Arterial Thrombosis Research Articles

Influence of Hematocrit Level and Integrin αIIbβIII Function on vWF-Mediated Platelet Adhesion and Shear-Induced Platelet Aggregation in a Sudden Expansion.

Shear-mediated thrombosis is a clinically relevant phenomenon that underlies excessive arterial thrombosis and device-induced thrombosis. Red blood cells are known to mechanically contribute to physiological hemostasis through margination of platelets and vWF, facilitating the unfurling of vWF multimers, and increasing the fraction of thrombus-contacting platelets. Shear also plays a role in this phenomenon, increasing both the degree of margination and the near-wall forces experienced by vWF and platelets leading to unfurling and activation. Despite this, the contribution of red blood cells in shear-induced platelet aggregation has not been fully investigated-specifically the effect of elevated hematocrit has not yet been demonstrated. Here, a microfluidic model of a sudden expansion is presented as a platform for investigating platelet adhesion at hematocrits ranging from 0 to 60% and shear rates ranging from 1000 to 10,000 s-1. The sudden expansion geometry models nonphysiological flow separation characteristic to mechanical circulatory support devices, and the validatory framework of the FDA benchmark nozzle. PDMS microchannels were fabricated and coated with human collagen. Platelets were fluorescently tagged, and blood was reconstituted at variable hematocrit prior to perfusion experiments. Integrin function of selected blood samples was inhibited by a blocking antibody, and platelet adhesion and aggregation over the course of perfusion was monitored. Increasing shear rates at physiological and elevated hematocrit levels facilitate robust platelet adhesion and formation of large aggregates. Shear-induced platelet aggregation is demonstrated to be dependent on both αIIbβIII function and the presence of red blood cells. Inhibition of αIIbβIII results in an 86.4% reduction in overall platelet adhesion and an 85.7% reduction in thrombus size at 20-60% hematocrit. Hematocrit levels of 20% are inadequate for effective platelet margination and subsequent vWF tethering, resulting in notable decreases in platelet adhesion at 5000 and 10,000 s-1 compared to 40% and 60%. Inhibition of αIIbβIII triggered dramatic reductions in overall thrombus coverage and large aggregate formation. Stability of platelets tethered by vWF are demonstrated to be αIIbβIII-dependent, as adhesion of single platelets treated with A2A9, an anti-αIIbβIII blocking antibody, is transient and did not lead to sustained thrombus formation. This study highlights driving factors in vWF-mediated platelet adhesion that are relevant to clinical suppression of shear-induced thrombosis and in vitro assays of platelet adhesion. Primarily, increasing hematocrit promotes platelet margination, permitting shear-induced platelet aggregation through αIIbβIII-mediated adhesion at supraphysiological shear rates. The online version contains supplementary material available at 10.1007/s12195-024-00796-0.

Postnatal distal arterial thrombosis, difficulties in newborns: About two cases

Postnatal distal arterial thrombosis, difficulties in newborns: About two cases

Efficacy and safety of transcatheter arterial embolization of omental artery aneurysm: A single-center experience.

Omental artery aneurysm (OAA) is an extremely rare visceral artery aneurysm. Ruptured OAAs are associated with a high mortality rate. Transcatheter arterial embolization (TAE) has been used to treat OAA in recent years. However, the risk of omental ischemia due to TAE remains unclear. Therefore, this study aimed to investigate the efficacy and safety of TAE of OAA as a first-line treatment. Fifteen patients with true aneurysms or pseudoaneurysms who underwent OAA-TAE between 1 April 2010 and 31 December 2022 were included in this study. The technical and clinical outcomes, the incidence of omental infarction after TAE as a major complication, OAA-TAE techniques, radiological findings on computed tomography angiography and angiogram, and patient characteristics were evaluated. Fifteen patients (nine men, six women; age, 69.8 ± 18.59 years) underwent TAE of OAAs (mean aneurysm size of 9.30 ± 6.10 mm) located in the right gastroepiploic (n = 9), left gastroepiploic (n = 1), and epiploic (n = 5) arteries. All patients with ruptured (n = 6) and unruptured (n = 9) OAA successfully underwent TAEs using coils, n-butyl-2-cyanoacrylate, or gelatin sponges. Hepatic artery thrombosis and coil migration were observed during the procedure; however, these adverse events were manageable. Transfusion of red blood cell units (4.66 ± 1.63 units) was required only in cases with ruptured OAAs after TAE. Additional surgery or TAE due to rupture or rerupture of OAA and omental infarction was not required during the postoperative and follow-up periods. The OAA-TAE can effectively treat ruptured and unruptured OAAs, and the risk of omental infarction after OAA-TAE may not be high.

