COVID-19, neurovascular thrombotic problem and short summary on blood coagulation disorder: a brief review

COVID-19 is the present global public health problem. This respiratory viral infection can manifest atypical presentation including neurological presentations. An important neurological problem in COVID-19 is neurovascular thrombosis. The basic pathogenesis of thrombosis in neurological system is explainable by the basic principle of thrombohemostasis. A hypercoagulability is a possible problem seen in some COVID-19 cases. In this brief review, the authors summarize venous and arterial thrombosis of neurovascular system as a complication of COVID-19. The updated pathophysiology of COVID-associated blood coagulation disorder is discussed. In addition, consideration regarding new COVID-19 vaccine related thrombotic adverse event is also raised.

Reference Values of Thromboelastometry Parameters in Healthy Term Neonates Using NATEM in Cord Blood Samples

Background: ROTEM assay has gained increasing acceptance as a method for rapid and specific coagulation pathway assessment. However, its use in the neonatal population remains limited since reference ranges have not yet been established. Aims: (1) to determine reference ranges for healthy term neonates of ROTEM parameters using non-activated assay (NATEM) in cord blood samples; (2) to assess whether delivery mode, gender, gestational age, birth weight and blood group (ABO and Rhesus) of the neonate, coagulation disorder and anticoagulant medication of the mother have an impact on NATEM parameters. Methods: NATEM assay was conducted in cord blood samples of 189 term neonates without any medical history. Results: Reference ranges (2.5th and 97.5th percentiles) are established for clotting time (CT), clot formation time (CFT), α-angle, clot amplitude at 5, 10 and 20 min (A5, A10, A20), maximum clot firmness (MCF), lysis index at 30 and 60 min (LI30, LI60, %) and maximum clot elasticity (MCE). Reference ranges for NATEM are CT 182–499 s, CFT 63–176 s, α-angle 58–78°, A5 28–52 mm, A10 37–61 mm, A20 42–66 mm, MCF 43–67 mm, LI30 97–100%, LI60 87–98% and MCE 75–203. Male neonates appear to be more hypocoagulable than females. Conclusions: We demonstrate reference ranges for healthy term neonates in NATEM assay that could be used as a reference group for future studies of neonates with an underlying pathology.

Lessons From Heat Stroke for Understanding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

We here provide an overview of the pathophysiological mechanisms during heat stroke and describe similar mechanisms found in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Both conditions are characterized by disturbed homeostasis in which inflammatory pathways play a central role. Splanchnic vasoconstriction, increased gut permeability, gut-related endotoxemia, systemic inflammatory response, central nervous system dysfunction, blood coagulation disorder, endothelial-cell injury, and mitochondrial dysfunction underlie heat stroke. These mechanisms have also been documented in ME/CFS. Moreover, initial transcriptomic studies suggest that similar gene expressions are altered in both heat stroke and ME/CFS. Finally, some predisposing factors for heat stroke, such as pre-existing inflammation or infection, overlap with those for ME/CFS. Notwithstanding important differences - and despite heat stroke being an acute condition - the overlaps between heat stroke and ME/CFS suggest common pathways in the physiological responses to very different forms of stressors, which are manifested in different clinical outcomes. The human studies and animal models of heat stroke provide an explanation for the self-perpetuation of homeostatic imbalance centered around intestinal wall injury, which could also inform the understanding of ME/CFS. Moreover, the studies of novel therapeutics for heat stroke might provide new avenues for the treatment of ME/CFS. Future research should be conducted to investigate the similarities between heat stroke and ME/CFS to help identify the potential treatments for ME/CFS.

A Comparison between the Effectiveness of Norethisterone and Dydrogesterone for treatment of Irregular Menstrual Cycle

Background: Abnormal uterine bleeding is defined as irregularities in the menstrual cycle involving frequency, regularity, duration, and volume of flow outside of pregnancy. Up to 1/3rd of women experience abnormal uterine bleeding in their life, with irregularities most commonly occurs at menarche and perimenopause due to disruption of the hypothalamic-pituitary-ovarian axis. Aim: To compare the effectiveness of Norethisterone and Dydrogesterone for the treatment of irregular menstrual cycles due to abnormal uterine bleeding of ovulatory or endometrial dysfunction and to check for patient satisfaction after the use of prescribed hormones by taking their feedback. Methods: This observational, comparative, cohort-prospective study was conducted on 100 nonpregnant women between the ages of 15-45 years who presented with complaints of irregular menstruation in gynae outdoor of AMTH for 6 months from April 2021 to September 2021. After excluding pelvic pathology, known thyroid disease, coagulation disorder, or use of the contraceptive method, the participants were divided into Group A and Group B, each having 50 participants. Results: The mean age±SD of the participants in Group A was 29±3.4 while Group B had mean age±SD was 29.5±3.6. In Group A, 38(76%) patients reported a regular menstrual cycle after 3 months of use while 12(24%) patients complained of persistent irregular menstrual cycle despite 3 months use of Norethisterone with compliance in Group B using Dydrogesterone, 22(44%) patients had regular menstrual cycles while 28(56%) patients had persistent irregular menstrual cycles after three months of use. Conclusion: So we concluded from our study that Norethisterone had a better cycle control than Dydrogesterone. Keywords: Abnormal uterine bleeding of ovulatory and/or endometrial dysfunction, Norethisterone, Dydrogesterone,

