This article discusses immune and infection-associated forms of neonatal thrombosis, including antiphospholipid syndrome (APS), catastrophic APS (CAPS), COVID-19-associated thrombosis, and vaccine-induced immune thrombotic thrombocytopenia (VITТ)-like conditions. Special attention is paid to the role of de novo synthesis of antiphospholipid and anti-PF4 antibodies in newborns, as well as the mechanism of thromboinflammation as the pathophysiological basis of these conditions. Data on epidemiology, pathogenesis, diagnosis and therapy are presented, and the need to revise diagnostic approaches considering immunological and inflammatory factors is emphasized. Conclusion. The management of patients with neonatal thrombosis requires a multidisciplinary and personalized approach. Key words: neonatal thrombosis, immune thrombosis, thromboinflammation, antiphospholipid syndrome, catastrophic APS, anti-PF4 antibodies, VITT, newborns, COVID-19, NETs

Combined oral contraceptives (COCs) remain one of the most popular reversible contraceptive methods worldwide. Still, regardless of the drug composition and duration of therapy, almost all COCs are associated with the risk of venous thrombosis. This review highlights the main pathogenetic mechanisms of thrombosis development during oral contraceptive use. Increase the production of certain clotting factors; a decrease in antithrombin and protein S levels; acquired resistance to activated protein C; a reduction in tissue factor pathway inhibitor (TFPI); indirect endothelial activation; inhibition of endogenous fibrinolysis; regulation of tissue factor by estradiol-sensitive microRNA; homocysteine imbalance caused by decreased intestinal reabsorption of folates and vitamin B-12; reduced bioavailability of nitric oxide (NO) due to high homocysteine levels; higher blood pressure, water retention, insulin resistance, increased levels of pro-inflammatory C-reactive protein (CRP) and uric acid, and antifibrinolytic (plasminogen activator inhibitor 1 type, PAI-1) biomarkers as consequences of NO deficiency; increased platelet adhesiveness and ADP-induced aggregation, which promote fibrinogen binding; and increased expression of pro-inflammatory cytokines are the main thrombotic effects of COCs use. Clinicians should carefully evaluate each patient's individual risk factors when prescribing COCs and conduct regular monitoring to reduce the risk of complications.

Background With the widespread use of direct oral anticoagulants (DOACs), there is an urgent need for a rapid assay to exclude clinically relevant plasma levels. Accurate and rapid determination of DOAC levels would guide medical decision-making to (1) determine the potential contribution of the DOAC to spontaneous or trauma-induced hemorrhage; (2) identify appropriate candidates for reversal, or (3) optimize the timing of urgent surgery or intervention. Methods and Results The DOAC Dipstick test uses a disposable strip to identify factor Xa- or thrombin inhibitors in a urine sample. Based on the results of a systematic literature search followed by an analysis of a simple pooling of five retrieved clinical studies, the test strip has a high sensitivity and an acceptably high negative predictive value when compared with levels measured with liquid chromatography tandem mass spectrometry or calibrated chromogenic assays to reliably exclude plasma DOAC concentrations ≥30 ng/mL. Conclusion Based on these data, a simple algorithm is proposed to enhance medical decision-making in acute care indications useful primarily in hospitals not having readily available quantitative tests and 24/7. This algorithm not only determines DOAC exposure but also differentiates between factor Xa and thrombin inhibitors to better guide clinical management.

Purpose: Cerebral vein thrombosis is a rare, life-threatening condition that has now become more commonly diagnosed due to advancements in imaging techniques. Our purpose is to improve understanding of pathogenesis, diagnosis and pregnancy and IVF management in patients with a history of cerebral thrombosis. Materials and methods: We present an overview of the modern tactics of anticoagulant therapy for cerebral thrombosis with a focus on pregnancy, the use of hormone therapy, and assisted reproductive technologies. Results: The most common risk factors for cerebral vein thrombosis are pregnancy, the postpartum period, and the use of oral contraceptives, which explains the high incidence of this pathology in women. The development of cerebral thrombosis is a vivid example of the interaction and synergetic effects of persistent factors that cause an increased risk of thrombotic complications, which include thrombophilia and acquired risk factors. Despite the possible risks, pregnancy after previously suffered cerebral thrombosis is not contraindicated provided adequate anticoagulant therapy. Conclusions: The most common provoking factors for the development of cerebral thrombosis in women are pregnancy and the use of estrogen-containing drugs. The issue of thromboprophylaxis during pregnancy, when using ART methods and the possibility of using hormonal therapy after cerebral vein thrombosis requires further study.