Systematic approach to obtain axillary arterial access for pediatric heart catheterizations.

Axillary arterial access (AAA) in pediatric heart catheterizations is undervalued. We retrospectively reviewed children with congenital heart diseases (CHDs) who received trans-axillary arterial catheterizations between January 2019 and February 2023. We aimed ultrasound-guided punctures in the proximal two-thirds of axillary arteries with diameters ≥2 mm to insert 7 cm/4 Fr short introducers. We administrated intra-arterial verapamil (1.25 mg) and heparin (100 UI/kg). We infiltrated per-operatively 2% lignocaine (10 mg) for arterial spasms, long sheaths use (≥5 Fr), and ≥60 min procedures in <3 kg patients. We identified 30 patients (66.7% males) with a median age of 1.1 months (IQR, 0.3-5.4), and a median weight of 3.1 kg (IQR, 2.7-3.7). 5/30 patients had six redo interventions after a median of 3.9 months (IQR, 1.7-5.1). Overall, 27/36 procedures were interventional, including 6 aortic valvuloplasties, 6 balloon angioplasties, and 15 stenting procedures. The median arterial axillary angiographic diameter was 2.6 mm (IQR, 2.4-3). Access was right-sided in 23/36 (63.9%) procedures and obtained using 21G/2.5 cm bevel needles in 25/36 (69.4%) procedures. No hemodynamical change occurred after introducing spasmolytic drugs. The median fluoroscopy time was 26.1 min (IQR, 19.2-34.8). There were two self-resolving arterial dissections, one sub-occlusive arterial thrombosis (resolved with 6 weeks of enoxaparin), and one occlusive arterial thrombosis (resolved with alteplase thrombolysis and 6 weeks of enoxaparin). Median follow-up was 11.7 months (IQR, 8-17.5). Four patients with complex univentricular hearts died from non-procedural causes at a median of 40 days (IQR, 31-161) postoperative. Systematic approach for AAA is the key to success and unlocks the many potentials of trans-axillary pediatric cardiology interventions.

Acute Mesenteric Ischemia: Imaging Findings and Mimics

Acute mesenteric ischemia is a rapidly life-threatening condition in which the radiologist may play a crucial role in early diagnosis and thus improve patient outcomes. Acute mesenteric ischemia can occur from arterial embolism or thrombosis, venous occlusive, or nonocclusive etiologies. Key findings for acute arterial occlusion include hypoenhancing bowel, which is usually not thickened or dilated. Venous occlusion often results in a hyperenhancing, thickened, and dilated bowel. Nonocclusive mesenteric ischemia should be considered in the appropriate clinical context, when there is no vascular occlusion on CT, and when there is involvement of watershed regions without specific vascular territory abnormalities. Venous congestion and increased vascular permeability can result in mesenteric edema and ascites; however, it is not predictive of mesenteric ischemia severity. Pneumatosis alone may not indicate presence of nonviable bowel; however, pneumatosis with portal venous gas or pneumoperitoneum has high sensitivity for nonviable bowel. Clinical history and laboratory results can often help differentiate between acute mesenteric ischemia and its mimics, such as inflammatory bowel disease, enteritis, and radiation injury.

