Risk Factor For Thrombotic Events Research Articles

Reevaluation of cardiovascular risk factors for thrombotic events in 580 Japanese patients with essential thrombocythemia.

Risk-adapted therapy is recommended to prevent thrombosis in essential thrombocythemia (ET) patients. An advanced age, a history of thrombosis, and the presence of the JAK2V617F mutation are well-defined risk factors for thrombosis in ET; however, the impact of cardiovascular risk (CVR) factors on thrombosis in ET remains elusive. Therefore, we herein investigated the impact of CVR factors on thrombosis in 580 ET patients who met the 2017 World Health Organization Classification diagnostic criteria. A univariate analysis identified hypertriglyceridemia and multiple CVR factors as strong risk factors for thrombosis (hazard ratio [HR] 3.530, 95% confidence interval [CI] 1.630-7.643, P = 0.001 and HR 3.368, 95% CI 1.284-8.833, P = 0.014, respectively) and hyper-LDL cholesterolemia as a potential risk factor (HR 2.191, 95% CI 0.966-4.971, P = 0.061). A multivariate analysis revealed that hypertriglyceridemia was an independent risk factor for thrombosis (HR 3.364, 95% CI 1.541-7.346, P = 0.002). Furthermore, poor thrombosis-free survival was observed in patients with a serum triglyceride level ≥ 1.2mmol/L (HR = 2.592, P = 0.026 vs. < 1.2mmol/L) or two or more CVR factors (P = 0.011 vs. no CVR factors and P = 0.005 vs. one CVR factor). These results revealed the impact of CVR factors on thrombosis in ET. Since CVR factors are manageable, lifestyle interventions, such as the control of serum triglyceride levels, may effectively prevent thrombosis in ET patients.

Neutrophil to Lymphocyte Ratio (NLR) at Diagnosis Is a Predictor of Venous Thrombosis and Poor Outcome in Patients with Prefibrotic Primary Myelofibrosis

Background Thrombosis is a common complication in patients (pts) with myeloproliferative disease: it represents the product of a dysfunctional interaction between erythrocytes, platelets, leukocytes and endothelium. A pro-inflammatory microenvironment appears to be associated with an increased thrombotic risk. Neutrophil-to-lymphocyte ratio (NLR) reflects the balance between systemic inflammation and immunity and is emerging as a prognostic biomarker in several diseases, including hematological ones. Recently Carobbio et al. [BCJ, 2022] described NLR as a predictor of venous thrombosis in Polycythemia Vera. No score was specifically developed to assess thrombotic risk in myelofibrosis (MF), and even less is known in the setting of prefibrotic primary myelofibrosis (pre-MF). Aims In a multicenter cohort of pre-MF pts, we retrospectively investigated the relationship between NLR values at diagnosis and the risk of: 1) thrombosis 2) disease progression into overt-MF, accelerated (AP) or blast phase (BP); 3) overall survival (OS). Methods We collected clinical, histopathological and hematological data of 176 pts with a diagnosis of pre-MF, revised according to 2016 World Health Organization criteria, followed at 4 Hematological Centers between 2002 and 2022. NLR values were calculated using data obtained from the complete blood count at diagnosis, as the ratio between absolute neutrophilic count (ANC) and absolute lymphocyte (ALP) count. Pts were dichotomized using the best threshold identified by ROC analysis. Thrombotic complications included arterial (ischemic stroke, myocardial infarction, peripheral arterial disease) and venous (deep vein thrombosis, pulmonary embolism, cerebral and splanchnic vein thrombosis) events. Thrombosis-free survival (TFS) and OS were determined from pre-PMF diagnosis to the first thrombotic event and to death or last contact, respectively. TFS/OS were estimated by Kaplan-Meier analysis; the log-rank test was used to compare TFS/OS differences between risk stratified groups. Results Overall, 176 pts were included in this study. Median age was 63.6 (range 25-80) years; 88 (50%) were male. Majority of pts were JAK2V617F mutated (76,1%). Median NLR value at diagnosis was 3 (range 0,64-41,5). By ROC analysis, 6 was identified as the best cut-off value to dichotomize pts based on NLR; 23 pts (13%) presented NLR >6 at diagnosis. A major thrombotic event occurred before or at diagnosis in 53 pts (30,1%): 29 arterial and 25 venous (one patient had both a venous and arterial event). During the follow-up (FU), 30 pts (17%) developed a thrombosis, for a total of 38 thrombotic events (20 venous and 18 arterial events, accounting for an incidence rate of 1,67 and 1,50 per 100 pts-year, respectively). In statistical analysis, factors significantly associated to thrombosis during the FU were previous thrombosis (p=0.05) and JAK2 V617F mutation (p=0.03). Total leucocyte and platelets count, as well as age, sex and IPSET thrombosis score did not correlate with thrombotic events. Pts with ANC > 9 x10^9/L or ALP count < 1,5x10^9/L at diagnosis showed a trend towards a greater incidence of thrombosis in FU (p=0.06 and p=0.07, respectively). Pts with NLR value > 6 at diagnosis had a significantly higher incidence of venous thrombotic events (p=0.03) and a shorter venous TFS (p=0.004, Figure 1) compared to patients with NLR <6. The NLR value was not predictive of arterial thrombotic risk. After a median FU of 6.14 years (range 0,5-27,96) years, 32 pts (18,2%) died; 22 pts (12,5%) had disease progression: of them, 13 (7,4%) experienced overt MF and 9 (5,1%) evolved into an AP or BP. Pts with NLR value > 6 at diagnosis had a significant shorter OS compared to the group with NLR <6 (median OS 4,93 vs 6,22 months respectively, p=0.02). Conclusions This multicenter study investigated for the first time whether the NLR value at diagnosis could be a predictive marker of thrombotic risk and poor outcome in pre-PMF setting. Previous thrombosis and JAK2V617F mutation are confirmed to be risk factors for thrombotic events also in pre-MF setting. Notably, NLR > 6 at diagnosis emerged as a simple marker to identify pts at higher risk of thrombosis and poor outcome in the pre-PMF setting: pts with a NLR value > 6 have a significantly higher venous thrombotic risk and a shorter venous TFS. Furthermore, NLR group > 6 appears to have a shorter OS. These data are promising but require to be confirmed on a larger scale. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Use of JAK 2 v617f As a Hypercoagulable Test in a Community Hospital