Background: Preeclampsia (PE) is a leading cause of maternal and perinatal morbidity worldwide, yet its mechanisms remain poorly understood. Dysregulated innate im-munity, specifically aberrant complement activation and excessive neutrophil extracel-lular traps (NETs) formation, contributes to endothelial dysfunction and inflammation in preeclampsia. However, the interaction between complement activation and NETs, as well as the differences between these immune pathways in early-onset and late-onset preeclampsia, remain unclear. To address this gap, we assessed complement components and NET markers across various preeclampsia phenotypes and examined their rela-tionships. Methods: Plasma samples were collected from 56 women with early-onset preeclampsia (EO-PE) before 34 weeks, 32 with late-onset preeclampsia (LO-PE) after 34 weeks, and 32 healthy pregnant women in the control group. Complement components (C1q, C3, C3a, C4, and the terminal complement complex, TCC) and NETs markers (MPO-DNA, cit-rullinated histone H3, and cathepsin G) were measured using ELISA. Group differences were assessed with non-parametric tests, and associations between markers and clinical variables were analyzed using Spearman correlations. Results: We observed higher levels of C1q, C3, C3a, and TCC in pregnant women with severe preeclampsia compared with healthy pregnancies (p < 0.001), while C4 levels remained unchanged. Among neutrophil trap biomarkers, MPO-DNA levels were el-evated in EO-PE (p = 0.019), while CitH3 and cathepsin G levels did not differ significantly between groups. Strong correlations were observed between MPO-DNA and TCC (ρ = 0.30, p = 0.013), as well as between cathepsin G and C3a (ρ = 0.40, p = 0.0007), indicating NETs–complement interactions. Patterns of complement and NETs activation were similar in early and late preeclampsia, despite differences in gestational age. Conclusions: The observed associations between MPO-DNA and TCC, and between cathepsin G and C3a, indicate meaningful crosstalk between NETs and complement ac-tivation. These findings support the role of innate immune dysregulation in preeclampsia and highlight NETs–complement interactions as potential targets for diagnostic and therapeutic approaches.

[This corrects the article DOI: 10.1055/s-0041-1736037.].

This article explores systemic inflammatory response syndrome (SIRS), thromboinflammation, and septic shock in fetuses and neonates, offering a comprehensive examination of their pathophysiology, diagnostic criteria, and clinical implications. It identifies SIRS as an exaggerated response to external stress, disrupting the balance between inflammation and adaptive mechanisms, driven by cytokines such as TNF-α and IL-1. The fetal inflammatory response syndrome (FIRS), a subset of SIRS, is noted for its role in adverse neonatal outcomes, including organ damage, inflammation, and long-term developmental disorders. The article discusses the extensive effects of FIRS on critical systems, including the blood, lungs, central nervous system, and kidneys. It highlights the challenges in diagnosing and managing septic shock in neonates, focusing on the relationship between inflammation and the hemostatic system. Additionally, the paper points out recent advancements, such as the convergent model of coagulation and emerging biomarkers like microRNAs for early detection. Despite this progress, gaps remain in understanding the molecular mechanisms underlying these conditions and in developing effective therapeutic strategies. This highlights the necessity for targeted research to mitigate the morbidity and mortality associated with septic shock in neonates.

