Predictors for the Development of Thromboembolic Events in Cancer Patients Treated with Bevacizumab, Ramucirumab, and Aflibercept: A Single-Institution Retrospective Analysis.

INTRODUCTION: The risk of thromboembolic events developing limits the dose of antiangiogenic agents, thereby reducing their efficacy. This retrospective study therefore sought to identify predictors for the development of antiangiogenic agent-induced thromboembolic events and to elucidate whether differences in the likelihood of thromboembolic events exist between different antiangiogenic agents or cancer types, to guide future strategies for optimizing safety, efficacy, and quality of life in patients receiving chemotherapy. METHODS: This study retrospectively investigated 468 cancer patients who received chemotherapy with bevacizumab, ramucirumab, or aflibercept at our outpatient chemotherapy center between December 2016 and April 2022. Variables related to the development of thromboembolic events were extracted from the medical records, and multivariate logistic regression analysis was performed to identify predictors for the development of thromboembolic events. The Wilcoxon/Kruskal-Wallis test was used to detect significant differences between groups. RESULTS: Significant factors included serum albumin level (odds ratio [OR] = 0.363, 95% confidence interval [CI] = 0.193-0.685; p = 0.0017) and diabetes mellitus (OR = 5.356, 95% CI = 1.711-16.769; p = 0.0039). Renin-angiotensin system inhibitors (OR = 0.307) had low OR, although it was not significant. No difference in the development of thromboembolic events was evident between cancer types (p = 0.0781), but differences were identified between the three antiangiogenic agents (p = 0.0132). Ramucirumab was associated with a lower likelihood of thromboembolic events. CONCLUSION: Serum albumin level and diabetes mellitus were identified as significant predictors for the development of antiangiogenic agent-induced thromboembolic events. In addition, the likelihood of thromboembolic events did not differ between cancer types but differed between antiangiogenic agents.

An international survey of venous thromboembolic events and current practices of peri-operative VTE prophylaxis after living donor hepatectomy.

BACKGROUND: Venous thromboembolic complications are an uncommon but significant cause of morbidity & mortality after live donor hepatectomy . The precise incidence of these events and the current practices of centers performing living donor liver transplantation worldwide are unknown. METHODS: An online survey was shared amongst living donor liver transplantation centers containing questions regarding center activity, center protocols for donor screening, peri-operative thromboembolic prophylaxis and an audit of -perioperative venous thromboembolic events after live donor hepatectomy in the previous five years (2016-2020). RESULTS: Fifty-one centers from twenty countries completed the survey. These centers had cumulatively performed 11500 living donor liver transplants between 2016-2020. All centers included pre-operative l assessment for thromboembolic risk amongst potential liver donors in their protocols. Testing for inherited prothrombotic conditions was performed by 58% of centers. Dual-mode prophylaxis was the most common practice (65%), while eight and four centers used single mode or no routine prophylaxis respectively. Twenty (39%) and 15 (29%) centers reported atleast one perioperative deep venous thrmobosis or pulmonary embolism event respectively. There was one donor mortality directly related to post-operative pulmonary embolism. Overall incidence of deep venous thrombosis and pulmonary embolism events was 3.65 and 1.74 per 1000 live donor hepatectomies respectively. Significant variations in center practices and incidence of thromboembolic events was identified in the survey primarily divided along world regions. 75% of participating centers agreed on the need for clear international guidelines. CONCLUSION: Venous thromboembolic events after live donor hepatectomy are an uncommon but important cause of donor morbidity. There is significant variation in practice among centers. Evidence-based guidelines regarding risk assessment, and peri-operative prophylaxis are needed.

Thromboembolic events after major bleeding events in patients with mechanical heart valves: a 13-year analysis.

