Coagulation Parameters In Patients Research Articles

Impact of Female Sex and Mild Cortisol Secretion on Coagulation Profile in Adrenal Incidentalomas.

Studies describing the coagulation profile in adrenal adenomas still need to be added. We explored how sex and mild autonomous cortisol secretion (MACS) affect coagulation parameters in patients with adrenal adenomas. Cross-sectional study. From January 2019 until April 2023, participants in the Impact of Adrenal IncidenTalomas and Possible Autonomous Cortisol Secretion on Cardiovascular and Metabolic Alterations trial (NCT04127552) diagnosed with adrenal adenoma were categorised according to the 1 mg overnight dexamethasone-suppression test (1 mg-DST). Coagulation parameters were evaluated, and two-way ANOVA was used to elucidate the cortisol-by-sex interaction. Of 153 patients screened, 90 were enrolled (62.2% female, mean age 62 ± 10 years): 41 with non-functioning adrenal tumour (1 mg-DST ≤ 1.8 µg/dL), and 49 with a MACS (1 mg-DST > 1.8 µg/dL). Platelet counts were higher in the MACS group (P = .01). Regression analysis identified female sex (B = 36.603, P = .011), 1mg-DST (B = 0.238, P = .042), and younger age (B = -1.452, P = .038) as independent predictors for elevated platelet count. In patients with MACS, women exhibited higher levels of procoagulant factors fibrinogen (P = .004) and factor VIII (P < .001), and coagulation inhibitors protein C (P = .003) and antithrombin III (P = .005) than males. No differences were observed in the non-functioning adrenal tumour group, providing a cortisol-by-sex interaction regarding fibrinogen (P = .047), factor VIII (P = .046), and protein C (P = .028). Our findings revealed a worse coagulation profile in women with MACS, underscoring the need for a sex-specific approach in clinical practice to manage thrombotic risks effectively. Dedicated prospective studies are needed to validate and integrate these findings into clinical strategies for thromboprophylaxis.

Study of Coagulation Parameters in Gastrointestinal Malignancies.

Introduction Gastrointestinal (GI) malignancies represent a diverse group of cancers affecting various parts of the digestive system. These malignancies encompass an important burden of cancer incidence and mortality globally, contributing to substantial morbidity and mortality worldwide. Studying the coagulation parameters of patients having GI malignancies is crucial for several reasons. It allows to identify the patients at an increased risk of thrombotic complications, enabling clinicians to implement appropriate prophylactic measures, such as anticoagulant therapy or mechanical thromboprophylaxis. Aim To study coagulation parameters in patients diagnosed with GI malignancies. Materials and methods The present study is a two-year prospective observational study, carried out in the Department of Pathology in our tertiary care institute from July 2022 to June 2024 to investigate the coagulation profile in patients diagnosed with GI malignancies. A total of 86 cases were studied. Results A significant increase in the mean values of coagulation parameters was noted with an increase in the grade of malignancy. Conclusion Early examination for the presence of coagulation abnormalities can help to prevent morbidity and mortality and other bleeding diathesis in GI malignancies as alterations in the coagulation pathway can lead to lethal complications.

Impact of Duration of Parkinsonism and Antiparkinsonian Drugs on Coagulation Parameters in Patients with Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder involving depletion of dopaminergic neurons. Pathogenetic mechanisms leading to striatonigral degeneration are debatable. Chronic inflammation is proposed as one of the mechanisms. In any disease with underlying inflammation, immune system mediators called cytokines are released, leading to a procoagulant state. Our aim was to study the coagulation parameters in patients with PD and find their correlation with disease duration and antiparkinsonian drugs. This cross-sectional study was conducted between January 2021 and December 2021 in a tertiary care center. Sixty-eight patients with PD were subcategorized based on disease duration (<5 and ≥5 years), number of antiparkinsonian drugs (one drug and ≥2 drugs), and levodopa equivalent daily dose (LEDD; <350 and ≥350 mg). Hemoglobin (Hb), prothrombin time (PT), fibrinogen, bleeding time, and platelet aggregation study with adenosine diphosphate and collagen were assessed. In our cohort of 68 patients, 53 were men and 15 were women. Mean disease duration was 5.97 ± 4.37 years. Hb was negatively associated with LEDD ( P = 0.012) and duration of the disease ( P = 0.02). Similarly, PT was negatively associated with disease duration ( P = 0.041) and number of antiparkinsonian drugs ( P = 0.03). LEDD showed a positive association with collagen-induced platelet aggregation ( P = 0.03). In our study, patients using multiple antiparkinsonian drugs and higher LEDD were observed to have a prothrombotic state. Further studies are needed to confirm these findings.