Thomas Wilson Meade. 21 January 1936—24 October 2022

Tom Meade made outstanding contributions to our understanding of the role of the haemostatic (clotting) system in the causation of cardiovascular disease by combining epidemiological approaches with rigorous standardization of laboratory methods. As director of the MRC Epidemiology and Medical Care Unit (EMCU) at Northwick Park Hospital he led major prospective studies to investigate the relationship between a range of haemostatic factors and cardiovascular disease outcomes. He also led several major randomized trials of interventions to reduce cardiovascular risk, notably the Thrombosis Prevention Trial. The EMCU also undertook several landmark studies on common and often neglected conditions to improve knowledge of the burden of ill health (for example from incontinence) and effective interventions, including for low back pain and stroke rehabilitation. In his later career he also set up and led a series of large case–control studies among myocardial infarction, stroke, deep vein thrombosis and pulmonary embolism cases, together with their matched controls using a primary care database, showing elevated risks of both arterial and venous thrombosis following respiratory infections. He had many major scientific leadership roles, including playing a significant role in guiding the UK Biobank at its inception and chairing the steering committee of the Heart Protection Study Collaborative Group.

Rare Case of Acute Renal Artery Thrombosis in Nephrotic Syndrome: The Unusual Presentations and Outcomes of Endovascular Manual Aspiration Thrombectomy

Renal artery thrombosis is a rare condition that requires early diagnosis and urgent intervention to prevent renal infarction and permanent renal damage. Possibility of renal artery thrombosis should be considered in patients with underlying hypercoagulable state presented with acute unremitting flank pain, nausea and vomiting. We report a case of a 35-year-old man with underlying nephrotic syndrome who presented with three days history of acute non-localized and non-resolving abdominal pain and vomiting. He was initially referred to general surgery for acute intestinal obstruction. Contrast-enhanced computed tomography (CECT) abdomen revealed acute left renal infarction secondary to total thrombotic occlusion of the left renal artery. The patient was treated with endovascular manual aspiration thrombectomy resulting in partial revascularization of left renal artery with restoration of renal function, complete resolution of symptom and good clinical outcomes. This case report serves as a reminder for physicians to include renal infarction in the differential diagnosis when evaluating a patient with acute abdomen, particularly in patient with hypercoagulable state. This case also aligns with other experiences demonstrating positive outcomes after endovascular thrombectomy, even in the presence of prolonged renal ischemia time of more than 72 hours.

Patient with relapsed minimal change disease presenting with bilateral lower extremity arterial thrombosis after COVID-19 infection: a case report

Patient with relapsed minimal change disease presenting with bilateral lower extremity arterial thrombosis after COVID-19 infection: a case report

Risk of arterial and venous thrombotic events among patients with cancer diagnosed with COVID-19: A real-world data analysis

AimThe risk of venous thromboembolism (VTE) and arterial thrombosis events (ATE) and potential corresponding risk factors were assessed in patients with cancer diagnosed with COVID-19. MethodsAdults with cancer treated in community health systems who were diagnosed with COVID-19 in 2020 were evaluated for absolute risk (risk) of ATE and VTE. Thrombotic events were ascertained in the 90-day window starting with COVID-19 diagnosis (index). ICD codes defined baseline comorbidities, COVID-19, and thrombotic events. Results7591 patients were included with median age of 67, 6% with cardiovascular disease (CVD), 4% with prior VTE, and 24% were hospitalized at index. Risk of ATE and VTE were 2.1% (95%CI: 1.8, 2.5) and 3.2% (95%CI: 2.8, 3.6), respectively. Patients with CVD had increased risk [ATE: 20.1% (95%CI: 16.7, 24.1); VTE: 4.9% (95%CI: 3.3, 7.3)] as did patients with prior VTE [ATE: 3.8% (95%CI: 2.2, 6.6; VTE: 20.5% (95%CI: 16.4, 25.3)] and patients hospitalized with ventilator support [(ATE: 5.7% (95%CI: 2.6, 11.8; VTE: 6.6% (95%CI: 3.2, 13.0)]. Incidence rates for ATE and VTE were 0.094 and 0.141 per person-year, respectively. ConclusionsThis study of cancer patients, conducted in a time period prior to vaccine availability, found patients with CVD, prior VTE, and with higher severity of COVID-19 were at increased risk for ATE and VTE. Identifying patients most at risk can help to target interventions.

