In vitro Effect of Dalteparin and Argatroban on Hemostasis in Critically Ill Sepsis Patients with New-Onset Thrombocytopenia.

Thrombocytopenia is common among critically ill sepsis patients, while they also hold an increased risk for thromboembolic events. Thus, the choice of anticoagulant prophylaxis for this patient population is challenging. We investigated the in vitro effect of low-molecular-weight heparin (dalteparin) and direct thrombin inhibitor (argatroban) on the hemostasis in blood from sepsis patients with new-onset thrombocytopenia. Thrombocytopenia was defined as a platelet count drop of ≥30% and/or from >100 × 10 9 /L to 30 to 100 × 10 9 /L within 24 hours prior to inclusion. We included five healthy individuals and ten patients. Analyses of thrombin generation (Calibrated Automated Thrombogram), thrombin-antithrombin (TAT) complex levels, prothrombin fragment 1+2 (F1+2), and rotational thromboelastometry (ROTEM) were performed. Based on dose-response relationships investigated in healthy blood, patient samples were spiked with prophylactic (0.25 IU/mL) and therapeutic (0.75 IU/mL) dalteparin and low (0.25 µg/mL) and high (0.50 µg/mL) argatroban concentrations, each with a sample without anticoagulant. In patients, the endogenous thrombin potential was markedly lower in therapeutic dalteparin samples than in samples without anticoagulant [median (range): 29 (0-388) vs. 795 (98-2121) nM × min]. In high argatroban concentration samples, thrombin lag time was longer than in samples without anticoagulant [median (range): 15.5 (10.5-20.2) versus 5.3 (2.8-7.3) min]. Dalteparin and argatroban both increased clotting time but did not affect maximum clot firmness in the ROTEM INTEM assay. Six patients had elevated TAT and eight patients had elevated F1 + 2. In conclusion, dalteparin mainly affected the amount of thrombin generated and argatroban delayed clot initiation in critically ill sepsis patients with new-onset thrombocytopenia. Neither anticoagulant affected clot strength.

Intravascular hemolysis and multitreatment predict thrombosis in patients with autoimmune hemolytic anemia.

BACKGROUND: Thrombosis may complicate autoimmune hemolytic anemia (AIHA), but its predictors are still lacking, and no clear-cut indications for anticoagulant prophylaxis are available. OBJECTIVES: To characterize frequency and severity of thromboses in AIHA patients and identify risk factors for thrombosis that may advise primary anticoagulant prophylaxis. PATIENTS/METHODS: A total of 287 consecutive AIHA patients diagnosed and followed from 1978 at a tertiary Italian center were retrospectively studied; 174 of them were prospectively evaluated from January 2020 until December 2021. AIHA relapse, thrombosis occurrence, and primary anticoagulant prophylaxis were evaluated. RESULTS: Thirty-three AIHA patients (11.4%) experienced thrombosis, 70% of whom hospitalized. The cumulative thrombosis incidence was higher in patients with lactate dehydrogenase (LDH) ≥ 1.5 (hazard ratio [HR] 3.22), in those experiencing infections (HR 3.57), receiving transfusions (HR 3.06), rituximab (HR 3.3), or cyclophosphamide (HR 2.67). By multivariable analysis, LDH, transfusions, rituximab, and cyclophosphamide treatment emerged as independent factors associated with thrombosis. Among 174 patients prospectively followed in the past 2 years, we observed 70 acute hemolytic episodes in 45 patients; 33/45 displayed LDH ≥1.5 × upper limit of normal, and 17 received anticoagulant prophylaxis with low molecular weight heparin for a median of 70 days (30-300). In those receiving prophylaxis no thrombotic complications occurred, whereas five thrombotic episodes were registered in the remaining 16 cases. CONCLUSIONS: Thrombosis was observed in about 11% of AIHA patients, mainly grade 3, and associated with intravascular hemolysis, need of transfusions, multitreatment, and infections, advising primary anticoagulant prophylaxis in these settings.

An impact evaluation of an education bundle for patients at risk of developing venous thromboembolism.

