[Newborn with phocomelia and thrombocytopenia. Case report].

PubMed

Maas, C; Arand, J; Orlikowsky, Th; Goelz, R

2002-01-01

Associated malformations and symptoms may be decisive in the differential diagnosis of neonatal phocomelia. We report on a neonate with phocomelia, petechiae and thrombocytopenia. This constellation is typical for the phocomelia-thrombocytopenia-syndrome, a variant of the thrombocytopenia-absent radius-(TAR) syndrome. During the neonatal period platelet transfusions were necessary. Relevant bleeding and development delays were not evident until the age of seven months. Cardinal symptoms of the TAR syndrome are bilaterally absent radius and neonatal thrombocytopenia. The patient presented with phocomelia of the upper extremities which occurs in only 5 - 10 % of the patients with TAR syndrome. Further abnormalities include additional bone and joint disorders and haematopoietic problems, such as thrombocytopenia. Bleeding episodes mainly occur in the first year of life, hence platelet transfusions may be necessary during this period. A new experimental approach is the Interleukin-6-mediated stimulation of thrombopoiesis. Usually platelet counts reach normal values in adults. The main problem remains a satisfactory management of various limb defects.

Thrombocytopenia in Small for Gestational Age Infants

PubMed Central

Christensen, Robert D.; Baer, Vickie L.; Henry, Erick; Snow, Gregory L.; Butler, Allison; Sola-Visner, Martha C.

2016-01-01

BACKGROUND Thrombocytopenia is common among small for gestational age neonates (SGA; birth weight <10th % reference range) but several aspects of this thrombocytopenia are unclear, including the incidence, typical nadir, duration, association with preeclampsia, mechanism, and risk of death. METHODS Using nine years of multihospital records we studied SGA neonates with ≥2 platelet counts <150,000/μL in their first week. RESULTS We found first-week thrombocytopenia in 31% (905 of 2891) of SGA neonates vs. 10% of non-SGA matched-controls (p<0.0001). One hundred-two of the 905 had a recognized cause of thrombocytopenia (DIC, early-onset sepsis, ECMO). This group had a 65% mortality rate. The remaining 803 did not have an obvious cause for their thrombocytopenia. We termed these the “thrombocytopenia of SGA”. They had a mortality rate of 2% (p<0.0001) and a mean nadir count on day 4 of 93,000/μL (standard deviation, 51,580/μL, 10th % 50,000/μL, 90th % 175,000/μL). By day 14, platelet counts were ≥150,000/μL in >half of the patients. Severely SGA neonates (<1st %) had lower counts and longer thrombocytopenia duration (p<0.001). High nucleated red cell counts at birth correlated with low platelets (p<0.0001). Platelet transfusions were given to 23% and counts typically >tripled. Thrombocytopenia was associated with SGA status more so than with the diagnosis of maternal preeclampsia. CONCLUSIONS SGA neonates with clearly recognized varieties of thrombocytopenia have a high mortality rate. In contrast the “thrombocytopenia of SGA” is a hyporegenerative condition of moderate severity and two weeks duration, associated with evidence of intrauterine hypoxia, and associated with a low mortality rate. PMID:26216323

Two cases of maternal alloimmunization against human neutrophil alloantigen-4b, one causing severe alloimmune neonatal neutropenia.

PubMed

Curtis, Brian R; Roman, Ashley S; Sullivan, Mia J; Raven, Cindy S; Larison, Judy; Weitekamp, Lee Ann

2016-01-01

Human neutrophil antigen (HNA)-4a/4bw is encoded by 230G>A in ITGAM, which results in an Arg61His substitution of the αM chain (CD11b) of complement receptor 3 (CR3; CD11b/18 or Mac-1). HNA-4a antibodies have been detected in the sera of female blood donors and in maternal sera that caused alloimmune neonatal neutropenia (ANN), in which maternal immunoglobulin (Ig)G antibodies against a paternally inherited HNA cross the placenta and destroy fetal and neonatal neutrophils. However, to date, antibodies specific for HNA-4b have not been reported. Here, we report the first two examples of HNA-4b antibodies. The two sera studied were both from previously pregnant females, one a multiparous female blood donor implicated in two separate transfusion reactions and the second a mother whose first pregnancy resulted in the birth of a severely neutropenic (0 × 10(6) neutrophils/L) infant affected with ANN. Serum neutrophil antibody testing was by flow cytometry and CD11b/18 monoclonal antibody immobilization of granulocyte antigens assay, and HNA genotyping was performed by polymerase chain reaction with sequence-specific priming and allele-specific 5' exonuclease assays. Sera from both women contained IgG antibodies reactive only with HNA-4b+ neutrophils and both typed HNA-4a/a. Both were immunized through pregnancy since their husbands and children all typed HNA-4a/b. The serologic results, together with the genotype results, confirm that these are the first reported cases of neutrophil antibodies specific for HNA-4b. © 2015 AABB.

Macular hemorrhages associated with neonatal polycythemia and thrombocytopenia: A case report.

PubMed

Cui, Z; Zhang, Y; Liang, L; Li, Z; Hao, Q

2017-02-01

Thrombocytopenia occurs in 51% of neonates with polycythemia and is independently associated with growth restriction. Increased hematocrit is associated with decreased platelet count. The possibility of a hemorrhage should be noted. A Chinese male newborn presented with elevated hemoglobin and hematocrit levels. The platelet count decreased to 10×10 9 /L during the 1st week after birth and remained abnormal at day 12. Vitreous turbidity of the right eye was detected 2 days later and was suspected of stemming from endophthalmitis or ocular inflammation. Two weeks later, vitreous turbidity decreased and a macular hemorrhage became visible. Optical coherence tomography confirmed the diagnosis of a retinal hemorrhage. Thrombocytopenia associated with polycythemia can induce a vitreous hemorrhage, which may be confused with ocular infection or inflammation. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Thrombocytopenia associated with the induction of neonatal tolerance to alloantigens: immunopathogenic mechanisms.

PubMed

Merino, J; Qin, H Y; Schurmans, S; Gretener, D; Grau, G E; Lambert, P H

1989-09-01

BALB/c mice rendered tolerant to alloantigens by neonatal injection of semi-allogeneic (C57BL/6 x BALB/c)F1 spleen cells develop a thrombocytopenia in association with an autoimmune lupus-like syndrome. The possible mechanisms involved in the thrombocytopenia were investigated. The development of thrombocytopenia was first detected at 3 weeks of age coinciding with the start of the other autoimmune manifestations and was always related to a state of tolerance and B cell chimerism. There was a significant increase of megakaryocytes in bone marrow and spleens from thrombocytopenic tolerant mice and radiolabeled platelets from these mice were more rapidly eliminated from the bloodstream than normal platelets when injected into normal recipients. A significant correlation between the spleen weight and the decrease of the circulating platelets was observed, although some mice with severe thrombocytopenia had only a moderate spleen enlargement. Thrombocytopenia significantly correlates with the levels of platelet-associated IgG (PAIgG) but not with anti-single-stranded DNA antibodies or circulating immune complexes. Platelets from mice with high levels of PAIgG had a shorter life-span when injected into normal mice than those from mice with low or normal PAIgG. The possibility that PAIgG are partially due to antibodies reacting specifically with platelet membrane components was analyzed. First, F(ab')2 Ig fragments from tolerant mice were shown to bind to normal platelets, in contrast to F(ab')2 Ig fragments from normal mice. Second, some monoclonal antibodies produced by hybridomas derived from tolerant mice reacted in vitro with platelets and induced a transient thrombocytopenia after i.v. injection into normal mice. These data suggest that the thrombocytopenia observed in tolerant mice is the result of a peripheral hyperdestruction of platelets associated with (a) hypersplenism, (b) nonspecific fixation of immunoglobulins, probably as immune complexes and (c) with

Alloimmunization in Congenital Deficiencies of Platelet Surface Glycoproteins: Focus on Glanzmann's Thrombasthenia and Bernard-Soulier's Syndrome.

PubMed

Poon, Man-Chiu; d'Oiron, Roseline

2018-06-07

Glanzmann's thrombasthenia (GT) and Bernard-Soulier's syndrome (BSS) are well-understood congenital bleeding disorders, showing defect/deficiency of platelet glycoprotein (GP) IIb/IIIa (integrin αIIbβ3) and GPIb-IX-V complexes respectively, with relevant clinical, laboratory, biochemical, and genetic features. Following platelet transfusion, affected patients may develop antiplatelet antibodies (to human leukocyte antigen [HLA], and/or αIIbβ3 in GT or GPIb-IX in BSS), which may render future platelet transfusion ineffective. Anti-αIIbβ3 and anti-GPIb-IX may also cross the placenta during pregnancy to cause thrombocytopenia and bleeding in the fetus/neonate. This review will focus particularly on the better studied GT to illustrate the natural history and complications of platelet alloimmunization. BSS will be more briefly discussed. Platelet transfusion, if unavoidable, should be given judiciously with good indications. Patients following platelet transfusion, and women during and after pregnancy, should be monitored for the development of platelet antibodies. There is now a collection of data suggesting the safety and effectiveness of recombinant activated factor VII in the management of affected patients with platelet antibodies. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Acoustic radiation force impulse elastosonography of placenta in maternal red blood cell alloimmunization: a preliminary and descriptive study.

PubMed

Cetin, Orkun; Karaman, Erbil; Arslan, Harun; Akbudak, Ibrahim; Yıldızhan, Recep; Kolusarı, Ali

2017-01-31

Maternal red blood cell alloimmunization is an important cause of fetal morbidity and mortality in the perinatal period, despite well-organized prophylaxis programs. The objective of the study was to evaluate placental elasticity by using Acoustic Radiation Force Impulse (ARFI) in Rhesus (Rh) alloimmunized pregnant women with hydropic and nonhydropic fetuses and to compare those with healthy pregnant women. This case-control and descriptive study comprised twenty-eight healthy pregnant women, 14 Rh alloimmunized pregnant women with nonhydropic fetuses, and 16 Rh alloimmunized pregnant women with hydropic fetuses in the third trimester of pregnancy. Placental elasticity measurements were performed by ARFI elastosonography at the day of delivery. The maternal characteristics and neonatal outcomes of the patients were also noted. The highest mean placental ARFI scores were observed in Rh alloimmunized pregnant women with hydropic fetuses (1.13 m/s) (p=0.001). Healthy controls and Rh alloimmunized pregnant women with nonhydropic fetuses had similar mean placenta ARFI scores (0.84 m/s, 0.88 m/s, respectively) (p<0.05). Based on the present findings, the placenta becomes stiffer in Rh alloimmunized pregnancies complicated with hydrops fetalis. The increased placental ARFI scores may be a supplemental marker for adverse pregnancy outcomes, additional to Doppler evaluation of middle cerebral artery. This data should be confirmed with a large sample size and prospective studies by using serial measurements of ARFI elastosonography in maternal red blood cell alloimmunization.

