Risk Factor For Thrombotic Events Research Articles

Особенности плазменного звена гемостаза у пациентов с Ph-негативными миелопролиферативными новообразованиями

Введение: Тромбозы являются одним из основных осложнений Ph-негативных миелопролиферативных новообразований (МПН), таких как истинная полицитемия (ИП), эссенциальная тромбоцитемия (ЭТ) и первичный миелофиброз (ПМФ). Имеются многочисленные свидетельства активации тромбоцитов, лейкоцитов, эндотелия и коагуляции при МПН; однако результаты определения показателей гемостаза, применимых в клинической практике для выявления протромботических состояний при МПН, неоднозначны. Цель исследования: оценить состояние плазменного звена гемостаза у пациентов с Ph-негативными МПН и выявить показатели, отражающие протромботическую направленность изменений в системе гемостаза при данных патологиях. Материалы и методы: В исследование было включено 116 пациентов с МПН (43 с ИП, 35 с ЭТ, 38 с ПМФ). Пациенты находились на антиагрегантной, циторедуктивной и таргетной терапии ингибиторами янус-киназ. Контрольная группа состояла из 43 практически здоровых лиц. В плазме крови всех обследованных определяли индекс активированного парциального тромбопластинового времени (АПТВ) — отношение АПТВ исследуемого образца к АПТВ нормальной плазмы, протромбиновый тест по Квику (ПТ), содержание фибриногена, активности фактора VIII (FVIII) и естественных антикоагулянтов антитромбина (АТ) и протеина С (PC), уровень свободного протеина S (PS), а также показатели теста генерации тромбина (ТГТ), в том числе с добавлением тромбомодулина (ТМ). Результаты: У пациентов с МПН по сравнению с контрольной группой наблюдали сдвиг АПТВ и ПТ в сторону гипокоагуляции, было удлинено время инициации генерации тромбина, снижена скорость и количественные показатели ТГТ без добавления ТМ. При проведении ТГТ с добавлением ТМ у больных МПН выявлено снижение чувствительности к ТМ, которое коррелировало с падением активности PC и уровня свободного PS. Содержание фибриногена и активность FVIII у обследованных пациентов были повышены. Заключение: Для пациентов с МПН характерны разнонаправленные изменения показателей плазменного звена гемостаза. Важной детерминантой развития протромботических состояний при МПН выступает недостаточная эффективность естественных антикоагулянтов системы протеина С, приводящая к выраженному дисбалансу в системе гемостаза. Background: Thromboses are one of the main complications of Ph-negative myeloproliferative neoplasms (MPN), such as polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). There are abundant evidences of platelet, leukocyte, endothelial, and coagulation activation in MPN; however, studies of hemostatic parameters applicable in clinical practice for revealing of prothrombotic states in MPN are not identical. Objectives: to assess plasma hemostasis in patients with Ph-negative MPN and to identify parameters reflecting the prothrombotic tendency of hemostatic changes in these pathologies. Patients/Methods: The study included 116 patients with MPN (43 with PV, 35 with ET, 38 with PMF). Patients were treated with antiplatelet, cytoreductive and targeted therapy with Janus kinases inhibitors. The control group consisted of 43 healthy individuals. In blood plasma of all examined persons we determined the index of activated partial thromboplastin time (APTT) — the ratio of APTT of the test sample to APTT of normal plasma, Quick prothrombin test (PT), fi brinogen content, activities of factor VIII (FVIII) and natural anticoagulants — antithrombin (AT) and protein C (PC), free protein S (PS) level, as well as thrombin generation assay (TGA) parameters, including thrombomodulin (TM) addition. Results: As compared with control group, in patients with MPN a shift in APTT and PV to hypocoagulation was observed, the initiation time of thrombin generation was prolonged, the rate and quantitative parameters of TGA without TM addition were decreased. In patients with MPN TGA with TM addition showed reduced sensitivity to TM that correlated with decreased PC activity and reduction of free PS level. Fibrinogen content and FVIII activity in the examined patients were increased. Conclusions: Patients with MPN are characterized by multidirectional changes of plasma hemostasis parameters. The important determinant of prothrombotic states development in MPN is insufficient effectiveness of the natural anticoagulants of protein C system that leads to expressed hemostasis imbalance.

