Hunting the Hidden: Surgical Treatment of Chronic Silent Thrombus in the Left Ventricle. A Case Report.

Background: Silent left ventricular thrombus is dangerous. The current standard anticoagulation therapy is not effective, and the outcomes are frustrated.Case presentation: A 33-year-old man with silent left ventricular thrombus, which was detected incidentally by transthoracic echocardiography. After admission, anticoagulation with low-molecular-weight heparin therapy was carried out. Unfortunately, acute left temporal embolism emerged 5 days later, then the patient was transferred to the neurology department for further treatment. One month later, the patient received coronary artery bypass grafting (CABG), ventricular aneurysm resection and left ventricular thrombectomy and was discharged uneventfully after surgery.Conclusions: For the patients with giant or hypermobile left ventricular thrombus or recurrent systemic emboli, surgical treatment should be a priority.

Testing for Heparin Induced Thrombocytopenia in Hospitalized Patients: In Line with Evidence?

Background: Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin. Both clinical probability and laboratory testing are needed for establishing a diagnosis of HIT. The 4Ts clinical scoring system, due to a very high negative predictive value when low, offers a robust means to exclude a diagnosis of HIT. However, these strategies are under-employed in clinical practice and limited evidence indicates a high prevalence of over-testing for HIT. Methods: This retrospective analysis was conducted to identify patients who underwent heparin/PF4 antibody testing over a period of 12 months. The testing was performed using an ELISA-based IgG anti-heparin/PF4 antibody assay and an optical density (OD) of 0.4 was used as a cut-off for a positive value. Electronic medical records were reviewed for 4T score documentation, anti-PF4 results, SRA testing and 4T scores were retrospectively calculated for all the patients. SAS v9.4 (Cary, NC) was used for statistical analysis. Results: A total of 105 patients who underwent anti-PF4 antibody testing were included for analysis. Majority of the patients in our cohort were admitted in an intensive care unit setting (75/105,71.4%). On chart review, only 17 patients (16.2%) were noted to have documentation of 4T score. Based on the retrospectively calculated 4T scores, 60 patients (57.1%) had low pre-test probability, 41 (39%) had intermediate pre-test probability and 4 (3.8%) patients were noted to have high pre-test probability. Anti-PF4/heparin antibodies were positive in 9 patients, of which 5 (55.5%) patients did not undergo concomitant SRA testing. Out of 9, 4 (44.4%) had weakly positive (0.4-1.0 OD units), 2 (21.1%) had strongly positive (1.0-2.0 OD units) and 2 (21.1%) patients had very strongly positive (>2 OD units) anti-PF4 antibody titers. Out of 105 patients, SRA was tested in 11 patients (10.5%) and was noted to be positive in 1 (0.95%). Overall, 2 patients were diagnosed and treated for HIT, out of which the diagnosis was not confirmed with SRA in 1 patient (due to high pre-test probability and very strong anti-PF4 titers). In the remaining patients, sepsis (48, 46.6%) and drug-induced thrombocytopenia (29, 28.2%) emerged as the most common possible causes of thrombocytopenia. Conclusion: Among hospitalized patients, over-testing for HIT is common. Practices to promote 4T score documentation and evidence-based anti-PF4 testing may help prevent unnecessary costs associated with serological testing and costly alternate anticoagulants. To improve overall outcomes, clinicians should also attempt to identify and treat other more likely causes of thrombocytopenia, especially in patients with low pre-test probability for HIT. Disclosures No relevant conflicts of interest to declare.

An ensemble model for predicting therapeutic response to unfractionated heparin therapy (Preprint)

BACKGROUND Unfractionated heparin (UFH), is an anticoagulant drug considered a high-risk medication in that an excessive dose can cause bleeding, while an insufficient dose can lead to a recurrent embolic event. Following initiation of intravenous (IV) UFH, the therapeutic response is monitored using a measure of blood clotting time known as the activated partial thromboplastin time (aPTT). Clinicians iteratively adjust the dose of UFH to a target aPTT range, with the usual therapeutic target range between 60 to 100 seconds. OBJECTIVE The aim of this study was to develop and validate a ML algorithm to predict, aPTT within 12 hours after a specified bolus and maintenance dose of UFH. METHODS This was a retrospective cohort study of 3273 episodes of care from January 2017 to August 2020 using data collected from electronic health records (EHR) of five hospitals in Queensland, Australia. Data from four hospitals were used to build and test ensemble models using cross validation, while the data from the fifth hospital was used for external validation. Modelling was performed using H2O Driverless AI® an automated ML tool, and 17 different experiments were conducted in an iterative process to optimise model accuracy. RESULTS In predicting aPTT, the best performing experiment produced an ensemble with 4x LightGBM models with a root mean square error (RMSE) of 31.35. This dataset was re-purposed as a multi-classification task (sub-therapeutic, therapeutic, and supra-therapeutic aPTT result) and achieved a 59.9% accuracy and area under the receiver operating characteristic curve (AUC) of 0.735. External validation yielded similar results: RMSE of 30.52 +/- 1.29 for the prediction model, and accuracy of 56.8% +/- 3.15 and AUC of 0.724 for the multi-classification model. CONCLUSIONS According to our knowledge, this is the first study of ML applied to IV UFH dosing that has been developed and externally validated in a multisite adult general medical inpatient setting. We present the processes of data collection, preparation, and feature engineering for purposes of replication.

