Evaluation Of Hemostasis Research Articles

Neonatal Platelet Transfusions and Future Areas of Research.

Thrombocytopenia affects approximately one fourth of neonates admitted to neonatal intensive care units, and prophylactic platelet transfusions are commonly administered to reduce bleeding risk. However, there are few evidence-based guidelines to inform clinicians' decision-making process. Developmental differences in hemostasis and differences in underlying disease processes make it difficult to apply platelet transfusion practices from other patient populations to neonates. Thrombocytopenia is a risk factor for common preterm complications such as intraventricular hemorrhage; however, a causal link has not been established, and platelet transfusions have not been shown to reduce risk of developing intraventricular hemorrhage. Platelet count frequently drives the decision of whether to transfuse platelets, although there is little evidence to demonstrate what a safe platelet nadir is in preterm neonates. Current clinical assays of platelet function often require large sample volumes and are not valid in the setting of thrombocytopenia; however, evaluation of platelet function and/or global hemostasis may aid in the identification of neonates who are at the highest risk of bleeding. Although platelets' primary role is in establishing hemostasis, platelets also carry pro- and antiangiogenic factors in their granules. Aberrant angiogenesis underpins common complications of prematurity including intraventricular hemorrhage and retinopathy of prematurity. In addition, platelets play an important role in host immune defenses. Infectious and inflammatory conditions such as sepsis and necrotizing enterocolitis are commonly associated with late-onset thrombocytopenia in neonates. Severity of thrombocytopenia is correlated with mortality risk. The nature of this association is unclear, but preclinical data suggest that thrombocytopenia contributes to mortality rather than simply being a proxy for disease severity. Neonates are a distinct patient population in whom thrombocytopenia is common. Their unique physiology and associated complications make the risks and benefits of platelet transfusions difficult to understand. The goal of this review was to highlight research areas that need to be addressed to better understand the risks and benefits of platelet transfusions in neonates. Specifically, it will be important to identify neonates at risk of bleeding who would benefit from a platelet transfusion and to determine whether platelet transfusions either abrogate or exacerbate common neonatal complications such as sepsis, chronic lung disease, necrotizing enterocolitis, and retinopathy of prematurity.

Thromboelastometric evaluation of hemostasis in dogs infected with Leishmania infantum.

Evaluation of hemostasis using thromboelastometry in dogs with leishmaniasis before and after treatment. Longitudinal observational study. University veterinary teaching hospital. Eighty-four adult, client-owned dogs. Whole blood samples for the coagulation profile were collected from symptomatic dogs with leishmaniasis (group S), asymptomatic dogs with leishmaniasis after treatment (group T), and a control group of healthy dogs (group H). Hemostasis was evaluated by means of standard coagulation profile (prothrombin time, activated partial thromboplastin time, and fibrinogen) and by thromboelastometry (ROTEM). Prothrombin time and activated partial thromboplastin time were within the upper reference range in all 3 groups. Comparison of the ROTEM variables between the 3 groups showed statistically significant differences between group S versus groups T and H, but remaining within the reference ranges. Statistically significant differences in hematocrit and fibrinogen concentrations were noted between groups (group S vs. H: hematocrit P = 0.001, fibrinogen P = 0.002; Group S vs. T: hematocrit P = 0.001, fibrinogen P = 0.001). These variations have interfered with some parameters of the ROTEM profile. This study showed normal standard coagulation profiles in all 3 groups evaluated. The ROTEM results did not fall outside of the maximum values of the reference ranges.

Highlights from the latest articles in nano-oncology.

Highlights from the latest articles in nano-oncology.

New capabilities of laboratory diagnosis of thromboses

The growing number of thromboses has been observed in various fields of medicine, which makes the issues of early diagnosis and investigation of thrombotic condition predictors more topical. Evaluation of hemostasis and investigation of risk factors of both thrombotic and hemorrhagic states is one of the most complex diagnostic problems. The objectives of laboratory diagnosis include not only studying of already known indicators of thrombovascular hemostasis and standard coagulation tests but also developing, automating, and improving of new methods for detection of biomarkers of hemostasis disturbances. According to the results of modern research, a high level of the subpopulation of procoagulant or coated platelets, known as COAT-platelets, in patient blood can be considered as this new marker for predicting thrombosis. COAT-platelets are a subpopulation of collagen and thrombin-activated platelets maintaining a high procoagulant activity of blood.