Introduction: We have anecdotally noticed that hypercoagulable workups are often performed unnecessarily within our community hospital in Orlando Florida. Some providers have a tendency to include JAK2 v617f, a test associated with high cost and one that can take weeks to have results return, as part of their panels. We hypothesize that this test is over utilized and will rarely be helpful in the workup of thrombosis without other reasons to suspect myeloproliferative disorders. We opted to look back at ordering patterns of JAK2 v617f and chart review the reasons it was ordered. Methods: Using a chart review, we pulled hundreds of charts in which a JAK2 v617f was ordered. We then scrolled through the charts to determine if thrombosis was an ordering reason. If so, we documented a positive or negative result and if the thrombotic event could be explained by other factors. Results: 120 charts were reviewed. Of the 120, 10 (8%) had JAK 2 v617f as part of a hypercoagulable panel. The remainder of testing was relegated to patients with erythrocytosis, thrombocytosis, or leukocytosis. When the JAK 2 test was used for hypercoagulable workup, it was negative in every case. The thrombosis included:Splanchnic vein in two casesSplenic infarct in one caseSingle episode of deep vein thrombosis or pulmonary embolism in three casesRecurrent deep vein thrombosis or pulmonary embolism in three casesCerebral vascular accident in one case Risk factors for thrombotic events were documented in seven cases. Conclusion While the majority of JAK2 v617f testing was done for reasons beyond thrombotic workup, when used of part of a thrombophilia workup, the testing was not useful. While there may be a limited role for testing in clots at unusual sites or unexplainable thrombotic events at a young age, most of the testing done at our institution did not fit this pattern. Routine testing should be looked at and discouraged in inappropriate situations. The cost of the test and the concerns about delaying hospital discharge or raising patient anxiety while awaiting results do not justify the limited utility of this test.

Severe adverse events related to vitamin K antagonists in children with congenital or acquired heart disease

Although increasingly used, vitamin K antagonists (VKA) remain difficult to manage for children with congenital or acquired heart disease (CAHD). To assess the occurrence of thrombosis and major bleeding events in children with CAHD treated with VKA and to determine associated risk factors. All children enrolled in the VKA dedicated educational program between 2008 and 2020 were prospectively included. Clinically suspected thrombotic events were confirmed by imaging, while major bleedings were defined according to the ISTH. Time in therapeutic range (TTR) was calculated to evaluate the stability of anticoagulant therapy. Statistical analysis included Cox proportional hazard models. We included 390 patients, median age at initiation was 6.6 (IQR: 12.8–3.2) years. Median follow-up was 17.7 months. The median TTR was 85.2% (IQR: 95.3%–74.4%). Thirteen thrombosis in 9 (2.3%) children and 24 major bleedings in 17 (4.4%) children were reported. At 6 years, 86.6% (CI95% [75.6%–92.4%]) and 95% (CI95% [89%–97.8%]) of patients were free of major bleeding and thrombotic events, respectively. In univariate analysis mitral valve replacement (MVR) was associated to major bleeding events (HR 3.32 [1.16–9.44], P = 0.025). In multivariable analysis, recurrent minor bleeding events (≥ 3) (HR 4.9 [1.7–13.8], P = 0.002) and global TTR under 70% (HR: 3.6 [1.1–10.9], P = 0.04) were risk factors associated to major bleeding events whereas MVR did not reach the level of significant association (HR: 1.92 [0.6; 5.9], P = 0.25). In multivariable analysis, Kawasaki disease (HR: 11.84 [2.7–52.6], P = 0.001) and global TTR under 80% (HR: 5.05 [1.2–20.7], P = 0.025) were main risk factors for thrombotic events. Overall, VKA use appears to be safe and effective in children with CAHD. Patients with Kawasaki disease and those with a TTR under 80% are at highest risk of thrombosis. A TTR under 70% and minor recurrent bleeding events are the main risk factors for major bleeding events.

