Coagulation Studies Research Articles

The role of extended coagulation screening in adult cranial neurosurgery

IntroductionPostoperative hemorrhage after adult cranial neurosurgery is a serious complication with substantial morbidity and mortality. Research questionWe investigated if an extended preoperative screening and an early treatment of previously undetected coagulopathies may decrease the risk of postoperative hemorrhage. MethodsA prospective study cohort of patients undergoing elective cranial surgery and receiving the extended coagulatory work-up were compared to a propensity matched historical control cohort. The extended work-up included a standardized questionnaire on the patient's bleeding history as well as coagulatory tests of Factor XIII, von-Willebrand-Factor and PFA-100®. Deficiencies were substituted perioperatively. The primary outcome was determined as the surgical revision rate due to postoperative hemorrhage. ResultsThe study cohort and the control cohort included 197 cases each, without any significant difference in the preoperative intake of anticoagulant medication (p ​= ​.546). Most common interventions were resections of malignant tumors (41%), benign tumors (27%) and neurovascular surgeries (9%) in both cohorts. Imaging revealed postoperative hemorrhage in 7 cases (3.6%) in the study cohort and 18 cases (9.1%) in the control cohort (p ​= ​.023). Of these, revision surgeries were significantly more common in the control cohort with 14 cases (9.1%) compared to 5 cases (2.5%) in the study cohort (p ​= ​.034). Differences in mean intraoperative blood loss were not significant with 528 ​ml in the study cohort and 486 ​ml in the control cohort (p ​= ​.376). ConclusionPreoperative extended coagulatory screening may allow for revealing previously undiagnosed coagulopathies with subsequent preoperative substitution and thereby reduction of risk for postoperative hemorrhage in adult cranial neurosurgery.

Технологические свойства и качественный состав молока и молочной сыворотки коров в зависимости от влияния генотипов по генам каппа- и бета-казеина

Studies were carried out on 118 cows of black and white Holsteinized breed with certain genotypes according to beta- (CSN2) and kappa-casein (CSN3) genes. The aim of the study was to examine the qualitative composition and technological properties of milk and milk whey of black and white Holsteinized cows obtained by the rennet coagulation studies in the relationship with the genotypes for beta- and kappa-casein genes. The distribution of alleles for the CSN2 gene in the studied population: A1 – 0,424 and A2 – 0,576. The distribution of alleles for the CSN3 gene: A – 0,754 and B – 0,246. Among the cows studied, most of the animals (55,9 %) are carriers of the A1A2 genotype, 29,7 % of the A2A2 and 14,4 % of the A1A1. Carriers of the AA genotype were 57,6 % of the animals, 35,6 % were AB and only 6,8 % were BB. The whey-to-milk ratio showed reliable differences and trends among the groups of animals of different genotypes by CSN2 and CSN3 genes for the indices of MFF, MFP lactose content, dry matter and casein content, which indicates the influence of genotype on the properties of milk during technological processing. Single-factor analysis of variance showed a significant effect of CSN2 gene genotype on rennet clotting and MFP in milk. Also a significant effect of CSN3 gene has been shown on rennet coagulation of milk, milk yield, MFF, MFP, casein content; in this connection it is the most perspective factor for further study and inclusion in breeding programs in order to increase genetic potential of milk productivity and qualitative composition of milk most suitable for processing in the populations of black and white Holstein breed.

The diagnosis and Management of HIV Associated Acquired Hemophilia A: A Case Series From Durban, South Africa.

In acquired hemophilia A (AHA), the body produces auto-antibodies against Factor VIII. Although AHA is rare, with an incidence of 1.5 patients/1 million population/year, there is a strong association with human immunodeficiency virus (HIV) infection. The accurate interpretation of screening coagulation tests is critical to identify patients with AHA, as the mortality rate secondary to bleeding is high. This was a retrospective case series which included all newly diagnosed AHA patients that were referred to Hemophilia care unit at King Edward VIII Hospital, Durban, South Africa from January 2011 to December 2021. The clinical presentation and laboratory results were documented. Five patients were included in this case series. All patients were females aged between 28 and 64 years of age and they were HIV seropositive. They presented with spontaneous cutaneous and intramuscular bleeding. Four patients were virologically suppressed on anti-retroviral therapy, and no patient had a family history of congenital bleeding diathesis. Laboratory investigations confirmed AHA with high Factor VIII inhibitor titers, which ranged from 41 to 900 Bethesda Units (BU). All patients were managed with bypassing agents and oral corticosteroids. The monitoring of patients after the initiation of treatment was difficult as they all defaulted treatment. In view of the prevalence of HIV in sub-Saharan Africa, there is a possibility that AHA is under-diagnosed in our setting. The clinician and the laboratory have a combined critical role in identifying patients with AHA as the investigation of a prolonged APTT is mandatory. There are challenges in managing AHA patients in a resource-constrained setting.