Immune Thrombocytopenia in Pregnancy

PubMed Central

Stavrou, Evi; McCrae, Keith R.

2009-01-01

SYNOPSIS Management of ITP in pregnancy can be a complex and challenging task, and may be complicated by fetal/neonatal thrombocytopenia. Though fetal intracranial hemorrhage is a rare complication of ITP in pregnancy, invasive studies designed to determine the fetal platelet count before delivery are associated with greater risk than that of fetal intracranial hemorrhage, and therefore are discouraged. Moreover, the risk of neonatal bleeding complications does not correlate with the mode of delivery, and thus cesarean section should be reserved for obstetric indications only. PMID:19932435

Successful management of a hydropic fetus with severe anemia and thrombocytopenia caused by anti-CD36 antibody.

PubMed

Xu, Xiuzhang; Li, Lin; Xia, Wenjie; Ding, Haoqiang; Chen, Dawei; Liu, Jing; Deng, Jing; Chen, Yangkai; He, Zhiming; Wang, Jiali; Shao, Yuan; Santoso, Sentot; Ye, Xin; Fang, Qun

2018-02-01

Cases of CD36 deficiency are not rare in Asian populations, foetal and neonatal alloimmune thrombocytopenia (FNAIT) caused by anti-CD36 isoantibodies appears more frequent than other HPA alloantibodies. However, little is known about the treatment of anti-CD36 mediated FNAIT in this region. A Chinese male foetus, whose mother had a history of multiple intrauterine foetal demise and/or hydrops, was diagnosed with severe FNAIT at 27 weeks of gestational age. Immunological analysis revealed total absence of CD36 on platelets and monocytes from mother, caused by a 329-330delAC mutation of the CD36 gene. Anti-CD36 and anti-HLA class I antibodies were detected in the maternal serum, whereas only anti-CD36 isoantibodies were detectable in the foetal blood sample. Serial intrauterine transfusions with red blood cells (RBC) and platelets from a CD36null donor were performed to improve the severe anaemia and thrombocytopenia. The baby (2250 g; Apgar scores 10) was delivered vaginally at 32 weeks of gestation with normal haemoglobin (186 g/L) but low platelet count (48 × 10 9 /L). After 2 days the platelet count rose to 121 × 10 9 /L. This report suggests that intrauterine transfusions with compatible RBC and CD36null platelets are useful in preventing the deleterious clinical effects of anti-CD36-mediated severe FNAIT.

Hemin controls T cell polarization in sickle cell alloimmunization.

PubMed

Zhong, Hui; Bao, Weili; Friedman, David; Yazdanbakhsh, Karina

2014-07-01

Patients with sickle cell disease (SCD) often require transfusions to treat and prevent worsening anemia and other SCD complications. However, transfusions can trigger alloimmunization against transfused RBCs with serious clinical sequelae. Risk factors for alloimmunization in SCD remain poorly understood. We recently reported altered regulatory T cell (Treg) and Th responses with higher circulating Th1 (IFN-γ(+)) cytokines in chronically transfused SCD patients with alloantibodies as compared with those without alloantibodies. Because monocytes play a critical role in polarization of T cell subsets and participate in clearance of transfused RBCs, we tested the hypothesis that in response to the RBC breakdown product hemin, monocyte control of T cell polarization will differ between alloimmunized and non-alloimmunized SCD patients. Exogenous hemin induced Treg polarization in purified T cell/monocyte cocultures from healthy volunteers through the monocyte anti-inflammatory heme-degrading enzyme heme oxygenase-1. Importantly, hemin primarily through its effect on CD16+ monocytes induced an anti-inflammatory (higher Treg/lower Th1) polarization state in the non-alloimmunized SCD group, whereas it had little effect in the alloimmunized group. Non-alloimmunized SCD CD16+ monocytes expressed higher basal levels of heme oxygenase-1. Furthermore, IL-12, which contributed to a proinflammatory polarization state (low Treg/high Th1) in SCD, was dampened in hemin-treated stimulated monocytes from non-alloimmunized SCD patients, but not in the alloimmunized group. These data suggest that unlike alloimmunized patients, non-alloimmunized SCD CD16+ monocytes in response to transfused RBC breakdown products promote an anti-inflammatory state that is less conducive to alloimmunization. Copyright © 2014 by The American Association of Immunologists, Inc.

Management of pregnancies complicated by anti-Fy(a) alloimmunization.

PubMed

Hughes, Laura H; Rossi, Karen Q; Krugh, David W; O'Shaughnessy, Richard W

2007-10-01

The objective was to evaluate the management and outcome of patients with anti-Fy(a) at the Ohio State University. A database search for patients with pregnancies complicated only by anti-Fy(a) from 1959 to 2004. Collected information included maternal testing, fetal therapy, and neonatal outcomes. The final data set included 18 pregnancies in 15 women where anti-Fy(a) was the only maternal alloantibody present and the fetus was Fy(a) antigen-positive. Maternal antibody titers of at least 32 and optical density at 450 nm values in modified Liley Zone IIB or III identified all fetuses or neonates with significant hemolytic disease (2/18, 11%). No fetuses had hydrops, and there were no deaths attributed to hemolytic disease of the fetus and newborn. Anti-Fy(a) has the potential to lead to significant fetal hemolysis. Management guidelines developed for D sensitization are appropriate for pregnancies complicated by anti-Fy(a) alloimmunization.

Identification of potential platelet alloantigens in the Equidae family by comparison of gene sequences encoding major platelet membrane glycoproteins.

PubMed

Boudreaux, Mary K; Humphries, Drew M

2013-12-01

Platelet alloantigens in horses may play an important role in the development of neonatal alloimmune thrombocytopenia (NAIT). The objective of this study was to evaluate genes encoding major platelet glycoproteins within the Equidae family in an effort to identify potential alloantigens. DNA was isolated from blood samples obtained from Equidae family members, including a Holsteiner-Oldenburg cross, a Quarter horse, a donkey, and a Plains zebra (Equus burchelli). Gene sequences encoding equine platelet membrane glycoproteins IIb, IIIa (integrin subunits αIIb and β3), Ia (integrin subunit α2), and Ibα were determined using PCR. Gene sequences were compared to the equine genome available on GenBank. Polymorphisms that would be predicted to result in amino acid changes on platelet surfaces were documented and compared with known alloantigenic sites documented on human platelets. Amino acid differences were predicted based on nucleotide sequences for all 4 genes. Nine differences were documented for αIIb, 5 differences were documented for β3, 7 differences were documented for α2, and 16 differences were documented for Ibα outside the macroglycopeptide region. This study represents the first effort at identifying potential platelet alloantigens in members of the Equidae Family based on evaluation of gene sequences. The data obtained form the groundwork for identifying potential platelet alloantigens involved in transfusion reactions and neonatal alloimmune thrombocytopenia (NAIT). More work is required to determine whether the predicted amino acid differences documented in this study play a role in alloimmunity, and whether other polymorphisms not detected in this study are present that may result in alloimmunity. © 2013 American Society for Veterinary Clinical Pathology.

Thrombocytopenia in pregnancy with different diagnoses

PubMed Central

Wang, Xiaoyue; Xu, Yan; Luo, Wenxiang; Feng, Hui; Luo, Yizhou; Wang, Yanli; Liao, Hui

2017-01-01

Abstract To investigate the clinical features and perinatal treatment of thrombocytopenia induced by different causes during pregnancy. Clinical data from 195 pregnant women with thrombocytopenia attending 2 tertiary hospitals from January 2014 to October 2016 were retrospectively studied. The obtained data were analyzed with SPSS 19.0 software. There were 117 (60.0%), 55 (28.2%), and 23 cases (11.8%) of pregnancy-associated thrombocytopenia (PAT), idiopathic thrombocytopenia (ITP), and hypertensive disorder in pregnancy (PIH), respectively. The percentage of nulliparous women, gestational age at delivery, date of diagnosis of thrombocytopenia, and delivery mode significantly differed between the patients in these 3 groups (P < .05). Patients with PIH had a higher percentage of premature delivery and of lower birth weight infants than patients in the other 2 groups. The 3 groups had similar incidences of postpartum hemorrhage, rates of stillbirth, and neonatal Apgar scores at 5 minutes. PAT and PIH patients had different platelet counts after delivery compared with at diagnosis, whereas the platelet counts of the ITP patients were similar at diagnosis and after delivery. ITP patients in the nontreatment group and the treatment group had significantly different platelet counts (P < .05), and in the treatment group, the maternal platelet count did not differ for treatment with intravenous immunoglobulin (IVIg) versus corticosteroids. The causes of thrombocytopenia in pregnancy are diverse, and the clinical features vary widely. Timely analysis is needed to determine the primary cause of thrombocytopenia, and appropriate therapy should then be selected to effectively improve the prognosis of pregnancies. PMID:28723784

Regulatory B cells (CD19(+)CD38(hi)CD24(hi)) in alloimmunized and non-alloimmunized children with β-thalassemia major.