Early Effects of Low Molecular Weight Heparin Therapy with Soft-Mist Inhaler for COVID-19-Induced Hypoxemia: A Phase IIb Trial

In COVID-19-induced acute respiratory distress syndrome, the lungs are incapable of filling with sufficient air, leading to hypoxemia that results in high mortality among hospitalized patients. In clinical trials, low-molecular-weight heparin was administered via a specially designed soft-mist inhaler device in an investigator initiated, single-center, open-label, phase-IIb clinical trial. Patients with evidently worse clinical presentations were classed as the “Device Group”; 40 patients were given low-molecular-weight heparin via a soft mist inhaler at a dose of 4000 IU per administration, twice a day. The Control Group, also made up of 40 patients, received the standard therapy. The predetermined severity of hypoxemia and the peripheral oxygen saturation of patients were measured on the 1st and 10th days of treatment. The improvement was particularly striking in cases of severe hypoxemia. In the 10-day treatment, low-molecular-weight heparin was shown to significantly improve breathing capability when delivered via a soft-mist inhaler.

Management and impact of atrial fibrillation in the COVID 19 era; concomitancy of two procoagulant phenomena

Background Atrial fibrillation (AF) is a widespread cause of prothrombotic state leading to long-term anticoagulant therapy. Literature describes coagulopathy as a key pathogenic mechanism of COVID-19 disease. Thus, antithrombotic therapy management is still a therapeutic challenge. During hospitalization, changing oral anticoagulant (OAC) therapies into subcutaneous heparin is common in daily clinical practice. Purpose The primary endpoint of this study is to analyze the impact of AF in mortality within 30 day since admission of COVID-19 patients. The secondary endpoint is to analyze the impact of the anticoagulant therapy strategy (therapeutic dose of subcutaneous heparin vs. OAC) in 30-day mortality of hospitalized COVID-19 patients with AF. Methods A total of 1001 consecutive patients hospitalized in our centre between 22nd August and 9th January 2021 with a confirmed microbiological diagnosis of COVID-19 by PCR were prospectively included. Of them, 134 had a previous diagnose of AF (13.5%). Cox regression analysis was performed to assess the impact of AF and the choice of anticoagulant therapy in 30-day mortality after adjusting for comorbidity (Charlson Comorbidity Index). Results After adjusting for comorbidities, AF was not independently associated with a higher 30-day mortality in patients hospitalized due to COVID-19 infection (HR 1.04, CI 0.77–1.43, p=0.760). In the group of patients with AF, changing OAC to heparin therapy was not associated with an improved prognosis (HR 0.85, CI 95% 0.46–1.56, p=0.604). Conclusions AF is not an independent prognostic factor in COVID-19 hospitalized patients. In hospitalized COVID-19 patients with AF, changing OAC to heparin therapy is not related to an improved prognosis. FUNDunding Acknowledgement Type of funding sources: None. Mortality heparin vs NOAC or AVK

Heparin-induced Thrombocytopenia in Patients with Coronavirus Disease 2019: Systematic Review and Meta-analysis

Heparin thromboprophylaxis is routinely administered during hospitalization for coronavirus disease 2019 (COVID-19). Due to the immune stimulation related to COVID-19, there is ongoing concern regarding a heightened incidence of heparin-induced thrombocytopenia (HIT). We performed a literature search using PubMed, EMBASE, Cochrane and, medRxiv database to identify studies that reported clinical and laboratory characteristics and/or the incidence of HIT in COVID-19 patients. The primary aim was to systematically review the clinical features and outcomes of COVID-19 patients with confirmed HIT. The secondary objective was to perform a meta-analysis to estimate the incidence of HIT in hospitalized COVID-19 patients. A meta-analysis of 7 studies including 5,849 patients revealed the pooled incidence of HIT in COVID-19 of 0.8% (95% confidence interval [CI], 0.2-3.2%; I2 = 89%). The estimated incidences were 1.2% (95%CI, 0.3-3.9%; I2 = 65%) versus 0.1% (95%CI, 0.0-0.4%; I2 = 0%) in therapeutic versus prophylactic heparin subgroups, respectively. The pooled incidences of HIT were higher in critically ill COVID-19 patients (2.2%, 95%CI, 0.6-8.3%; I2 = 72.5%) compared to non-critically ill patients (0.1%, 95%CI, 0.0-0.4%: I2 = 0%). There were 19 cases of confirmed HIT and one with autoimmune HIT for clinical and laboratory characterization. The median time from heparin initiation to HIT diagnosis was 13.5 (interquartile range [IQR], 10.75, 16.25) days. Twelve (63%) developed thromboembolism after heparin therapy. In conclusion, the incidence of HIT in COVID-19 patients was comparable to non-COVID-19 medical patients, with higher incidences with therapeutic anticoagulation and in critically ill patients.

