survival analysis was performed comparing patients with levels of biomarkers above and below the median values at that time point. We found significant differences in survival for sTNFR2 in acute samples ( p = 0.0151) and for both sTNFR1 and sTNFR2 in samples 1–3 days after PCI ( p = 0.0054 and p = 0.0003, respectively). Survival analyses suggest that sTNFR1 or sTNFR2 could be promising markers to predict mortality in STEMI patients after PCI.

In flow cytometry, individual cells are investigated. Platelet activation is normally reported in form of percentage of platelets expressing the marker (positive platelets) and/or mean/median fluorescence intensity (MFI) for the entire analyzed population. None of these take into account the variance of the marker expression between individual platelets. This can be obtained as data on coefficient of variation (CV). This study explores if CV provides additional information regarding platelet function. Samples from platelet concentrates (PCs) prepared by apheresis- (n = 13) and interim platelet unit (IPU) technique (n = 26) and stored for 6-7 days were included and compared. Spontaneous- and agonist-induced expression of activation markers (fibrinogen binding and exposure of P-selectin, LAMP-1, and CD63) was investigated as percentage positive platelets, MFI and CV. Spontaneous expression of P-selectin as percentage positive platelets and MFI was higher for IPU PCs than apheresis PCs, which in contrast had higher agonist-induced activation. CV for spontaneous fibrinogen binding and P-selectin exposure was larger for apheresis PCs, while IPU PCs generally had larger CV for P-selectin, LAMP-1, and CD63 after agonist stimulation. Our findings show that CV adds additional information when assessing platelet activation by providing data on the variation in activation responses within the platelet population.

INTRODUCTION:Platelet function tests are used to screen and diagnose patients with possible inherited platelet function defects (IPFD). Some acquired platelet dysfunction may be caused by certain drugs or comorbidities, which need to be excluded before testing. AIMS:To identify current practice among centres performing platelet function tests in Northern Europe. METHODS:A total of 14 clinical centres from Sweden (six), Finland (two), Denmark (two), Norway (one), Estonia (two) and Iceland (one) completed the survey questionnaire, the population capture area of about 29.5 million. RESULTS:Six of the 14 (42.8%) centres providing platelet function assessment represent comprehensive treatment centres (EUHANET status). A Bleeding score (BS) or ISTH bleeding assessment tool (ISTH BAT score) is evaluated in 11/14 (78.6%) centres and family history in all. Five/14 centres (35.7%) use structured preanalytical patient instructions, and 10/14 (71.4%) recorded questionnaire on the preassessment of avoidance of any drugs or natural products affecting platelet functions. Preliminary investigations of screening tests of coagulation are performed in 10/14 (71.4%), while in 4/14 (28.6%), the diagnostic work-up of IPFD and von Willebrand disease (VWD) is performed simultaneously. The work-up of IPFD includes peripheral blood smear in 10/14 (71.4%), platelet aggregometry in all, flow cytometry in 10/14 (71.4%) and Platelet Function Analysis (PFA) in 3/11 (28.6%). Molecular genetic diagnosis is available in 7/14 (50%) centres. CONCLUSIONS:The considerable variability in the current practice illustrates the need for harmonization between the Northern European centres according to the international registers (i.e. EUHASS) and IPFD guidelines (ISTH, EHA).