bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haemostasis Alterations in Sickle Cell Disease.
Authors: Van Dreden Patrick , Rousseau Aurelie , Exner Thomas , Vasse Marc , Lahary Agnes , Vannier Jean Pierre , Woodhams Barry 
Published: April 2020

Abstract
Sickle cell disease (SCD) is considered by many workers to be a hypercoagulable state. The vaso-occlusion in sickle cell disease is complex, involving adhesive processes between sickle red blood cells, leukocytes, and the activated endothelium. Loss of normal membrane phospholipids asymetry with the appearance of phosphatidylserine on the erythrocyte surface has been documented as promoting an exacerbation of the anaemia and an activation of coagulation. The aim of this study was to monitor changes in coagulation and platelet activation (monitored by measuring the levels of procoagulant phospholipids microparticles - PPM) in SCD (both in steady state and crisis). Coagulation screening tests (PT, APPT), Protein S (PS), D-Dimer (D-Di) and PPM were measured in plasma samples obtained from 18 patients with SCD (8 in crisis state and 10 in steady state) and in twenty one normal volunteers as control. All blood samples were collected and the plasma prepared in the same hospital using the same conditions. All plasma samples were stored at -80°C until assayed. PT, aPTT, PS and D-dimers were measured using reagents from Diagnostica Stago, Asniéres, France. PPM was monitored with a novel factor Xa-based coagulation assay. In this assay shortened clotting times are associated with increased levels of PPM and thus platelet activation.
APTT Sec. PT % PPM Sec PS % D-Di μg/l Controls 34.6 (29.4–39.6) 93.1 (79–109) 57.5 (51.1–74.9) 88.8 (62–112) 0.22 (0.22–0.45) Sickle cell – in crisis 37.3 (33.4–47.4) 71.1 (56.5–86.5) 44.6 (34.0–60.0) 48.9 (25.0–89.5) 1.6 (0.6–2.6) Sickle cell – steady state. 38.0 (33.0–47.5) 75.0 (61.0–93.0) 52.2 (42.5–62.8) 84.7 (76.5–103.0) 0.7 (0.2–1.0)
In sickle cell crisis a significant increase in both coagulation and platelet activation, as monitored by PPM, was found (all at p &lt; 0.001). The decrease in % PT and PS levels confirms the findings of others. In steady state only DDi levels are significantly higher than controls. Further studies are needed to explain these findings. Although this was a small pilot study and further studies are needed it is interesting to speculate on the possible usefulness of the PPM assay in monitoring SCD crisis.
Haemostasis Disturbances in Type I and II Diabetes Mellitus.
Authors: Van Dreden Patrick , Rousseau Aurelie , Exner Thomas , Vasse Marc , Ozenne Geneviéve , Woodhams Barry 
Published: April 2020

Abstract
Diabetes is associated with disturbances in haemostasis that are thought to result in an increased incidence of thrombotic complications and cardiovascular disease. The aim of this pilot study was to monitor activation of haemostasis using specific markers for platelet activation and coagulation. Plasma samples (all blood collected and plasma prepared in the same hospital under the same conditions) were obtained from twenty diabetic patients (8 with type I and 12 with type II) and twenty one normal control volunteers. To monitor coagulation these samples were evaluated with the partial thromboplastin time (APTT), prothrombin time (PT) and D-dimer (D-Di) - all reagents from Diagnostica Stago, Asniéres, France. Platelet activation was monitored with a novel method for monitoring procoagulant phospholipids microparticles (PPM) using a factor Xa-based coagulation assay. In this assay shortened clotting times are associated with increased levels of PPM and thus platelet activation.
APTT Sec. PT % PPM Sec. D-Di μg/l Controls 34.6 (29.4–39.6) 93.1 (79–109) 57.5 (51.1–74.9) 0.22 (0.22–0.45) Type I Diabetes 34.5 (33.1–36.7) 96.9 (92–102.5) 33.8 (19.1–44.2) 1.6 (0.22–3.6) Type II Diabetes 36.8 (33.2–40.4) 96 (59.4–112.5) 48.3 (44.2–51.2) 0.7 (0.22–1.7)
Significantly higher levels of both PPM and DD were found in Type I diabetes patients compared with controls (both P&lt;0.001). In type II diabetes the levels of both were lower than those found in Type I diabetes but both were still higher than the controls (PPM and DDi at p&lt;0.001 and p&lt;0.01 level respectively), only the differences in levels of PPM reaching significance between type I and type II diabetes (p&lt;0.01). The more severe the diabetes (type I &gt; type II) the greater the level activation of haemostasis that is observed. The increases in PPM could account in part for the development or progression of arthrosclerosis in patients with diabetes mellitus. The increased level of D-Di confirms the increased hypercoagulability of these patients. Although this was a small pilot study and further studies are needed to confirm these findings it is interesting to speculate on the usefulness of both the PPM assay and D-Di assays in monitoring the development/severity of diabetes and its complications. The PPM assay may prove to be especially useful in monitoring progression of the disease.
A Relatively Low Frequency of Bleeding in Patients with Severe Factor XI Deficiency Who Undergo Surgery Involving Tissues with Low Fibrinolytic Activity Supports on Demand Rather Than Prophylactic Use of Plasma.
Authors: Salomon Ophira , Steinberg David M. , Seligsohn Uri 
Published: April 2020