Aim: Among hospitalized patients, venous thromboembolism (VTE) is a preventable cause of morbidity and mortality. This study analyzed the effects of a large-scale adoption of a prompt response and education protocol to increase VTE prophylaxis adherence in the USA. Methods: A Markov model was developed that simulates outcomes and costs of delivering a VTE education bundle versus not, to hospitalized at-risk patients. Results: The education bundle could avert more than 134,000 VTEs, 552,000 hospital days and 19,000 deaths over 5 years. Patients could save 13 million hours in work absenteeism and travel time, valued at US$237 million. Total societal savings could amount to US$2.8 billion. In scenario analyses with assumed lower-effectiveness estimates, the bundle averts 16,000 VTEs, 67,000 hospital days and 2000 deaths. Conclusion: A nationwide rollout of an education bundle to reduce missed doses of prescribed prophylaxis could improve quality of care, resulting in a decline in VTEs and mortality.

In a previous study, an education bundle was designed to increase administration of medication to prevent blood clotting among hospitalized patients at risk of venous thromboembolism (VTE). The education bundle led to a decrease in patients missing those needed doses of medication. The current study estimates the economic impacts of a nationwide rollout of the education bundle for patients at risk of VTE. The results show that if the education bundle were rolled out nationally, it could result in 134,000 fewer VTEs, 552,000 fewer days spent in the hospital and 19,000 fewer deaths over 5 years. As a result of reduced medical care, less time off work, and informal caregiving needed, societal cost savings could be as much as US$2.8 billion.

[Venous thromboembolic complications in patients with intracerebral hemorrhage]. / Venoznye tromboembolicheskie oslozhneniya u patsientov s gemorragicheskim insul'tom.

OBJECTIVE: To evaluate the effectiveness and safety of various heparin therapy regimens for venous thromboembolic complications in patients with acute cerebral circulatory disorders of the hemorrhagic type. MATERIAL AND METHODS: In a prospective single-center study, treatment results of 62 patients with hypertensive brain hematoma were analyzed. All patients were divided into two comparable groups: the group of «very early¼ prophylactic heparin therapy or the first 48 hours from the moment of the disease (n=35) and the group of «early¼ prophylactic heparin therapy, or later than 48 hours from the moment of the intracerebral hematoma development (n=27). The end points of the study were: venous thrombosis, pulmonary embolism (fatal and non-fatal), recurrent intracerebral hemorrhage, other clinically significant hemorrhagic complications, and intrahospital mortality. RESULTS: In the group of «very early¼ and «early¼ prophylactic heparin therapy, the results were as follows: venous thrombosis 22.9% vs. 29.6% (p=0.36), total rate of PE 2.9% vs. 11.1% (p=0.03), nonfatal PE 0% vs. 7.4% (p=0.007), fatal PE 2.9% vs. 3.7% (p=0.76), recurrent intracerebral hemorrhage and other hemorrhagic complications 0% in both groups, intrahospital mortality was 54.3% versus 48.1% (p=0.54). CONCLUSION: The earliest administration of direct anticoagulants in prophylactic doses in patients with hemorrhagic stroke leads to the decrease in the frequency of venous thrombosis and thromboembolic complications, without being accompanied by the development of repeated intracranial and other hemorrhagic events.

Isolated Basilic Vein Thrombosis as a Rare Presentation of COVID-19 in a Young Patient.

COVID-19 has not spared a single system in the human body. Although acute respiratory failure culminating sometimes in death remains the most common manifestation of severe infection, hypercoagulability leading to deep vein thrombosis (DVT), pulmonary embolism (PE), and stroke have also been identified widely. Here, we describe a young patient with a COVID-19 infection who developed right basilic vein thrombosis. This case demonstrates how thrombosis can occur in uncommon sites and how clinicians should be vigilant for thrombotic complications in both the inpatient and outpatient settings.

Autoimmune Hemolytic Anemia and Pulmonary Embolism: An Association to Consider.