Analysis of Bleeding Phenotype of Severe Hemophilia a Carriers and Comparation with a Working Population Group. Impact on Quality of Life

INTRODUCTIONWe have little information about if there is a particular bleeding phenotype of severe haemophilia A female carriers. In the literature, an increased bleeding tendency is described in this group, justified even by levels of factor VIII (FVIII) very close to normal values, in absens of primary hemostasis evaluation in many cases. There is no published evidence about quality of life (QoL) of these women and the relationship between QoL and this bleeding tendency. OBJECTIVES• To evalute the hemorrhagic phenotype of severe haemophilia A carrier and to compare them with the general population.• To identify symptomatic carriers and to study from laboratory point of view the reasons for that bleeding tendency.• To define the bleeding profile of symptomatic carriers.• To analyze the quality of life and state of anxiety/depression in carriers and to compare them with the general population. PATIENTS AND METHODSThis is a descriptive cross-sectional, non-interventional, single center study. Ethics Committee evaluation and written informed consent are requested to be included for carriers and controls. The target population are severe Haemophilia A carriers from our area aged between 18 and 70 years old. The control group are women from regular health laboral checkings. We will evaluate family bleeding, ischemic and thrombotic personal and familiar antecedents, bleeding profile (ISTH/SSC bleeding assessment tool, ISTH BAT, and pictorial blood assessment chart, PBAC), carrier genetic study, complete blood count, basic biochemistry, haemostasis (aPTT, PT, fibrinogen, platelet function tests, FVIIIc, FvWAg and FvWRCo, FXIII). QoL has been studied trough SF-36 (Spanish version 1,4 1999) and anxiety and depression states using Goldberg questionary (1998, Spanish version Gzempp, 1993).The controls have been studied in the same way except for laboratory studies of hemostasis. Only in controls with pathological ISTH BAT (greater than 3) basic and primary hemostasis have been studied. RESULTSOut of a total of 81 carriers identified between August 2012 to December 2013. We have evaluated 69 carriers. To achieve a confidence level of 95% with 50% heterogeneity we have recruited 138 controls. The mean and standard deviation (SD) age of the carrier and controls was 43.7+/-15 and 41.5+/-11.7 years old (p 0.308). In the population of carriers, the mean and SD of FVIII levels are 87.2+/-35.7%. We found no relationship between levels of FVIII:c and haemophilia genetic defect (34.8% substitutions, 34.8% intron 22, 27.5% mutations). 20.3% of carriers and 2.2% of controls present a pathologic ISTH BAT score (p 0.001). There are 14 carriers with a pathologic ISTH BAT score (median 5.5, range 4-11). In this group we found FVIII levels less than 40% in 4 carriers, 1 thrombopathy and levels of VWF:RCo and VWF:Ag compatible with von Willebrand disease in other 4 carriers. The remaining 5 present ISTH BAT score between 4 and 6 (low), FVIII levels above 60% and no other laboratory abnormal results to justify bleeding tendency. In the 3 controls with pathologic ISTH BAT score (4-5), we have not found any hemostatic disorder from laboratory point of view. The carrier group has a higher incidence of abnormal bleeding at wounds (1.5% vs. 14.5% p 0.000), tooth extraction (3.6% vs. 11.6%, p 0.028), surgery (0% vs. 11.6 %, p 0.028) and methrorragia (13.8% vs 43.5%, p 0.000). However when methrorrragia is analysed with an objective scale of menstrual bleeding as PBAC, methrorragia incidence in carriers is similar to controls (23.2% carriers vs 31.5% controls, p 0.071). Regarding quality of life, the population of carriers presented worse scores in the domains of social activity (p 0.01) and mental health (p 0.014). In the group of symptomatic carriers there are no differences in quality of life with the control group. The control population has a higher incidence of anxiety (42.3% vs 21.7%, p 0.002), with no differences in the presence of depression. CONCLUSIONSIn our series, women with symptomatic severe hemophilia A are those with FVIII lower than 40% or another disorder of hemostasis associated to carrier condition. The hemorrhagic symtoms able to define a severe haemophilia A carrier could be abnormal bleedings from wounds (surgical or traumatic) and in dental extractions. Quality of life in women with hemophilia is worse in the mental health and social activity fields, but for reasons other than their own bleeding phenotype. DisclosuresNo relevant conflicts of interest to declare.

