Coagulation In Patients Research Articles

Editorial introductions

Editorial introductions

Fatal Vitamin K-Dependent Coagulopathy Associated with Cefoperazone/Sulbactam: A Case Report.

This case report describes a suspected and fatal adverse reaction involving vitamin K-dependent coagulopathy that might be associated with cefoperazone/sulbactam (CPZ/SAM), a combined antimicrobial formulation. We reported a patient diagnosed with acute cerebral infarction and secondary pulmonary infection who was treated with an intravenous infusion of CPZ/SAM at 3 g twice daily. After receiving treatment with CPZ/SAM, the patient developed a fatal adverse reaction of CPZ-induced hemorrhage. The Naranjo assessment score in this report was 5, suggesting that the patient’s coagulation function disorder was potentially associated with the use of CPZ/SAM. To prevent vitamin K-dependent coagulopathy caused by CPZ/SAM, it is suggested to avoid cephalosporins in patients with a high risk of bleeding unless the need for cephalosporins is compelling.

Intramyocardial dissecting haematoma mimicking left ventricular clot, a rare complication of myocardial infarction: a case report

BackgroundIntramyocardial dissecting haematoma is a rare complication of myocardial infarction (MI) associated with high mortality rates. Studies and research of this occurrence are limited largely to isolated case reports or case series.Case summaryWe report a case of late presenting MI, where on initial echocardiogram had what was thought to be an intraventricular clot. However, upon further evaluation, the patient actually had an intramyocardial haematoma, with the supporting echocardiographic features to distinguish it from typical left ventricular (LV) clot. While this prevented the patient from receiving otherwise unnecessary anticoagulation, this diagnosis also put him at a much higher risk of mortality. Despite exhaustive medical and supportive management, death as consequence of pump failure occurred after 2 weeks.DiscussionThis report highlights the features seen on echocardiography which support the diagnosis of an intramyocardial haematoma rather than an LV clot, notably the various acoustic densities, a well visualized myocardial dissecting tear leading into a neocavity filled with blood, and an independent endocardial layer seen above the haematoma. Based on this report, we wish to highlight the importance of differentiating intramyocardial haematomas from intraventricular clots in patients with recent MI.

Гиперкоагуляция плазмы крови со спонтанными сгустками как биологический маркер степени выраженности психических расстройств

Introduction: currently, it is proved that the pathogenesis of schizophrenia is associated with the formation of chronic foci of aseptic inflammation (neuroinflammation) in the brain of patients. It is also known that chronic neuroinflammation quickly turns into systemic inflammation. Permeability of the blood-brain barrier impaired. Proinflammatory cytokines and other inflammatory factors release into the blood. Systemic inflammation leads to activation of all cells of the immune system and blood platelets. Activation of platelets is accompanied by а generation of a large number of procoagulant platelet-derived microparticles, which can cause an increase in blood clotting. Objective: to identify the impairments of thrombodynamic coagulation parameters in adults and children suffering from different forms of schizophrenia in the acute stage. Patients: the study included 3 groups of patients with schizophrenia with different type of course. Group 1: 79 patients with attack-like or progredient attack-like type of schizophrenia; group 2: 28 patients with schizotypal disorder; group 3: 28 patients with child schizophrenia. Methods: to determine the coagulation parameters, the Thrombodynamics method (TD) was used on the thrombodynamics device T-2 according to the instructions of the manufacturer of the device (Hemacore, Moscow, Russia). Results: the presence of spontaneous clots was shown in all three groups of patients. The analysis of the results of TD was carried out. For group 1 shows a significant increase of parameters Vi, Vst, V and CS. The Tsp parameter is significantly lower than normal values. For the second group, the 3 parameters, such as Vst, V and Tsp, differ significantly from the normal values. Velocity indicators are significantly higher than the norm, Tsp — below the norm. For the third group, parameters Vi, Vst, V and CS are statistically significantly higher than normal. Tsp is statistically significantly lower than normal. Conclusion: Using the thrombodynamics test (TD) it was shown that there is a hypercoagulation of blood plasma accompanied by the generation of spontaneous clots in patients with schizophrenia in the acute stage. The TD test reveals a tendency to hypercoagulation at an early stage, when other methods are not yet sensitive enough.

An introduction to point-of-care testing in extracorporeal circulation and LVADs.

