Activation Of Coagulation System Research Articles

The effects of emicizumab on in vitro coagulation and fibrinolysis parameters in patients with disseminated intravascular coagulation with and without addition of anti-FVIII antibody.

Emicizumab (Emi) is used as haemostatic prophylaxis for patients with haemophilia A (PwHA). Disseminated intravascular coagulation (DIC) is a condition characterized by persistent systemic activation of coagulation, but there is yet no information on coagulation and fibrinolysis potentials in Emi-treated PwHA with DIC. To examine the effect of Emi on coagulation and fibrinolysis potentials in HA-model DIC plasmas. Plasma from a patient with sepsis-DIC (seven patients) was treated with anti-factor (F)VIII monoclonal antibody (HA-model DIC plasma) and incubated with Emi (50µg/mL). The plasma was then assessed using clot-fibrinolysis waveform analysis (CFWA). Coagulation and fibrinolysis parameters were expressed as ratios relative to normal plasma (|min1|-ratio and |FL-min1|-ratio, respectively). In case 1, coagulant potential was slightly high and fibrinolytic potential was extremely low, presenting a coagulant-dominant state (|min1|-ratio/|FL-min1|-ratio: 1.1/.38). In cases 2-5, fibrinolytic potential was not suppressed, but there were marked hypercoagulant potentials, indicating relative coagulant-dominant states. In case 6, coagulant and fibrinolytic potentials were increased but well balanced (|min1|-ratio/|FL-min1|-ratio: 1.38/1.28). In case 7, both potentials were severely deteriorated in not only CFWA but also the thrombin/plasmin generation assay. The addition of Emi into the HA-model DIC plasmas increased |min1|-ratio values in all cases, but the coagulant potentials did not exceed the initial ones (DIC plasma before treatment with anti-FVIII antibody). The presence of Emi in the HA-model DIC plasma improved coagulation potentials, but did not increase coagulation potentials beyond those of DIC plasma in non-HA states.

Role of microbiota-derived corisin in coagulation activation during SARS-CoV-2 infection

BackgroundCoagulopathy is a major cause of morbidity and mortality in COVID-19 patients. Hypercoagulability in COVID-19 results in deep vein thrombosis, thromboembolic complications, and diffuse intravascular coagulation. Microbiome dysbiosis influences the clinical course of COVID-19. However, the role of dysbiosis in COVID-19-associated coagulopathy is not fully understood. ObjectivesThe present study tested the hypothesis that the microbiota-derived proapoptotic corisin is involved in the coagulation system activation during SARS-CoV-2 infection. MethodsThis cross-sectional study included 47 consecutive patients who consulted for symptoms of COVID-19. A mouse acute lung injury model was used to recapitulate the clinical findings. A549 alveolar epithelial, THP-1, and human umbilical vein endothelial cells were used to evaluate procoagulant and anticoagulant activity of corisin. ResultsCOVID-19 patients showed significantly high circulating levels of corisin, thrombin-antithrombin complex, D-dimer, soluble thrombomodulin, tumor necrosis factor-α, and monocyte-chemoattractant protein-1 with reduced levels of free protein S compared with healthy subjects. The levels of thrombin-antithrombin complex, D-dimer, and corisin were significantly correlated. A monoclonal anticorisin-neutralizing antibody significantly inhibited the inflammatory response and coagulation system activation in a SARS-CoV-2 spike protein-associated acute lung injury mouse model, and the levels of corisin and thrombin-antithrombin complex were significantly correlated. In an in vitro experiment, corisin increased the tissue factor activity and decreased the anticoagulant activity of thrombomodulin in epithelial, endothelial, and monocytic cells. ConclusionThe microbiota-derived corisin is significantly increased and correlated with activation of the coagulation system during SARS-CoV-2 infection, and corisin may directly increase the procoagulant activity in epithelial, endothelial, and monocytic cells.

