bluuebunny/crossref_metadata_2025_split huggingface dataset:
Von Willebrand Factor Cleaving Protease (ADAMTS-13) Antigen Levels Are Decreased in Patients with Heparin-Induced Thrombocytopenia.
Authors: Hoppensteadt Debra , Cunanan Josephine , Walenga Jeanine M. , Ero Michael P. , Jeske Walter P. , Bick Rodger , Fareed Jawed 
Published: April 2020

Abstract
Heparin-induced thrombocytopenia (HIT) represents a complex pathologic syndrome including all components of the hemostatic system and inflammatory response. ADAMTS-13 is a metalloprotease which mediates the cleavage of von Willebrand factor (vWF) multimers. A deficiency or decreased activity of this protease may result in a TTP-related syndrome manifested by the development of intravascular platelet aggregates, thrombocytopenia, endothelial dysfunction and the deposition of vWF at thrombotic sites. Several recent reports have described decreased functionality of ADAMTS-13 in patients with HIV. This may be due to antibodies than inhibit ADAMTS-13. HIT is characterized by the generation of heparin-induced anti-heparin platelet factor 4 antibodies which are molecularly and functionally heterogeneous. No data is available on the effect of these antibodies on ADAMTS-13. However, increased vWF levels and the generation of ultrahigh molecular weight vWF multimers have been reported in HIT patients. This study was designed to determine the ADAMTS-13 antigen levels in HIT patient plasma samples (n=30) prior to and after treatment with the direct anti-thrombin agent argatroban (ARG 911 study). Plasma samples from normal healthy volunteers (n=30) were used as controls for comparison purposes. ADAMTS-13 antigen levels were quantitated using a newly developed ELISA method from American Diagnostica (Stamford, CT). vWF antigen levels were also measured using an ELISA-based method. The levels of ADAMTS-13 and vWF antigen were reported as percent normal based on the results obtained with the samples from healthy volunteers. The baseline ADAMTS-13 antigen levels varied widely among the HIT patients enrolled in the ARG 911 trial (30–180% NHP) with a mean of 62 ± 24% NHP. On treatment day 1, no significant changes were noted in the ADAMTS-13 levels in HIT patients. However, on the third and 5th-7th day following initiation of argatroban treatment, ADAMTS-13 levels were increased to 81 ± 6% NHP and 86 ± 24% NHP, respectively. The HIT patient group also exhibited higher levels of vWF antigen at baseline (170 ± 27% NHP) which were marginally decreased following treatment with argatroban. During argatroban treatment, a decrease in anti-heparin platelet factor 4 antibody titer and an improvement in platelet count were noted. These results are highly suggestive of a pathogenic role of vWF multimers in HIT syndrome. Furthermore, a decreased ADAMTS-13 antigen level indicates that its regulation in HIT patients may be altered. Additional results on ADAMTS-13 functionality, ADAMTS-13-factor XI complexes and autoantibodies to the metalloprotease may provide additional insights into the pathogenesis of HIT and the pathologic role of vWF related proteins.
Response to Splenectomy Is Durable after a Certain Point in Time in Adult ITP Patients.
Authors: Johansson Eva , Engervall Per , Landgren Ola , Grimfors (deceased) Gunnar , Widell Susanne , Rezai Shahideh , Bjorkholm Magnus 
Published: April 2020

Abstract
Background. Splenectomy is the recommended treatment in adult patients with immune thrombocytopenic purpura (ITP) who fail to respond to corticosteroid treatment or who require unacceptably high doses to maintain a safe platelet level. For these patients splenectomy may produce a good response in 60–80% of patients. However, the observation time after splenectomy has in most published studies been relatively short. Thus, the true long-term response to splenectomy still remains less well defined. The efficacy and safety of splenectomy were assessed in a cohort of adult ITP patients followed for a very long period of time.