Idiopathic purpura fulminans with anti-PS antibodies in children: a multicenter case series and systematic review

Idiopathic purpura fulminans (IPF) is a rare but severe pro-thrombotic coagulation disorder that can occur after chickenpox or HHV6 infection. IPF leads to an autoantibody-mediated decrease in the protein S plasma concentration. We conducted a retrospective multicenter study involving IPF patients from 13 French pediatric centers and a systematic review of literature-published cases. Eighteen patients were included in our case series, and thirty-four as literature review cases. The median age was 4.9 years and the diagnostic delay after the first signs of viral infection was 7 days. The lower limbs were involved in 49 (94%) patients with typical lesions. A recent history of VZV or HHV6 infection was present in 41 (78%) and 7 (14%) of cases, respectively. Most of the patients received heparin (n=51, 98%) and fresh frozen plasma transfusions (n=41, 79%); other treatment options were immunoglobulin infusion, platelet transfusion, corticosteroid therapy, plasmapheresis, and coagulation regulator concentrate infusion. The antithrombin level and platelet count at diagnosis appeared to be associated with severe complications. Given the rarity of this disease, the creation of a prospective international registry is required to consolidate these findings.

Clinical correlation between coagulation disorders and sepsis in patients with liver failure

OBJECTIVE: This study aimed to explore the clinical detection and prognosis of coagulation function in patients with liver failure and sepsis. METHODS: The plasma fibrinogen (FIB), factor II, factor VII, factor V, factor IV, antithrombin III (ATIII), platelet (PLT), mean PLT volume (MPV), D-dimer, prothrombin activity (PTA), and fibrin degradation product (FDP) levels and thromboelastogram values were detected in patients with liver failure complicated with sepsis and compared with those in the liver failure and liver cirrhosis groups. The patients with liver failure complicated with sepsis were analyzed by univariate and multivariate logistic regression, and the regression equation was established. RESULTS: The levels of FIB, factor II, factor VII, factor V, ATIII, PLT, MPV, D-dimer, and FDP in the patients with liver failure complicated with sepsis were compared with those in the control group patients, and the differences were statistically significant (p < 0.05). Among the thromboelastography parameters in the patients with liver failure and sepsis, the differences in the K-value, R-value, angle, maximum amplitude, and coagulation index values compared with those of the control group were statistically significant (p < 0.05). The logistic regression model obtained was as follows: p = 1/(1 + e [–0.128×X1–0.058×X2 + 0.211×X3 + 0.2×X4 + 0.25]). The specificity, sensitivity, and accuracy values of the regression equation in determining the prognosis were 92%, 93.9%, and 92.8%, respectively. Among the 11 factors, factor VII, PLT, FDP, and D-dimer were included in the regression equation. CONCLUSION: Coagulation disorder is exacerbated in patients with liver failure and sepsis. Among the 11 coagulation-related factors, factor VII, PLT, FDP, and D-dimer may be the independent factors influencing the prognosis of patients with acute liver failure and sepsis.

Progression of Fibrinogen Decrease during High Dose Tigecycline Therapy in Critically Ill Patients: A Retrospective Analysis

Tigecycline is a novel glycylcycline broad-spectrum antibiotic offering good coverage for critically ill patients experiencing complicated infections. A known side effect is a coagulation disorder with distinct hypofibrinogenemia. To date, the information on possible risk factors and outcomes is sparse. Therefore, the aim of this study is to examine the time course of fibrinogen level changes during tigecycline therapy in critically ill patients. Moreover, we sought to identify risk factors for coagulopathy and to report on clinically important outcomes. We retrospectively reviewed all intensive care patients admitted to our General and Surgical Intensive Care Unit receiving tigecycline between 2010 and 2018. A total of 130 patients were stratified into two groups based on the extent of fibrinogen decrease. Patients with a greater fibrinogen decrease received a higher dose, a longer treatment and more dose changes of tigecycline, respectively. In regard to the underlying pathology, these patients showed higher inflammation markers as well as a slightly reduced liver synthesis capacity. We, therefore, conclude that such a fibrinogen decrease may be based upon further impairment of liver synthesis during severe inflammatory states. To decrease the risk of bleeding, cautious monitoring of coagulation in critically ill patients treated with high-dose tigecycline is warranted.

