Venous Thrombotic Complications Research Articles

Early Cold Stored Platelet Transfusion Following Severe Injury: A Randomized Clinical Trial.

To determine the feasibility, efficacy, and safety of early cold stored platelet transfusion compared to standard care resuscitation in patients with hemorrhagic shock. Data demonstrating the safety and efficacy of early cold stored platelet transfusion are lacking following severe injury. A phase 2, multicenter, randomized, open label, clinical trial was performed at five U.S. trauma centers. Injured patients at risk of large volume blood transfusion and the need for hemorrhage control procedures were enrolled and randomized. The intervention was the early transfusion of a single apheresis cold stored platelet unit, stored for up to 14 days vs. standard care resuscitation. The primary outcome was feasibility and the principal clinical outcome for efficacy and safety was 24-hour mortality. Mortality at 24 hours was 5.9% in patients who were randomized to early cold stored platelet transfusion compared to 10.2% in the standard care arm (difference, -4.3%; 95% CI, -12.8% to 3.5%; P=0.26). No significant differences were found for any of the prespecified ancillary outcomes. Rates of arterial and/or venous thromboembolism and adverse events did not differ across treatment groups. In severely injured patients, early cold stored platelet transfusion is feasible, safe and did not result in a significant lower rate of 24-hour mortality. Early cold stored platelet transfusion did not result in a higher incidence of arterial and/or venous thrombotic complications or adverse events. The storage age of the cold stored platelet product was not associated with significant outcome differences.

Features of various options for anticoagulant therapy for a new coronavirus infection against the background of obesity

BACKGROUND: When treating a new coronavirus infection, the prevention of venous thromboembolic complications in obese patients is of particular importance.
 AIM: To analyze various options for anticoagulant therapy in obese and non-obese patients in the treatment of a new coronavirus infection.
 MATERIAL AND METHODS: The patients were divided into two groups: the first group — obese patients — 151 (40.8%) people [average age 63 (56–69) years], the second group without obesity — 219 (59.2%) people [average age 63 (51.5–71.0) years], p=0.998. According to the prescribed anticoagulant and the presence of obesity, patients were divided into subgroups: subgroup 1 — non-obese + low-molecular-weight heparin (n=114), subgroup 2 — non-obese + unfractionated heparin (n=58), subgroup 3 — obesity + low-molecular-weight heparin (n=76), subgroup 4 — obesity + unfractionated heparin (n=66). Venous thrombotic complications and bleeding rates were assessed. Analysis of qualitative indicators was performed using Pearson χ2 and Fisher tests. The distribution of quantitative indicators was assessed using the Kolmogorov–Smirnov and Shapiro–Wilk tests (p 0.05). Due to the non-normal distribution of indicators, mean values were presented as median (Me) and interquartile range (Q1–Q3), and analysis was carried out using Wilcoxon, Mann–Whitney and Kruskal–Wallis tests.
 RESULTS: In nonobese patients, a comparable incidence of deep vein thrombosis was noted on low molecular weight heparin and unfractionated heparin — 1 (0.9%) case versus 3 (5.2%) cases (p=0.102). At the same time, there was a statistically significant difference in the frequency of pulmonary embolism without a source according to autopsy data — 2 (1.8%) versus 4 (6.9%) cases (p=0.004). In obese patients receiving unfractionated heparin, the incidence of this complication was higher and amounted to 9 (13.6%), and in patients receiving low molecular weight heparin — 2 (2.6%) cases (p=0.004). A higher incidence of bleeding was observed in patients with obesity compared to patients without it (10.6 vs 4.7% of cases, p=0.045). When analyzing hemorrhagic complications, it was found that the incidence of major and significant bleeding was higher in patients receiving unfractionated heparin rather than low molecular weight heparin (16.7 vs 5.3% of cases, p 0.001).
 CONCLUSION: The use of low molecular weight heparin in obese patients with new coronavirus infection was associated with a low incidence of pulmonary embolism and bleeding compared with patients receiving unfractionated heparin.

Assessing the Feasibility of Thromboprophylaxis with Apixaban in JAK2-Positive Myeloproliferative Neoplasm Patients: The Airport-MPN Trial