Aggressive Vaccine-Induced Immune Thrombocytopenia and Thrombosis in a Young Woman with a Past Mild SARS-CoV-2 Infection

Vaccine- induced immune thrombocytopenia and thrombosis (VITT) is a rare adverse event occurring after immunization with adenoviral vector-based vaccines against SARS-CoV-2. This life-threatening condition is characterized by thrombocytopenia, systemic activation of coagulation, and anti-platelet factor 4 antibodies, often resulting in extensive venous thrombosis. Arterial thrombosis is less common and mainly affects the aorta, peripheral arteries, heart, and brain. Several cases of ischemic stroke have been reported in VITT patients, frequently being associated with large vessel occlusion (LVO). Here, we present a case of aggressive VITT in a 46-year-old woman with a past mild SARS-CoV-2 infection, who was admitted with a left-middle cerebral artery (MCA) territory stroke and thrombocytopenia eight days after her first dose of the ChAdOx1 nCoV-19 vaccine. The patient developed a diffuse arterial thrombosis with concomitant thrombotic events in the intrahepatic portal branches. The patient’s clinical condition worsened rapidly due to a significant enlargement of the ischemic cerebral lesion in the left hemisphere, cerebral herniation, and incipient hydrocephalus requiring decompressive neurosurgery with an unfavorable outcome. Our observations may be indicative of a stroke variant in VITT and highlight the diverse clinical manifestations of the syndrome.

The Inhibition of Serine Proteases by Serpins Is Augmented by Negatively Charged Heparin: A Concise Review of Some Clinically Relevant Interactions.

Serine proteases are members of a large family of hydrolytic enzymes in which a particular serine residue in the active site performs an essential role as a nucleophile, which is required for their proteolytic cleavage function. The array of functions performed by serine proteases is vast and includes, among others, the following: (i) the ability to fight infections; (ii) the activation of blood coagulation or blood clot lysis systems; (iii) the activation of digestive enzymes; and (iv) reproduction. Serine protease activity is highly regulated by multiple families of protease inhibitors, known collectively as the SERine Protease INhibitor (SERPIN). The serpins use a conformational change mechanism to inhibit proteases in an irreversible way. The unusual conformational change required for serpin function provides an elegant opportunity for allosteric regulation by the binding of cofactors, of which the most well-studied is heparin. The goal of this review is to discuss some of the clinically relevant serine protease-serpin interactions that may be enhanced by heparin or other negatively charged polysaccharides. The paired serine protease-serpin in the framework of heparin that we review includes the following: thrombin-antithrombin III, plasmin-anti-plasmin, C1 esterase/kallikrein-C1 esterase inhibitor, and furin/TMPRSS2 (serine protease Transmembrane Protease 2)-alpha-1-antitrypsin, with the latter in the context of COVID-19 and prostate cancer.

Cardiovascular Manifestations in Inflammatory Bowel Disease.

Inflammatory bowel disease is a group of long-term systemic inflammatory disorders affecting the gastrointestinal tract, including Crohn's disease and ulcerative colitis, which may be associated with an increased risk of developing extraintestinal manifestations, including cardiovascular disease, thereby decreasing the quality of life. Pathophysiological changes associated with inflammatory bowel disease include alterations of the microbiome, endotoxemia, and changes to glucose and lipid metabolism. Inflammatory bowel disease patients have higher carotid intima-media thickness, lower flow-mediated dilatation, and increased carotid-femoral pulse wave velocity, which are markers of elevated cardiovascular risk. In addition, inflammatory bowel disease patients are at an increased risk for developing venous and arterial thrombotic events due to a hypercoagulable state caused by thrombocytosis and coagulation system activation. To reduce the risk of developing cardiovascular disease, lifestyle modifications, such as smoking cessation, dietary changes, and increased physical activity alongside management with appropriate medication, should be considered. This research paper examines how inflammatory bowel disease can influence the risk of cardiovascular complications and the involvement of drug therapy. Methods: PubMed was searched using keywords, such as inflammatory bowel disease, Crohn's disease, ulcerative colitis, cardiovascular disease, pericarditis, thromboembolism, and many more. Relevant literature up to March 2023 has been examined and summarized, which consisted of data from various clinical trials, meta-analyses, retrospective/prospective cohort studies, and current guidelines.

Damage-associated cellular markers in the clinical and pathogenic profile of vaccine-induced immune thrombotic thrombocytopenia

