History Of Coagulation Disorder Research Articles

Prevalence of Subarachnoid Hemorrhage in Traumatic Brain Injury Patients: A Cross-Sectional Study

Background: One of the clinical manifestations and complications of traumatic brain injury patients is traumatic intracranial hemorrhages, divided into primary and secondary hemorrhages. Objectives: The present study was conducted to determine the prevalence of subarachnoid hemorrhage (SAH) in traumatic brain injury (TBI) patients. Methods: The present cross-sectional study was conducted on all TBI patients with SAH for one year. Data collection tools include a demographic profile form and a researcher-made checklist. The severity of TBI is divided according to the Glasgow Coma Scale (GCS) score. The patient’s history and clinical examinations were considered when admitting to the hospital. The consciousness level was measured at 6-to-24-hour intervals, a computed tomography (CT) scan was performed, and any abnormal SAH-related clinical findings and symptoms were recorded. If the patient had other hemorrhages besides SAH, the hematoma volume was recorded. The collected data were entered into and analyzed by SPSS version 16 software. Results: A total of 534 patients were investigated, of whom 84 (15.3%) had intracranial hemorrhage. Out of 84 patients with intracranial hemorrhage, 12 (2.2%) had SAH, of whom ten were male and 2 were female. Also, SAH occurred to traffic accidents, falls, and other related reasons in 7 (58.3%), 4 (33.3%), and 1 (8.3%) patients, respectively. It was also shown that 1 (8.3%), 2 (16.6%), and 9 (75%) patients with SAH had mild, moderate, and severe consciousness, respectively. Regarding the frequency of SAH-related diseases, it was shown that 2 (16.6%) and 10 (82.3%) patients were diabetic and non-diabetic, 4 (33.3%) and 8(66.6%) patients were hypertensive and non-hypertensive, and 7 (58.3%) and 5 (41.6%) patients were with and without a history of skull fractures, respectively, 12 (100%) of them had a history of coagulation disorders. Conclusions: The prevalence of intracranial hemorrhage and SAH in TBI patients is significantly high, which should be taken into consideration when performing diagnostic and therapeutic procedures for these patients.

Thromboprophylaxis with unilateral pneumatic device led to less edema and blood loss compared to enoxaparin after knee arthroplasty: randomized trial

BackgroundPharmacological and mechanical thromboprophylaxis are frequently used together after total knee arthroplasty (TKA). Most studies in this context compare anticoagulants versus a combination of these drugs with an intermittent pneumatic compression device (IPCD). However, there is uncertainty about the need for the combination of both and whether a unilateral IPCD would alone affect other important clinical outcomes: edema and blood loss. We compared the effects of enoxaparin versus unilateral portable IPCD after TKA on edema and blood loss. We hypothesised that unilateral IPCD would cause the same level of edema and the same blood loss as enoxaparin.MethodsIn this open, randomized trial (1:1), adults with no history of coagulation disorders, anticoagulant use, venous thromboembolism, liver or malignant diseases underwent TKA. For 10 days, participants received the IPCD, used 24 h/day on the operated leg from the end of surgery, or 40 mg of enoxaparin, starting 12 h after surgery. All underwent the same rehabilitation and were encouraged to walk on the same day of surgery. We measured edema (thigh, leg and ankle circumference) before and on the third postoperative day. Blood loss (volume accumulated in the suction drain and drop of hemoglobin and hematocrit in 48 h) was a secondary outcome.ResultsWe randomized 150 patients and lost 3 to follow-up with enoxaparin and 2 with IPCD. There was no case of symptomatic venous thromboembolism. Four patients needed transfusions (three receiving enoxaparin), one had infection and one hemarthrosis (both in the enoxaparin group). Leg circumference increased by approximately 2 cm for enoxaparin group and 1.5 cm in IPCD (p < 0.001). The increase in ankle circumference was about 1.5 cm in the enoxaparin group (p < 0.001), and almost zero in IPCD (p = 0.447). Enoxaparin group lost 566.1 ml (standard deviation, SD, 174.5) of blood in the first 48 h, versus 420.8 ml (SD 142.5) in the IPCD.ConclusionsExclusively mechanical prophylaxis after TKA with portable IPCD only on the operated leg reduces leg and ankle swelling and post-operative blood loss compared to exclusively pharmacological prophylaxis with enoxaparin. Portable devices that can prevent deep vein thrombosis and pulmonary embolism without increasing blood loss or other risks should be further investigated.Trial registrationREBEC RBR-8k2vpx. Registration date: 06/04/2019.