Introduction: Thrombosis is a major cause of mortality and morbidity in myeloproliferative neoplasms (MPN). In patients classified as high-risk for thrombosis, current guidelines recommend the use of cytoreduction therapy and low-dose aspirin (e.g., ASA 81 mg daily) to decrease the risk of thrombotic events. However, use of low-dose aspirin is based on limited evidence and is associated with a significant failure rate. Thromboprophylaxis with low-dose direct oral anticoagulants (e.g., apixaban 2.5 mg BID) is an appealing option in MPN, specifically when patients carry the JAK2 mutation, based on the pathophysiology of thrombus formation associated with this driver mutation. In other populations, thromboprophylaxis with a low-dose direct oral anticoagulant has been associated with a reduced risk of arterial and venous thrombotic complications, when compared to low-dose aspirin. Hence, we conducted a pilot trial to assess the feasibility of conducting a randomized controlled trial evaluating the efficacy and safety of apixaban (2.5 mg BID) compared to aspirin (81 mg daily) to prevent thrombotic complications in patients with JAK2-positive MPN (JAK2MPN). Methods: This was a multi-centre, prospective, open-label, blinded endpoint pilot trial (NCT04243122), conducted in three Canadian centers (Ottawa, Calgary, Sherbrooke). Adult patients with a confirmed diagnosis of polycythemia vera, JAK2-positive essential thrombocythemia or JAK2-positive pre-fibrotic myelofibrosis (per local clinical definitions) requiring low-dose aspirin for thromboprophylaxis were eligible. Both patients with an incident diagnosis of JAK2MPN (defined as diagnosed within 1 year) and patients with prevalent disease were targeted for recruitment. Exclusion criteria included a contraindication to thromboprophylaxis or the need for a specific anticoagulant or non-aspirin anti-platelet agent. Patients with a prior history of venous thromboembolism were eligible if they had completed a minimum of 6 months of anticoagulation therapy. Participants were randomized 1:1 to receive apixaban 2.5mg BID or aspirin 81mg daily, along with cytoreductive therapy (per guidelines). The study treatment duration was 6 months. Follow-up occurred at 3, 6 and 7 months after allocation of the study medication. The primary study outcome for feasibility was the monthly recruitment rate per study site over a 6-month follow-up period. Secondary outcomes included rates of thrombotic and bleeding complications. The total estimated sample size was 44 participants (22 per arm). Due to the COVID-19 pandemic, not all sites were able to start recruitment at the same time and the total recruitment period spanned over 24 months. Results: During this 24-month recruitment period, 93 JAK2MPN patients were screened for eligibility. Of these, 69 were eligible and 64% of eligible patients consented to participate. We therefore recruited 44 participants, for a recruitment rate of 0.8 patient per centre per month. Baseline characteristics of participants are presented in Table 1. A total of 29 prevalent cases and 15 incident cases were included. Secondary efficacy, safety, and feasibility outcomes (relating to thrombotic events, bleeding complications, and study compliance) will be available at the ASH Meeting, since all participants will have completed the 6-month treatment duration by October 2023. Discussion: Despite the challenges of the COVID-19 pandemic, we have recruited 100% of our target population. Given the chronicity of MPN, most outpatient clinics functioned remotely during the pandemic, precluding recruitment. Nevertheless, by adapting to the realities of the pandemic, we achieved our recruitment target demonstrating feasibility of a larger trial. The strategies adopted during this pilot trial to recruit participants, such as active screening of clinic lists for potential participants and direct communication with MPN specialists, will be applied to our larger scale trial. Conclusion: This pilot trial demonstrated the feasibility of conducting a large-scale trial evaluating the superiority of apixaban over aspirin for the thromboprophylaxis of JAK2MPN patients. As JAK2MPN are rare diseases, we have partnered with counterparts in France to conduct an international study on the efficacy and safety of direct oral anticoagulant thromboprophylaxis in JAK2MPN patients.

Validation of Townes As Mice As a Model of Chronic Kidney Disease and Venous Thrombosis Associated with Sickle Cell Trait

