Disorders Of Hemostasis Research Articles

The signi‹cance of urine study in the diagnostics of diseases of the blood system (lecture for practitioning doctors)

In the diagnosis of diseases of the blood system, an important place is given to the patient's complaints, a carefully collected anamnesis, an objective examination, and, along with the use of special laboratory and instrumental studies, routine blood and urine tests. It is necessary to pay attention to the change in the color of urine, which is observed during hemolysis, cold, marching, paroxysmal nocturnal hemoglobinuria, autoimmune hemolytic anemia, porphyria and other conditions. Hematuria is characteristic of disorders of coagulation and platelet hemostasis of hereditary and acquired origin, von Willebrand disease of mild and moderate severity, overdose of anticoagulants and inhibitors of platelet hemostasis. Proteinuria is a characteristic syndrome in paraproteinemic hemoblastoses, AL-amyloidosis, Immerslund-Gresbeck disease, etc. Competent interpretation of the urine test in combination with the clinical picture is the key to a successful diagnosis.

Femoral and Lateral Femoral Cutaneous Nerve Block as Anesthesia for High-Risk Intertrochanteric Fracture Repair Patients.

Introduction. Intertrochanteric fracture (IF) is a common injury among the elderly. Due to significant comorbidities, anesthesia for IF repair may be challenging. The authors propose femoral nerve block together with a lateral femoral cutaneous nerve block and sedation as an anesthetic technique for most severe cases of IF with contraindications to spinal anesthesia. Methods. In total, 61 patients were enrolled prospectively in a study, 19 received general anesthesia (GA group), 22 spinal anesthesia (SA group), and 20 nerve blocks with sedation (PNB group). Results. Groups were comparable in terms of age, gender, independence, and several comorbidities: diabetes, obesity, underweight, cardiovascular, and cerebrovascular incidents in the past, dementia, chronic obstructive pulmonary disease, and frailty. Heart failure (p = 0.033), hemoglobin < 10 g/dL (p = 0.001) and eGFR < 30 mL/min (p = 0.039) were more frequent in PNB group. PNB group had higher American Society of Anesthesiologists (ASA) (p < 0.001), Nottingham Hip Fracture Score (NHFS) (p < 0.001), and Charlson Comorbidity Index (CCI) (p = 0.002) scales scores, and lower probability of 10-year survival according to CCI (p = 0.012). GA group had more frequent active malignancy (p = 0.041). GA and PNB groups had a higher frequency of hemostasis disorder (p < 0.001). Surgery was completed under the scheduled anesthesia technique. Survival, frequency of cardio and cerebrovascular incidents after surgery, loss of independence, and postoperative delirium were comparable between groups, as well as the length of postoperative stay. Conclusions. Surgical repair of intertrochanteric fracture with intramedullary nailing system among elderly, frail, and sick patients can be conducted under peripheral nerve block. FNB and LFCNB in the combination is a viable option for IT fracture repair.

Portal vein thrombosis as a manifestation of post-COVID syndrome: a case study

Introduction. Hemostasis disorders presented in the form of thrombosis in various vascular territories are one of the main causes of death against the background of COVID-19. Their threat persists even after recovery as part of the post-COVID syndrome. Recent studies demonstrate that the development of thromboin-flammatory syndrome is possible not only in the lungs. At the same time, the frequency of revealed venous thrombosis is 10–35% and 60% according to autopsy data. One of the localizations of venous thrombosis in COVID-19 may be the portal system. Portal vein thrombosis is a rarely diagnosed disease that remains asymptomatic for a long period, which makes its timely diagnosis difficult. At the same time, the prognosis for PVT is mostly unfavorable with deaths occurring in half of the cases.The purpose of the study is to demonstrate the features of diagnosis and treatment of PVT on the example of a clinical case in a patient who had a mild coronavirus infection.Description of clinical case. The article describes a clinical case of diagnosis and successful treatment of extended thrombosis of the portal, splenic and superior mesenteric veins against the background of direct anticoagulant therapy and thrombolysis by means of the percutaneous transhepatic portal access. The disease in patient K.V.A., 49 years old who had a moderate coronavirus infection (liver disease and congenital thrombophilia as a cause of thrombosis are excluded) was complicated by spleen infarcts, hydroperitoneum, partial small bowel obstruction.Conclusion. This clinical case is of interest for the possibility of a successful combination of anticoagulant and regional thrombolytic therapy without surgical intervention in complicated thrombosis of the portal vein and its tributaries in a patient in the post-COVID period, and also dictates the need for a personalized approach to the duration and choice of doses of anticoagulant therapy after a COVID-19 infection.