There is a delicate balance between bleeding and clotting in patients on circuits such as ventricular assist devices or extracorporeal membrane oxygenation. Traditional coagulation tests, prothrombin time, activated partial thromboplastin time, and anti-factor Xa levels, are used to monitor patients on these devices. However, turnaround times and inability to assess global hemostasis, including platelets and fibrinogen have contributed to a recognition that faster, accurate, and more informative coagulation tests are needed. Activated clotting time is used to monitor heparin in patients on circuits and has the advantages of being a near-patient point-of-care test. However, its utility is limited to heparin monitoring. Viscoelastic tests (thromboelastometry and thromboelastography) are global, whole-blood coagulation tests, and whole-blood platelet aggregometry evaluates platelet function. Ideally, these tests can ensure that patients are within the therapeutic range of their antithrombotic medications, identify patients at risk for hemorrhagic or thrombotic complications, and guide management of acute bleeding complications. This ideal is currently hampered by a lack of studies that delineate clear ranges that are clinically relevant. Future research is needed to better understand the optimal use of point-of-care coagulation testing in patients on extracorporeal circuits and ventricular assist devices.

Implications of deranged activated partial thromboplastin time for anaesthesia and surgery.

Bleeding during and after surgery ranges from trivial to fatal. Bleeding is in part determined by the patient's coagulation status. The UK National Institute for Health and Care Excellence recommends a pre-operative clotting test for patients with a history of abnormal bleeding. Anaesthetists are familiar with the prothrombin time assay, used to monitor warfarin effect, but anaesthetists may be less familiar with the activated partial thromboplastin time (APTT), which tests the function of the 'intrinsic' clotting pathway. The activated partial thromboplastin time may be prolonged due to contamination, anticoagulant therapy, clotting factor deficiencies, lupus anticoagulant or acquired inhibitors of specific clotting factors. A prolonged activated partial thromboplastin time should lead to: further testing to exclude heparin contamination or therapy, mixing studies to identify factor deficiencies and if necessary dynamic studies, such as the dilute Russell's viper venom time and the Actin FS-activated partial thromboplastin time, to identify direct factor inhibitors. These tests identify abnormalities and their implications for bleeding, helping anaesthetists and haematologists to manage haemostasis for individual patients.

Management of Microsurgical Patients using Intraoperative Unfractionated Heparin and Thromboelastography.

Maintaining optimal coagulation is vital for successful microvascular tissue transfer. The viscoelastic thromboelastography (TEG) is a modern and dynamic method to assess a patient's coagulation status. The aim of this study was to evaluate its diagnostic capabilities of identifying microvascular complications. A retrospective chart review was conducted for the most recent 100 cases of abdominal free flap breast reconstruction of a single surgeon. Patient demographics, medical history, clinical, and operative details were documented. Thrombocyte counts, prothrombin time (PT), activated partial thromboplastin time (aPTT), and various TEG parameters were gathered for preoperative, intraoperative, and two postoperative time points. A total of hundred patients were identified, who underwent 172 abdominal-based free flaps for breast reconstruction. TEG was more dynamic compared with PT or aPTT and demonstrated borderline hypocoagulate values intraoperatively upon unfractionated heparin administration and hypercoagulate values postoperatively. In contrast, PT and aPTT demonstrated a continuously hypocoagulable state. Complications included five thrombotic events and three hematomas. The thrombotic cases had much steeper increases of TEG-G between surgery and postoperative day 2 (p = 0.049), while PT and aPTT failed to identify these patients. Of those, two resulted in flap loss (1.2%) that both occurred in patients with abdominal scars from previous surgery. The TEG is a useful adjunct for monitoring coagulation status in microsurgical breast reconstruction. When thrombosis at the anastomosis occurs, TEG correlates with a more rapid rebound from an intraoperative hypocoagulable state to a postoperative hypercoagulable state, when using the TEG. The TEG is a valuable tool for a more dynamic assessment of the patients' changing coagulation status.

Preoperative coagulation abnormalities as a risk factor for adverse events after pancreas surgery.

To determine whether elevated INR or PTT values predicted 30-day postoperative adverse events following elective pancreatectomy. The American college of surgeons national surgical quality improvement program (ACS-NSQIP) database was used to identify 14 747 patients undergoing elective pancreatectomy from 2005 to 2013. The association of elevated INR or PTT with 30-day postoperative outcomes of morbidity and mortality was examined using multivariate logistic regression analysis. The overall 30-day mortality rate increased from 1.8% to 3.3% from the control to the high INR or PTT group (P = <0.001). An elevated INR/PTT increased the odds for bleeding requiring transfusion, superficial SSI, sepsis, unplanned intubation or >48 h on a ventilator, cardiac arrest or myocardial infarction, acute renal failure, return to the OR, and prolonged length of stay. With the exception of superficial SSI, multivariate logistic regression models revealed that these same events remained statistically significant after controlling for potential confounders. Prolonged bleeding times (high INR/PTT) is associated with increased mortality and adverse outcomes after pancreas surgery. A patient's coagulation profile may serve as a risk stratification tool to identify higher risk patients that require more resources.