The Predictive Value of Neutrophil-Lymphocyte Ratio in Patients with Polycythemia Vera at the Time of Initial Diagnosis for Thrombotic Events.

Objective To investigate and discuss the predictive value of the neutrophil-to-lymphocyte ratio (NLR) in patients with polycythemia vera (PV) at the time of initial diagnosis, as well as its clinical significance in predicting the occurrence of thrombotic events and the progression of future thrombotic events during follow-ups, with the goal of providing a reference for the early identification of high-risk PV patients and the early intervention necessary to improve the prognosis of PV patients. Method A total of 170 patients diagnosed with PV for the first time were enrolled in this study. The risk factors affecting the occurrence and development of thrombotic events in these patients were statistically analyzed. Results NLR (P = 0.030), WBC count (P = 0.045), and history of previous thrombosis (P < 0.001) were independent risk factors for thrombotic events at the time of initial diagnosis. Age ≥ 60 years (P = 0.004), NLR (P = 0.025), history of previous thrombosis (P < 0.001), and fibrinogen (P = 0.042) were independent risk factors for the progression of future thrombotic events during follow-ups. The receiver operating characteristic curve (ROC curves) showed that NLR was more effective in predicting the progression of future thrombotic events than age ≥ 60 years, history of previous thrombosis, and fibrinogen. Kaplan-Meier survival analysis showed progression-free survival time of thrombotic events in the high NLR value group (NLR ≥ 4.713) (median survival time 22.033 months, 95% CI: 4.226-35.840), which was significantly lower compared to the low NLR value group (NLR < 4.713) (median overall survival time 66.000 months, 95% CI: 50.670-81.330); the observed difference was statistically significant (P < 0.001). The 60-month progression-free survival in the low NLR value group was 58.8%, while it was 32.8% in the high NLR value group. Conclusion Peripheral blood NLR levels in patients with PV resulted as an independent risk factor for the occurrence of thrombotic events at the time of initial diagnosis and for the progression of future thrombotic events during follow-ups. Peripheral blood NLR levels at the time of initial diagnosis and treatment had better diagnostic and predictive value for the progression of future thrombotic events in patients with PV than age ≥ 60 years, history of previous thrombosis, and fibrinogen.

Full Characterization of Thrombotic Events in All Hospitalized COVID-19 Patients in a Spanish Tertiary Hospital during the First 18 Months of the Pandemic.

The presence of a procoagulant state, COVID-19-related coagulopathy, and an increased rate of thrombotic events (TEs) is widely known about. However, descriptive studies are scarce. Here, we conducted a large retrospective study including 2894 hospitalized COVID-19 patients followed up during the first 18 months of the pandemic to completely characterize any TE. Major TEs showed a 3.45% incidence rate. TEs were associated with increased intubation/90-day mortality risk [OR = 1.71, 95% CI (1.12–2.61), p < 0.013]. Venous thrombotic events (VTEs) were more frequent than arterial thrombotic events (ATEs) (72% vs. 28%), associated with enhanced levels of D-dimer (cross-linked fibrin derivatives formed during thrombolysis), which were related to mortality but more useful for early detection of thrombosis. In this regard, D-dimer plasma levels above 2014 µg/mL at hospital admission identify TEs with 91% accuracy (AUC = 0.91, p < 0.001), rising to almost 95% (AUC = 0.94, p < 0.001) with a cut-off value of 2666 µg/mL in VTEs. Moreover, 41% of TEs occurred in patients receiving LMWH thromboprophylactic treatments in hospital or domiciliary therapies. SARS-CoV-2 infection along with a sedentary lifestyle derived from the confinement in 2020 could be more determinant than a procoagulant state in patients with risk factors for TEs. Furthermore, the normal results obtained from the thrombophilia study after the acute process are linked to this independent procoagulant state and to SARS-CoV-2-derived coagulopathy.

Report of Low Incidence of Thrombosis with Early Prophylaxis in Hospitalized Patients with COVID-19 from Two Saudi Tertiary Centers.