Patients and methods. The study included 59 ITP patients (M/F=25/34, median age at splenectomy; 39 yrs, range 14–75 yrs). The median time from diagnosis to splenectomy was 5.5 mos (range 0.4–199 mos). Criteria used to define response to splenectomy were: CR; platelet count &gt;150 x 109/l lasting ≥4 weeks, PR; platelet count ≥50–150 x 109/l lasting ≥4 weeks and, NR; failure to achieve platelet counts ≥50 x 109/l. The criterion for relapse in CR/PR patients was a decrease in platelet counts to &lt;50 x 109/l.
Results. The median follow-up time after splenectomy was 18 yrs (range 2–32 yrs). No serious surgical complications occurred. The overall response rate was 78% with 59% CR and 19% PR. CR and PR patients were younger than NR patients at time of diagnosis (median age: 36 yrs vs 48 yrs, p=0.03) and at splenectomy (median age: 38 yrs vs 51 yrs, p=0.02). Among the 46 responding patients 17 eventually relapsed. A plateau in the progression free survival curve was identified after 12.1 and 7.3 years for patients in CR or PR, respectively.
Figure Figure
At follow-up, 5 of 17 patients relapsing after splenectomy were in CR. Bacteremia was recorded in two patients during a total of 1023 patient years at risk.
Conclusions
We conclude that splenctomy is an effective and safe treatment in adult patients with chronic ITP failing to respond to corticosteroid treatment. The complication rate was low and our findings support the view that response to splenectomy is durable after a certain point in time.
The Prevalence of Pantoprozole Associated Thrombocytopenia in a Community Hospital - A Retrospective Study.
Authors: Katz Randi , Bratcher Jason , Dotan Efrat , Wasserman Carrie , Liebman Michelene , Reddy Sivakumar , Michael Amy , Arastu Aliasad , Panagopoulos Georgia , Spaccavento Colette 
Published: April 2020

Abstract
Proton Pump Inhibitors (PPIs) are widely used in the treatment of peptic ulcer disease, Helicobacter pylori (H pylori) gastritis and gastro-esophageal reflux disease. PPIs are known to be relatively safe medications, with the most common adverse reactions reported as diarrhea, nausea, vomiting, abdominal pain and headache. Thrombocytopenia has not been found to be a significant side effect of PPI use. Furthermore, successful treatment of H pylori associated immune thrombocytopenic purpura (ITP) with PPI therapy has been reported in the literature. In clinical practice, however, PPI use has been thought to be associated with medication-induced thrombocytopenia, although the precise prevalence of this consequence has not been quantified. The purpose of this study is to determine the prevalence of thrombocytopenia in hospitalized patients treated with pantoprazole, a commonly prescribed PPI, compared to non-medicated controls. In this retrospective, case-controlled analysis, we analyzed the platelet counts of 626 patients between 18 and 80 years of age who were admitted to an urban, community-based hospital and were medicated with pantoprazole for at least three days during their hospital stay. Thrombocytopenia was defined as a drop in the platelet count to below 150,000/ml, or a drop of at least 50% from baseline. Patients who had a platelet count below 150,000/ml on admission or were hospitalized for less than 3 days were excluded from the study. A control group of 560 patients with the same inclusion criteria who had not been prescribed pantoprazole was analyzed for comparison. 626 patients were included in the study group and 560 patients in the control group. The median age was 67 years in study group, and 61 years in the control group. The mean platelet count on admission was 260,00/ml in the study group, and 257,000/ml in the control group. Of the subject group, 39 patients (6.2%) met our definition of thrombocytopenia, which was not statistically different from the 35 patients (6.2%) with thrombocytopenia in the control group (p=0.90). Our study compared patients who received PPI therapy with pantoprazole for at least three hospital days to patients without treatment. We found no difference in the rate of thrombocytopenia between hospitalized patients treated with pantoprazole and the non-medicated controls. The rate of thrombocytopenia that we observed is probably an estimate of the overall thrombocytopenia rate in hospitalized patients irrespective of specific medications. While our report did not control for variables such as concurrent medication use, comorbid illnesses, and patient demographics, we are confident that the sample size selected for this study is large enough to provide sufficient evidence that thrombocytopenia is not a significant side effect of pantoprazole therapy.