A Novel Multiplex HRM Assay to Detect Clopidogrel Resistance

Clopidogrel is an antiplatelet medicine used to prevent blood clots in patients who have had a heart attack, stroke, or other symptoms. Variability in the clinical response to clopidogrel treatment has been attributed to genetic factors. In particular, five SNPs of rs4244285, rs4986893, rs12248560, rs662 and rs1045642 have been associated with resistance to clopidogrel therapy in Chinese population. This work involves the development of a multiplex high-resolution melting (HRM) assay to genotype all five of these loci in 2 tubes. Amplicons corresponding to distinct SNPs in a common tube were designed with the aid of uMelt prediction software to have different melting temperatures Tm by addition of a GC-rich tail to the 5′ end of the certain primers. Two kinds of commercial methods, Digital Fluorescence Molecular Hybridization (DFMH) and Sanger sequencing, were used as a control. Three hundred sixteen DFMH pretested samples from consecutive acute coronary syndrome patients were used for a blinded study of multiplex HRM. The sensitivity of HRM was 100% and the specificity was 99.93% reflecting detection of variants other than the known resistance SNPs. Multiplex HRM is an effective closed-tube, highly accurate, fast, and inexpensive method for genotyping the 5 clopidogrel resistance associated SNPs.

Editorial introductions

Editorial introductions

Blood clot parameters: Thromboelastography and scanning electron microscopy in research and clinical practice

BackgroundClotting parameters are informative of overall haematological healthiness of an individual. Particularly, clotting parameters can be used as a measure of the degree of pathology of the coagulation system. Thromboelastography (TEG) is a well-known technique that is an important point-of-care method, as well as research method. Scanning electron microscopy (SEM) is a novel research method, but with possible clinical application. However, there are no clear standardized guidelines for TEG and SEM result interpretation. Materials and methodsWe have an extensive database of results from TEG of hypercoagulable, hypocoagulable and healthy whole blood (WB) and platelet poor plasma (PPP). These results were generated using citrated PPP or WB, followed by the addition of CaCl2, to initiate clot formation. We also have an extensive and comprehensive database of thousands of clot micrographs, prepared for SEM. We reanalysed all our data to compile a user-friendly guideline for TEG and SEM. We also discuss the effects of different storage times on both WB and PPP. ResultsWe provide a quick and informative guide that discusses each TEG parameter, in both WB and PPP. Increases or decreases in the various parameters are indicative of either hyper- or hypocoagulability. We also show how hypo- and hypercoagulable clots look like, compared with healthy clots, using SEM analysis of clots created by adding thrombin to PPP. ConclusionFor optimal and speedy interpretation of a patient's coagulation status, it is essential for the clinician to make an informed and precise decision regarding clotting propensity. We believe this guideline will add to the standardization of TEG parameters, and ultimately contribute to the treatment of patients. These guidelines will also allow researchers to standardize their data interpretations and ultimately allow for the use of a global and inclusive database that might be included in precision medicine approaches.

Coagulation Profile of Patients with Adolescent Idiopathic Scoliosis Undergoing Posterior Spinal Fusion.

Blood loss and transfusion requirements during posterior spinal fusion for adolescent idiopathic scoliosis remain a concern. The mechanism of bleeding in these patients is poorly characterized. Thromboelastography is a comprehensive test of a patient's coagulation system commonly used in cardiac surgical procedures. It has not been well studied for use in patients with adolescent idiopathic scoliosis. A prospective, observational study of the coagulation profile of patients with adolescent idiopathic scoliosis undergoing posterior spinal fusion is presented. Healthy patients with adolescent idiopathic scoliosis without a bleeding abnormality were analyzed during posterior spinal fusion. Standard coagulation laboratory and thromboelastogram measures were obtained at the time of the incision and at 1-hour intervals during the surgical procedure. Laboratory values were analyzed in relation to outcomes such as bleeding, transfusion, and a fibrinolysis score. Fifty-eight patients were observed. Eighty-one percent of patients were female, the mean age was 13.5 years, a mean of 11.1 levels were fused, the median estimated blood loss was 645 mL, and 47% of patients received blood products. Overall, laboratory values remained stable throughout the surgical procedure. Mild increases in prothrombin time and partial thromboplastin time were observed, and platelets remained stable. From thromboelastogram analysis, an acceleration of clot formation (decreased reaction time) and a slight increase in clot lysis (increased lysis percentage at 30 minutes) were observed. A fibrinolysis score compiled from the presence of fibrin degradation products, the presence of D-dimers, and increased prothrombin time rose steadily over surgical time. The fibrinolysis score was predictive of both transfusion and greater estimated blood loss per level. The stress of posterior spinal fusion induces a hypercoagulable state in patients with adolescent idiopathic scoliosis. Over the first 2 hours of a surgical procedure, varying degrees of fibrinolysis develop. Platelets and coagulation factors are not depleted. Our data support the use of antifibrinolytic therapy for patients with adolescent idiopathic scoliosis.