BackgroundThrombotic events can increase the COVID-19 associated disease mortality. The administration of prophylactic anticoagulants had been shown to decrease the incidence of thrombosis, mortality, and ICU admission rates in COVID-19 patients.AimsThe present study investigates the rate of thrombosis with early anticoagulation prophylaxis, the various risk factors for thrombotic events, and the overall survival rate in hospitalized COVID-19 cases.MethodsIn this prospective observational study, 425 patients aged ≥14 years were included in the study who were hospitalized with COVID-19 related symptoms from March to October 2020 at two tertiary care hospitals in the Kingdom of Saudi Arabia. Venous thromboembolism (VTE) score was evaluated, and VTE prophylaxis was administered according to the hospital guidelines. Patients’ demographics, comorbidities, disease presentation, and sequential hematological profiles were also recorded. Samples were collected at different time points to determine the hematological profiles.ResultsOut of 425 with positive COVID-19 subjects, eight (1.9%) patients developed thrombosis during admission, with pulmonary embolism being the most common type. VTE prophylaxis was administered to 394 (92.7%) patients. These anticoagulants included enoxaparin (86.3%), heparin (12.7%), warfarin (0.8%) and apixaban (0.3%). Comorbid conditions were recorded in 253 (59.5%) patients. ICU admission rate was 28% (n = 119), with a median time to transfer to ICU of 1 day (r: 0-33 days). A trend of high VTE score (5.0) with ICU admission and mortality (P = <.001) was observed. The observed mortality rate for our cohort was 5.9% (25 events out of 425); however, for patients admitted in ICU, it was 16% (19 events out of 119 admissions).ConclusionWe are reporting a low incidence of thrombosis in COVID-19 patients. We have demonstrated that the early administration of prophylactic anticoagulants might reduce the risk of thrombotic events and the associated mortality. We observed a higher VTE score and thrombosis in patients admitted to the ICU.

A rare complication in a child undergoing chemotherapy for Hodgkin lymphoma - multiple cerebral venous sinus thrombosis

Introduction. Risk factors for thrombotic events in patients receiving treatment for Hodgkin lymphoma are not well known. Administration of some cytostatic medication, especially via central venous catheter, corticosteroids, and hyperlipidemia can present some of them. Case outline. A case of a 15-year-old boy that had been newly diagnosed with Hodgkin lymphoma is presented here. Chemotherapy according to vincristine, etoposide, prednisone, and doxorubicin (OEPA) protocol was introduced a month before headache and vomiting occurred, so subsequently, brain computer tomography was performed, and reviled laminar subdural pseudo-hemorrhage in the right occipital region. After performing magnetic resonance imaging (MRI) venous thrombosis of the posterior part of superior sagittal sinus, right transverses, and sigmoid sinus were presented. Low-molecular-weight heparin (LMWH) and anti-edematous therapy was immediately initiated. Two weeks later, the patient resumed the second cycle of chemotherapy combined with LMWH, as the previous symptoms of intracranial hypertension resolved. Two years later, MRI showed an almost complete resolution of the finding. The boy was in good clinical condition. Conclusion. Although administration of oral corticosteroids, could be rarely a risk factor per se for cerebral sinus venous thrombosis in Hodgkin lymphoma patients, it remains an important treatment option. Adequate and prompt diagnostics and therapy are mandatory in cases of wide intracranial venous thrombosis as the prevention of possible intracranial hypertension and even fatal outcome.

Clinical features and outcomes of JAK2 V617F-positive polycythemia vera and essential thrombocythemia according to the JAK2 V617F allele burden.

BackgroundJAK2 mutation status is a well-known risk factor for thrombosis in patients with myeloproliferative neoplasms. However, the clinical usefulness of JAK2 V617F allele burden is under investigation.MethodsWe retrospectively evaluated the impact of the JAK2 V617F allele burden on clinical characteristics and outcomes of JAK2 V617F-positive polycythemia vera (PV) and essential thrombocythemia (ET). The JAK2 V617F allele burden was measured using sequencing.ResultsAltogether, 127 patients with JAK2 V617F mutation (PV, N=61; ET, N=66) were included in this study. JAK2 V617F allele burdens were positively correlated with white blood cell counts, hemoglobin values, lactate dehydrogenase levels, and platelet counts. The median values of JAK2 V617F allele burden in patients with PV and ET were 58% and 30%, respectively. A JAK2 V617F allele burden of ≥30%, older age, and a higher hemoglobin level were risk factors for thrombotic events in ET. In patients with PV, older age was the only thrombotic risk factor. The 8-year probabilities of overall survival (OS) were 82.9% in all patients. A high JAK2 V617F allele burden (≥58%) was associated with poor OS in patients with PV. For the patients with ET, the difference in 8-year OS based on the JAK2 V617F allele burden was not significant.ConclusionThe JAK2 V617F allele burden was correlated with hematologic parameters and clinical outcomes. Assessing the JAK2 V617F allele burden can be helpful in predicting the thrombotic risk and disease course in patients with JAK2 V617F-positive PV and ET.