CHANGES IN THE PARAMETERS OF THROMBODYNAMICS AND BLOOD CLOT CONTRACTION IN PATIENTS WITH RHEUMATOID ARTHRITIS

Autoimmune diseases, including rheumatoid arthritis (RA), are risk factors for thrombotic events. Understanding the pathogenetic role of hemostatic changes in RA can assist in developing measures for prevention, prognosis, early diagnosis, and treatment of immune thromboses. Objective: to investigate the state of platelet and plasma hemostasis in patients with RA, as compared to other laboratory parameters and clinical manifestations of the disease. Subjects and methods. Hemostasis was investigated using two relatively new laboratory tests: thrombodynamics and kinetics of blood clot contraction (BCC). Examinations were made in 60 patients with RA and in 50 apparently healthy individuals of the control group. Results and discussion. In patients with RA, the parameters of thrombodynamics and BCC were found to be significantly different from the normal values. According to thrombodynamics, there was an increase in plasma clot growth rate, size, and density, which indicates chronic hypercoagulation. The rate and completeness of BCC were substantially reduced due to platelet dysfunction in patients with RA compared to healthy individuals. The changes in the parameters of thrombodynamics and BCC correlated with the laboratory signs of systemic inflammation and depended on the radiographic stage of the disease. Conclusion. The results of this investigation confirm that hemostatic disorders are present in RA and indicate the informative value of thrombodynamics and BCC tests as indicators of a pre-thrombotic state, including autoimmune pathology.

\u201cNon-criteria\u201d antiphospholipid antibodies add value to antiphospholipid syndrome diagnoses in a large Chinese cohort

BackgroundDespite expansion in the 2006 Sydney antiphospholipid syndrome (APS) classification criteria to include IgG/IgM anti-β2-glycoprotein (aβ2GPI) antibodies in addition to IgG/IgM anti-cardiolipin antibodies (aCL) and lupus anticoagulant (LAC), some individuals with clinical features of APS remain seronegative (seronegative APS or SNAPS) and are at risk of recurrent thrombosis and pregnancy morbidities. Our aim was to assess the value of “non-criteria” aPL antibodies to detect these SNAPS patients.MethodsOne hundred ninety-two APS patients, 90 SNAPS patients, 193 autoimmune disease controls, and 120 healthy controls were evaluated. Ten antiphospholipid antibodies (aPLs) were tested using commercial kits, including 5 non-criteria aPLs: anti-phosphatidylserine/prothrombin antibodies (aPS/PT) IgG/IgM, aCL IgA, aβ2GPI IgA, and anti-β2GPI Domain 1 (aβ2GPI-D1) IgG.ResultsUp to 60.9% of the SNAPS and 93.5% of APS patients were detected by at least one non-criteria aPL. aPS/PT IgG had the highest Youden index in classifying APS and SNAPS from controls. aPS/PT IgG and aβ2GPI Domain 1 IgG seem to be the most significant risk factors for thrombotic events and pregnancy morbidity, respectively. aPS/PT IgG/IgM and aβ2GPI-D1 IgG were detected in some SNAPS patients, while IgA isotypes of aCL/aβ2GPI tended to appear together with other biomarkers. The combined analysis showed enhanced diagnostic performance with the inclusion of non-criteria aPLs.ConclusionsRecognition of SNAPS patients is critical for clinical management and prevention of potential thrombotic and obstetric adverse events. The non-criteria antiphospholipid antibodies help to identify a considerable portion (60.9%) of these patients who otherwise may remain untreated and at clinical risk.

Correlation Between PAI-1 Gene 4G/5G Polymorphism and the Risk of Thrombosis in Ph Chromosome-Negative Myeloproliferative Neoplasms.

Thrombosis has been recognized as one of the most significant risk factors of high mortality and disability in patients with Philadelphia (Ph) chromosome negative myeloproliferative neoplasms (MPNs). However, the risk factors of thrombotic events in these patients have not been completely understood. In this study, the clinical data of 58 patients with Ph-MPNs were obtained and analyzed, including 34 cases of essential thrombocytopenia (ET), 23 thrombotic events happened in 21 (36%) patients, among which 60% (14 of 23) with cerebral infarction, 17% (4 of 23) with coronary heart disease and 23% (5 of 23) with venous thrombosis. There were no significant differences in age, sex, and blood cell count between polycythemia vera (PV) and ET patients who have experienced thrombotic events and those who have not. In ET patients, the incidence of thrombotic events in plasminogen activator inhibitor-1 (PAI-1) genotype 4G4G was significantly higher than that in genotype 4G5G and genotype 5G5G (P < .05). The incidence of thrombotic events in PV and ET patients with infection was higher than those without infection (P < .05). Using logistic regression analysis, we found that PAI-1 genotype 4G4G and infection were associated with thrombotic events (odds ratio 6.744, 95% CI: 1.195-38.056 and 15.641 95% CI: 3.327-73.522). The 4G/4G polymorphism of PAI-1 gene and infection are independent risk factors of thrombotic events in patients with Ph-MPNs. PAI-1 gene 4G4G and infection in ET and PV patients with Janus kinase 2 (JAK2) V617F mutation were shown to be high risk of thrombotic events. Therefore, clinical doctors should put more attention on PAI-1 genotype 4G4G and infection in JAK2 V617F mutated patients with Ph-MPNs to prevent the thrombosis.