Gerinnungsdiagnostik im klinischen Alltag – Teil 1

This article on coagulation diagnostics is published in two parts covering five common clinical scenarios for coagulation diagnostics. Part1 deals with the diagnostics prior to invasive interventions and coagulation diagnostics to clarify atendency to bleeding. The global parameters Quick and activated partial thromboplastin time are established for monitoring certain anticoagulants; however, they are not predictive with respect to the risk of bleeding prior to elective invasive interventions. In this context, disorders of primary hemostasis are frequent, which are insufficiently detected by the global parameters. Most clinical bleeding tendencies are due to acquired causes. These include anticoagulants and diseases which can be accompanied by tendency to bleeding. For coagulation tests preanalytical issues are essential in order to avoid false results. The interpretation should always be made in the context of the current physiological state.

Hemostasis disorder as a reason of periodontitis in patients with diabetes mellitus

In diabetes mellitus II type hyperglycemia contributes to the development of endothelial dysfunction. It leads to hypercoagulation and severe microcirculation disorders, which are the cause of ischemia in periodontal tissues and the development of inflammatory processes. The aim of the study hemostasis indicators associated with endothelial dysfunction to study the etiology of periodontitis in patients with type II diabetes mellitus. Materials and methods. 46 people aged 50–80 years were examined. 20 patients planned hospitalized, with compensated type II diabetes mellitus without complications and other diseases and 26 healthy people were examined as a control group, comparable in age and sex to the patients with SDS. Blood was taken when patients were admitted to the hospital before the treatment. For all studied parameters, a multiple and pairwise comparison was carried out. Results. Considerable changes in endothelial function were found in patients with DFS. There was a significant increase in the concentration in blood serum of indicators such as d-dimers (10.5 times more compared with the control values), factor XIIa (8.4 times more), Willibrand factor (2 times more). The increase in the concentration of fibrinogen, INR and antiplasmin in the plasma of patients with DFS was also revealed. In addition, there was a significant decrease in antithrombin content by 17% compared to control values. Conclusions. The hemostatic system is involved in a wide variety of pathogenetic links in the inflammatory process in periodontal tissues. Due to endothelial disfunction and the damaging effect of hyperglycemia on the cell membranes, hemostasis is activated, so it leads to the thrombosis. This is the cause of severe microcirculation disorders, which further contribute to changes in the periodontal tissues and to the development of inflammatory processes in patients with type II diabetes mellitus.

Haemostatic wound dressing and pharmacologic agents for management of bleeding in dentistry

Haemostasis is a mechanism that, through different interdependent biologic processes, has the purpose of ensuring the integrity and permeability of the circulatory system. Haemostasis term means prevention the loss of blood. Interventions or treatments in the oral cavity, in particular those with a possibility of bleeding, represent a risk for patients with disorders of haemostasis. Prevention is the key to avoid bleeding complications after oral surgical procedures and therefore it is essential a detailed medical history of the patient. This paper investigates the effects of wound dressing and local pharmacologic treatments on haemostasis.

Case reports: spondylodiscitis and epiduritis after suffering COVID-19

Background: The study analyzes a possible rare complication of COVID-19 in the form of spondylodiscitis, including that followed by epiduritis, in patients who survived COVID-19 characterized by severe pneumonia, respiratory failure and systemic inflammatory response syndrome (SIRS).&#x0D; Clinical case description: Three clinical cases of patients are presented, each of whom had high fever, SIRS with a significant increase in the laboratory markers of inflammation (C-reactive protein (CRP), leukocytosis, erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, ferritin), bacterial pneumonia, and severe hemostasis disorders. Despite an antibiotic therapy with broad-spectrum drugs, the development of spondylodiscitis was observed, manifested as acute pain syndrome in the lumbar spine. In the first patient, against the background of a massive antibacterial therapy, revisions of purulent foci, therapy with glucocorticosteroids (GCS), and a surgical treatment, there was significant positive dynamics in the form of the pain syndrome relief. The second patient showed positive dynamics against the background of a conservative antibacterial therapy. The third patient, with a paravertebral abscess at the level of developed spondylodiscitis, received a massive antibiotic therapy combined with GCS, and was operated for the spinal cord decompression.&#x0D; Conclusion: Spondylodiscitis and epiduritis may be possible complications of COVID-19, including those resulting from the immunosuppressive therapy, which is actively used to stop the cytokine storm.

