DIC, SIC or CAC - the haemostatic profile in COVID-19 patients hospitalised in the intensive care unit: a single-centre retrospective analysis.

INTRODUCTION: Infection with SARS-CoV-2 in its most severe form leads to acute respiratory distress syndrome requiring mechanical ventilation under the conditions of the Intensive Care Unit (ICU). The state of hypercoagulation described in COVID-19 may deepen respiratory failure, leading to increased mortality. The aim of the presented study is to characterise the haemostatic profile based on the results of clotting system parameters and risk assessment of thromboembolic complications of patients hospitalised in the ICU. MATERIAL AND METHODS: This retrospective study covered the first 10 adult patients hospitalised in the ICU of the Hospital for Infectious Diseases in Warsaw in the second quarter of 2020. Demographic, clinical and laboratory parameters of the coagulation system and the risk of thromboembolic complications were assessed. Well known criteria of haemostatic disorders were used to classify the observed derangements. RESULTS: The most frequently observed deviations in the coagulation system were high concentrations of D-dimer and fibrinogen. In select cases the clotting time was prolonged. No severe thrombocytopenia was observed. All patients presented a high risk of thromboembolic complications as assesed by the Padua score. The observed clotting abnormalities did not meet the criteria for DIC (disseminated intravascular coagulation) and SIC (sepsis-induced coagulopathy) diagnosis. CONCLUSIONS: The main elements of coagulopathy that were observed in our cases differ from those usually seen in patients with recognised sepsis. The unique haemostatic profile of COVID-19 patients treated in the ICU has been described as CAC (COVID-19-associated coagulopathy).

COVID-19: coagulation disorders and anticoagulant treatment in patients hospitalised in ICU.

Patients hospitalized in the intensive care unit (ICU) due to the COVID-19 experience a high incidence (up to 43%) of venous thromboembolic events. While laboratory findings in COVID-19-associated coagulopathy (CAC) show increased D-dimer and fibrinogen levels, the abnormalities in standard coagulation tests and platelet count are minimal. Recent studies suggest contribution of fibrinolysis shutdown to this phenomenon. Endothelial injury and alteration of its antithrombotic activity can lead to micro- and macrovascular thrombosis in the lungs, occurrence of which is associated with poor clinical outcome in critically ill patients with COVID-19. Additionally, the hypercoagulability induced by activation of coagulation pathways during the immune response to SARS-CoV-2 infection contributes to impaired organ perfusion. This, alongside with hypoxemia, leads to multiorgan failure. Various diagnostic regimens, some of which include global assays of haemostasis, are currently being published and discussed. Numerous guidelines and recommendations of scientific societies and groups of specialists have been published. However, there is no single optimal algorithm for anticoagulation treatment and monitoring specific to the ICU patients with COVID-19. The authors have attempted to summarize the data related to CAC and thrombotic disease and develop an algorithm consistent with the latest clinical practice guideline recommendations.

Assessment of haemostasis and impact of fibrinogen supplementation on clot properties using global haemostasis assays in patients on chronic dialysis.

BACKGORUND: Multifactorial haemostasis disorders are typical of patients with end-stage renal disease (ESRD) on chronic haemodialysis (HD). Thromboelastometry and impedance aggregometry allow for a comprehensive assessment of clot formation, lysis, and platelet (PLT) function. This study aims to determine the haemostatic profile in a group of patients with ESRD on chronic, interrupted dialysis, especially in terms of PLT function and the impact of in vitro fibrinogen concentrate supplementation on clot properties. METHODS: A total of 22 patients on chronic HD and 22 healthy controls (HC) were enrolled in the prospective study with a control group. Global haemostasis assays (GHA) were used to describe the haemostasis profile and to assess the effect of fibrinogen concentrate supplementation on improving clot quality. RESULTS: Despite the lack of considerable differences in the number of PLTs, there was a significantly lower potential of PLT aggregation in the HD group (922 ±163 AU*min). A higher concentration of fibrinogen was also observed in this group which presented considerably higher maximum clot firmness (MCF) FIBTEM (22 ±5.3 mm). Clotting time (CT) EXTEM was also prolonged (72 ±23 s). No hyperfibrinolysis was reported. In vitro fibrinogen concentrate supplementation resulted in significant improvement in MCF FIBTEM (30 mm vs. 22 mm; P < 0.001). However, it also led to a deterioration in PLT aggregation as assessed by TRAPtest. CONCLUSIONS: The haemostasis profile of ESRD patients demonstrates a limited potential of PLT aggregation, with no improvement after fibrinogen addition.

Thrombocytopenia: the most frequent haemostatic disorder in the ICU.

Thrombocytopenia is the most common haemostatic disorder in patients admitted to Intensive Care Units (ICUs). The mechanisms contributing to a decrease in the platelet count in critically ill patients are multifactorial, among which sepsis and trauma are the most frequent. A differential diagnosis of profound thrombocytopenia is crucial for effective treatment. A low platelet count is a strong independent predictor of morbidity and mortality because it is associated with life-threatening bleeding or thrombosis. This article aims to outline the definition and pathophysiology of thrombocytopenia and present a three-step algorithm of the clinical management of this haemostatic disorder.