PubMed

Zahran, Asmaa M; Elsayh, Khalid I; Saad, Khaled; Embaby, Mostafa; Ali, Ahmed M

2016-03-01

β-Thalassemia major (BTM) is considered the most common hemoglobinopathy in Egypt and is one of the major health problems in our locality. We investigated the frequency of B-regulatory cells (CD19(+)CD38(hi)CD24(hi)); (Bregs) among polytransfused alloimmunized and non-alloimmunized children with BTM. The study included 110 polytransfused pediatric patients with β-thalassemia major. Clinical and transfusion records of all studied patients were reviewed. Indirect antiglobulin test was performed to detect the presence of alloantibodies. We used flow cytometry for detection of CD19(+)CD38(hi)CD24(hi) regulatory B cells. Alloimmunization was detected in 35.5% of thalassemic patients (39/110). The analysis of our data showed a significantly higher frequency of Bregs (CD19(+)CD38(hi)CD24(hi)) in the peripheral blood of both alloimmunized and non-alloimmunized patients as compared to healthy controls. Our data showed that the frequencies of CD19(+)CD24(hi)CD38(hi) Bregs cells were significantly increased in children with BTM. Our data suggested that Bregs cells could play a role in the clinical course of BTM. The relationship of Bregs to immune disorders in BTM children remains to be determined. Further longitudinal study with a larger sample size is warranted to explore the mechanisms of Breg cells in the disease process in BTM patients. Copyright © 2016 Elsevier Inc. All rights reserved.

The Association of CD81 Polymorphisms with Alloimmunization in Sickle Cell Disease

PubMed Central

Tatari-Calderone, Zohreh; Tamouza, Ryad; Le Bouder, Gama P.; Dewan, Ramita; Luban, Naomi L. C.; Lasserre, Jacqueline; Maury, Jacqueline; Lionnet, François; Krishnamoorthy, Rajagopal; Girot, Robert

2013-01-01

The goal of the present work was to identify the candidate genetic markers predictive of alloimmunization in sickle cell disease (SCD). Red blood cell (RBC) transfusion is indicated for acute treatment, prevention, and abrogation of some complications of SCD. A well-known consequence of multiple RBC transfusions is alloimmunization. Given that a subset of SCD patients develop multiple RBC allo-/autoantibodies, while others do not in a similar multiple transfusional setting, we investigated a possible genetic basis for alloimmunization. Biomarker(s) which predicts (predict) susceptibility to alloimmunization could identify patients at risk before the onset of a transfusion program and thus may have important implications for clinical management. In addition, such markers could shed light on the mechanism(s) underlying alloimmunization. We genotyped 27 single nucleotide polymorphisms (SNPs) in the CD81, CHRNA10, and ARHG genes in two groups of SCD patients. One group (35) of patients developed alloantibodies, and another (40) had no alloantibodies despite having received multiple transfusions. Two SNPs in the CD81 gene, that encodes molecule involved in the signal modulation of B lymphocytes, show a strong association with alloimmunization. If confirmed in prospective studies with larger cohorts, the two SNPs identified in this retrospective study could serve as predictive biomarkers for alloimmunization. PMID:23762099

Donors With Immune Thrombocytopenia: Do They Pose a Risk to Transplant Recipients?

PubMed

Trotter, P B; Robb, M; Summers, D; Watson, C J E; Clatworthy, M; Bradley, J A; Hill, Q A; Neuberger, J

2017-03-01

Transplant-mediated alloimmune thrombocytopenia (TMAT) from donors with immune thrombocytopenia (ITP) can result in significant bleeding complications in the recipient. The risk to a recipient of TMAT if they receive an organ from a donor with ITP is unknown. The outcomes of recipients of organs from deceased donors with ITP recorded in the UK Transplant Registry between 2000 and 2015 were reviewed. Twenty-one deceased organ donors had a predonation diagnosis of ITP. These donors were significantly more likely to have died from intracranial hemorrhage than were all other deceased organ donors (85% vs. 57%, p < 0.001). Organs from donors with ITP resulted in 49 organ transplants (31 kidney, 14 liver, four heart), with only one case of TMAT, which occurred in a liver transplant recipient and resulted in death from bleeding complications 18 days posttransplantation. The recipient of a kidney from the same organ donor was not affected. Unadjusted 5-year patient and graft survival was significantly worse for liver transplant recipients from donors with ITP compared with liver transplant recipients from donors without ITP (64% vs. 85%, p = 0.012). Organs from donors with ITP may be considered for transplantation, but livers should be used with caution. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Red cell alloimmunization is associated with development of autoantibodies and increased red cell transfusion requirements in myelodysplastic syndrome

PubMed Central

Singhal, Deepak; Kutyna, Monika M.; Chhetri, Rakchha; Wee, Li Yan A.; Hague, Sophia; Nath, Lakshmi; Nath, Shriram V.; Sinha, Romi; Wickham, Nicholas; Lewis, Ian D.; Ross, David M.; Bardy, Peter G.; To, Luen Bik; Reynolds, John; Wood, Erica M.; Roxby, David J.; Hiwase, Devendra K.

2017-01-01

Up to 90% of patients with a myelodysplastic syndrome require red blood cell transfusion; nevertheless, comprehensive data on red cell alloimmunization in such patients are limited. This study evaluates the incidence and clinical impact of red cell alloimmunization in a large cohort of patients with myelodysplastic syndrome registered in the statewide South Australian-MDS registry. The median age of the 817 patients studied was 73 years, and 66% were male. The cumulative incidence of alloimmunization was 11%. Disease-modifying therapy was associated with a lower risk of alloimmunization while alloimmunization was significantly higher in patients with a revised International Prognostic Scoring System classification of Very Low, Low or Intermediate risk compared to those with a High or Very High risk (P=0.03). Alloantibodies were most commonly directed against antigens in the Rh (54%) and Kell (24%) systems. Multiple alloantibodies were present in 49% of alloimmunized patients. Although 73% of alloimmunized patients developed alloantibodies during the period in which they received their first 20 red cell units, the total number of units transfused was significantly higher in alloimmunized patients than in non-alloimmunized patients (90±100 versus 30±52; P<0.0001). In individual patients, red cell transfusion intensity increased significantly following alloimmunization (2.8±1.3 versus 4.1±2.0; P<0.0001). A significantly higher proportion of alloimmunized patients than non-alloimmunized patients had detectable autoantibodies (65% versus 18%; P<0.0001) and the majority of autoantibodies were detected within a short period of alloimmunization. In conclusion, this study characterizes alloimmunization in a large cohort of patients with myelodysplastic syndrome and demonstrates a signficant increase in red cell transfusion requirements following alloimmunization, most probably due to development of additional alloantibodies and autoantibodies, resulting in subclinical

High-dose immunoglobulin during pregnancy for recurrent neonatal haemochromatosis.

PubMed

Whitington, Peter F; Hibbard, Judith U

Neonatal haemochromatosis is a rare disease of gestation that results in severe fetal liver injury. We hypothesised an alloimmune aetiology for the disorder on the basis of its high recurrence rate in sibships. In this study, we assessed the effectiveness in preventing or changing the severity of recurrent neonatal haemochromatosis of administering during pregnancy high-dose intravenous immunoglobulin (IVIG) derived from pooled serum of multiple donors. Women whose most recent pregnancy ended in documented neonatal haemochromatosis were treated with IVIG, 1 g/kg bodyweight, weekly from the 18th week until the end of gestation in their subsequent pregnancy. The outcomes of treated pregnancies were compared with those of randomly selected previous affected pregnancies for each woman, which were used as historical controls. 15 women were treated through 16 pregnancies. All pregnancies progressed uneventfully and resulted in live babies with normal physical examinations and birthweights that were appropriate for gestational age. 12 babies had evidence of liver involvement with neonatal haemochromatosis: 11 had higher than normal concentrations of serum alpha-fetoprotein and ferritin or serum alpha-fetoprotein alone, including four with coagulopathy (international normalised ratio >1.5), and one had coagulopathy alone. All babies survived with medical or no treatment and were healthy at follow-up within the past 6 months. In analysis on a per-mother basis comparing outcomes of treated gestations with those of randomly selected previous affected gestations, gestational IVIG therapy was associated with better infant survival (15 good outcomes vs two in previous pregnancies; p=0.0009). Treatment with high-dose IVIG during gestation appears to have modified recurrent neonatal haemochromatosis so that it was not lethal to the fetus or neonate. These results further support an alloimmune mechanism for recurrent neonatal haemochromatosis.

Predictors of Red Cell Alloimmunization in Kurdish Multi Transfused Patients with Hemoglobinopathies in Iraq.

PubMed

Al-Mousawi, Muqdad M N; Al-Allawi, Nasir A S; Alnaqshabandi, Rubad

2015-01-01

Hemoglobinopathies are significant health problems in Iraq, including its Northern Kurdistan region. One of the essential components of management of these disorders is regular lifelong blood transfusions. The latter is associated with several complications including red cell alloimmunization. No study has looked at the frequency of alloimmunization and its associations in the country. To address the latter issue, 401 multi transfused patients [311 with β-thalassemia (β-thal) syndrome and 90 with sickle cell disease], registered at a large thalassemia care center in Iraqi Kurdistan had their records reviewed, and their sera tested for atypical antibodies using screening and extended red cell panels. Red cell alloimmunization was detected in 18 patients (4.5%) with a total of 20 alloantibodies, while no autoantibodies were detected. The most frequent alloantibody was anti-E, followed by anti-D, anti-K, anti-C(w), anti-C, anti-c and anti-Le(a). Ethnicity was an important predictor of alloimmunization, while age at start of transfusion (>2 vs. ≤2 years) (p = 0.005), Rhesus D (RhD) negative status (p = 0.0017) and history of previous transfusion reactions (p = 0.007) showed a statistically significant higher rate of alloimmunization. However, patients' age, gender, number of units transfused, underlying diagnosis and splenectomy were not significantly associated with alloimmunization. Based on our observations, measures to reduce alloimmunization rates may include extended matching for Rhesus and Kell antigens and early initiation of blood transfusions.

Frequency and specificity of red blood cell alloimmunization in chilean transfused patients.

PubMed

Caamaño, José; Musante, Evangelina; Contreras, Margarita; Ulloa, Hernán; Reyes, Carolina; Inaipil, Verónica; Saavedra, Nicolás; Guzmán, Neftalí

2015-01-01

Alloimmunization is an adverse effect of blood transfusions. In Chile, alloimmunization frequency is not established, and for this reason the aim of this study was to investigate the prevalence and specificity of red blood cell (RBC) alloantibodies in Chilean transfused subjects. Records from 4,716 multi-transfused patients were analyzed. In these patients, antibody screening was carried out prior to cross-matching with a commercially available two-cell panel by the microcolum gel test, and samples with a positive screen were analyzed for the specificity of the alloantibody with a 16-cell identification panel. The incidence of RBC alloimmunization in transfused patients was 1.02% (48/4,716) with a higher prevalence in women (40/48). We detected 52 antibodies, the most frequent specificities identified were anti-E (30.8%), anti-K (26.9%), anti-D (7.7%), and anti-Fy(a) (5.8%). The highest incidence of alloantibodies was observed in cancer and gastroenterology patients. The data demonstrated a low alloimmunization frequency in Chilean transfused patients, principally associated with antibodies anti-E, anti-K, anti-D, and anti-Fy(a).