Characterization of the Rate, Predictors, and Thrombotic Complications of Thrombocytosis in Iron Deficiency Anemia

Introduction: Iron deficiency anemia (IDA) is the most common cause of anemia worldwide and is frequently untreated or undertreated (Kesselbaum et al. 2014). The association of thrombocytosis with IDA is well-recognized, with recent work elucidating its underlying physiology (Xavier-Ferrucio et al. 2018). Thrombocytosis in IDA may predispose to thrombotic complications, as described in many case reports. Given that IDA is ubiquitous, even minor increases in thrombotic risk due to thrombocytosis have dramatic public health implications. Data describing the rate, predictors, and risk of thrombotic complications are limited. This study characterizes these features of thrombocytosis in IDA. Methods: We queried a large institutional patient data repository containing comprehensive chart data for over 5.8 million patients to identify patients with IDA with and without thrombocytosis and thrombotic events over a 40-year time period (1979 to 2019). Demographic information, hematological parameters, thrombosis history, and other medical history were collected at time of peak thrombocytosis, time of IDA diagnosis, and clinical baseline (before IDA diagnosis or after resolution). The fidelity of query data was assessed by performing detailed manual chart review of 700 total patients. Clinical diagnoses of IDA were verified by confirming ferritin values &amp;lt;30 ng/ml and consistent CBC parameters. Temporal association of thrombocytosis with IDA was confirmed and patients with other causes of thrombocytosis (including active malignancy, infection, inflammatory bowel disease, recent surgery/trauma, inflammatory arthritis, and myeloproliferative neoplasms) were excluded. Only arterial and venous thrombotic events occurring concurrently with IDA or IDA with thrombocytosis were included. Data were analyzed using t-tests, chi-square tests, Pearson correlations, and multivariate regression. Results: Our queries identified 36,327 IDA cases and 15,022 IDA with thrombocytosis cases. Query fidelity rates were 95% and 75%, respectively, yielding a true thrombocytosis rate of 32.6% in patients with IDA. After excluding cases with other causes of thrombocytosis, we calculated a 7.8% rate of thrombosis in patients with IDA and a 15.8% rate of thrombosis in patients with reactive thrombocytosis secondary to IDA (Table 1, Figure). The odds ratio for thrombosis in IDA with thrombocytosis vs IDA alone was 2.23 (2.09-2.38, p&amp;lt;0.0001). Both venous and arterial thrombotic events were more likely in patients with IDA and thrombocytosis (Table 1). Risk factors for thrombotic events were slightly more common in patients with IDA and thrombosis (OR 1.28, Table 1). Mean duration of IDA episode (from IDA diagnosis to normalization of hemoglobin and platelet count) was 2.03 years. Among patients with IDA and thrombocytosis, ferritin and hemoglobin (Hgb) were both moderately negatively correlated with platelet count (Plt) (Table 2). Platelet mass index (Plt x MPV) at time of IDA diagnosis and peak thrombocytosis was significantly higher than baseline. Platelet mass index and Hgb were strongly negatively correlated at peak thrombocytosis. Multivariate regression including age, sex, WBC count, Hgb, Plt, and MCV demonstrated a significant predictive relation between decreasing Hgb and increasing Plt at peak thrombocytosis. Conclusions: In this large retrospective analysis, we describe the rate and predictors of thrombocytosis in IDA in addition to rates of thrombosis in IDA patients with and without reactive thrombocytosis. Combining queries of a massive clinical database with manual chart review to ensure data validity, we found a 32.6% rate of thrombocytosis in IDA, negative correlations between both Hgb/ferritin and Plt, and a 2-fold increased thrombotic risk in patients with thrombocytosis reactive to IDA relative to IDA alone. We also found increased total body platelet mass in IDA patients with thrombocytosis, which may contribute to this increased thrombotic risk. Thrombosis rates overall were high, possibly due to database inclusion of more morbid inpatients in addition to outpatients. Given the global burden of untreated and undertreated IDA, our findings suggest that adequate IDA treatment may reduce thrombotic complications and associated morbidity and mortality. Acknowledgements: A. Song is the recipient of the American Society of Hematology HONORS Award (provides research support). Disclosures Kuter: Daiichi Sankyo: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Merck Sharp Dohme: Consultancy, Honoraria; Up-to-Date: Consultancy, Honoraria, Patents &amp; Royalties: 3 Up-to-Date chapters; Caremark: Consultancy, Honoraria; Bristol Myers Squibb (BMS): Consultancy, Honoraria, Research Funding; Platelet Disorder Support Association: Consultancy, Honoraria; Alnylam: Consultancy, Honoraria, Research Funding; Zafgen: Consultancy, Honoraria; UCB: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria; Kezar: Research Funding; Principia: Consultancy, Honoraria, Research Funding; Shire: Consultancy, Honoraria; Takeda (Bioverativ): Consultancy, Honoraria, Research Funding; Kyowa-Kirin: Consultancy, Honoraria; Momenta: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Argenx: Consultancy, Honoraria, Research Funding; Agios: Consultancy, Honoraria, Research Funding; Actelion (Syntimmune): Consultancy, Honoraria, Research Funding; Dova: Consultancy, Honoraria; Protalix: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Protalex: Consultancy, Honoraria, Research Funding; Shinogi: Consultancy, Honoraria; Rigel: Consultancy, Honoraria, Research Funding. Al-Samkari:Agios: Consultancy, Research Funding; Dova: Consultancy, Research Funding; Moderna: Consultancy.