Percutaneous embolization of renal pseudoaneurysms: A retrospective study.

We evaluated the efficacy of the mixture of autologous blood and a hemostatic agent, oxidized regenerative cellulose (ORC), as an alternative material for ultrasound (US)-guided percutaneous embolization of renal pseudoaneurysm (PA). In this retrospective study, consecutive patients diagnosed with renal PA were included. The exclusion criteria were: PA of the main renal artery, tiny PA not visualized on the colour doppler ultrasonography, PA more than 3 cm in max diameter or extracapsular PA with the possibility of massive bleeding, and patients with a history of coagulation disorders. After localizing the PA, a mixture of autologous blood and ORC was injected under US guidance with a 15G coaxial needle. Patients were followed up for at least 6 months. Twenty-nine patients with PA were included, of which 26 had a history of percutaneous nephrolithotomy, and three patients had a history of renal biopsy (24 men and five women with an average age of 44.3 years). Gross hematuria was the most common mode of presentation. The mean size of the PA was 16.6 mm and the mean duration of follow-up was 9 months. The clinical and the technical success rate was 100%. The PA could be thrombosed in all the patients with a single-session of injection. No acute (hematoma, infection, and bleeding) or chronic (thromboembolic events, renal cortical atrophy, and recurrence) complications were seen. Percutaneous embolization of renal PA under US guidance with a mixture of autologous blood and ORC is an efficient and easily available first-line method to treat this potentially life-threatening condition when endovascular embolization or other expensive thrombotic agents are not available.

Hypofibrinogenemia caused by tigecycline use in a patient with acute cholecystitis: a case report and review of the literature

Tigecycline is the first member of glicylcycline class of antibiotics, which has a broad spectrum of action. In previous reports, coagulopathy and hypofibrinogenemia caused by tigecycline use was described. We aimed to present a case of hypofibrinogenemia in association with tigecycline use. A 79-years-old male was admitted to medical intensive care unit for acute cholecystitis and acute renal failure. He had no history of coagulation disorder. He was receiving meropenem for septic shock on the admission. On the 7th day of meropenem, his infection didn’t improve and fever continued. Because of that tigecycline was added to treatment. Patient’s infection parameters improved, his fever dropped under treatment, but his prothrombin time, international normalized ratio and activated partial thromboplastin time levels increased and fibrinogen level decreased (0.96 g/L). Tigecycline was discontinued that day. On the fifth day after cessasion of tigecycline, his fibrinogen levels and other coagulation parameters returned to normal ranges. The mechanisms of coagulopathy and hypofibrinogenemia should be elucidated in futher studies. We strictly suggest, regular monitoring of coagulation parameters in patients receiving tigecycline treatment.

Immune complement and coagulation dysfunction in adverse outcomes of SARS-CoV-2 infection.

Understanding the pathophysiology of SARS-CoV-2 infection is critical for therapeutic and public health strategies. Viral-host interactions can guide discovery of disease regulators, and protein structure function analysis points to several immune pathways, including complement and coagulation, as targets of coronaviruses. To determine whether conditions associated with dysregulated complement or coagulation systems impact disease, we performed a retrospective observational study and found that history of macular degeneration (a proxy for complement-activation disorders) and history of coagulation disorders (thrombocytopenia, thrombosis and hemorrhage) are risk factors for SARS-CoV-2-associated morbidity and mortality-effects that are independent of age, sex or history of smoking. Transcriptional profiling of nasopharyngeal swabs demonstrated that in addition to type-I interferon and interleukin-6-dependent inflammatory responses, infection results in robust engagement of the complement and coagulation pathways. Finally, in a candidate-driven genetic association study of severe SARS-CoV-2 disease, we identified putative complement and coagulation-associated loci including missense, eQTL and sQTL variants of critical complement and coagulation regulators. In addition to providing evidence that complement function modulates SARS-CoV-2 infection outcome, the data point to putative transcriptional genetic markers of susceptibility. The results highlight the value of using a multimodal analytical approach to reveal determinants and predictors of immunity, susceptibility and clinical outcome associated with infection.