BackgroundAdenoviral vector-based COVID-19 vaccine-induced immune thrombotic thrombocytopenia (VITT) is rare but carries significant risks of mortality and long-term morbidity. The underlying pathophysiology of severe disease is still not fully understood. The objectives were to explore the pathophysiological profile and examine for clinically informative biomarkers in patients with severe VITT. MethodsTwenty-two hospitalized patients with VITT, 9 pre- and 21 post-ChAdOx1 vaccine controls, were recruited across England, United Kingdom. Admission blood samples were analyzed for cytokine profiles, cell death markers (lactate dehydrogenase and circulating histones), neutrophil extracellular traps, and coagulation parameters. Tissue specimens from deceased patients were analyzed. ResultsThere were strong immune responses characterized by significant elevations in proinflammatory cytokines and T helper 1 and 2 cell activation in patients with VITT. Markers of systemic endothelial activation and coagulation activation in both circulation and organ sections were also significantly elevated. About 70% (n = 15/22) of patients met the International Society for Thrombosis and Haemostasis criteria for disseminated intravascular coagulation despite negligible changes in the prothrombin time. The increased neutrophil extracellular trap formation, in conjunction with marked lymphopenia, elevated lactate dehydrogenase, and circulating histone levels, indicates systemic immune cell injury or death. Both lymphopenia and circulating histone levels independently predicted 28-day mortality in patients with VITT. ConclusionThe coupling of systemic cell damage and death with strong immune-inflammatory and coagulant responses are pathophysiologically dominant and clinically relevant in severe VITT.

Perioperative hemorheological status of oncological patients with primary knee replacement

Introduction. Endoprosthesis of large joints is associated with high risk of venous thromboembolism. Researchers focus on biochemical characteristics of homeostasis, blood clotting in particular, as the main reason for abnormal blood flow. At the same time, biophysical condition of homeostasis, namely decreased blood fluidity, is rarely considered. Study of rheological behavior of blood after primary oncological endoprosthesis of large joints in patients can potentially affect the selection of perioperative thromboprophylaxis and patient rehabilitation approach.Aim. To study the indicators of the hemorheological status of patients with tumours of long bones in the preand postoperative periods of primary oncological knee replacement.Materials and methods. The study included 36 patients (26 men and 10 women, mean age 46 years) without cardiovascular diseases and pathology of the veins of the lower limb admitted to the Russian Scientific Center of Roentgen Radiology for oncological endoprosthesis of the knee joint. All patients were prescribed: an antiplatelet agent (acetylsalicylic acid) and an anticoagulant (enoxaparin sodium 40 mg daily). Distal resection of the femur (on average 14 cm) was performed in 28 patients, and proximal resection of the tibia (on average 12 cm) in 8 patients, followed by knee replacement. Before the operation, on the 1st and 6th days after the operation, the hemorheological status and the state of the hemostasis system were evaluated in all patients. To determine the reference values, 24 healthy people were examined, comparable in gender and age. Statistical analysis using Statistica 10.0.Results. During the preoperative examination, integral assessment showed the differences in the severity of hemorheological disorders between patients, and two groups were identified: Group 1 – 21 (61 %) patients whose hemorheological disorders were classified as severity degree I, and Group 2 – 14 (39 %) patients with severity degree II d. On day 1 after the surgery, both patient groups showed negative dynamics: hemorheological disorders in group 1 worsened from grade I to II d., and in group 2 to III d. (critical) (p <0.05). On day 6, the parameters did not change significantly in all patients. Similar dynamic changes were observed in the haemostasis system.Conclusion. Activation of the blood coagulation system and deterioration of hemorheology occurred after surgery during administration of anticoagulant and antiplatelet therapy. None of the patients had venous thromboembolic complications, however the risk of their development remained high. A differential model describing hemorheological status can be useful for selection of thromboprophylaxis and rehabilitation methods which include physical factors that improve the hemorheological profile: low-frequency magnetic and/or laser therapy in patients.

Association between Hereditary Angioedema and Venous Thromboembolism in a Large Population-Based Case-Control Study

