Risk Factors For Thromboembolic Events Research Articles

The triglyceride-glucose index is a marker of thromboembolic events in atrial fibrillation patient under oral anticoagulation therapy

Abstract Background Atrial fibrillation (AF) increases the risk of stroke and thromboembolism; and appropriate risk stratification is central for better targeted patient management. The triglyceride-glucose (TyG) index indirectly assesses insulin resistance, and has been associated with cardiovascular risk. Purpose To investigate whether the TyG index could be a biomarker for assessing the risk of thromboembolic events in patients with AF. Methods We performed an observational prospective cohort study including outpatients diagnosed with AF starting vitamin K antagonist (VKA) or direct-acting oral anticoagulants (DOAC) therapy from January, 2016 to November, 2021. The primary endpoint was a combination of thromboembolic events, considered as the composite of myocardial infarction, and/or venous thromboembolism, and/or ischemic stroke/transient ischemic attack, over 2 years of follow-up. The TyG index was calculated as the natural logarithm (Ln) of the product of baseline plasma glucose and triglyceride using the following formula: Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)]/2. Patients were stratified into tertiles according to their TyG index (ie. first tertile: TyG index <4.59; second tertile: TyG index 4.59-4.83; third tertile: TyG index >4.83). Results We included 2907 patients (median age 77 [70-83] years; 52.5% female). The median TyG index was 4.71 (4.53-4.91), and 34% (989) where in the third tertile of TyG index. During a follow-up of 2 years, 209 (7.2%) patients suffered a thromboembolic event. Compared to patients in the first or second tertiles of TyG index, patients in the third tertile had an increased annual event rate of thromboembolic events (3.40 per 100 patient-years vs. 4.76 per 100 patient-years, p=0.043; and 3.41 per 100 patient-years vs. 4.76 per 100 patient-years, p=0.044), and higher incidence rate ratio (1.41 [95% CI 1.01-1.98], p=0.044 vs. first tertile; 1.40 [95% CI 1.01-1.97], p=0.044 vs. second tertile). Cox regression analyses adjusted for several risk factors demonstrated that the TyG index was an independent predictor for thromboembolic events (aHR 1.82; 95% CI 1.15-2.89; p=0.011). Patients in the third tertile of TyG index presented a 64% higher risk of thromboembolic events (aHR 1.64; 95% CI 1.17-2.29; p=0.004) (Table), with significantly lower event free survival (log-rank test p-value = 0.016) (Figure). Conclusions In this real-world cohort of AF patients under oral anticoagulation therapy, elevated TyG index was an independent risk factor for thromboembolic events. The TyG index is a simple, low-cost indicator, that could be used as a screening tool in everyday clinical practice.

Risk factors of thromboembolic events in patients with scrub typhus.

Thromboembolic events are a well-recognized cause of in-hospital deaths of patients with infectious diseases. However, thromboembolic events in patients with scrub typhus, caused by Orientia tsutsugamushi have rarely been reported. This study aimed to assess risk factors associated with thromboembolic events in patients with scrub typhus. All 93 scrub typhus patients' diagnoses were confirmed serologically or by positive nested polymerase chain reaction (PCR). The clinical and laboratory findings from 12 scrub typhus patients with thromboembolic events and 81 scrub typhus patients with nonthromboembolic events were retrospectively studied. To determine the factors implicated in thromboembolic events, we performed multivariate logistic regression analysis using the six independent factors identified by the univariate analysis. The mean age of the patients in the thromboembolic group was 76.4 years (median, 76 years), and in nonthromboembolic group it was 64.6 years (median, 65 years) (P<0·001). Thromboembolic events were observed in 12 patients. These events included acute coronary syndrome (n = 5), acute limb ischemia (n = 4), ischemic stroke (n = 1), deep vein thrombosis combined with pulmonary thromboembolism (n = 1), and left common iliac artery aneurysm with a thrombus (n = 1). According to multivariate analysis, the following four factors were significantly associated with the thromboembolic events: 1) treatment with rifampin (OR = 57.6; CI 1.2-2700.3), 2) Taguchi genotype (OR = 41.5, P = 0.028; CI 1.5-1154.6), 3) atrial fibrillation (OR = 9.4, P = 0.034; CI 1.2-74.0), and 4) age (OR = 1.1, P = 0.046; CI 1.0-1.3). Our study suggests that clinicians should be cautious when managing patients with scrub typhus to avoid the development of thromboembolic events, especially in patients with risk factors such as treatment with rifampin, Taguchi genotype, atrial fibrillation, and advanced age.

Impact of Paroxysmal Atrial Tachycardia on Thromboembolic Events and Major Adverse Cardiovascular Events: A Single-Center Retrospective Study.