Impact of Treatment with Direct Antivirals on Coagulation Parameters in Patients with Hepatitis C Virus-Related Liver Cirrhosis and Sustained Virological Response.

Background and Objectives: Sustained virologic responses (SVRs) lead to a decrease in portal hypertension, the regression of fibrosis, and the improvement in the hepatic synthesis of procoagulant and anticoagulant factors. We aimed to assess the influence of SVR on coagulation parameters in cirrhotic patients with HCV treated with DAAs. Methods: We performed a prospective study in the Institute of Gastroenterology and Hepatology Iasi, Romania, between January 2022 and February 2024. We included patients diagnosed with compensated and decompensated HCV-related liver cirrhosis, treated with direct antivirals (PrOD ± RBV or SOF/LED ± RBV) for 12/24 weeks. Blood samples for biochemical, immunological, and coagulation tests were collected at the baseline, end of treatment (EOT), and once sustained virological response had been achieved over a period of 12/24 weeks (SVR12/24). Results: We analyzed a group of 52 patients with HCV-related liver cirrhosis, predominantly female (68.0%), and the degree of severity of cirrhosis placed the patients mainly in Child-Pugh classes B (40%) and C (36%). All patients achieved SVRs. The MELD score decreased at EOT (13.48 ± 4.273; p = 0.001) and SVR (9.88 ± 2.774; p = 0.000), compared to the baseline (14.92 ± 4.707). The FibroScan values decreased at SVR (17.596 ± 3.7276; p = 0.000) compared to the baseline (26.068 ± 7.0954). For all common coagulation parameters (platelets, INR, PT, fibrinogen, aPTT), there was a trend towards improvement during treatment, including changes which were statistically significant for the majority of patients. Factor II was low at the baseline (75.40 ± 7.506) but increased at EOT (87.40 ± 9.587) and, later, at SVR (99.12 ± 11.695; p = 0.000). The FVIII values increased at the baseline (175.52 ± 16.414) and decreased at EOT (151.48 ± 13.703) and SVR (143.40 ± 13.937). The FvW values decreased during treatment (146.84 ± 9.428, at baseline; 141.32 ± 9.690, p = 0.000, at EOT; and 126.68 ± 17.960, at SVR). In regard to the anticoagulant factors (PC, PS, ATIII), a significant improvement was brought on by SVR. Advanced stages of liver disease showed the most diminished FII activity, while at the baseline and in Child-Pugh C patients we recorded the highest values of FVIII and FvW. Conclusions: Our study proved that the "reset" of coagulopathy might be due to the improvement in liver function due to viral eradication secondary to AAD therapy.

Analysis of laboratory parameters in non-traumatic epistaxis

Objective: The present study investigated the relationship between epistaxis and age, sex, hemogram and coagulation parameters and aimed to set a standard in the approach to epistaxis. Materials and Methods: Patients over the age of 18 who presented due to epistaxis between July 1, 2022, and July 1, 2023, were included in this study, and the files of these patients were examined retrospectively. Patients with trauma and chronic hypertension (HT), individuals with diseases that might predispose to bleeding and with a history of bleeding-related drug use such as coumadin derivatives or individuals with malignancy, those who were found to have active infection during the study, patients who were determined to be in the postoperative period, patients whose blood pressure was determined to be above 140/90 mmHg at the time of admission, and those who were found to have blood samples with hemolysis detected in the file records were excluded from the study. Results: The data of a total of 100 patients, including 62 male and 38 female patients, who presented with complaints of epistaxis, were examined. It was found that more patients at older ages presented to emergency departments with complaints of epistaxis and the number of male patients with epistaxis was higher than female patients. It was concluded that headache is the most common early symptom before spontaneous bleeding in nosebleeds, which are more common in older adults, and platelet values, which are negatively correlated with age and positive correlated with activated partial thromboplastin time ( aPTT ) and hemoglobin (HGB ) are an essential marker for nosebleeds. Furthermore, it was concluded that it is meaningless to check coagulation parameters in patients who are not coumadinized, while checking the hemogram remains important.