Risk factors for thrombotic events in Korean patients with systemic lupus erythematosus

Thrombotic events (TE), including deep vein thrombosis, stroke, and myocardial infarction, occur in 30–40% of patients with systemic lupus erythematosus (SLE) resulting in substantial morbidity and mortality. We explored the risk factors for TE in SLE patients. We analyzed data obtained during a prospective cohort based on the KORean lupus NETwork (KORNET) registry, and enrolled 259 SLE patients with clinical data available at the onset of SLE. TE was defined as the presence of arterial or venous thrombosis. Multivariate Cox-proportional hazards analysis was performed to investigate risk factors for TE. During a mean follow-up of 103.3 months (SD 53.4), 27 patients (10.4%) had a TE. In multivariate analysis, hypertension (hazard ratio [HR] 7.805, 95% confidence interval [CI]: 1.929–31.581; P = 0.004), anti-phospholipid syndrome (APS) (HR 12.600, 95% CI: 4.305–36.292; P < 0.001), mean daily prednisolone > 5 mg/day (HR 3.666, 95% CI: 1.318–10.197; P = 0.013), and SLICC/ACR Damage Index (SDI) score (HR 1.992, 95% CI: 1.465–2.709; P < 0.001) were significantly associated with the development of TE in SLE patients. Instead, use of an ACEi or ARB (HR 0.159, 95% CI: 0.043–0.594; P = 0.006) was a protective factor against TE development in these patients. In conclusion, hypertension, higher mean daily dose of prednisolone, diagnosis of APS, and higher SDI were risk factors for TE in patients with SLE. On the other hand, the use of an ACEi or ARB was associated with a reduced risk of TE.

Prophylaxis and management of venous thromboembolism during pregnancy and postpartum period

Introduction. Venous thromboembolism (VTE) is one of the lead causes for maternal mortality and morbidity during pregnancy in the majority of developed countries. The incidence rate of VTE per pregnancy-year increases during pregnancy and postpartum period about by 4-fold and at least 14-fold, respectively.Aim: to analyze and summarize current view on risk factors of thrombotic events during gestation and to discuss recent guidelines for the management of venous thromboembolic complications during pregnancy and postpartum, by taking into account a balance between risks and benefits of using anticoagulants.Materials and Methods. The literature search covering the last 10 years was carried out in the electronic scientific databases RSCI, PubMed/MEDLINE, and Embase. While formulating a search strategy for evidence-based information, the PICO method (P = Patient; I = Intervention; C = Comparison; O = Outcome) and the key terms “venous thromboembolism” and “pregnancy” were used.Results. Risk factors were found to include a personal history of VTE, verified inherited or acquired thrombophilia, a family history of VTE and general medical conditions, such as immobilization, overweight, varicose veins, some hematological diseases and autoimmune disorders. VTE is considered being potentially preventable upon prophylactic administration of anticoagulants, but no high confidence randomized clinical trials comparing diverse strategies of thromboprophylaxis in pregnant women have been proposed so far. Because heparins do not cross the placenta, weight-adjusted therapeutic-dose low molecular weight heparins (LMWH) represent the anticoagulant treatment of choice for VTE during pregnancy. Once- and twice-daily dosing regimens are acceptable. However, no evidence suggesting benefits for measurement of factor Xa activities and consecutive LMWH dose adjustments to improve clinical outcomes are available. In case of uncomplicated pregnancy-related VTE, no routine administration of vitamin K antagonists, direct thrombin or factor Xa inhibitors, fondaparinux, or danaparoid is recommended. Lactating women may switch from applying LMWH to warfarin. Anticoagulation therapy should be continued for 6 weeks postpartum with total duration lasting at least for 3 months.Conclusion. VTE is a challenging task in pregnant women expecting to apply a multi-faceted approach for its efficient solution by taking into account updated recommendations and personalized patient-oriented features.

The relationship between elevated antiphospholipid antibodies and thrombosis in hospitalized patients