Khorana score as a predictive tool of venous thromboembolism in cancer patients in rural practice.

e24049 Background: The Centers for Disease Control and Prevention (CDC) estimates that 60,000 to 100,000 Americans die from venous thromboembolism (VTE) annually, costing the U.S. healthcare system $7–10 billion each year. VTE is a leading cause of mortality in cancer patients, and risk is particularly elevated in rural areas, where cancer death rates are higher than in metropolitan areas. The Khorana score has been shown to predict VTE incidence before starting treatment and as such identify those patients that would benefit most from VTE prophylaxis. We aimed to replicate the utility of the Khorana score on a rural population of cancer patients to help address VTE in advance. Methods: From our electronic health records system, we extracted data from cancer patients (age ≥ 18 years) who had begun chemotherapy from 2017-January through 2019-August. Patients who were pregnant, had undergone hormonal therapy or major surgeries within three months prior to VTE diagnosis, or had a history of coagulation disorders or VTE prior to starting chemotherapy were excluded. A Khorana score (0—6, interval = 1) was calculated for each prior to their starting chemotherapy and was used for VTE risk stratification, 0 – low; 1,2 – intermediate; ≥3 – high. We hypothesized that VTE occurrence during the first 6 months following the start of treatment would be positively associated with risk category. Results: The 144, mostly female (64%), cancer patients meeting inclusion had a mean age of 75 years (range 48—95) and VTE risk stratification: 10% (15) high, 67% (96) intermediate, and 23% (33) low. In the first 6 months of starting treatment, 6% (9/144) developed VTE, with a prevalence of 20% (3/15) amongst patients stratified as high risk, 5% (5/96) of intermediate, and 3% (1/33) of the low risk group. A linear-by-linear association of the observed Khorana scores with VTE occurrence implies a meaningful positive association between VTE risk stratification by Khorana score and VTE, chi-square (1,144) = 4.018, p = .045. Conclusions: The trend of higher VTE prevalence in intermediate and high risk patients supports the observed positive association between Khorana score VTE risk category and a greater percentage of patients experiencing VTEs with increasing risk. This trend may likely be amplified with application to a larger number of patients. The study limitations include the lack of diversity of organ affection and sample size, specifically upon risk stratification. However, initiating a discussion about the risks and benefits of VTE prophylaxis prior to starting treatment is of outmost importance.

A Rare Case of Pulmonary Embolism: A Case Report

Pulmonary embolism in an old patient with a history of coagulation disorder, any recent major surgeries or in a chronic heart or lung diseases is widely reported. Also, a recent history of travel by air with flight distance of more than 5000km or BMI greater than 35 kg/m2 increase risk. However, we report here, a suggestive case of acute pulmonary embolism in a previously well male of 38 years, with a BMI of 25.71kg/m2 without any history of chronic illness or acute exacerbations.&#x0D; The patient presented in health facility with sudden onset of radiating chest pain and some other nonspecific symptoms. Neither any other significant personal risk factors except smoking, nor any family history of heart/lung diseases were ruled out during initial assessments. On investigations, other routine examinations were normal but T-wave inversion was noticed in lead V1-4 in ECG, Troponin-I was positive and CPK-MB was slightly elevated (27 U/L). Furthermore, no any remarkable changes were noticed in Chest X-ray. Then, the patient was referred to higher center with cardiac facility with provisional diagnosis of Acute Coronary Syndrome for further evaluation and management.&#x0D; Thereupon, Coronary Angiogram (CAG) was done and the report was normal but echocardiography findings were suggestive of pulmonary Embolism. D-dimer was also elevated (8279.05 ng/ml) but venous doppler study of bilateral lower limb was normal. Finally, CT-PA showed partially occluding thrombus in main pulmonary bifurcation extending into left and right pulmonary artery, its bilateral segmental branches and calcified granuloma was seen in right lobe of liver. Patient was under inj. LMWH and other supportive management during hospitalization. After an uneventful hospital stay for 12 days, general condition was improved and eventually, patient was discharged, with oral warfarin.&#x0D; Keywords: chest pain; Nepal; pulmonary embolism; risk factors.