The protective effect of resveratrol on diazinon‐induced oxidative stress and glucose hemostasis disorder in rats' liver

This study was intended to assess the possible protective effect of resveratrol (Res) against oxidative stress and glucose hemostasis disorder in rats exposed to diazinon (DZN) for 4 weeks. Totally 25 Sprague-Dawley rats were divided randomly into five groups: Control (orally received corn oil), DZN group (orally received 70 mg/kg/day), and Res groups (received DZN 70 mg/kg/day plus Res doses of 5, 10, and 20 mg/kg bodyweight/-day), respectively. DZN significantly inhibited serum acetylcholinesterase enzyme (Ach E), serum and liver catalase, glutathione peroxidase activities, also total antioxidant capacities. On the other hand, DZN increased serum and liver malondialdehyde. DZN significantly increased Forkhead box protein O1 (Foxo1) expression and decreased phosphatase and tensin homolog (PTEN) and sirtuin 1 (Sirt-1) expression. DZN impaired glucose hemostasis. Instead, Res treatment significantly reversed status of oxidative stress and antioxidant enzymes activities induced by DZN. Also, Res improved glucose hemostasis. Res increased PTEN and Sirt-1 expression and reduced Foxo1 expression. Res administration ameliorated liver histopathological changes induced by DZN. These data confirmed that DZN significantly enhances oxidative stress and impairs glucose hemostasis. While Res showed a protective effect against the toxicity induced by DZN in rats.

Snakebite envenomation in children: An ongoing burden in Morocco

IntroductionSnakebites are a leading cause of mortality and permanent disabilities especially among children in tropical countries and rural areas such as Morocco. Thus, a nationwide management protocol including specific antivenom therapy along with prevention strategies was implemented to reduce the overall snakebites morbimortality. Patients and methodsOur retrospective study aimed to describe the clinical aspects of snakebite envenomation before and after the implementation of this protocol in children admitted to the pediatric intensive care unit (PICU) in Marrakesh-Morocco for a period of 11 years. ResultsA total of 75 cases were included and were mostly male (70%) with a mean age of 10 years old. Most envenomations were mild or severe (75%) and often occurred during outdoor activities in limb extremities. Altered hemostasis frequently occurred in 67% of cases but was rarely associated with severe exteriorized hemorrhage. Moderate anemia and PNN- predominant leukocytosis were often observed at admission (52.2% and 58%) but quickly tended to normalize before 48 h. Local symptoms were the main dread as they quickly evolve to a compartment syndrome and necrosis in the absence of antivenom therapy. Fasciotomy was performed in 33% of cases while 5 children required limb amputation. Antivenom administration (n = 39) was statistically significant for rapid improvement in hemostasis disorders, reduced blood transfusions and fasciotomy for compartment syndrome as well as a shortened length of stay in PICU. The onset of acute kidney injury was observed in 18 cases but restored in most patients within 48 h (77%). Five children died of which only two had received delayed antivenom immunotherapy due to its unavailability and deferred hospital admission. ConclusionThe advent of specific serotherapy has made it possible to optimize the management of patients and to prevent and treat local and systemic complications thus improving the overall prognosis; nevertheless, primary prevention remains the key to reducing snakebites morbimortality.