Covered versus bare-metal stenting of the mesenteric arteries in patients with chronic mesenteric ischaemia (CoBaGI): a multicentre, patient-blinded and investigator-blinded, randomised controlled trial

Mesenteric artery stenting with a bare-metal stent is the current treatment for atherosclerotic chronic mesenteric ischaemia. Long-term patency of bare-metal stents is unsatisfactory due to in-stent intimal hyperplasia. Use of covered stents might improve long-term patency. We aimed to compare the patency of covered stents and bare-metal stents in patients with chronic mesenteric ischaemia. We conducted a multicentre, patient-blinded and investigator-blinded, randomised controlled trial including patients with chronic mesenteric ischaemia undergoing mesenteric artery stenting. Six centres in the Netherlands participated in this study, including two national chronic mesenteric ischaemia expert centres. Patients aged 18 years or older were eligible for inclusion when an endovascular mesenteric artery revascularisation was scheduled and a consensus diagnosis of chronic mesenteric ischaemia was made by a multidisciplinary team of gastroenterologists, interventional radiologists, and vascular surgeons. Exclusion criteria were stenosis length of 25 mm or greater, stenosis caused by median arcuate ligament syndrome or vasculitis, contraindication for CT angiography, or previous target vessel revascularisation. Digital 1:1 block randomisation with block sizes of four or six and stratification by inclusion centre was used to allocate patients to undergo stenting with bare-metal stents or covered stents at the start of the procedure. Patients, physicians performing follow-up, investigators, and radiologists were masked to treatment allocation. Interventionalists performing the procedure were not masked. The primary study outcome was the primary patency of covered stents and bare-metal stents at 24 months of follow-up, evaluated in the modified intention-to-treat population, in which stents with missing data for the outcome were excluded. Loss of primary patency was defined as the performance of a re-intervention to preserve patency, or 75% or greater luminal surface area reduction of the target vessel. CT angiography was performed at 6 months, 12 months, and 24 months post intervention to assess patency. The study is registered with ClinicalTrials.gov (NCT02428582) and is complete. Between April 6, 2015, and March 11, 2019, 158 eligible patients underwent mesenteric artery stenting procedures, of whom 94 patients (with 128 stents) provided consent and were included in the study. 47 patients (62 stents) were assigned to the covered stents group (median age 69·0 years [IQR 63·0-76·5], 28 [60%] female) and 47 patients (66 stents) were assigned to the bare-metal stents group (median age 70·0 years [63·5-76·5], 33 [70%] female). At 24 months, the primary patency of covered stents (42 [81%] of 52 stents) was superior to that of bare-metal stents (26 [49%] of 53; odds ratio [OR] 4·4 [95% CI 1·8-10·5]; p<0·0001). A procedure-related adverse event occurred in 17 (36%) of 47 patients in the covered stents group versus nine (19%) of 47 in the bare-metal stent group (OR 2·4 [95% CI 0·9-6·3]; p=0·065). Most adverse events were related to the access site, including haematoma (five [11%] in the covered stents group vs six [13%] in the bare-metal stents group), pseudoaneurysm (five [11%] vs two [4%]), radial artery thrombosis (one [2%] vs none), and intravascular closure device (none vs one [2%]). Six (13%) patients in the covered stent group versus one (2%) in the bare-metal stent group had procedure-related adverse events not related to the access site, including stent luxation (three [6%] vs none), major bleeding (two (4%) vs none), mesenteric artery perforation (one [2%] vs one [2%]), mesenteric artery dissection (one [2%] vs one [2%]), and death (one [2%] vs none). The findings of this trial support the use of covered stents for mesenteric artery stenting in patients with chronic mesenteric ischaemia. Atrium Maquet Getinge Group.

Platelets and Thrombotic Antiphospholipid Syndrome

Antiphospholipid antibody syndrome (APS) is an autoimmune disorder characterised by thrombosis and the presence of antiphospholipid antibodies (aPL): lupus anticoagulant and/or IgG/IgM anti-β2-glycoprotein I and anticardiolipin antibodies. APS carries significant morbidity for a relatively young patient population from recurrent thrombosis in any vascular bed (arterial, venous, or microvascular), often despite current standard of care, which is anticoagulation with vitamin K antagonists (VKA). Platelets have established roles in thrombosis at any site, and platelet hyperreactivity is clearly demonstrated in the pathophysiology of APS. Together with excess thrombin generation, platelet activation and aggregation are the common end result of all the pathophysiological pathways leading to thrombosis in APS. However, antiplatelet therapies play little role in APS, reserved as a possible option of low dose aspirin in addition to VKA in arterial or refractory thrombosis. This review outlines the current evidence and mechanisms for excessive platelet activation in APS, how it plays a central role in APS-related thrombosis, what evidence for antiplatelets is available in clinical outcomes studies, and potential future avenues to define how to target platelet hyperreactivity better with minimal impact on haemostasis.