Atrial fibrillation (AF) is known to increase the risk of thromboembolic events and major adverse cardiovascular events (MACE). The impact of paroxysmal atrial tachycardia (PAT) on these risks remains unclear. This retrospective cohort study was conducted involving 889 patients diagnosed with PAT and 1106 control patients without PAT, all of whom underwent their initial 24-hour ECG monitoring between 2015 to 2020. Kaplan-Meier survival analysis and Cox regression analysiswere used to evaluate the association between PAT and the study endpoints, including thromboembolic events and MACE. Over a mean follow-up period of 50.3 months, the incidence of thromboembolic events and MACE was significantly higher in the PAT group compared to the control group (6.5% vs 1.7% and 19.1% vs 9.9%, respectively). After adjusting for common risk factors and baseline imbalances, the PAT group exhibited a significantly elevated risk of thromboembolic events (hazard ratio [HR] 3.782, 95% confidence interval [CI] 2.212-6.467; P <0.001) and MACE (HR 1.795, 95% CI 1.398-2.305; P <0.001). However, the frequency of PAT episodes, heart rate, and maximum heart rate were not significantly associated with theseoutcomes. Within the PAT group, a history of stroke, transient ischemic attack, and chronic renal failure were identified as independent risk factors for thromboembolic events, while hypertension, coronaryheart disease, heart failure, and chronic renal failure were independently associated with MACE. PAT, as detected by 24-hour dynamic ECG, is associated with an increased risk of thromboembolic events and MACE.

Abstract A099: Pulmonary thromboembolism secondary to iron deficiency anemia: A case study

Abstract Introduction: Pulmonary thromboembolism (PTE) is a significant clinical issue associated with high morbidity and mortality. Risk factors for thromboembolic events include immobilization, myocardial infarction, cerebrovascular accident, surgery, and trauma. Iron deficiency anemia (IDA) can cause reactive thrombocytosis, increasing thromboembolic risk. This study presents a 30-year-old female admitted for PTE, possibly secondary to IDA. Case Presentation: A 30-year-old female with IDA and heavy menstrual bleeding presented with right-sided chest pain and shortness of breath. Her pain, exacerbated by inspiration, and relieved by leaning forward, had worsened over four days. She also reported dizziness and agonal breathing. On arrival, her vitals included a blood pressure of 95/62 mmHg, heart rate of 110 bpm, respiratory rate of 22 breaths/min, and a temperature of 37°C. Physical examination revealed tachycardia, tachypnea, and diminished breath sounds in the right lower lung field. Laboratory tests showed a hemoglobin level of 4.6 g/dL and a platelet count of 745 × 10^9/L, low ferritin, low serum Iron, and high total iron-binding capacity (TIBC). A CT pulmonary angiogram revealed a wedge-shaped infarct in the right lower lobe, consistent with pulmonary embolism. CT abdomen/pelvis showed a thrombus in the right iliac vein, indicative of deep vein thrombosis. The echocardiogram showed left ventricular ejection fraction &amp;gt;55% with no right chamber strain. A pelvic ultrasound revealed no significant pathology. Treatment included heparin and blood transfusions, increasing hemoglobin to 9.0 g/dL. Hemolytic workup including prothrombin gene abnormalities, Factor V Leiden mutation, and protein C activity was negative. However, Protein S activity was low, and PTT-la positive, implying that the patient may be positive for lupus anticoagulant, later ruled out by serial antibody tests.Subsequently, the patient was discharged home on Eliquis and Ferrous sulfate with outpatient hematology follow-up. Discussion: The association between venous thromboembolism and IDA can be explained by several mechanisms. One study suggests that iron deficiency causes hypercoagulability through reactive thrombocytosis, increased oxidative stress, and altered blood viscosity. Another hypothesis is that the hyperdynamic state in anemic patients leads to vascular endothelial injury due to shear forces. This case highlights the importance of considering IDA as a potential risk factor for thromboembolism, especially in patients without other evident prothrombotic conditions. Conclusion: Iron deficiency may be an underestimated risk factor for thromboembolic events. This case underscores the need for a comprehensive workup for VTE that includes assessing for IDA. Iron replacement therapy could serve as an effective preventive strategy in patients with a history of IDA and those at risk for thromboembolism. Further research is warranted to explore the mechanisms linking IDA with increased thrombotic risk and to establish appropriate preventive measures. Citation Format: Aliya M Khan, Maria Toustsoglou, Sandy Philippeaux, David Del sol, Mehmet Hepgur. Pulmonary thromboembolism secondary to iron deficiency anemia: A case study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A099.

The risk of thromboembolic events in patients with nephrotic syndrome and relatively high albumin levels: a study over 10 years

BackgroundLow albumin level is a risk factor for thromboembolic events in patients with NS (nephrotic syndrome). However, little is known about the proportion and characteristics of patients with NS who experience thromboembolic events with relatively high albumin levels (≥ 25 g/L). Therefore, we explored the features of this specific group of patients.MethodsThis study included all hospitalized patients in our center for the past 10 years who had diagnoses of NS and relevant thromboembolic events. We divided them into 2 groups based on their serum albumin level when the thromboembolic event occurred. The clinical data were analyzed with SPSS software.ResultsThere were 312 patients enrolled in our study. Eighty-four (26.9%) of them had relatively high albumin levels (≥ 25 g/L). Patients with NS with high albumin levels had significantly lower levels of 24-h proteinuria (P < 0.01) and a higher rate of autoimmune disease (P = 0.03) than the low-albumin group. Membranous nephropathy (MN) was the most frequent pathological type of NS in patients with thromboembolic events, regardless of their albumin level. There were significantly fewer patients with anti-PLA2R (M-type phospholipase A2 receptor)-positive MN in the high-albumin group than in the low-albumin group (P < 0.01).ConclusionsOur study found that there was still a high risk for patients with NS and relatively high albumin levels to develop thromboembolic events.