Individuals with sickle cell trait (SCT) are heterozygous carriers of the sickle beta-globin gene. Systematic analyses of large cohort studies over the past decade have established that SCT is a risk factor for a limited number of complications, most notably chronic kidney disease (CKD) and venous thrombosis (VT). SCT red blood cells (RBCs) can undergo sickling, although the degree and duration of hypoxia required to produce sickling are much greater than in sickle cell disease due to the lower intra-erythrocyte sickle hemoglobin beta (HbS) concentration of 25-45%. Hypoxia-mediated HbS polymerization can be enhanced by cellular dehydration, hyperosmolarity and/or acidosis that may be encountered in the renal inner medulla. Furthermore, prolonged exposure of SCT RBCs to profound hypoxia, such as in the nidus of a venous clot, will also result in sickling. The objective of this study was to determine if Townes AS mice manifest kidney dysfunction analogous to their SCT human counterparts. Furthermore, we evaluated whether VT was more pronounced in a well-described model of inferior vena cava (IVC) stasis. We used humanized male sickle cell trait (AS) and age-matched genetic control (AA) mice (n=7-16). Analysis of urinary renal biomarkers (albuminuria, proteinuria, kidney injury marker 1 (KIM-1), osmolality) and kidney function (transcutaneous measurement of glomerular filtration rate (GFR)) were conducted at 4-week intervals from 8 to 40 weeks of age. VT was induced by complete occlusion of the IVC in AA and AS mice. Sickling of RBCs was determined by histological and electron microscopy analysis of the IVC clot. Senicapoc, an oral Gardos channel inhibitor, was administered twice daily (20mg/kg, bid) for 2 weeks to prevent AS RBC dehydration and subsequent sickling. Human HbS accounts for 30.1% of total Hb expression in AS mice. Consistent with human SCT, peripheral blood counts did not differ from AA controls. Basal plasma thrombin-antithrombin complex levels were also not different between AA and AS mice. We performed a longitudinal study of renal structure and function in AA and AS mice over 40 weeks. At 8 weeks of age, AS mice exhibited no differences in any parameter compared to AA controls. However, AS mice subsequently developed albuminuria and a moderate but statistically significant increase in GFR (Figure 1). At 36 and 40 weeks of age, we observed progressive loss of kidney function demonstrated by statistically significant decreased GFR accompanied by a significant increase in albuminuria in AS mice (Figure 1). Over time, proteinuria gradually increased in AS mice, and had doubled by 40 weeks of age compared to AA controls (4.6 ±1.1 vs. 2.3 ±0.4 mg/24h, p<0.05). Increased levels of urinary KIM-1, a marker of tubular damage, were observed in AS mice throughout the duration of the study, with the highest levels at 16 weeks (228.3 ± 32.6 pg/24h vs. 53.8 ± 8.5 pg/24h, respectively, p˂0.05). Urine osmolality was not different at 8 weeks of age, but progressively declined in AS mice with statistically significant changes vs. controls starting at 24 weeks until the end of study (1946 ±63 vs. 2672 ±135 mOsm/kg at 40 weeks, p=0.002). Histologic analysis confirmed glomerular injury (congestion, glomerulosclerosis) and tubular injury (medullary congestion, interstitial fibrosis) in 40 week old AS mice. Following 24 hours of IVC stasis, thrombus weight was significantly increased (p<0.01) in AS mice (mean±SEM; 29.0 mg +/- 1.7; n=8) compared to AA controls (20.0 mg ± 1.7; n=7). Histologic and electron microscopic evaluation demonstrated that severe hypoxia (pO 2 ≈ 10 mm Hg) present in the nidus of venous thrombi was associated with extensive sickling of RBCs in AS mice. To determine if the enhancement of VT observed in AS mice was mediated by RBC sickling, mice were pretreated with Senicapoc or vehicle. Compared to vehicle-treated AS mice (27.3 mg ± 2.2 n=9) pre-treatment with Senicapoc significantly reduced (p<0.05) clot weight (18.1mg ± 1.1; n=7) to that observed in untreated AA controls. In aggregate, our data demonstrate that Townes AS murine nephropathy closely mimics the renal abnormalities (impaired urinary concentration and albuminuria with later onset loss of GFR) described in humans with SCT. Furthermore, we have established a mouse model of the venous thrombotic complications associated with SCT and have demonstrated that hypoxia-induced sickling of RBCs may contribute to enhanced VT observed in AS mice.

Cardiovascular risk in a contemporary cohort of patients with myeloproliferative neoplasms’

BackgroundMyeloproliferative neoplasms (MPNs) are a group of disorders of clonal haemopoiesis associated with an inherent risk of arterial and venous thrombotic complications. The prevalence of thrombotic complications and the impact of cardiovascular risk factors (CVRFs) in contemporary patient cohorts within the current era of MPN treatments have not been completely defined. ObjectivesWe aim to characterise the cardiovascular risk of patients with MPN by identifying the prevalence of CVRFs and describing the pattern of thrombotic events. We also aim to utilise the QRISK3 algorithm, which is a validated model used to estimate an individual's risk of developing cardiovascular disease, to further phenotype this cohort of patients. MethodsWe perform a retrospective analysis on a single-centre cohort of 438 patients with MPN. ResultsMPN patients continue to carry a high burden of vascular morbidity with a prevalence of arterial thrombotic events in 15.8 % (69/438) and venous thrombotic events in 13.2 % (58/438) of the cohort. The novel use of the QRISK3 algorithm, which showed a mean score of 13.7 % across the MPN population, provides further evidence to suggest an increased cardiovascular risk in MPN patients. ConclusionWith an increased risk of cardiovascular disease in patients with MPN, we propose an integrated approach between primary and specialised healthcare services using risk stratification tools such as QRISK3, which will allow aggressive optimisation of CVRFs to prevent thrombosis and reduce the overall morbidity and mortality in patients with MPN.

Выбор метода профилактики тромботических осложнений у пациентов с хирургическими заболеваниями желудка высокого риска