Platelet factor 4 polyanion immune complexes: heparin induced thrombocytopenia and vaccine-induced immune thrombotic thrombocytopenia

Background This is a review article on heparin-induced thrombocytopenia, an adverse effect of heparin therapy, and vaccine-induced immune thrombotic thrombocytopenia, occurring in some patients administered certain coronavirus vaccines. Main body/text Immune-mediated thrombocytopenia occurs when specific antibodies bind to platelet factor 4 /heparin complexes. Platelet factor 4 is a naturally occurring chemokine, and under certain conditions, may complex with negatively charged molecules and polyanions, including heparin. The antibody-platelet factor 4/heparin complex may lead to platelet activation, accompanied by other cascading reactions, resulting in cerebral sinus thrombosis, deep vein thrombosis, lower limb arterial thrombosis, myocardial infarction, pulmonary embolism, skin necrosis, and thrombotic stroke. If untreated, heparin-induced thrombocytopenia can be life threatening. In parallel, rare incidents of spontaneous vaccine-induced immune thrombotic thrombocytopenia can also occur in some patients administered certain coronavirus vaccines. The role of platelet factor 4 in vaccine-induced thrombosis with thrombocytopenia syndrome further reinforces the importance the platelet factor 4/polyanion immune complexes and the complications that this might pose to susceptible individuals. These findings demonstrate, how auxiliary factors can complicate heparin therapy and drug development. An increasing interest in biomanufacturing heparins from non-animal sources has driven a growing interest in understanding the biology of immune-mediated heparin-induced thrombocytopenia, and therefore, the development of safe and effective biosynthetic heparins. Short conclusion In conclusion, these findings further reinforce the importance of the binding of platelet factor 4 with known and unknown polyanions, and the complications that these might pose to susceptible patients. In parallel, these findings also demonstrate how auxiliary factors can complicate the heparin drug development.

Successful management of a pregnant woman with COVID-19 and multiple severe complications

We report a case of a 36-year-old gravida 2 para 1 woman at 38 weeks of gestation. A caesarean section was performed for severe pre-eclampsia, intrauterine growth restriction and oligohydramnios. The patient suffered postoperative bleeding, and exploratory laparotomy was performed. Uterine atonia, Couvelaire uterus and left adnexal haematoma were found, requiring a supracervical hysterectomy. As COVID-19 pneumonia and superimposed bacterial infection developed, the patient was mechanically ventilated in the intensive care unit. Remdesivir and meropenem were initially administered, but were changed to levofloxacin and ciprofloxacin following antibiotic sensitivity tests. Blood culture grew Enterococcus galinarum. Meanwhile, bleeding of the incisional wound occurred, which was controlled by the cessation of heparin therapy and regular wound care. With intensive monitoring and multidisciplinary management, the patient’s condition improved, and she was discharged from the hospital on day 25 from admission.

Risk factors and prevention of placenta-associated diseases

The review presents modern data on the preventive effect of antiplatelet and anticoagulant therapy of placenta-associated diseases. The review includes data from foreign and Russian articles published over the past 15 years on the Scopus, Web of Science, MedLine, The Cochrane Library, EMBASE, Global Health, CyberLeninka, Pubmed databases. In recent years, there have been reports of the effectiveness of low molecular weight heparins in the prevention of placenta-associated complications. M. Rodger et al. In their study (2016), report on the effect of low molecular weight heparins on the development of placenta-associated complications. Patients whose previous pregnancy was complicated by preeclampsia or fetal growth restriction were randomized into 2 groups. The first group of pregnant women began to receive injections of low molecular weight heparins at an early stage of pregnancy (before 12 weeks), the second group did not receive low molecular weight heparins. Thus, only 19% of women receiving low molecular weight heparin therapy and 43% of women not receiving it developed placenta-associated complications, which may indicate the effectiveness of low molecular weight heparins. This data shows the urgency of the problem of placenta-associated complications, and the development of effective methods of early prevention of these diseases can improve the outcomes of the pregnancy.