Thrombotic microangiopathy (TMA) encompasses a range of disorders characterized by blood clotting in small blood vessels, leading to organ damage. It can manifest as various syndromes, including thrombotic thrombocytopenic purpura (TTP), hemolytic-uremic syndrome (HUS), and others, each with distinct causes and pathophysiology. Thrombo-inflammation plays a significant role in TMA pathogenesis: inflammatory mediators induce endothelial injury and activation of platelet and coagulation cascade, contributing to microvascular thrombosis. Primary TMA, such as TTP, is primarily caused by deficient ADAMTS13 metalloproteinase activity, either due to antibody-mediated inhibition or intrinsic enzyme synthesis defects. In cancer patients, a significant reduction in ADAMTS13 levels and a corresponding increase in VWF levels is observed. Chemotherapy further decreased ADAMTS13 levels and increased VWF levels, leading to an elevated VWF/ADAMTS13 ratio and increased thrombotic risk. Drug-induced TMA (DITMA) can result from immune-mediated or non-immune-mediated mechanisms. Severe cases of COVID-19 may lead to a convergence of syndromes, including disseminated intravascular coagulation (DIC), systemic inflammatory response syndrome (SIRS), and TMA. Treatment of TMA involves identifying the underlying cause, implementing therapies to inhibit complement activation, and providing supportive care to manage complications. Plasmapheresis may be beneficial in conditions like TTP. Prompt diagnosis and treatment are crucial to prevent serious complications and improve outcomes.

Unlike classic APS, CAPS causes multiple microthrombosis due to an increased inflammatory response, known as a “thrombotic storm”. CAPS typically develops after infection, trauma, or surgery and begins with the following symptoms: fever, thrombocytopenia, muscle weakness, visual and cognitive disturbances, abdominal pain, renal failure, and disseminated intravascular coagulation. Although the presence of antiphospholipid antibodies in the blood is one of the diagnostic criteria, the level of these antibodies can fluctuate significantly, which complicates the diagnostic process and can lead to erroneous interpretation of rapidly developing symptoms. Triple therapy is often used to treat CAPS, which includes the use of anticoagulants, plasmapheresis, and high doses of glucocorticosteroids and, in some cases, additional intravenous immunoglobulins. The use of LMWH is recommended as the drug of choice due to its anti-inflammatory and anticoagulant properties. CAPS is a multifactorial disease that requires not only an interdisciplinary approach but also highly qualified medical care, adequate and timely diagnosis, and appropriate prevention in the context of relapse or occurrence of the disease. Improved new clinical protocols and education of medical personnel regarding CAPS can significantly improve the therapeutic approach and reduce mortality rates.

IMPORTANCE:Antiphospholipid syndrome in neonates and children is a rare, but in some cases life-threatening condition with arterial and/or venous thrombosis and/or non-thrombotic neurological, skin, ophthalmological and other manifestations. OBSERVATIONS:This review highlights the available information about the features of pediatric APS, including the rare catastrophic form, the differences between pediatric and adult APS, and the role of genetic thrombophilia in APS manifestation. CONCLUSIONS AND RELEVANCE:The clinical manifestations and treatment options for APS in children may differ from those in adults, and prescribing therapy can be challenging due to the unique clinical and morphological characteristics of the pediatric patient. Pediatric APS may be a predictor of the development of certain autoimmune diseases and classic manifestations of APS in adulthood, therefore, a revision of the existing criteria for the diagnosis and treatment of APS in children is necessary.