Comprehensive Evaluation of Hemostasis in Normal Women

Women with mild bleeding disorders (MBDs) pose a diagnostic challenge and menorrhagia, the most common presenting symptom that remains underreported. We tested the hypothesis that screening apparently normal females using general and gynecological bleeding assessment tools and a global hemostatic assay together with platelet aggregation can help predict MBDs. We assessed 47 women using electronic bleeding assessment tools; e-bleeding questionnaire; and e-Pictorial Bleeding Assessment Chart (e-PBAC) based on previously validated methods, thrombelastography (TEG), and platelet aggregation together with basic coagulation testing. Three women had elevated bleeding score with von Willebrand disease diagnosis confirmed in one case and eleven cases had elevated e-PBAC. We report normal ranges for TEG and platelet aggregation in women during the first half of the menstrual cycle and show 23.4% of apparently normal women may have general or heavy menstrual bleeding. This is a prelude to a larger study to determine the validity of bleeding assessment tools in screening for MBDs in women.

Thromboelastometry as a supplementary tool for evaluation of hemostasis in severe sepsis and septic shock

Sepsis leads to disruption of hemostasis, making early evaluation of coagulation essential. The aim of this study was to provide a detailed investigation of coagulation and the use of blood products in patients with severe sepsis or septic shock, admitted to a multidisciplinary intensive care unit. Thirty-six patients with severe sepsis or septic shock were included in this prospective observational study. Blood samples and information on transfusion of blood products were obtained for up to 3 consecutive days, and day 7 if the patient was still in the intensive care unit. Thromboelastometry (ROTEM(®)), analyses of thrombin generation, and conventional coagulation tests were performed. ROTEM(®) revealed an overall normo-coagulable state among patients with severe sepsis or septic shock. Conventional coagulation analyses showed divergent results with hypercoagulable trends in terms of reduced antithrombin and acute phase response with increased fibrinogen and fibrin d-dimer, and on the other hand, coagulation disturbances with a decreased prothrombin time and prolonged activated partial thromboplastin time. This hypocoagulabe state was supported by a delayed and reduced thrombin generation. Twelve patients experienced 21 independent transfusion episodes with fresh frozen plasma. Of these, only five (22%) transfusions were performed because of active bleeding. ROTEM(®) demonstrated an overall normo-coagulation, whereas the conventional coagulation tests and thrombin generation analyses mainly reflected hypocoagulation. Given the dynamic and global features of ROTEM(®), this analysis may be a relevant supplementary tool for the assessment of hemostasis in patients with severe sepsis or septic shock.

External Quality Assessment/Proficiency Testing and Internal Quality Control for the PFA-100 and PFA-200: An Update

Platelet function testing is an essential component of comprehensive hemostasis evaluation within the framework of bleeding and/or bruising investigations, and it may also be performed to evaluate antiplatelet medication effects. Globally, the platelet function analyzer (PFA)-100 (Siemens Healthcare, Marburg, Germany) is the most used primary hemostasis-screening instrument and has also been recently remodeled/upgraded to the PFA-200. The PFA-100 is sensitive to a wide range of associated disorders, including platelet function defects and von Willebrand disease (VWD), as well as to various antiplatelet medications. The PFA-100 is also useful in therapy monitoring, especially in VWD. External quality assessment (EQA) (or proficiency testing) and internal quality control (IQC) are critical to ensuring quality of test practice, inclusive of all hemostasis tests. However, both EQA and IQC for platelet function testing, including the PFA-100, is logistically challenging, given theoretical requirements for production, storage, and shipment of large volumes of "stabilized" normal and pathological blood/platelets covering both normal function plus a wide variety of potential defects. We accordingly describe the development and testing of novel feasible approaches to both EQA and IQC of PFA-100/PFA-200 instruments, whereby a range of formulated "platelet function antagonist" materials are utilized. For EQA purposes, these are distributed to participants, and citrated normal whole blood collected on site is then added locally, thereby creating test material that can be locally evaluated. Several exercises have been conducted by the Royal College of Pathologists of Australasia Quality Assurance Program (RCPAQAP) over the past 6 years. A total of 26 challenges, with most designed to mimic moderate to severe primary hemostasis defects, have been tested in 26 to 50 laboratories depending on the year of dispatch. Numerical results for PFA-100/PFA-200 closure times (CTs) and interpretive comments supplied by participants are analyzed by the RCPAQAP. During this period, reported CTs for each challenge were within limits of expectation and good reproducibility was evidenced by repeated challenges. Coefficients of variation (CVs) generated for challenges using the two major PFA-100/PFA-200 cartridge types (collagen/adenosine diphosphate and collagen/epinephrine) are always similar to those obtained using native whole blood, and in general range from 15 to 25%. Interpretations are also in general consistent with expectations and test data provided by laboratories. The EQA created material has also been assessed within the context of possible IQC material. In conclusion, EQA and IQC processes for the PFA-100/PFA-200 have been developed that include highly reproducible test challenge processes, not only supporting the concept that EQA/IQC is possible for platelet function testing but also providing a valuable mechanism for monitoring and improving laboratory performance in this area.