Retraction: Superior Mesenteric Artery Thrombosis Following Severe COVID-19 Pneumonia.

[This retracts the article DOI: 10.7759/cureus.19954.].

P358 Impact of end-ileostomy versus ileal pouch-anal anastomosis on graft-survival following liver transplantation for primary sclerosing cholangitis

Abstract Background IBD-PSC patients may require both liver transplantation and ileoanal pouch (IPAA) construction. Recently, concerns have been raised regarding an increased rates of hepatic artery thrombosis, biliary strictures, and graft loss in individuals who underwent IPAA after liver transplantation compared to those who underwent end-ileostomy (EI). We hypothesized that graft survival was not negatively affected by IPAA compared with EI. Methods A prospectively maintained database from a large tertiary center was searched for patients meeting the inclusion criteria for liver transplantation, primary sclerosing cholangitis, ulcerative colitis, and total colectomy with IPAA or EI. Univariate analysis and Kaplan-Meier survival curves were calculated. Results Between January 1990 and December 2023, 55 patients met inclusion criteria. Of these, 46 (83.6%) underwent IPAA, and 9 (16.4%) underwent EI. The average age at colectomy (41.7 vs. 45.7 years; p=0.44), sex distribution (female: 26.1% vs. 22.2%, p=1), and MELD score before transplantation (20.3 vs. 14; p=0.06) were comparable between patients with IPAA and EI patients. The rates of re-transplantation (21.7% vs. 22.2%; p=1), hepatic artery thrombosis (8.7% vs. 0; p=1), episodes of acute rejection (32.6% vs. 44.4%; p=0.7), chronic rejection (4.3% vs. 11.1%; p=0.42), recurrence of primary sclerosing cholangitis (23.9% vs. 22.2%; p=1), and biliary complications (21.7% vs. 33.3%; p=0.43) were similar between the IPAA and EI groups, respectively. None of the EI patients developed parastomal varices. Survival analyses for time to re-transplantation (p=0.97), overall survival (p=0.3), and time to graft loss or mortality (p=0.73) were similar. Conclusion In contrast to a previous study, we observed similar rates of liver transplant graft loss, biliary complications, and recurrent PSC after IPAA compared to those after end-ileostomy. IPAA may be associated with an increased rate of hepatic artery thrombosis.

Genomic classification and outcomes of young patients with polycythemia vera and essential thrombocythemia according to the presence of splanchnic vein thrombosis and its chronology

To elucidate the role of splanchnic vein thrombosis (SVT) and genomic characteristics in prognosis and survival, we compared patients with polycythemia vera (PV) or essential thrombocythemia (ET) presenting SVT at diagnosis (n = 69, median age 43 years) or during follow-up (n = 21, median age 46 years) to a sex- and age-matched control group of PV/ET without SVT (n = 165, median age 48 years). The majority of patients presenting with SVT at diagnosis were classified as myeloproliferative neoplasm with heterozygous JAK2 mutation (87% of cases vs. 69% in PV/ET control group, p < 0.05), characterized by low JAK2 allele burden and no high-risk mutations. Despite this lower molecular complexity, patients presenting with SVT showed a higher risk of death (HR 3.0, 95% CI 1.5-6.0, p = 0.003) and lower event-free survival (HR 3.0, 95% CI 1.9–4.8, p < 0.001) than age- and sex-matched PV/ET controls. In patients presenting with SVT, molecular high-risk was associated with increased risk of venous re-thrombosis (HR 5.8, 95% CI 1.4–24.0, p = 0.01). Patients developing SVT during follow-up were more frequently allocated in molecular high-risk than those with SVT at diagnosis (52% versus 13%, p < 0.05). In the whole cohort of patients, molecular classification identified PV/ET patients at higher risk of disease progression whereas DNMT3A/TET2/ASXL1 mutations were associated with higher risk of arterial thrombosis. In conclusion, clinical and molecular characteristics are different in PV/ET patients with SVT, depending on whether it occurs at diagnosis or at follow-up. Molecular characterization by NGS is useful for assessing the risk of thrombosis and disease progression in young patients with PV/ET.