Effect of Concomitant COPD on Blood Clotting in Patients with Stage II Hypertension

We know that comorbidity COPD and arterial hypertension has an adverse effect on the disease and the presence of complications in such patients. To determine the state of coagulation link of hemostasis, we have examined 150 people: 15 healthy (control), 36 patients with COPD II-III without GC (I group), 69 patients with essential hypertension with concomitant COPD (second group) and 30 patients GC II stage (third group). We found that comorbid course AH and COPD leads to imbalance in the blood coagulation system, which is manifested by slowing prothrombinase formation (coagulation I phase) evidenced prolongation of APTT and lebetoks test, combined with a strong activation of the final phase of clot formation, a reflection of what there is a significant increase in fibrinogen and RFMK and shortening ehitoks and antsystron tests.

Biatrial appendages clots in a rheumatic heart disease patient – an important lesson to remember

Patients with Atrial fibrillation (AF) are quite prone to develop atrial clots due to stasis from impaired atrial contractile function. While left atrial (LA) and left atrial appendage (LAA) thrombi are quite common, right atrial (RA) and right atrial appendage (RAA) clots are uncommonly seen. Structural and functional differences between RAA and LAA have been implicated in lower prevalence of RAA clots in AF patients. We report here simultaneous LAA and RAA clots in a patient with Rheumatic heart disease, mitral stenosis and Atrial fibrillation. Though current guidelines do not make a specific mention of RAA assessment, we highlight the fact that a comprehensive echocardiographic evaluation of both atrial appendages is of paramount importance in atrial fibrillation patients especially those who are planned to undergo balloon mitral valvotomy or cardio version. Key words: Right atrial appendage, Left atrial appendage, atrial fibrillation, Mitral stenosis, clot.

Alterations in Fibrin Structure in Patients with Liver Diseases.

The hemostatic balance in patients with liver diseases is relatively well preserved due to concomitant alterations in pro- and antihemostatic pathways. Thrombin generation studies support the notion of hemostatic competence in liver diseases, but in such tests alterations in fibrinogen level and function are not taken into account. We have recently studied structural and functional properties of the fibrin clot in patients with liver diseases. Although we have confirmed previous findings that hypersialylation of the fibrinogen molecule in patients with liver diseases contributes to a defective fibrinogen-to-fibrin conversion, we have found that once the clot has been formed, it has a thrombogenic nature as assessed by permeability assays. These thrombogenic properties of the fibrin clot in cirrhosis relate to incompletely characterized intrinsic changes in the fibrinogen molecule, which may include oxidation and hypersialylation. In addition, in patients with nonalcoholic fatty liver disease thrombogenic properties of the fibrin clot are not only due to liver disease but also to obesity and the metabolic syndrome. During liver transplantation, the clot normalizes and becomes increasingly permeable, and the functional properties of the fibrin clot are markedly normalized by fibrinogen concentrate, when added to plasma samples in vitro. These new insights in the functional properties of the fibrin clot in patients with liver diseases facilitate a more rational approach to treatment and prevention of both bleeding and thrombotic complications.

Cefoperazone/Sulbactam-Induced Abdominal Wall Hematoma and Upper Gastrointestinal Bleeding: A Case Report and Review of the Literature.

An 87-year-old woman developed abdominal wall hematoma and upper gastrointestinal bleeding during treatment with cefoperazone/sulbactam for pneumonia. The woman received cefoperazone/sulbactam at 4.5 g twice daily for intravenous infusion. After 7 days, she developed sudden onset of left lower abdominal pain, associated with subcutaneous mass, and vomited a coffee-colored liquid. Investigations revealed a coagulation index abnormality and activated partial thromboplastin time and prothrombin time increased obviously. She was diagnosed with cefoperazone-induced hemorrhage. Cefoperazone/sulbactam was discontinued and the patient received vitamin K1. The blood coagulation function improved and hematoma disappeared after 3 days. A Naranjo assessment score of 6 was obtained, indicating a probable relationship between the patient’s coagulation function disorder and her use of the suspect drug.