Gene mutation spectrum and clinical characteristics analysis of 178 patients with essential thrombocytosis

目的分析原发性血小板增多症（ET）患者基因突变谱及临床特征。方法对2009年2月1日至2018年11月1日收治的178例初诊ET患者进行回顾性分析。结果全部178例患者中，男89例，女89例，中位初诊年龄为49.5（3~86）岁。JAK2V617F基因突变频率为16.45%（1.67%~43.90%），CALR基因突变频率为40.00%（10.00%~49.15%），MPL基因突变频率为25.10%（25.00%~40.00%）。与CALR基因突变的患者相比，JAK2V617F基因突变患者具有较高的发病年龄（P=0.035）、初诊白细胞计数（P=0.040）、初诊血红蛋白浓度（P=0.001）和较低的初诊血小板计数（P=0.002）。47例（27.01%）患者诊断ET前发生血栓事件，3例（1.72%）诊断ET后发生血栓事件。多因素分析结果显示，年龄>60岁（P=0.013，OR=4.595，95%CI1.382~15.282）、心血管危险因素（P<0.001，OR=8.873，95%CI2.921~26.955）为血栓事件的危险因素，CALR基因突变（P=0.032，OR=0.126，95%CI0.019~0.838）为血栓事件的保护性因素。年龄>60岁（P=0.042，OR=4.045，95%CI1.053~15.534）是影响ET患者总生存时间的危险因素。年龄≤60岁、年龄>60岁患者的OS时间分别为（115.231±1.899）、（83.291±4.991）个月（χ2=6.406，P=0.011）。结论心血管危险因素、年龄>60岁为ET患者血栓事件的危险因素，CALR基因突变为血栓事件的保护性因素。年龄>60岁是影响ET患者总生存的危险因素。

Thrombosis as a treatment complication in Hodgkin lymphoma patients: a comprehensive analysis of three prospective randomized German Hodgkin Study Group (GHSG) trials.

The prognosis of Hodgkin lymphoma (HL) is excellent rendering research into treatment complications highly important. An important complication of cancer and its treatment is thrombosis. Thrombotic events are regularly observed in HL patients but precise information on incidence and risk factors is lacking and the value of prophylactic anticoagulation unclear. Thus, we comprehensively studied thrombotic events in 5773 patients from the German Hodgkin Study Group (GHSG) HD13-15 trials in early-favorable, intermediate and advanced HL. We estimated the incidence of and identified risk factors for thrombotic events. Additionally, we provide detailed data on the time course and characteristics of thrombotic events. A total of 193 thrombotic events occurred for an incidence of 3.3%. Out of these, 175 (90.7%) were venous thromboses, 3 (1.5%) newly emerging post-thrombotic syndromes and 15 (7.8%) arterial thromboses. There were 11 (0.7%) events in early-favorable, 27 (1.3%) in early-unfavorable and 155 (7.3%) in advanced patients, the latter incidence being significantly higher (P < 0.001). The most common locations were deep vein thrombosis of the arm (46.3%) and leg (24.6%). Most venous thrombotic events occurred during chemotherapy (78.9%). We observed 59 (30.6%) catheter-associated events and a descriptively increased risk of venous thrombotic events in patients with oral contraception use during treatment (6.8% versus 3.9%). In advanced HL, the incidence of venous thrombotic events was increased upon treatment with BEACOPP-14 (9.4%, P = 0.0079) compared with 5.1% with 6×BEACOPPesc and 5.7% with 8×BEACOPPesc. Among commonly applied risk factors, including the Khorana score, only age and smoking were prognostic. The incidence of thrombotic events in advanced stage HL is comparable to other high-risk cancer patients, especially if treated with dose-dense regimens. Additional risk factors are higher age and smoking. Selected HL patients could benefit from prophylactic anticoagulation, however, further interventional studies are needed before general recommendations can be made.