Background The link between blood hypercoagulability, endothelial cell activation and infertility or in vitro fertilization (IVF) failure is a puzzling issue. Activation of platelets, endothelial cells and blood coagulation, proinflammatory and angiogenetic potential play important role in implantation and early embryonic development. Biomarkers of cellular hypercoagulability are associated with high risk of IVF failure. Soluble Leukemia Inhibitory Factor (LIF), an interleukin 6 class cytokine expressed in the trophectoderm of the developing embryo is an important regulator in the establishment of pregnancy. Endoglin (Eng), a co-receptor for TGF-β1 and TGF-β3 is implicated in vascular complications of pregnancy and particularly in preeclampsia. Aim: The prospective longitudinal monocentric observational cohort study ROADMAP-IVF, evaluated the synergistic prognostic value of LIF and Eng with the biomarkers of cellular hypercoagulability in predicting the endometrial receptivity of fresh IVF cycles. Materials and Methods. The ROADMAP-IVF enrolled 40 women eligible for IVF with normal blood count, PT, aPTT, Fg, renal and liver function. The control group (CG) consisted of 30 healthy women with history of uncomplicated pregnancies. Exclusion criteria: Use of anticoagulant or antiplatelet agents during the last 30 days before inclusion. Known cardiovascular disease, active cancer. Active corticosteroid treatment. Primary end-point: Echographically documented pregnancy at 7 weeks from implantation. Blood was collected on day 2 (D2) from the natural cycle and 6 days after hormone treatment initiation corresponding to D8 of the cycle. Procoagulant phospholipid-dependent clotting time (PPL-ct), tissue factor (TF), thrombomodulin (TM), von Willebrand factor (vWF) and D-Dimers (DDi) were measured with assays from Diagnostica Stago (Asnieres, France). P- and E-Selectin, LIF and Eng were measured with ELISA. Thrombin generation (TG) with the TF 5 pM PPP-Reagent ® was assessed on Calibrated Automated Thrombogram (Stago, France). The cut-off values for studied biomarkers have been selected on the basis of ROC analysis. Univariate and multivariate logistic regression analysis examined the associations between the biomarkers and the study outcome. Results: 40 women were enrolled in the study. In 11 women pregnancy was confirmed with ultrasound and in 23 women no pregnancy was echographically documented. Age was not significantly different between the IVF (41 ys; range 22 - 48 ys) and the control group (40 ys; range 20 - 46 ys). At D2 and D8 the DDi and LIF were significantly higher in IVFG as compared to the CG. At D2 most of the patients had PPL-ct, DDi and MRI of TG higher than the upper normal limit (UNL). At D8 only TF was significantly increased as compared to the CG. Analytical data are presented in Table 1. Age did not correlate with the levels of the studied biomarkers. Significant correlations (p<0.05) were found between DDi and ETP (r=0.35); TM, TF and P-Selectin (r=0.4) at D2; TF, LIF and Eng (r=0.5) at D2 and D8; P-Selectin and PPL-ct (r=-0.4) at D2; P-Selectin and TM (r=0.4), E-Selectin (r=0.5), LIF (0.4) at D2; E-Selectin and P-Selectin (r=0.5), TF (r=0.3), and LIF (r=0.4) at D2. The ROC analysis showed that IVF failure was associate with DDi increase at D2 (AUC = 0.64); P-Selectin increase at D2(AUC = 0.57) and D8 (AUC = 0.61); TM increase at D8 (AUC = 0.61); TF increase at D8 (AUC = 0.57); LIF increase at D8 (AUC = 0.59); ETP increase at D2 (AUC = 0.67) and D8 (AUC = 0.67); Peak increase at D2 (AUC = 0.64) and D8 (AUC = 0.61). Prolongation of PPL-ct on D8 was predictive for positive pregnancy outcome(AUC 0.64). Conclusion The ROADMAP-IVF study showed that at least one out of four women eligible for IVF present biological evidence of activation of platelets, endothelial cells, blood coagulation or LIF upregulation. Hormone treatment administration does not significantly alter the proinflammatory or the hypercoagulable state. Among the studied biomarkers the levels of LIF, DDi, P-Selectine, TM and TF as well as the status of thrombin generation and PPL-ct showed a significant predictive value for the IVF outcome, particularly when measured at 6 days after hormone treatment administration. These findings will lead to the elaboration of an risk assessment model for IVF failure combining the selected biomarkers of hypercoagulability with LIF.