Evaluation of Qualitative Platelet Disorders in Patients with Hemophilia.
Authors: Kraut Eric H. , Cataland Spero R. , Witkoff Leslie , Jordan Sylvia , Gunning William T. 
Published: April 2020

Abstract
The hemophilias are inherited disorders of the coagulation system with no apparent effects on primary hemostasis. However, bleeding times and platelet aggregation have been reported as abnormal. These observations have been ascribed to undiagnosed Von Willebrand’s Disease (VWD), effects of factor replacement, or drugs. We evaluated three patients with hemophilia including one patient with factor VIII deficiency, one with factor VIII and inhibitor, and one factor IX who had persistent bleeding despite their standard treatment. Initial evaluation of primary hemostasis demonstrated abnormal bleeding time and or platelet function analysis (PFA-100). VWD antigen and ristocetin cofactor were normal. Electron microscopy demonstrated alpha and or delta granule storage pool deficiency. Careful review of all drugs the patients were on did not explain this finding. Repeat evaluation of one patient over time demonstrated persistence of abnormal function. Treatment with DDAVP(Desmopressin) normalized in vitro function in 2 patients. After documentation of these abnormalities, two patients were treated with DDAVP with or without platelets as well as factor replacement or in face of inhibitors FEIBA or FVIIa. Clinical improvement was seen in the 2 patients after this intervention. A prospective study of our hemophilia population has been initiated with the goal of documenting the frequency of storage pool deficiency, the importance of the disorder to bleeding episodes and treatment response, and to determine whether this is inherited or acquired.
Effect of Erythropoietin on Platelet Function and Glycoprotein Expression in Patients with MDS.
Authors: Girtovitis Fotis F.I. , Bougiouklis Dimitrios D. , Makris Michel M.P. , Pithara Elefteria E. , Makris Pantelis P.E. 
Published: April 2020

Abstract
Aim: We decide to study the effect of erythropoietin on the platelet function and glycoproteins expression in patients (pts) with myelodysplastic syndrome (MDS). All patients suffered from primary MDS but none of them received any special treatment. From our study pts that suffered from diseases or they were receiving medication that affect the function of platelets were excluded. Furthermore pts with platelet count&lt;50,000/μl were excluded also because we were unable to check the aggregation of platelets.
Material: 41 subjects were studied, 15 normal subject (10 men and 5 women mean age 66,6±14 years old)and 26 pts (17 men and 9 women with mean age70,9±7,4 years old) suffered from all types of MDS according to FAB criteria (9 with RA, 3 with RARS, 7 RAEB, 4 with CMML and 3 with RAEB-t). We divided them in 2 groups: 1st - 7 Pts receiving human recombinant erythropoietin (rEPO) with mean dose 30.000 iu subcutaneous weekly and 2nd - 19 without rEPO.
Methods.
1- The platelet function was studied in Platelet Ionized Calcium Aggregometer (PICA) using Ristocetin, ADP, Collagen and Adrenalin as stimulators.
2- The expression of platelet glycoproteins (GPIb, IX, IIb, IIIa and P-selectin) was studied using the flow cytometry and special monoclonal antibodies.
This way the percentage of glycoprotein expressed in platelet membrane and MFI were estimated. We performed the statistical analysis of our results using the t-test with common standard deviation..
Results: our results concerning the aggregation test and flow cytometry are presented in tables 1,2 and 3. From the study of our results we can see that
while the decrease of aggregation between the patients under EPO and normal subjects is statistically non significant (p&lt;0.1)the decrease of the corresponding values between the pts that did not received EPO and normal subjects was statistically very significant for all stimulators (p &lt;0,001). pts under EPO show an important increase of platelet expressing GPIIb percentage grater than the expressed percentage of patients without EPO (60% vs. 46,1% correspondingly, p&lt;0.001). The difference of expressed MFI was not statistically significant.