Effects of catheter ablation of atrial fibrillation on the biomarker profile.

Following catheter ablation for atrial fibrillation (AF), there are dynamic changes in the atrial myocardium associated with damage to and necrosis of atrial tissue and other procedure related changes in rhythm and anticoagulation. Early time-dependent changes in biomarkers of necrosis, inflammation, and coagulation have been reported. This study examines mid-term (4-8weeks post-ablation) changes in biomarkers and explores their ability to predict AF recurrence at one-year. Twenty-seven patients (mean age 65.4±9.7 years, 30% female) undergoing catheter ablation for AF had peripheral venous blood samples obtained at the time of ablation and 4-8weeks later. All samples were processed to obtain plasma which was frozen for subsequent analysis. Coagulation studies were performed at the Northwestern Special Hemostasis Laboratory: VWF, ADAMTS13, PAI-1, D-dimer, and TAT complexes. A commercial lab analyzed samples for CRP, cystatin C, fibrinogen, galectin, IL-6, MMP-2, myoglobin, NT-proBNP, PAI-1, TIMP-1, TIMP-2, TPA, and VWF. Significant changes were noted with higher levels of ADAMTS13 (p <0.0001), fibrinogen (p =0.004), MMP-2 (p =0.0002), TIMP-2 (p =0.003), and TPA (p =0.001) compared to lower levels of TAT (p <0.0001) and NT-proBNP (p =0.0001) at follow up post-ablation. One year after ablation, AF had recurred in 11/26 (42%) of patients. None of the biomarker changes predicted the 1-year outcome, and there was no significant association with the use of warfarin versus rivaroxaban. In patients undergoing catheter ablation for AF, there were significant changes in pre- vs post-ablation levels of multiple biomarkers. However, these changes were not associated with 1-year outcome of AF recurrence.

Features of clinical and laboratory diagnosis of rare coagulopathy – acquired hemophilia

Introduction. The formation of circulating autoantibodies capable of inhibiting factors of the blood coagulation system is accompanied by the occurrence of spontaneous and/or post-traumatic bleeding in patients without a history of previous disorders of the hemostasis system. One of the reasons for the development of such conditions is acquired hemophilia.Aim – to present algorithms for laboratory diagnosis of acquired hemophilia.Main findings. Primary diagnosis and control of therapy of the disease are carried out based on the results of coagulation studies, the decoding and interpretation of which often causes difficulties due to the low awareness of doctors about the algorithms for laboratory diagnosis and tactics for managing patients. In acquired hemophilia there is no direct relationship between the results of laboratory tests and the clinical manifestations of the disease, which is determined by the kinetics of the interaction of autoantibodies with blood coagulation factor (F) VIII. There is a «false» in vitro decrease in the activity of factors of the internal pathway (FIX, FXI and FXII), associated with the effect of a rapid inhibitor in high titers. An important laboratory task is the determination of lupus anticoagulant, which makes it difficult to timely diagnose and verify the diagnosis.

The Role of Thromboelastography in Identifying Coagulopathy Among Geriatric Traumatic Brain Injury Patients.

Background The geriatric population has the highest incidence of head injury, and those who are anticoagulated have an increased risk of traumatic intracranial hemorrhage (ICH). The availability of viscoelastic coagulation studies has coincided with the development of many anticoagulation reversal agents. In this study, our objective was to assess whether the thromboelastography (TEG) assay affected clinical decision-making regarding reversal agent administration among geriatric patients with ICH caused by blunt head trauma. Methodology We prospectively screened adults aged 65 and older with head trauma presenting to the emergency departments of two level-one trauma centers. International Classification of Diseases, Tenth Revision codes S00-09 were used to identify the diagnosis of head injury. Patients with CT head imaging positive for acute ICH were included. Each patient was assessed for home use of antiplatelet or anticoagulant medications, as well as in-hospital use of any reversal agents. Reversal agent administration and mortality were compared between patients who received TEG and those who did not. Results A total of 680 patients had acute ICH on head CT, and 324 (48%) patients received TEG. More patients screened with TEG were transfused platelets (30.2% vs. 10.7%, p < 0.001). This remained significant for patients taking anticoagulants, antiplatelets, or neither. There were no differences in the administration of other reversal agents (prothrombin complex concentrate or fresh frozen plasma) or mortality whether or not TEG was performed. Conclusions Patients who had TEG performed were more likely to receive platelet reversal agents, regardless of antiplatelet medication usage. Among elderly adults with ICH, TEG is a rapid screening test that may help identify patients with platelet function abnormalities requiring reversal.

