bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantification Of Malondialdehyde Adducts In Platelet Activation As An Indicator Of Proinflammatory and Prothombotic State
Authors: Zagol-Ikapite Irene , Sosa Iberia Romina , Judd Audra M , Boutaud Olivier , Oates John A 
Published: October 2019

Background
The formation of malondialdehyde (MDA) has been previously described as a product of the thromboxane synthase. However, the reported approaches for its quantification have not been reliable, stymieing its use in research. As a reactive di-carbonyl, MDA reacts with primary amines, notably lysines on proteins, to form covalent adducts of several types. Three of the products of the reaction of MDA with lysine are an N-propenal adduct, a dihydropyridine ring adduct (N-lysyl-4-methyl-2, 6-dihydropyridine-3, 5-dicarbaldehyde), and a lysyl-MDA crosslink. Measurement of platelet protein modifications, such as MDA adducts, could provide a specific marker of in vivo activation of platelets, since these modifications accumulate over the lifespan of the platelet.

Methods and Results
To investigate thromboxane synthase-dependent formation of MDA adducts on platelet proteins, we developed an LC/MS/MS method for analysis of one of the MDA adducts, the lysyl-MDA crosslink, employing a [13C12] labeled internal standard. We demonstrated that levels of lysyl-MDA crosslink in human platelets are increased following its activation with arachidonic acid. This increase is inhibited by aspirin, the thromboxane synthase inhibitor, ozagrel and by γ-ketoaldehyde specific scavengers: 3-Methoxysalicylamine (3-MOSA) and Salicylamine (SA). To determine whether lysyl-MDA crosslinks reflect in vivo platelet activation, we analyzed samples from patients with medical conditions known to be associated with increased platelet activation. We employed traditional methods of measuring platelet activation: flow cytometry of p-selectin and reticulated platelets, and serum thromboxane, to measure platelet activation in patients with metabolic syndrome and sickle cell disease. These assays were compared with the levels of lysyl-MDA-crosslinks. In both populations, the levels of MDA-lysine-crosslink are increased by 2.5 fold compared to healthy volunteers and provide greater discrimination between groups than p-selectin expression and reticulated platelets. The inhibition of the lysyl-MDA crosslink adduct in patients taking NSAIDs further confirms the specificity for thromboxane synthase-dependent MDA modifications on platelet proteins.

Discussion
The results of this study provide compelling evidence that MDA-protein adducts in platelets may be a useful marker of in vivo platelet activation in humans and potentially helpful in predicting thrombotic risk and the benefit of antiplatelet therapy in patients with medical conditions associated with platelet hyperactivity.

Disclosures:
No relevant conflicts of interest to declare.
Platelet Delta Storage Pool Deficiency In Children : A Case Series
Authors: Abraham Shirley M. , Boayue Koh , Ahmed Ibrahim 
Published: October 2019

Introduction
Delta storage pool deficiency (δ-SPD) is a rare group of platelet disorders characterized by a reduction in the number or content of dense granules. δ-SPD causes a mild to moderate bleeding diathesis characterized mainly by mucocutaneous bleeding. A suspected case of δ-SPD can be diagnosed by the patient’s presentation, a family history and suggestive clinical bleeding or preliminary laboratory results such as a typical platelet aggregation pattern, characterized by normal aggregation with ristocetin and lack of second wave of aggregation with ADP or epinephrine. However not all patients have a typical presentation. This is a review of 6 pediatric patients with δ-SPD at our institution.

Results
We have 3 male and 3 female children with a confirmed diagnosis of δ-SPD. Their current age ranges from 19 months-17 years. Four of the 6 patients are Hispanic and 2 Caucasian. A positive family history of excessive bleeding was obtained in 4 patients. The youngest patient was 2 weeks at diagnosis. Epistaxis was the most common presenting symptom. The youngest patients in the group presented with subdural hematomas before the age of 2. The 17 year old presented with significant menorrhagia and anemia, requiring red cells and platelet transfusions in addition to antifibrinolytic agents and oral contraceptives.
The preliminary work up in all patients included a CBC, PT, PTT and platelet function analysis (PFA).PFA was reported as abnormal in only 1 patient and was not accurate in another patient due to platelet clumping. Platelet aggregation studies and Von Willebrand’s panel were done and reported as normal in 5 patients. Platelet count ranged from 248,000- 552,000/mm3. Electron microscopy ranged from 1.69-3.59 dense granule/platelet (normal 4-6 dense granule/platelet).
All of the patients were primarily managed by preventive measures and antifibrinolytic agents. Platelet transfusions have been reserved for life threatening bleeds or surgical procedures.