Evaluation of selected haematological and coagulation parameters in patients with intracranial aneurysms

Evaluation of selected haematological and coagulation parameters in patients with intracranial aneurysms

Clinical value of coagulation parameters in predicting the severity of severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus infection with a high lethality rate. The purpose of this study was to investigate the changes in coagulation parameters in patients with SFTS, aiming to provide clinical evidence for early diagnosis, treatment, and disease analysis. A total of 40 patients with SFTS attended from April 1, 2020 to May 21, 2022 in Nanjing Drum Tower Hospital were selected and grouped according to the duration of the disease, mild and severe disease, cure and death, with 50 healthy physical examiners as controls, and the risk of severe and death disease was predicted using ROC curves. Comparison between the healthy, mild and severe groups revealed that PT, INR, APTT, TT, D-D and vWF levels were higher than those in the healthy control group, and FII, FIX, FX, FXI, FXII, PC and PS levels were lower than those in the healthy control group, the differences were statistically significant (p < 0.05). Comparing the results of SFTS patients with different course times, the results of Fib, FV, FVII, FVIII, FIX, FX, FXI were statistically significant (p < 0.05). Among the survived and deceased patients, the PT, INR, DD and PS results of the deceased patients were higher than those of the survived patients, and the FVIII, FIX, FXI, FXII and PC were lower than those of the survived patients. The area under the ROC curve showed that D-D had higher predictive ability for the risk of severe disease (AUROC 0.93, sensitivity and specificity at a Cut-off value of 1.50 mg/L were 90.0 and 86.5%, respectively) and the risk of death occurring (AUROC 0.84, sensitivity and specificity at a Cut-off value of 3.39 mg/L were 87.5 and 80.0%, respectively). The monitoring of the coagulation parameters in patients with SFTS is great significance for identifying the severity and death of the patient's condition, and it is of great clinical value to provide early attention, timely intervention and maximum reduction of the mortality rate for patients at risk of severe disease.

Levels of peripheral blood routine, biochemical and coagulation parameters in patients with hemorrhagic fever with renal syndrome and their relationship with prognosis: an observational cohort study

BackgroundHantaan virus (HTNV), Seoul virus (SEOV) and Puumala virus (PUUV) are major serotypes of the Hantavirus, which can cause hemorrhagic fever with renal syndrome (HFRS). The pathophysiology of HFRS in humans is complex and the determinants associated with mortality, especially the coagulation and fibrinolysis disorders, are still not been fully elucidated. Severe patients usually manifest multiple complications except for acute kidney injury (AKI). The aim of this study was to observe the levels of peripheral blood routine, biochemical and coagulation parameters during the early stage, so as to find independent risk factors closely related to the prognosis, which may provide theoretical basis for targeted treatment and evaluation.MethodsA total of 395 HFRS patients from December 2015 to December 2018 were retrospectively enrolled. According to prognosis, they were divided into a survival group (n = 368) and a death group (n = 27). The peripheral blood routine, biochemical and coagulation parameters were compared between the two groups on admission. The relationship between the parameters mentioned above and prognosis was analyzed, and the dynamic changes of the coagulation and fibrinolysis parameters during the first week after admission were further observed.ResultsIn addition to AKI, liver injury was also common among the enrolled patients. Patients in the death group manifested higher levels of white blood cell counts (WBC) on admission. 27.30% (107/392) of the patients enrolled presented with disseminated intravascular coagulation (DIC) on admission and DIC is more common in the death group; The death patients manifested longer prothrombin time (PT) and activated partial thromboplastin time (APTT), higher D-dimer and fibrinogen degradation product (FDP), and lower levels of platelets (PLT) and fibrinogen (Fib) compared with those of the survival patients. The proportion of D-dimer and FDP abnormalities are higher than PT, APTT and Fib. Prolonged PT, low level of Fib and elevated total bilirubin (TBIL) on admission were considered as independent risk factors for prognosis (death).ConclusionsDetection of PT, Fib and TBIL on admission is necessary, which might be benefit to early predicting prognosis. It is also important to pay attention to the dynamic coagulation disorders and hyperfibrinolysis during the early stage in the severe HFRS patients.

CA125-Associated Activated Partial Thromboplastin Time and Thrombin Time Decrease in Patients with Adenomyosis.