633: LABORATORY MONITORING DURING THE FIRST 24 HOURS OF PEDIATRIC EXTRACORPOREAL MEMBRANE OXYGENATION

Introduction: Pediatric extracorporeal membrane oxygenation (ECMO) is a potentially lifesaving intervention for cardiopulmonary failure. Anticoagulation protocols are necessary to prevent complications. Limited data exist on how traditional coagulation tests correlate with early bleeding complications in this population. This study evaluates pre-and-post cannulation coagulation parameters during the first 24 hours of ECMO initiation in pediatric patients. Methods: This is an IRB approved retrospective cohort study. Included are 116 children that received ECMO at our academic institution from January 2017 to March 2022. Children with no hematologic events and acute bleeding events were compared. Routine pre-and-post-cannulation coagulation profiles in the initial 24-hours of ECMO were evaluated. Data was analyzed between groups using Mann Whitney U test with SPSS Statistics version 10.0. Results: Patients were grouped into “no event” (N=88) and “bleed event” (N=28). Average age was 43.3 months. Children with major bleeding events in the first 24 hours of ECMO had a longer time until target ACT was reached, 5 vs 3.5 hours (p=0.003). These patients also had more prolonged post-cannulation prothrombin time (PT), 19.2 vs 16.1 seconds (p=0.002), and international normalized ratio (INR), 1.9 vs 1.6 (p=0.002). Also, bleeding patients had lower pre-and-post-cannulation fibrinogen levels, 135 vs 229 (p=0.008) and 106.5 vs 181 (p=< 0.001), respectively, and lower post-cannulation platelet counts, 82.5 vs 109.5 (p=0.035). No differences were seen for the initial ACT, heparin dose, baseline platelet count, or pre-and-post hemoglobin and activated partial thromboplastin time. Conclusions: Major bleeding events occurred within 24 hours in approximately 24% of our cohort. Identifying risk factors for bleeding may aid in reducing morbidity and mortality. Our data shows that consideration of fibrinogen levels, platelet count, PT and ACT may help to identify pediatric patients at risk of early bleeding during ECMO. Attention to these baseline and immediate post-cannulation laboratory values may be important to determine initial bolus dosing and adjustment of anticoagulation in these patients. Continued multi-center collaboration and incorporation of other coagulation studies, like anti-FXa and thromboelastography, is needed.

1071: QUANTIFYING PASSIVE CLINICAL DECISION SUPPORT AND REDUCING LABORATORY RESULT FATIGUE

Introduction: Clinical decision support (CDS) systems are intended to improve adherence to standard practices, enhance awareness, and increase care quality. Excessive passive decision support, such as laboratory result highlighting, can reduce CDS effectiveness. We quantify result highlighting burden across two institutions, and measure change in highlighting burden when applying published data-driven cutoffs to identify abnormal laboratory values. Methods: This multi-site retrospective study includes patients admitted to the pediatric ICU between 9/2016 and 9/2019. We describe the frequency of abnormal laboratory result highlighting by laboratory group, compared across sites. We use a logistic regression model to analyze the relationship between abnormal result highlighting to selected covariates and report odds ratios. We apply modified cutoff values based on mortality odds ratios (MOR) [Pollack et al, Peds Crit Care Med, 2021], indicating “abnormal” results when MOR >2.0. We re-calculate the frequency of abnormal result highlighting and compare to existing cutoffs. Results: We report a total of 19,087 ICU encounters and 12,507 unique patients. Across all laboratory groups, abnormal result highlighting differed significantly by institution (A: 54% vs B: 50%, p < 0.001). Percent of results with passive alerts was greatest in coagulation studies (A: 77%, B: 36%) and least in basic chemistry panels (A: 47%, B: 43%). In a logistic regression model, the only covariate consistently associated with an abnormal result was “collected < 24 hours from ICU admission,” for which odds of an abnormal result decreased [A: 12% decrease; B: 15% decrease]. When MOR-based cutoffs were applied, abnormal result highlight significantly decreased across all laboratory groups by >14%, except for complete blood counts (A: 14% increase, B: 16% increase). Conclusions: Abnormal result highlighting is a pervasive form of passive decision support that is differentially present across PICUs. Modifying laboratory result thresholds using data-driven MOR-based cutoffs reduces this passive CDS burden, which may better allow providers to identify physiologic signals from data noise. This work represents a first step in improving upon passive CDS to improve patient care quality and safety.