Incidence and risk factors for thromboembolic events in pediatric-onset inflammatory bowel disease: A French population-based study

IntroductionPatients with inflammatory bowel disease (IBD) are at higher risk of thromboembolic events (TE). In pediatric-onset IBD, more data on incidence and risk factors of venous (VTE) and arterial events (ATE) at the population level are needed to guide thromboprophylaxis. MethodsAll patients aged ≤ 16 years diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 1988 and 2011 in the prospective EPIMAD population-based registry were followed until 2013. Every TE occurring during the follow-up period was included. ResultsA total of 1,344 patients were included: 1,007 with CD and 337 with UC, and a median diagnosis age of 14.3 years. After a median follow-up of 8.3 years, 2 (0.15 %) ATE and 15 (1.1 %) VTE occurred at median age of 20.4 years. The global incidence rate of thromboembolic events was 1.32 per 1000 person-years. Periods of active disease (HR=8.4, p = 0.0002), the 3-month-period following surgery (HR=16.4, p = 0.0002) and hospitalization (HR=21.7, p < 0.0001) were found to be associated with an increased risk of VTE. A lower rate of VTE was found in patients treated with 5-aminosalicylates (HR=0.1, p = 0.002). ConclusionThe risk of TE was low in this population. VTE were strongly associated with active disease, surgery and hospitalization.

The presence of spontaneous echo contrast didn't increase the risk for left atrial appendage closure: A propensity score matching analysis based on the CLACBAC study

BackgroundLeft atrial appendage closure (LAAC) was effective in preventing thromboembolic events and stroke in patients with atrial fibrillation (AF). However, whether left atrial spontaneous echo contrast (LA-SEC) poses a higher risk for thromboembolism is contradictory. We aimed to investigate whether LA-SEC is a risk factor for thromboembolic events in patients who underwent LAAC. Methods258 consecutive patients who underwent successful LAAC were enrolled and divided according to the presence or absence of LA-SEC detected by transesophageal echocardiography (TEE). Propensity score matching (PSM) was used to eliminate covariate imbalances. Baseline characteristics, periprocedural details, and clinical outcomes were compared between LA-SEC and non-LA-SEC groups and PSM-matched groups. ResultsOf the 258 patients enrolled, mean age was 71.8 ± 8.3 years and 59.3 % were male. LA-SEC group had a higher percentage of persistent AF and worse cardiac function. No significant difference in peri-procedure parameters was found. Through follow-up of 38.1 ± 10.7 months, the total incidence of thromboembolic events and stroke was 7.8 % and 6.6 %, respectively. Though the event-free survival rate of thromboembolic events (Log-Rank P = 0.042) and stroke (Log-Rank P = 0.010) was significantly lower in the LA-SEC group, multivariable COX regression analysis showed LA-SEC was not an independent predictor of thromboembolic events (Hazard ratio 2.073, 95 % Confidence interval 0.845–5.082, P = 0.111). Further survival analysis between PSM-matched groups with comparable baseline characteristics presented no significant difference in survival free from thromboembolic events (Log-Rank P = 0.616) and stroke (Log-Rank P = 0.312). ConclusionPatients with LA-SEC had worse condition, while LA-SEC per se did not increase the incidence of thromboembolic events and stroke for patients who underwent LAAC.

Risk Factors, Antithrombotic Management, and Long-Term Outcomes of Patients Undergoing Endovascular Treatment of Unruptured Intracranial Aneurysms.

Patients receiving endovascular treatment for unruptured intracranial aneurysms (UIAs) face varying risks and benefits with antithrombotic management. This study aimed to evaluate the perioperative and long-term effects of antithrombotic strategies, identify the populations that would benefit, and explore the predictive factors affecting the long-term outcomes. UIA patients undergoing endovascular treatment including stent-assisted coiling or flow diversion between June 2019 and June 2022 were enrolled. We compared perioperative and long-term complications between tirofiban and dual antiplatelet therapy groups. Optimal candidates for each antithrombotic treatment were identified using multivariate logistic regression. Nomograms were developed to determine the significant predictors for thromboembolic complications during follow-up. Among 181 propensity-score matched pairs, the tirofiban group showed a trend toward a lower rate of thromboembolic complications than the DAPT group without elevating major bleeding risk in either period. Homocysteine (Hcy) level ≥10 μmol/L was a significant independent factor associated with thromboembolic complication in both periods. Subgroup analysis highlighted that in patients with high Hcy levels, tirofiban and sustained antiplatelet treatment for ≥12 months were protective factors, while a history of stroke was an independent risk factor for thromboembolic events in follow-up. Four variables were selected to construct a prognostic nomogram, history of hypertension, prior stroke, Hcy level, and the duration of antiplatelet therapy. Perioperative low-dose tirofiban and extended antiplatelet therapy demonstrated a favorable trend in long-term outcomes for UIA patients with preoperative Hcy levels ≥10 μmol/L undergoing endovascular treatment. The prognostic model offers reliable risk prediction and guides antithrombotic strategy decisions.