Adenomyosis patients are in a hypercoagulable state, and studies have shown that carbohydrate antigen125 (CA125) may relate to the hypercoagulability and thrombosis of patients with adenomyosis, but there is still a lack of clarity regarding the changes in CA125-related coagulation indicators. This study was to explore the changes and influencing factors of CA125-related coagulation parameters in patients with adenomyosis. Retrospective observational study conducted on 200 patients with adenomyosis (AM group), 240 patients with uterine leiomyoma (LM group) and 81 patients with cervical intraepithelial neoplasia (CIN)-III (control group), of which the coagulation parameters were detected by clinical blood sample collection and statistical method analysis and informed consent was obtained. The level of CA125 in the AM group was significantly higher than that in the LM group and control group. However, thrombin time (TT) shortened in the AM group when compared with the LM and control group. Activated partial thromboplastin time (APTT) in the AM group was shorter than in the control group. Multivariate logistic regression analysis found that adenomyosis was associated with CA125 level (OR=323.860, 95% CI 90.424-1159.924, P<0.001), APTT (OR=1.295, 95% CI 1.050-1.598, P=0.016), TT (OR=0.642, 95% CI 0.439-0.938, P=0.022), menorrhagia (OR=7.363, 95% CI 2.544-21.315, P<0.001), dysmenorrhea (OR=22.590, 95% CI 8.185-62.347, P<0.001). Correlation analysis revealed that APTT (r= -0.207) and TT (r = -0.174) were negatively correlated with the level of CA125. The shortening of CA125-related APTT and TT indicates that it is meaningful to detect coagulation parameters of patients with elevated CA125 levels early, dysmenorrhea and menorrhagia, and maybe further discover the hypercoagulability and prevent the occurrence of thrombus in adenomyosis.

Effect of 3D laparoscopy versus traditional laparotomy on serum tumor markers and coagulation function in patients with early-stage endometrial cancer

ObjectivesTo investigate the impact of Three-Dimensional (3D) laparoscopy compared to traditional laparotomy on serum tumor markers and coagulation function in patients diagnosed with early-stage Endometrial Cancer (EC). MethodThe authors retrospectively analyzed the clinical data of 75 patients diagnosed with early-stage EC and categorized them into two groups based on the surgical techniques employed. The 3D group consisted of 36 patients who underwent 3D laparoscopic surgery, while the Laparotomy group comprised 39 patients who underwent traditional laparotomy. The authors then compared the alterations in serum tumor markers and coagulation function between the two groups. ResultsPostoperatively, serum levels of CA125, CA199, and HE4 were notably reduced in both groups on the third day, with the levels being more diminished in the 3D group than in the Laparotomy Group (p < 0.05). Conversely, FIB levels escalated significantly in both groups on the third-day post-surgery, with a more pronounced increase in the 3D group. Additionally, PT and APTT durations were reduced and were more so in the 3D group than in the laparotomy group (p < 0.05). ConclusionsWhen juxtaposed with traditional laparotomy, 3D laparoscopic surgery for early-stage EC appears to be more efficacious, characterized by reduced complications, and expedited recovery. It can effectively mitigate serum tumor marker levels, attenuate the inflammatory response and damage to immune function, foster urinary function recovery, and enhance the quality of life. However, it exerts a more significant influence on the patient's coagulation parameters, necessitating meticulous prevention and treatment strategies for thromboembolic events in clinical settings.

The interplay between tamoxifen and endoxifen plasma concentrations and coagulation parameters in patients with primary breast cancer