Pharmacokinetics and tolerability of the dual TORC1/2 inhibitor sapanisertib in combination with the MEK inhibitor trametinib in dogs.

Activation of one or both the Ras/MAPK and PI3K/Akt/mTOR signal transduction pathways are known to mediate oncogenicity of several canine and human cancers, including mucosal melanomas. Reciprocal cross activation between the two pathways can be a source of drug resistance. Consequently, oral dosing for plasma pharmacokinetic (PK) analysis and tolerability to a combination of sapanisertib, a dual TORC1/2 inhibitor, and trametinib, a MEK inhibitor, was evaluated in nontumor-bearing laboratory dogs for its potential application in parallel pathway targeting. Twelve dogs, divided into three equal cohorts, received either the combination or single agents. Animals were monitored for PK following single dose and 17-day repeat dosing, and by clinical observations, hematology, serum biochemistry, coagulation studies and urinalyses. A single trametinib dose (0.025 mg/kg), sulfated as dimethyl sulfoxide which enhanced its absorption, reached mean maximum concentration (Cmax) 0.64 ng/mL [18% coefficient of variation (CV)] at a median time to maximum concentration (Tmax) of 1.5 h (hr), and mean area under the concentration-time curve (AUC) 16.8 hr*ng/mL (14%CV), which were similar when given alone or in combination with sapanisertib. A prolonged half-life afforded 3-4-fold plasma accumulation of trametinib with daily dosing, analogous to humans. Trametinib PK mirrored previous regulatory data in dogs, while exposure approximated some published human values but generally not all patients. Sapanisertib-alone in canine plasma following single 0.1 mg/kg dose [mean Cmax 26.3 ng/mL (21%CV), median Tmax 2.0 hr, and mean AUC 248 hr*ng/mL (41%CV)] resembled levels in human therapeutic trials; whereas canine sapanisertib exposure was reduced when combined with trametinib, a known cytochrome P450 CYP3A4 inducer. Sex differences were not observed for either drug. Side effects upon repeat dosing with either or both drugs may include body weight loss, maldigestion, and cutaneous discoloration. The combination was tolerated without dose limiting toxicity, although clinical laboratory analyses revealed drug-induced acute-phase inflammation, proteinuria, and decreased blood reticulocytes, mild changes not necessitating intervention. Short-term results in dogs with this combination would appear to hold translational promise for clinical trial evaluation to target canine and possibly human melanoma, as well as other cancers having one or both signal transduction pathway activations.

A seasonal eruption in an unusual distribution.

We present the case of a 23-year-old equestrian who presented with violaceous plaques on the lateral thighs. Blood tests including a full autoimmune screen, coagulation screen, cold agglutinins and cryoglobulins revealed no abnormalities. Histological findings were consistent with a low-grade lymphocytic vasculitis.

Lessons learned from the COVID-19 pandemic: Improving initial investigations with the implementation of a COVID-19 blood request panel.

During the COVID-19 pandemic, the Hillingdon Hospitals NHS Foundation Trust produced trust guidelines for the initial blood investigation of COVID-19 inpatients. However, insufficient education meant inconsistent adherence to this guidance. To examine whether the implementation of a COVID-19 blood request panel improves adherence to local trust guidelines. Between March and April 2020, initial blood investigations performed for positive COVID-19 cases were compared to guidelines. Results were presented locally and a COVID-19 panel was added to the electronic system that provided prompts for appropriate investigations. A re-audit between May and June 2020 was conducted to assess adherence post-intervention. 383 patients were identified in the initial audit cohort and a sample of 20 patients were re-audited. Adherence to Full Blood Count, Urea and Electrolytes, C-reactive Protein and Liver Function Tests increased to 100% from 99.7% (p =0.8), 99.2% (p =0.69), 98.7% (p =0.61), and 96.6% (p =0.4) respectively. Coagulation screen adherence increased to 90% from 72.8% (p =0.09). Appropriate requesting of D dimers increased to 50% from 19.9% (p =0.001). Inappropriate troponin requesting decreased to 26.3% from 38.9% (p =0.23). A user-friendly COVID-19 panel of investigations resulted in improved adherence to guidelines. Clear communication and education are essential to help alleviate uncertainty during a pandemic.