Introduction: Hereditary Angioedema (HAE) is a rare congenital disorder primarily caused by mutations in the SERPING1 gene that results in C1 inhibitor (C1INH) deficiency or dysfunction. C1INH is a multifunctional serine protease inhibitor that functions as a major endogenous negative regulator of the kallikrein-kinin, contact pathway of coagulation and complement systems. HAE typically presents with episodes of unpredictable subcutaneous and submucosal swelling. However, HAE patients also have evidence of systemic activation of coagulation including elevated plasma prothrombin fragments, thrombin antithrombin complexes and D-dimers. Further, patients with HAE have recently been reported to have an increased risk of venous thromboembolism (VTE). Methods: To evaluate the risk of VTE in patients with HAE we conducted a large population-based case-control study leveraging data from the United Kingdom Clinical Practice Research Datalink (CPRD). The CPRD Aurum dataset used here maintains anonymized electronic medical records of over 40 million individuals from over 1600 primary care practices in the United Kingdom. SNOMED CT medical codes were used to identify a cohort of 2,198 patients diagnosed with HAE between 1992 and 2022 in the CPRD Aurum dataset with a matched (age, gender, family practice, and index date for HAE) cohort of 4,376 controls selected. VTE events including deep vein thrombosis (DVT) and pulmonary embolism in the HAE case and control cohorts were identified using SNOMED CT medical codes. The Cox proportional hazards model was used to determine hazard ratios (HR) for VTE events in HAE cases versus controls adjusting for covariates age, sex, body mass index, blood pressure, smoking status and a number of co-morbidities specifically; neoplasm, type 2 diabetes, ischemic heart disease, chronic obstructive pulmonary disease, chronic kidney disease, autoimmune disorders and depression. Results: A greater proportion of the HAE cases were female (62%) with a mean age at HAE diagnosis of 37 years. The median follow-up period for both cases and controls was 17 years (interquartile range (IQR):8-28 years). The overall incidence of VTE in HAE cases was 1.1/1000 patient years versus 0.6/1000 patient years in the control cohort. In unadjusted analyses HAE was associated with a significantly increased risk of VTE (HR 1.70, 95% CI 1.37-2.22, P<0.0001). Importantly, in adjusted analyses HAE remained significantly associated with an increased risk of VTE (HR 1.44, 95% CI 1.12-1.83, P=0.004, Figure 1). Of note, this association is similar in magnitude to that previously reported for heterozygous carriers of FV Leiden, the prothrombin gene mutation and high confidence loss of function mutations in Protein C and Protein S in comparable population-based case-control studies. In adjusted sub-analyses HAE was associated with a significantly increased risk of DVT (HR: 1.42, 95% CI 1.09-1.87, P=0.01) with a trend towards an increased risk of PE (HR 1.37, 95% CI 0.84-2.27, P=0.2). Conclusions: The results of this population-based case-control study, roughly an order of magnitude larger in size than prior reports, demonstrate that HAE is associated with a significantly increased risk of VTE similar to that reported for common hereditary thrombophilias. These findings reinforce the important role of endogenous C1INH as a negative regulator of prothrombotic processes involved in VTE in the setting of HAE.

Decoding the DIC-Lymphoma Relationship: A Nationwide Analysis of Increased Risk in Adult Patients

Background: Disseminated intravascular coagulation (DIC) is a severe, often fatal condition characterized by systemic coagulation activation leading to both widespread microvascular thrombosis and profuse hemorrhaging. Frequently associated with malignancies, DIC represents a serious clinical challenge. Lymphomas, characterized by their clinical diversity and varying prognoses, may present differing DIC risks across their subtypes. Aim of the study The study aims to understand how various lymphoma subtypes influence the development of DIC in hospitalized individuals, utilizing data from a national inpatient sample. Methods and Materials This study retrospectively examines a cohort of adult patients in the United States, hospitalized with DIC, both with and without lymphoma, utilizing the 2020 National Inpatient Sample (NIS). Patients were identified using the International Classification of Diseases (ICD-10) codes. Patients who were younger than age 18 years were excluded from the study. We used STATA for our analyses. Fisher's exact test was utilized for comparing proportions, while Student's t-test was employed for the comparison of continuous variables. We performed a multivariate logistic regression analysis, taking into consideration various patient, and hospital characteristics including age, gender, race, median zip income, insurance status, hospital geographical region and location, bed size, urban or rural setting, teaching status to identify the adjusted odds ratio for the development of DIC in different lymphoma subtypes. The Charlson comorbidity index was utilized to account for the burden of comorbidities in the analysis. Results Among 48,310 adult DIC patients in the 2020 NIS dataset, 2.48% concurrently had lymphoma. A significant disparity was noted in gender distribution, with fewer females in the lymphoma group (40% vs 49%, p=0.0135). Patients with lymphoma were, on average, older with a mean age of 62.72 years. The racial composition between the two groups was not significantly different (p=0.651). The odds of developing DIC were significantly increased overall in lymphoma patients (aOR=2.14, p <0.001). Of the lymphoma subtypes, other specified types of T/NK- cell lymphoma (natural killer) (grouped under the ICD-10 code: C86, and further sub-categorized into extra-nodal NK/T cell lymphoma, hepatosplenic, intestinal, subcutaneous, angioimmunoblastic, primary cutaneous T cell lymphoma, and blastic NK-cell lymphoma) exhibited the highest risk of DIC development (aOR=16.85, p <0.001). Non-follicular, mature T-NK-cell, other specified and unspecified types of Non-Hodgkin, and Hodgkin lymphomas also showed significant DIC risks (p<0.05), whereas no statistically significant risks were found in follicular lymphoma (p=0.753) and malignant immunoproliferative diseases and certain other B-cell lymphomas (p=0.726). See Table 1 for further details. Conclusion: This study underlines a significant association between lymphoma and elevated risk of DIC, with the highest odds observed in other specified types of T/NK- cell lymphoma. Clinical diversity within lymphoma subtypes influenced DIC risks differently, underlining the importance of individualized care. In clinical practice, increased vigilance for DIC is suggested in lymphoma patients. Prompt identification and management of DIC in this patient population could potentially improve outcomes in healthcare optimization. Further studies are warranted to elucidate the underlying mechanisms and to explore potential targeted interventions.