Response to the article "Perioperative standards for the treatment of coagulation disorders and usage of blood products in patients undergoing liver transplantation used in the Clinic for Transplant Surgery in Wroclaw".

We read with interest the article by Lukaszewski et al. published in Advances in Clinical and Experimental Medicine:1211-1215, published online on July 18th, 2018, as ahead of print). As enthusiasts of promoting global assays of hemostasis, we would like to commend the authors for their commitment and effort in their implementation and clinical application. As the authors rightly pointed out in the article, perioperative care of liver transplantation (OLTx) patients is challenging for transplant team members due to the risk of severe changes in global hemostasis. Lukaszewski et al. presented a single center experience in using rotational thromboelastometry (ROTEM) to monitor hemostasis during liver transplantation. In our center, this method has been used routinely since 2008. So far it has been used in over 400 patients undergoing OLTx. Considering the potential contribution to thrombotic complications (including portal vein thrombosis after liver transplantation), we believe that antifibrinolytic treatment should be reserved for patients with active bleeding and hyperfibrinolysis confirmed by ROTEM. The available literature indicates an increased risk of thrombotic complications in patients receiving antifibrinolytic therapy. This raises an important question for the authors about the reason for using Exacyl® in all 12 of the cases presented, even in patients who did not require any blood product transfusion. We hope that our letter will open up further discussion on this subject, which is undoubtedly crucial for OLTx patients' safety.

The assessment of platelet function using multiple electrode aggregometry in practical procedures in anaesthesia.

BACKGROUND: Platelets are responsible for primary haemostasis. Patients with suspected platelet dysfunction require prompt clinical assessment when qualifying for emergency surgical procedures. The purpose of this article is to present our experience in platelet function assessment using whole-blood multiple electrode aggregometry (MEA) in various clinical conditions. CASE REPORTS: Retrospective analysis of three patients with thrombocytopathy associated with normal platelet counts was performed using standard laboratory tests complemented by MEA. In two cases, platelet dysfunction was due to antiplatelet drugs, while in one other case it was caused by chronic kidney disease. CONCLUSIONS: Anaesthesiologists strive to make the perioperative period as safe as possible. Platelet function assessment should be considered in every patient in whom haemostatic disturbances are suspected. MEA provides support for clinical decision-making, especially in patients who undergo haemodialysis or require antiplatelet therapy, and are in need of emergency surgery.

Multiple electrode aggregometry as a method for platelet function assessment according to the European guidelines.

Platelets play an essential role in haemostasis. Assessment of their function is vital for anaesthesiologists evaluating haemostatic potential, especially during emergency operations. The monitoring of platelets function had been implemented into the European recommendations for management of perioperative and posttraumatic bleeding. One of the diagnostic methods described in the recommendations is multiple electrode aggregometry. As antiplatelet therapy becomes more widely used in modern medicine, this method, in contrast to standard laboratory tests, can significantly help to identify patients with drug-induced thrombocytopaty. The aggregometry enables prompt evaluation of the platelets aggregation which is very useful for everyday decision-making in goal-directed hemostatic therapy.

Is Hydroxyethyl Starch Irrelevant to Hemostasis in Patients Undergoing Liver Transplantation?--In vitro Analysis Based on Thromboelastometry.

BACKGROUND: Liver transplantation may be associated with severe bleeding that requires intensive fluid management. Aggressive fluid administration could result in hemodilution, triggering dilutional coagulopathy that intensifies bleeding. Colloids are plasma expanders used in daily practice. Fibrinogen, malfunctioning in liver cirrhosis, is the earliest decreasing clotting factor while bleeding. Fibrinogen supplementation is recommended as the first-choice therapy in such cases. Therefore, the influence of hemodilution on fibrin clot formation among patients with liver cirrhosis was analyzed, followed by the assessment of fibrinogen supplementation in clot restitution. MATERIAL AND METHODS: Blood collected from 22 patients with post-inflammatory liver cirrhosis was diluted up to 30% and 60% with crystalloid (0.9% NaCl) or colloid (6% hydroxyethyl starch 130/0.4), followed by fibrinogen supplementation corresponding to an overall dose of 4 g. The influence of hemodilution on plasma fibrinogen concentration and on thromboelastometry FIBTEM test was analyzed, as well as the influence of fibrinogen supplementation. RESULTS: Hemodilution lowers fibrinogen concentration and decreases fibrin clot formation. The higher the grade of dilution, the more profound the disturbances observed; 6% hydroxyethyl starch 130/0.4 cause more intense effect on fibrin clot formation than 0.9% NaCl. Fibrinogen supplementation improves fibrin clot formation as assessed in FIBTEM. CONCLUSIONS: Fibrinogen supplementation among patients with liver cirrhosis might improve fibrin clot formation during hemodilution. Fibrinogen supplementation might by considered as a possible treatment of coagulopathy during liver transplantation, but further clinical studies need to be performed.