Conclusions
The presentation of this rare bleeding disorder is not limited to mucocutaneous bleeding. Presenting symptoms in the very young could be limited to an intracranial hemorrhage. Electron microscopy to diagnose this condition should be pursued despite normal platelet function and aggregation studies, especially in patients with a high index of suspicion based on their clinical presentation or family history.

Disclosures:
No relevant conflicts of interest to declare.
Anti-Rh(D) Utilization Prior To and Following The FDA Mandate For Hemoglobinuria Screening 03/11/10
Authors: Varma Mala , Melinscak Hrvoje , Shapira Ilan , Sara Gabriel , Grossbard Michael L. 
Published: October 2019

Background
Anti-Rh(D) has appeal for use in immune thrombocytopenia (ITP) due its rapid onset of action (24 hours) and short infusion time (10 minutes). There is reluctance by some physicians to use anti-Rh(D), however, following FDA reports in 2000 of 15 cases of acute hemoglobinemia and/or hemoglobinuria (Gaines Blood 2000) and in 2005 of 6 cases of disseminated intravascular coagulation in association with acute hemoglobinemia and/or hemoglobinuria (Gaines Blood 2005). On 03/11/10, the FDA issued a black box warning stating that patients with ITP treated with WinRho (anti-Rh(D)) should be monitored in a healthcare setting for 8 hours following infusion for symptoms of intravascular hemolysis and for hemoglobinuria. Our institution adopted this 8-hour monitoring practice.

Specific Aims
To determine if the FDA black box warning has impacted on anti-Rh(D) utilization at St. Luke's-Roosevelt Hospital Center, New York, NY.

Methods
Institutional Review Board approval was obtained. The charts of consecutive patients with ITP treated with anti-Rh(D) who were followed in a hematology-oncology practice between 01/01/06 and 06/30/13 were reviewed. The ICD-9 code 287.31 for ITP was used to identify inpatients treated with anti-Rh(D) between 01/01/06 and 06/30/13. The number of outpatient and inpatient anti-Rh(D) infusions per annum was computed.

Results
The annual number of outpatient and inpatient anti-Rh(D) infusions is shown in Table 1. Infusions occurred predominantly in the outpatient setting. Eight-hour monitoring has been adhered to. While there has been some fluctuation in anti-Rh(D) utilization, there has not been a significant decline.

Conclusion
Despite the FDA requirement for patients to spend increased time at health care centers following anti-Rh(D) infusions, anti-Rh(D) utilization at our institution has not declined.

Disclosures:
No relevant conflicts of interest to declare.
The PAI-I Gene 4G/5G Polymorphism and Central Nervous System Bleeding In Factor XIII Deficiency
Authors: Naderi Majid , Dorgalaleh Akbar , Alizadeh Shaban , Tabibian Shadi , Taregh Bamedi , Karimi Mehran 
Published: October 2019

Background
FXIII deficiency is one of the rare bleeding disorder (RBD) that has a highest incidence in Sistan and Baluchistan province around the world. This disorder represents with different clinical manifestations ranging from mild to severe bleeding tendency including CNS bleeding. The aim of this study is to evaluate the role of PAI-14G/5Gpolymorphism in central nervous bleeding (intra and extracranial hemorrhage) system in factor XIII deficiency.

Methods
In this case control study was studied 32 FXIII deficient patients with CNS bleeding and also 32 patients with factor XIII deficiency without history of CNS bleeding as control group. Initially both groups were evaluated for the previously reported polymorphism of factor XIII (Trp187Argpolymorphism) in order to confirm their disorder. Then all patients were assessed for PAI-14G/5G polymorphism. Eventually obtained data was analyzed by SPSS software.