Objective: Assess the relationship between elevated antiphospholipid antibodies and thrombosis in hospitalized patients. Methods: Case control study. A total of 385 patients (149 males and 236 females, aged from 1 to 105 years, with a median age of 37 years) who were hospitalized in Peking University First Hospital from January 2015 to December 2019 and tested positive for any one of the anti-phospholipid antibodies were included in the study. All subjects were divided into thrombotic group and non-thrombotic group according to whether thrombus was detected by imaging examination during hospitalization. In thrombosis group, there were 66 males and 36 females, aged from 3 to 105 years, with a median age of 58 years. In non-thrombosis group, there were 83 males and 200 females, aged from 1 to 94 years, with a median age of 31 years. Clinical data and laboratory data of patients were recorded. ACL-IgM/IgG and anti-β2GPI-IgM/IgG were detected by ELISA and LA was detected by dRVVT and SCT on automatic coagulation analyzer. The rates of age, gender, smoking, obesity, hypertension, hyperlipidemia, diabetes and the median level of antiphospholipid antibodies were compared between two groups. Logistic multivariate regression analysis was used to determine the risk factors for thrombotic events. The mid-to-high titer value of aCL was established by the χ2-trend test and verified by logistic regression. Results: The median age (58 years) and the rates of male (64.7%), smoking (16.7%), hypertension (63.7%) and diabetes (28.4%) in thrombus group were significantly higher than those in non-thrombus group (Z=7.685, χ²=38.077, 16.312, 37.769, 24.749 respectively; P<0.01). The positive rate of anti-β2GPI-IgG and dRVVT in thrombosis group (11.8% and 78.4%) was significantly higher than that in non-thrombosis group (5.3% and 60.1%), as well as the median level of dRVVT (1.29 RU/ml vs 1.23 RU/ml) (χ²=3.864 and 10.309, Z=3.539; P<0.05). The median level of aCL-IgM was higher in non-thrombosis group (2.3 MPL vs 2.0 MPL). The positive rate of aCL-IgG was slightly higher in thrombosis group (18.6% vs 10.6%). Logistic regression analysis showed that men, hypertension, diabetes, advanced age, elevated dRVVT, and elevated anti-β2GPI-IgG are risk factors for thrombosis. Taking 36 GPL as the medium-to-high titer value of aCL-IgG, the risk of thrombosis increased by 2.45 times. Conclusions: In the anti-phospholipid antibody profile, LA detected by dRVVT method, anti-β2GPI-IgG and aCL-IgG may be valuable laboratory indicators for inpatient thrombotic events. The mid-to-high titer value of aCL-IgG is set at 36 GPL to distinguish the risk of thrombosis.

Epidemiologic study of patients with thrombotic events referred to a tertiary hospital in Southern Iran

Background and aimThromboembolic events mainly occur in older age is related with high morbidity and mortality, and considerable health-care costs particularly in developing countries. Both arterial and venous thromboembolism has known risk factors such as hyperlipidemia, obesity, diabetes, cancer, major surgery, central catheter. We aimed to evaluate the occurrence of thrombotic events and related risk factors in a group of Iranian patients. MethodsIn this cross-sectional study, all patients (n = 99) who were complicated by thrombotic events referred to the Hematology Research Center of Shiraz University of Medical Sciences were investigated from 2015 to 2017, in Shiraz, Southern Iran. Data were collected from their medical records by a designed data gathering form. ResultsThe median age of the occurrence of thrombosis was 51 (IQR: 31) years. From all thrombotic events 52.5% occurred in females. Venous thrombosis was more prevalent than arterial (61.6% vs. 38.4%). Hypertension, diabetes mellitus and ischemic heart disease were the most associated disease with thrombosis. Most of the patients (79.8%) had no episodes of relapse and the occurrence of relapse had no significant relationship with thrombophilia and underlying disease. Acceptable response rate for warfarin therapy was achieved in 46.5% with 5 mg and 43.4% with 5–7.5 mg. ConclusionKnowing the frequency and risk factors for thrombotic events lead to timely diagnosis and management of thrombosis. Atrial fibrillation and valvular rheumatic heart disease are the most common risk factors of thrombosis in our study showing prophylaxis is necessary in high-risk patients.

Thrombotic Risk Factors, Antithrombotic Therapy, and Outcomes of Asymptomatic Carriers of Antiphospholipid Antibodies and Patients with Antiphospholipid Syndrome