Ретроспективный анализ факторов риска тромботических осложнений при приеме комбинированных оральных контрацептивов

Ретроспективный анализ факторов риска тромботических осложнений при приеме комбинированных оральных контрацептивов

PF684 ANAGRELIDE MODULATES PROPLATELET FORMATION RESULTING IN DECREASED NUMBER AND INCREASED SIZE OF PLATELETS

Background:In patients with essential thrombocythemia (ET) who have high risk factors for thrombotic events, cytoreductive therapy with anagrelide (ANA) or hydroxycarbamide (HC) is one of the treatment options. Despite the clinically evident platelet‐lowering effect of ANA, the detailed mechanism of its effect remains to be elucidated. In addition to the previously reported inhibition of megakaryocytic differentiation, we hypothesized that ANA affects the formation of proplatelets, the final process of platelet release.Aims:To determine platelet size change and proplatelet formation with ANA treatment, we retrospectively analyzed patients’ data and analyzed data obtained from an experimental model using a human megakaryocytic cell line (MEG‐01 cells), an accepted model of thrombopoiesis.Methods:We retrospectively evaluated 48 patients diagnosed with ET in Hokkaido University Hospital (male/female: 14/34, age, 18 to 87 years; median age, 61.5 years; ANA only, 3 patients; ANA after HC due to insufficient decrease in platelets, 11; HC only, 18; observed without ANA or HC, 16). We analyzed changes in platelet counts and mean platelet volume (MPV) after administering each medicine. This study was approved by the Institutional Review Board of Hokkaido University Hospital. Megakaryocytic differentiation of MEG‐01 cells was induced by PMA treatment with or without ANA. Morphological change of proplatelets and size of platelet‐like particles (PLPs) were analyzed.Results:The figure shows the relationship between decrease in platelet count and MPV change in each patient at the time of maximum response to ANA or HC. In patients treated with ANA (n = 14), the degree of platelet count reduction (‐83.4% to −27.1%; median, −56.6%) was strongly correlated with increase of MPV (‐6.6% to +28.7%; median, +16.7%) (left panel; R = 0.777, P = 0.001). On the other hand, in patients treated with HC (n = 29), the degree of platelet count reduction (‐78.7% to −20.8%; median, −55.5%) was not correlated with change of MPV (‐10.3% to +12.9%; median, +1.0%) (right panel; R = 0.245, P = 0.21). PMA‐induced megakaryocytic differentiation of MEG‐01 cells promoted production of PLPs. The number of PLPs was decreased in PMA + ANA‐treated MEG‐01 cells (P &lt; 0.01 vs. PMA alone). PLP size measured by flow cytometry was significantly increased in PMA + ANA‐treated MEG‐01 cells (P &lt; 0.05 vs. PMA alone). These results are consistent with the clinical findings. MGG staining of MEG‐01 cells revealed that ANA modified the formation of cytoplasmic protrusions (proplatelets). We compared morphological parameters including the length, width and number of protrusions. The protrusions were shorter and thicker and the number of protrusions was decreased in PMA + ANA‐treated MEG‐01 cells (P &lt; 0.01 vs. PMA alone).The FAK‐RhoA‐ROCK‐MLC2‐myosin IIA pathway is an important pathway for the formation of proplatelets and production of platelets from megakaryocytes. We evaluated the effect of ANA on phosphorylation of FAK and MLC2. Western blot analysis showed that ANA treatment caused reduced phosphorylation of FAK and increased phosphorylation of MLC2 (PMA vs. PMA+ANA 5 μM, P &lt; 0.01), which presumably resulted in suppression of actin remodeling.Summary/Conclusion:ANA reduces platelet counts and increases platelet size in ET patients. Analysis of ANA‐treated MEG‐01 cells suggested that suppression of proplatelet formation through modulation of the FAK‐RhoA‐ROCK‐MLC2‐myosin IIA pathway is a key mechanism. Morphological observation suggested that ANA induces premature release of platelets, resulting in increased platelet size.image

Relationship between Thrombotic Events and Peripheral Neutrophil-to-lymphocyte Ratio in Patients with Newly Diagnosed Essential Thrombocythemia

To explore the role of neutrophil-to-lymphocyte ratio（NLR) in patients with newly diagnosed essential thrombocythemia（ET) and its relationship with thrombotic events. The clinical and follow-up data of 150 ET patients were retrospectively analyzed. The risk factors of thrombotic events and role of NLR by statistical methods. Age (P<0.01) and JAK2V617F mutation (P<0.01) were the independent risk factors for thrombotic events at diagnosis; WBC count (P<0.05), NLR (P<0.01), age (P<0.05) and thrombosis history at diagnosis (P<0.05) were independent risk factors for future thrombotic events. The ROC curve showed that NLR for prediction of future thrombotic events was suprior to other risk factors. The Kaplan-Meier analysis showed that the progress-free survival time in thrombotic events patients with higher NLR (median survival 22.3 months, 95% CI:17.8-26.8) was significantly shorter than that of patients with lower NLR (median survival 55.5 months, 95% CI:53.4-57.5) . After follow-up 60 months, the thrombosis progress-free survival in lower NLR patients reached 97.4%, while that in the patients with higher NLR was rate 46.7%. NLR at diagnosis is a better predictive parameter for future thrombotic events than other clinical parameters in ET patients, but without corralations with thrombosis at diagnosis.