Results
The result of this study revealed that all study patients were homozygote for Trp187Arg polymorphism. We also found that the equal numbers of patients (4 individuals) in case and control groups were heterozygote for PAI-14G/5G polymorphism and none of patients were homozygote for this polymorphism. All heterozygote patients had intracranial hemorrhage and patients with extracranial hemorrhage had no mutation of PAI-14G/5G. Intraparenchymal was the most common site of hemorrhage and was observed in 26 patients (92.8%).We also observed subdural and epidural hemorrhage in two patients (7.1%).Anatomic regions in patients with intraparenchymal hemorrhage, were temporal in nine (32.2%), occipital in eight (28.6%), diffused intraparenchymal hemorrhage in seven (25%), tempro-occipital in two (7.1%) and subdural with temporal in two (7.1%) patients. Conclusion: It seems that PAI-14G/5G polymorphism did not any effect on occurrence of intra and extracranial hemorrhage in patients with factor XIII deficiency.

Disclosures:
No relevant conflicts of interest to declare.
Is a Standardized Preoperative Questionnaire a Good Tool To Detected Coagulation Disorders In Children
Authors: Halimeh Susan , Rott Hannelore , Kappert Guenther , Siebert Manuela 
Published: October 2019

Introduction
In our study 144 children were send to our coagulation centre with a positive anamnesis (such as haematomas or nose bleeding’s) a positive family anamnesis (p.e. Mother with Menorrhagie) or a prolonged aPTT during a standardized preoperative examination.

Samples and Methods
We analyzed samples of 144 children by conduction the following tests: Blood count, VWF:RCo, VWF:Ag, VWF:CB, Fibrinogen (Clauss), activities of FII, FV, FVII, FVIII (clotting and chromogenic), FIX, FX, FXI, FXII, FXIII.

Results
In 107 of 144 children (74.3%) a bleeding disorder could be detected. In those with a bleeding disorder the distribution was as followed: 23.6% had a von Willebrand disease, 27.8% had a prolonged bleeding time and 5.6% a factor XIII-deficiency. The remaining 43% hat other bleeding.
disorders (e.g. FVIII-deficiency, FVII-deficiency and other mild factor deficiencies).

Discussion
A standardized preoperative questionnaire can be useful in clinical practice. In our study 74.3% children with one or more positive evidence in the anamnesis suffer from a bleeding disorder. It is specifically noticeable that we found in 68% of the children which mother has a menorrhagia a bleeding disorder. In 31.8% of the children we found a von Willebrand disease.
In our more coagulation disorders could be detected if a standardized preoperative questionnaire would be used and if we pay more attention to children with would a mothers with menorrhagia.

Conclusions
Children from mothers with menorrhagia suffer more frequently from a bleeding disorder. In our patients in 75% of the children with a mother with menorrhagia a bleeding disorder was found.
To avoid an unexpected bleeding during a planned surgery or a postoperative bleeding a standardized preoperative questionnaire should be performed.

Disclosures:
Halimeh: Octapharma AG: Investigator Other, Research Funding.
Dose Adjustment Of Low Molecular Weight Heparins (LMWH) Improves Pregnancy Outcome In Thrombophilic Women
Authors: Catania Gioacchino , Pini Massimo , Laura Contino , Flavia Salvi 
Published: October 2019

Introduction
Acquired and inherited thrombophilias are associated with unfavourable pregnancy outcome. Low-molecular-weight heparin (LMWH) has demonstrated utility in the prevention and treatment of thrombosis during the pregnancy. There is no consensus on the dose of LMWH for prophylaxis, between fixed dose and “adjusted” dose according to anti-Xa levels.
We report our experience the management of heparin-therapy during pregnancy in thrombophilic women.

Methods
We performed a retrospective analysis of patients with high risk of venous thromboembolism (VTE) and obstetric complications during pregnancy. Table 1 shows the risk factors of VTE in pregnancy. The obstetric complications considered were: preeclampsia, fetal growth restriction, fetal death and recurrent miscarriages. All patients were prescribed enoxaparin 70-100 IU /Kg SC once daily. To determine the dose of LMWH we evaluated levels of anti-factor Xa (chromogenic test) and the utero-placental circulation with color Doppler ultrasound. Dose adjustment was performed if the activity of factor Xa was suboptimal (prophylaxis range > 0.4IU/ml and < 0.8 IU/ml anti-Xa value) or were detected alteration in the utero-placental circulation.