Thrombosis of the superior mesenteric vein after laparoscopic sleeve gastrectomy – Case report and review of the literature

IntroductionBariatric surgery is the most effective treatment for patients with obesity. Laparoscopic sleeve gastrectomy (LSG) is the most performed bariatric procedure worldwide. Although complication rate is low, thrombosis of the superior mesenteric vein (SMV) may be a rare but life-threatening complication after bariatric surgery. Presentation of the caseA 33-year-old female patient, BMI 51.8 kg/m², underwent an uneventful LSG at our center for bariatric and metabolic surgery in Hannover, Germany. 70 mg enoxaparin once daily was given as prophylactic anticoagulation until discharge.After an uneventful postoperative course and discharge at postoperative day 3, the patient presented 9 days later with epigastric and back pain in the emergency room. The CT scan showed thrombosis of the SMV.After thrombectomy of the SMV, several abdominal washouts, creation of a laparostoma and highly complex treatment at the intensive care unit the patient was discharged 8 weeks after revisional surgery. DiscussionThe incidence of thrombosis of the SMV after bariatric surgery is low, but mortality is high (up to 50 %). In the literature, only case reports and small series are reported. Possible causes and the management of the disease are variable and depend on the patients´ situation.Although thrombosis of the SMV is a rare complication after bariatric surgery, it should be considered or ruled out, if a patient presents with abdominal pain after a recently performed bariatric procedure. Treatment should be initiated immediately and may include therapeutic anticoagulation, interventional or surgical procedure. ConclusionEven if risk factors for thromboembolic events are unknown, every bariatric surgeon should be aware that patients with obesity are at risk.

Risk factors for thromboembolic events in pediatric patients with ventricular assist devices

ObjectivePediatric patients on ventricular assist devices (VAD) are at risk of thromboembolic (TE) complications. Our objective was to identify factors associated with TE events, including the role of initial anticoagulation strategy and device type in the pediatric VAD population. MethodsThis was a retrospective, single-center review (2005-2022) of children who were implanted with paracorporeal pulsatile (PP), paracorporeal continuous (PC), or a combination of devices. Patient- and device-related factors were collected. Kaplan-Meier survival analysis was performed to determine freedom from TE. Cox proportional hazard analysis was conducted to look for factors associated with TE events. ResultsNinety-five patients included with a median age of 0.9 years (interquartile range, 0.3, 5.4); median weight of 8.4 kg (interquartile range, 4.5, 17.8), and 63.2% with noncongenital heart disease. Device breakdown included 47.4% PC, 24.2% PP, and 23.2% combination of devices. Initial anticoagulation was either heparin (61.5%) or bivalirudin (38.5%). In Kaplan-Meier analysis, unadjusted freedom from a TE event was significantly greater in those who received bivalirudin as their initial anticoagulation strategy (P = .02) and PP VADs (P = .02). In multivariate analysis, initial anticoagulation strategy with bivalirudin (hazard ratio, 0.30; 95% confidence interval, 0.12-0.75, P = .01) was associated with a reduced hazard of TE events, whereas PC device strategy was found to be associated with an increased hazard (hazard ratio, 2.78; 95% confidence interval, 1.12-6.88, P = .03). ConclusionsThis study suggests that PC device strategy and heparin as an initial anticoagulation strategy are associated with increased hazard of TE events. Further research is required to understand the interaction between device type and initial anticoagulation strategy.

Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Phase3 Roxadustat Trials in Japan.

Thromboembolic events have occurred in clinical trials of roxadustat. This post hoc analysis explored potential factors related to thromboembolic events in dialysis-dependent patients treated with roxadustat in four phase3 clinical trials in Japan. Thromboembolic events with onset before and after week12 were evaluated. Baseline risk factors for thromboembolic events were investigated by Cox regression analyses. Nested case-control analyses using conditional logistic models with matched pairs of case-control data explored relationships between thromboembolic events and laboratory parameters. Of the 444 patients, 56 thromboembolic events were observed in 44 patients during ≤ 52weeks of treatment. The proportion of venous and arterial thromboembolic events gradually increased after week12. Baseline risk factors included hemodialysis (vs peritoneal dialysis), advanced age (≥ 65years), shorter dialysis vintage (< 4 months), and history of thromboembolism. The absence of concomitant intravenous or oral iron therapy (including ferric citrate) was associated with thromboembolic events before week12 (hazard ratio 11.25; 95% confidence interval [CI] 3.36-37.71; vs presence). Case-control analysis revealed that low average transferrin saturation (< 10%; unadjusted odds ratio [OR] 6.25; 95%CI 1.52-25.62; vs ≥ 20%), high average transferrin level (≥ 2.5 g/L; unadjusted OR 4.36; 95%CI 1.23-15.39; vs < 2.0 g/L), and high average roxadustat dose (≥ 150mg; unadjusted OR 5.95; 95%CI 1.07-33.16; vs < 50mg) over the previous 8weeks before the event onset were associated with thromboembolic events after week12. However, adjustment for iron status extinguished the significant relationship between roxadustat dose and events. Multivariate case-control analysis showed that increased transferrin from baseline (≥ 1.0 g/L; adjusted OR 7.85; 95%CI 1.82-33.90; vs < 0.5 g/dL) and decreased mean corpuscular volume (< - 2fL; adjusted OR 5.55; 95%CI 1.73-17.83; vs ≥ 0fL) were associated with increased risk of thromboembolic events. In addition to established risk factors, iron deficiency may be related to thromboembolic events. Graphical Abstract available for this article. NCT02780726, NCT02952092, NCT02780141, NCT02779764.