Abstract WP217: Sex Differences in Coagulation After Stroke: Factor XI Levels Drop After Acute Ischemic Stroke

Introduction: Sex differences in coagulation have been well documented, but it is unknown if post-stroke coagulation factor levels differ by sex. High levels of Factor XI (FXI) and Factor XII (FXII) have been associated with increased incidence of acute ischemic stroke (AIS), especially in women. Hypothesis: This study investigates the hypothesis that levels of FXI, FXII and Plasminogen Activating Inhibitor (PAI1) are different after AIS in men and women. Methods: This was a retrospective study using a biomarker database of patients who presented to the emergency department with stroke. Sample collection occurred 24 hours after AIS onset. Plasma levels of FXI, FXII and PAI1 were assessed with ELISA in a population of 73 patients with no prior history of coagulation disorders, including 29 controls and 44 AIS patients confirmed by MRI, mean age = 68.7+/- 15.1, and 47% female. Log transformation was done before fitting the model. ANOVA was used to investigate the relationship between factor levels in sex and stroke. Tukey-Kramer multiple comparison tests were used for paired group comparisons. Results: FXI levels were significantly higher in control subjects compared to AIS (p-value=0.007). FXI levels were also higher in females than in males, nearing statistical significance (p-value=0.053). PAI1 and FXII levels were not statistically different in men vs. women, or in control vs. AIS patients. Female controls had higher FXI levels than male AIS patients (0.487, 95% CI 0.085-0.889). Conclusion: Stroke patients were found to have significantly lower levels of FXI compared to controls. This demonstrates that the pathological process of AIS may result in depletion of circulating plasma FXI at 24 hours after stroke onset. Overall, in stroke and control patients, there was a trend for females to have higher levels of FXI than men. No significant sex or stroke differences were found in FXII or PAI1 levels, likely due to sample size. Additional samples are being evaluated to determine if this stroke-induced decrease in FXI levels is associated with functional outcomes.

Economic impact of bleeding complications after mastectomy

BackgroundWe sought to determine the incidence of postmastectomy bleeding, identify bleeding predictors, and evaluate the economic impact. MethodsUsing the 2011 Healthcare Cost and Utilization Project-Nationwide Inpatient Sample, hospital discharges for a primary diagnosis of breast cancer were extracted using International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes 85.34–85.48 for mastectomy and diagnosis codes 174.0–174.9 for breast cancer. Discharges with postoperative bleeding were identified using International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes 998.11 and 998.12. Discharges with male gender or a history of coagulation disorders were excluded. Bleeding complication rates and reoperation rates were assessed. Predictors and the impact of bleeding on length of stay and hospital costs were determined using regression analysis and projected to the national level. ResultsA total of 7907 discharges met inclusion criteria; 201 had bleeding complications (2.54%), with 42 cases requiring reoperation. On univariate analysis, the presence of congestive heart failure (CHF), obesity, diabetes, chronic pulmonary disease, and the absence of concomitant reconstruction were associated with increased bleeding events. On multivariate analysis, only the presence of CHF remained as a significant predictor of bleeding complications (odds ratio [95% confidence interval], 2.45, [1.25–4.92], P = 0.009). On average, bleeding complications extended the length of stay by 1.3 d (P < 0.0001) while increasing hospital costs by $5495 per admission (P < 0.0001). Projected to a national level, bleeding complications accounted for an additional 1254 d of hospital care at a cost exceeding $5.3 million. ConclusionsPostmastectomy bleeding complications had an incidence of 2.54%, with CHF the only independent predictor identified. Such bleeding events, although infrequent, are associated with substantial economic costs.

Chorionic bump on first-trimester sonography: not necessarily a poor prognostic indicator for pregnancy.

The purpose of this study was to determine the live birth rate of pregnancies with a diagnosis of a chorionic bump, a convex bulge from the choriodecidual surface into the first-trimester gestational sac. Pregnant patients at least 18 years old with the finding of a chorionic bump on first-trimester sonography were included in this prospective observational study. The independent variables were chorionic bump size and number and presence or absence of a history of infertility or coagulation disorder. The primary end point was pregnancy outcome. During the 4-year study period, 52 pregnancies had a diagnosis of a chorionic bump. Overall, 34 resulted in live births, corresponding to an absolute live birth rate of 65%, and 18 were nonviable. Forty-one chorionic bump pregnancies were otherwise normal (ie, pregnancies in which a gestational sac, yolk sac, and embryo with heartbeat were seen at some point), and in this subset, the live birth rate was 83% (34 of 41). All pregnancies with more than 1 chorionic bump (4) ended in demise (100%). The average maximum dimension of the chorionic bump was 1.3 cm (range, 0.5-3.8 cm); however there was not a statistically significant correlation between chorionic bump size and pregnancy outcome (P = .5866; odds ratio, 0.54; 95% confidence interval, 0.06-5.01). Nine patients (17%) had a history of infertility treatment, and 4 (8%) had a history of coagulation disorder. Only 1 chorionic bump pregnancy was associated with a birth defect. The live birth rate in our chorionic bump cohort was 65% overall and even higher (83%) if the pregnancy was otherwise normal. The clinical implication is that a chorionic bump on first-trimester sonography is not necessarily associated with a guarded prognosis.