Clinical data, clinicopathologic findings and outcome in dogs with amegakaryocytic thrombocytopenia and primary immune-mediated thrombocytopenia.

PubMed

Cooper, S A; Huang, A A; Raskin, R E; Weng, H-Y; Scott-Moncrieff, J C

2016-03-01

The aim of this study was to identify distinguishing characteristics between dogs diagnosed with amegakaryocytic thrombocytopenia and those diagnosed with presumed primary peripheral immune-mediated thrombocytopenia. Presenting clinical and clinicopathologic data and outcomes were compared between the two groups. Retrospective study performed on seven client-owned dogs diagnosed with amegakaryocytic thrombocytopenia and 34 client-owned dogs with primary peripheral immune-mediated thrombocytopenia. All dogs in the amegakaryocytic thrombocytopenia group were anaemic on presentation with a median haematocrit of 23% (range 9·4 to 36), while the primary peripheral immune-mediated thrombocytopoenia group had a median presenting haematocrit of 35% (range 10 to 53). Dogs with amegakaryocytic thrombocytopenia had a median of five (range 4 to 7) clinical signs of bleeding compared to a median of three (range 0 to 6) in the primary peripheral immune-mediated thrombocytopenia group with 86% (6 of 7) of amegakaryocytic thrombocytopenia dogs requiring a blood transfusion compared to 41% (14 of 34) of primary peripheral immune-mediated thrombocytopenia dogs. Six of the seven amegakaryocytic thrombocytopenia dogs did not survive to discharge, while only five of the 34 primary peripheral immune-mediated thrombocytopenia dogs did not survive to discharge. The clinical presentation of dogs with amegakaryocytic thrombocytopenia and primary peripheral immune-mediated thrombocytopenia is similar, but dogs with amegakaryocytic thrombocytopenia had a more severe clinical course compared to primary peripheral immune-mediated thrombocytopenia dogs. The prognosis for dogs with amegakaryocytic thrombocytopenia is poor. © 2016 British Small Animal Veterinary Association.

Immune Thrombocytopenia

PubMed Central

Kistanguri, Gaurav; McCrae, Keith R.

2013-01-01

Immune thrombocytopenia (ITP) is a common hematologic disorder characterized by isolated thrombocytopenia. ITP presents as a primary form characterized by isolated thrombocytopenia (platelet count < 100 × 109/L) in the absence of other causes or disorders that may be associated with thrombocytopenia, or a secondary form in which immune thrombocytopenia develops in association with another disorder that is usually immune or infectious. ITP may affect individuals of all ages, with peaks during childhood and in the elderly, in whom the age specific incidence of ITP is greatest. Bleeding is the most common clinical manifestation of ITP, with the risk of bleeding and related morbidity increased in elderly patients. The pathogenesis of ITP is complex, involving alterations in humoral and cellular immunity. Thrombocytopenia is caused by antibodies that react with glycoproteins expressed on platelets and megakaryocytes (glycoprotein IIb/IIIa, Ib/IX and others), causing shortened survival of circulating platelets and impairing platelet production. Diminished numbers and function of regulatory T cells, as well as the effects of cytotoxic T cells also contribute to the pathogenesis of ITP. Corticosteroids remain the most common first line therapy for ITP, occasionally in conjunction with intravenous immunoglobulin (IVIg) and anti-Rh(D). However, these agents do not lead to durable remissions in the majority of adults with ITP, and considerable heterogeneity exists in the use of second line approaches, which may include splenectomy, Rituximab, or thrombopoietin receptor agonists (TRAs). This review summarizes the classification and diagnosis of primary and secondary ITP, as well as the pathogenesis and options for treatment. Remarkable advances in the understanding and management of ITP have been achieved over the last decade, though many questions remain. PMID:23714309

Emerging science, emerging ethical issues: who should fund innate alloimmunity-suppressing drugs?

PubMed

Land, W G; Gutmann, Th; Daar, A S

2008-01-01

An emerging body of evidence suggests that the innate immune system plays a critical role in allograft rejection. Any injury to the donor organ, e.g. the reperfusion injury, induces an inflammatory milieu in the allograft which appears to be the initial event for activation of the innate immune system. Injury-induced intragraft damage- associated molecular patterns (DAMPs) are recognized by donor-derived and recipient-derived, TLR4/2-bearing immature dendritic cells (iDCs). After recognition, these cells mature and initiate allorecognition/alloactivation in the lymphoid system of the recipient. Indeed, the key "innate" event, leading to activation of the adaptive alloimmune response, is the injury-induced, TLR4-triggered, and NFkappaB-mediated maturation of DCs ("innate alloimmunity"). Time-restricted treatment of innate immune events would include 1) treatment of the donor during organ removal, 2) in-situ/ex-vivo treatment of the donor organs alone, and 3) treatment of the recipient during allograft reperfusion and immediately postoperatively. Treatment modalities would include 1) minimization of the oxidative allograft injury with the use of antioxidants; 2) prevention of the TLR4-triggered maturation of DCs with the use of TLR4-antagonists; 3) inhibition of complement activation with the use of complement inhibiting agents. According to data from clinical and experimental studies it can be assumed that successful suppression of innate alloimmune events results in either subsequent significant reduction in, or even complete avoidance of the currently applied adaptive alloimmunity-suppressing drugs. However, in view of the time-restricted period of treatment, and the fear to potentially destroy its own business with currently applied alloimmunity-suppressing drugs, the pharmaceutical industry is still, but quite legitimately, reluctant to invest in the high cost of clinical development of those drugs for transplant patients because there are no marketing interests

[Inherited thrombocytopenias].

PubMed

Leverger, G; Petit, A; Fasola, S; Landman-Parker, J; Favier, R

2010-08-01

Secondary causes of thrombocytopenia as immunologic thrombopenia purpura, or ITP, are far more common than inherited causes, which even as a group, are rare. Nevertheless, diagnosis is important and progress made in uncovering the molecular basis of these disorders has contributed greatly to our knowledge of these diseases. Inherited thrombocytopenias are a heterogeneous group of disorders. Different criteria have been suggested to classify the forms, such as the inheritance mechanism and the platelet volume as well as the associated platelet dysfunctions or clinical abnormality. This paper describes the clinical and biological data, and current knowledge of the molecular findings of inherited thrombocytopenia, allowing a diagnostic approach to these diseases. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

Protective Effect of HLA-DQB1 Alleles Against Alloimmunization in Patients with Sickle Cell Disease

PubMed Central

Tatari-Calderone, Zohreh; Gordish-Dressman, Heather; Fasano, Ross; Riggs, Michael; Fortier, Catherine; Andrew; Campbell, D.; Charron, Dominique; Gordeuk, Victor R.; Luban, Naomi L.C.; Vukmanovic, Stanislav; Tamouza, Ryad

2015-01-01

Background Alloimmunization or the development of alloantibodies to Red Blood Cell (RBC) antigens is considered one of the major complications after RBC transfusions in patients with sickle cell disease (SCD) and can lead to both acute and delayed hemolytic reactions. It has been suggested that polymorphisms in HLA genes, may play a role in alloimmunization. We conducted a retrospective study analyzing the influence of HLA-DRB1 and DQB1 genetic diversity on RBC-alloimmunization. Study design Two-hundred four multi-transfused SCD patients with and without RBC-alloimmunization were typed at low/medium resolution by PCR-SSO, using IMGT-HLA Database. HLA-DRB1 and DQB1 allele frequencies were analyzed using logistic regression models, and global p-value was calculated using multiple logistic regression. Results While only trends towards associations between HLA-DR diversity and alloimmunization were observed, analysis of HLA-DQ showed that HLA-DQ2 (p=0.02), -DQ3 (p=0.02) and -DQ5 (p=0.01) alleles were significantly higher in non-alloimmunized patients, likely behaving as protective alleles. In addition, multiple logistic regression analysis showed both HLA-DQ2/6 (p=0.01) and HLA-DQ5/5 (p=0.03) combinations constitute additional predictor of protective status. Conclusion Our data suggest that particular HLA-DQ alleles influence the clinical course of RBC transfusion in patients with SCD, which could pave the way towards predictive strategies. PMID:26476208

Simultaneous human platelet antigen genotyping and detection of novel single nucleotide polymorphisms by targeted next-generation sequencing.

PubMed

Davey, Sue; Navarrete, Cristina; Brown, Colin

2017-06-01

Twenty-nine human platelet antigen systems have been described to date, but the majority of current genotyping methods are restricted to the identification of those most commonly associated with alloantibody production in a clinical context. This can result in a protracted investigation if causative human platelet antigens are rare or novel. A targeted next-generation sequencing approach was designed to detect all known human platelet antigens with the additional capability of identifying novel mutations in the encoding genes. A targeted enrichment, high-sensitivity HaloPlex assay was designed to sequence all exons and flanking regions of the six genes known to encode human platelet antigens. Indexed DNA libraries were prepared from 47 previously human platelet antigen-genotyped samples and subsequently combined into one of three pools for sequencing on an Illumina MiSeq platform. The generated FASTQ files were aligned and scrutinized for each human platelet antigen polymorphism using SureCall data analysis software. Forty-six samples were successfully genotyped for human platelet antigens 1 through 29bw, with an average per base coverage depth of 1144. Concordance with historical human platelet antigen genotypes was 100%. A putative novel mutation in Exon 10 of the integrin β-3 (ITGB3) gene from an unsolved case of fetal neonatal alloimmune thrombocytopenia was also detected. A next-generation sequencing-based method that can accurately define all known human platelet antigen polymorphisms was developed. With the ability to sequence up to 96 samples simultaneously, our HaloPlex design could be used for high-throughput human platelet antigen genotyping. This method is also applicable for investigating fetal neonatal alloimmune thrombocytopenia when rare or novel human platelet antigens are suspected. © 2017 AABB.