Thromboembolic risk of movable type left atrial appendage thrombi in patients with atrial fibrillation under widespread use of anticoagulants

Background Left atrial appendage thrombi (LAAT), especially movable type LAAT, have been reported to be high-risk for thromboembolic events in patients with atrial fibrillation (AF). However, thromboembolic risk of the movable-type LAAT under widespread use of anticoagulant therapy remains unclear. Methods We retrospectively studied 65 LAAT patients taking anticoagulants out of 1381 consecutive patients who underwent transthoracic echocardiography prior to cardioversion or catheter ablation for AF. Patients with significant valvular disease and coagulation disorder were excluded. Clinical data were evaluated at the time of TEE. The LAAT were classified into movable and fixed type LAAT by three independent observers. Results Sixteen of 65 LAAT patients showed movable type LAAT. During follow-up (42±34 months), one patient underwent emergency thrombectomy, 5 patients developed thromboembolic event, and 12 patients died. There were no differences in clinical data, parameters, thrombectomy/thromboembolic event, and survival rate between patients with movable and fixed type LAAT. Conclusion Thromboembolic risk of the movable-type LAAT is the same as fixed type LAAT, under widespread use of anticoagulant therapy. FUNDunding Acknowledgement Type of funding sources: None.

Early Coagulation Disorder Is Associated With an Increased Risk of Atrial Fibrillation in Septic Patients

Background: Atrial fibrillation (AF) and coagulation disorder, two common complications of sepsis, are associated with the mortality. However, the relationship between early coagulation disorder and AF in sepsis remains elusive. This study aimed to evaluate the interaction between AF and early coagulation disorder on mortality.Methods: In this retrospective study, all data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Septic patients with coagulation tests during the first 24 h after admission to intensive care units (ICUs) meeting study criteria were included in the analysis. Early coagulation disorder is defined by abnormalities in platelet count (PLT), international normalized ratio (INR) and activated partial thromboplastin time (APTT) within the first 24 h after admission, whose score was defined with reference to sepsis-induced coagulopathy (SIC) and coagulopathy. Patients meeting study criteria were divided into AF and non-AF groups.Results: In total, 7,528 septic patients were enrolled, including 1,243 (16.51%) with AF and 5,112 (67.91%) with early coagulation disorder. Compared with patients in the non-AF group, patients in the AF group had higher levels of INR and APTT (P &lt; 0.001). Multivariable logistic regression analyses showed that stroke, early coagulation disorder, age, gender, congestive heart failure (CHF), chronic pulmonary disease, renal failure, and chronic liver disease were independent risk factors for AF. In addition, AF was related to in-hospital mortality and 90-day mortality. In the subgroup analysis stratified by the scores of early coagulation disorder, AF was associated with an increased risk of 90-day mortality when the scores of early coagulation disorder were 1 or 2 and 3 or 4.Conclusion: In sepsis, coagulation disorder within the first 24 h after admission to the ICUs is an independent risk factor for AF. The effect of AF on 90-day mortality varies with the severity of early coagulation disorder.

Paracetamol and Ibuprofen in the Treatment of Fever and Acute Mild–Moderate Pain in Children: Italian Experts’ Consensus Statements

Fever and pain are challenging symptoms in children and adolescents and are common reasons for consultations in primary care and hospital. Paracetamol and ibuprofen are currently the only recommended drugs for treating fever in Italy, but the therapeutic approaches are discrepant in the different settings. In Italy, paracetamol and ibuprofen are the most prescribed analgesics for acute mild–moderate pain in children; however, their use is often inappropriate in that fever is over-treated and pain is under-treated. An Italian board of experts analyzed the motivations for the misalignment between daily practice and guidelines of fever and acute mild–moderate pain management of the territory and hospitals. The expert opinion consensus process underscored the appropriate use of paracetamol and ibuprofen according to clinical scenarios, patients’ profiles, and the safety features of the drugs. Although patients’ profiles can indicate different benefits from paracetamol or ibuprofen, critical issues of fever and acute mild–moderate pain management persist in primary care and hospitals. These expert opinion consensus statements can be an across-the-board tool to harmonize the routine practice between the territory and hospitals, especially under special conditions (at-risk for dehydration, coagulation disorder patients, etc.). It can also promote educational activity about fever and acute mild–moderate pain management to enhance the milestones already achieved by Italian pediatricians.