Background: There is marked heterogeneity in the clinical presentation of patients with antiphospholipid antibodies (aPL) and antiphospholipid syndrome (APS) and a variable thrombotic risk. Putative thrombotic risk factors include male gender, high titer aPL serology with IgG isotype, triple positivity and concomitant autoimmune disease. However, the evidence is conflicting for some, and the patient heterogeneity makes risk stratification challenging. Thus, long-term antithrombotic management decisions remain primarily driven by clinical judgment. Decisions such as discontinuation of therapy, use of direct oral anticoagulants (DOAC), and the role of hydroxychloroquine (HCQ) and immunosuppressive therapy remain areas of ongoing research.Objectives: To outline clinical risk factors of thrombotic events in antiphospholipid patients and describe outcomes of different antithrombotic strategies in this heterogeneous cohort.Methods: We retrospectively identified all adult patients followed at Weill Cornell Hematology with aPL or APS. Patients were included if they met laboratory criteria for APS. Data on patient demographics, concomitant thrombophilia, autoimmune disease, and family history of thrombosis, aPL isotype and titer, thrombotic events prior to and during follow-up, and antithrombotic therapies were collected. Time to event analysis was used to identify clinical risk factors for thrombosis. The time varying effects of antithrombotic therapies were also evaluated.Results: A total of 122 patients were identified with a median age of 43 (range 19-86 yrs.). Ninety-three (76%) were female and 29 (24%) were male. Eighty-four patients (69%) were diagnosed with APS prior to their initial visit and the remaining 38 (31%) were aPL positive. Of the 84 APS patients, 63 (74%) had a history of a single thrombotic event and 22 (20%) had recurring events. Those were venous thromboembolic events (VTE) in 45 patients (53%), Arterial (AT) in 19 (22%), pregnancy morbidity (PM) in 12 (14%), and combinations of VTE, AT, and PM in the remaining 9 patients (11%). Of the 38 aPL positive carriers, 25 (66%) were asymptomatic, tested mainly for prolonged aPTT (68%), and 13 (44%) had non-criteria events that prompted testing. Autoimmune disease was present in 37 (30%), of which 16 (43%) were SLE. Hereditary thrombophilia was identified in 7 (6%) and a family history of thrombosis, aPL positivity, or APS was noted in 15 (12%).During a median follow-up duration of 47 months, 19 patients had an event (16%). A significantly higher rate of thrombosis was observed in patients with autoimmune disease (HR 4.64, p<0.01), and in Blacks vs. Whites (HR 8.37 p<0.01). Triple positivity, found in 45 patients (37%), was not associated with an increased thrombotic risk. The risk of thrombosis was significantly lowest among patients on therapeutic dose anticoagulant therapy (ac) with low-molecular weight heparin (LMWH) or vitamin K antagonist (VKA) (Figure 1). In comparison, patients on antiplatelet therapy (apt) alone had 5.4 times the risk (HR 5.432, p=0.01). DOACs were used in 9 (10%) of the APS patients, with a median follow-up of 19 months (2-37) and a single event occurring in a young male without the aforementioned risk factors. Thirteen patients (11%) were on HCQ, 8 (7%) with autoimmune disease and 5 (4%) without, for a median duration of 20 months, with a single event occurring in a patient on HCQ alone.Conclusions: In this study, concomitant autoimmune disease and Black race were risk factors for thrombotic events in antiphospholipid patients. Anticoagulation with LMWH or VKA remains the most effective therapy. Deciding on who can safely discontinue anticoagulation and who may benefit from additional antithrombotic and immunosuppressive therapies remains a matter of clinical judgment until multicenter, prospective studies are carried out. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Risk factors of thrombosis in Chinese subjects with acute promyelocytic leukemia

BackgroundAcute promyelocytic leukemia (APL) is a special type of acute myeloid leukemia Thrombosis is at increased risk complication in patients with this disease. However, the risk factors of thrombosis related to Chinese APL patients are not fully understood.MethodsIn this study, clinical and laboratory data of 44 consecutively Chinese APL patients were collected and analyzed.ResultsOne arterial and 6 venous thrombosis occurred in 44 patients, including 22 males and 22 females, with a median age of 44 years (range from 18 to 74 years). The ratio of male and female gender, age, white blood cell count, hemoglobin, platelets, disease risk stratification, CD2, Khorana score, differentiation syndrome (DS) and gene mutation related to prognosis of APL, including DNMT3A, TET2, IDH1, IDH2, NRAS and ASXL1 in the two groups with and without thrombosis were not statistically significant. The detection rate of PAI-1 genotype 4G4G was 71.4% (5/7) in 7 patients with thrombosis, while the detection rate of PAI-1 genotype 4G4G in 37 patients without thrombosis was 8.1% (3/37). The differences between the two groups in WT-1 (P = 0.01), PAI-1 4G4G (P = 0.0009), bcr3 (P = 0.027), CD15 (P = 0.005), and FLT3-ITD mutation (P = 0.0008) were statistically significant. Using multivariate analysis, the risk factors of venous thrombosis in APL were CD15 (P = 0.043), PAI-1 4G4G (P = 0.009), WT-1 (P = 0.043) and FLT3/ITD (P = 0.013), respectively.ConclusionOur results suggested the PAI-1 gene 4G4G type, CD15, WT-1 and FLT3-ITD mutations excluding DNMT3A, TET2, IDH1/2, NRAS and ASXL1 are risk factors of thrombotic events in Chinese APL patients.

Prevalence and risk factors of thrombotic events on patients with COVID-19: a systematic review and meta\u2010analysis

BackgroundCoagulation abnormalities in COVID-19 patients accompanied with poor prognosis. This study aimed to determine the prevalence and risk factors of thrombotic events on COVID-19 patients.Methods.We systematically reviewed all the studies about thrombotic events on COVID-19 patients in PubMed, Embase, Web of Science, MedRxiv, bioRxiv, from Dec 1, 2019 to July 5, 2020. The weighted mean difference (MD) or odds ratio (OR) or relative risk (RR) with 95 % confidence intervals (CI) for clinical data in COVID-19 patients with or without thrombotic events was calculated.Results12 articles contained 1083 patients were included for meta-analysis. The prevalence of thrombosis was 22 % (95 % CI 0.08–0.40) in COVID-19 patients and increased to 43 % (95 % CI 0.29–0.65) after admission to the intensive care unit (ICU). Compared with non-thrombotic patients, thrombotic patients had higher levels of D-dimer (MD = 2.79 μg/ml, 95 % CI 2.27–3.31 μg/ml), lactate dehydrogenase (LDH) (MD = 112.71 U/L, 95 % CI 62.40–163.02 U/L), and white blood cells (WBC) (MD = 1.14 *109/L, 95 % CI 0.47–1.81*109/L) while decreased lymphocytes (MD= -0.20*109/L, 95 % CI -0.38 – -0.02*109/L). Age, platelet counts, and male sex tended to be risks while diabetes tended to be a protection for thrombosis for COVID-19 patients, although no statistical difference was achieved. Finally, patients with thrombosis were at a higher risk of death (OR = 2.39, 95 % CI 1.36–4.20).ConclusionsPrevalence of thrombosis in COVID-19 patients was high, especially in ICU, though pharmacologic thromboembolism prophylaxis was applied. Therefore, higher levels of D-dimer, LDH, WBC, and decreased lymphocytes needed to be paid close attention to in patients with COVID-19.