The COVID-19 pandemic has become the greatest challenge to humanity of this century and has raised many new questions in various fields, primarily in medicine—in the field of microbiology, pathological anatomy and pathophysiology, immunology, clinical hemostasis, and almost all clinical disciplines, including, of course, obstetrics and perinatology. Systemic effects of SARS-CoV-2 are largely associated with thromboinflammation. The cause of death from COVID-19 is mainly pulmonary insufficiency and/or thrombosis (macro- and microcirculation). Pregnancy, even under normal conditions, is accompanied by changes in hemostasis with a shift toward hypercoagulation and increased inflammation, mainly in the third trimester of pregnancy. This in itself creates conditions for unfavorable outcomes for the mother and fetus. At the same time, pregnancy is a unique condition when a semiallogeneic fetus is reliably protected by the placenta from pathogenic influences under normal conditions. Despite this, the issue of transplacental transmission of the SARS-CoV-2 virus from mother to fetus is still debatable—individual observations allow us to judge this possibility. The issue of vaccination in pregnant women and its effect on the fetus is also extremely relevant. The chapter discusses the pathogenesis of complications in COVID-19, epidemiology, as well as possible ways to predict and prevent SARS-CoV-2-mediated pregnancy complications.

Identifying adherence to direct oral anticoagulants (DOACs) plays a major role in treatment efficacy and safety. The DOAC Dipstick can detect DOACs in urine samples of acutely diseased patients at plasma thresholds of about 30 ng/mL. A prospective observational consecutive cohort study was performed on outpatients taking DOACs. The presence of direct oral factor Xa inhibitors (DXIs) in patient urine samples were independently evaluated by visual interpretation of the DOAC Dipstick pad colors. DOAC plasma concentration was assessed using STA®-Liquid Anti-Xa and STA®-Liquid Anti-IIa chromogenic substrate assays. Positive DOAC Dipstick results were compared with a threshold plasma of DOAC concentration ≥30 ng/mL. Of 120 patients (age 55.4  +  16.1 years, female n  =  63), 77 were on rivaroxaban and 43 on apixaban. Plasma concentrations were 129  ±  118 ng/mL for rivaroxaban, and 163  ±  130 ng/mL for apixaban, DOAC Dipstick test has a sensitivity of 97.2% and a positive predictive value of 89.5% at 30 ng/mL. No differences occurred between DXIs. Specificity and negative predictive value could not be determined due to the low number of true negative values. There were no differences in the interpretation of rivaroxaban and apixaban pad colors between observers (Kappa 1.0). Results show that DOAC Dipstick may be a useful tool for identifying DXIs in urine samples in an outpatient setting at a plasma threshold ≥ 30 ng/mL. Further studies should include patients treated with dabigatran, vitamin K antagonists, or other anticoagulants.

Backround: Thromboembolism occurs in about 10% of patients with multiple myeloma (MM). The incidence of VTE is higher in newly diagnosed MM patients as compared to those with relapsed or refractory disease and it is higher during the first 3 to 6 months after the initial diagnosis and treatment initiation. Some of the treatments administered to patients with MM are independent risk factors for VTE. Immunomodulatory agents (IMiDs) among anti-myeloma treatments stand out as having a considerable prothrombotic effect. Recognizing the significant risk associated with the use of immunomodulatory agents (the International Myeloma Working Group (IMWG) 2014 statement, and the European Myeloma Network Guidelines in 2015 both included guidance on the prevention of VTE in MM patients who receive IMiDs. The prospective, longitudinal observational study ROADMAP-MM CAT was designed to explore alternative strategies for the development of risk stratification tools in patients with multiple myeloma. To this target we evaluated the baseline profile of hypercoagulability in multiple myeloma patients with various disease status. Blood borne hypercoagulabity partly consisted of enhanced thrombin generation, a common phenomenon in patients with malignancies . It remains to be seen whether this phenomenon appears for multiple myeloma patients during the physical course of the disease. Aim: We conducted a study to explore the relationship between stages of MM and alterations of various thrombosis-related biomarkers in patients with MM and their relationship with MM therapy. Materials and Methods Patients with MM (n=162) were recruited and stratified to the following groups: 59 newly diagnosed treatment-naïve patients (ND), 49 patients receiving IMiDs (IM), 52 in complete remission (CR) and 12 patients in partial remission on IMiDs (PR/IM). Patients on anticoagulant treatment were excluded from the study. The control group (CG) consisted of 30 healthy age and sex-matched individuals. Samples of platelet-poor plasma (PPP) were assessed for thrombin generation (TG) with the TF 5pM PPP-Reagent® on Calibrated Automated Thrombogram (Diagnostica Stago, France). Plasminogen activator inhibitor-1 (PAI-1), soluble endothelial protein C receptor (sEPCR), and soluble vascular cell adhesion molecule-1 (sVCAM-1), Procoag-PPL were measured using antibody-based ELISA kits (Invitrogen International Inc., CA, USA, and Diagnostica Stago, France ). TF expression MPC-derived microparticles (MPC-dMPs) were detected using a Zymuphen MP-TF activity kit (Hyphen BioMed, Neuville sur Oise, France). The upper and lower normal limits (LNL and UNL) were calculated by the mean±2 SD. Results A total of 162 patients were enrolled (age 66.0±12.0 yrs; 53% male). Distribution of disease stage was as follows: 32% ISS I, 23% ISS II, 45% ISS III. Bone disease was present in 71% of patients and 19% of patients had high risk cytogenetic lesions. Patients with ongoing MM (ND, IM, PR/IM) had significantly lower Peak, ETP and MRI as compared to the CG. In contrast, patients in CR had Peak, ETP, MRI values similar to the CG. Patients with PR had lower ETP and MRI values as compared to the CR group. In ND 9% had TG >UNL and 22% had TGUNL and 67% had TGUNL and 35% had TGUNL and 12% had TG