Final Diagnosis of Pediatric Patients with Prolonged in Activated Partial Thromboplastin Time Preoperative Study

Introduction: Activated partial thromboplastin time (aPTT) is one of the most used coagulation tests in preoperative evaluation. Incidental detection of a prolonged aPTT is a problem in primary care, in which the general pediatrician should be able to attend its initial management. Objective: To describe final diagnosis of patients with prolonged aPTT in preoperative study. Materials and Methods: This is a descriptive study of patients referred from otorhinolaryngology. Results: Totally, 508 adenoidectomies and/or tonsillectomies were performed in our center, 38 of which referred patients (7.5%) with prolonged aPTT, and 30 of which met inclusion criteria. The median age was 4 years. 56.6% of patients were males. 76.6% of patients normalized aPTT at the second follow-up. Among these, 73.9% showed a normal study, 4.3% ha2d lupus anticoagulant and in 21.7% Von Willebrand disease was detected. Among patients that persisted with prolonged aPTT, 42.8% had coagulant factors deficiency, 28.5% had lupus anticoagulant and in 28.5% of patients a diagnosis could not be achieved with the tests used in the present study. Multivariate analysis did not show correlation between final diagnosis and the variables measured. Conclusion: The presence of a prolonged aPTT in children under preoperative study is due to a pre-analytic factor in the majority of cases or to the presence of lupus anticoagulant, normalizing values on follow-up. We suggest that a new aPTT be performed on these patients, and only those that persist altered or present a symptoms and family history of coagulation disorders be referred to hematology.

Normal range of bleeding time in urban and rural areas of Borujerd, west of Iran.

Bleeding time (BT) is the oldest and simplest test for assessing the platelets (Plts) function. BT can affect by several factors such as race and diet, which has a wide reference range. The aim of this project is to determine the normal range of BT in Borujerd, Iran. Determining the normal range of BT can help us to modify the definition of bleeding disorder and aspirin resistance. This was cross-sectional study carried out in 2011-2012. Subjects with a history of coagulation disorders or a positive family history of coagulation disorders, consumption of anti-Plts, anti-histamines, and phenothiazine in the previous month and subject with Plt less than 150,000 were excluded. The samples were 505 volunteers who were referred from 16 urban and 9 rural clusters to research center. BT of the samples was determined according to Ivy simplate method considering national standard protocol in the selected persons. Normal range was calculated as mean ± 2 standard deviation. Of 505 volunteers, 50.4% were female. The range of BT was 2.8-2.95 min with mean of 2.79 ± 0.78 min. Range and mean of BT in women was 2.83-3.06 min and 2.88 ± 0.87 min, and range and mean of BT in men was 2.7-2.9 min and 2.69 ± 0.67 min; this difference was significant (P = 0.012). BT in urban and rural participants was 2.78 ± 0.79 and 2.77 ± 0.73 min. There was no significant difference between BT in urban and rural participants. The normal range of BT in Boroujerd was in the lower limit of the normal universal range. In this study, BT was significantly different in both genders, but its correlation with age, blood group, and place of residency was not significant.