Anticoagulation in patients with mechanical heart valves (MHV) is associated with a risk of major bleeding episodes (MBE). In case of MBE, anticoagulant interruption is advocated. However, there is lack of data regarding the thrombo-embolic events (TE) risk associated with anticoagulant interruption. The main objective of the study was to evaluate the rate and risk factors of 6-months of TEs in patients with MHV experiencing MBE. This observational study was conducted over a 13-year period. Adult patients with a MHV presenting with a MBE were included. The main study endpoint was 6-month TEs, defined by clinical TEs or an echocardiographic documented thrombosis, occurring during an ICU stay or within 6-months. Thromboembolic events were recorded at ICU discharge, and 6 months after discharge. Seventy-nine MBEs were analysed, the rate of TEs at 6-months was 19% CI [11-29%]. The only difference of presentation and management between 6-month TEs and free-TE patients was the time without effective anticoagulation (TWA). The Receiver Operator Characteristic curve identified the value of 122 h of TWA as a cut-off. The multivariate analysis identified early bleeding recurrences (OR 3.62, 95% CI [1.07-12.25], p = 0.039), and TWA longer than 122 h (OR 4.24, 95% CI [1.24-14.5], p = 0.021), as independent risk factors for 6-month TEs. A higher rate of TE was associated with anticoagulation interruption longer than 5 days and early bleeding recurrences. However, the management should still be personalized and discussed for each case given the heterogeneity of causes of MBE and possibilities of haemostatic procedures.

Effect of direct oral anticoagulants on bleeding during and after cataract surgery.

PURPOSE: To assess the risk for intraoperative and postoperative ocular bleeding associated with direct oral anticoagulant treatment in patients undergoing phacoemulsification surgery. METHODS: Consecutive patients had phacoemulsification and intraocular lens implantation while taking uninterrupted direct oral anticoagulants (dabigatran, rivaroxaban, or apixaban). Gender and age-matched patients without antithrombotic therapy were used as the control group. Patients were examined one week postoperatively. Intraoperative and postoperative hemorrhagic and non-hemorrhagic complications were assessed. RESULTS: Forty patients (56 eyes) on direct oral anticoagulants and 120 patients (172 eyes) without anticoagulation, at a mean age of 77 years, had phacoemulsification. There was no significant difference between the groups in the rate of intraoperative and postoperative bleeding. One eye (1.8%) in the treatment group and 3 eyes (1.7%) in the control group had hyphema (p = 0.72). No patient had thromboembolic event during or after surgery. CONCLUSIONS: Cataract surgery was safely performed while continuing direct oral anticoagulation.

Early-onset venous thromboembolisms in newly diagnosed non-promyelocytic acute myeloid leukemia patients undergoing intensive induction chemotherapy.

OBJECTIVES AND METHODS: Venous thromboembolic (VTE) events are emerging as frequent complications in acute myeloid leukemia (AML); however, there is insufficient data regarding epidemiology, risk factors, and impact on outcomes. The optimal approach to balance risks of thrombosis and hemorrhage remains unclear. This retrospective single-center study in AML patients undergoing induction chemotherapy between 2007 and 2018 assessed incidence, risk factors, features, and outcomes of early-onset VTE. RESULTS: 423 patients (median age 59 years) were enrolled. VTE was diagnosed in 31 patients (7.3%) within 3 months of admission. The median time to VTE was 3 days. Non-central venous catheter (CVC)-related VTE occurred in 19 patients (61%). Main risk factor for VTE was leukocytosis at admission, independent of platelet counts/INR. Four patients (13%) exhibited VTE recurrence. No deaths directly related to VTE or major bleeding events associated with platelet-adjusted anticoagulation in patients with VTE were recorded. There was no clear impact of VTE on 1-year overall survival; however, non-CVC-related VTE may be associated with adverse outcomes. CONCLUSIONS: Early-onset VTE is a common complication in newly diagnosed AML patients admitted for induction chemotherapy. Leukocytosis is an independent VTE risk factor. The potentially adverse impact of non-CVC-related VTE merits further study.

Geometrical Changes of the Aorta as Predictors for Thromboembolic Events After EVAR With the Anaconda Stent-Graft.