Should patients taking direct oral anticoagulants be routinely monitored with coagulation studies?

Consenstein, Caleb MD; Duckworth, Drake MD; Kane, Lucas DO; Price, Dakota MD Author Information

Report of two cases of subconjunctival haemorrhage as first sign of post‐pregnancy acquired haemophilia a (AHA)

AbstractPurpose: To show that subconjunctival haemorrhage may be the first sign of post‐pregnancy acquired A haemophilia (AHA), a potentially fatal bleeding disorder.Methods: Case reports.Results: Two thirty‐year‐old caucasic women at first pregnancy presented slight pain without visual loss 2 weeks after uncomplicated spontaneous full‐term delivery. The only clinical findings were a subconjunctival bleeding for both and a small haematoma in the first case. The clinical history was negative for spontaneous bleeding also in infantile age and at previous surgery and no bleeding tendency was observed in the main relatives. The first patient was lost on follow‐up and admitted to urgent haemathologic evaluation due to large multiple cutaneous hematomas, a massive deep muscle haematoma, asthenia and dyspnea. In the second case quick routine coagulation labs were performed immediately after the subconjunctival bleeding. In both cases PTT ratio was increased. An extensive study of blood coagulation suggested the presence of a circulating inhibitor against factor VIII [1,2], confirming the diagnosis of AHA. First case was treated with a bypassing agent, however the eradication was obtained only with immunosuppressive therapy. Second case was initially placed in close follow‐up, since the post‐pregnancy form is often self‐limiting, however an immunosuppressive therapy was set after clinical progression due to the appearance of spontaneous hematoma.Conclusions: AHA is a relevant acquired bleeding disorder that can be fatal if not quickly recognized and treated even when the initial clinical signs are minor [3], how it can happen in post‐pregancy mainly in the first month [4]. Since it may present as spontaneous subconjunctival haemorrhage, routine hemathological and coagulation labs should be performed to exclude this serious condition or once identified, allow for proper clinical management.

A health economic evaluation of the unnecessary ordering of coagulation studies and blood grouping prior to elective surgery.

Unnecessary pathology tests add significant financial burden to health care expenditures while offering limited benefit to patients. Current guidelines do not support indiscriminate ordering of preoperative coagulation studies and ABO blood typing. We sought to estimate the incidence and financial cost of the indiscriminate ordering of these investigations in our institution. A single centre retrospective electronic chart review was performed in patients who underwent preoperative coagulation studies or ABO blood typing prior to elective surgery over a ten-month period. Using local evidence-based guidelines, only 9% of coagulation studies and 75% of ABO blood typing studies were indicated. The estimated cost of unnecessary tests in our cohort of 2688 patients was approximately AUD35,500. Interventions such as directed education and clinician feedback should be considered to combat the high incidence of indiscriminate ordering of preoperative coagulation studies and ABO blood typing.

A Phase II Study to Evaluate the Safety and Efficacy of Defibrotide in Sickle Cell Disease-Related Acute Chest Syndrome (IND 127812)