Newborns are the most vulnerable patients for thrombosis development among all children, with critically ill and premature infants being in the highest risk group. The upward trend in the rate of neonatal thrombosis could be attributed to progress in the treatment of severe neonatal conditions and the increased survival in premature babies. There are physiological differences in the hemostatic system between neonates and adults. Neonates differ in concentrations and rate of synthesis of most coagulation factors, turnover rates, the ability to regulate thrombin and plasmin, and in greater variability compared to adults. Natural inhibitors of coagulation (protein C, protein S, antithrombin, heparin cofactor II) and vitamin K-dependent coagulation factors (factors II, VII, IX, X) are low, but factor VIII and von Willebrand factor are elevated. Newborns have decreased fibrinolytic activity. In the healthy neonate, the balance is maintained but appears more easily converted into thrombosis. Neonatal hemostasis has less buffer capacity, and almost 95% of thrombosis is provoked. Different triggering risk factors are responsible for thrombosis in neonates, but the most important risk factors for thrombosis are central catheters, fluid fluctuations, liver dysfunction, and septic and inflammatory conditions. Low-molecular-weight heparins are the agents of choice for anticoagulation.

Cancer-associated venous thrombosis (CAT) is a common, multifactor event known to complicate the course of cancer and jeopardize a patient's prognosis. The current guidelines regarding the prevention of CAT are sometimes considered insufficiently precise about specific situations, or are poorly applied. The expected benefits of thromboprophylaxis are balanced by the risk of major bleeding induced by anticoagulation, which implies a need to accurately identify ambulatory patients at high risk of thrombosis or hemorrhage. The Khorana score is commonly used for this, but is limited by the non-reproducibility of predicted performance across cancer types, and by the fact that antitumor treatment and cardiovascular risks are not included. The COMPASS-CAT score, which includes those two aspects, was found to be a more accurate predictor of venous thromboembolism in patients with lung cancer, and to better distinguish between patients at low or high risk of thrombosis. The frailty of patients with cancer is also a major issue, and should be taken into account when thromboprophylaxis is considered. According to current guidelines, CAT prophylaxis should be considered for hospitalized patients, those for whom surgery is scheduled, or those with pancreatic cancers. In ambulatory patients, decisions should be made according to patient, cancer and antitumoral treatment characteristics. Low molecular weight heparin is the gold standard of CAT prophylaxis. Despite increased risks of bleeding or drug-drug interactions in cancer patients, direct oral anticoagulants could be alternate options for high-risk ambulatory patients that should be accompanied by a careful global analysis of benefits, harms, and patient preferences.