Abstract
Severe factor XI (FXI) deficiency is an injury related bleeding tendency. Fresh frozen plasma (FFP) or FXI concentrate are usually used for achieving hemostasis in such patients undergoing surgery but this can lead to inhibitor formation in 33% of patients with FXI level &lt;1 U/dL (Blood101:4783, 2002). Based on observations in a limited number of patients with severe FXI deficiency, we previously suggested that surgery at tissues with known fibrinolytic activity is accompanied by bleeding more frequently than in other sites (NEJM325:153, 1991). In this study we retrospectively assessed the frequency of post surgical bleeding in 165 unrelated patients with severe FXI deficiency who were not treated by hemostatic means. Criteria for bleeding included local hematoma, need for surgical arrest of bleeding, or use of blood components. Bleeding occurred in 7/57 (12.3%) patients operated at tisues with low fibrinolytic activity, and in 29/48 (60.4%) patients operated at fibrinolytic sites (Table). Bleeding following circumcision (a non-fibrinolytic site) was accompanied by bleeding only in 1/64 (1.6%) and following oral surgery in 55/110 patients (50%). The relatively low frequency of bleeding following surgery at non-fibrinolytic sites advocates on demand rather than prophylactic replacement therapy when such surgery is performed.
SITE OF SURGERY N BLEEDERS % BLEEDERS Non-fibrinolytic Appendicectomy 22 1 1.6 Gastric 3 0 0 Cholecystectomy 5 1 20 Herniotomy 13 3 23 Hysterectomy 5 2 40 Orthopedic 9 0 0 Fibrinolytic Tonsillectomy 33 20 60.6 Nose 12 7 58.3 Prostatectomy 3 2 66.6 Circumcision 64 1 1.6 Oral Tooth extractions 100 49 49 Gum 10 6 60
Co-Interaction and Increased Release of Tissue Factor Pathway Inhibitor by Heparanase.
Authors: Nadir Yona , Brenner Benjamin , Zetser Anna , Levy-Adam Flonia , Kaplan Victoria , Zcharia Eyal , Goldshmidt Orit , Vlodavsky Israel 
Published: April 2020

Abstract
Background and objectives. Tissue factor pathway inhibitor (TFPI) is a potent direct inhibitor of factor Xa and factor VIIa-tissue factor complex. In addition, TFPI was shown to be an inhibitor of angiogenesis and metastasis. Heparanase is an endo-beta-D-glucuronidase of 65 kDa that cleaves heparan sulfate chains on cell surfaces and in the extra-cellular matrix an activity that closely correlates with cell invasion, angiogenesis and tumor growth. The study hypothesis was that heparanase may reduce the level of TFPI or release it from the cell surface in an attempt to increase heparanase prometastatic potential.
Material and methods. The effect of exogenous heparanase on TFPI expression and release to the medium was studied in HUVEC by immunoblotting, real time RT-PCR, and flow-cytometry. Human cell lines (MDA-MB-435 breast carcinoma; U87 glioma; HEK-293 embryonic kidney) were transfected to over express heparanase and the effect on TFPI was studied. TFPI expression was explored in heparanase transgenic mice by immunoblotting and immunostaining. Transfections with various modified forms of heparanase were used to further explore the effect of heparanase. Interaction between TFPI and heparanase was studied by co-immunoprecipitation analysis.
Results. Heparanase was found to increase the release of TFPI to the medium, reduce the level of TFPI at the cell surface, and to up-regulate its expression in the cells. These results were verified in HUVEC, tumor cell lines, and in the animal model. The effect was independent of heparanase activity or interaction with heparan sulfate, and dependent on heparanase secretion. A protein co-interaction between TFPI and heparanase was found.
Conclusions. Overall, a cell surface interaction is suggested in which heparanase impose increased release of TFPI from the cell surface to the medium, providing a local procoagulant and a systemic anticoagulant environment.
Activation of Endothelial Cells, Coagulation and Fibrinolysis in Thai Children with Dengue Virus Infection.
Authors: Sosothikul Darintr , Lusher Jeanne M. 
Published: April 2020