P1151 Incidence and risk factors of thromboembolic events in Pediatric-Onset Inflammatory Bowel Disease: a population-based study

Abstract Background Patients with inflammatory bowel disease (IBD) are known to be more susceptible to thromboembolic events. However, limited data on the incidence and risk factors for both venous (VTE) and arterial thromboembolic events (ATE) have been documented at the population level, especially in pediatric-onset IBD. Methods All patients diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC) before the age of 17 years from 1988 to 2011 in a prospective population-based registry were retrospectively followed until 2013. Every VTE and ATE occurring during the follow-up period were included. Cox proportional hazard models with hazard ratio (HR) were performed using time dependent variable except for patient’s characteristics at diagnosis. Results A total of 1,344 patients diagnosed with IBD between 1988 and 2011, including 1,007 (75%) patients with CD and 337 (25%) with UC, with a median age at diagnosis of 14.3, IQR [11.7-16.0] years were included. After a median follow-up of 8.3, IQR [4.3–13.9] years, 15 (1.1%) VTE and 2 (0.15%) ATE occurred at a median age of 20.4, IQR [16.6-24.5] years (younger age: 14.8 years). The global incidence rate for both VTE and ATE was 1.32 per 1000 person-years, 95%CI [0.77 - 2.11]. In CD patients, the incidence of VTE was 1.41 per 1000 person-years, 95%CI [0.77 - 2.37], whereas it stood at 0.33 per 1000 person-years, 95%CI [0.01 - 1.85] in UC patients. The risk of VTE and ATE did not change over the study period. Periods of active disease (HR 8.4 [2.3-30.5], p=0.0002), the 3-months postoperative period (HR 16.4 [5.2-52.3], p=0.0002) and hospitalization (HR 21.7 [7.5-62.9], p&amp;lt;0.0001) were found to be associated with an increased risk of VTE. Conclusion The risk of both arterial and venous thromboembolism was low in this pediatric-onset IBD population-based cohort. VTE were strongly associated with active disease, surgery and hospitalization among IBD patients.

Association between COVID-19 Infection or Vaccination Outcomes and Methylenetetrahydrofolate Reductase Gene Polymorphism: A Systematic Review of the Literature.

Thrombosis is a detrimental sequala of COVID-19 infection; thus, prophylactic anti-coagulant therapy has been deemed mandatory in treatment unless serious contraindications are present. Susceptibility to thromboembolic events in COVID-19, or following COVID-19 vaccination, is likely attributable to an interplay of factors, including a patient's baseline clinical status and comorbidities, alongside genetic risk factors. In Europe, 8-20% of the population are homozygous for the MTHFR (methylene tetrahydrofolate reductase) variant, which compromises folate metabolism and elevates homocysteine levels. While heightened homocysteine levels are considered a risk factor for thromboembolic events, the precise clinical significance remains a contentious issue. However, recent research suggests elevated homocysteine levels may predict the course and severity of COVID-19 infection. Given the lack of reliable biomarkers predictive of COVID-19 thrombotic risk existing in practice, and the accessibility of MTHFR screening, we established two main outcomes for this study: (1) to determine the association between hereditary MTHFR mutations and COVID-19 severity and thromboembolic events and (2) to determine the link between MTHFR variants and adverse thrombotic events following COVID-19 vaccination. The review was conducted in accordance with PRISMA guidelines. Medline, Scopus, and Web of Science databases were searched from pandemic inception (11 March 2020) to 30 October 2023. Eligibility criteria were applied, and data extraction performed. From 63 citations identified, a total of 14 articles met the full inclusion criteria (8 of which were cross-sectional or observational studies, and 6 were case studies or reports). Among the eight observational and cross-sectional studies evaluating the relationship between MTHFR variants (C667T; A1298C) and thromboembolic events in COVID-19 infection, four studies established a connection (n = 2200), while the remaining four studies failed to demonstrate any significant association (n = 38). This systematic review demonstrated a possible association between the MTHFR gene variants and COVID-19 severity, thromboembolic events, and adverse events following vaccination. However, the paucity of robust data precluded any firm conclusions being drawn. Further prospective trials are required to determine the connection between the MTHFR gene variant and COVID-19 infection and vaccination outcomes.

Phenotypic Heterogeneity and Outcomes in Severe Protein C Deficiency: A Report of Two Patients