Autoimmune hemolytic anemia (AIHA) is increasingly recognized as a strong risk factor for venous thrombosis. However, there are currently no guidelines on thromboembolism prevention and management during AIHA. Here, we describe the case of a patient with AIHA and pulmonary embolism and resume the current knowledge on epidemiology, risk factors, treatment, and pathophysiology of thrombosis during AIHA, as well as new therapeutic perspectives to prevent thrombus formation during AIHA.

Efficacy and safety of anticoagulant prophylaxis for prevention of postoperative venous thromboembolism in Japanese patients undergoing laparoscopic colorectal cancer surgery.

AIM: To investigate the efficacy and safety of anticoagulant prophylaxis to prevent postoperative venous thromboembolism (VTE) during laparoscopic colorectal cancer (CRC) surgery, which is unknown in Japanese patients. METHODS: We conducted this randomized controlled trial at nine institutions in Japan from 2011 to 2015. It included 302 eligible patients aged 20 years or older who underwent elective laparoscopic surgery for CRC. Patients were randomly assigned to an intermittent pneumatic compression (IPC) therapy group or to an IPC + anticoagulation therapy group. Anticoagulation therapy comprised fondaparinux or enoxaparin for postoperative VTE prophylaxis. Postoperative VTE was diagnosed based on enhanced multi-detector helical computed tomography. The primary endpoint was VTE incidence, including asymptomatic cases, the secondary endpoint was incidence of major bleeding, and we conducted an intention-to-treat analysis. This study is registered in UMINCTR (UMIN000008435). RESULTS: Postoperative VTE incidence was 5.10% with IPC therapy (n = 157) and 2.76% with IPC + anticoagulant therapy (n = 145; P = .293). We identified no symptomatic VTE cases. The major bleeding rates were 1.27% with IPC alone and 1.38% with the combination (P = .936). The overall bleeding rates were 7.69% for enoxaparin and 13.6% for fondaparinux (P = .500), and there were no bleeding-related deaths. CONCLUSION: Anticoagulant prophylaxis did not reduce the incidence of VTE and the incidence of major bleeding was comparable between the two groups. Usefulness of perioperative anticoagulation was not demonstrated in this study. Pharmacological prophylaxis must be restricted in Japanese patients with higher risk of VTE.

Beneficial effects of pre-stroke statins use in cardioembolic stroke patients with atrial fibrillation: a hospital-based retrospective analysis.

INTRODUCTION: Statins are widely used in stroke patients. The AHA/ASA guidelines recommend aggressive statin therapy in atherosclerotic stroke patients. Their beneficial effects are due to both their hypolipemic and pleiotropic properties. The aim of this study was to establish potential benefits from statin use in ischemic stroke patients with the diagnosis of atrial fibrillation (AF). MATERIAL AND METHODS: Ischemic stroke patients with AF were enrolled in the study. Group I, the statin group (n = 181), consisted of patients who had been treated with statins before stroke. Group II, the non-statin group (n = 153), consisted of patients who had not received such treatment in the last year. In-hospital mortality and neurological deficit on admission and at discharge were analyzed using the National Institutes of Health Stroke Scale (NIHSS) score. RESULTS: Patients from the non-statin group had greater initial and discharge NIHSS scores (10 vs. 11.9, probability value p < 0.05; 7.6 vs. 9.5, p < 0.05 respectively). The improvement in NIHSS score was greater in the statin group (73.5% vs. 59.5%, p < 0.01). In-hospital mortality was more frequent in the non-statin group (9.9% vs. 18.3%, p < 0.05). CONCLUSIONS: Despite the predominant use of statins in atherothrombotic stroke patients, we demonstrated the beneficial effects of statins in cardioembolic stroke patients. Detailed cardiovascular screening for statin therapy should be carried out in all AF patients with regard to primary and secondary stroke prevention.

Integrin beta-3 genetic variants and risk of venous thromboembolism in colorectal cancer patients.