PURPOSE: Thromboembolic events (TE), including limb graft occlusion (LGO) and distal limb embolization (DLE), are common complications after endovascular aneurysm repair (EVAR). The aim of this study was to find predictors for TE in patients treated with the Anaconda stent-graft for infrarenal aneurysms. MATERIALS AND METHODS: Geometrical and anatomical variables were retrospectively analyzed in a consecutive Anaconda cohort. Pre- and postoperative CT scans were used to derive geometrical parameters length, curvature, torsion, and tortuosity index (TI) from the center lumen lines (CLLs). Limb characteristics, pre-to-post EVAR and mid-term-follow-up changes in the parameters were evaluated for their predictive value for TE. RESULTS: Eighty-four patients (mean age 74±8.3 years, 74 men) were enrolled. The risk of TE was lowered with pre-to-post implant decreasing TI (steps of 0.05: OR: 1.30, 95% CI: 1.01-1.66, p=0.04), pre-to-post implant decreasing mean curvature (OR: 1.08, 95% CI: 1.01-1.16, p=0.03), and a larger degree of circumferential common iliac artery (CIA) calcification (OR: 0.98, 95% CI: 0.97-1.00, p=0.03). The only LGO predictor was the caudal relocation of maximal curvature after EVAR (OR: 1.01, 95% CI: 1.00-1.01, p=0.04). Preventors of DLE were CIA diameter (OR: 0.87, 95% CI: 0.76-0.99, p=0.04), circumferential CIA calcification (OR: 0.97, 95% CI: 0.95-1.00, p=0.03), mean and maximal curvature of the preoperative aortoiliac trajectory (OR: 0.86, 95% CI: 0.79-0.94, p<0.01 and OR: 0.97, 95% CI: 0.95-1.00, p=0.03, respectively) and pre-to-postoperative decrease in mean curvature (OR: 1.11, 95% CI: 1.02-1.21, p=0.02). Midterm TE predictors were length (OR: 0.95, 95% CI: 0.89-1.01, p=0.08) and torsion maximum location (OR: 1.01, 95% CI: 0.99-1.01, p=0.10). CONCLUSION: The present study confirms that treatment of infrarenal AAA with an Anaconda stent-graft is related to a relatively high TE rate which decreases with a pre-to-postoperative reduction in curvature and TI, and a larger degree of circumferential CIA calcification. In other words, more aortoiliac straightening and more circumferential CIA calcification may prevent TE development after EVAR with this stent-graft.

Recurrent, life-threatening PE in the setting of popliteal vein aneurysm in pregnancy: a case report.

BACKGROUND: Popliteal vein aneurysms (PVA) are a rare clinical entity with unknown etiology that pose a significant risk for venous thromboembolic events (VTE). The current literature supports anticoagulation and operative management. There are few case reports of PVA in pregnancy. We present a unique case of a pregnant patient with recurrent pulmonary embolism (PE) in the setting of PVA with intra-aneurysmal thrombosis who ultimately underwent surgical excision. CASE PRESENTATION: A previously healthy 34-year-old G2P1 at 30 weeks gestation presented to the emergency department with shortness of breath and chest pain. She was diagnosed with PE and subsequently required intensive care unit (ICU) admission and thrombolysis for a massive PE. While on a therapeutic dose of tinzaparin she had recurrence of PE in the post-partum period. She was treated with supratherapeutic tinzaparin and subsequently transitioned to warfarin. She was found to have a PVA and ultimately underwent successful PVA ligation. She remains on anticoagulation for secondary prevention of VTE. CONCLUSIONS: PVA are a rare but potentially fatal source of VTE. Patients most commonly present with symptoms of PE. The risk of VTE is elevated in the pro-thrombotic states of pregnancy and the post-partum period due to both physiologic and anatomical changes. The recommended management of PVA with PE is anticoagulation and surgical resection of the aneurysm, however this can be complicated in the setting of pregnancy. We demonstrated that pregnant patients with PVA can be temporized with medical management to avoid surgical intervention during pregnancy, but require close symptom monitoring and serial imaging to reassess the PVA, with high index of suspicion for recurrent VTE. Ultimately, patients with PVA and PE should undergo surgical resection to reduce the risk of recurrence and long-term complications. The ideal duration of post-operative anticoagulation remains unclear, and should likely be decided on based on risks, benefits, values, and shared decision making with the patient and their care provider.