Abstract
Dengue virus is an arthropod borne flavivirus that most commonly causes a non-specific febrile illness: Dengue Fever (DF), and less frequently causes a life-threatening illness: Dengue Hemorrhagic Fever (DHF). The fatality rates of DHF are varying from 1 to 5% in tropical countries. Although severe bleeding remains the major cause of death, the pathogenesis of bleeding is poorly understood. This study was primarily designed to determine the extent of activation of endothelial cells, coagulation cascade and fibrinolysis in correlation with clinical severity and also to detect the best prognostic factor(s) for DHF during the febrile phase. We conducted a prospective cohort study in 42 children with Dengue infections (20 with DF and 22 with DHF); 38 age-matched normal Thai children served as the control group. Endothelial cell activation, coagulation and fibrinolysis parameters were measured in each patient during 3 phases of illness: febrile (Days 1–4), toxic (Days 5–6) and convalescent (Day 7–10). Bleeding scores (Buchanan G, et al, J Pediatr 2002) were also classified.
Results: In DHF patients, during the febrile phase, plasma levels of von Willebrand Factor Antigen (VWF:Ag), tissue factor (TF), Thrombin-Antithrombin Complex (TAT), and D-dimer were significantly high, while platelet counts, fibrinogen, Protein C activity (PC:Ac) and thrombin activatable fibrinolysis inhibitor (TAFIa) were significantly low compared to the control group. During the toxic phase, activated Factor VII (FVIIa:c), tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) were significantly increased compared to the control group. In DF patients, during the febrile phase, only plasma levels of VWF:Ag were significantly elevated, while platelet count, PC:Ac and TAFIa were significantly lowered compared to the control group. During the toxic phase, soluble thrombomodulin (sTM), FVIIa:c, and TAT were significantly raised compared to the control group. Compared to DF patients, DHF patients had significantly higher plasma concentrations of vWF:Ag (p=0.02), TF (p=0.01), and PAI-1 (p=0.038) during the febrile phase. Bleeding scores were positively correlated with plasma t-PA and clinical severity, and negatively correlated with plasma Factor VIII:C and TAFIa. Using logistic regression analysis, we found that an increase in plasma VWF:Ag was the only significant predictor (p=0.049) of progression to DHF. The endothelial cell injury and release of procoagulant components, activation of the coagulation cascade with thrombin generation, increased antifibrinolytic factors and consumption of natural anticoagulants each play important roles in the development of hemorrhage in Dengue patients. Plasma VWF:Ag is the best indicator of progression to DHF.
Ferritin Levels in a Cohort of Affected Males of Mild Hemophilia A Carriers and Their Unaffected Siblings.
Authors: Kawaja M. , Scully M.F. , Barrett B. , Walsh M. , MacGregor D. 
Published: April 2020

Abstract
Iron deficiency is often used as a surrogate marker of bleeding. According to (multiple) studies, suboptimal iron stores can affect cognitive function, energy level and hence, quality of life. Due to a founder affect certain regions of the Canadian province of Newfoundland and Labrador have a very high prevalence of mild Hemophilia A. To accurately plan for future health related needs of these patients, a base-line cross-sectional study of a large cohort segregating a known founder mutation (Val2016Ala) was undertaken. Serum ferritin concentrations, complete blood counts (CBCs), menstrual blood loss assessed using Pictorial Blood Loss Assessment Chart (PBAC), bleeding histories, BMIs, and quality of life data using the SF-36 questionnaire were collected.
Prevalence(%) of Suboptimal Iron Status for Women and Men Sub-Grouped By Menstrual Status and Mutation Status Serum Ferritin Cut-off(ug/L) **P Chi-Square &lt;0.001 *P Chi-Square &lt;0.01 Cohort &lt;11 &lt;24 &lt;40 &lt;50 Females(n=141) 12.1* 37.6** 55.3** 62.4** Males(n=77) 1.3* 4.1** 6.5** 6.5** Menstruating Women(n=81) 15.0 54.3** 71.6** 80.2** Non-Menstruating Women(n=58) 8.6 15.5** 31.0** 36.2** Menstruating Carriers(n=46) 8.7 50.0 65.2 73.9 Menstruating Controls(n=35) 23.5 60.0 80.0 88.6 Affected Males(n=46) 0.0 4.3 6.5 6.5 Control Males(n=31) 3.2 3.2 6.5 6.5
§ Six women had hemoglobin concentrations less than 120 g/L and 11 men had concentrations less than 140 g/L, with anemia comparably observed in patients with or without the mutation(data not shown).
Women in general reported a lower mean General Health Scale score (63.9, 59.9–67.9 vs. 70.6, 69.5–71.7) and a higher mean Role Emotional Scale score (89.3, 85.8–92.8 vs 79.5, 77.7–81.3) than norms for the general U.S. population. Men with a history of severe bleeding had significantly lower ferritin levels than men without a history of severe bleeding (123.4 g/L, 63.6–186.3 g/L, 105.9–301.5; p &lt;0,05). Mutation status did not influence iron status in either sex or menstrual blood loss in women as measured by the PBAC. Serum ferritin level was not associated with PBAC score. Neither the means of the eight SF-36 domains, health transition scale, nor the two component summary measures were significantly lower for mildly iron-deficient or iron-deficient women. The SF-36 is a general measure of various quality of life domains and may not be sensitive enough to measure the effects iron deficiency could potentially have on women’s cognition and fatigue. A study using measures more sensitive to these affects would better investigate the impact of iron deficiency. Further research is also required to determine whether the low ferritin levels observed in women could possible be a result of inadequate dietary intake of iron or insufficient iron absorption in addition to menstrual blood loss.
Assessment of Menorrhagia in Females Followed for Bleeding Disorders at the Hemophilia Center of Western New York-Correlation between Clinical Presentation and Laboratory Parameters.
Authors: Bush Eric , Smiley Shannon , Belling Linda , Bernstein Zale P. 
Published: April 2020