INTRODUCTION: Despite the significant advances in the prevention and treatment of venous thromboembolic complications (VTEC), pulmonary embolism (PE) remains the most common preventable cause of hospital postoperative mortality. One of the causes of thrombosis is surgical operations, especially laparoscopic, associated with the activation of the hemostasis system. Aim: The choice of a prevention method of thrombotic complications in comorbid patients with signs of varicose veins of the lower extremities requiring laparoscopic surgical treatment of benign gastric diseases (BGD). MATERIALS AND METHODS: The study is based on a treatment analysis of 128 patients with BGD in combination with a high comorbid background. The treatment of these patients was divided into several stages, which included both vascular interventions for the prevention of VTEC and a laparoscopic stage aimed at treating the underlying disease. The patients were divided into 3 groups comparable in gender and age. The first group, consisting of 45 people, VTEC prevention was carried out using a standard conservative technique (anticoagulant therapy in combination with mechanical prophylaxis). The second group included 43 patients who underwent both standard conservative therapy and open surgery aimed at correcting venous insufficiency in the great saphenous vein system. The third group is represented by 40 patients who, in addition to the standard conservative prevention of VTEC, underwent a combined surgical treatment (crossectomy and endovenous laser coagulation (EVLC) of the trunk of the great saphenous vein by retrograde method). All patients underwent coagulogram analysis and ultrasound triplex scanning of the veins of the lower extremities at each stage of the treatment. RESULTS: In the first group of patients, the largest number of thrombotic complications was noted — 24.4%, in the second group their number was 14%, while in the third group, thrombotic complications were detected in only 7.5% of patients. In the second and third groups, there was no development of PE, both after the first operation and after the main laparoscopic stage of treatment. In the first group, on the contrary, 2 episodes of PE (4.4%) were noted after the main surgical treatment. In turn, the standard anticoagulant therapy carried out in all three groups led to the development of both small and large hemorrhagic complications. At the same time, it should be noted that their frequency was comparable in all three groups, and their number did not exceed the number of such complications based on literature data. CONCLUSION: Carrying out active operative prevention of thrombotic complications significantly reduces their frequency in comorbid patients with signs of varicose veins of the lower extremities, thereby allowing to improve the result of the treatment. Considering that laparoscopic surgical interventions on the stomach increase the risk of developing VTEC in comorbid patients, according to our data, performing EVLC in combination with crossectomy, as the first stage of prophylaxis, prevents the development of PE and reduces the risk of venous thrombotic complications by 16.9%.

Scary Acute Left Main Coronary Artery Thrombus as an Initial Presentation of a Hereditary Thrombophilia: When to Go Out of Routine?

Patients with either hereditary or acquired thrombophilia can present with arterial and venous thrombotic complications. However, it is unclear to whom the thrombophilia panel should be assessed, particularly in patients presenting with a common cardiovascular risk factor and acute coronary thrombus. Herein, we presented the management of an active smoker female patient who presented to our emergency room with inferior acute ST-segment elevation myocardial infarction, and hereditary thrombophilia has been diagnosed due to the presence of substantial left main coronary artery thrombus.

Rarely Seen Vascular Complication After Treatment in a Covid-19 Patient: Renal Artery Thrombosis

Although respiratory symptoms are dominant in COVID-19 (coronavirus disease-2019) infection, extrapulmonary systemic findings may be seen in the extremely sick group. Studies are showing that patients have a high incidence of arterial and venous thrombotic complications in COVID-19. Acute renal artery thrombosis represents a rarer type of arterial thromboembolism, even among the thrombotic complications of COVID-19 disease. Such complications appear especially during the active phase of the infection. In this article, a rare case of renal artery thrombus in a discharged patient after treatment for COVID-19 pneumonia despite prophylactic antithrombotic treatment is offered.

Diagnosis, management and prevention of thrombotic complications in microsurgical breast reconstruction: a review of the literature

Autologous free tissue transfer is a safe and effective option for breast reconstruction. It is an increasingly utilized technique with well-demonstrated improved patient satisfaction and quality of life. Microvascular thrombosis is a rare but significant complication of microsurgical breast reconstruction, often resulting in flap failure. Proper diagnosis and timely management of this complication are essential to free flap salvage. While microvascular thrombosis poses a threat to flap survival, several methods may be employed to mitigate its more devastating effects. Here, we present a comprehensive review of arterial and venous thrombotic complications in both the intraoperative and postoperative settings. We discuss preoperative risk assessment, methods for flap monitoring, and operative and medical management of thrombotic complications. We present an updated algorithm for the intraoperative management of microvascular thrombosis adapted to reflect the most recent literature and our novel algorithm for the postoperative management of microvascular thrombosis.

Эффективность антикоагулянтов в профилактике тромбоэмболических осложнений у пациентов с сердечно-сосудистой патологией, переболевших COVID-19

At the moment, there is a lot of data demonstrating the effectiveness of anticoagulants in the acute period of COVID-19; as for their effectiveness in patients after discharge, there are relatively few data, especially in patients with concomitant cardiological pathology. The purpose — is to evaluate the relationship of taking anticoagulants, within one month after discharge, with the development of cardiovascular events and deaths in patients with cardiovascular pathology during 3 months of follow-up. Material and methods. A retrospective, cohort, observational study of 317 patients who had COVID-19 and had a history (before COVID-19) of cardiovascular pathology was conducted. Results. Within three months after discharge from the hospital, 15 (4.73%) cardiovascular events were registered. The frequency of arterial thrombotic complications was 3.79% (n = 12), venous thrombotic complications 0.95% (n = 3). All cardiovascular events were reported in patients not using anticoagulants (n = 15; 6.28%), p = 0.026. When analyzing concomitant cardiovascular pathology in patients with registered events, it was revealed that the incidence of atrial fibrillation and ischemic stroke in their anamnesis was statistically significantly higher (33.33 and 40%), relative to the comparison group (10.03 and 7.9%; p = 0.002; p = 0.001, respectively). Conclusions. The use of anticoagulants in patients with cardiovascular pathology during treatment in a COVID hospital and within one month after discharge was associated with a significant decrease in thromboembolic events over 3 months of follow-up. Predictors of thromboembolic events in patients with cardiovascular pathology and those who have had COVID-19 are: senior age; atrial fibrillation and ischemic stroke in the anamnesis.