Background: Protein C is a zymogen that suppresses the coagulation cascade through proteolysis of factors V and VIII, and therefore its deficiency is a risk factor for thromboembolic events 1. There are two main subtypes of protein C deficiency. In type I protein C deficiency, both protein C antigen and activity levels are decreased, resulting in low protein C or inadequate protein lifespan 2. In type II deficiency, the activity level is lower than the antigen level due to abnormal protein activity 2. Inherited protein C deficiency is caused by either compound heterozygous or homozygous pathogenic variants in the POMC gene. Objective: To describe the clinical presentation and outcomes of 2 severe protein C deficiency cases. Patient #1 is an 8-year-old male with history of neonatal stroke, dense left hemiplegia, and cerebral palsy, who underwent whole exome sequencing due to MRI findings (Figure 1a). This identified an apparently homozygous variant in POMC, c.1154T&amp;gt;C (p. Met385Thr)in exon 9. Both parents were confirmed to be heterozygous carriers. The patient was found to have a normal antigen of 62% and a severely low activity of &amp;lt;10%, suggesting a diagnosis of type II protein C deficiency. He is being considered for extended anticoagulation with a direct Xa or IIa inhibitor or a vitamin K antagonist. Patient #2 was born at 34 weeks and presented immediately following birth with a large occlusive thrombus in the ascending to proximal aorta as well as left ventricular dysfunction and mitral regurgitation (Figure 1b). She was not a candidate for thrombectomy or catheter-directed tissue plasminogen activator (TPA) due to her age and procedural risks. She was given systemic TPA due to severe end organ dysfunction followed by unfractionated heparin (UFH). Due to neurological changes and intracranial hemorrhage (ICH), TPA and UFH were discontinued. Fresh frozen plasma and protein C concentrate were administered and UFH was resumed. Due to worsening ICH, UFH was again stopped, and she developed a left ventricular thrombus, impairing her systemic circulation. Her clinical status worsened, and she became unresponsive to resuscitation efforts, and passed away on DOL 16. Testing identified a protein C antigen and activity level of 10% and &amp;lt;15% respectively. This patient was found to have 2 variants in the PROC gene, c.30C&amp;gt;T (p. Phe10Phe), which is a variant of uncertain significance, and c.1019C&amp;gt;T (p. Thr340Met), which is known to be pathogenic. Discussion: Both cases highlight uncommon presentations of severe protein C deficiency without purpura fulminans. Management of severe protein C deficiency consists of protein C replacement or long-term anticoagulation with warfarin as the standard of care 3,4. However protein C concentrate is costly, requires intravenous access, and can cause hypersensitivity reactions and hemorrhage. Long-term warfarin treatment is burdensome for families, requiring frequent laboratory monitoring with variable time in the therapeutic range. The only curative option for protein C deficiency is liver transplantation, which has additional risks and has rarely been reported in the literature 3,4. Conclusions: These cases illustrate the phenotypic heterogeneity of inherited severe protein C deficiency and demonstrate the challenges of clinical management in this patient population. The International Society on Thrombosis and Haemostasis initiated a severe protein C deficiency registry in 2013 which will standardize and improve treatment of this rare condition.

Incidence and Risk Factors for Thrombosis in Cancer Patients with COVID-19

Introduction: Cancer is a leading cause of morbidity and mortality in the United States, and cancer patients infected with COVID-19 are at increased risk of death. Given that cancer and COVID-19 are both risk factors for thrombosis, it has been hypothesized that cancer patients with COVID-19 may be at greater risk for thromboembolic events than patients with COVID-19 alone. This risk could necessitate the need for more vigilant thrombosis prophylaxis. However, studies investigating risk factors for thromboembolic events in this population are limited with mixed results. We aimed to determine the incidence and risk factors for thromboembolic events in patients with cancer and COVID-19. Methods: We performed a retrospective cohort review of all cancer patients hospitalized with COVID-19 at our institution between January 1, 2021 and April 1, 2023. Patients over the age of 18 who had previously been diagnosed with cancer, received treatment within the prior 6 months, and had been hospitalized due to COVID-19 were included in the study. We assessed whether patients had experienced a thromboembolic event during their hospital stay, which included thrombosis of the extracorporeal circuit, distal or proximal lower extremity deep venous thrombosis (DVT), upper extremity DVT, pulmonary embolism, superficial thrombophlebitis, ischemic stroke, or other arterial event. Information regarding comorbidities and clinical course was extracted from the patient's record. Descriptive analysis was performed, and association between qualitative variables was studied with the Chi-squared test and the Fisher Exact test, when appropriate. For quantitative variables, the t-test or the Mann-Whitney U test was performed. Multivariate logistic regression was used to assess variables predictive of thromboembolic events. Results: 456 patients with cancer and COVID-19 were included in the study. The median age was 69 years (IQR 62 - 78) and 55% of patients were male. The majority (85%) of patients were White. Most patients had either lung (19%) or bone marrow (17%) cancer, and 196 (43%) had received chemotherapy in the 6 months prior to hospitalization. 37 patients (8.1%) had thromboembolic events during their hospital stay. Age, race, receipt of chemotherapy, and history of hypertension, heart disease, obesity, and stroke were not predictive of thromboembolic events. Patients with thromboembolic events experienced significantly longer lengths of hospital stay than those without thromboembolic events (9 days vs 12 days, p&amp;lt;0.05). Conclusion: Thromboembolic events affect many cancer patients with COVID-19 and may complicate their treatment course during hospitalization. Patients who experienced a thromboembolic event had prolonged hospital stays, which may lead to increased financial and emotional burden in this patient population. Evidence-based strategies for preventing thrombosis, including pharmacologic and mechanical methods, should be emphasized in hospitalized cancer patients with COVID-19, which may decrease thrombotic complications. Further, methods of secondary thrombosis prophylaxis, such as early detection with screening methods or treatment of subclinical methods, should be encouraged. Future studies should promote risk classification in this patient population and optimal prophylaxis paradigms.