Differences in referral to a chronic thromboembolic pulmonary hypertension center following acute pulmonary embolism: a locoregional experience.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a treatable complication of acute pulmonary embolism (PE). Identification of factors that impact referral to a comprehensive CTEPH center may improve disease awareness and patient outcomes. We conducted a study of patients with acute PE. Cases were identified through a natural language processing algorithm. ICD coding was used to assess clinical documentation for dyspnea or CTEPH placed at least 90 days after their acute PE diagnosis. We analyzed characteristics of patients who were referred vs. not referred, as well as referral patterns for "at risk" patients. 2454 patients with acute PE were identified, of which 4.9% (120/2454) were referred for CTEPH evaluation. Patients who were not referred were older (61 vs. 54 years, p < 0.001), had higher rates of cancer (28% vs. 10%, p < 0.001), and lived further from the referral center (9.1 miles vs. 6.7 miles, p = 0.03). Of 175 patients identified as "at risk," 12% (21/175) were referred. In the 'at risk' cohort, distance from referral center among referred and not referred was significant (5.7 miles vs. 8.8 miles, p = 0.04). There were low rates of referral to CTEPH center in post-PE patients, and in patients with symptoms who may be at higher risk of CTEPH. Age, co-morbid conditions, distance from comprehensive center, and presence of a primary care provider contribute to differences in referral to a comprehensive CTEPH center. Clinician education about CTEPH is important to ensure optimal care to patients with or at risk for chronic complications of acute PE.

Risk of thromboembolic events in relation to the management of anticoagulant and antiagregant therapy in patients subjected to endoscopic retrograde cholangiopancreatography. / Riesgo de eventos tromboembólicos en función del manejo de la terapia anticoagulante y antiagregante en pacientes sometidos a colangiopancreatografía retrógrada endoscópica.

BACKGROUND AND OBJECTIVES: The main clinical practice guidelines recommend adequate periprocedural withdrawal and reintroduction of antithrombotic drugs in case of invasive techniques. The main objective of this study was to assess whether, in patients receiving anticoagulant or antiplatelet therapy, the suppression or reduction of the pharmacological dose for the performance of endoscopic retrograde cholangiopancreatography (ERCP) implies a greater risk of thromboembolic events. PATIENTS AND METHODS: A prospective observational study was carried out, which included 644ERCP performed with therapeutic intention during 2019 at the Reina Sofía University Hospital with follow-up during the 30days after the endoscopic intervention. RESULTS: Six patients presented a thromboembolic event, finding no differences between the incorrect withdrawal/reintroduction of antithrombotic treatment and a higher proportion of thromboembolic or hemorrhagic events after the procedure (P>.05). The incidence of thrombotic events was significantly higher in patients treated with heparin or apixaban (P=.001), as well as with a history of atrial fibrillation (P=.05), rheumatic valve disease (P=.037) and recurrent pulmonary embolism (P=.035), this being also an independent risk factor. Likewise, the incidence of hemorrhage in the 30days post-sphincterotomy was significantly lower in those with implantation of a biliary prosthesis (P=.04). CONCLUSIONS: Inadequate periprocedural management of antithrombotic therapy is not associated with a significant increase in the incidence of thromboembolic events in the 30days after ERCP. However, close follow-up and surveillance during the days after this is essential in those patients with a condition that significantly increases the risk of thrombosis.

Safety and efficacy of low-dose non-vitamin K antagonist oral anticoagulants versus warfarin after left atrial appendage closure with the Watchman device.

BACKGROUND/PURPOSE: Anticoagulant therapy is suggested within 45 days after Watchman device implantation for stroke prevention in patients with atrial fibrillation (AF). A previous study demonstrated that non-vitamin K antagonist oral anticoagulants (NOACs) were a feasible peri- and postprocedural alternative to warfarin. The present study aimed to compare the safety and efficacy of using different anticoagulants (low-dose NOACs vs. warfarin) within 45 days after Watchman device implantation in a Chinese population. METHODS: Patients with successful Watchman device implantation from October 2014 to June 2020 were included. All patients received anticoagulants within 45 days after the procedure, and those patients were divided into three groups according to the type of postprocedural anticoagulants. Transesophageal echocardiography follow-up was performed 45 days post procedure to assess residual flow and the occurrence of device-related thrombus (DRT). RESULTS: A total of 368 patients were enrolled in the study. The study population was divided into three groups: the warfarin group (n = 77), the dabigatran group (n = 165) and the rivaroxaban group (n = 126). Periprocedural major bleeding was higher in the warfarin group (2.6% vs. 0% vs. 0%, P = 0.043), while minor bleeding was comparable among the groups (3.9% vs. 1.2% vs. 0.8%, P = 0.230). No periprocedural transient ischemic attack/stroke occurred. At follow-up, the incidence of DRT was higher in the warfarin group than in the other groups (4.2% vs. 0.6% vs. 0.8%; P = 0.116), but the difference was not statistically significant. The rates of thromboembolic and bleeding events were similar in the three groups. CONCLUSION: The safety and efficacy of low-dose dabigatran and rivaroxaban were comparable to those of warfarin within 45 days after Watchman device implantation in a Chinese population.