Risk factors of thromboembolism in nonvalvular atrial fibrillation patients with low CHA2DS2-VASc score.

The risk of thromboembolism in patients with CHA2DS2-VASc score of 0 to 1 was low, and the anticoagulant therapy was not recommended. Although the CHA2DS2-VASc score was low, there were still many patients suffered from thrombotic events and stroke. We aim to investigate the risk factors of thrombotic events in nonvalvular atrial fibrillation (NVAF) patients with low CHA2DS2-VASc score.We retrospectively enrolled 595 consecutive NVAF patients with low CHA2DS2-VASc score (male: CHA2DS2-VASc = 0, female: CHA2DS2-VASc = 1). The general clinical data, blood biochemical data, and echocardiography results of the 595 patients were collected. Multivariate logistic regression models were used to evaluate risk factors of thrombosis. Receiver operating characteristic curve was used to identify the optimal cut-off value of the independent risk factors. A P value of <.05 (2-sided) was considered to be statistically significant.In multivariate analysis, lipoprotein (a) (Lp(a)) plasma level and left atrium diameter (LAD) were positively related to thromboembolism in NVAF patients with CHA2DS2-VASc score of 0 to 1 after adjustment for age, gender, and other variables (odds ratio [OR] = 1.02, 95% confidence interval [CI]: 1.01–1.03; OR = 1.13, 95% CI: 1.06–1.18). Lp(a) exerted a significant predictive value with area under the curve (AUC) of 0.62 (95% CI: 0.55–0.68, P < .01). The optimal cut-off value for Lp(a) predicting thrombotic events was 27.2 mg/dL (sensitivity 45.7%, specificity 73.4%). LAD showed a significant predictive value with AUC of 0.71 (95% CI: 0.64–0.78, P < .01). The optimal cut-off point for LAD predicting thrombotic events was 43.5 mm (sensitivity 47.1%, specificity 85.8%).High Lp(a) plasma level and left atrial dilatation might be independent risk factors of thrombotic events for NVAF patients with low CHA2DS2-VASc score.

Low incidence of thromboembolism in multiple myeloma patients receiving immunomodulatory drugs; a retrospective single-institution analysis.

Anti-platelet agents or anticoagulants are administered for patients with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs) to prevent thrombotic events (TEs). However, there is a discrepancy between current guidelines and clinical practice in thromboprophylaxis and the varied incidence of TEs depending on patient cohort. Therefore, a consensus on the optimal thromboprophylactic strategy is needed. To determine an appropriate strategy for the prevention of TEs in MM patients receiving IMiDs, we performed a retrospective single-institution analysis. In total, 95 MM patients (62% male, median age 65 years, range 30-85years) from November 2008 to January 2018 were recruited, and 140 cases were analyzed in the medical-record-based study. Thromboprophylactic drugs were given to 69% of patients, anti-platelet agents to 66%, and anticoagulants to 3.0%. Seven TEs (5.0%) and six bleeding events (4.3%) were observed, but no patients died from thrombohemorrhage. The median follow-up period was 184days (range 21-2224), and the cumulative TE incidence was 1.7% at 3 months, 7.0% at 1 year, and 12.5% at 3years. Multivariate analysis determined that age > 70years (p = 0.012) and BMI < 18.5kg/m2 (p = 0.042) were the significant risk factors of TE. A low incidence of TEs was observed despite the low adherence to guideline recommendations for anticoagulant administration. These results suggest that anti-platelet agents are sufficient for thromboprophylaxis. A high-risk group of TEs in MM patients receiving IMiDs was identified, and a larger study is needed to confirm these findings.

A Study about the Relationship between Thrombotic Events and Peripheral Neutrophil-to-Lymphocyte Ratio in Patients with Newly Diagnosed Essential Thrombocythemia

To explore the role of neutrophil-to-lymphocyte ratio (NLR) in patients with newly diagnosed essential thrombocythemia (ET) and the relationship with thrombotic events.150 ET patients with ET from January 2013 to December 2017 were retrospectively enrolled in this study to investigate the risk factors of thrombosis and analyse the role of NLR in thrombotic events. The following parameters were evaluated: age, sex, blood routine examination, JAK2V617F mutation, cardiovascular risk factors, history of previous thrombosis, thrombosis during follow-up, examination and biopsy of bone marrow.Age(P=0.001) and JAK2 V617F mutation(P=0.003) were independent risk factors for thrombotic events at diagnosis after Logistic multivariate analysis. WBC count (P=0.047), NLR (P<0.001), age (P=0.037) and thrombosis at diagnosis (P=0.036) were independent risk factors for future thrombotic events and NLR was better for prediction of future thrombotic events than other risk factors in ROC curve. The thrombosis-free survival of thrombotic events in patients with higher NLR(median survival 22.3 months, 95% CI:17.8-26.8) was significantly shorter than that of patients with lower NLR(median survival 55.5 months, 95% CI:53.4-57.5) in Kaplan-Meier analysis (P<0.001). After 60 months of follow-up, patients with lower NLR had a thrombosis-free survival of 97.4%, while patients with higher NLR had a thrombosis-free survival of 46.7%. NLR at diagnosis was a better predictive parameter for future thrombotic events than other clinical parameters in ET patients, but was not associated with thrombosis at diagnosis. DisclosuresNo relevant conflicts of interest to declare.