Indices predictive of circuit clotting in patients treated with continuous renal replacement therapy

Indices predictive of circuit clotting in patients treated with continuous renal replacement therapy

Contraction (retraction) of blood clots in patients with ischemic stroke

To study a possible pathogenetic role of the blood clot contraction and its disturbances in the acute stage of ischemic stroke (IS). Using a new instrumental technique to study the dynamics of clot contraction in vitro, the authors have determined quantitative parameters of clot contraction (the extent and rate of contraction, duration of the lag-period) in the blood of 85 patients with acute IS. The contractile activity of blood clots was substantially reduced compared to the blood of healthy subjects. Correlations between hemostatic and contractile parameters suggest that the reduced clot contraction in stroke is due to the lower platelet count and impaired platelet functionality, higher levels of fibrinogen and antithrombin III as well as higher hematocrit and hemoglobin contents, leukocytosis, and changes in the biochemical blood composition. The results show that the reduced ability of clots may be a novel pathogenic mechanism that aggravates the course and outcomes of IS.

Clinical characteristics of in-situ pulmonary artery thrombosis in Korea.

Little is known regarding the clinical features and course of in-situ pulmonary artery thrombosis (PAT). The aim of the present study was to investigate the clinical characteristics of PAT. Patients with PAT were retrospectively identified from a tertiary referral center in South Korea. A control group consisted of patients with pulmonary embolism in whom the right or left pulmonary artery was the largest pulmonary embolism-involved site. We compared various clinical parameters between the two groups. Of the 23 PAT patients, the most common underlying condition was tuberculosis-destroyed lung [11 (47.8%)], followed by pulmonary artery stump after lobectomy or pneumonectomy [7 (30.4%)]. In all patients except one, PAT was located in the right or left pulmonary artery. Computed tomography scans demonstrated that clots were completely or partially resolved less frequently in the PAT group than in the control group [4 (25%) versus 62 (90%); P < 0.001]. In the PAT group, three of the seven patients (43%) who had undergone anticoagulation therapy exhibited improvement, and one of the nine patients (11%) who had not received anticoagulation therapy experienced improvement; however, the difference was not significant. Tuberculosis-destroyed lung was the most common underlying condition in Korean PAT patients, followed by pulmonary artery stump after lung resection. The clots in patients with PAT were mostly located in the right or left pulmonary artery, and clot resolution was less frequent in the PAT group compared to the pulmonary embolism group.

Trauma, Time, and Transfusions: A Longitudinal Analysis of Coagulation Markers in Severely Injured Trauma Patients Receiving Modified Whole Blood or Component Blood Products.

The current study leveraged data from the Early Whole Blood (EWB) trial to explore the effects of modified whole blood (mWB) versus component (COMP) transfusions on coagulation parameters over time using longitudinal statistical methods. The EWB study was a single-center randomized controlled trial, approved by the local IRB. Adult patients at highest-level trauma activations were randomized into mWB or COMP groups. Coagulation status was evaluated (at times 0, 3, 6, 12, and 24 h postadmission) using thrombelastography, platelet aggregometry, and calibrated automated thrombograms. Longitudinal statistical analyses with generalized estimating equations (GEE) were used to evaluate the effects of group, time, transfusion types, and their respective interactions on changes in measured coagulation markers. A total of 59 patients were enrolled and adhered to protocol in the EWB trial, 25 in the mWB group, and 34 in the COMP group. Patients in both the mWB and COMP groups demonstrated a significant decline in their thrombelastography parameters during the first 3-6 h, specifically K-time, α-angle, maximum amplitude, G, and LY30. Patients receiving mWB exhibited improved thrombin potential than those receiving COMP. Platelet count and function declined over time in both mWB and COMP groups; however, platelet aggregation in response to ristocetin in the mWB group was significantly improved at 12 h compared with the COMP group. The longitudinal GEE model revealed significant group-time interactive effects on the changes in coagulation markers and significant effect of platelet transfusions on improvements in coagulation profile. We observed significant interactive group-time effects, indicating that the types of transfusion as well as the time of transfusion significantly affect the patient's coagulation status. Our pilot data suggest that there is an improvement in platelet function with mWB, but further studies are needed. Regardless, platelet transfusions were associated with improvements in coagulation over time in both the groups.