bluuebunny/crossref_metadata_2025_split huggingface dataset:
Derived/Clauss Fibrinogen Ratio as a Potential Adjunct to D-Dimer in the Diagnosis of DVT.
Authors: Wakeman Lisa J. , Munro Roger C. , Blundell Victoria , Al-Ismail Saad , Benton Ann , Dorward Nick , Beddall Andrew , Morris Keith 
Published: April 2020

Abstract
Introduction
Along with clinical assessment, D-dimer (D-d) assays are routinely used to exclude DVT. It has been suggested that measurement of derived fibrinogen (DF) may be an effective reflection of endogenously-derived thrombin generation and that ratios between this and Clauss-derived fibrinogen (CF) may be useful in determining whether patients have experienced, or are vulnerable to thromboembolic events. Some studies indicate that a D-d/fibrinogen ratio is significantly higher among patients with confirmed DVT. The purpose of this study was to determine whether DF/CF ratios in individuals are a useful adjunct to D-d assays in the detection of DVT compared to D-d assay in isolation.
Methods
Venous samples were collected into glass B-D Vacutainers containing tri-sodium citrate (Becton-Dickinson, Plymouth, UKRef: 367691) from 162 out-patients presenting to the medical admissions unit with suspected DVT. Laboratory staff (N=100) served as the normal control group. D-dimer (MiniVidas, BioMerieux), DF and CF (Dade-Behring reagents in combination with a CA1500 coagulometer) were measured on all patients and normal control samples within two hours of collection.
Results
Following clinical assessment (Wells scoring), 85 patients were considered not to have had a DVT. Doppler scanning confirmed DVT in 38 of the remaining patients and 39 were shown to be negative. Two sample t-test analysis of the data showed significant differences between DF and CF levels in the normal group (n=100), patients who did not have a DVT (n=124) and those who did have a DVT (n=38), (p = &lt;0.05 in each group). There was a significant difference in the DF/CF ratios between the three groups (p = 0.014, one-way ANOVA). The mean DF/CF ratios in the normal control group, patient negative group and patient positive group were 1.16, 1.22 and 1.24 respectively. There was no overall correlation between D-d and DF (correlation co-efficient = 0.646), D-d and CF (correlation co-efficient = 0.581) nor between D-d and DF/CF. Of the DVT positive patients, 26 had a raised DF whereas only 12 had a raised CF.
Conclusion
Our data suggest that DF/CF ratios cannot be used as an adjunctive marker of DVT when used in combination with D-d values. DF/CF ratios are significantly higher in patients attending for clinical assessment irrespective of whether they are DVT positive or DVT negative. This may be because fibrinogen is an acute phase protein which increases with various pathological states and stressful events such as the experience of attending hospital for investigation and assessment. Further work is required to determine whether DF/CF ratios can be used adjunctively when the D-d cut off value is significantly higher than that used conventionally.
Homozygosity in the Single Nucleotide Polymorphism Ser128Arg in the E-Selectin Gene Is Associated with Recurrent Venous Thromboembolism.
Authors: Hron Gregor , Jilma Bernd , Marsik Claudia L. , Endler Georg , Eichinger Sabine , Kyrle Paul Alexander 
Published: April 2020

Abstract
Objective: The single nucleotide polymorphism (SNP) Ser128Arg in the E-selectin gene is over-represented in certain patient populations with atherosclerosis or restenosis. As this SNP enhances tissue factor triggered coagulation in humans during systemic inflammation, we hypothesized that it may also predispose for the development of recurrent venous thromboembolism (VTE).
Methods and Results: Patients (n=585) after first VTE were prospectively followed up for recurrent, objectively documented, symptomatic VTE. Patients with secondary VTE, homozygous Factor V Leiden, natural inhibitor deficiencies, lupus anticoagulant, or long term anticoagulation were excluded. The S128R SNP was genotyped by mutagenically separated PCR. One-hundred and two patients (17.4%) were heterozygous and 11 were homozygous (1.9%) for the Ser128Arg mutation. Ninety patients (15.4%) suffered from recurrent VTE during follow-up. Homozygosity for the Ser128Arg SNP increased the cumulative likelihood particularly for early recurrent VTE (log rank test p&lt;0.05) and was an independent predictor of recurrent VTE (hazard ratio: 4.1; 95% CI 1.5–11.4) in a multivariate Cox Regression model. In contrast, heterozygosity for the polymorphism was associated with an unaltered hazard ratio (HR: 1.1; 95% CI 0.6–1.9) for recurrent VTE.
Conclusion: Homozygosity for the S128R E-selectin allele appears to increase the risk for recurrent VTE several-fold, and -if confirmed- may represent a novel risk factor for recurrent VTE. These results also expand our knowledge on the association of this SNP with thrombotic disorders.
Factor V Leiden and Prothrombin G20210A Gene Mutations Should Not Be Routinely Screened among Venous Thromboembolism (VTE) Patients in Singapore - This and Patterns of Other Thrombophilic Conditions among Our VTE Patients.
Authors: Ng Heng Joo , Lee Lai Heng , Liu Te-Chih , Tan Lip Kun , Kuperan Ponnudurai 
Published: April 2020