Preoperative Assessment for Children Requiring Dental Treatment Under General Anesthesia

This study aimed to describe children <6 years requiring general anesthesia for dental treatment and factors associated with a change in medical management prior to surgery. This case series reviewed the past medical history and preoperative assessment of patients referred for dental preoperative evaluations at a single institution (2005-2008). A "deflection" was defined as a recommendation to change preoperative or operative care based on the preoperative assessment. The sample was analyzed using descriptive, bivariate, and multivariate analyses. Of 648 subjects (aged 9 months to 6 years, mean 3.9 years), 63% had a past medical history abnormality and 38% had previous surgery. In total, 14% were deflected, most commonly because of the addition of infective endocarditis prophylaxis (29%). A history of coagulation disorder had the strongest association with deflection (P < .0001, odds ratio = 10.0, 95% confidence interval = 4.6-22.1), followed by cardiac anomalies. Preoperative assessments for pediatric dental treatment frequently identify medical problems resulting in treatment plan alterations.

Two Independant Assays Demonstrate High Phospholipid Procoagulant Activity In Poor Platelet Plasma of Sickle Cell Disease Children.

AbstractAbstract 1630Sickle cell disease (SCD) is considered as a hypercoagulable state through still a mechanism poorly understood. Our hypothesis is that poor platelet plasma (PPP) from SCD children may contain a high phospholipids procoagulant activity.This study aimed 1° at using and comparing two different assays to detect the procoagulant activity of endogenous phospholipids (ePL) in the PPP of SCD children in steady state compared to normal controls, 2° at assessing the influence of the clinical state and treatment on this procoagulant activity. Patients:A group of 30 SCD children aged between 2 – 20 years (median=9, 16 males, 14 females) were studied: 12/30 didn't receive any specific treatment, 6/30 were chronically transfused (TRX) and 12/30 were treated by hydroxyurea (HU). 11/30 were previously admitted because of a vaso-occlusive crisis (VOC). 24 SCD patients were HbSS, 4 HbSC, and 2 HbSβ. Controls:18 remaining samples from children aged between 3 – 20 years (median=9, 11 males, 7 females) undergoing minor elective surgery, with no history of coagulation disorder, normal routine coagulation tests, normal CRP, liver and kidney functions tests. The controls were not matched for the age neither sex.Venous blood was collected into 0,109M citrated tubes using a 23G butterfly needle. PPP was obtained after 2 steps of centrifugation (3200g for 15 min and 16000g for 2 min) within 2 hours following venipuncture, and stored at -80°C. Procoagulant activity of ePL was assessed using two independent assays: a commercial fully automated factor Xa-based clotting time assay (XACT: sec) as described by Exner et al (ProcoagPPL® Stago, Asnières sur Seine, France), and a thrombin generation assay (TGA) using calibrated automated thrombinography (CAT) as described by Hemker et al (Thrombinoscope®, Maastricht, The Netherland). TGA was triggered with 10pM tissue factor (TF) alone and with a combination of 10pM TF and 4μM synthetic PL (positive control). Four TGA parameters were analysed: lag time (LT), Peak, Velocity Index (VI) and Endogenous Thrombin Potential (ETP). For each parameter, the result was also expressed as a % of the positive control, to minimize the influence of age. Correlations were assessed between XACT and TGA parameters using the Spearman's coefficient. Group comparison was assessed using non parametric tests.Significant correlations were found between XACT and Peak (r= -0,76, p<0,0001), VI (r= -0,73, p<0,0001), ETP (r= -0,47, p<0,0001) measured without addition of PL, and also between XACT and % Peak (r= -0,73, p<0,0001), %VI (r= -0,63, p<0,0001) and % ETP (r= -0,60, p<0,0001). No correlation was found between XACT and LT (r= 0,20, p = 0,096).The table shows median and range values obtained from SCD patients in steady state as compared to those of normal controls, using both methods. The TGA values are those obtained with 10pM alone, and are also expressed as a percentage of positive control.Concerning the clinical state and treatment, XACT and all CAT parameters failed to show significant differences between subgroups of SCD (steady vs. CVO, n=11), and their treatment (TRX vs. HU vs. No specific treatment). For the patients undergoing chronic exchange transfusion, no significant difference was observed between the samples collected before and few hours after transfusion exchange.In SCD children in steady state, XACT is significantly shortened compared to normal controls. Velocity index and Peak thrombin are significantly increased when using a high TF concentration alone as trigger. Each test showed similar performance to detect a higher procoagulant activity of ePL in SCD patients, which could contribute to the hypercoagulable state observed in those patients. In our study, ePL procoagulant activity was not influenced by the clinical state, neither the type of treatment, but this could be due to the relatively small number of patients included till now. We are currently studying more patients to confirm our results in a larger group and in particular to analyze the effects of treatment. Disclosures:Noubouossie:Belgian Kid's Fund: Grant's recipient of the Belgian Kid's Funds.