Sex-dependent effects of finerenone on hemostasis in normoglycemic and streptozotocin-induced diabetic mice

Diabetes is associated with aldosterone excess and the overactivation of its mineralocorticoid receptor (MR) which leads to the development of many cardiovascular dysfunctions. Therefore, MR antagonists have been found to exert favorable effects on the cardiovascular system. Finerenone is a new nonsteroidal MR antagonist approved for the treatment of chronic kidney disease associated with type 2 diabetes. Clinical studies have demonstrated that finerenone improves cardiovascular outcomes. However, its influence on hemostasis in the cardioprotective effect is unknown. Therefore, the main aim of our study was to evaluate the effects of finerenone (10 mg/kg, p.o.) on selected hemostasis parameters in streptozotocin (180 mg/kg, i.p.)-induced diabetes. Since regulation of the MR activity is sex-dependent, the study was conducted in both female and male mice. The most beneficial effects of finerenone were observed in diabetic female mice which included a decrease in thrombus formation, attenuation of platelet activity, inhibition of the coagulation system, and activation of fibrinolysis. In contrast, in male diabetic mice only an attenuation of the coagulation system was observed. Furthermore, finerenone also exerted unfavorable effects, but only in normoglycemic mice, manifested as a slight increase in platelet activity in males and an enhancement of the coagulation system activity in females. Our study is the first to show the sex-dependent and glycemia-dependent effects of finerenone on hemostasis in diabetes. The occurrence of beneficial effects only in female diabetic mice requires in-depth study.

The use of d-dimer in the diagnosis and risk assessment of intracardiac thrombus among patients with dilated cardiomyopathy

d-dimer is a biomarker of coagulation and fibrinolytic system activation in response to the body's hypercoagulable state. The study aims to investigate the usefulness of d-dimer in diagnosing and assessing the risk of intracardiac thrombus in patients with dilated cardiomyopathy (DCM). Consecutively enrolled in this study were patients with DCM who were admitted to our center for the first time. The diagnostic value was evaluated using the receiver operating characteristic (ROC) curve. Additionally, we used univariate and multivariate logistic regression to investigate the association between d-dimer and intracardiac thrombus. We also performed smooth curve fitting, threshold saturation effect analysis, and subgroup analysis. In total, 534 patients were enrolled in the study, and among them, 65 patients had intracardiac thrombus. Mural thrombus was the predominant type of thrombus, which was mainly located in the left ventricular apex. The optimal cut-off value of d-dimer for the diagnosis of intracardiac thrombus was 484 ng/mL, with a sensitivity and specificity of 0.769 and 0.646, respectively. In both unadjusted and adjusted logistic regression models, a positive association was found between d-dimer and intracardiac thrombus. Curve fitting and threshold effect analysis revealed two inflection points in the relationship between d-dimer and intracardiac thrombus (non-linear test: P = 0.032). When d-dimer was equal to 362 ng/mL, the odds ratio (OR) was 1, and the risk of thrombus gradually increased until it reached 4096 ng/mL, after which the trend no longer increased. Within this range, a twofold increase in d-dimer was associated with a 103.2% increased risk (OR = 2.032; 95% CI 1.293–3.193; P < 0.01). In the subgroup analysis, there was a significant interaction between d-dimer and BMI on intracardiac thrombus (P value for interaction was 0.013), and the risk was higher in patients with a BMI ≥ 25 kg/m2 (OR = 3.44; 95% CI 1.86–6.36; P < 0.01).