Consistency of thromboelastometry analysis under scrutiny: Results of a systematic evaluation within and between analysers

While the use of thromboelastometry analysis (ROTEM®) in evaluation of haemostasis is rapidly increasing, important validity parameters of testing remain inadequately examined. We aimed to study systematically the consistency of thromboelastometry parameters within individual tests regarding measurements between different analysers, between different channels of the same analyser, between morning and afternoon measurements (circadian variation), and if measured four weeks apart. Citrated whole blood samples from 40 healthy volunteers were analysed with two analysers in parallel. EXTEM, INTEM, FIBTEM, HEPTEM and APTEM tests were conducted. A Bland-Altman comparison was performed and homogeneity of variances was tested using the pitman test. P-value ranges were used to classify the level of homogeneity (p<0.15 - low homogeneity, p = 0.15 to 0.5 - intermediate homogeneity, p>0.5 high homogeneity). Less than half of all comparisons made showed high homogeneity of variances (p>0.5) and in about a fifth of comparisons data distributions were heterogeneous (p<0.15). There was no clear pattern for homogeneity. On average, comparisons of MCF, ML and LI30 measurements tended to be better, but none of the tests assessed outperformed another. In conclusion, systematic investigation reveals large differences in the results of some thromboelastometry parameters and lack of consistency. Clinicians and scientists should take these inconsistencies into account and focus on parameters with a higher homogeneity such as MCF.

Monitoring strategies for patients treated with the new oral anticoagulants and the need for laboratory evaluation of hemostasis

New oral anticoagulants that directly inhibit Factor IIa (dabigatran) or Factor Xa (rivaroxaban, apixaban) are currently available for prevention of venous thromboembolism (VTE) after orthopedic surgery, treatment of acute VTE, and prevention of arterial thromboembolism in non-valvular atrial fibrillation. These agents offer advantages over vitamin K antagonists including rapid onset, shorter half-lives, fewer drug interactions, and the lack of a need for routine monitoring. The fact that monitoring is not required should not, however, lead to lack of surveillance or a fire and forget medicine approach because there are several medical conditions that require careful clinical surveillance and, sometimes, laboratory monitoring. The main situations that require close monitoring are major bleeding, assessment of compliance (in particular during comorbidities other than vascular disease, e.g. dementia), overdose, sudden or progressive renal dysfunction, extreme body weight, concomitant use of other drugs that may induce impairment of new oral anticoagulants, need for urgent surgery.

Colonic diverticular hemorrhage: the hood method for detecting responsible diverticula and endoscopic band ligation for hemostasis

Although colonic diverticular hemorrhage is a common cause of lower gastrointestinal bleeding, the low rate of detection of the diverticula responsible for bleeding, together with inadequate evaluation of endoscopic hemostasis, remain unsatisfactory. Over 3 years, we employed the hood method to diagnose diverticular hemorrhage in 53 patients and applied endoscopic band ligation (EBL) for hemostasis in 27 patients with responsible diverticula. The hood method revealed active bleeding in 13 patients (24.5%), nonbleeding visible vessels in 14 patients (26.4%), and presumptive diverticular hemorrhage in 26 patients (49.1%). The nonbleeding visible vessels were located in the diverticular dome in 13 patients and at the diverticular orifice in one patient. EBL was performed in 27 patients, and a hemostasis rate of 96.3% was achieved. In 9 of 12 patients treated with EBL, follow-up colonoscopy revealed resolution of the responsible diverticula. The hood method improves the detection rate of diverticula responsible for bleeding by revealing potential nonbleeding visible vessels in the diverticular dome. EBL may become an effective procedure for hemostasis of colonic diverticular hemorrhage.