Abstract
Introduction: Emerging good quality evidence has suggested that the prevalence of VTE among Asians is significant and was largely underestimated previously.
Objective and methods: We conducted a study of thrombophilic markers among our population of VTE patients to determine their prevalence and help determine the best screening strategy among our increasing number of VTE patients. Three major hospitals in the country were involved in this study.
Results: Of 254 patients recruited, ethnic distribution was as follows: Chinese 68.1%, Malays 17.3%, Indians 12.6%, Others 2%. The ratio of males to females was 2:3. Major risk factors such as surgery, trauma and malignancy was recordedand identified in about 80% of the population. Twenty-one percent of patients had pulmonary embolism. Positive results of thrombophilic markers were as follows: protein C deficiency, 4 patients (1.52%); protein S deficency, 26 (10.24%), antithrombin III deficiency, 11 (4.33%); lupus anticoagulant, 9 (3.54%); anticardiolipin antibody IgG, 3 (1.18%); anticardiolipin antibody IgM, 6 (2.36%); hyperhomocysteinemia, 32 (12.6%); factor V Leiden gene mutation, 0 (0%); prothrombin 20210 gene mutation, 0 (0%). The prevalence of at least one thrombophilic condition was found in about one third of our patients. The relative risks of these thrombophilic conditions will be compared with a healthy control population.
Conclusion: Among our VTE patients, the most commonly associated thrombophilic conditions were protein S and antithrombin III deficiencies. The factor V Leiden and prothrombin G20210A mutation did not feature at all in our patient population and is consistent with other studies on Asian populations. These tests should not be included as part of our thrombophilic screening.
Preemptive Immunotherapy with Highly Purified CD56+/CD3− Natural Killer Cells after Haploidentical Stem Cell Transplantation. A Prospective Phase II Study in 2 Centers.
Authors: Passweg Jakob R. , Koehl Ulrike , Stern Martin , Tonn Torsten , Meyer-Monard Sandrine , Bader Peter , Rischewski Johannes , Soerensen Jan , Paulussen Michael , Gratwohl Alois , Klingebiel Thomas , Tichelli Andre , Schwabe Dirk 
Published: April 2020