Synchronous Pulmonary Arterial and Pulmonary Venous Thrombosis in Pancreatic Cancer.

Synchronous Pulmonary Arterial and Pulmonary Venous Thrombosis in Pancreatic Cancer.

Predictors of Death in Comorbid Patients with Thrombotic Complications: a Single-Center Retrospective Cross- Sectional Study

INTRODUCTION. Despite the improvements and success in the management of thrombosis, the prognosis of thrombotic complications in comorbid patients remains extremely unfavorable. Understanding this problem suggests that it is rational to pay more attention to the prevention of thrombosis in order to avoid thrombotic complications in the first place, and there is an urgent need to improve the ability to predict the development of complications and, most importantly, death. Therefore, some inexpensive, but effective methods of risk assessment need to be developed and integrated in clinical practice. AIM OF STUDY. To assess which laboratory markers can be associated with higher probability of fatal outcome in patients with thrombotic complications. MATERIAL AND METHODS. The retrospective cross-sectional study included 283 patients who were admitted to the N.V. Sklifosovsky Research Institute for Emergency Medicine in 2021. Minimum age was 21 years, maximum age was 96 years, median age – 68 (59,0; 76,5) years. 161 (56,9 %) patients were males, 122 (43,1 %) – females. Group I included 226 patients with thrombotic complications; Group II included 57 (20,1 %) patients who died during hospitalization. The patients were diagnosed with the following thrombotic complications: pulmonary embolism (PE) was diagnosed in 28 (9.9 %), acute coronary syndrome with ST segment elevation in 38 (13.4 %), arterial thrombosis in 84 (29.7 %), venous thrombosis in 54 (19.1 %), thrombophlebitis in 22 (7.8 %), and systemic thromboembolism in 7 (2.5 %) patients. RESULTS. It was established that the decrease in the estimated glomerular filtration to the levels of stage 3 (and lower) chronic kidney disease (AUC — 0,881, sensitivity — 86.92 %, specificity — 85.71 %), hemoglobin level — to less than 120 g/L (AUC — 0,690, sensitivity — 77,21 %, specificity — 55,1 %), as well as hypoalbuminemia (AUC — 0,905, sensitivity — 78,89 %, specificity — 91,18 %) statistically significantly increased the likelihood of death by 19 (OR 19.276, 95 % CI [7,792–47.687], p &lt; 0.001), 4 (OR 4.158, 95 % CI [2.177–7.939], p &lt; 0.001), and 30 (OR 30,000, 95 % CI [9.93–90,610], p &lt; 0.001) times, respectively. The statistical analysis using the univariate logistic regression model revealed that such diseases as coronary artery disease (OR 8,6, 95 % CI [2,6–28,466], p &lt; 0.001), chronic heart failure (CHF) (OR 13,714, 95 % CI [4,784–39,313], p &lt; 0.001), atrial fibrillation (OR 3,455, 95 % CI [1,830–6,525], p &lt; 0.001), type 2 diabetes (OR 2.5, 95 % CI [1,286–4,858[, p = 0.007), postinfarction cardiosclerosis (OR 3,734, 95 % CI [1,953–7,142], p &lt; 0.001), and previous stroke (OR 3,319, 95 % CI [1,519–6,490], p = 0.002) made an independent contribution to death prediction. During the study, we calculated the patients’ serum albumin-to-creatinine ratio (sACR). ROC analysis revealed a cut-off point for sACR to be 0.33 g/mmol as having the best predictive ability of death (AUC — 0.920, 84.3 % sensitivity, 85.29 % specificity). It was established that sACR less than 0.33 g/mmol increased the probability of death by 26 times (OR 26.3806, 95 % CI [9.4573.57], p &lt; 0.001). CONCLUSION. Serum albumin-to-creatinine content ratio can be used as a predictor of fatal outcome in comorbid patients with thrombotic complications.