Correlates of agitation and depression in nursing home residents with dementia.

BACKGROUND: The purpose of this study was to investigate the relationship between dementia severity, age, gender, and prescription of psychotropics, and syndromes of agitation and depression in a sample of nursing home residents with dementia. METHODS: The Cohen-Mansfield Agitation Inventory (CMAI) was administered to residents with dementia (N = 304) of 18 nursing homes. Agitation symptoms were clustered using factorial analysis. Depression was estimated using the Dementia Mood Assessment Scale (DMAS). Dementia severity was assessed categorically using predefined cut-off scores derived from the Mini-Mental State Examination (MMSE). The relationship between agitation and its sub-syndromes, depression, and dementia severity was calculated using χ 2-statistics. Linear regression analyses were used to calculate the effect of dementia severity and psychotropic prescriptions on agitation and depression, controlling for age and gender. RESULTS: Increasing stages of dementia severity were associated with higher risk for physically aggressive (p < 0.001) and non-aggressive (p < 0.01) behaviors, verbally agitated behavior (p < 0.05), and depression (p < 0.001). Depressive symptoms were associated with physically aggressive (p < 0.001) and verbally agitated (p < 0.05) behaviors, beyond the effects of dementia severity. Prescription of antipsychotics was correlated with depression and all agitation sub-syndromes except hiding and hoarding. CONCLUSIONS: Dementia severity is a predictor for agitation and depression. Beyond that, depression increased with dementia severity, and the severity of depression was associated with both physically and verbally aggressive behaviors, indicating that, in advanced stages of dementia, depression in some patients might underlie aggressive behavior.

The pharmacotherapy of neuropsychiatric symptoms of dementia: a cross-sectional study in 18 homes for the elderly in Berlin.

BACKGROUND: The neuropsychiatric symptoms of dementia, including aggressiveness, agitation, depression, and apathy are often treated with psychotropic drugs and are a frequent reason for hospitalization, placing an economic burden on the health care system. International guidelines recommend syndrome-specific pharmacotherapy. We studied the question whether drug-prescribing practices are, in fact, syndrome-specific. METHODS: In a cross-sectional study in 18 homes for the elderly in Berlin, we used syndrome-specific scales to determine the prevalence of apathy, depression, and aggressiveness and the quantity of psychotropic drugs prescribed, in defined daily dosages (DDD), among 304 demented inhabitants. The diagnosis of dementia was ascertained by chart review and confirmed by administration of a mini mental status test. RESULTS: More than 90% of the demented patients had neuropsychiatric symptoms, most commonly apathy (78%). 52% were treated with neuroleptic drugs, 30% with antidepressants and 17% with anti-dementia agents. There was no significant difference between the frequency of neuroleptic treatment given to apathetic and depressed patients and that given to aggressive patients (chi(2) = 7.03; p = 0.32). CONCLUSION: Although our sample of patients was not representative, these findings suggest that neuropsychiatric symptoms in demented patients are not being treated in syndrome-specific fashion. This is troubling, because neuroleptic medications administered to demented patients can have serious adverse effects, including an elevated mortality. The German guidelines for the treatment of neuropsychiatric disturbances were recently published; the findings presented here suggest that their implementation would be advantageous.

[Pharmacotherapy of neuropsychiatric symptoms in dementia in nursing homes: a comparison of service provision by psychiatric outpatient clinics and primary care psychiatrists]. / Pharmakotherapie von neuropsychiatrischen Symptomen bei Demenz in Altenpflegeheimen: Ein Vergleich der Versorgung durch psychiatrische Institutsambulanzen und niedergelassene Fachärzte.

BACKGROUND: Neuropsychiatric symptoms of dementia like agitation, depression and apathy often result in increased prescriptions of psychotropics. In Germany, outpatient clinics at psychiatric hospitals play an important role in the treatment of neuropsychiatric symptoms in nursing homes. The aim of this study was to test whether the severity and pharmacotherapy differed in patients treated by outpatient clinics at psychiatric hospitals, as compared to primary care specialists. METHODS: A cross-sectional study of the prevalence of agitation, apathy, and depression, and the amount of psychotropics prescribed in defined daily dosages (DDD) in 304 residents with dementia in 18 Berlin nursing homes. RESULTS: Patients treated by outpatient clinics at psychiatric hospitals suffered from more severe neuropsychiatric symptoms (p < 0.05), were prescribed more antidepressants and antidementia agents (p < 0.05) and, when adjusting for the severity of agitation, less neuroleptics (p < 0.05) as compared to primary care specialists. CONCLUSION: Psychiatric outpatient clinics at hospitals treat more severely demented patients who suffer from severe neuropsychiatric symptoms. The pharmacotherapy provided by these clinics displays a favourable profile according to established treatment guidelines.