Acute femoral artery occlusion in a male with Duhring disease and COVID-19 pneumonia treated with baricitinib.

Arterial thromboembolic events (ATE) in COVID-19, similarly as venous thromboembolism (VTE), are observed mainly in severely ill patients. ATE include brain, heart, aortic, and peripheral ischemic complications which usually aggravate a course of the disease leading to lifethreatening conditions. A CASE REPORT: The authors describe a case of a 53-year-old male with Duhring disease in the remission period admitted due to severe COVID-19 pneumonia. The patient was treated with ceftriaxone (2000 mg once daily), dexamethasone (8 mg once daily), enoxaparin (60 mg twice daily), baricitinib (4 mg once daily), and remdesivir (200 mg on the first day, followed by 100 mg within 4 consecutive days); he required high flow oxygen therapy. On day 5 of hospitalization, he began to suffer from pain of the right lower extremity; in physical examination the limb was cold with absent femoral, popliteal, and pedal pulses. Urgent computed tomography angiography revealed total occlusion of the right superficial femoral artery (SFA) in the absence of any atherosclerotic plaques in the aorta. The patient was intubated and transferred to department of vascular surgery, where a giant clot was removed from SFA. Unfortunately, the patient outcome was unfavorable due to respiratory failure progression. The authors underline that ATE may occur even in anticoagulated patients and that association of some therapeutic options of COVID-19, like janus kinase (JAK) inhibitors use with an increased risk of ATE, should not be excluded.

Pathological findings in rotation thromboelastometry associated with thromboembolic events in COVID-19 patients.

BACKGROUND: Severe thromboembolic events are one of the major complications associated with COVID-19 infection, especially among critically ill patients. We analysed ROTEM measurements in COVID-19 patients with a severe disease course and in patients with severe sepsis. METHODS: In this study, data obtained by extended analysis of haemostasis with standard laboratory tests and thromboelastometry of 20 patients with severe course of COVID-19 were retrospectively analysed and compared with similar data from 20 patients with severe sepsis but no COVID-19. RESULTS: The thromboelastometry values obtained from 20 sepsis patients contained a maximum clot firmness above the normal range but among COVID-19 patients, hypercoagulability was much more pronounced, with significantly higher maximum clot firmness (FIBTEM: 38.4 ± 10.1 mm vs. 29.6 ± 10.8 mm; P  = 0.012; EXTEM: 70.4 ± 10.4 mm vs. 60.6 ± 14.8 mm; P  = 0.022). Additionally, fibrinogen levels were significantly higher among COVID-19 patients (757 ± 135 mg/dl vs. 498 ± 132 mg/dl, P < 0.0001). Furthermore, thromboelastometry showed fibrinolysis shutdown among COVID-19 patients with significantly lower maximum of lysis than among sepsis patients (EXTEM: 0.6 ± 1.2 % vs. 3.3 ± 3.7 %; P  = 0.013). Seven of 20 COVID-19 patients experienced thromboembolic events, whereas no patient in the sepsis group experienced such events. CONCLUSIONS: ROTEM analysis showed significantly different pathological findings characterized by hypercoagulability and fibrinolysis shutdown among COVID-19 patients with a severe disease course compared to patients with severe sepsis. These abnormalities seem to be associated with thromboembolic events.

Indications and long-term outcomes of preoperative inferior vena caval filters in 111 patients at high risk of pulmonary embolism undergoing major abdominal surgery.