Impact of Genetic Variations on Thromboembolic Risk in Saudis with Sickle Cell Disease.

Sickle cell disease (SCD) is a Mendelian disease characterized by multigenic phenotypes. Previous reports indicated a higher rate of thromboembolic events (TEEs) in SCD patients. A number of candidate polymorphisms in certain genes (e.g., FVL, PRT, and MTHFR) were previously reported as risk factors for TEEs in different clinical conditions. This study aimed to genotype these genes and other loci predicted to underlie TEEs in SCD patients. A multi-center genome-wide association study (GWAS) involving Saudi SCD adult patients with a history of TEEs (n = 65) and control patients without TEE history (n = 285) was performed. Genotyping used the 10× Affymetrix Axiom array, which includes 683,030 markers. Fisher's exact test was used to generate p-values of TEE associations with each single-nucleotide polymorphism (SNP). The haplotype analysis software tool version 1.05, designed by the University of Göttingen, Germany, was used to identify the common inherited haplotypes. No association was identified between the targeted single-nucleotide polymorphism rs1801133 in MTHFR and TEEs in SCD (p = 0.79). The allele frequency of rs6025 in FVL and rs1799963 in PRT in our cohort was extremely low (<0.01); thus, both variants were excluded from the analysis as no meaningful comparison was possible. In contrast, the GWAS analysis showed novel genome-wide associations (p < 5 × 10-8) with seven signals; five of them were located on Chr 11 (rs35390334, rs331532, rs317777, rs147062602, and rs372091), one SNP on Chr 20 (rs139341092), and another on Chr 9 (rs76076035). The other 34 SNPs located on known genes were also detected at a signal threshold of p < 5 × 10-6. Seven of the identified variants are located in olfactory receptor family 51 genes (OR51B5, OR51V1, OR51A1P, and OR51E2), and five variants were related to family 52 genes (OR52A5, OR52K1, OR52K2, and OR52T1P). The previously reported association between rs5006884-A in OR51B5 and fetal hemoglobin (HbF) levels was confirmed in our study, which showed significantly lower levels of HbF (p = 0.002) and less allele frequency (p = 0.003) in the TEE cases than in the controls. The assessment of the haplotype inheritance pattern involved the top ten significant markers with no LD (rs353988334, rs317777, rs14788626882, rs49188823, rs139349992, rs76076035, rs73395847, rs1368823, rs8888834548, and rs1455957). A haplotype analysis revealed significant associations between two haplotypes (a risk, TT-AA-del-AA-ins-CT-TT-CC-CC-AA, and a reverse protective, CC-GG-ins-GG-del-TT-CC-TT-GG-GG) and TEEs in SCD (p = 0.024, OR = 6.16, CI = 1.34-28.24, and p = 0.019, OR = 0.33, CI = 0.13-0.85, respectively). Seven markers showed novel genome-wide associations; two of them were exonic variants (rs317777 in OLFM5P and rs147062602 in OR51B5), and less significant associations (p < 5 × 10-6) were identified for 34 other variants in known genes with TEEs in SCD. Moreover, two 10-SNP common haplotypes were determined with contradictory effects. Further replication of these findings is needed.

Role of antiphospholipid antibodies in Covid-19 and its correlation with disease progression

Abstract Background The SARS-CoV2 infection that leads to COVID-19 is a condition with an erratic and changeable course. The majority of patients have the mildest form, which frequently has flu-like symptoms so mild that the illness can go unnoticed. Acute respiratory distress syndrome (ARDS), progressive hypoxemia, and unilateral or bilateral pneumonia are among the severe manifestations that occur in about 15% of infected patients and may necessitate mechanical ventilation support. When systemic hyperinflammation is in its worst, multiple organs are affected (cytokine storm), lymphopenia is present, and levels of ferritin, D-dimers, C-reactive protein, chemokines and cytokines, are markedly elevated. Aim of the work To research the association between COVID-19 patient antiphospholipid (APL) markers and thrombotic events. Patients and methodology Our study was a cross-sectional study and patients were selected from ward and ICU unit in Dar El Shefa Hospital, Cairo governorate. Results Our study demonstrated that cases with risk factors for thromboembolic events had worse outcomes more frequently; obesity was a statistically significant factor in these differences. Additionally, we discovered that cases with cytokine storm had worse outcomes more frequently, and that the differences in thromboembolic events and deep venous thrombosis were statistically significant. Conclusion In COVID-19 pneumonia patients, the clinical significance of antiphospholipid syndrome (APAs) is still unknown. Furthermore, it is still unclear how long these APAs last and how much they contribute to thrombotic events in patients.