D-DIMER AS A MARKER OF HYPERCOAGULATION AND VENOUS THROMBOEMBOLIC DISEASE COMPLICATIONS

Quantitative determination of D-dimer concentration is the most reliable test to confirm blood clotting process activation as a result of tissue damage or development of diseases causing venous thrombosis or thromboembolism (VTE). The increased D-dimer level is an indicator of the coagulation system hyperactivation, and its concentration above threshold level is a marker of venous thrombotic complications. This article describes several D-dimer assay methods and the laboratory application of these methods

Heparin-Induced Venous and Arterial Thromboembolic Disease: Case Report and Literature Data

HIT results from the development of F4P-specific IgG antibodies. It usually begins 5-14 days after initiation of heparin therapy with a drop in platelet count of more than 50% from a pretreatment value, associated in one in two patients with venous and/or arterial thrombotic complications. This is a rarer problem that occurs in 1-5% with UFH and 0.1-0.2% with LMWH and requires prompt management. Forty-seven-year-old patient, alcoholic at 3g/d for 10 years, hospitalized for APO complicating an ethylic CMD, LVEF 33% in tachy ACFA at 150batt/min. The patient was treated with furosemide and risordan. Injectable Cordarone was administered and LMWH in curative dose for 7 days. The evolution was marked by a resumption of sinus rhythm, disappearance of crepitus rales, after one week, but an installation of thrombenia at 22000/mm3, a pulmonary embolism, left popliteal DVT and thrombosis of the iliac and then left femoral arteries. The diagnosis of HIT type 2 was confirmed by the presence of anti-PF4 antibodies in association with the platelet activation test. LMWH was stopped, the patient received Fondaparinux 7.5mg/d until platelets normalized after 10 days and then substituted with rivaroxaban for 6 months after clinical improvement and normalization of arteriovenous Doppler ultrasound and chest angioscan.

Inpatient Burden, Characteristics and Outcomes Associated with Venous Thrombotic Complications Among Patients with Paroxysmal Nocturnal Hemoglobinuria

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, clonal hematopoietic stem cell disease caused by mutations in an X-linked gene called phosphatidylinositol glycan class A (PIG-A). Venous thromboembolism (VTE) is known to be a leading cause of death in patients with PNH and is considered to be a clinical emergency, warranting treatment with eculizumab and therapeutic anticoagulation. Although several studies have analyzed the overall disease burden and predictors of outcomes associated with VTE in patients with PNH, data on inpatient burden and outcomes are scarce. We sought to investigate the inpatient burden, characteristics and overall outcomes associated with VTE-related complications among patients with PNH using a large nation-wide database. Methods: The current nation-wide retrospective analysis was conducted using the National Inpatient Sample (NIS), which includes administrative and demographic data from a 20% sample of inpatient hospitalizations in the United States. We interrogated the NIS for admissions among patients with PNH from 2016-2019 using appropriate ICD-10 diagnosis codes. Admissions with known hypercoagulable conditions such as anti-phospholipid antibody syndrome, factor V Leiden mutation, prothrombin gene mutation, protein C and S deficiency, etc. were excluded. Hospitalizations with PNH were further assessed for VTE-related complications using appropriate ICD-10 codes and data on baseline characteristics and inpatient outcomes were collected and analyzed. Chi-square test was used for categorical data and Student's t-test was used for continuous variables. A p-value < 0.05 was considered statistically significant. SAS version 9.4 (SAS Institute Inc.) was used for statistical analysis. Results: A total of 3,600 hospitalizations were included for analysis, out of which, 345 (9.6%) were associated with VTE. Lower extremity deep vein thrombosis (DVT) was noted to be the most common (100/345, 29%) followed by hepatic vein thrombosis/ Budd Chiari syndrome (80/345, 23.2%), portal vein thrombosis (70/345, 20.3%), pulmonary embolism (60/345, 17.4%), upper extremity DVT (60/345, 17.4%), non-specific VTE (15/345, 4.3%) and renal vein thrombosis (5/345, 1.5%). Table 1 shows baseline characteristics and co-morbidities in hospitalizations associated with and without VTE. Patients in the VTE group were significantly younger (47.3±17.4 vs 50.4±22.1, p=0.01) and had a higher prevalence of co-morbid obesity (27.5% vs 10.1%, <0.001) and chronic liver disease (23.2% vs 8.3%, p<0.001). The prevalence of myelodysplastic syndrome (5.8% vs 11.4%, p=0.002) and aplastic anemia (20.3% vs 27.2%, p=0.006) was noted to be significantly lower in the VTE group, while no difference was noted with iron deficiency anemia (4.3% vs 4.1%, p=0.85) and primary myelofibrosis (2.9% vs 1.5%, p=0.06). No patients with acute myeloid leukemia could be captured in our cohort in either of the groups. Overall, there was no difference in all-cause inpatient mortality between groups with and without VTE (1.4% vs 2.5%, p=0.24), however, hospitalizations with VTE-related complications were associated with longer average length of stay (10 days vs 6.3 days, p<0.001), higher average cost of hospitalizations ($178,143 vs $100,547, p<0.001) and lower rate of discharge to home (66.7% vs 72.5%, p=0.02). Conclusions: Overall, 10% of the hospitalizations in our analysis were associated with VTE, out of which, lower extremity DVT, hepatic and portal vein thrombosis were the most common sites (approximately 75% of the VTE burden). Patients with VTE were younger and had a higher prevalence of co-morbid obesity and chronic liver disease. Prevalence of myelodysplastic syndrome and aplastic anemia was noted to be significantly lower in the VTE group, however, further prospective clinical data are needed to analyze the impact of these diagnoses on overall risk of VTE in patients with PNH. Although VTE did not appear to increase all-cause inpatient mortality; associated increase in average length of stay, average cost of hospitalization and decreased likelihood of discharge to home were noted. Concerted efforts to strengthen and enhance care for patients with PNH in the ambulatory setting are needed to prevent inpatient hospitalizations with VTE and reduce associated healthcare burden and costs. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