Сompliance with therapy in patients with von Willebrand's disease

Von Willebrand's disease (VWD) bleeding is less likely to endanger life, unlike hemophilia. The lack of a significant decrease the quality of life leads to decrease in the compliance of patients with VWD. To improve the situation, the staff of the Department of Hemostasis Disorders, Russian National Research Center for Hematology conducted this program in Moscow and the Moscow region. Determine the patients' compliance to therapy, as well as the difficulties and wishes associated with the treatment of VWD. Survey of patients with VWD on a visit to a hematologist or via phone calls. Questions included information on diagnosis, safety, efficacy, and convenience of replacement therapy, communication, bleeding control, and social standing. The study was approved by the Independent Ethics Committee and the Scientific Council of the National Medical Research Centre for Hematology of the Ministry of Healthcare of the Russian Federation. 41 patients took a part in it: 17 male and 24 female. The majority of initial visits to a specialist are associated with bleeding from the nose and gums (26%), with hematomas (20%), dental operations (13%) and injuries (11%). Most often, the diagnosis was installed by a pediatrician (47%), less often by a surgeon (14%) or genetic inheritance (14%), gynecologists (9%), dentists (7%), otorhinolaryngologists (2%) and doctors of other specialties (7%). Completely satisfied with the therapy are 76% of the respondents. However, one patient considers the therapy ineffective. VWD is the most common coagulopathy, which can be encountered by a doctor of any specialty. Our survey identified a need to educate patients about intravenous injections. The communication between patient and doctor and the therapy correction on time could be improve compliance and reduce the cost of the state for the treatment of complications associated with non-compliance of patients.

The Non-Activated Thromboelastometry (NATEM) Assay's Application among Adults and Neonatal/Pediatric Population: A Systematic Review.

The non-activated thromboelastometry (NATEM) assay is a point-of-care assay that can provide a comprehensive insight into the actual hemostatic mechanism. However, there are very limited data about its use in clinical practice. The aim of this study was to systematically review the literature for any data regarding the use of NATEM in several clinical settings. A systematic review of PubMed and Scopus databases was conducted through 20 January 2022 for studies evaluating the use of the NATEM assay in different clinical settings. The literature search yielded a total of 47 publications, 30 of which met the eligibility criteria for this review. Evaluation of NATEM’s detecting ability for hemostasis disorders is limited in the literature. The results of the included studies indicate that NATEM seems to be a sensitive method for the detection of hyperfibrinolysis and may have an advantage in the diagnosis of hemostatic disorders. It could be more informative than the other ROTEM assays for detecting changes in coagulation parameters in patients who receive anticoagulants. However, the reported outcomes are highly varying among the included studies. NATEM has a high sensitivity to detect hypo- or hypercoagulability and provides a detailed insight into the whole hemostatic process from clot formation to clot breakdown. It could be a useful technique in variable fields of medicine, not only in adults, but also in pediatric and neonatal populations, to guide different hemostatic treatments and predict coagulation disorders or mortality/morbidity; this issue remains to be further investigated.

Acquired hemophilia

Acquired hemophilia is a hemostasis disorder that occurs due to the presence of inhibitory autoantibodies that are directed against coagulation factor VIII. Clinically, it is manifested by spontaneous bleeding mainly in the skin and soft tissues, and unlike hereditary hemophilia ,the presence of hemarthrosis is infrequent. Although many cases are idiopathic, secondary causes must be sought since their treatment is key in the prognosis of the disease. Among these, the presence of autoimmune diseases, neoplasms, drugs, pregnancy, and postpartum stand out. Treatment is based on hemostatic measures to control the bleeding, and therapies to erradicate the autoantibody. In the following manuscript we describe four patients with acquired hemophilia its etiology, treatment, and prognosis. All four patients had resolution of the bleeding after specific treatment. Acquired hemophilia is a rare disorder of hemostasis that should be suspected in patients with extensive spontaneous hematomas without prior coagulopathy. Although in many cases an underlying etiology is not found, secondary causes must be sought since their treatment is key to the patient's evolution.

Routine and Advanced Laboratory Tests for Hemostasis Disorders in COVID-19 Patients: A Prospective Cohort Study.