BackgroundTamoxifen is an effective treatment for primary breast cancer but increases the risk for venous thromboembolism. Tamoxifen decreases anticoagulant proteins, including antithrombin (AT), protein C (PC) and tissue factor (TF) pathway inhibitor, and enhances thrombin generation (TG). However, the relation between plasma concentrations of both tamoxifen and its active metabolite endoxifen and coagulation remains unknown. MethodsTamoxifen and endoxifen were measured in 141 patients from the prospective open-label intervention TOTAM-study after 3 months (m) and 6 m of tamoxifen treatment. Levels of AT and PC, the procoagulant TF, and TG parameters were determined at both timepoints if samples were available (n = 53–135 per analysis). Levels of coagulation proteins and TG parameters were correlated and compared between: 1) quartiles of tamoxifen and endoxifen levels, and 2) 3 m and 6 m of treatment. ResultsAt 3 m, levels of AT, PC, TF and TG parameters were not associated with tamoxifen nor endoxifen levels. At 6 m, median TF levels were lower in patients in the 3rd (56.6 [33] pg/mL), and 4th (50.1 [19] pg/mL) endoxifen quartiles compared to the 1st (lowest) quartile (76 [69] pg/mL) (P=0.027 and P=0.018, respectively), but no differences in anticoagulant proteins or TG parameters were observed. An increase in circulating TF levels (3 m: 46.0 [15] versus 6 m: 54.4 [39] pg/mL, P < 0.001) and TG parameters was observed at the 6 m treatment timepoint, while AT and PC levels remained stable. ConclusionsOur results indicate that higher tamoxifen and endoxifen levels are not correlated with an increased procoagulant state, suggesting tamoxifen dose escalation does not further promote hypercoagulability.

Association of Broad-Spectrum Antibiotic Therapy and Vitamin E Supplementation with Vitamin K Deficiency-Induced Coagulopathy: A Case Report and Narrative Review of the Literature.

Vitamin K is a lipid-soluble vitamin that is normally maintained within appropriate levels by means of dietary intake and bacterial production in the intestinal microflora. It holds a central role in coagulation homeostasis, and thus its depletion leads to hypocoagulation and haemorrhagic diathesis. The association of antibiotic therapy and vitamin E supplementation with vitamin K deficiency was previously described in animal experiments, clinical studies, and case reports. Broad-spectrum antibiotic therapy potentially leads to intestinal microflora dysbiosis and restriction of vitamin K-producing bacterial populations, resulting in decreased vitamin K levels, whereas antibiotics of the cephalosporin class with 1-N-methyl-5-thiotetrazole (NMTT) or 2-methyl-1,3,4-thiadiazole (MTD) side groups inhibit vitamin K function. Vitamin E supplementation interferes with both the bioavailability and function of vitamin K, yet its mechanisms are not fully understood. We present the case of a 45-year-old male patient, with a history of epilepsy and schizophrenia, catatonically incapacitated and immobilised, who was hospitalised in our centre for the investigation and management of aspiration pneumonia. He demonstrated a progressively worsening prolongation of international normalised ratio (INR), which was attributed to both broad-spectrum antibiotic therapy and vitamin E supplementation and was reversed upon administration of vitamin K. We highlight the need for close monitoring of coagulation parameters in patients receiving broad-spectrum antibiotic therapy, especially those with underlying malnutritive or malabsorptive conditions, and we further recommend the avoidance of NMTT- or MTD-containing antibiotics or vitamin E supplementation, unless absolutely necessary, in those patients.

PB2666: MAIN DISORDERS AND COAGULATION PARAMETERS IN PATIENTS WITH COVID-19

PB2666: MAIN DISORDERS AND COAGULATION PARAMETERS IN PATIENTS WITH COVID-19

Comprehensive Analyses of Coagulation Parameters in Patients with Vascular Anomalies

Vascular anomalies comprise a diverse group of rare diseases with altered blood flow and are often associated with coagulation disorders. The most common example is a localized intravascular coagulopathy in venous malformations leading to elevated D-dimers. In severe cases, this may progress to a disseminated intravascular coagulopathy with subsequent consumption of fibrinogen and thrombocytes predisposing to serious bleeding. A separate coagulopathy is the Kasabach-Merritt phenomenon in kaposiform hemangioendothelioma characterized by platelet trapping leading to thrombocytopenia and eventually consumptive coagulopathy. Our previous work showed impaired von Willebrand factor and platelet aggregometry due to abnormal blood flow, i.e., in ventricular assist devices or extracorporeal membrane oxygenation. With altered blood flow also present in vascular anomalies, we hypothesized that, in particular, the von Willebrand factor parameters and the platelet function may be similarly impacted. We prospectively recruited 73 patients with different vascular anomaly entities and analyzed their coagulation parameters. Acquired von Willebrand syndrome was observed in both of our patients with Kasabach-Merritt phenomenon. In six out of nine patients with complex lymphatic anomalies, both the vWF antigen and activity were upregulated. Platelet aggregometry was impaired in both patients with Kasabach-Merritt phenomenon and in seven out of eight patients with an arteriovenous malformation. The analysis of coagulation parameters in our patients with vascular anomalies advanced our understanding of the underlying pathophysiologies of the observed coagulopathies. This may lead to new treatment options for the, in part, life-threatening bleeding risks in these patients in the future.