COVID-19 Thrombotic Complications and Therapeutic Strategies.

Shortly after the emergence of coronavirus disease 2019 (COVID-19) in late 2019, clinicians rapidly recognized an apparent association between the disease and both arterial and venous thrombotic complications, which was confirmed in epidemiologic studies. Based on these data, hospitals empirically developed and implemented protocols with different strategies for anticoagulation of hospitalized COVID-19 patients. Subsequent randomized controlled trials (RCTs) clarified the role of anticoagulation in patients hospitalized with COVID-19 and recently discharged from the hospital. In this review, we discuss the epidemiology and pathophysiology of thrombosis in patients with COVID-19, observational comparative effectiveness analyses that provided hints of a benefit from anticoagulation, and finally the RCTs that established which patients with COVID-19 benefit from treatment-dose anticoagulation. These RCTs have demonstrated that hospitalized, noncritically ill patients with COVID-19 benefit from treatment-dose anticoagulation, but patients who are hospitalized and critically ill, discharged from the hospital, or not hospitalized do not benefit.

Abstract 445: Natural history of coagulopathy in patients with cancer infected with COVID19: A real-world data (RWD) analysis

Abstract Background and Objective: Studies of hospitalized patients (pts) with COVID19 indicate that arterial or venous thrombotic complications occur in up to half of pts. Risk of these severe complications in pts with cancer is unknown. We estimated the incidence of arterial thrombosis (AT) and venous thromboembolism (VT) using RWD from pts with active or history of cancer with COVID19. Methods: Adult pts with cancer receiving treatment in community health systems, with COVID19 identified via ICD code or lab confirmation in 2020, were reviewed for incident AT and VT in a 90 day window following COVID19 diagnosis (index). AT was acute myocardial infarction (MI) or acute ischemic or embolic stroke (S). VT was acute deep venous thrombosis (DVT) or acute pulmonary embolism (PE). Medication use (anticoagulant, antiplatelet, statin) and comorbidities were assessed 6 months and 1 year prior to index, respectively. Results: Median age of 7,591 pts with cancer and COVID19 was 67 years and median follow up was 90 days. 32% of pts were hospitalized within 14 days, 2% received ventilator support, 6% had cardiovascular disease (CVD) and 1% had prior VT. Absolute risk of VT was significantly higher than AT (3% vs. 2%, chi square p= &amp;lt; 0.001), with 161 pts experiencing AT [81 (1%) MI; 80 (1%) S] and 240 pts experiencing VT [99 (1%) DVT; 158 (2%) PE]. This trend held across most subgroups (Table 1). The incidence rate per person-year was 0.094 for AT (0.047 MI, 0.046 S) and 0.141 for VT (0.058 DVT, 0.092 PE). CoxPH models did not show age, sex, comorbidities or medication use as significantly associated with higher probability of AT or VT. Conclusions: RWD showed pts with cancer and COVID19 were at higher risk for VT than AT. Pts who received ventilator support, or had prior VT or prior CVD had highest risk for these events. Severity of these outcomes emphasizes the need for risk reducing interventions. Acknowledgement of Reagan-Udall Foundation and Friends of Cancer Research COVID19 Evidence Accelerator. Table 1. Incidence of arterial and venous events stratified by baseline characteristics at COVID-19 diagnosis among n= 7,591 patients with cancer and infected with COVID19 Absolute Risk, N(%) Incidence Rate Total, N Arterial thrombosis Venous thromboembolism Chi square p-value Arterial thrombosis Venous thromboembolism p-value All 7,591 160 (2.1) 240 (3.2) &amp;lt;0.001 0.0935 0.1414 &amp;lt;0.001 Age 18-44 669 10 (1.5) 10 (1.5) 0.008 0.012 0.061 0.020 45-54 922 4 (0.4) 18 (2) 0.018 0.08 0.003 55-64 1751 26 (1.5) 54 (3.1) 0.062 0.129 0.001 65-74 2054 49 (2.4) 78 (3.8) 0.104 0.165 0.008 75-84 1506 55 (3.7) 60 (4) 0.169 0.184 0.557 85+ 689 24 (3.5) 20 (2.9) 0.18 0.15 0.542 Sex Female 4142 75 (1.8) 126 (3) 0.338 0.078 0.131 0.000 Male 3449 85 (2.5) 114 (3.3) 0.11 0.148 0.030 Race Black 1437 31 (2.2) 61 (4.2) 0.215 0.095 0.187 0.001 White 5054 113 (2.2) 157 (3.1) 0.098 0.137 0.003 Other/Unknown 1100 16 (1.5) 22 (2) 0.061 0.084 0.724 Severity of infection at diagnosis Not hospitalized 5815 78 (1.3) 141 (2.4) 0.0676 0.06 0.105 &amp;lt;0.001 Hospitalized, no ventilator support 1710 76 (4.4) 92 (5.4) 0.21 0.261 0.143 Hospitalized with ventilator support 106 6 (9.1) 7 (10.6) 0.326 0.326 0.965 Existing Cardiovascular disease Yes 467 94 (20.2) 23 (4.9) &amp;lt;0.001 0.105 0.06 &amp;lt;0.001 No 7124 66 (0.9) 217 (3) 0.21 0.261 &amp;lt;0.001 And baseline anticoagulant use 122 27 (22.1) 9 (7.4) &amp;lt;0.001 0.326 0.326 0.602 And no baseline anticoagulant use 7469 67 (19.5) 14 (4.1) 0.088 0.054 &amp;lt;0.001 Previous Venous thromboembolism Yes 312 12 (3.8) 64 (20.5) &amp;lt;0.001 0.184 0.981 &amp;lt;0.001 No 7279 148 (2.0) 176 (2.3) 0.089 0.105 0.542 And baseline anticoagulant use 121 9 (4.7) 22 (11.6) 0.273 0.397 0.969 &amp;lt;0.001 And no baseline anticoagulant use 7470 3 (1.6) 42 (22.1) 0.088 0.127 0.003 Existing Thrombocytosis (via ICD or platelet count &amp;gt;450 x 10^9/L) Yes 185 5 (2.7) 7 (3.8) 1 0.123 0.172 0.087 No 7406 155 (2.1) 233 (3.1) 0.091 0.137 &amp;lt;0.001 Citation Format: Jeanna Wallenta Law, Danny Idyro, Andrew Schrag, Frank Wolf, Thomas D. Brown. Natural history of coagulopathy in patients with cancer infected with COVID19: A real-world data (RWD) analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 445.