Risk Factors for Thromboembolic and Bleeding Events in Patients After the Fontan Operation (Insights from the National Database of Health Insurance Claims of Japan)

Risk stratification of thromboembolic events (TEs) and bleeding events is important for the appropriate selection of thromboprophylaxis in patients after the Fontan operation. Therefore, we clarified the risk factors for TEs and bleeding events in patients after the Fontan operation using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. We conducted a retrospective cohort study including 2,515 patients who underwent the Fontan operation between June 2011 and September 2019. The end points were TEs and bleeding events within 1year of the Fontan operation analysis. We analyzed the risk factors for these end points using a multivariate analysis. In total, 1,903 patients were included in the analysis. The median age at the time of the Fontan operation was 3 (1 to 22) years, and 1,067 patients (56%) were male. The incidence rates of TEs and bleeding events were 12% and 11%, respectively. Age (odds ratio [OR] 1.1 per 1 year older, p <0.05) was an independent risk factor for TEs. Thromboprophylaxis with aspirin after the Fontan operation significantly reduced TEs (OR 0.3, p <0.05). A history of postoperative hemorrhage (OR 1.5, p <0.05) and the use of a potassium channel blocker (OR 2.1, p <0.05) were independent risk factors for bleeding events. In conclusion, aspirin was found to reduce the risk of TEs within 1 year of the Fontan operation. The results of this study will be useful in selecting effective and safe thromboprophylaxis in patients after the Fontan operation.

Fostamatinib or Thrombopoietin for the Treatment of Chronic Immune Thrombocytopenia in Adult Patients: A Real-World Assessment of Safety, Effectiveness and Cost

Introduction: Chronic immune thrombocytopenia purpura (ITP) in adults is a serious autoimmune disease in which platelets are prematurely destroyed, leaving the patient vulnerable to bruising and bleeding. Initial treatment starts with corticosteroids. In patients who become resistant or intolerant to corticosteroids, the thrombopoietic agents (TPOs), consisting of romiplostim (ROM), eltrombopag (ELT), and avatrombopag (AVA), or the spleen tyrosine kinase inhibitor fostamatinib (FOS), are appropriate next lines of therapy. In this study, the comparative safety, effectiveness, and cost of care between fostamatinib and the TPOs were evaluated in a real-world setting. Methods: A retrospective analysis of 17 community hematology practices across the USA was conducted to identify adult ITP patients who received one of the four agents. Data collection consisted of patient demographics, disease characteristics, as well as number and type of prior treatments. From the first day until the end of treatment, data were also collected on platelet (PLT) counts, adverse events, the use of rescue IVIG, platelet transfusions, and corticosteroids. Multivariable logistic regression analysis was used to compare PLT-related endpoints between agents. Results: A sample of 179 ITP patients who had received at least one of the four agents was identified. This resulted in a final sample of 51, 87, 127, and 44 patients who received FOS, ELT, ROM, or AVA, respectively. At month six, there were no significant differences between FOS and the TPOs in terms of the proportion of patients with the PLT count being ≥30 × 103/μL, ≥50 × 103/μL as well as the proportion of patients whose PLT levels doubled relative to baseline. The frequency of thromboembolic events (TEs) was 3.9% in FOS patients compared to 9.2%, 4.7%, and 11.4% in the ELT, ROM, and AVA groups. The mean cost per patient with FOS was $99,209 (95% CI: $59,595–$115,074), compared to $92,426 (95% CI: $68,331–$115,519), $108,482 (95% CI: $84,782–$132,182), and $131,050 (95% CI: $83,327–$179,897) for ELT, ROM, or AVA, respectively. Conclusions: In this real-world analysis, FOS was comparable to the TPOs in maintaining PLTs at clinically beneficial levels. Given these findings, the choice of therapy should be based on overall patient safety, preexisting risk factors for TEs, and cost effectiveness.

Patients with atrial fibrillation and a low risk of thromboembolic events: prescription rate of anticoagulant therapy according to a retrospective analysis

Aim. To conduct a retrospective analysis of the prevalence of main risk factors for thromboembolic events (TEEs) and the prescription rate of anticoagulant therapy (ACT) in patients with atrial fibrillation (AF) and a low CHA2DS2-VASc score in certain Russian regions using artificial intelligence technologies.Material and methods. The information was obtained from the Webiomed predictive analytics platform. The sample included 87601 patients with AF aged 18-74 years (men, 49,5%, mean age, 59,3±12,3 years, mean CHA2DS2-VASc score, 2,3±1,5) who received care in medical organizations in 6 constituent entities of the Russian Federation in the period from 2016 to 2019. CHA2DS2VASc score of 1 and 2 in a man and a woman, respectively, was regarded as a moderate risk, while score of 0 and 1, respectively, as a low risk of TEEs.Results. There were 22337 (25,5%) patients with AF at moderate risk and 18366 (21,0%) patients at low risk of TEEs. With a moderate risk of TEEs, CHA2DS2-VASc score of 1 in 70,4% of cases was determined by hypertension, while in 15,7% — by age 65-74 years, in 9,0% — by heart failure, in 2,9% — by myocardial infarction and/or peripheral arterial disease, in 2,0% — by type 2 diabetes. In patients with AF and a moderate risk of TEEs, ACT was prescribed in 4927 (22,1%) patients, while with a low risk of TEEs — in 1833 (10,0%). Among patients with AF and a high risk of TEEs (n=46898, 53,5%), 1216 (24,6%) patients with ischemic stroke (IS) did not initially have a high CHA2DS2-VASc risk.Conclusion. In clinical practice, among patients with AF aged 18-74 years, there are quite often individuals with CHA2DS2-VASc score of 1 not associated with sex. These patients need an individualized approach in ACT, which is the basis for prospective studies in order to optimize the assessment of cardioembolic IS risk, as well as to analyze the efficacy and safety of long-term ACT.