BACKGROUND: Integrin ß3 is involved in tumor and endothelial cell biology as well as in platelet aggregation. Herein, we evaluated the predictive potential of three germline single nucleotide polymorphisms (SNPs) in the integrin ß3 gene (rs3809865, rs5918 and rs4642) to predict the risk of venous thromboembolism (VTE) in colorectal cancer (CRC) patients, which is one of the leading causes of death among cancer patients. METHODS: 112 patients diagnosed with CRC enrolled in the prospective Vienna Cancer and Thrombosis Study (CATS) were assessed with a median follow-up of 46 months. DNA was isolated from venous blood samples and SNPs were analyzed by the PCR-RFLP method. RESULTS: VTE occurred in 12% (n=13) of all patients. The SNPs rs5918 and rs4642 were not associated with VTE risk. For rs3809565, 23% (n=11) of patients had the A/A genotype, 4% (n=2) had the A/T genotype, but none (0%) had the T/T genotype. In the univariate analysis, patients with the A/A genotype had a significantly higher risk to develop VTE compared to the other polymorphisms (P=0.0005 after Fine and Gray). In the multivariable analysis, the predictive value remained significant. CONCLUSIONS: This study identified the rs3809865 A/A genotype as an independent risk factor for VTE in CRC patients. Our findings would help identify high risk patients and would be essential for tailored anticoagulant prophylaxis.

Atrial fibrillation and stroke - Coexistence and attitude to preventive therapy on the basis of Szczecin and Szczecin region patients.

Atrial fibrillation (AF) is an independent factor increasing the risk of an ischemic stroke (IS) fivefold. The objective of the study was to evaluate the frequency of coexistence of non-valvular AF and IS during the acute stroke and to analyze the attitude of AF patients to treatment. The study included 3712 successive patients presenting either an IS or a transient ischemic attack. The analysis revealed a significant increase in the rate of patients with AF and IS in the years 2010-2013 (31.9%) compared with 2002-2005 (20.2%). A rise in the proportion of AF and IS patients was recorded over the course of consecutive years in group II. The proportion of newly detected AF cases during hospital stay differed significantly between the groups (16.9% vs. 31.9%). Group I and II patients differed essentially with regards to hypertension incidence and female rates. Antiplatelet medications or OACs were taken by a significantly greater number of AF patients in group II. Low number of therapeutic levels of INR was recorded in both groups. IS and AF coexist more frequently than indicated by previous assessments and demographic data from other countries. Increase in the number of IS and AF patients may result from higher detectability of AF and older age of patients affected with stroke, women in particular. Despite a well grounded knowledge about the benefits of OACs use in the prophylaxis of thrombotic-embolic events in AF patients, they are rarely used. A surprisingly low proportion of patients taking OACs reaches a therapeutic INR level.

Pharmacological prevention of venous thromboembolism in orthopaedic surgery.

The prophylaxis of venous thromboembolism (VTE) with anticoagulant drugs is a long-established practice in hip and knee replacement surgery, as well as in the treatment of femoral neck fractures, while there are few data regarding the prevention of VTE in other fields of orthopaedic surgery and traumatology. In order to provide practical recommendations for daily management of VTE prophylaxis in orthopaedic patients, recently the Italian Societies of Thrombosis and Haemostasis, Orthopaedics and Traumatology and Anaesthesia have drawn up a first Intersociety Consensus on antithrombotic prophylaxis in total hip and knee replacement surgery, and in the treatment of femoral neck fracture, then updated in 2013, and a subsequent Intersocietary Consensus, in cooperation also with the Society of general practitioners, concerning antithrombotic prophylaxis in other types of orthopaedic surgery and traumatology. Before starting any prophylactic treatment it is of crucial importance the assessment of both thrombotic and bleeding risk of patients undergoing surgery. Thromboembolic prophylaxis is recommended with low molecular weight heparins (LMWH), fondaparinux (FON) or with the new oral anticoagulants (NOA) in patients undergoing hip and knee replacement surgery while patients undergoing treatment of femoral neck fracture should be treated with LMWH or FON. Regarding the non-prosthetic orthopaedic surgery and traumatology, it is recommended prophylaxis with LMWH or FON in situations of high thromboembolic risk or in the case of interventions or trauma involving pelvis, acetabulum or knee.