Background: Acute Chest Syndrome (ACS) is the greatest contributor to the morbidity and mortality of Sickle Cell Disease (SCD) patients with a rate of 12.8 cases per 100 patient-years. The mortality rates of ACS are 4 times higher in adults than in children (Children 1.1% vs Adults 4.3%) (Vichinsky et al, Blood, 1997). The root cause of ACS in SCD is related to endothelial dysfunction (Paul et all, European Journal of Hematology 2011). While existing therapies target infection, inflammation, and alveolar hypoxia, they do not work to repair loss of integrity within the endothelial barrier that ultimately causes ACS. Defibrotide is a polydisperse mixture of predominantly single stranded oligonucleotides derived from porcine intestinal mucosa. Several pre-clinical studies indicate that Defibrotide primarily protects endothelium, particularly in small vessels, and appears to reduce endothelial cell injury (Falanga et al, Leukemia, 2003). In a randomized, phase III study, a decrease in incidence of SOS/VOD was observed in pediatric hematopoietic stem cell transplantation patients who received prophylactic Defibrotide (Corbacioglu et al, 2012). We hypothesized that Defibrotide is safe and well tolerated in SCD-associated ACS. Primary Aims: To determine the safety and efficacy of defibrotide in the treatment of SCD-associated ACS. Design/Methods: Patients with SCD- (Homozygous Hemoglobin S disease, Hemoglobin SC Disease or Hemoglobin Sβ0/+ Thalassemia) associated ACS aged 2 to 40 years of age were enrolled. Defibrotide, generously supplied by Jazz Pharmaceuticals, was administered at 6.25 mg/kg IV Q6H (total daily dose 25 mg/kg/day) within 24 hours of consent and continued for 7 days or until the patient was discharged from hospital, whichever occurred first (IND 127812) (NCT 03805581). All patients were treated with current standard of care, including: antibiotics, analgesics, oxygen, intravenous fluids, and packed red blood cells (PRBC)/exchange transfusion. Complete blood counts and coagulation studies were performed at baseline, day 7 and day 30, while chest radiograph (CXR), CT chest angiogram (CTA), pulmonary function test (PFT), and transthoracic echocardiogram (ECHO) were performed at baseline and 30 days after Defibrotide was first given for disease assessment. Results: We have enrolled 20 patients (median age 9.5 years) with a gender ratio of M/F 8/12. Patients had hemoglobin SS (n=14), hemoglobin Sβ0/+ (n=2), or hemoglobin SC (n=4). The median doses of Defibrotide per patient was 18.5 (range 6-28) and the average hospital admission length was 6.1 days (range 3-13 days). There were no serious adverse events probably or directly related to Defibrotide, as judged by investigators. Two patients had a grade I/II epistaxis that did not disrupt Defibrotide's course. Pulmonary infiltrate on CXR and/or CTA was the most common finding at diagnosis, with 18/20 participants (90%) (Figure 1a). Thirteen patients had fever as a presenting symptom, and the average duration of the fever from diagnosis was 2.8 days (range 1-6 days) (Figure 1b). Nine patients required O2 supplementation, with an average duration of 4.1 days (range 2-7 days). Among patients who underwent Day 30 CXR or CTA, 87.5% and 92%, respectfully, showed improvement or resolution of pulmonary consolidation, only 4 patients had a day 30 ECHO, however, all of them had a resolution of previous findings. Thirteen patients were treated with blood transfusions with a median of 1.9 units (PRBC unit was defined as 15ml/kg) transfused per patient (range, 1-5 units) and 1 patient underwent an exchange transfusion. Conclusion: Our data suggests that Defibrotide is safe and well tolerated in SCD patients with ACS. No serious adverse events were observed. A randomized phase II/III multi-center clinical trial will need to be conducted to further investigate its efficacy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A Two Part Case Series on Acquired Hemophilia A

Abstract Introduction/Objective Acquired Hemophilia A is a rare condition with an incidence of 1 per 1.5 million per year. The average age at presentation is 74 years. It is due to spontaneous production of IgG autoantibodies that target endogenous factor viii. This disease should be considered when a patient presents with bleeding, an abnormal prolongation of activated partial thromboplastin time and /or no prior personal or family history of bleeding. Autoimmune disorders and malignancy are common associations. Pregnancy and surgery are common presenting scenarios. Methods/Case Report Case 1: 71 year old female with a history of deep venous thrombosis, and rheumatoid arthritis. Patient presented to the emergency department with a hemoglobin of 4.7 and coagulation studies showed a prolonged partial thromboplastin time of 119 seconds. Imaging revealed retroperitoneal bleeding. A mixing study showed no correction of partial thromboplastin time. The patient was treated with packed red blood cell transfusions until hemodynamically stable. Further coagulation studies revealed a factor VIII activity of 3L and factor VIII inhibitor level of 103 bethesda units. This confirmed suspicion of an acquired factor VIII inhibitor associated with the patient’s rheumatoid arthritis as the source of abnormal lab values and bleeding. Patient was treated with recombinant factor VIIa, novoseven, along with continuous prednisone and cyclophosphamide. Case 2: 82 year old male with history of IgG Kappa Monoclonal Gammopathy of Undetermined Significance. Patient presented with gastrointestinal bleeding and 4g/Dl hemoglobin. He received 5 units of packed red blood cells. Sigmoidoscopy revealed a rectal ulcer causing lower gastrointestinal bleeding. An advanced coagulation study revealed factor VIII activity of 1%, and inhibitor levels of 17 bethesda units. Patient was started on prednisone initially, followed by cyclophosphamide. However, bleeding continued. He was treated with 6 units of recombinant factor VIIa and packed red blood cell transfusions as required to keep hemoglobin levels at 7g/Dl. He was continued on prednisone at an increased dosage and discharged. Results (if a Case Study enter NA) NA. Conclusion Acquired Hemophilia A is a rare disease. It should be suspected anytime there is unprecedented bleeding and/or unexplained prolongation of partial thromboplastin time. It is diagnosed with factor VIII panel, including inhibitor. Treatment includes immunosuppresants, intravenous immunoglobulins, and recombinant factor VIIa.