Background: Thrombosis is frequent during COVID-19 disease, and thus, identifying predictive factors of hemostasis associated with a poor prognosis is of interest. The objective was to explore coagulation disorders as early predictors of worsening critical conditions in the intensive care unit (ICU) using routine and more advanced explorations. Materials: Blood samples within 24 h of ICU admission for viscoelastic point-of-care testing, (VET), advanced laboratory tests: absolute immature platelet count (A-IPC), von Willebrand-GPIb activity (vWF-GpIb), prothrombin fragments 1 + 2 (F1 + 2), and the thrombin generation assay (TGA) were used. An association with worse outcomes was explored using univariable and multivariable analyses. Worsening was defined as death or the need for organ support. Results: An amount of 85 patients with 33 in critical condition were included. A-IPC were lower in worsening patients (9.6 [6.4–12.5] vs. 12.3 [8.3–20.7], p = 0.02) while fibrinogen (6.9 [6.1–7.7] vs. 6.2 [5.4–6.9], p = 0.03), vWF-GpIb (286 [265–389] vs. 268 [216–326], p = 0.03) and F1 + 2 (226 [151–578] vs. 155 [129–248], p = 0.01) were higher. There was no difference observed for D-dimer, TGA or VET. SAPS-II and A-IPC were independently associated with worsening (OR = 1.11 [1.06–1.17] and OR = 0.47 [0.25–0.76] respectively). The association of a SAPS-II ≥ 33 and an A-IPC ≤ 12.6 G/L predicted the worsening of patients (sensitivity 58%, specificity 89%). Conclusions: Immature platelets are early predictors of worsening in severe COVID-19 patients, suggesting a key role of thrombopoiesis in the adaption of an organism to SARS-CoV-2 infection.

Congenital and acquired disorders of secondary hemostasis

: Hemostasis depends on a large number of interdependent processes to prevent spontaneous bleeding and to stop hemorrhage when vascular injury occurs. Although it is commonly divided into primary and secondary for the purpose of simplification and patient evaluation, both processes occur almost simultaneously in vivo. The goal of secondary hemostasis is to produce a firm, cross-linked fibrin clot to stabilize the platelet plug. Fibrin is generated from a series of enzymatic reactions that comprise the coagulation cascade. In this review, we describe the background, physiology, diagnosis, and treatment of congenital and acquired coagulation factor deficiencies. For each condition, we discuss the appropriate laboratory assays as well as the most current treatment modalities. In addition, we describe in detail the oral and parenteral anticoagulants currently available in the United States, their mechanism of action, laboratory monitoring (if appropriate), and how to reverse their effect in case of hemorrhage or need for an emergent procedure. Finally, we review the effect of systemic conditions such as liver disease and disseminated intravascular coagulation (DIC) on the coagulation cascade.

Congenital and acquired disorders of primary hemostasis

Congenital and acquired disorders of primary hemostasis

Platelets mediate inflammatory monocyte activation by SARS-CoV-2 spike protein.

Infection with SARS-CoV-2, the causative agent of COVID-19, causes mild to moderate disease in most patients but carries a risk of morbidity and mortality. Seriously affected individuals manifest disorders of hemostasis and a cytokine storm, but it is not understood how these manifestations of severe COVID-19 are linked. Here, we showed that the SARS-CoV-2 spike protein engaged the CD42b receptor to activate platelets via 2 distinct signaling pathways and promoted platelet-monocyte communication through the engagement of P selectin/PGSL-1 and CD40L/CD40, which led to proinflammatory cytokine production by monocytes. These results explain why hypercoagulation, monocyte activation, and a cytokine storm are correlated in patients severely affected by COVID-19 and suggest a potential target for therapeutic intervention.

Diagnosis and treatment of brain compression in children with hemostasis disorders

We describe the diagnosis of and treatment for brain compression on background of hemostasis disorders in 6 out of 37 patients with hemorrhagic strokes treated in the Ivano-Matreninskaya Children’s Clinical Hospital in 2017–2018. Laboratory examination revealed factor VIII deficiency (hemophilia A) in 3 patients, factor XIII deficiency in one patient; 2 children were carriers of thrombophilia genetic polymorphisms. The age of study participants varied between 15 days and 2 years; all of them were males. They have undergone neurological examination, laboratory testing (hemostasis), neurosonography, multislice computed tomography, and magnetic resonance imaging. Conservative therapy with quarantined fresh frozen plasma (15–25 mL/kg) was used to correct coagulopathy and stop bleeding. Two patients had surgeries: decompressive craniectomy and drainage and endoscopic removal of hematoma. Children that were operated on received transfusion of fresh frozen plasma and red blood cells. Both of them had regression of neurological symptoms and restoration of consciousness in the postoperative period. None of the patients died. In this article, we discuss diagnostics and strategy of conservative and surgical treatment for children with brain compression and coagulopathies.