Conclusion: The findings of our study show us that erythropoietin improves the function of platelets in patients with MDS, probably through the increase of platelet percentage which express glycoproteins.
Table 1 Comparison of the mean value of aggregation between the groups Table 2 Comparison of the mean values of the platelets expressing corresponding glycoproteins percentage between the groups Table 3 Comparison of the mean value of MFI between the groups
Hereditary αδ-Storage Pool Deficiency with the Abnormal Structures of the Platelet Microtubules.
Authors: Miyazaki Koji , Kawakami Hayato , Higashihara Masaaki 
Published: April 2020

Abstract
The case is a 27-year-old man, who referred to us presenting the mild bleeding tendency after extraction of a tooth. Bleeding time was 3 minutes by the Duke method, and his platelet count was slightly decreased (7x10 10 /l). His mother also has the similar platelet abnormality. They have no albinism. The peripheral smear demonstrated the abnormal platelet morphology with hypo or agranular and large forms. Almost normal platelets were also present on the smear. A platelet adhesion test showed the impaired collagen adhesion. A platelet aggregation study revealed the abnormally poor responses to adenosine diphosphate, collagen, arachidonate, U-46619, and a relatively retained response to ristocetin. Electron microscopy of the platelets demonstrated 2 populations: one with almost normal distribution of the granules, the other with marked decrease in both α and dense granules, even though the former population had the abnormal granules and the obvious vacuoles in the platelets. Flow cytometry revealed the reduced Mepacrine positive platelets and the decreased surface CD62P induced with phorbor ester in the patient. The patient platelets contained the reduced concentration of both adenosine triphosphate and serotonin, compared with the normal control. The cytoskeleton structures were examined with immunocytochemistry using the specific antibodies. Most platelets of the patient lost the typical coiled marginal bands and showed the yarnball-like structures of the microtubules, although the actin microfilaments were relatively retained. In other words, the platelets even with the almost normal distribution of the granules have a disturbed tubulin organization, which were not apparent in the leukocytes. These results suggested that some platelet-specific proteins, such as β1 tubulin, involved in the formation of the microtubules could be causative for this hereditary storage pool deficiency.
The Comparative Analysis of Serum Proteomes for the Discovery of Biomarkers for Essential Thrombocythemia.
Authors: Kwak Jae-Yong , Lee Na-Ri , Song Eun-Kee , Yim Chang-Yeol , Kwak Yong-Geun 
Published: April 2020

Abstract
Background: Essential thrombocythemia(ET) is a clonal disorder involving a hematopoietic progenitor cell and is manifested by the overproduction of platelets. There is as yet no pathognomonic diagnostic test. In our study, to identify the biomarkers for an initial diagnosis by a lesser invasive method, serum proteins reflecting alteration their proteomes were analysed.
Methods: We compared two-dimensional electrophoresis patterns of human sera of twelve patients with ET with that of normal twelve subjects. The differentially expressed spots were identified by matrix-assisted laser desorption/ionization-time-of flight(MALDI-TOF) and electrospray ionization quadupole time of flight(ESI-Q-TOF)mass spectrometry.
Results: Twenty two spots that expressed differentially in ET group were found. The expression levels of fibrinogen γ, fibrinogen γ-A chain precursor, ALB protein, α-2 macroglobulin, H factor-1, α-2-macroglobulin precursor, ceruloplasmin, α-1-B-glycoprotein, α-2-plasmin inhibitor, α-1-B-glycoprotein and an unknown protein were up-regulated in serum of ET patients, whereas the other proteins including complement fator B preproprotein, afamin precursor, inter-α inhibitor H4, immunoglobulin heavy chain constant region γ 1, immunoglobulin κ light chain and an unknown protein down-regulated.
Conclusion: These results suggest that these proteins can be used as less invasive diagnostic and follow-up biomarkers of ET if further studies were done.