Non-invasive Prenatal Diagnosis of Feto-Maternal Platelet Incompatibility by Cold High Resolution Melting Analysis.

PubMed

Ferro, Marta; Macher, Hada C; Noguerol, Pilar; Jimenez-Arriscado, Pilar; Molinero, Patrocinio; Guerrero, Juan M; Rubio, Amalia

2016-01-01

Fetal and Neonatal alloimmune thrombocytopenia (FNAIT) is a condition which could occur when pregnant women develop an alloimmunization against paternally inherited antigens of the fetal platelets. Approximately 80 % of FNAIT cases are caused by anti-HPA-1a, about 15 % by anti-HPA-5b and 5 % by other HPA antibodies. Only 2 % of the total population is HPA-1a negative (HPA-1b1b). The HPA-1a allele differs by one single nucleotide from HPA-1b allele, yet it represents around 27 % of total severe thrombocytopenias. HPA-1 was studied in serum cDNA from 12 volunteer pregnant women to determine their HPA-1 genotype by HRM (high resolution melting) PCR. When an homozygous HPA-1 gene was detected in a mother, a COLD HRM was performed to determine whether or not the fetal genotype differs from the mother's.The differences in the melting curve shapes allow us to accurately distinguish the three pregnants genotypes. The fetal heterozygous genotype of homozygous pregnant women was correctly detected by COLD PCR HRM in maternal serum. HPA-1 genotyping by HRM may be a useful aproach for genotyping all pregnant women in inexpensively. Moreover, when HPA-1 homozygosis was detected in a pregnant woman, fetal heterozygosis may be diagnosed by COLD HRM to select pregnancies for preventive monitoring.

Pyrazinamide induced thrombocytopenia

PubMed Central

Kant, Surya; Verma, Sanjay Kumar; Gupta, Vaibhav; Anand, Sunish C.; Prasad, Rajendra

2010-01-01

Thrombocytopenia is an uncommon but potentially life-threatening complication of certain antitubercular drugs and is characterized by rapid destruction of platelets whenever offending drug is taken by a susceptible person. We report a case of pyrazinamide-induced thrombocytopenia in a patient receiving anti tubercular drugs. PMID:20711377

Whole-exome sequencing for RH genotyping and alloimmunization risk in children with sickle cell anemia

PubMed Central

Flanagan, Jonathan M.; Vege, Sunitha; Luban, Naomi L. C.; Brown, R. Clark; Ware, Russell E.; Westhoff, Connie M.

2017-01-01

RH genes are highly polymorphic and encode the most complex of the 35 human blood group systems. This genetic diversity contributes to Rh alloimmunization in patients with sickle cell anemia (SCA) and is not avoided by serologic Rh-matched red cell transfusions. Standard serologic testing does not distinguish variant Rh antigens. Single nucleotide polymorphism (SNP)–based DNA arrays detect many RHD and RHCE variants, but the number of alleles tested is limited. We explored a next-generation sequencing (NGS) approach using whole-exome sequencing (WES) in 27 Rh alloimmunized and 27 matched non-alloimmunized patients with SCA who received chronic red cell transfusions and were enrolled in a multicenter study. We demonstrate that WES provides a comprehensive RH genotype, identifies SNPs not interrogated by DNA array, and accurately determines RHD zygosity. Among this multicenter cohort, we demonstrate an association between an altered RH genotype and Rh alloimmunization: 52% of Rh immunized vs 19% of non-immunized patients expressed variant Rh without co-expression of the conventional protein. Our findings suggest that RH allele variation in patients with SCA is clinically relevant, and NGS technology can offer a comprehensive alternative to targeted SNP-based testing. This is particularly relevant as NGS data becomes more widely available and could provide the means for reducing Rh alloimmunization in children with SCA. PMID:29296782

Hematologic Complications of Pregnancy

PubMed Central

Townsley, Danielle M.

2013-01-01

Pregnancy induces a number of physiologic changes that affect the hematologic indices, either directly or indirectly. Recognizing and treating hematologic disorders that occur during pregnancy is difficult owing to the paucity of evidence available to guide consultants. This paper specifically reviews the diagnosis and management of benign hematologic disorders occurring during pregnancy. Anemia secondary to iron deficiency is the most frequent hematologic complication and is easily treated with oral iron formulations,; however care must be taken not to miss other causes of anemia, such as sickle cell disease. Thrombocytopenia is also a common reason for consulting the hematologist and distinguishing gestational thrombocytopenia from immune thrombocytopenia (ITP), preeclampsia, HELLP syndrome, or thrombotic thrombocytopenic purpura (TTP) is essential since the treatment differs widely. Occasionally the management of mother and infant involves the expeditious recognition of neonatal alloimmune thrombocytopenia (NAIT), a condition that is responsible for severe life-threatening bleeding of the newborn. Additionally, inherited and acquired bleeding disorders affect pregnant women disproportionately and often require careful monitoring of coagulation parameters in order to prevent bleeding in the puerperium. Finally, venous thromboembolism (VTE) during pregnancy is still largely responsible for mortality during pregnancy and the diagnosis, treatment options and guidelines for prevention of VTE during pregnancy are explored. PMID:23953339

Hematologic complications of pregnancy.

PubMed

Townsley, Danielle M

2013-07-01

Pregnancy induces a number of physiologic changes that affect the hematologic indices, either directly or indirectly. Recognizing and treating hematologic disorders that occur during pregnancy is difficult owing to the paucity of evidence available to guide consultants. This review discusses specifically the diagnosis and management of benign hematologic disorders occurring during pregnancy. Anemia secondary to iron deficiency is the most frequent hematologic complication and is easily treated with oral iron formulations; however, care must be taken not to miss other causes of anemia, such as sickle cell disease. Thrombocytopenia is also a common reason for consulting the hematologist, and distinguishing gestational thrombocytopenia from immune thrombocytopenia (ITP), preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), or thrombotic thrombocytopenic purpura (TTP) is essential since the treatment differs widely. Occasionally the management of mother and infant involves the expeditious recognition of neonatal alloimmune thrombocytopenia (NAIT), a condition that is responsible for severe life-threatening bleeding of the newborn. Additionally, inherited and acquired bleeding disorders affect pregnant women disproportionately and often require careful monitoring of coagulation parameters to prevent bleeding in the puerperium. Finally, venous thromboembolism (VTE) during pregnancy is still largely responsible for mortality during pregnancy, and the diagnosis, treatment options and guidelines for prevention of VTE during pregnancy are explored. Published by Elsevier Inc.

Iron deficiency thrombocytopenia: a case report.

PubMed

Shah, Binay Kumar; Shah, Tara

2011-01-01

To describe a rare case of thrombocytopenia secondary to iron deficiency. A 34-year-old woman presented with severe microcytic hypochromic anemia and thrombocytopenia. Her ferritin was 1 ng/dl. A diagnosis of iron deficiency anemia and thrombocytopenia was made and the patient was treated with packed red blood cell transfusion and intravenous iron. Thrombocytopenia rapidly improved to normal. This case showed that iron deficiency should be considered as a cause of thrombocytopenia in the appropriate setting after ruling out common causes. Copyright © 2011 S. Karger AG, Basel.

Red blood cell and leukocyte alloimmunization in patients awaiting kidney transplantation

PubMed Central

da Silva, Silvia Fernandes Ribeiro; Ferreira, Gláucia Maria; da Silva, Sonia Leite; Alves, Tânia Maria de Oliveira; Ribeiro, Ilana Farias; Ribeiro, Thyciana Rodrigues; Cavalcante, Maria do Carmo Serpa

2013-01-01

Objective To determine the rates of red blood cell and leukocyte alloimmunization in patients with chronic kidney disease awaiting kidney transplantation. Methods In this cross-sectional and prospective study, the serum of 393 chronic kidney disease patients on a transplant waiting list in Ceará, Northeastern Brazil were tested for red cell and leukocyte antibodies. In addition, demographic, clinical and laboratory data were collected. Results The average age in the sample of 393 patients was 34.1 ± 14 years. Slightly more than half (208; 52.9%) were male. The average numbers of transfusions and gestations were 3.1 ± 3.3 and 1.6 ± 6, respectively. One third (33.6%) were alloimmunized: 78% with leukocyte antibodies, 9.1% with red cell antibodies and 12.9% with both. Red cell antibodies were detected in 29 cases (7.4%), 17 of whom were women, who had received more transfusions than the males (p-value < 0.0001). The most frequently detected red cell antibodies belonged to the Rh (24.1%) and Kell (13.8%) blood group systems. Leukocyte antibodies were detected in 30.5% of cases, 83 of whom were women, who had received more transfusions than the males (p-value < 0.0001) and were more reactive to panel reactive antibodies (p-value < 0.0001). The mean alloreactivity to panel reactive antibodies was 47.7 ± 31.2%. Conclusion Chronic kidney disease patients on the transplant waiting list in Ceará, Brazil, display high rates of red cell (7.4%) and leukocyte (30.5%) alloimmunization. In this sample, alloimmunization was significantly associated with the number of transfusions and gender. PMID:23904808

IL-21 Is an Antitolerogenic Cytokine of the Late-Phase Alloimmune Response

PubMed Central

Petrelli, Alessandra; Carvello, Michele; Vergani, Andrea; Lee, Kang Mi; Tezza, Sara; Du, Ming; Kleffel, Sonja; Chengwen, Liu; Mfarrej, Bechara G.; Hwu, Patrick; Secchi, Antonio; Leonard, Warren J.; Young, Deborah; Sayegh, Mohamed H.; Markmann, James F.; Zajac, Allan J.; Fiorina, Paolo