One thousand patients with essential thrombocythemia: the Mayo Clinic experience

We describe 1000 patients with essential thrombocythemia seen at the Mayo Clinic between 1967 and 2023: median age 58 years (18–90), females 63%, JAK2/CALR/MPL-mutated 62%/27%/3%, triple-negative (TN) 8%, extreme thrombocytosis (ExT; platelets ≥1000 × 109/L) 26%, leukocytosis (leukocyte count >11 × 109/L) 20%, and abnormal karyotype 6%. JAK2-mutated patients were older (median 71 years), and CALR mutated (52 years), and TN (50 years) younger (p < 0.01). Female gender clustered with TN (73%) and JAK2 (69%) vs. CALR/MPL (49%/47%) mutations (p < 0.01). ExT clustered with CALR (type-2 more than type-1) and TN and leukocytosis with JAK2 mutation (p < 0.01). In multivariable analysis, risk factors for overall survival were older age (p < 0.01), male gender (HR 1.8), absolute neutrophil count (ANC) ≥ 8 × 109/L (HR 1.6), absolute lymphocyte count (ALC) < 1.7 × 109/L (HR 1.5), hypertension (HR 1.7), and arterial thrombosis history (HR 1.7); for leukemia-free survival, ExT (HR 2.3) and abnormal karyotype (HR 3.1); for myelofibrosis-free survival, ANC ≥ 8 × 109/L (HR 2.3) and MPL mutation (HR 3.9); for arterial thrombosis-free survival, age ≥60 years (HR 1.9), male gender (HR 1.6), arterial thrombosis history (HR 1.7), hypertension (HR 1.7), and JAK2 mutation (HR 1.8); for venous thrombosis-free survival, male gender (HR 1.8) and venous thrombosis history (HR 3.0). Associations between ExT and leukemic transformation and between ANC and fibrotic progression were limited to JAK2-mutated cases. Aspirin therapy appeared to mitigate both arterial (HR 0.4) and venous (HR 0.4) thrombosis risk. HR-based risk models delineated patients with median survivals ranging from 10 years to not reached and 20-year leukemia/myelofibrosis incidences from 3%/21% to 12.8%/49%. The current study provides both novel and confirmatory observations of essential thrombocythemia.

One thousand patients with essential thrombocythemia: the Florence-CRIMM experience

We describe 1000 patients with essential thrombocythemia seen at the Center Research and Innovation of Myeloproliferative Neoplasms (CRIMM), Florence, Italy, between 1980 and 2023: median age 59 years (18–95), females 65%, JAK2/CALR/MPL-mutated 66%/19%/4%, triple-negative (TN) 11%. Extreme thrombocytosis (ExT, platelets ≥1000 × 109/L) in 16%, leukocytosis (leukocytes >11 × 109/L) in 16%, and at least one cardiovascular risk factor in 52% of cases. JAK2-mutated patients were older (median 62 years) and CALR-mutated and TN (53 years for both) younger (p < 0.001). Female gender clustered with TN (76%) and JAK2 (67%) vs CALR (46%) mutations (p < 0.001). ExT clustered with CALR (type-2 more than type-1), TN and MPL, and leukocytosis with JAK2 mutation (p < 0.001). In multivariable analysis, risk factors for arterial thrombosis-free survival were age ≥60 years (HR 2.0; p < 0.001) and JAK2 mutation (HR 1.3; p = 0.02) with borderline significance for male gender (p = 0.08) and cardiovascular risk factors (p = 0.08); for venous thrombosis-free survival, JAK2 mutation (HR 1.9; p = 0.03) with borderline significance for venous thrombosis history (p = 0.07); for overall survival, older age (p < 0.001), male gender (HR 1.9; p < 0.001), absolute neutrophil count (ANC) ≥ 8 × 109/L (HR 1.8; p = 0.01), absolute lymphocyte count (ALC) < 1.7 × 109/L (HR 1.2; p = 0.03); for myelofibrosis-free survival, CALR mutation (HR 2.7; p < 0.001, particularly for CALR type 1/1-like, HR 3.3) and MPL mutation (HR 3.9; p = 0.001); for leukemia-free survival, older age (p = 0.03). Cytoreductive therapy appeared to mitigate both venous (HR 0.3; p = 0.01) and arterial thrombosis (HR 4; p = 0.04); there was a trend for aspirin in preventing arterial thrombosis recurrence. The current study provides real-world observations in essential thrombocythemia, representing a valid source document for interpreting current literature and planning future studies.