Accuracy of D-dimer as a Predictive Biomarker for Outcome in Head Injured Patients at Dr. Mohammad Hoesin General Hospital, Palembang, Indonesia

Introduction: D-dimer reflects the upregulation of the overall hemostatic system upon admission. If D-dimer levels increase, coagulation disorders appear. This is considered a poor prognostic factor. High D-dimer levels reflect the severity of brain injury. Activation of systemic coagulation causes extensive intravascular fibrin deposition and a decrease in platelets and coagulation factors. This study aimed to assess the accuracy of D-dimer as a predictive biomarker for outcomes in head injury patients at Dr. Mohammad Hoesin General Hospital, Palembang, Indonesia.&#x0D; Methods: This study is a prospective prognostic test study to test the sensitivity and specificity of D-dimer for prediction mortality in patients with severe head injuries at Dr. Mohammad Hoesin General Hospital (RSMH) Palembang in the period June 2023 to August 2023. A total of 47 research subjects participated in this study.&#x0D; Results: Post 24-hour D-dimer levels have a cut-off point of 11.78 mg/L, which has high accuracy in poor outcomes. D-dimer levels after 5 days have a cut-off point value of 2.3 mg/L and have high sensitivity in predicting poor outcomes, and the value of the difference in changes in D-dimer based on poor outcome patients have a cut-off point of 3.33 mg/L, which has a high sensitivity in predicting a poor prognosis.&#x0D; Conclusion: D-dimer levels are quite accurate as a predictive biomarker for outcomes in head injury patients at Dr. Mohammad Hoesin General Hospital, Palembang, Indonesia.

Coagulation markers as independent predictors of prostate cancer aggressiveness: a retrospective cohort study

Coagulation system activation is commonly observed in tumor patients, including prostate cancer (PCa), with coagulation markers proposed as potential prognostic indicators for cancer severity. However, the correlation between these markers and clinicopathological features in PCa remains unclear. Thus, this study investigates the association between comprehensive coagulation markers and clinicopathological characteristics in PCa patients. A retrospective evaluation of 162 PCa patients diagnosed and categorized into low-intermediate-risk or high-risk groups based on clinical and pathological features was conducted. Coagulation markers, including fibrinogen (FIB), d-dimer (DD), activated partial thromboplastin time (APTT), prothrombin time (PT), prothrombin activity (PTA), thrombin time (TT), platelet count (PLT), and international normalized ratio (INR), were assessed. Univariate and multivariate logistic regression analyses were performed to determine associations with clinicopathological features. FIB and DD were confirmed as independent factors associated with high-risk PCa. Furthermore, FIB and DD levels showed significant positive correlations with clinical parameters, including PSA levels, ISUP grade, T stage, N stage, and M stage. Our findings suggest that FIB and DD hold promise as independent prognostic biomarkers for risk stratification in PCa. These coagulation markers may aid in assessing PCa severity and guiding personalized treatment strategies.

The problem of inpatient thrombosis of coronary arteries in patients with COVID-19 on the background of intensive antithrombotic therapy

Myocardial infarction claims million lives on the planet each year. Pharmacotherapy in combination with percutaneous coronary interventions have significantly reduced morbidity and mortality in this cohort. Despite optimal therapy and prophylaxis, there is a group of patients with recurrent, often fatal, coronary thromboses. During the COVID-19 pandemic, some patients developed episodes of thrombosis in blood vessels of various organs, including brain, heart or lungs, even on therapeutic anticoagulation. The patient was admitted to the department of cardiology and reperfusion therapy, with a confirmed diagnosis of COVID-19 resulted in acute ST-segment elevation myocardial infarction. Patient underwent urgent coronary angiography with thromboaspiration and stenting of the infarct-dependent right coronary artery followed by optimal medical treatment with the use of triple antithrombotic therapy. His condition became stable with the resolution of ST-segment elevation on electrocardiogram. A few days later, the condition of the patient deteriorated again with recurrent of chest pain and a new ST segment elevation. Repeated coronary angiography revealed recurrent thrombosis in the right coronary artery. The mechanisms of thrombosis in COVID-19 are not fully understood. Among possible, the direct effect of the virus on tissues, activation of pro-inflammatory system and coagulation system, impaired vasodilation, and decreased fibrinolytic activity are discussed. These mechanisms may lead to vascular thrombosis in different organs, particularly heart, lungs, and brain.