Outcome Measures
Time of delivery, birth weights and Apgar-index.

Results
70 pregnancies for 68 women were recruited between January 2008 and December 2012. The median age of patients was 35 years (range 25- 43years) and 7 (10%) were over 40. Twenty-four patients had a previous VTE and thirty-six had an obstetric complications.
No one patients reported thrombotic and/or hemorrhagic complications during heparin treatment. In 97 % of cases the time of delivery occurred after 36th weeks of pregnancy, with a birth weight greater than 2600 grams and Apgar score index higher than 7.
The dose of LMWH had to be adjusted at least once during the course of the pregnancy and the mean daily dose was increased from 4.000UI to 8.000UI between the 12th and 32th week of gestation.

Conclusion
In pregnancy LMWH thromboprophylaxis enables the modulation of systemic haemostatic parameters by the inhibition of factor Xa and by increasing TFPI levels. In the literature-in some high risk pregnancy- the weight-based dosing of LMWH could seem to fail achieving a prophylactic anticoagulation.
In our experience adjusted doses prevent unfavourable events and improve fetal growth.
°Carriage of defects of antithrombin, protein C or S, factor V Leiden, G20210A prothrombin mutation, antiphospholipid syndrom

Disclosures:
No relevant conflicts of interest to declare.
Venous Thromboembolism (VTE) In Patients With Pancreatic Cancer
Authors: Kim Kyoung Ha , Yoon Seug Yun , Yoon Jina , Kim Han Jo , Kim Se Hyung , Kim Hyun Jung , Lee Sang-Cheol , Bae Sang Byung , Kim Chan-Kyu , Lee Namsu , Park Sung Kyu , Won Jong-Ho , Hong Dae Sik , Park Hee Sook 
Published: October 2019

Background
Venous thromboembolism (VTE) is a critical complication of malignant disease. Pancreatic cancer is one of the cancers most commonly associated VTE. In general, the VTE incidence rate of Asians is lower than that of Caucasians. In 2007, a Korean study reported that only four cases of VTE (5.3%) occurred in Seventy five patients with advanced pancreatic adenocarcinoma. We evaluated VTE incidence in pancreatic cancer and characteristics of pancreatic cancer patients with VTE.
(We found out that VTE incidence rate among Asians was not lower, and the event of VTE was poor prognosis.)

Method
We retrospectively reviewed the medical records of patients with histopathologically proven pancreatic cancer from January 2006 to December 2012 at Soonchunhyang university hospital. We detected VTE through CT (chest CT, pulmonary embolism CT) and low extremity ultrasoundgraphy.

Results
Five hundred and fourteen patients with pancreatic adenocarcinoma were enrolled. (M: F, 300:214, localized: locally advanced: metastatic=31:230:253, mean age: 66.7 years). Ninety six of 514 patients (18.6%, symptomatic: aymptomatic=38:58, PE: DVT: PE+DVT: visceral thrombosis=20:19:19:38) were diagnosed as VTE. At the time of DVT diagnosis, cancer status of 50 patients cancer was progression, and that of 15 was stable. Thirty one patients were diagnosed with the pancreatic cancer and VTE, at the same time. They all had metastatic lesions. Fifty VTE patients were treated with antithrombotic therapy. Ninety three of 96 patients died, and three of them have probability that cause of death was VTE. The others died of pancreatic cancer progression. From pancreatic cancer diagnosis to VTE diagnosis, the period is 1.7month. (95%CI 1.1-2.3 month). Median overall survival (OS) was not significantly different between pancreatic cancer with VTE or without VTE. OS was significantly longer VTE patients after pancreatic cancer diagnosis than VTE patients with pancreatic cancer at the same time (10.73m vs. 1.7, p=0.00).

Conclusion
The incidence of VTE (18.6%) in Soonchunhyang university hospital with pancreatic cancer was not lower than that in western groups.