Increased risk of venous thrombosis in breast cancer patients receiving chemotherapy treatment after COVID-19.

e24106 Background: Immune suppression and coagulopathy development in cancer patients receiving chemotherapy determines a high incidence of complications, including venous thrombosis, and mortality from COVID-19 infection. There are still no explicit data on managing cancer patients when anticancer treatment is resumed after coronavirus disease. According to clinical guidelines for the prevention of venous thromboembolic complications in cancer patients receiving chemotherapy, patients with breast cancer are classified as having a low risk of these complications and do not require prophylactic anticoagulation. The purpose of this study was to assess the parameters of the blood coagulation system and the frequency of venous thrombosis in breast cancer patients with chemotherapy resumption after coronavirus disease. Methods: The study included 30 patients receiving anticancer medical therapy for breast cancer after COVID-19. Anticancer treatment was resumed no earlier than 4 weeks after clinical recovery, absence of SARS-CoV-2 RNAs in nasopharyngeal swabs, infiltrative lung damage according to a chest CT scan, exclusion of venous thrombosis by a lower extremity venous ultrasound. Control group included 20 breast cancer patients without a history of COVID-19. Stage I tumors were registered in 26.6% in the main group vs 15% controls; II - 40% vs 60%; III - 20% vs 15%. Some patients were diagnosed with distant metastases (stage IV- 13.3% vs 10%). Results: Initially, before chemotherapy resumption in the main group, half of the patients had elevated levels of fibrinogen and D-dimer compared with the control group (66.7% vs. 35%, p &gt; 0.05). After a cycle of chemotherapy, a significant difference in the coagulation system parameters was noted (73.3% vs 30%). A lower extremity venous ultrasound after the end of the therapy cycle in the main group showed venous thrombosis in 3 patients (catheter-related n = 2, distal vein thrombosis of the lower extremities n = 1), while no venous thrombotic complications were detected in the control group (10% vs. 0%). Conclusions: Breast cancer patients after coronavirus disease 2019 have hemostasis abnormalities and higher risk of venous thrombosis, and the resumption of anticancer treatment increases the incidence of thrombotic complications. COVID-19 should be considered an additional risk factor of venous thrombosis in cancer patients and requires reconsideration of indications for prophylactic anticoagulation when resuming anticancer treatment for patients with breast cancer.