Serum D-dimer Level in Patients with Acute Leukemia in a Tertiary Care Hospital

D-dimer is a molecule, formed by the breakdown of excessive fibrin from the activation of coagulation system. Ample evidence suggests that increased activation of coagulation system in patients with acute leukemia (AL) leads to higher D-dimer levels. Considering shortage of evidence in our perspective, the study was designed to observe the D-dimer level in acute leukemia in different morphological types and phases among the patients admitted in a tertiary care hospital. This hospital based cross-sectional study was conducted at the Department of Medicine and Department of Hematology in Dhaka Medical College Hospital, for a period of 6 months following approval of this protocol. Patients with New case (NC) of AL, at complete remission (CR) and in patient’s wither lapsed (R) AL were included in the study. Purposive sampling methods were followed for sample selection. Written informed consents were taken from the all study subjects and ethical issues were ensured. Data were collected by interview using a structured questionnaire. All study population were subjected to details history taking, physical examination and relevant investigations of D-dimer level. Collected data were analyzed by the SPSS version 20.0. Among 50 patients, 58% were males and 42% were females. Mean age was 34±5.6 SD years and the height number of patients (40%) belonged to age group 21-30 years. Three fourth of the patient (76%) had diagnosed as AML and rest of them 24% had ALL. The most common subtype of Acute Myeloblastic Leukemia M3 (AML) was 47, 37% and most common subtype of ALL L2 was 50%. Most of the respondents were found as new case (80%) followed by in decreasing order complete remission case 14% and relapse case 6%. Overall, D-dimer level was 3.69 mg/dl (0.1mg/dl-40 mg/dl), and D-dimer level is slightly higher in AML group than ALL patient (4.26 vs 2.18mg/dl). Moreover, new cases have higher level of D-dimer (4.2 mg/dl) in comparison with complete remission (1.2 mg/dl) or relapse case (2.7 mg/dl). It was also found that APL patients has higher D-dimer level than other form of leukemia. D-dimer level in acute leukaemia patients 3.69 mg/dl. Higher value of AML was found in patients than ALL and increased D-dimer level is also evident in newer case particularly APL. D-dimer level rises in acute leukemia patients. However, further study is recommended with appropriate study design. Bangladesh Med J. 2021 Sept; 51(1): 8-17

PECAM-1/Thrombus Ratio Correlates with Blood Loss during Off-Pump Coronary Artery Bypass Grafting (OPCAB) Surgery: A Preliminary Study.

Platelet endothelial cell adhesion molecule 1 (PECAM-1) is considered an antiplatelet molecule. Previously, we introduced a new parameter called the PECAM-1/thrombus ratio, which indicates the proportion of PECAM-1 in the thrombus and provides a precise description of human platelet activity (in vitro). The aim of this study was to determine whether the PECAM-1/thrombus ratio could serve as a predictive factor for bleeding events during off-pump coronary artery bypass grafting (OPCAB). To achieve this, we collected blood samples from 20 patients scheduled to undergo OPCAB surgery. We assessed the PECAM-1/thrombus ratio by evaluating thrombus formation on collagen fibers under flow conditions. Subsequently, we compared the ability of the PECAM-1/thrombus ratio in predicting bleeding risk with other methods that evaluate hemostasis activity. These methods included assessing platelet P-selectin secretion, platelet exposure of phosphatidylserine, plasma coagulation and fibrinolysis system activity, and thrombus formation using the T-TAS assay. Our findings revealed a positive correlation between the PECAM-1/thrombus ratio and the amount of blood component units transfused (BCUT) during the OPCAB surgery. Furthermore, BCUT did not show any significant correlation with other measured hemostasis parameters. This preliminary study suggests that the PECAM-1/thrombus ratio might be a good predictor of bleeding risk during the OPCAB procedure.

Prothrombotic status in COVID‑19 with diabetes mellitus (Review).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused an important social and health impact worldwide and the coronavirus disease-19 (COVID-19) has elicited devastating economy problems. The pathogenesis of SARS-CoV-2 infection is a complex mechanism and is considered to be the result of a challenging interaction, in which host and virus immune responses are the key elements. In this process, several inflammatory pathways are involved, and their initiation can have multiple consequences with a considerable impact on evolution, such as hyperinflammation and cytokine storm, thereby promoting activation of the coagulation system and fibrinolytic activity suppression. It is commonly recognized that COVID-19 severity involves multiple factors, including diabetes which increases the risk of developing different complications. This could be as a result of the low-grade inflammation as well as the innate and adaptive immune response dysfunction that is observed in patients with diabetes mellitus. In patients with diabetes, multiple metabolic disturbances which have a major impact in disturbing the balance between coagulation and fibrinolysis were discovered, thus the risk for thrombotic events is increased. Diabetes has been recognized as an important severity prognosis factor in COVID-19 cases and considering there is a significant association between diabetes and prothrombotic status, it could be responsible for the increased risk of thrombotic events with a worse prognosis.