STUDY OF THE PROCESSES OF WASTEWATER TREATMENT FOR REUSE IN THE PULP AND PAPER INDUSTRY

Nowadays, more than 80% of cardboard and paper products of Ukrainian mills are made from waste paper – secondary fibers that differ in their chemical and physical properties from primary cellulosic fibers. Characteristic feature of secondary fibers is the presence of a large number of small fibers, which negatively affects the quality of finished products, mass retention on the grid during the formation of paper or cardboard, which leads to pollution of wastewaters. Despite its environmental friendliness and economy, waste paper is also characterized by the presence of various pollutants, the formation of which is associated with the process of paper formation, storage of finished products, and their use. As a result of the preparation of the mass from secondary fibers, there is a transition of pollutants from the waste paper to the wastewater in the form of colloidally dispersed and soluble substances, which lead to the pollution of circulating water. Purification of water and its reuse in technological processes is an important task of paper industry mills. The results show that more than 90% of the secondary fibers have a length that does not exceed 1 mm, while in the primary cellulose fiber from coniferous wood about 53% of the fibers have a length of more than 1 mm. The high content of short fibers in the paper mass affects the processes of paper formation, worsening them, and a decrease in the retention of the fiber on the grid of the paper or cardboard machine is observed, causing the pollution of wastewater. The results of the study of coagulation of industrial wastewater with the content of suspended solids 1520 and 3200 mg/dm3 from the production of cardboard from recycling paper show that the best coagulants are A1(OH)C12 and A12(OH)5C1. The maximum efficiency of water purification of only 92.5% was achieved at the suspended solids content of 1520 mg/dm3, while for wastewater with a suspended solids concentration of 3200 mg/dm3 98.0% was obtained. To develop a scheme for deep purification of wastewaters, it is important to understand which components are removed from water more easily and which are more difficult during coagulation. For this purpose, studies on coagulation of model suspensions of starches, bentonite and kaolin using inorganic coagulants were conducted. It was established that coagulation of native corn starch suspension with inorganic coagulants is effective. However, in the case of using modified starches, the removal of cationic starches is reduced. The efficiency of water purification in the removal of bentonite by sedimentation-filtration with the use of coagulants is quite high. The degree of purification reaches 80.8-98.1%. The filtering stage allows the degree of purification to be further increased. Research on the processes of purification of model kaolin suspensions shows that mechanical and physico-chemical methods are ineffective in removing this mineral filler.

Hemostatic Alginate/Nano-Hydroxyapatite Composite Aerogel Loaded with Tranexamic Acid for the Potential Protection against Alveolar Osteitis.

Wound control in patients on anticoagulants is challenging and often leads to poor hemostasis. They have a higher tendency to develop alveolar osteitis after tooth extraction. The application of a hemostatic dressing that has a high absorbing capacity and is loaded with an antifibrinolytic drug could help in controlling the bleeding. Alginate/nano-hydroxyapatite (SA/Nano-HA) composite aerogels loaded with tranexamic acid (TXA) were prepared. Nano-HA served as a reinforcing material for the alginate matrix and a source of calcium ions that helps in blood clotting. It influenced the porosity and the water uptake capacity. TXA release from SA/Nano-HA aerogels showed a biphasic profile for up to 4 h. Blood coagulation studies were performed on human whole blood. The TXA-loaded aerogel significantly reduced the clotting time by 69% compared to the control (p < 0.0001). Recalcification time was significantly reduced by 80% (p < 0.0001). Scanning electron microscopy analysis revealed the porous nature of the aerogels and the ability of the optimum aerogel to activate and adhere platelets to its porous surface. The cell migration assay showed that there was a delay in wound healing caused by the TXA aerogel compared to the control sample after treating human fibroblasts. Results suggest that the developed aerogel is a promising dressing that will help in hemostasis after tooth extraction.