Plasma Treated with Methylene Blue and Light: Clinical Efficacy and Safety Profile

Methylene blue (MB) was the first method developed for pathogen inactivation of a labile blood component that was introduced in 1991. MB and light (MBL) inactivates most lipid-enveloped viruses and those non-enveloped are, in general, resistant. MBL treatment affects several coagulation factors, most noticeably fibrinogen and factor VIII with a loss of approximately 30%. Using endogenous thrombin potential, a global hemostasis evaluation, MBL treatment of plasma resulted in a 7% to 10% of reduction in thrombin potential. Although, originally, the scientific evidence of its efficacy and safety were scarce, the 4.4 million of units transfused have provided a wide body of evidence of its efficacy and safety in most of clinical situations. Nevertheless, some doubts have arisen about the efficacy of MBL plasma when used as a replacement solution for plasma exchange in the treatment of patients suffering from TTP. Probably only randomized controlled trials would provide definite evidence to clarify this point. Reports of severe allergic reactions in a few patients receiving MBL plasma have provoked the recent decision to remove the product from the market in France. Interestingly hemovigilance data in countries such as the same France, Spain, and United Kingdom have not corroborated an increase in severe allergic reaction. Close monitoring of the patients receiving plasma and suffering from allergic reactions and reporting to hemovigilance schemes hopefully will provide the needed data to definitely establish the exact risk of this complication for MBL vs other types of plasma.

Reference values and repeatability of buccal mucosal bleeding time in healthy sedated cats.

Bleeding time is a screening test for the evaluation of primary haemostasis. As there is currently limited information on the reference interval (RI) and repeatability of the test in the cat compared with the dog, the purpose of the study was to establish the RI of buccal mucosa bleeding time (BMBT) in healthy cats and to investigate the intra-observer repeatability of the test. Fifty-six cats were prospectively enrolled in the study. The animals were deemed to be healthy based on history, physical examination, complete blood count, serum biochemistry, and negative serological testing for feline leukaemia and immunodeficiency viruses. All cats were sedated with ketamine, dexmedetomidine and morphine, and the BMBT was sequentially measured in the left and right exposed buccal mucosa following a standardised incision made by a commercially available, disposable, bleeding time device. The mean BMBT was 58.6 s and the RIs ranged from 34 to 105 s (Bootstrap estimation). The intra-observer repeatability was up to 87 s (Bland-Altman plot). The results of this study imply that the combination of ketamine, dexmedetomidine and morphine is a safe and useful sedative protocol allowing for the reliable measurement of BMBT in the cat. The RI of feline BMBT may range from 34 to 105 s and the BMBT may differ by up to 87 s for any two consecutive readings for an individual cat.

Case Scenario: Management of Trauma-induced Coagulopathy in a Severe Blunt Trauma Patient

Case Scenario: Management of Trauma-induced Coagulopathy in a Severe Blunt Trauma Patient

Regulation in Hemostasis and Thrombosis: Part I—In Vitro Diagnostics

The diagnostic or test-performance process, as associated to the evaluation or diagnosis of hemostasis and thrombosis and related disorders, is influenced or controlled by the activity of a large number of professional, expert, and government organizations. These may be involved in driving standardization or harmonization, providing professional or expert guidelines, or in regulation of therapeutic products and diagnostic products such as in vitro diagnostic devices or reagents (IVDs). Although all organizations involved in this activity would propose an intention to drive improvements in diagnostics and human health and although there are benefits to the overall process of standardization and regulation for tests of hemostasis and thrombosis, it should also be recognized there are several specific problems and limitations to this process. As highlighted in this report, which specifically relates to the regulation of IVDs, several case studies are used as examples to show that regulation, aimed to reduce risks associated with the implementation of diagnostic testing, may instead encourage the adverse outcome of locking out clinically useful, new, and improved technologies and locking in old and outdated technologies. This has a potential for significant adverse outcomes related to the clinical diagnosis and management of hemostasis and thrombosis-related disorders.