Study of the Effect of Low-Intensity Sub- and Millimeter Waves on the Induction of Adaptation Reactions in Experimental Burn

Burns are an actual problem of modern medicine. Oxidative stress, microcirculation, and hemostasis disorders are important links in the pathogenesis of burn disease. It is shown that these processes are significantly influenced by the point effect of low-intensity (LI) electromagnetic radiation (EMR) of the millimeter (MM) and submillimeter (subMM) ranges. However, the final opinion on the advantages of a particular range has not been formed. We have given a comparative assessment of the results of the effects of various frequency-energy parameters of microwaves on the indicators of adaptive reactions in rats under experimental thermal trauma and viscoelastic properties of blood in the case of burn disease.

Comparative analysis of hemostasis system state indicators in severe COVID-19

Introduction. Clinical experience in managing patients with a new coronavirus infection caused by the SARS-CoV-2 allowed to identify specific hemostasis disorders, and enables to introduce the concept of COVID-associated coagulopathy. The aim of the study was to assess the direction of coagulogram parameter changes, whole blood clotting parameters and characteristics of platelet and plasma hemostasis in patients with severe COVID-19. Materials and methods. The parameters of the hemostasis system were assessed using venous blood of 12 patients with severe COVID-19 and 16 healthy volunteers. The whole blood clotting process was investigated by low-frequency piezothromboelastography. The platelet count and indicators of spontaneous and ADP-induced platelet aggregation were estimated with the help of a laser platelet aggregation analyzer. Fibrinolytic activity of plasma, plasminogen activity, content of fibrinogen, D-dimer, PTT, APTT, PTI and INR were assessed. Results. An increased level of fibrinogen, a 6-fold increased D-dimer level, and increased PTT were found in patients with severe COVID-19. The patient platelets count was reduced by 51 % (p &lt;0.05), spontaneous platelet aggregation remained at nearly normal level. Almost complete inhibition of ADP-induced platelet reactivity and inhibition of XIIa-dependent fibrinolysis was revealed, despite an increased by 19.3 % (p &lt;0.05) plasminogen activity. Parameters of the whole blood coagulation process pointed a pronounced activation of platelet hemostasis, a significant intensification of the polymerization stage of clot formation and an increased intensity of clot lysis and retraction. Conclusion. The significant increase of D-dimer level and paradoxical inhibition of plasma fibrinolytic activity revealed by test of XIIa-dependent fibrinolysis (in contrast to the increased intensity of clot lysis when assessing the coagulation of whole blood) indicate the complex pathogenic mechanisms of coagulopathy caused by SARS-CoV-2 infection, and the involvement of blood cells and the vascular wall in the process of pathological thrombus formation.

Effect of lactic acid addition to equine whole blood on platelet aggregation measured by impedance aggregometry

Acidemia in sick or injured horses is often due to lactic acid accumulation. Alterations in platelet function and hemostasis are among numerous deleterious effects caused by decreased physiologic pH. We aimed to evaluate the effect of hyperlactatemia and resultant acidemia on platelet aggregation in equine whole blood using impedance aggregometry. Platelet aggregation was measured using the Multiplate analyzer in whole blood from 34 healthy horses at baseline and after in vitro addition of lactic acid to adjust the pH. Platelet aggregation of each sample was quantified by the area under the curve measurement reported by the Multiplate system. The association between platelet aggregation and pH was analyzed using a linear mixed-effects model. The association of baseline platelet aggregation with hematocrits (Hcts), white blood cell (WBC) counts, and platelet counts was evaluated using Pearson's correlations. There was a significant association between acidemia and decreased platelet aggregation. No significant correlations were detected between platelet aggregation and Hct, WBC count, or platelet count. Platelet aggregation measured in healthy horses using the Multiplate analyzer showed substantial variation between animals. Acidemia caused by the addition of lactic acid to equine whole blood was associated with a mild though statistically significant decrease in platelet aggregation. In conjunction with other factors, this change may contribute to morbidity-related disorders of hemostasis, although its precise clinical relevance is uncertain.