Tranexamic Acid Administration During Liver Transplantation Is Not Associated With Lower Blood Loss or With Reduced Utilization of Red Blood Cell Transfusion.

Current clinical guidelines recommend antifibrinolytic treatment for liver transplantation to reduce blood loss and transfusion utilization. However, the clinical relevance of fibrinolysis during liver transplantation is questionable, a benefit of tranexamic acid (TXA) in this context is not supported by sufficient evidence, and adverse effects are also conceivable. Therefore, we tested the hypothesis that use of TXA is associated with reduced blood loss. We performed a retrospective cohort study on patients who underwent liver transplantation between 2004 and 2017 at Heidelberg University Hospital, Heidelberg, Germany. Univariable and multivariable linear regression analyses were used to determine the association between TXA administration and the primary end point intraoperative blood loss and the secondary end point intra- and postoperative red blood cell (RBC) transfusions. For further secondary outcome analyses, the time to the first occurrence of a composite end point of hepatic artery thrombosis, portal vein thrombosis, and thrombosis of the inferior vena cava were analyzed using a univariable and multivariable Cox proportional hazards model. Data from 779 transplantations were included in the final analysis. The median intraoperative blood loss was 3000 mL (1600-5500 mL). Intraoperative TXA administration occurred in 262 patients (33.6%) with an average dose of 1.4 ± 0.7 g and was not associated with intraoperative blood loss (regression coefficient B, -0.020 [-0.051 to 0.012], P = .226) or any of the secondary end points (intraoperative RBC transfusion; regression coefficient B, 0.023 [-0.006 to 0.053], P = .116), postoperative RBC transfusion (regression coefficient B, 0.007 [-0.032 to 0.046], P = .717), and occurrence of thrombosis (hazard ratio [HR], 1.110 [0.903-1.365], P = .321). Our data do not support the use of TXA during liver transplantation. Physicians should exercise caution and consider individual factors when deciding whether or not to administer TXA.

A comparative study of altered hemodynamics in iliac vein compression syndrome.

Introduction: Iliac vein compression syndrome (IVCS) is present in over 20% of the population and is associated with left leg pain, swelling, and thrombosis. IVCS symptoms are thought to be induced by altered pelvic hemodynamics, however, there currently exists a knowledge gap on the hemodynamic differences between IVCS and healthy patients. To elucidate those differences, we carried out a patient-specific, computational modeling comparative study. Methods: Computed tomography and ultrasound velocity and area data were used to build and validate computational models for a cohort of IVCS (N = 4, Subject group) and control (N = 4, Control group) patients. Flow, cross-sectional area, and shear rate were compared between the right common iliac vein (RCIV) and left common iliac vein (LCIV) for each group and between the Subject and Control groups for the same vessel. Results: For the IVCS patients, LCIV mean shear rate was higher than RCIV mean shear rate (550 ± 103s-1 vs. 113 ± 48s-1, p = 0.0009). Furthermore, LCIV mean shear rate was higher in the Subject group than in the Control group (550 ± 103s-1 vs. 75 ± 37s-1, p = 0.0001). Lastly, the LCIV/RCIV shear rate ratio was 4.6 times greater in the Subject group than in the Control group (6.56 ± 0.9 vs. 1.43 ± 0.6, p = 0.00008). Discussion: Our analyses revealed that IVCS patients have elevated shear rates which may explain a higher thrombosis risk and suggest that their thrombus initiation process may share aspects of arterial thrombosis. We have identified hemodynamic metrics that revealed profound differences between IVCS patients and Controls, and between RCIV and LCIV in the IVCS patients. Based on these metrics, we propose that non-invasive measurement of shear rate may aid with stratification of patients with moderate compression in which treatment is highly variable. More investigation is needed to assess the prognostic value of shear rate and shear rate ratio as clinical metrics and to understand the mechanisms of thrombus formation in IVCS patients.