Hemostasis in a Noncompressible Hemorrhage Model: An End-User Evaluation of Hemostatic Agents in a Proximal Arterial Injury

1. Evaluate hemostatic bandages by the end user using subjective and objective criteria. 2. Determine if user training and education level impact overall hemostatic outcomes. 3. Our hypothesis was that prior medical training would be directly linked to improved hemostatic outcomes in noncompressible hemorrhage indepen- dent of dressing used. Military personnel were given standardized instruction on hemostatic dressings as part of a tactical combat casualty care course (TC3). Soldiers were randomized to a hemostatic dressing. Proximal arterial (femoral and axillary) injuries were created in extremities of live tissue models (goat or pig). Participants attempted hemostasis through standardized dressing application. Evaluation of hemostasis was performed at 2- and 4-minute intervals by physicians blinded to participants' training level. Military personnel that are due to deploy are given "refresher" instruction by their units as well as participating in the TC3 to further hone their medical skills prior to deployment. The TC3 is simulation training designed to simulate combat environments and real-life trauma scenarios. Military personnel due to deploy, physicians (residents and board certified surgeons), animal care technicians, and veterinarian support. Celox 42 (33%), ChitoGauze 11 (9%), Combat Gauze 45 (35%), and HemCon wafer 28 (22%) bandages were applied in 126 arterial injuries created in 45 animals in a standardized model of hemorrhage. Overall, no significant difference in hemostasis and volume of blood loss was seen between the 4 dressings at 2 or 4 minutes. Combat gauze was the most effective at controlling hemorrhage, achieving 83% hemostasis by 4 minutes. Combat gauze was also rated as the easiest dressing to use by the soldiers (p<0.05). When compared to nonmedical personnel, active duty soldiers with prior medical training improved hemostasis at 4 minutes by 20% (p = 0.05). There is no significant difference in hemostasis between hemostatic bandages for proximal arterial hemorrhage. Hemostasis significantly improves between 2 and 4 minutes using direct pressure and hemostatic agents. Prior medical training leads to 20% greater efficacy when using hemostatic dressings.

In vitro evaluation of canine hemostasis following dilution with hydroxyethyl starch (130/0.4) via thromboelastometry

To assess the effects of in vitro hemodilution of canine blood with a low molecular weight hy-droxyethyl starch (HES 130/0.4) by means of thromboelastometry (TEM). In vitro experimental study. University Teaching Hospital. Ten healthy adult staff-owned dogs were sampled for the purposes of the study. Samples were also collected from 45 clinically normal dogs to establish thromboelastometric reference intervals. For each dog whole blood was collected by jugular venipuncture and placed into tubes containing 3.8% trisodium citrate and stored at 37°C. Two standard dilutions (1:4 and 1:10) from canine blood specimens were prepared with HES 130/0.4 and saline 0.9%. The effects of dilution were studied by TEM. No statistically significant differences were observed between the TEM values of the control samples and the samples diluted with saline solution (ratio 1:10 and 1:4). In contrast, hypocoagulability was observed in the samples treated with HES 130/0.4, with more severe effects at 1:4 dilution than at 1:10 dilution. The 1:4 dilution with HES 130/0.4 produced marked alterations: CT (P = 0.035) and CFT (P = 0.0007) on the ex-TEM profile, CT (P = 0.0005) and ML (P = 0.0017) on the fib-TEM profile and CFT (P = 0.0043) on the in-TEM, were all significantly increased (P < 0.05), whereas MCF (P = 0.0042) and alpha angle (P = 0.002) on the in-TEM and MCF (P = 0.011) and alpha angle (P = 0.001) ex-TEM profiles and MCF (P = 0.0001) on the fib-TEM profile were significantly decreased (P < 0.05). Dilution of canine blood with HES 130/0.4 results in a thromboelastometric pattern consistent with hypocoagulation and this effect appears to result from a dose-dependent alteration in fibrinogen concentration and inhibition of platelet function. As this is an in vitro study, further in vivo investigations are necessary to confirm the results.

Ménorragies par déficit congénital en facteur V chez une adolescente

The frequency of menometrorrhagia in adolescence is estimated at 2-5%. The functional origin is the most common. Hemostasis abnormalities account for 20% of cases, and they should be sought whenever there is a personal history of known or suggestive of hemostasis disorders (epistaxis, gingival bleeding, postoperative bleeding, bruising, etc.) or there is a family history of hemostasis disorders. Organic origins are rare, but these must be sought when the characteristics of bleeding point in this direction. The workup aims to investigate the cause and assess the impact of the hemorrhage. It may include an NFS, blood group and rhesus±β-HCG, hemostasis evaluation, determination of hemostasis factors, and a pelvic ultrasound. Whatever the cause of menometrorrhagia, the therapeutic options are the same and are oriented by the severity of bleeding. The treatment is mainly medical and hormonal. The surgical option should be a choice of last resort. We report a case of a 13-year-old girl admitted in hemorrhagic shock due to abundant metrorrhagia. Her laboratory tests showed an isolated deficiency of factor V with a 2% rate. Congenital factor V deficiency is a rare autosomal recessive coagulation disorder. It can be diagnosed at any age when a bleeding disorder of varying severity is observed. The diagnosis is based on the hemostasis evaluation with quantitative determination of factor V. Because no FV-specific concentrate is available, fresh frozen plasma remains the mainstay of treatment. Antifibrinolytics can also be beneficial, and platelet transfusions have been successfully used, associated with hormone therapy. These patients may best be managed in cooperation with both a gynecologist and a hematologist.