The proteins significantly changed in sera of ET Spot no. Name Accession no. % coverage Mw(KDa)/pI(Measured) Mw(KDa)/pI(database) ET(%) 67 fibrinogen γ 223170 39 50.57/5.6 46.82/5.5 2.54±0.52 69 ” 223170 33 50.57/5.6 46.83/5.5 3.93±1.19 73 fibrinogen γ-A chain precursor 71827 23 48.93/5.6 50.11/5.7 3.89±0.98 74 ” 71827 22 48.93/5.8 50.11/5.7 3.10±0.91 77 ALB protein 27692693 21 50.57/5.9 48.65/6.0 3.77±0.58 89 α-2-macroglobulin 177872 14 263.89/6.1 71.35/5.5 1.95±0.32 100 H factor 1 4504875 20 248.95/5.7 143.79/6.3 5.8±1.78 112 α-2-macroglobulin precursor 4557225 9 151.38/5.7 164.69/6.0 2.18±0.38 125 complement factor B preproprotein 4502397 14 151.38/5.7 86.86/6.6 0.49±0.07 138 afamin precursor 4501987 12 65.01/5.1 85.53/6.3 0.31±0.07 139 ” 4501987 12 65.01/5.1 85.53/6.3 0.36±0.09 140 inter- α inhibitor H4 31542984 12 93.33/5.3 103.57/6.5 0.36±0.08 154 ceruloplasmin 4557485 8 132.89/5.3 123.04/5.4 3.34±0.80 161 α-1-B-glycoprotein 69990 21 84.50/5.0 52.49/5.6 4.23±0.98 162 α-2-plasmin inhibitor 11386143 14 78.58/5.0 54.92/5.8 1.95±0.38 167 α-1-B-glycoprotein 69990 28 80.87/5.3 52.49/5.6 1.73±0.04 210 Not identified - - 38.47/4.6 - 2.77±0.20 249 immunoglobulin heavy chain constant regionγ 1 12054072 15 39.021/8.1 36.65/8.8 0.40±0.09 250 ” 12054072 18 38.79/8.2 36.65/8.8 0.34±0.14 252 ” 12054072 19 38.50/8.3 36.65/8.8 0.37±0.09 262 unknown 15679996 36 24.73/8.2 23.32/8.6 0.30±0.13 265 immunoglobulinκ light chain 2765423 22 25.75/8.8 25.93/9.2 0.28±0.12 Figure Figure
Rituximab in Three Cases of Refractory Thrombotic Thrombocytopenic Purpura.
Authors: Alcaraz Jesus , González-García Consuelo , Majado Maria Juliana , Pérez Raul , Molina José A. , Tamayo Manuel , Moreno Manuel , Morales Alfonso 
Published: April 2020

Abstract
Thrombotic Thrombocytopenic Purpura (TTP) etiology remains elusive, recently has been associated with von-Willebrand Factor-cleavage protein inhibitory antibodies. Plasma exchange (PE) remains the gold standard therapy, however there are some cases resistant to it. Rituximab has been proved useful in antibody mediated immune disorders. We report our experience in 3 consecutive TTP patients, refractory to PE and successfully treated with Rituximab 375 mg/m2 weekly x 6.
Case 1. A 41 years old female diagnosed with Hasimoto thyroiditis 4 years before. In January 2003 she was admitted to hospital with headache, abnormal behaviour, 16x109/L platelets and 4–5% schistocytes. 47 PE sessions with a total of 235 fresh frozen plasma units (FFP) for replacement were made. Corticosteroids, IVIG and vincristine were added, but no improvement was achieved. Then, Rituximab was administered, after the second dose a complete clinical response was attained, and she remains well by now.
Case 2. A 21 years old female was into hospital in October 2003 with bruises, paraesthesia, skin pallor and jaundice. Hb 6.5 g/dL, platelets 4.6x109/L, LDH 1223 U/L and 13% schistocytes. She received 24 PE with 96 FFP units, plus corticosteroids and vincristine, with no response. Rituximab was administered, after the third dose she experienced a complete response, and remains stable since then.