Tetranor PGDM, an Abundant Urinary Metabolite Reflects Biosynthesis of Prostaglandin D2 in Mice and Humans

Prostaglandin D(2) (PGD(2)) is a cyclooxygenase (COX) product of arachidonic acid that activates D prostanoid receptors to modulate vascular, platelet, and leukocyte function in vitro. However, little is known about its enzymatic origin or its formation in vivo in cardiovascular or inflammatory disease. 11,15-dioxo-9alpha-hydroxy-2,3,4,5-tetranorprostan-1,20-dioic acid (tetranor PGDM) was identified by mass spectrometry as a metabolite of infused PGD(2) that is detectable in mouse and human urine. Using liquid chromatography-tandem mass spectrometry, tetranor PGDM was much more abundant than the PGD(2) metabolites, 11beta-PGF(2alpha) and 2,3-dinor-11beta-PGF(2alpha), in human urine and was the only endogenous metabolite detectable in mouse urine. Infusion of PGD(2) dose dependently increased urinary tetranor PGDM > 2,3-dinor-11beta-PGF(2alpha) > 11beta-PGF(2alpha) in mice. Deletion of either lipocalin-type or hemopoietic PGD synthase enzymes decreased urinary tetranor PGDM. Deletion or knockdown of COX-1, but not deletion of COX-2, decreased urinary tetranor PGDM in mice. Correspondingly, both PGDM and 2,3-dinor-11beta-PGF(2alpha) were suppressed by inhibition of COX-1 and COX-2, but not by selective inhibition of COX-2 in humans. PGD(2) has been implicated in both the development and resolution of inflammation. Administration of bacterial lipopolysaccharide coordinately elevated tetranor PGDM and 2,3-dinor-11beta-PGF(2alpha) in volunteers, coincident with a pyrexial and systemic inflammatory response, but both metabolites fell during the resolution phase. Niacin increased tetranor PGDM and 2,3-dinor-11beta-PGF(2alpha) in humans coincident with facial flushing. Tetranor PGDM is an abundant metabolite in urine that reflects modulated biosynthesis of PGD(2) in humans and mice.

Angiomatous Rash in a Pregnant Woman

The patient was a 27-year-old woman of 5 months gestation who was seen for a rash on the trunk that had developed towards the end of the first trimester of pregnancy. The relevant findings in her past medical history were that she was a hepatitis C virus carrier and had had an uncomplicated previous pregnancy and a voluntary abortion. She had not received any treatment in the previous months except for vitamin supplements and did not report easy bleeding or a personal or family history of coagulation disorders.

Influence of antidepressants on hemostasis

Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), are widely used for the treatment of depression and anxious disorders. The observation that depression is an independent risk factor for cardiovascular mortality and morbidity in patients with ischemic heart disease, the assessment of the central role of serotonin in pathophysiological mechanisms of depression, and reports of cases of abnormal bleeding associated with antidepressant therapy have led to investigations of the influence of antidepressants on hemostasis markers. In this review, we summarize data regarding modifications of these markers, drawn from clinical studies and case reports. We observed an association between the type of antidepressant drug and the number of abnormal bleeding case reports, with or without modifications of hemostasis markers. Drugs with the highest degree of serotonin reuptake inhibition--fluoxetine, paroxetine, and sertraline--are more frequently associated with abnormal bleeding and modifications of hemostasis markers. The most frequent hemostatic abnormalities are decreased platelet aggregability and activity, and prolongation of bleeding time. Patients with a history of coagulation disorders, especially suspected or documented thrombocytopenia or platelet disorder, should be monitored in case of prescription of any serotonin reuptake inhibitor (SRI). Platelet dysfunction, coagulation disorder, and von Willebrand disease should be sought in any case of abnormal bleeding occurring during treatment with an SRI. Also, a non-SSRI antidepressant should be favored over an SSRI or an SRI in such a context. Considering the difficulty in performing platelet aggregation tests, which are the most sensitive in SRI-associated bleeding, and the low sensitivity of hemostasis tests when performed in case of uncomplicated bleeding in the general population, establishing guidelines for the assessment of SRI-associated bleeding complications remains a challenge.