AIMS: Patients with abdominal cancer requiring major surgical intervention are at high risk of venous thromboembolic events (VTE), particularly pulmonary emboli (PE). A proportion of patients with cancer can present with, or have had, major VTEs prior to definitive surgical treatment. Preoperative percutaneous inferior venal caval filters (IVCF) may reduce the risk of PE. The aim of this study was to assess the indications, complications, retrieval rates, and long-term outcome of IVCFs in patients undergoing major abdominal surgery. METHODS: This was a retrospective analysis of a prospective IVCF database between 2007 and 2018 of all patients with IVCF insertion prior to major abdominal surgery. The indications for an IVCF, procedural complications and surgical interventions were recorded. RESULTS: Overall, 111 patients had IVCF insertion. IVCF placement failed in one patient with gross abdominal disease. Indications for an IVCF were: prior PE in 65/111 (59%) and major vein thrombus in 42 (38%). Overall, 26/111 (23%) had the IVCF removed at a median of 91 days. In two patients IVCF removal failed. At follow-up of the 85 patients who had the IVCF left in situ, six developed filter-related thrombus and 13 a deep vein thrombosis (DVT). Four patients had a PE with an indwelling IVCF. CONCLUSION: Preoperative IVCF may reduce perioperative PE in patients at high risk of thrombosis undergoing major abdominal surgery where early anticoagulation is contraindicated. Long-term follow-up of retained IVCF suggests that major problems are infrequent, though further thrombosis may occur and long-term anticoagulation may be needed.

Cost-effectiveness of apixaban for prevention of venous thromboembolic events in patients after gynecologic cancer surgery.

OBJECTIVE: The cost-effectiveness of apixaban was compared with enoxaparin for prevention of postoperative venothromboembolic events (VTE) in gynecologic oncology patients. Current guidelines recommend thromboprophylaxis with low molecular weight heparin for 28 days following gynecologic cancer surgery, but recent trials suggest that oral apixaban may be a safe, patient-preferred alternative. Apixaban was superior to enoxaparin in a Canadian cost-effectiveness analysis using orthopedics trial data. METHODS: Medication costs, adherence rates, event rates, event costs, and utility decrements were estimated using prior clinical trial data and literature review for input into a short-term decision model to simulate outcomes in a hypothetical cohort of 1000 patients. Incremental cost-effectiveness ratios (ICERs) were calculated as net cost difference per quality-adjusted life year (QALY) gained. Input values at which net costs and QALYs were equivalent and ICERs at upper and lower bounds were evaluated. RESULTS: Using aggregated costs, apixaban was less expensive and more effective than enoxaparin, and remained so or had high value in all scenarios on sensitivity analysis. Examining disaggregated ICERs, apixaban was cost-effective for deep venous thrombosis (DVT); of high value for clinically-relevant non-major bleeding (CRNMB) ($411); low value for major bleeding ($183,465), VTE-related death ($2,711,229), and all-cause mortality ($297,522); and not cost-effective for pulmonary embolism prevention. CONCLUSIONS: Apixaban is more cost-effective than enoxaparin for the prevention of postoperative VTE in patients with gynecologic cancer. This appears to be driven largely by DVT and CRNMB prevention.

Extent of Late Gadolinium Enhancement Predicts Thromboembolic Events in Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: Thromboembolic complications such as ischemic stroke or peripheral arterial thromboembolism are known complications in hypertrophic cardiomyopathy (HCM). We sought to assess the clinical and cardiovascular magnetic resonance (CMR) characteristics of patients with HCM suffering from thromboembolic events and analyzed the predictors of these unfavorable outcomes.Methods and Results:The 115 HCM patients underwent late gadolinium enhanced (LGE) CMR and were included in the study. Follow-up was 5.6±3.6 years. The primary endpoint was the occurrence of thromboembolic events (ischemic stroke or peripheral arterial thromboembolism). It occurred in 17 (14.8%) patients (event group, EG), of whom 64.7% (11) were men. During follow-up, 10 (8.7%) patients died. Patients in the EG showed more comorbidities, such as heart failure (EG 41.2% vs. NEG (non-event group) 14.3%, P<0.01) and atrial fibrillation (AF: EG 70.6% vs. NEG 36.7%, P<0.01). Left atrial end-diastolic volume was significantly higher in the EG (EG 73±24 vs. NEG 50±33 mL/m2, P<0.01). Both the presence and extent of LGE were enhanced in the EG (extent% EG 23±15% vs. NEG 8±9%, P<0.0001). No patient without LGE experienced a thromboembolic event. Multivariate analysis revealed AF and LGE extent as independent predictors. CONCLUSIONS: LGE extent (>14.4%) is an independent predictor for thromboembolic complications in patients with HCM and might therefore be considered as an important risk marker. The risk for thromboembolic events is significantly elevated if accompanied by AF.