Background: Hypercoagulability is a common blood alteration in newly diagnosed chemotherapy naïve patients with multiple myeloma. Multiple myeloma (MM) figures among malignancies that significantly increase the risk of venous thromboembolism (VTE). The rate of VTE is higher at the time of diagnosis and during the first months following initiation of first line therapy; approximately 10% of newly diagnosed MM (NDMM) will develop a VTE. Despite adequate thromboprophylaxis as per guidelines, the risk of residual VTE is not eliminated and remains as high as 12%. The optimization of VTE prevention in patients with MM is an unmet need. The exact mechanism of the increased risk of VTE is not yet fully understood. The identification of the procoagulant potential of cancer cells, which is related principally to tissue factor (TF) expression, attracts particular interest. Aim: We conducted a longitudinal prospective observational study, to explore the relationship of MM with cellular and plasma hypercoagulability as well as tissue factor positive microparticles, aiming to identify the most relevant biomarkers, which could be used in a Risk Assessment Model (RAM) for VTE in combination with clinical risk factors. Methods: Newly diagnosed patients (182) with multiple myeloma (NDMM) were prospectively enrolled. Patients were followed up for 12 months and the primary end-point was symptomatic objectively confirmed VTE. Patients were risk stratified and received thromboprophylaxis (none, aspirin on low molecular weight heparin (LMWH) based on previously published recommendations by the IMWG and EMN. Prior to treatment initiation and thromboprophylaxis initiation baseline biomarkers were obtained: Thrombin generation (TGT) in citrated PPP was assessed with the Thrombogram-Thrombinoscope® assay using PPP-reagent® 5 pm TF by Diagnostica Stago. The levels of P-Selectin and heparanase in plasma were measured with ELISA Kit (Cusabio Biotech and R&D Systems respectively). The procoagulant phospholipids clotting time was measured with STA-Procoag-PPL®, Levels of Factor VIIa were measured by Staclot VIIa-rTF®, D-Dimers (DDi) by Liatest D-Di (Diagnostica Stago, France), and Tissue Factor activity (TFa) by specific clotting based home test. TF expression MPC-derived microparticles (MPC-dMPs) were detected using a Zymuphen MP-TF activity kit (Hyphen BioMed, Neuville sur Oise, France). These were compared against values in a population of healthy individuals (n=30). Results: The distribution of patients enrolled in the study is as follows: Median age was 67 years (36-86) and 52% of the population was male. Median time to follow up was 7 months (1-12 months). The control group (30 healthy individuals). The overall rate of symptomatic VTE during follow-up was 11.5% (n = 21 patients). Eleven out of 21 events (52%) occurred within 3 months from treatment initiation. Six of these patients did not receive any thromboprophylaxis; six patients were on aspirin at the time of the event and three were on LMWH.At inclusion, patients showed significantly increased levels of TFa, FVIIa, D-Dimers and FM, and significantly shorter Procoag-PPL® as compared to the group of healthy individuals. Levels of P-selectin and TM were significantly lower in patients as compared to healthy individuals. The levels of heparanase were not significantly different in the group of patients as compared to the healthy individuals. Overall thrombin generation was attenuated in patients compared to healthy individuals. Lag-time and ttPeak were significantly increased and Peak, MRI, and ETP were significantly lower as compared to the control group, MP-TF activity measured in NDMM significantly increased 1.46± 0.38 pg/mL compared to control subjects 0.19 ± 0.05 pg/mL (Table 1). Multivariate logistic regression analysis demonstrated that ETP, Procoag-PPL® and MP-TF were independently associated with VTE occurrence. (Table 2) Conclusion: The prospective ROADMAP-CAT-MM study demonstrates the presence of pronounced cellular hypercoagulability in newly diagnosed chemotherapy naïve patients with MM characterized by decreased Procoag-PPL® clotting time, enhanced endothelial cell activation, and exhausted thrombin generation. The Procoag-PPL clotting time and the ETP and MP-TF were found to be independently associated with the risk of VTE and can be prospectively incorporated into a RAM for VTE in MM.