'Massive transfusion protocols and the use of tranexamic acid'.

We review recent articles pertaining to the use of tranexamic acid (TXA) in populations at risk for massive transfusion. Although there are no recent studies that specifically examine the use of TXA in massive transfusion protocols (MTPs), there are a few studies with subgroups of massive transfusion patients. In recent years, many publications have discussed outcomes and safety associated with the addition of TXA to treatment plans for bleeding pediatric, trauma, and postpartum hemorrhage patients. In general, TXA appears to decrease mortality and transfusion requirements. TXA was shown to decrease mortality in several bleeding populations. It is now a common addition to MTPs. There is conflicting evidence regarding the potential of TXA as a risk factor for thrombotic events. Ongoing studies should provide additional evidence regarding the thrombotic risk of TXA in massive transfusion.

The role of SCUBE1 in the development of late stent thrombosis presenting with ST-elevation myocardial infarction

Introduction and AimThere is an important link between platelets and inflammation, thrombosis, and vascular and tissue repair mechanisms. SCUBE1 (signal peptide-CUB-EGF domain-containing protein 1) may function as a novel platelet-endothelial adhesion molecule and play pathological roles in cardiovascular biology. Stent thrombosis (ST) following percutaneous coronary intervention is an uncommon and potentially catastrophic event that can manifest as myocardial infarction and sudden death. High platelet reactivity is a risk factor for thrombotic events, including late ST. For this reason, in the current study, we researched the role of SCUBE1 in the development of late coronary ST. MethodsWe included 40 patients admitted to our hospital with a diagnosis of ST-elevation myocardial infarction (STEMI) and signs of late ST on a coronary angiogram. For the control group, we recruited 50 healthy gender- and age-matched individuals who were seen for health check-ups. We also randomly included 100 patients with a diagnosis of STEMI without ST. ResultsThere were no significant differences between the groups in terms of baseline and demographic characteristics. The mean SCUBE1 level in patients with STEMI with late ST at admission and the STEMI without ST group was significantly higher than in the control group (p<0.01). The mean SCUBE1 level in the STEMI with late ST group was significantly higher than in the STEMI without ST group (p=0.03). In multivariate regression analysis, serum SCUBE1 (odds ratio [OR]: 1.022; 95% confidence interval [CI]: 1.011-1.033, p<0.001) remained an independent predictor for the presence of late ST. In addition, receiver operating characteristic curve analysis was used to determine the optimal SCUBE1 cut-off value for predicting late ST. The area under the curve was 0.972 (95% CI 0.95-0.98). The SCUBE1 cut-off value was 59.2 ng/ml, with a sensitivity of 95.4% and specificity of 82.9%. ConclusionThe present work is the first clinical study to demonstrate that serum SCUBE1 levels are significantly higher in patients with late ST and serum SCUBE1 was an independent predictor for the presence of late ST in our study population.

Thrombosis in multiple myeloma

Reportedly, patients with cancer have an increased risk (four- to seven-fold) of developing thrombotic events (TEs) compared with healthy volunteers. Multiple myeloma (MM) is one of the neoplasms that exhibit a high incidence of TEs, and approximately 10% patients with MM develop TEs during their clinical courses. The underlying risk factors of TEs are classified into patient-, disease-, and treatment-related factors. Specific treatment-related risk factors comprise the use of immunomodulatory drugs combined with dexamethasone. As the occurrence of TE in patients hampers the treatment for MM itself, which results in unfavorable outcomes, elucidating TE pathogenesis and adequate prophylaxis for each patient are essential to prevent MM-related TEs.