Protein C and Protein S Levels in ß-Thalassemia Major Patients in Erbil, Kurdistan Region.

Oxygen is transported in the blood through red blood cells and a protein called hemoglobin. The protein consists of two alpha and two beta chains. The lack of any of these chains is caused by the malfunction of the genes that produce them, and can lead to a genetic disease called thalassemia. In ß-thalassemia, hemoglobin does not produce enough beta protein. According to mild to severe effects on the body, ß-thalassemia is divided into three types minor, interstitial and major thalassemia. There are increasing risks for thrombosis complications in thalassemia major. The purpose of this study was to evaluate protein C and protein S levels in ß-thalassemia major and their association to the hypercoagulable state. Seventy patients with ß-thalassemia major and 35 apparently healthy subjects as a control group were investigated for protein C and protein S. The mean of protein C (71.31%) and protein S (34.3%) levels were significantly reduced in ß- thalassemia major patients in comparison with control subjects (p-value <0.001). Mean of fibrinogen level (2.42) g/l was significantly decreased in ß-thalassemia major patients while the mean of D dimer level (0.43) µg/ml was significantly increased in comparison to control subjects (p-value 0.001). This study demonstrates a chronic hypercoagulable state in B- thalassemia major patients.

Cerebral Microembolization in Left Ventricular Assist Device Associated Ischemic Events.

INTRODUCTION: The significance of microembolic signals (MES) detected by transcranial Doppler ultrasound emboli monitoring (TCD-e) in patients supported with left ventricular assist devices (LVAD) remains unclear. We aimed to investigate the relationship between cerebral microembolization detected by TCD-e and acute ischemic events in LVAD patients. METHODS: We reviewed consecutive patients with acute ischemic stroke or transient ischemic attack (TIA) in a prospectively collected database of LVAD patients. TCD-e exams consisted of monitoring the middle cerebral arteries for microembolic signals (MES) over 30 minutes. RESULTS: Of 515 persons with LVAD, 41 TCD-e studies were performed in 35 patients with acute ischemic stroke or transient ischemic attack (TIA) in a median of 1 day (Interquartile range [IQR]: 0-2) after the event. MES were present in 15 (44%) TCD-e studies with a median MES count of 4 (IQR: 2-15.5). Bloodstream infections were more common in patients with MES (38% versus 8%, P = .039). There were trends for lower international normalized ratio (1.39 versus 1.69, P = .214), lower activated partial thromboplastin (33.2 versus 36.6, P = .577), higher lactate dehydrogenase (531 versus 409, P = .323) and a higher frequency of pump thrombosis (13% versus 8%, P = .637) in patients with MES compared with those without MES. CONCLUSIONS: LVAD patients with acute ischemic stroke or TIA have a high prevalence of MES on TCD-e, which may serve as a marker for a prothrombotic state. Further study of MES in LVAD patients is warranted.

Clinical Risk Factors of Thromboembolic and Major Bleeding Events for Patients with Atrial Fibrillation Treated with Rivaroxaban in Japan.

BACKGROUND: It is important to understand the risk of thromboembolism and bleeding in patients with nonvalvular atrial fibrillation (NVAF) receiving direct oral anticoagulants; however, data on risk factors in Japanese patients are limited. METHODS: XAPASS (Xarelto Post-Authorization Safety and Effectiveness Study in Japanese Patients with Atrial Fibrillation) is a prospective observational study examining the safety and effectiveness of rivaroxaban in Japanese real-world clinical practice. We investigated risk factors for stroke/noncentral nervous system systemic embolism (non-CNS SE)/myocardial infarction (MI) and major bleeding using 1-year follow-up data. Associations between baseline characteristics and outcomes were examined by Cox regression analysis. RESULTS: During April 2012-June 2014, 11,308 patients newly started with rivaroxaban treatment were enrolled. Of 9578 patients with 1-year data fixed as of September 2017, 6220 patients who received appropriate dosages of rivaroxaban for their creatinine clearance were included in the present safety outcomes subanalysis, and 6198 were included in the effectiveness outcomes analysis. Stroke/non-CNS SE/MI was observed in 97 of 6198 patients (1.6%, 1.8 events/100 patient-years), and major bleeding occurred in 102 of 6220 patients (1.6%, 1.9 events/100 patient-years). Age greater than or equal to 75 years (hazard ratio [HR]: 2.27; [95% confidence interval (CI): 1.49, 3.47]), prior ischemic stroke/transient ischemic attack (2.08; [1.38, 3.13]), and antiplatelet use (3.23; [1.83, 5.70]) were associated with stroke/non-CNS SE/MI. Creatinine clearance less than 50 mL/min (HR: 1.86; [95% CI: 1.26, 2.75]), diabetes (1.55; [1.02, 2.35]), and antiplatelet use (3.04; [1.70, 5.45]) were associated with major bleeding. CONCLUSIONS: These results would help physicians to assess risks in Japanese patients with NVAF receiving rivaroxaban.