Tissue factor activates the coagulation cascade in mouse models of acute promyelocytic leukemia

AbstractAcute promyelocytic leukemia (APL) is associated with a high risk of bleeding and thrombosis. APL patients have an activated coagulation system, hyperfibrinolysis, and thrombocytopenia. APL cells express tissue factor (TF), a receptor and cofactor for factor VII/VIIa. This study had 2 goals. Firstly, we measured biomarkers of coagulation and fibrinolysis activation as well as platelet counts and bleeding in both mouse xenograft and allograft models of APL. Secondly, we determined the effect of inhibiting TF on the activation of coagulation in these models. We observed increased levels of plasma thrombin-antithrombin complexes (TAT), D-dimer, and plasmin-antiplasmin complexes, reduced platelet counts, and increased tail bleeding in both mouse models of APL. Fibrinogen levels decreased in the xenograft model but not in the allograft model. In contrast, the red blood cell count decreased in the allograft model but not in the xenograft model. Inhibition of APL-derived human TF with an anti-human TF monoclonal antibody reduced the level of TAT, increased platelet count, and normalized tail bleeding in a xenograft model. Inhibition of all sources of TF (APL cells and host cells) in the allograft model with a rat anti-mouse TF monoclonal antibody decreased the levels of TAT but did not affect the platelet count. Our study demonstrates that TF plays a central role in the activation of coagulation in both the xenograft and allograft mouse models of APL. These APL mouse models can be used to investigate the mechanisms of coagulopathy and thrombocytopenia in APL.

Unveiling the uncommon: Disseminated intravascular coagulation as an unusual presentation of metastatic carcinoma prostate

We present a rare case of disseminated intravascular coagulation (DIC) as the initial manifestation of metastatic carcinoma of the prostate. DIC is a life-threatening condition characterized by systemic activation of coagulation and widespread microvascular thrombosis, leading to organ dysfunction. Although DIC is commonly associated with hematological malignancies and sepsis, its occurrence as a paraneoplastic syndrome in solid tumors is extremely rare. Our case highlights the importance of considering DIC as a potential complication in patients with advanced prostate cancer, even in the absence of typical symptoms.

Regulation of coagulation activation in newly diagnosed AML by the heme enzyme myeloperoxidase

IntroductionPatients with acute myeloid leukemia (AML) are at increased risk of thrombohemorrhagic complications. Overexpressed tissue factor (TF) on AML blasts contributes to systemic coagulation activation. We have recently shown that the heme enzyme myeloperoxidase (MPO) negatively regulates TF procoagulant activity (PCA) on myelomonocytic cells in vitro. We now aimed to further characterize the functional interaction of MPO and TF in AML in vivo. MethodsWe prospectively recruited 66 patients with newly diagnosed AML. TF PCA of isolated peripheral blood mononuclear cells (PBMC) was assessed by single-stage clotting assay in the presence or absence of inhibitors against MPO catalytic activity (ABAH) or against MPO-binding integrins (anti-CD18). MPO in plasma and in AML blasts was measured by ELISA, and plasma D-dimers and prothrombin fragment F1+2 were quantified by automated immunoturbidimetric and chemiluminescence assays, respectively. ResultsPatients with AML had significantly higher MPO plasma levels compared to healthy controls and exhibited increased levels of D-dimers and F1+2. In vivo thrombin generation was mediated by TF PCA on circulating PBMC. Ex vivo incubation of isolated PBMC with ABAH or anti-CD18 antibody resulted in either increased or decreased TF PCA. The strong and robust correlation of F1+2 with TF PCA of circulating PBMC was abrogated at MPO plasma levels higher than 150 ng/mL, indicating a modulatory role for MPO on TF-mediated in vivo thrombin generation above this threshold. ConclusionOur study indicates that catalytically active MPO released by circulating myeloblasts regulates TF-dependent coagulation in patients with newly diagnosed AML in a CD18-dependent manner.