2011-01-01

OBJECTIVE Interleukin-21 (IL-21) is a proinflammatory cytokine that has been shown to affect Treg/Teff balance. However, the mechanism by which IL-21 orchestrates alloimmune response and interplays with Tregs is still unclear. RESEARCH DESIGN AND METHODS The interplay between IL-21/IL-21R signaling, FoxP3 expression, and Treg survival and function was evaluated in vitro in immunologically relevant assays and in vivo in allogenic and autoimmune models of islet transplantation. RESULTS IL-21R expression decreases on T cells and B cells in vitro and increases in the graft in vivo, while IL-21 levels increase in vitro and in vivo during anti-CD3/anti-CD28 stimulation/allostimulation in the late phase of the alloimmune response. In vitro, IL-21/IL-21R signaling (by using rmIL-21 or genetically modified CD4+ T cells [IL-21 pOrf plasmid–treated or hIL-21-Tg mice]) enhances the T-cell response during anti-CD3/anti-CD28 stimulation/allostimulation, prevents Treg generation, inhibits Treg function, induces Treg apoptosis, and reduces FoxP3 and FoxP3-dependent gene transcripts without affecting FoxP3 methylation status. In vivo targeting of IL-21/IL-21R expands intragraft and peripheral Tregs, promotes Treg neogenesis, and regulates the antidonor immune response, whereas IL-21/IL-21R signaling in Doxa-inducible ROSA-rtTA-IL-21-Tg mice expands Teffs and FoxP3− cells. Treatment with a combination of mIL-21R.Fc and CTLA4-Ig (an inhibitor of the early alloimmune response) leads to robust graft tolerance in a purely alloimmune setting and prolonged islet graft survival in NOD mice. CONCLUSIONS IL-21 interferes with different checkpoints of the FoxP3 Treg chain in the late phase of alloimmune response and, thus, acts as an antitolerogenic cytokine. Blockade of the IL-21/IL-21R pathway could be a precondition for tolerogenic protocols in transplantation. PMID:22013017

Genetics Home Reference: X-linked thrombocytopenia

MedlinePlus

... Facebook Twitter Home Health Conditions X-linked thrombocytopenia X-linked thrombocytopenia Printable PDF Open All Close All ... Javascript to view the expand/collapse boxes. Description X-linked thrombocytopenia is a bleeding disorder that primarily ...

Red blood cell alloimmunization among sickle cell Kuwaiti Arab patients who received red blood cell transfusion.

PubMed

Ameen, Reem; Al Shemmari, Salem; Al-Bashir, Abdulaziz

2009-08-01

Sickle cell disease (SCD) is common in the Arabian Gulf region. Most cases require a red blood cell (RBC) transfusion, increasing the potential for RBC alloantibody development. The incidence of RBC alloimmunization among Kuwaiti Arab SCD patients is not yet known. This study retrospectively assessed the effect of using two different matching protocols on the incidence of alloimmunization among multiply transfused Kuwaiti Arab SCD patients. A total of 233 Kuwaiti Arab SCD patients were divided into two groups: Group 1 (n = 110) received RBC transfusion through standard ABO- and D-matched nonleukoreduced blood; Group 2 (n = 123) received RBCs matched for ABO, Rh, and K1 poststorage-leukoreduced blood. Multivariate analysis was performed on the factors associated with RBC alloimmunization and antibody specificity. Sixty-five percent of patients in Group 1 developed clinically significant RBC alloantibody with an increased prevalence in females; in patients in Group 2, 23.6% developed RBC alloantibodies (p = 0.01). In Group 1, 72 patients (65.5%) had alloantibodies directed against Rh and Kell systems (p = 0.01). Multivariate analysis further confirmed the results, showing that blood transfusion type and sex have significant effects on the rate of alloimmunizations. This study confirms the importance of selecting RBCs matched for Rh and Kell to reduce the risk of alloimmunizations among Kuwaiti Arab SCD patients.

Biphasic rattlesnake venom-induced thrombocytopenia.

PubMed

Offerman, Steven R; Barry, J David; Schneir, Aaron; Clark, Richard F

2003-04-01

Thrombocytopenia is a common occurrence in moderate to severe crotaline envenomation. The exact mechanism by which rattlesnake venom leads to thrombocytopenia is unclear, but aggressive treatment with crotaline-specific antivenom often leads to resolution of this disorder. Crotalinae Polyvalent Immune Fab (CroFab(TM), Protherics Inc., Nashville, TN) (crotaline Fab) is now available for the treatment of symptomatic rattlesnake envenomation. Although recurrence of thrombocytopenia has been reported in patients after envenomation treated with crotaline Fab, cases refractory to this therapy have not been described. We report a case of severe crotaline envenomation that appears to have exhibited two separate episodes of thrombocytopenia, only one of which responded to antivenom. The second, later phase was refractory to both crotaline Fab as well as traditional Antivenin (Crotalinae) Polyvalent (Wyeth-Ayerst Pharmaceuticals, Philadelphia, PA) (ACP). By reviewing the literature regarding venom-induced thrombocytopenia, we attempt to explain this "biphasic" phenomenon and the inability of crotaline Fab to reverse this toxic effect.

Immunopathology of thrombocytopenia in experimental malaria.

PubMed

Grau, G E; Piguet, P F; Gretener, D; Vesin, C; Lambert, P H

1988-12-01

An early thrombocytopenia was observed in CBA mice during acute infection with Plasmodium berghei. This was associated with an increase in bone marrow megakaryocytes and a reduction of normal syngeneic 111Indium-labelled platelet life span. Malaria-induced thrombocytopenia was thus considered to be the result of increased peripheral platelet destruction rather than central hypoproduction. The occurrence of thrombocytopenia was modulated by T-cell depletion. Indeed, thymectomized, irradiated or anti-CD4 monoclonal antibody-treated mice failed to develop thrombocytopenia, although they were infected to the same extent. Conversely, a significant thrombocytopenia was observed in thymectomized mice reconstituted with CD4+ T cells. During the course of infection, a significant inverse correlation was found between platelet counts and platelet-associated IgG. Normal mice passively transferred with serum from syngeneic malaria-infected mice developed thrombocytopenia. The possibility to raise monoclonal anti-platelet antibodies from P. berghei-infected animals further suggested a role for an antibody-mediated platelet destruction during acute murine malaria infection. These results indicate that in murine malaria, thrombocytopenia is mediated by immune mechanisms and that CD4+ T cells might be significantly involved.

Immunopathology of thrombocytopenia in experimental malaria.

PubMed Central

Grau, G E; Piguet, P F; Gretener, D; Vesin, C; Lambert, P H

1988-01-01

An early thrombocytopenia was observed in CBA mice during acute infection with Plasmodium berghei. This was associated with an increase in bone marrow megakaryocytes and a reduction of normal syngeneic 111Indium-labelled platelet life span. Malaria-induced thrombocytopenia was thus considered to be the result of increased peripheral platelet destruction rather than central hypoproduction. The occurrence of thrombocytopenia was modulated by T-cell depletion. Indeed, thymectomized, irradiated or anti-CD4 monoclonal antibody-treated mice failed to develop thrombocytopenia, although they were infected to the same extent. Conversely, a significant thrombocytopenia was observed in thymectomized mice reconstituted with CD4+ T cells. During the course of infection, a significant inverse correlation was found between platelet counts and platelet-associated IgG. Normal mice passively transferred with serum from syngeneic malaria-infected mice developed thrombocytopenia. The possibility to raise monoclonal anti-platelet antibodies from P. berghei-infected animals further suggested a role for an antibody-mediated platelet destruction during acute murine malaria infection. These results indicate that in murine malaria, thrombocytopenia is mediated by immune mechanisms and that CD4+ T cells might be significantly involved. PMID:3065215

Frequency of Red Cell Alloimmunization and Autoimmunization in Thalassemia Patients: A Report from Eastern India.

PubMed

Datta, Suvro Sankha; Mukherjee, Somnath; Talukder, Biplabendu; Bhattacharya, Prasun; Mukherjee, Krishnendu

2015-01-01

Introduction. Red blood cell (RBC) alloimmunization and autoimmunization remain a major problem in transfusion dependent thalassemic patients. There is a paucity of data on the incidence of RBC alloimmunization and autoimmunization in thalassemic patients from eastern part of India, as pretransfusion antibody screening is not routinely performed. Aims. To assess the incidence of RBC alloimmunization and autoimmunization in transfusion dependent thalassemic patients in eastern India. Materials and Methods. Total 500 thalassemia cases were evaluated. The antibody screening and identification were performed with commercially available panel cells (Diapanel, Bio-rad, Switzerland) by column agglutination method. To detect autoantibodies, autocontrol and direct antiglobulin tests were carried out using polyspecific coombs (IgG + C3d) gel cards in all patients. Results. A total of 28 patients developed RBC alloimmunization (5.6%) and 5 patients had autoantibodies (1%). Alloantibody against c had the highest incidence (28.57%) followed by E (21.42%). Five out of 28 (17.85%) patients had developed antibodies against both c and E. Conclusion. Data from this study demonstrate that the RBC alloantibody and autoantibody development rates are significant in our region. Thus, pretransfusion antibody screening needs to be initiated in eastern India in order to ensure safe transfusion practice.

Frequency of Red Cell Alloimmunization and Autoimmunization in Thalassemia Patients: A Report from Eastern India

PubMed Central

Datta, Suvro Sankha; Talukder, Biplabendu; Bhattacharya, Prasun; Mukherjee, Krishnendu

2015-01-01

Introduction. Red blood cell (RBC) alloimmunization and autoimmunization remain a major problem in transfusion dependent thalassemic patients. There is a paucity of data on the incidence of RBC alloimmunization and autoimmunization in thalassemic patients from eastern part of India, as pretransfusion antibody screening is not routinely performed. Aims. To assess the incidence of RBC alloimmunization and autoimmunization in transfusion dependent thalassemic patients in eastern India. Materials and Methods. Total 500 thalassemia cases were evaluated. The antibody screening and identification were performed with commercially available panel cells (Diapanel, Bio-rad, Switzerland) by column agglutination method. To detect autoantibodies, autocontrol and direct antiglobulin tests were carried out using polyspecific coombs (IgG + C3d) gel cards in all patients. Results. A total of 28 patients developed RBC alloimmunization (5.6%) and 5 patients had autoantibodies (1%). Alloantibody against c had the highest incidence (28.57%) followed by E (21.42%). Five out of 28 (17.85%) patients had developed antibodies against both c and E. Conclusion. Data from this study demonstrate that the RBC alloantibody and autoantibody development rates are significant in our region. Thus, pretransfusion antibody screening needs to be initiated in eastern India in order to ensure safe transfusion practice. PMID:26425124

Red blood cell alloimmunization in sickle cell disease: pathophysiology, risk factors, and transfusion management.