Abstract
Allogeneic natural killer cells may exert cytotoxic activity against HLA-nonidentical tumor cells. This effect may be exploited after T-cell depleted haploidentical hematopoetic stem cell transplantation (HSCT) by using donor NK-cell infusions (NK-DLI) as adoptive immunotherapy.
In a prospective phase II study in 2 centers we treated 15 patients with NK-DLI preemptively with the goals to demonstrate feasibility and to explore whether such infusions would contribute to stabilize engraftment and exert graft versus leukemia activity without causing GvHD.
Patients were adults (6) or children (8) receiving transplants from haploidentical donors to treat AML (7) ALL (5) Hodgkin lymphoma (2) or sarcoma (1). Donors were haplotype mismatched siblings in 3 and parents in 12.
Donor NK cells were selected from unstimulated leukapheresis using immunomagnetic T cell depletion with anti-CD3 and NK cell enrichment with anti-CD56 coated microbeads on the CliniMACS ® device. Per protocol, patients in center A received NK-DLI on days +40 and +100 and in center B on days +3, +40 and +100. NK-DLI were either freshly infused or cryopreserved and thawed.
Center A Center B N 8 7 Adults / Children 6/2 0/7 Disease: AML/ALL/HD/oth 6/1/1/0 1/4/1/1 Number of NK-DLI per patient 1/2/3 2/5/1 2/3/2 Median NK-cell recovery (%) 62 37 NK-cell dose (10e7/kg) (median, range) 1.2 (0.5–3.4) 1.4 (0.66–3.23) T-cell dose (10e4/kg) (median, range) 0.2 (0–7.2) 0.23 (0–5.3) Events: graft failure / progression / GvHD (III–IV) 2/2/1 1/2/1 Alive / Dead 3/5 5/2 Cause of death: graft failure/progression/GvHD 2/2/1 0/2/0
NK-cell collection and ex vivo purification was successful in all donors. Outcome is shown in the Table. Of note: One patient in each center developed severe (grade III / grade IV) GvHD respectively. These 2 patients had received the highest T-cell dose. The remaining patients tolerated NK-DLI well and did not develop GvHD. Two patients in Center A experienced graft failure after NK-DLI in spite of NK-alloreactivity in GvHD direction.
In conclusion: highly purified NK cells may be infused in recipients of haploidentical HSCT recipients. None of the patients receiving &lt; 10e4/kg CD3+ cells developed GvHD. Further studies are needed to determine the optimal dose and timing of NK-DLI for anti-tumor activity in this setting.
Treatment of Deep Vein Thrombosis with Continuous I.V. Infusion of LMWH in Children - Safe and Efficient Alternative to S.C. Application.
Authors: Fiamoli Veronika , Blatny Jan , Zapletal Ondrej , Kohlerova Svetlana , Penka Miroslav 
Published: April 2020

Abstract
Incidence of the thrombosis is age dependent with the lowest risk is in the childhood. Children mostly suffer from vein thrombosis (DVT/PE). Occurrence of thrombosis in children is 0,07/10 000, among hospitalized children is higher 3,5/10 000. In comparison with adults, these numbers are very low. LMWH is preferred in the treatment of DVT in children. UFH is used as second choice medication. LMWH is widely used in prevention of recurrence of DVT and sometimes it substitutes (especially in very young children) vitamin K antagonists. The most frequent form of application of LMWH is via subcutaneous injection. A few articles can be found in literature about treatment by intravenous continuous infusion in infants and in several cases in older children. The treatment by continuous infusion has certain advantages, especially for hospitalized patient with permanent i.v. access (painless, shorter half-life consecutively lower risk of bleeding, easier control). We present group of 27 children with DVT, who were treated with LMWH for first thrombosis from 2003 till 2005. We did the screening of thrombophilia in all of those children. We found FVleiden heterozygous in 38,1%, FII G2021OA heterozygous in 4,76, inherited deficiency of AT in 14,29%, BCP in 9,52 % and CVL was inserted in 52,38% of our patients.All patients had at least one of the risk factors of thrombophilia. We started to treat all patients with LMWH and the dose was adjusted to reach the level of antiXa between 0,5–1 IU/ml. We treated 6 patients (22,22%) by subcutaneous injection (average LMWH dose 215,54IU/kg/d) and 21 patients (77,78%) by continuous infusion (average dose 254,94IU/kg/d). Duration of the treatment was modified in accordance with the course of thrombosis (monitored by Doppler ultrasound with compression), but it went on for at least 7 days and was followed by the prophylaxis with LMWH or vitamin K antagonists. The treatment with LMWH (both i.v. or s.c.) lead to recanalisation of the vein in 26 cases (96,29%), 58% of them without any residue or mural thrombosis. We did not notice any bleeding as adverse event of the treatment in our patients.We would like to point out that treatment of DVT with continuous infusion of LMWH in children might be efficient and safe alternative of to s.c. application in certain circumstances. When administered by continuous infusion, LMWH has shorter half-life and it could be useful especially in hospitalized children and in children who are endangered by risk of bleeding complications.
Transplantation without Hemolysis in a Kell Antigen Positive Patient Undergoing Peripheral Hematopoietic Stem Cell Transplant from a Donor with Anti-Kell Antibodies.
Authors: Crawford Regina D. , Krugh David , Blum William , Devine Steven 
Published: April 2020