Effect of Propofol Anesthesia on Blood Coagulation and Fibrinolysis: An Assessment Using Thromboelastograph at Clipping of Cerebral Aneurysms

Background: Propofol may cause perioperative bleeding because it has an inhibitory effect on platelet aggregation and an accelerative effect on blood fibrinolysis in vitro. The aim of this study was to evaluate the perioperative effect of propofol anesthesia on blood coagulation and fibrinolysis with a thromboelastograph in patients undergoing clipping of cerebral aneurysms. Methods: Fifteen patients who had cerebral aneurysms and no history of coagulation disorders were studied. Anesthesia was induced with a target controlled infusion of propofol to reach a calculated target blood concentration of /ml, and in addition, fentanyl /kg, lidocaine 1 mg/kg, esmolol 0.3 mg/kg and vecuronium 0.1 mg/kg were given intravenously. Anesthesia was maintained by propofol at target concentrations of 3-/ml with nitrous oxide (67%) and oxygen (33%). The hemoglobin concentration, platelet count and a thromboelastogram were measured at before, during and after anesthesia. Results: There was no significant difference in the perioperative hemoglobin concentration and platelet count. In terms of the thromboelastogram, r time (reaction time for clot formation) and k time (clot formation time) during and after anesthesia were shorter than hose before anesthesia (P

Perioperative Changes of Blood Coagulation by a Thromboelastograph in Patients Undergoing Clipping of Cerebral Aneurysms

Background: Patients undergoing brain surgery have a high risk of developing a number of perioperative coagulation disorders. Anesthesia and surgical stress may affect blood coagulation and fibrinolysis. The aim of this study was to evaluate perioperative changes in hemostatic parameters of patients undergoing clipping of cerebral aneurysms with a thromboelastograph (TEG) in combination with simple laboratory tests. Methods: Twenty adult patients who had cerebral aneurysms and no history of coagulation disorders were studied. Isoflurane and N2O were used for all anesthetic proceedings. Preanesthetic, intraoperative (after skin incision and after clipping of cerebral aneurysms) and postanesthetic measurements included a TEG and simple laboratory tests. The TEG variables included r time (reaction time for clot formation), k time (clot formation time), α angle (rate of clot growth), MA (maximal amplitude of clot strength) and LY30 (fibrinolytic index). Results: In simple laboratory tests, prothrombin time (PT) and partial thromboplastin time (PTT) at intraoperation and postanesthesia were longer than those at preanesthesia (p < 0.05). In the TEG, r and k time at intraoperation and postanesthesia were shorter than those at preanesthesia (p < 0.05). however the α angle at intraoperation and postanesthesia was longer than that at preanesthesia (p < 0.05). There was no significant difference in MA and LY30 except an increase in MA after the skin incision (p < 0.05) compared to the MA at preanesthesia. Conclusions: These results indicate a general hypercoagulability during and after a cerebral aneurysms operation in terms of TEG, although, the level of the PT and PTT can be at the upper limits within normal. Therefore perioperative use of coagulants in cerebral aneurysms may increase the risk of a thromboembolism because of accelerating blood coagulability. By early intraoperative and postoperative

重篤な出血傾向を呈した抗第ＶＩＩＩ因子抗体症候群の１例

An 81-year-old woman with no history of coagulation disorder was admitted due to swelling and pain in the right thigh. Computed tomography (CT) and magnetic resonance imaging (MRI) showed hemorrhaging in the muscles of the right thigh. Abdominal CT during hospitalization retroperitoneal bleeding. Laboratory examination revealed rapidly progressive anemia, prolonged activated partial thromboplastin time (aPTT), markedly decreased factor VIII activity, and positive factor VIII inhibitor titer. She was diagnosed with coagulopathy due to spontaneously acquired factor VIII inhibitor. Her bleeding did not respond to the infusion of factor VIII concentrate, but was successfully treated by activated prothrombin complex concentrate (aPCC) and PCC. To reduce the production of factor VIII inhibitor, an immunosuppressive regimen, including prednisone and cyclophosphamide, was started. Inhibitor titer gradually decreased and no further bleeding occurred, but the patient died of sepsis caused by a nosocomial airway and urinary tract infection. This suggests that the dose of immunosuppressive drugs should be lower than in the ordinary regimen in such elderly patients.