Association of lipid indicators with blood coagulation parameters in patients with coronary artery disease

Association of lipid indicators with blood coagulation parameters in patients with coronary artery disease

Preoperative evaluation of coagulation status in neuromodulation patients.

The incidence of hemorrhage in patients who undergo deep brain stimulation (DBS) and spinal cord stimulation (SCS) is between 0.5% and 2.5%. Coagulation status is one of the factors that can predispose patients to the development of these complications. As a routine part of preoperative assessment, the authors obtain prothrombin time (PT), partial thromboplastin time (PTT), and platelet count. However, insurers often cover only PT/PTT laboratory tests if the patient is receiving warfarin/heparin. The authors aimed to examine their experience with abnormal coagulation parameters in patients who underwent neuromodulation. Patients who underwent neuromodulation (SCS, DBS, or intrathecal pump implantation) over a 9-year period and had preoperative laboratory values available were included. The authors determined abnormal values on the basis of a clinical protocol utilized at their practice, which combined the normal ranges of the laboratory tests and clinical relevance. This protocol had cutoff values of 12 seconds and 39 seconds for PT and PTT, respectively, and < 120,000 platelets/μl. The authors identified risk factors for these abnormalities and described interventions. Of the 1767 patients who met the inclusion criteria, 136 had abnormal preoperative laboratory values. Five of these 136 patients had values that were misclassified as abnormal because they were within the normal ranges at the outside facility where they were tested. Fifty-one patients had laboratory values outside the ranges of our protocol, but the surgeons reviewed and approved these patients without further intervention. Of the remaining 80 patients, 8 had known coagulopathies and 24 were receiving warfarin/heparin. The remaining 48 patients were receiving other anticoagulant/antiplatelet medications. These included apixaban/rivaroxaban/dabigatran anticoagulants (n = 22; mean ± SD PT 13.7 ± 2.5 seconds) and aspirin/clopidogrel/other antiplatelet medications (n = 26; mean ± SD PT 14.4 ± 5.8 seconds). Eight new coagulopathies were identified and further investigated with hematological analysis. New anticoagulants and antiplatelet medications are not monitored with PT/PTT, but they affect coagulation status and laboratory values. Although platelet function tests aid in a subset of medications, it is more difficult to assess the coagulation status of patients receiving novel anticoagulants. PT/PTT may provide value preoperatively.

STAY ALERT ABOUT COAGULATION PARAMETERS - IMPLICATIONS OF THROMBOSIS TREATMENT IN COVID-19

Objective: The case report presents two patients with COVID-19 history. The first patient, treated with enoxaparin, was diagnosed with pulmonary embolism, and later developed heparin-induced thrombocytopenia. The second patient with history of chronic pulmonary thromboembolism and multiple comorbidities, treated with rivaroxaban and acetylsalicylic acid, reported haemorrhagic events. The objective of this case report is to highlight possible complications of anticoagulant treatment and the role of accurate and rapid response of clinicians in COVID-19 patients. Design and method: Case report of two patients with COVID-19 - related thrombotic complications treated respectively with low molecular weight heparin and rivaroxaban. Observation of the treatment process revealed complications in both cases, demanding change of medications within the same group of drugs. Results: Development of thrombotic episodes was noticed and treated in time. Both patients developed complications of treatment. Modifications of anticoagulation drugs (low molecular weight heparin replaced with fondaparinux and rivaroxaban with apixaban respectively) were provided with positive outcomes. Conclusions: SARS-CoV-2 infection is associated with a high risk of thrombotic events whereas anticoagulant treatment can also lead to various complications. The necessity of watchful observation of coagulation parameters in patients with COVID-19, but also potential complications of any anticoagulant treatment is crucial for the positive long-term outcomes.