Abstract
Red blood cell (RBC) antibody formation, with or without hemolysis, is a well known post-transplant complication of ABO and non-ABO mismatched patients and is seen in both solid organ and hematopoietic stem cell transplants (HSCT). Hemolysis secondary to donor lymphocytes transfused during transplant, which produce antibodies directed toward the patient’s remaining red blood cells, is most commonly reported among HSCT donor-recipients with minor ABO blood group mismatching. Passenger Lymphocyte Syndrome (PLS) has been noted to occur in non-ABO group mismatched HSCTs involving the following blood group systems: Rh, Kidd, Lewis, MNS and Duffy. We present a case of a patient with acute myeloid leukemia (AML) in first complete remission who was Kell antigen positive and underwent a non-myeloablative peripheral blood HSCT from a 10/10 HLA matched, related donor who had anti-Kell antibodies. The patient was a 69-year-old male with AML in first remission who consented for transplant with non-myeloablative conditioning on CALGB 100103. At the time of transplantation, the patient was ABO type A positive, had a negative antibody screen, and was positive for the Kell (K1) antigen. The patient had not been transfused RBC or platelets for 4 months prior to HSCT. The related donor was found to be A positive and had anti-Kell that was reactive 1+ at antihuman globulin phase (GEL) prior to filgrastim mobilized peripheral blood HSC collection. The patient received a conditioning regimen of fludarabine 30mg/m2 daily (days -7 to -3) and bulsulfan 0.8mg/kg IV every 6 hours for 8 doses (days -4 to -3). GVHD prophylaxis consisted of methotrexate (5mg/m2) on day +1, +3, and +6 and tacrolimus starting on day -2. After HSCT, no RBC or platelet transfusions were required throughout the patient’s course. Neutrophil and platelet engraftment occurred by day +20. Chimerism studies on peripheral blood[c1] at day +30 revealed 61% donor CD3 T cells, 99% CD14 and CD15, myeloid cells, 90% CD19, B cells, and 96% donor whole blood. Weekly direct antiglobulin tests were performed (day +7 through day +21) with monitoring of hemoglobin, hematocrit, LDH, total and direct bilirbuin, BUN, and creatinine to evaluate for hemolysis. No evidence of hemolysis was seen in the immediate post-transplant period, and the patient’s antibody screen has remained negative to date through day +100. In conclusion, this case demonstrates that peripheral blood HSCT may be done safely in the setting of non-ABO incompatibility due to Kell in the donor-recipient direction. Given the increasing use of non-myeloablative conditioning regimens and peripheral blood HSCT, both of which increase the risk of PLS, the case highlights that the risks of hemolysis for HSCT are evolving and demonstrates the successful implementation of one strategy for monitoring at risk patients.
Coagulopathy from Severe Postpartum Hemorrhage.
Authors: James Andra H. , Paglia Michael , Grotegut Chad , Thames Betty , Gernsheimer Terry 
Published: April 2020

Abstract
OBJECTIVE: The purpose of this study was to estimate the incidence and risk factors associated with coagulopathy from severe postpartum hemorrhage.
STUDY DESIGN: After approval by the Institutional Review Board at Duke University Medical Center, records with the ICD-9 code 666.12 for immediate postpartum hemorrhage were reviewed for the 5-year period from January 1, 2000, to December 31, 2004. Severe postpartum hemorrhage was defined as postpartum hemorrhage requiring transfusion. Coagulopathy from postpartum hemorrhage was defined as severe postpartum hemorrhage requiring factor replacement.
RESULTS: During this period there were 12,476 deliveries. 108 had severe postpartum hemorrhage. 30/108 became coagulopathic. They received a total of 108 units of fresh frozen plasma (FFP) and 12 units of cryoprecipitate (cryo). 28/30 also received 1 to 20 units of packed red blood cells and 5/30 received 1 to 3 units of platelets. All of the women who received cryo had also received FFP. The trigger for administration of factor replacement was clinical (oozing, continued bleeding) in 13/30 cases and a prolonged partial thromboplastin time (PTT) in 17/30 cases. Peak PTTs ranged from 27 to &gt; 150 seconds. Lowest fibrinogen levels ranged from 27 to 580. In 2 cases, however, no fibrinogen levels were obtained. Hemorrhage was attributed to uterine atony in 11/30 cases, placenta accreta in 6/30, lacerations or incisions in 6/30, HELLP syndrome in 2/30, acute fatty liver of pregnancy in 1/30, amniotic fluid embolism in 1/30, fibroids, in 1/30, hemorrhage into an ovarian fibroma in 1/30, and chronic hepatitis B in 1/30. 22/30 cases were associated with cesarean delivery. In 12/30 cases hysterectomy was performed. Hospital length of stay ranged from 2 to 11 days with a mean of 5.4. 9/30 women spent from 1 to 3 days in the ICU. There were no deaths. 2 women had evidence of organ dysfunction from HELLP syndrome or acute fatty liver of pregnancy, but none developed organ dysfunction as a consequence of severe postpartum hemorrhage.
CONCLUSION: 2.4 per 1000 women developed coagulopathy as a result of severe postpartum hemorrhage. They received an average of 4 units of either FFP or cryo. 90% of the units were FFP and 10% were cryo. While 30% of the women required intensive care, all survived with no sequelae.
Dynamin 3 Is Differentially Expressed during Human Megakaryocyte Development.
Authors: Reems Jo Anna , Wang Wenjing , Tsubata Ken , Sundell Birgitta , Gilligan Diana M. 
Published: April 2020