Abstract
Menorrhagia is a common problem among women. The pathophysiology has been attributed to Von Willebrand’s disease in some patients. The lab diagnosis and confirmation of this condition in these women is often difficult. The need for easily reproducible, validated lab investigations is recognized. The platelet function analyzer (PFA-100) (described below) has recently been used as an adjunct for lab diagnosis of this condition. Use of this device is relatively recent, thus clinical correlation with its results have been lacking. Therefore, we initiated a study to determine if a correlation could be established between pictorial blood assessment chart (PBAC), PFA-100, and Von Willebrand’s screening (VWF antigen and co-factor activity levels).
Materials and methods: After obtaining informed consent 15 female patients with a diagnosis of von Villebrand’s disease were enrolled in the above study. All received verbal and written instructions of how to record their tampon/pad use on the PBAC. The PBAC was then scored on a validated and well-established point system for lightly (1point), moderately (2points) and heavily (3points) soiled pads or tampons. In addition their blood samples were analyzed for von Willebrand antigen, Ristocetin Co-Factor and on the PFA-100 (pre and post DDAVP). The PFA-100, is a high shear-inducing device which simulates primary hemostasis after injury to small vessel, which consists of a reservoir for whole blood and a small capillary surmounted by a collagen-coated membrane with a central aperture. Platelet agonist which is either epinephrine or ADP is present on the membrane. Closure time is reported as a variable which describes von Willebrand factor function. All blood samples were forwarded to Children’s Hospital of Buffalo Special Coagulation lab for examination of the PFA-100(pre and post DDAVP),and von Willebrand panel.
Conclusion: There was correlation between the number of points self-assessed on the PBAC and the PFA-100.
Summary Data Patient # Age # points/PBAC VWF Ristocetin Co Factor Factor VIII PFA 100 Pre DDAVP 1 48 10 56 52 70 104 2 47 23 73 53 138 90 3 21 9 69 70 63 151 4 47 180 75 51 120 280 5 44 25 107 68 114 124 6 49 47 102 93 74 63 7 25 12 74 51 84 177 8 26 8 30 28 77 216 9 30 24 47 64 115 125 10 27 11 76 45 60 118 11 25 10 66 49 79 136 12 48 11 51 48 121 117 13 25 9 59 42 44 99 14 23 41 33 11 34 275 15 46 84 3 2 11 300
Enhanced Fibrin Clot Formation and Stability with a Superactive Analog of Factor VIIa in an In Vitro Model of Hemophilia.
Authors: Wolberg Alisa S. , Ezban Mirella , Hedner Ulla , Persson Egon 
Published: April 2020