PubMed

Yazdanbakhsh, Karina; Ware, Russell E; Noizat-Pirenne, France

2012-07-19

Red blood cell transfusions have reduced morbidity and mortality for patients with sickle cell disease. Transfusions can lead to erythrocyte alloimmunization, however, with serious complications for the patient including life-threatening delayed hemolytic transfusion reactions and difficulty in finding compatible units, which can cause transfusion delays. In this review, we discuss the risk factors associated with alloimmunization with emphasis on possible mechanisms that can trigger delayed hemolytic transfusion reactions in sickle cell disease, and we describe the challenges in transfusion management of these patients, including opportunities and emerging approaches for minimizing this life-threatening complication.

Corticosteroids compared with intravenous immunoglobulin for the treatment of immune thrombocytopenia in pregnancy.

PubMed

Sun, Dongmei; Shehata, Nadine; Ye, Xiang Y; Gregorovich, Sandra; De France, Bryon; Arnold, Donald M; Shah, Prakesh S; Malinowski, Ann Kinga

2016-09-08

Treatment options for immune thrombocytopenia (ITP) in pregnancy are limited, and evidence to guide management decisions is lacking. This retrospective study of singleton pregnancies from 2 tertiary centers compared the effectiveness of intravenous immunoglobulin (IVIg) and corticosteroids in treatment of ITP. Data from 195 women who had 235 pregnancies were reviewed. Treatment was not required in 137 pregnancies (58%). Of the remaining 98 pregnancies in 91 women, 47 (48%) were treated with IVIg and 51 were treated with corticosteroids as the initial intervention. Mean maternal platelet count at birth did not differ between groups (IVIg 69 × 10(9)/L vs corticosteroids 77 × 10(9)/L; P = .71) nor did the proportion of mothers who achieved a platelet count response (IVIg 38% vs corticosteroids 39%; P = .85). There were no fatal or severe maternal, fetal, or neonatal hemorrhages. Of 203 neonates in whom platelet counts were available, 56 (28%) had a birth platelet count <150 × 10(9)/L and 18 (9%) had platelet counts <50 × 10(9)/L. Nadir platelet counts for most affected neonates occurred at birth, although for some neonates, nadir platelet counts occurred up to 6 days postnatally. Intracranial hemorrhage was noted in 2 neonates (nadir platelet counts were 135 and 18 × 10(9)/L). There were no neonatal deaths. The majority of pregnant women with a history of ITP did not require treatment, and neonatal outcomes were comparable for mothers who received IVIg or corticosteroids for treatment of maternal ITP. © 2016 by The American Society of Hematology.

Alloimmunity and Tolerance in Corneal Transplantation.

PubMed

Amouzegar, Afsaneh; Chauhan, Sunil K; Dana, Reza

2016-05-15

Corneal transplantation is one of the most prevalent and successful forms of solid tissue transplantation. Despite favorable outcomes, immune-mediated graft rejection remains the major cause of corneal allograft failure. Although low-risk graft recipients with uninflamed graft beds enjoy a success rate ∼90%, the rejection rates in inflamed graft beds or high-risk recipients often exceed 50%, despite maximal immune suppression. In this review, we discuss the critical facets of corneal alloimmunity, including immune and angiogenic privilege, mechanisms of allosensitization, cellular and molecular mediators of graft rejection, and allotolerance induction. Copyright © 2016 by The American Association of Immunologists, Inc.

Alloimmunization and autoimmunization in transfusion dependent thalassemia major patients: Study on 319 patients

PubMed Central

Dhawan, Hari Krishan; Kumawat, Vijay; Marwaha, Neelam; Sharma, Ratti Ram; Sachdev, Suchet; Bansal, Deepak; Marwaha, Ram Kumar; Arora, Satyam

2014-01-01

Background: The development of anti-red blood cell antibodies (both allo-and autoantibodies) remains a major problem in thalassemia major patients. We studied the frequency of red blood cell (RBC) alloimmunization and autoimmunization among thalassemia patients who received regular transfusions at our center and analyzed the factors, which may be responsible for development of these antibodies. Materials and Methods: The study was carried out on 319 multiply transfused patients with β-thalassemia major registered with thalassemia clinic at our institute. Clinical and transfusion records of all the patients were examined for age of patients, age at initiation of transfusion therapy, total number of blood units transfused, transfusion interval, status of splenectomy or other interventions. Alloantibody screening and identification was done using three cell and 11 cell panel (Diapanel, Bio-rad, Switzerland) respectively. To detect autoantibodies, autocontrol was carried out using polyspecific coombs (IgG + C3d) gel cards. Results: Eighteen patients out of total 319 patients (5.64%) developed alloantibodies and 90 (28.2%) developed autoantibodies. Nine out of 18 patients with alloantibodies also had autoantibodies. Age at first transfusion was significantly higher in alloimmunized than non-immunized patients (P = 0.042). Out of 23 alloantibodies, 52.17% belonged to Rh blood group system (Anti-E = 17%, Anti D = 13%, Anti-C = 13%, Anti-Cw = 9%), 35% belonged to Kell blood group system, 9% of Kidd and 4% of Xg blood group system. Conclusion: Alloimmunization was detected in 5.64% of multitransfused thalassemia patients. Rh and Kell blood group system antibodies accounted for more than 80% of alloantibodies. This study re-emphasizes the need for RBC antigen typing before first transfusion and issue of antigen matched blood (at least for Rh and Kell antigen). Early institution of transfusion therapy after diagnosis is another means of decreasing alloimmunization. PMID

Alloimmunization and autoimmunization in transfusion dependent thalassemia major patients: Study on 319 patients.

PubMed

Dhawan, Hari Krishan; Kumawat, Vijay; Marwaha, Neelam; Sharma, Ratti Ram; Sachdev, Suchet; Bansal, Deepak; Marwaha, Ram Kumar; Arora, Satyam

2014-07-01

The development of anti-red blood cell antibodies (both allo-and autoantibodies) remains a major problem in thalassemia major patients. We studied the frequency of red blood cell (RBC) alloimmunization and autoimmunization among thalassemia patients who received regular transfusions at our center and analyzed the factors, which may be responsible for development of these antibodies. The study was carried out on 319 multiply transfused patients with β-thalassemia major registered with thalassemia clinic at our institute. Clinical and transfusion records of all the patients were examined for age of patients, age at initiation of transfusion therapy, total number of blood units transfused, transfusion interval, status of splenectomy or other interventions. Alloantibody screening and identification was done using three cell and 11 cell panel (Diapanel, Bio-rad, Switzerland) respectively. To detect autoantibodies, autocontrol was carried out using polyspecific coombs (IgG + C3d) gel cards. Eighteen patients out of total 319 patients (5.64%) developed alloantibodies and 90 (28.2%) developed autoantibodies. Nine out of 18 patients with alloantibodies also had autoantibodies. Age at first transfusion was significantly higher in alloimmunized than non-immunized patients (P = 0.042). Out of 23 alloantibodies, 52.17% belonged to Rh blood group system (Anti-E = 17%, Anti D = 13%, Anti-C = 13%, Anti-C(w) = 9%), 35% belonged to Kell blood group system, 9% of Kidd and 4% of Xg blood group system. Alloimmunization was detected in 5.64% of multitransfused thalassemia patients. Rh and Kell blood group system antibodies accounted for more than 80% of alloantibodies. This study re-emphasizes the need for RBC antigen typing before first transfusion and issue of antigen matched blood (at least for Rh and Kell antigen). Early institution of transfusion therapy after diagnosis is another means of decreasing alloimmunization.

Thrombocytopenia in leukemia: Pathogenesis and prognosis.

PubMed

Shahrabi, Saeid; Behzad, Masumeh Maleki; Jaseb, Kaveh; Saki, Najmaldin

2018-02-20

Leukemias, a heterogeneous group of hematological disorders, are characterized by ineffective hematopoiesis and morphologic abnormalities of hematopoietic cells. Thrombocytopenia is a common problem among leukemia types that can lead to hemorrhagic complications in patients. The purpose of this review article is to identify the conditions associated with the incidence of thrombocytopenia in leukemias. It can be stated that although translocations have been considered responsible for this complication in many studies, other factors such as bone marrow failure, genes polymorphism, a mutation in some transcription factors, and the adverse effects of treatment could be associated with pathogenesis and poor prognosis of thrombocytopenia in leukemias. Considering the importance of thrombocytopenia in leukemias, it is hoped that the recognition of risk factors increasing the incidence of this complication in leukemic patients would be useful for prevention and treatment of this disorder.

Alloimmunization is associated with older age of transfused red blood cells in sickle cell disease.

PubMed

Desai, Payal C; Deal, Allison M; Pfaff, Emily R; Qaqish, Bahjat; Hebden, Leyna M; Park, Yara A; Ataga, Kenneth I

2015-08-01

Red blood cell (RBC) alloimmunization is a significant clinical complication of sickle cell disease (SCD). It can lead to difficulty with cross-matching for future transfusions and may sometimes trigger life-threatening delayed hemolytic transfusion reactions. We conducted a retrospective study to explore the association of clinical complications and age of RBC with alloimmunization in patients with SCD followed at a single institution from 2005 to 2012. One hundred and sixty six patients with a total of 488 RBC transfusions were evaluated. Nineteen patients (11%) developed new alloantibodies following blood transfusions during the period of review. The median age of RBC units was 20 days (interquartile range: 14-27 days). RBC antibody formation was significantly associated with the age of RBC units (P = 0.002), with a hazard ratio of 3.5 (95% CI: 1.71-7.11) for a RBC unit that was 7 days old and 9.8 (95% CI: 2.66-35.97) for a unit that was 35 days old, 28 days after the blood transfusion. No association was observed between RBC alloimmunization and acute vaso-occlusive complications. Although increased echocardiography-derived tricuspid regurgitant jet velocity (TRV) was associated with the presence of RBC alloantibodies (P = 0.02), TRV was not significantly associated with alloimmunization when adjusted for patient age and number of transfused RBC units. Our study suggests that RBC antibody formation is significantly associated with older age of RBCs at the time of transfusion. Prospective studies in patients with SCD are required to confirm this finding. © 2015 Wiley Periodicals, Inc.

Clinical picture of heparin-induced thrombocytopenia (HIT) and its differentiation from non-HIT thrombocytopenia.