External validation of the MidiCAT variant of thrombography: Comparison with calibrated automated thrombography and study of the centrifugation scheme

To perform Calibrated Automated Thrombography (CAT), the use of reduced plasma volumes (referred to as "MidiCAT") makes it possible to more efficiently use limited volumes of valuable biobanked plasma samples and decreases expenses for reagents. It is, however, unclear whether the MidiCAT procedure is suitable when thrombin generation (TG) is studied in the presence of added thrombomodulin (TG-TM). Moreover, a simplified centrifugation scheme would facilitate biobanking, if appropriate, for more sensitive coagulation studies. We aimed to compare the results of "MidiCAT" (halved plasma and reagent volumes) with those from regular CAT, in the absence or presence of TM, as well as to study the impact of a single-centrifugation scheme for plasma preparation before freezing. Plasma samples were prepared from the citrated blood from 20 Geneva hospital diverse patients without gross coagulation abnormalities with a single- or double-centrifugation scheme. Samples were kept frozen at -80°C and thawed just before the TG assay in duplicate under two conditions: 1 pM tissue factor (TF) or 5 pM TF + TM. (1) We externally validated "MidiCAT" and also extended the validation to TG-TM. Whatever the method (CAT or MidiCAT), intra-assay (assessed with duplicates) CV was below 6% (1 pM TF) or below 10% (5 pM TF + TM) for ETP. Agreement between the MidiCAT and CAT results was satisfactory; the p coefficients were above 0.95 for ETP and above 0.90 for most other parameters; biases for ETP were +10.0% (1 pM FT) and +13.5% (5 pM + TM). (2) The centrifugation scheme markedly affected the results obtained in the presence of TM, whereas the bias and limit of agreement (difference plots) were low for the no TM condition. The bias in the presence of TM was obvious, more marked with plasma samples sensitive to TM when double centrifuged: the lower the ETP-TM, the greater the relative difference between the ETP-TM of plasma samples prepared with just single centrifugation and the reference plasma samples. Thus, a single-centrifugation procedure, as is often used for plasma biobanking, is suitable for TG study only if it is not performed in the presence of TM.

Estradiol provokes hypercoagulability and affects fibrin biology: A mechanistic exploration of sex dimorphisms in coagulation.

Sex dimorphisms in coagulation are well established, with female-specific hypercoagulability conferring a survival benefit in the setting of trauma-induced coagulopathy (TIC). The mechanism behind these phenomena remains to be elucidated. We hypothesize that estradiol provokes a hypercoagulable profile and alters clot proteomics and fibrin crosslinking. Whole blood was collected from healthy adult volunteers (n = 30). A battery of thrombelastography (TEG) assays (native, kaolin, platelet-mapping, functional fibrinogen), whole blood thrombin generation, proteomics, and clot structure architecture (via analysis of fibrin crosslinks and fluorescent fibrinogen-visualized clots) were performed after pre-treatment of the blood with physiologic concentrations of beta-estradiol. In addition, a prospective study of coagulation through the menstrual cycle was conducted by collecting blood from women on peak and nadir estrogen days in the standard 28-day menstrual cycle. On TEG, in females, estradiol provoked a hypercoagulable phenotype, specifically a shorter time to clot formation and greater thrombin generation, greater rate of clot propagation and functional fibrinogen, higher clot strength, and diminished clot fibrinolysis. In both males and females, estradiol increased platelet hyperactivity. Similar changes were seen in time to clot formation and clot strength in vivo during peak estrus of the menstrual cycle. On proteomic analysis, in both males and females, estradiol was associated with increases in abundance of several procoagulant and antifibrinolytic proteins. Crosslinking mass spectrometry analysis showed addition of estradiol increased the abundance of several FXIII crosslinks within the FIBA alpha chain in both sexes. Fluorescent fibrinogen analysis revealed a trend toward increased fiber resolvability index after addition of estradiol. Estradiol provokes a hypercoagulable phenotype, affecting time to clot formation, clot propagation, clot strength, clot fibrinolysis, and clot structure. In sum, these data highlight the role of estradiol is driving female-specific hypercoagulability and highlights its potential role as a therapeutic adjunct in resuscitation of TIC.