Abstract
Recombinant factor VIIa (rFVIIa, NovoSeven; Novo Nordisk A/S, Copenhagen, Denmark) has demonstrated its clinical efficacy in treating bleeding in hemophilia patients with inhibitors. Using in vitro assays, we and others have previously shown that high dose rFVIIa shortens the onset of fibrin clot formation and normalizes the fibrin structure and porosity of clots formed under hemophilic conditions (absence of factors VIII and/or IX (Wolberg et al. (2001) 98(11): 826a). Recently, several superactive analogs of rFVIIa have been described, demonstrating increased thrombin-generating activity on platelets (Persson et al. (2001) 98(24): 13583–8), and increased capability to reduce the tail bleeding time and total blood loss in a mouse model of hemophilia A (Tranholm et al. (2003) 102(10): 3615–20).
In the current study, we have used a cell-based reconstituted model system of coagulation to compare the abilities of rFVIIa and one of the superactive analogues, NN1731, to modulate the onset and rate of fibrin clot formation, as well as the ability of these molecules to increase the stability of fibrin clots formed in the presence of a fibrinolytic challenge. The model system consists of tissue factor-bearing monocytes, purified pro- and anti-coagulant proteins (XI, X, IX, VIII, VIIa, V, II, AT, TFPI), freshly-isolated, unactivated platelets and fibrinogen. This system permits the inclusion of protein and cell concentrations at their physiologic levels. “Coagulation” is initiated by combining the components and following clot formation by optical density. “Hemophilia” is simulated by omitting factors IX and VIII. We observed that NN1731 shortened the clot time of hemophilic conditions to normal and did so at lower doses than were required of rFVIIa. Further, NN1731 increased the rate of clot formation to normal. To test the ability of clots to form in a fibrinolytic environment, we performed a Plasmin Challenge Assay, in which clot formation is initiated in the presence of a low concentration of plasmin. In this assay, clot formation is indicated as an increase in turbidity, and clot lysis is seen as a subsequent decrease in turbidity. There is no turbidity development (no clot formation) under hemophilic conditions. We observed that NN1731 increased the rate of clot formation and the length of time that fibrin was present under hemophilic conditions, and did so at lower concentrations than were required for rFVIIa. Moreover, in all of these assays, NN1731 normalized hemophilic conditions. Our results suggest that NN1731 promotes clot formation and stability to a greater degree than equal doses of rFVIIa and may possess clinical utility in patients that are refractory to current doses of rFVIIa.
Management of Recurring Epistaxis in Hereditary Hemorrhagic Teleangectasia.
Authors: Corinaldesi Giorgio , Corinaldesi Christian 
Published: April 2020

Abstract
The hereditary hemorrhagic teleangectasia of Rendu-Osler-Weber (HHT), is an autosomal dominant disease with a genetic angiodysplasia affecting multiple organs: skin, lung, gastrointestinal and genitourinary tract, and brain; the diagnosis is based on the following criteria: familiarity, epistaxis, teleangectasies, and visceral arterovenous malformations with a different degree of expression. The HHT is genetically heterogeneous involving two loci: HHT-1 (chromosome 9q-34.1), and HHT-2 (chromosome 12q11-q14). The loci have been identified as endoglin (ENG) CD105, and activin receptor like-kinase-1 (ALK-1) serine/threonine kinase receptor type-1 of TGF-beta superfamily.
We have studied a 52 years old patient presented with a story of recurrent bleeding and acute anemia secondary to strong epistaxis and upper bleeding: the endoscopic study disclosed multiple spots of duodeno-jejunal angiodysplasia with mucous angectasia spider-like 1–2 mm, macular spots, tortuous vessels. This patients also had frequent spontaneous epistaxis, in particular the management of most common anterior forms (locus Valsalvae, Kiesselbach area) is based on nostril pinching and the former abstersion of clots, irrigation with antifibrinolytic drugs and also on more packing with Lyofoam, Surgical, or Merocel leaflet or with Clauden or Vasenol lint which has to stay on site for 3–4 days with an antibiotic coverage, the relapsing cases were treated with sequential photocoagulation with argon-laser. In order to control high posterior epistaxis in case of emergency, the super-selective angiographic embolization with jelly sponge, polyvinyl-alcohol particles, detachable or endoscopic ultraligation of the anterior ethmoidal and or the sphenopalatine artery. All recurrent bleeding events responded to initial standard treatment strategies: blood transfusion with fresh frozen plasma, PRBC, drugs therapy including A-PCCS, tranexamic acid until 6 g/day, danazol, combined estrogen/progesterone therapy, octreotide (50 mcg iv followed by an infusion of 30 mcg/h for 5 days), anaemia required iron supplement. Recently severe clinical symptoms and a severe epistaxis and hematemesis combined with an hemodinamic instability required an urgent EGS followed by endoscopic therapy with termal probes together with high dose rFVII (220 mcg/kg), obtaining immediate benefit; no bleeding recurrence was detected after six months. This therapeutical approach may require some more studies, but it can be a great choice for controlling refractory re-bleeding in selected patients.