Case 3. female, 35, she was into hospital in January 2005 with diarrhoea, vomiting, jaundice, seizures and bruises, Hb 4.5 g/dL, platelets 10x109/L, LDH 2486 U/L and 20% schistocytes. She received 43 PE with 129 FFP units and corticosteroids, but her neurological situation worsened. Rituximab was administered, after the first dose she experienced a complete response which maintains nowadays
Conclusions: intense PE remains the gold standard therapy, it is expensive, scarce, and not free of secondary effects. In a group of patients refractory to PE Rituximab is emerging as useful safe option, it was very well tolerated in ours cases. Unfortunately, we were not able to test the vWF-CP activity and its inhibitor. Our results encourage us to use Rituximab earlier than the first case, in order to avoid too much PE, and now we are considering Rituximab as a second option in patients refractory to PE, but much more cases must be considered.
Evaluation of Platelets Obtained from Premature Neonates To Determine Whether Platelet Dysfunction Mediates the Development of Intraventricular Hemorrhage.
Authors: McCarthy Sean T. , Stein Howard , Stein Dagmar , Ohler Sue , Lachant Neil A. , Gunning William T. 
Published: April 2020

Abstract
Hemorrhagic complications occur in neonates, including intraventricular hemorrhage (IVH) in premature babies. The premature infant appears to be at greatest risk for a head bleed from days 2–3 until day 7 after birth. A relationship exists that suggests that the shorter the gestation, the greater the risk for this potentially fatal hemorrhagic event. The basis of intra-ventricular brain hemorrhage (IVH) in the premature infant is unknown. Premature birth is not necessarily the cause of IVH. The neonate is known to have a transient platelet dysfunction at the time of birth. Studies to define the transient platelet dysfunction in the neonate have been limited. Explanations in the literature include:
a diminished response to physiologic agonists, defective platelet (PL) dense granule (DG) secretion, and/or ineffective mobilization of intracellular calcium in platelets.
We and others have found that the adenine nucleotide content of platelets obtained from umbilical cord blood is significantly less than seen in adults. We have found that platelets obtained from umbilical cord blood have an average of 0.79±0.08 DG/PL (n=62), which is significantly decreased compared to the adult population (4–6 DG/PL) (Blood, 100(11):691a, 2002). Although the concentration of ADP and ATP were found to be decreased compared to normal adult platelets, the ATP/ADP ratio in neonatal platelets is 1.95 (n=61), consistent with established adult normal range ratio values (1.4–1.95). The current studies are ultimately intended to evaluate infants that have survived severe IVH for platelet dysfunction due to platelet dense granule deficiency (δ-SPD). Preliminary data have been obtained on peripheral blood from premature infants (n=15) obtained 3–5 d after birth. Their values (mean±2sd) are: gestational age 31±4.8 weeks and wt 1506±474 gr. The DG number (1.01±0.16/PL) is significantly decreased compared to normal adults, while the ATP (3.19±0.36 μM/1011 PL), ADP (2.63±0.54 μM/1011 PL) and ATP/ADP ratio (1.46±0.13) are normal. The decreased DG number in premature PL is strikingly similar to the DG content in cord blood PLs. We have studied one infant’s cord blood (2.41 DG/PL)and day 1 peripheral blood (3.87 DG/PL). The parents have had a normal DG number and adenine nucleotide content. These results would suggest that the premature infant platelets may have an incomplete incorporation of calcium into the dense granules 3–5 days after birth when compared to the normal adenine nucleotide content. A decrease in DG calcium would explain the decreased numbers of DGs calculated from whole mounted PLs by EM. Calcium is electron dense and if lacking in DGs, would result in an artificially low number of DGs determined by this method. To date, we have not obtained blood from a premature infant with a significant IVH or its parents to evaluate δ-SPD as a potential etiology of severe IVH.