TPA or not tPA? Lysis therapy in the setting of COVID‐19 and ECMO

We read with interest the recent article entitled, “Using lysis therapy to treat five critically ill COVID-19 patients who show echocardiographic criteria of right ventricular strain” by Mahdy et al., which described five patients who underwent lysis therapy for COVID-19-associated critical illness with respiratory failure and right heart strain. We find this topic especially relevant in the context of the global COVID-19 pandemic, which has now claimed over 800,000 American lives and over 1.5 million worldwide. Critical illness secondary to COVID-19 is associated with an inflammatory state and coagulopathy; the mechanisms underlying this state are still under investigation [1-4]. There are multiple case reports describing adverse thrombotic events in this population [1-4] and we are particularly interested in the authors’ report of Patient 5, who was receiving extracorporeal membranous oxygenation (ECMO) at the time of lysis therapy. ECMO generally requires systemic anticoagulation due to a hypercoagulable state induced by contact of the patient's blood with the cannulas, but the choice of medication and the intensity of therapy vary in different settings and in patients with different medical conditions. The increased volume of distribution caused by the circuit also calls the standard dosing of alteplase into question. The balance between thrombotic events and bleeding complications is a delicate one without even accounting for the coagulopathy associated with COVID-19. Recently, we provided veno-venous ECMO for a 47-year-old man with severe hypoxemia secondary to acute respiratory distress syndrome (ARDS) associated with COVID-19 pneumonia. His hypoxemia was refractory to mechanical ventilation, neuromuscular blockade, and prone positioning. In addition, the patient had completed a course of dexamethasone and remdesivir as targeted therapy for COVID-19. His medical history was significant for obesity, congenital solitary kidney, hypothyroidism, and hyperlipidemia. While on ECMO, he received therapeutic anticoagulation with unfractionated heparin. On hospital day 17 (ICU day 13 and day 21 since symptom onset), our patient developed a massive pulmonary embolism with acute right ventricle (RV) failure (Figure 1). The patient's coagulation parameters on this day were as follows: PTT 102.3 s, INR 2, d-dimer 85,940 FEU. He was too hemodynamically unstable to transfer for thrombectomy. After a multidisciplinary discussion, we gave intravenous alteplase (10 mg bolus over 1 min followed by 90 mg infusion over 2 h). Within minutes, he stabilized and there were no associated bleeding complications. Anticoagulation decreases mortality in COVID-19-associated critical illness and is recommended while patients are on ECMO [2-4], but studies reporting thrombotic complications despite therapeutic heparin are common [5]. The ideal anticoagulation strategy for these patients is still unclear. Prior to the pandemic, there were scant reports on the use of thrombolytics while on ECMO, leaving little guidance for clinicians at the bedside. We are curious if the authors of this case series are able to report more on Patient 5's coagulation studies, how they chose their alteplase dose, their consideration of bleeding risks, and if they have other recommendations for clinicians considering lytic therapy for patients with COVID-19 disease requiring veno-venous ECMO. We are grateful to the patient described here, and to the patient's family who consented to the publication of this report. The authors declare no conflict of interest. The authors received no specific funding for this work.

Predictive Value of Blood Coagulation Parameters in Poor Outcomes in COVID-19 Patients: A Retrospective Observational Study in Romania

SARS-CoV-2 infection produces alterations in blood clotting, especially in severe cases of COVID-19. Abnormal coagulation parameters in patients with COVID-19 are important prognostic factors of disease severity. The objective of this study was to evaluate the predictive value of aPTT, D-dimer, INR and PT in the mortality of patients with COVID-19. A retrospective, single-center, observational study was conducted on COVID-19 patients admitted to the Municipal Emergency Clinical Hospital in Timisoara, Romania, between August and October 2021. Patients were confirmed as COVID-19 positive by reverse transcription-polymerase chain reaction (RT-PCR) assay. After applying the inclusion/exclusion criteria, a total of 82 patients were included in the analysis. Receiver operating characteristic (ROC) curves of D-Dimer, INR, PT and aPTT were generated to assess whether the baseline of each of these biomarkers was accurately predictive for mortality in patients with COVID-19. Mortality among patients enrolled in this study was 20.7%, associated with older age and presence of heart disease. The areas under the ROC curve (AUC-ROC) of D-Dimer, INR, PT, and aPTT were 0.751, 0.724, 0.706 and 0.753. Differences in survival for patients with coagulation biomarker levels above cut-off values compared to patients below these values were statistically significant. All evaluated parameters had significant differences and good performance in predicting mortality of COVID-19 patients, except fibrinogen, which had no significant difference. Moreover, aPTT and D-dimer were the best performing parameters in predicting mortality in patients with SARS-CoV-2 infection.

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.