Disclosures:
No relevant conflicts of interest to declare.
Elevated Factor VIII Activity In Patients With Hypercoagulability Syndrome
Authors: Gonzalez F. , Paredes Hanrry J 
Published: October 2019

Patients with hypercoagulability syndrome can have a wide variety of risk factors that predispose them to develop a thrombotic event. Factor VIII increased levels has been reported as one of these. In this retrospective study we report the frequency of increased levels of factor VIII activity found in patients referred for hypercoagulability assessment to our reference center.

Material and methods
Review of clinical and laboratory database of patients referred for hypercoagulability assessment. Results are presented as percentages.

Results
Of 323 patients with hypercoagulability syndrome, 98 (30.3%) had increased levels of Factor VIII activity, male-female ratio 1:1.8, mean age 49.8 ± 15 y-o. Sixty (61.2%) patients had a venous thrombotic event and 73.3% of them had recurrence. Ten (10.2%) had an arterial thrombotic event and 23 a combined arterial and venous thrombosis with recurrent episodes of 70.0 and 82.6% respectively. Five patients had no clotting events. Thrombosis in unusual sites was found in 22 patients.

Conclusion
Increased levels of Factor VIII activity are found in 30.3 % of patients with hypercoagulability syndromes, almost two thirds develop a venous thrombotic event and recurrences occur in 75.3%.

Disclosures:
No relevant conflicts of interest to declare.
Thrombosis and Acute Myeloid Leukemia In Morocco: Management, Difficulties and Adapted Guidelines
Authors: Anoun Soumaya , Lamchahab Mouna , Moussali Nadia , Oukkache Bouchra , Benchekroun Said , Quessar Asmaa 
Published: October 2019

Background
Thromboembolism is a well-known fatal complication of malignancies. Acute lymphoid leukaemia and non-Hodgkin lymphomas are the most common haematological malignancies associated to thrombosis. The management of thrombosis involve anticoagulant treatment which is difficult to administrate in thrombocytopenic patients especially in conditions where supportive care by platelet transfusion is not well developed, and the cost of low molecular weight heparin is high comparing to population monthly income.
Our aim is to define the incidence of thrombosis in AML patients, to relate difficulties of anticoagulant management and to develop adapted guidelines for the use of anticoagulation in developing countries.

Patients and methods
We conducted a retrospective study on 1000 patients with newly diagnosed AML admitted to our institution from January 2003 to June 2013. Diagnosis of AML was essentially based on French–American–British (FAB) guidelines. Moreover, diagnosis of acute promyelocytic leukemia (APL) was confirmed by karyotype. Deep venous thrombosis (DVT) was confirmed by Doppler ultrasonography and cerebral thrombosis (CT) was confirmed by angio cerebral MRI. The thrombosis scoring was according to Khorana and well scores. Patients started chemotherapy induction treatment as soon as diagnosed and anticoagulation treatment was initiated when the patient was stable. Platelet transfusions were given when platelet count became less than 10 G/L, or 20G/ L in the case of fever or bleeding. Were included in the study all patients with inaugural thrombosis at diagnosis. And were excluded all secondary thrombosis (catheter related thrombosis. etc.)

Results
Only five cases of inaugural thrombosis were collected in our series. The incidence of thrombosis is 0.5/ 100 cases /year. Thrombosis is well misdiagnosed in our conditions. The mean age was 40 years (range 28-48 years). Sex ratio showed male predominance. The mean platelet count (Plt) at diagnosis was at 36.6 G/l (range 4- 98 G/l). Hyperleucocytosis was seen in two cases with a mean of white blood count (WBC) of 21.6 G/l (range 1- 82 G/l). One patient was diagnosed as APL. Wells score was less than three in all patients. Khorana score classed all patients in low or intermediate risk. Four patients had DVT and one patient complained from CT. The time from thrombosis to anticoagulant treatment ranged from 1 day to 3 days. Two patients were treated by LMWH and died (one from pulmonary embolism). The three others were treated by unfractionated heparin (UNH) and achieved complete remission (CR). (Table).

Conclusion
UNH is the best adapted treatment of thrombosis in developing countries AML patients. Supportive care by platelet transfusion twice a day stays the best way to well manage AML and anticoagulant complications by keeping platelet count more than 50G/l.

Disclosures:
No relevant conflicts of interest to declare.