MIS-C is a risk factor for thrombotic events.

MIS-C is a risk factor for thrombotic events.

The evaluation of patients with essential thrombocythemia in terms of risk of thrombosis.

The aim of this study was to compare the incidence of factors associated with an increased risk of thrombosis in patients with essential thrombocythemia. A total of 200 patients followed-up in our unit with a diagnosis of essential thrombocythemia in 13 years were analyzed retrospectively. Of the study participants, 60.5% were females and 39.5% were males, with an overall mean (±SD) age of 54.93 (±14.21) years. In 119 patients, Janus Kinase 2 was positive with 56.3% of cases. When two patient categories were defined as those with or without history of thrombosis, no significant differences were found in terms of Janus Kinase 2 positivity, mean age, as well as white blood cells and platelet counts (p>0.05). Also, no significant differences in thrombotic event incidence were found between patient categories defined on the basis of cut-off values for white blood cells (cut-off values of 15×103/mm3 and 8.7×103/mm3) and platelets (cut-off values of 1500×103/mm3) (p>0.05). Although our results are generally in line with the published data, some divergence from previous results has been observed with respect to risk factors for thrombotic events. Absence of a correlation between leukocytosis and thrombosis may be related with the significant decline in white blood cells after treatment. Also, a significant reduction in platelet counts occurring in association with treatment is linked with a lowered incidence of thrombosis. Janus Kinase 2-positive patients had a similar thrombosis frequency with that reported in the literature.

Risk Factors for Thrombotic Events in Patients with PNH: A Nested Case-Control Study in the International PNH Registry

Risk Factors for Thrombotic Events in Patients with PNH: A Nested Case-Control Study in the International PNH Registry

Validation of the adjusted global antiphospholipid syndrome score in systemic lupus erythematosus patients in Argentina.

Assessment of risk both for pregnancy morbidity and thrombosis in the presence of anti-phospholipid antibodies (aPL) is still a challenge in Systemic Lupus Erythematosus (SLE) patients. The Global Antiphospholipid Syndrome Score (GAPSS) takes into account the aPL profile (criteria and non-criteria aPL), the conventional cardiovascular risk factors and the autoimmune antibody profile. An adjusted model of the score (aGAPSS) excluding anti-phosphatidylserine/Prothrombin (aPS/PT), suggests that the score is able to stratify patients for their rate of events making it widely applicable in daily clinical practice. To validate the aGAPSS in a multicentric cohort of SLE patients in Argentina. consecutive SLE patients with and with andwithout thrombotic events from seven Rheumatologist centers were included. Traditional cardiovascular risk factors, aPL antibodies and medications received (aspirin, hydroxychloroquine and anticoagulation) were collected. The score aGAPSS was calculated for each patient at the last visit by adding together the points corresponding to the risk factors: 1 for hypertension, 3 for dyslipidemia, 4 for LA and B2GPI (IgM or IgG) antibodies and 5 for aCL (IgM or IgG) antibodies. The discriminative ability of the aGAPSS was calculated by measuring the area under the receiver operating characteristic curve (AUC). Multivariate logistic regression analysis was performed to examine the impact of multiple cardiovascular risk factors and laboratory parameters on the occurrence of thrombosis. Two hundred and ninety-six SLE patients were included. One-hundred and twenty-one patients (40.9%) presented thrombotic and/or pregnancy complications. Median aGAPSS was significantly higher in patients who experienced an event (thrombosis and/or pregnancy morbidity) compared with those without [4 (IQR 1-9) versus 1 (IQR 0-5); p < 0.001]. The best cut off point for the diagnosis of thrombosis and/or pregnancy complications was aGAPSS ≥4. Multivariate logistic regression analysis showed that aCL antibodies [OR 2.1 (95% CI 1.16-3.90); p = 0.015] were an independent risk factors for thrombotic events. This score is a simple tool, easy to apply to SLE patients in daily practice. The use of the aGAPSS could change the non-pharmacologic and pharmacologic treatment in higher risk patients to improve their survival.