Abstract
We found that expression of dynamin 3 (DNM3) is increased significantly when human CD34+/CD38lo cells are induced to develop along the megakaryocyte (MK) lineage. DNM3 is a member of a family of mechanochemical enzymes which participate in membrane dynamics. Of the 3 family members (DNM1, DNM2 and DNM3), cDNA microarray analysis showed that only DNM3 significantly increased by 9.5±1.8-fold (mean±SEM; p≤0.001). mRNAs for DNM1 and DNM2 were detectable, but their expression levels remained essentially unchanged during MK differentiation. Consistent with our microarray data, real time quantitative RT-PCR confirmed that DNM3 expression levels increased by as much as 20.0±7.3 fold during megakaryocytopoiesis. Western Blot analysis showed that protein expression patterns for each of the 3 dynamins differ in MKs/platelets. DNM3 protein expression levels are greater in MKs than in platelets. DNM1 was not detectable in MKs, but was present in platelets. Although DNM2 protein was detectable in both MKs and platelets, the relative mobility for DNM2 was slightly lower in platelets than MKs. Indirect immunofluorescent microscopy showed that DNM3 was predominantly in the cytoplasm with localization to sites that appear to be regions of pro-platelet formation. The cDNA encoding DNM3 was amplified from culture derived human MKs, cloned and sequenced. Sequence analysis revealed that the cloned product matched a DNM3 transcriptional splice variant in the Ensemble Human GeneView database (i.e. ENST00000367731). Together these results are the first evidence indicating that members of the dynamin family of mechanochemical proteins are present in human MKs and suggest that they may play an important role in MK membrane dynamics.
Continuous Erythroblastosis Is Observed during Early Recovery Period after Allogeneic Umbilical Cord Blood Transplantation.
Authors: Noguchi Mitsuho , Tashiro Haruko , Shirasaki Ryosuke , Gotoh Moritaka , Kawasugi Kazuo , Shirafuji Naoki 
Published: April 2020

Abstract
Objectives: The repopulation characteristics on human hematopoietic cells are crucial for clinical performance after allogeneic hematopoietic stem cell transplantation. We observed and compared the changes of blood cells during the early recovery period after allogeneic HSCT.
Method: The study included patients from 19 to 62 years of age who were admitted to our hospital during Dec. 2000 to Mar. 2005 for the allogeneic HSCT, and in whom no serious complications were observed on transplantation. A total of 25 patients were eligible (10 patients of U-CBT with stable engraftment, 2 patients of U-CBT with no engraftment and autologous recovery thereafter, 8 patients of BMT and 5 patients of PBSCT). All the patients received G-CSF. From day 0 of transplantation, the number of blood cells was calculated mechanically and microscopically, and their morphology was microscopically determined with the stained smear-slide. Five smear slide glasses were made by hand on each of the two days, and the cells were stained with May-Giemsa solution.
Result: Continuous erythroblastosis was observed in all the engrafted U-CBT cases, which was firstly observed between the same days as when blood WBC was increased in number, and five days later (on day 15 on average). Neither correlation of the ABO incompatibilities was observed to erythroblastosis, nor prominent hemolysis was observed. However, in BMT cases and in PBSCT cases, continuous erythroblastosis was observed in a few cases. Neither continuous erythroblastosis was observed in U-CBT cases that showed no engraftment of the transplanted graft.
Discussion: These observations indicate that continuous erythroblastosis during early recovery period is specific for U-CBT, and may reflect the difference in the characters of hematopoietic stem cells.