Pathogenesis of vaccine-induced immune thrombotic thrombocytopenia (VITT)

Vaccine-induced immune thrombotic thrombocytopenia (VITT; synonym, thrombosis with thrombocytopenia syndrome, is associated with high-titer immunoglobulin G antibodies directed against platelet factor 4 (PF4). These antibodies activate platelets via platelet FcγIIa receptors, with platelet activation greatly enhanced by PF4. Here we summarize the current concepts in the pathogenesis of VITT. We first address parallels between heparin-induced thrombocytopenia and VITT, and provide recent findings on binding of PF4 to adenovirus particles and non-assembled adenovirus proteins in the 2 adenovirus vector-based COVID-19 vaccines, ChAdOx1 nCoV-19 and Ad26.COV2.S. Further, we discuss the potential role of vaccine constituents such as glycosaminoglycans, EDTA, polysorbate 80, human cell-line proteins and nucleotides as potential binding partners of PF4. The immune response towards PF4 in VITT is likely triggered by a proinflammatory milieu. Human cell-line proteins, non-assembled virus proteins, and potentially EDTA may contribute to the proinflammatory state. The transient nature of the immune response towards PF4 in VITT makes it likely that—as in heparin-induced thrombocytopenia —marginal zone B cells are key for antibody production. Once high-titer anti-PF4 antibodies have been formed 5 to 20 days after vaccination, they activate platelets and granulocytes. Activated granulocytes undergo NETosis and the released DNA also forms complexes with PF4, which fuels the Fcγ receptor-dependent cell activation process, ultimately leading to massive thrombin generation. Finally, we summarize our initial observations indicating that VITT-like antibodies might also be present in rare patients with recurrent venous and arterial thrombotic complications, independent of vaccination.

Risk factors for portal vein thrombosis or venous thromboembolism in a large cohort of hospitalized cirrhotic patients

BackgroundPortal vein thrombosis (PVT) and venous thromboembolism (VTE) are fearsome complications of liver cirrhosis.ObjectivesTo assess the prevalence and the main risk factors for venous thrombotic complications in hospitalized cirrhotic patients.Patients/methodsWe retrospectively reviewed electronic administrative discharge data of 19461 cirrhotic patients hospitalized over a 35-year period; univariate and multivariate logistic regression was used to asses risk factors for PVT or VTE and their impact on hospital stay and mortality.Results382 out of 7445 patients (5.1%) were diagnosed with PVT and 95 (1.3%) with VTE. Liver cirrhosis complications were observed in 45% of patients. Hepatic encephalopathy (HE) (OR 13.88 [10.76–17.98] p < 0.0001), endoscopic signs of portal hypertension (OR 1.33 [1.02–1.75] p = 0.02), hepatocellular carcinoma (HCC) (OR 4.59 [3.6–5.84] p < 0.0001), diabetes (OR 1.68 [1.27–2.22] p = 0.0001), abdominal surgery/invasive procedures (OR 2.03 [1.56–2.64] p < 0.0001) emerged as independent predictors of PVT. Higher risk of VTE was observed in patients with HE (OR 3.21 [1.78–5.79] p < 0.0001), HCC (OR 1.98 [1.23–3.19] p = 0.002) or other tumors (OR 2.48 [1.42–4.32] p = 0.001), acute illnesses (infections OR 3.01 [1.84–5.05] p = 0.0001; cardiac/respiratory insufficiency OR 2.4 [1.27–4.53] p = 0.003; acute myocardial infarction/stroke OR 7.86 [1.76–35.12] p = 0.003). VTE was the only independent predictor of in-hospital mortality (OR 4.45 [1.05–18.81] p = 0.042).ConclusionsLiver disease complications related to portal hypertension, HCC or other tumors, diabetes, acute illnesses (i.e. infections, cardiac/pulmonary insufficiency, acute myocardial infarction/stroke) and abdominal interventions are associated with increased risk of PVT or VTE in hospitalized cirrhotic patients, and should be considered to define personalized preemptive approaches.

Arterial and Venous Thrombotic Complications in Patients with COVID-19: A Report of Three Cases

Coronavirus Disease 2019 (COVID-19) has had an enormous impact on both the medical community as well as society as a whole. Research on the pathogenesis and the treatment of the disease is rapidly emerging, with new observations and hypotheses appearing daily. One aspect that has been receiving increasing attention is the occurrence of both arterial and venous thrombotic complications in patients with COVID-19. We report three cases of thromboembolic complications in patients affected by COVID-19 and discuss clinical features, pathophysiology, and the proposed approaches to management of vascular complications in these patients. Through our discussion, we also urge physicians to be vigilant for any symptoms or signs suggestive of thrombosis in patients with COVID-19.

A COVID-19 Patient with Simultaneous Renal Infarct, Splenic Infarct and Aortic Thrombosis during the Severe Disease

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with a high incidence of arterial and venous thrombotic complications. However, thromboembolic events in unusual sites such as limb and visceral arterial ischemia are reported rarely in the literature. Herein, we describe a rare case of a patient with severe coronavirus disease 2019 (COVID-19) infection who experienced severe abdominal pain during the hospitalization and presented simultaneously renal artery, splenic artery and vein as well as aortic thrombi despite prophylactic antithrombotic treatment. Information about his follow-up post discharge is also provided. This case report raises significant clinical implications regarding the correct dose of antithrombotic treatment during the acute phase of the severe COVID-19 infection and highlights the need for incessant vigilance in order to detect thrombosis at unusual sites as a possible diagnosis when severe abdominal pain is present in severe COVID-19 patients.