Bleeding and Thromboembolism After Traumatic Brain Injury in the Elderly: A Real Conundrum.

BACKGROUND: Elderly patients presenting with a traumatic brain injury (TBI) often have comorbidities that increase risk of thromboembolic (TE) disease and recurrent TBI. A significant number are on anticoagulant therapy at the time of injury and studies suggest that continuing anticoagulation can prevent TE events. Understanding bleeding, recurrent TBI, and TE risk after TBI can help to guide therapy. Our objectives were to 1) evaluate the incidence of bleeding, recurrent TBI, and TE events after an initial TBI in older adults and 2) identify which factors contribute to this risk. METHODS: Retrospective analysis of Medicare claims between May 30, 2006 and December 31, 2009 for patients hospitalized with TBI was performed. We defined TBI for the index admission, and hemorrhage (gastrointestinal bleeding or hemorrhagic stroke), recurrent TBI, and TE events (stroke, myocardial infarction, deep venous thrombosis, or pulmonary embolism) over the following year using ICD-9 codes. Unadjusted incidence rates and 95% confidence intervals (CIs) were calculated. Risk factors of these events were identified using logistic regression. RESULTS: Among beneficiaries hospitalized with TBI, incidence of TE events (58.6 events/1000 person-years; 95% CI 56.2, 60.8) was significantly higher than bleeding (23.6 events/1000 person-years; 95% CI 22.2, 25.1) and recurrent TBI events (26.0 events/1000 person-years; 95% CI 24.5, 27.6). Several common factors predisposed to bleeding, recurrent TBI, and TE outcomes. CONCLUSIONS: Among Medicare patients hospitalized with TBI, the incidence of TE was significantly higher than that of bleeding or recurrent TBI. Specific risk factors of bleeding and TE events were identified which may guide care of older adults after TBI.

Lower Extremity Duplex Ultrasound Screening Protocol for Moderate- and High-Risk Trauma Patients.

BACKGROUND: Deep vein thrombosis (DVT) remains a significant cause of morbidity after injury. Lower extremity duplex ultrasound screening (LEDUS) is designed to identify early, asymptomatic DVTs in moderate and high risk patients. We sought to describe when thrombus is detected and identify which trauma patients benefit from LEDUS. MATERIALS AND METHODS: A retrospective review was conducted on trauma patients who were moderate or high risk for venous thromboembolism based on risk assessment profile (RAP) scoring. Patients with RAP scores ≥5 underwent LEDUS on hospital Day 4 and then weekly. We defined moderate venous thromboembolism risk as an RAP score of 5-9 and high risk as an RAP score of ≥10. Demographics, injury characteristics, and chemoprophylaxis type and timing were analyzed. RESULTS: A total of 579 trauma patients underwent a total of 820 ultrasounds in 1 y. Eighty-eight acute DVTs were identified. There was only one progression of a below- to above-the-knee DVT. Patients with RAP scores ≥10 had significantly higher rates of DVTs compared with patients with lower RAP scores in addition to longer lengths of stay and time to DVT prophylaxis. Moderate- and high-risk patients had similar rates of pulmonary embolism. Two-thirds of all DVTs were diagnosed on the first screening examination. The rate of DVTs in patients with RAP scores 7-9 was 15.4% compared with 6.1% of those with RAP scores of 5-6. CONCLUSIONS: LEDUS allows for early identification of asymptomatic DVTs. Moderate-risk patients with RAP scores of ≥7 should be considered for LEDUS, given higher rates of DVT.