Low Mean Cell Haemoglobin is a Valuable Parameter of Thrombotic Risk Stratification in Patients with Polycythemia Vera

Objectives: Thrombosis is a leading cause of morbidity and mortality in patients with Philadelphia negative chronic myeloproliferative neoplasms (MPNs). There are many thrombosis risk stratifications used in this patient group taking into consideration the age, thrombosis history and cardiovascular factors (hypertension, hypercholesterinaemia, hyper-trigliceridaemia, thrombocytosis, smoking and diabetes mellitus). In this work we evaluated the possible role of iron deficiency in thrombotic events (TE) of the polycythaemia vera (PV) patients. Methods: We considered the low mean cell haemoglobin (MCH <28 pg) value as a parameter to assess the iron deficiency in the multicentre database (15 Hungarian haematology centres) of our HUMYPRON GROUP (Hungarian MPN Working Group). The MCH values, recorded at the time of diagnosis of 296 patients with polycythemia vera, were retrospectively analysed.Results: The low MCH, at the diagnosis, was found to be a risk factor for thrombotic events occurring after diagnosis (OR: 1.966). It was also shown as an additive and independent parameter in the Tefferi high-risk patient groups, and combining it with Tefferi risk stratification an extremely high thrombotic risk group could be determined (Nagelkerke R square: 0.084). We have supposed that low MCH in PV reveals a disease form featured with a high proliferation activity. Our hypothesis was confirmed with a sub-study (n=52) showing that the high JAK2V617F allele burden was significantly correlated with the low MCH (p=0.005) and the high white blood cell count (WBC) (p<0.001).Conclusions: Iron deficiency, existing at the time of diagnosis of PV, was proven to be a risk factor for imminent thrombotic events. The low MCH was found to be a strong additive factor when it was combined with the known thrombotic risk stratification systems. The low MCH showed significant correlation with the high JAK2V617F allele burden.

Assessment of thrombotic events in children: A hospital based study

Background: There is scarcity of information on the incidence of inherited thrombophilia from our country. The present study was conducted to assess thrombotic events in children. Materials & Methods: The present study was conducted in the department of Pediatrics. It comprised of 38 children. Patients were subjected to complete hemogram, sickling test, immunological evaluation etc. Risk factors for thrombotic events were recorded. Results: Out of 38 patients, 16 were of VTE and 22 were of ATE. The most common VTE was due to central venous catheter seen in 6 cases. Most common ATE was due to thrombophilias seen in 5 cases. Other reasons in VTE were immobilization seen in 2, trauma in 1, infections in 2, dehydration in 2. Other reasons in ATE were immobilization seen in 2, trauma in 4, infections in 3, dehydration in 3 and unknown in 4 cases. The difference was significant (P< 0.05). Conclusion: Thrombotic events in children are emerging problem. The most common reason for VTE was central venous catheters and in ATE was thrombophilias.

Comparison of two methods for factor five Leiden detection in patients with thromboembolism

Introduction: Factor five Leiden is one of the most important hereditary risk factors for thrombotic events, especially in an early age and during pregnancy patients. Therefore, detection of the factor in the thrombotic events is one of the diagnostic priorities. We can detect this factor in the laboratory thorough two common tests such as Activated protein C resistance and molecular methods especially PCR-RFLP. In this study we evaluated the sensitivity and specificity of the APCR test in comparison of PCR-RFLP the golden diagnostic test for Factor Five Leiden. Materials and Methods: In this research, we have been studied fifty six patients with vascular thrombosis, who visited thrombosis clinical center in Imam Khomeini Hospital. After confirming the DVT diagnosis and pulmonary embolism, blood samples were collected in 3.2% sodium citrate tubes for APCR test, and in K2EDTA CBC tubes for molecular tests. Results: Fifty six DVT patients, including 26 males (44.6%) and 30 females (55.4%), from 1 year up to 50 years old with mean age of 28.9 ± 10.76 were studied. According to PCR-RFLP test out of the 56 patients, 15 (26.7%) had heterozygous and 5 (8.9%) homozygous mutation for factor V Leiden. The very same 20 patients had positive APCR results (Rate of less than 2 and time less than 120 seconds were considered positive), in conclusion the results of the two tests were 100% compatible. Discussion and Conclusion: In populations where other mutations resistant to active protein C such as factor V Cambridge, R2 polymorphism and factor V Liverpool have low prevalence, by removing the intervening factors such as Lupus Anticoagulant antibody, the APCR test could be considered equally sensitive and specific as PCR-RFLP test and can be used for factor V Leiden detection by spending less time and money.

Antiphospholipid syndrome and IgA anti-beta2-glycoprotein I antibodies: when Cinderella becomes a princess.

IgA anti-beta2-glycoprotein I (IgA-aB2GPI) antibodies are currently not included as a laboratory criterion of antiphospholipid syndrome (APS). In the 13th International Congress on Antiphospholipid Antibodies, Galveston, TX, (USA) in 2010, these antibodies were accepted as an APS laboratory criterion in patients who had clinical manifestations of APS but were negative for "consensus" antiphospholipid antibodies (aPL) (IgG and IgM isotypes). Consequently, individuals with thrombotic events who are negative for consensus aPL may be undiagnosed for APS. The most recent publications have confirmed that IgA-aB2GPI antibodies are a risk factor for thrombotic events. In this viewpoint, we propose that IgA-aB2GPI antibodies should be included as an APS consensus criterion and that we have to help Cinderella become a princess.