Evaluation of Primary Haemostasis in Patients Undergoing Cardiac Surgery Using a Novel Automated Microchip Flow-Chamber System (T-TAS).

AbstractAbstract 2171Post operative bleeding is a common complication of cardiac surgery; its aetiology may be multifactorial but is often attributed to platelet dysfunction. However, at present no reliable point of care test (POCT) is available for this and patients are often managed empirically; approximately 40% receive pooled platelet transfusions but many require re-sternotomy. An automated microchip flow chamber system that directly measures platelet-collagen interaction under shear (1500s−1) has recently been developed (T-TAS; Total Thrombus-formation system; Zakros, Fujmori Kogyto, Japan). We hypothesized that this could be developed as a POCT to assess platelet function under shear, allowing targeted and more rational use of blood products. We used this system to study 20 patients aged 19–72 years, before and after cardiac surgery. The T-TAS was used to determine the onset of occlusion (time to 10kPa, T10) and primary haemostatic potential (AUCend-area under pressure curve). Haematocrit (Hct), platelet count and von Willebrand factor (VWF) levels and thromboelastography (TEG) were measured at the corresponding time points.Surgery resulted in a significant increase in time to occlusion onset (T10) (p=0.006; n=20, Figure 1A). Similarly, the AUCend significantly decreased after surgery (p=0.001, n=19; Figure 1B) with the majority of cases (12 out of 20) failing to occlude within 30 minutes. The change in T10 inversely correlated with change in AUCend(r=-0.5, p=0.02).VWF is essential for platelet adhesion to collagen under high shear stress. Higher VWF levels appeared to be associated with lower T10, but this was not significant and only observed prior to surgery. Moreover, no significant correlation between the change in T10 or AUCend and changes in VWF pre- and post-surgery was observed.Surprisingly, pre and post-operative hematocrit were both negatively correlated with AUCend (r=-0.5, p=0.03, n=11 and r=-0.5, p=0.02,n=11 respectively).No correlation was observed between platelet count and the T-TAS parameters. However, the change in AUCend (but not T10) was shown to correlate with the change in platelet count before and after surgery (r = 0.58, p = 0.01).Finally, T10 and AUCend values were not significantly altered in patients given anti-platelet drugs: aspirin and/or clopidrogel. This implies that the T-TAS is sensitive to the initial adhesion of platelets to VWF-collagen rather than to platelet activation and aggregation.These data demonstrate that cardiac bypass surgery affects VWF mediated platelet adhesion to collagen under flow and this can be detected using a microchip flow chamber system. The lack of correlation with VWF levels and apparently paradoxical effect of haematocrit suggest that the dominant mechanism for the impaired postoperative haemostasis is a decline in platelet function and in particular a decrease in adhesive function. This is likely to result from altered exposure and/or function of GPIb resulting from surgery and cardio-pulmonary bypass.Current POCTs are largely insensitive to primary haemostatic mechanisms, while conventional laboratory measures of primary haemostasis are non-physiological, and require a considerable expertise and time. As expected, TEG gave similar values pre and post-surgery for all subjects, indicating that a flow system is required to adequately evaluate primary haemostasis. The advantages of this novel automated microchip flow chamber system are the small blood volume required and the rapidity of results. Our data suggest a place for this system in a point-of care setting, providing useful assessment of haemostatic status following surgery and with the potential to improve patient management. Further studies are warranted. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

520 Diagnosis and Treatment Peculiarities in an Infant with Bleeding Disorder

Background and AimsOne of bleeding causes due to vitamin K deficiency is gut flora destruction secondary to antibiotic treatment early in life. Authors emphasize diagnosis and treatment difficulties for an...