PubMed

Warkentin, Theodore E

2016-10-28

HIT is an acquired antibody-mediated disorder strongly associated with thrombosis, including microthrombosis secondary to disseminated intravascular dissemination (DIC). The clinical features of HIT are reviewed from the perspective of the 4Ts scoring system for HIT, which emphasises its characteristic timing of onset of thrombocytopenia. HIT antibodies recognize multimolecular complexes of platelet factor 4 (PF4)/heparin. However, a subset of HIT sera recognise PF4 bound to platelet chondroitin sulfate; these antibodies activate platelets in vitro and in vivo even in the absence of heparin, thus explaining: delayed-onset HIT (where HIT begins or worsens after stopping heparin); persisting HIT (where HIT takes several weeks to recover); spontaneous HIT syndrome (a disorder clinically and serologically resembling HIT but without proximate heparin exposure); and fondaparinux-associated HIT (four distinct syndromes featuring thrombocytopenia that begins or worsens during treatment with fondaparinux), with a new patient case presented with ongoing thrombocytopenia (and fatal haemorrhage) during treatment of HIT with fondaparinux, with fondaparinux-dependent platelet activation induced by patient serum ("fondaparinux cross-reactivity"). Ironically, despite existence of fondaparinux-associated HIT, this pentasaccharide anticoagulant is a frequent treatment for HIT (including one used by the author). HIT can be confused with other disorders, including those with a) timing similar to HIT (e. g. abciximab-associated thrombocytopenia of delayed-onset); b) combined thrombocytopenia/thrombosis (e. g. symmetrical peripheral gangrene secondary to acute DIC and shock liver); and c) both timing of onset and thrombosis (e. g. warfarin-associated venous limb gangrene complicating cancer-associated DIC). By understanding clinical and pathophysiological similarities and differences between HIT and non-HIT mimicking disorders, the clinician is better able to make the correct

Granulocyte colony stimulating factor treatment for neonatal neutropenia.

PubMed Central

Russell, A. R.; Davies, E. G.; Ball, S. E.; Gordon-Smith, E.

1995-01-01

In a pilot study recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered to 12 neutropenic preterm infants to determine if neonatal neutropenia is secondary to decreased endogenous G-CSF production. Respiratory variables were monitored because of the possible link between inflammatory cells and hyaline membrane disease. All infants showed increased neutrophil counts. The only possible side effect observed was an exacerbation of thrombocytopenia. PMID:7538031

Severe Thrombocytopenia after Zika Virus Infection, Guadeloupe, 2016.

PubMed

Boyer Chammard, Timothée; Schepers, Kinda; Breurec, Sébastien; Messiaen, Thierry; Destrem, Anne-Laure; Mahevas, Matthieu; Soulillou, Adrien; Janaud, Ludovic; Curlier, Elodie; Herrmann-Storck, Cécile; Hoen, Bruno

2017-04-01

Severe thrombocytopenia during or after the course of Zika virus infection has been rarely reported. We report 7 cases of severe thrombocytopenia and hemorrhagic signs and symptoms in Guadeloupe after infection with this virus. Clinical course and laboratory findings strongly suggest a causal link between Zika virus infection and immune-mediated thrombocytopenia.

Severe Thrombocytopenia after Zika Virus Infection, Guadeloupe, 2016

PubMed Central

Boyer Chammard, Timothée; Schepers, Kinda; Breurec, Sébastien; Messiaen, Thierry; Destrem, Anne-Laure; Mahevas, Matthieu; Soulillou, Adrien; Janaud, Ludovic; Curlier, Elodie; Herrmann-Storck, Cécile

2017-01-01

Severe thrombocytopenia during or after the course of Zika virus infection has been rarely reported. We report 7 cases of severe thrombocytopenia and hemorrhagic signs and symptoms in Guadeloupe after infection with this virus. Clinical course and laboratory findings strongly suggest a causal link between Zika virus infection and immune-mediated thrombocytopenia. PMID:27997330

Significant correlation between spleen volume and thrombocytopenia in liver transplant patients: a concept for predicting persistent thrombocytopenia.

PubMed

Ohira, Masahiro; Ishifuro, Minoru; Ide, Kentaro; Irei, Toshimitsu; Tashiro, Hirotaka; Itamoto, Toshiyuki; Ito, Katsuhide; Chayama, Kazuaki; Asahara, Toshimasa; Ohdan, Hideki

2009-02-01

Interferon (IFN) therapy with or without ribavirin treatment is well established as a standard antiviral treatment for hepatitis C virus (HCV)-infected patients. However, susceptibility to thrombocytopenia is a major obstacle for initiating or continuing this therapy, particularly in liver transplant (LTx) recipients with HCV. Studies have reported that splenectomy performed concurrently with LTx is a feasible strategy for conditioning patients for anti-HCV IFN therapy. However, the relationship between the severity of splenomegaly and alterations in the blood cytopenia in LTx recipients remains to be clarified. Here, we analyzed the relationship between spleen volume (SV) and thrombocytopenia in 45 patients who underwent LTx at Hiroshima University Hospital. The extent of pre-LTx splenomegaly [the SV to body surface area (BSA) ratio in an individual] was inversely correlated with both the post-LTx white blood cell count and platelet (PLT) count (P < 0.001). Furthermore, the PLT count of patients with thrombocytopenia (PLT count thrombocytopenia coexist (PLT count or= 400), persistent thrombocytopenia is predictable after LTx. (c) 2009 AASLD.

Transfusion-related alloimmune neutropenia with no pulmonary complications: one donor-five cases.

PubMed

Hauck-Dlimi, Barbara; Ruppel, Renate; Zimmermann, Robert; Strobel, Julian; Reil, Angelika; Eckstein, Reinhold; Zingsem, Juergen

2016-01-01

Neutrophil alloantibodies are well-known triggers of transfusion-related acute lung injury (TRALI) and also cause immune neutropenia. Alloimmune neutropenia due to transfusion is an isolated phenomenon that is only rarely identified. Its incidence is specified in the literature as being less than one in 10,000 transfused plasma-containing units. We expect that this phenomenon is underreported. We observed five cases of alloimmune neutropenia with no respiratory complications with only one case initially reported as a suspected transfusion reaction. The other four cases were detected in the course of the subsequent lookback investigation. The first case was reported as a potential transfusion reaction when a female patient showed a decrease in the white blood cell count after a platelet (PLT) transfusion. Examinations of the donor blood revealed an antibody against the human neutrophil antigen HNA-1b; the recipient was typed HNA-1b positive and HNA-1a negative. After examining the blood counts of other patients who previously received PLT concentrates from the same donor, we identified four other patients with an unreported decrease in the leukocyte and/or granulocyte count of more than approximately 50% after transfusion. HNA antibodies are generally regarded as potential triggers of TRALI. Here we describe an HNA antibody that reproducibly caused transfusion-related neutropenia only without pulmonary complications. Factors predisposing patients to TRALI development are widely discussed. Our case suggests that antibody characteristics are also relevant in the development of TRALI. Current measures to prevent TRALI should also prevent transfusion-related alloimmune neutropenia. © 2015 AABB.

Genetics Home Reference: thrombocytopenia-absent radius syndrome

MedlinePlus

... half of affected individuals have allergic reactions to cow's milk that may worsen the thrombocytopenia associated with ... Central Mokha J, Serrano M. Thrombocytopenia associated with cow's milk protein allergy: a case report. Clin Pediatr ( ...

Immune thrombocytopenia and autoimmune thyroid disease: a controversial overlap.

PubMed

Marta, Guilherme Nader; de Campos, Fernando Peixoto Ferraz

2015-01-01

Immune thrombocytopenia (ITP) is an entity characterized by a platelet count of less than 100 × 10(9)/L in the absence of other causes of thrombocytopenia, such as viral infections, rheumatic diseases, or drugs. Grave's disease is also an autoimmune condition in which thrombocytopenia is often observed. Moreover, in the literature, many reports show a marked interference of the thyroid dysfunction (mainly hyperthyroidism) in the control of thrombocytopenia. Although this issue still remains debatable, the authors report the case of a young woman with a previous diagnosis of ITP with a brilliant initial response to corticotherapy. Some years after this diagnosis, the patient presented thyrotoxicosis due to Grave's disease and the thrombocytopenia relapsed, but this time there was no response to the glucocorticoids. Only after the radioiodine I-131 thyroid ablation the control of thrombocytopenia was achieved. The authors call attention to this overlap and for testing thyroid function in every patient with an unexpected negative response to corticotherapy.

Immune thrombocytopenia and autoimmune thyroid disease: a controversial overlap

PubMed Central

de Campos, Fernando Peixoto Ferraz

2015-01-01

Immune thrombocytopenia (ITP) is an entity characterized by a platelet count of less than 100 × 109/L in the absence of other causes of thrombocytopenia, such as viral infections, rheumatic diseases, or drugs. Grave’s disease is also an autoimmune condition in which thrombocytopenia is often observed. Moreover, in the literature, many reports show a marked interference of the thyroid dysfunction (mainly hyperthyroidism) in the control of thrombocytopenia. Although this issue still remains debatable, the authors report the case of a young woman with a previous diagnosis of ITP with a brilliant initial response to corticotherapy. Some years after this diagnosis, the patient presented thyrotoxicosis due to Grave’s disease and the thrombocytopenia relapsed, but this time there was no response to the glucocorticoids. Only after the radioiodine I-131 thyroid ablation the control of thrombocytopenia was achieved. The authors call attention to this overlap and for testing thyroid function in every patient with an unexpected negative response to corticotherapy. PMID:26484334

Nucleated red blood cells in growth-restricted fetuses: associations with short-term neonatal outcome.

PubMed

Minior, V K; Bernstein, P S; Divon, M Y

2000-01-01

To determine the utility of the neonatal nucleated red blood cell (NRBC) count as an independent predictor of short-term perinatal outcome in growth-restricted fetuses. Hospital charts of neonates with a discharge diagnosis indicating a birth weight <10th percentile were reviewed for perinatal outcome. We studied all eligible neonates who had a complete blood count on the first day of life. After multiple gestations, anomalous fetuses and diabetic pregnancies were excluded; 73 neonates comprised the study group. Statistical analysis included ANOVA, simple and stepwise regression. Elevated NRBC counts were significantly associated with cesarean section for non-reassuring fetal status, neonatal intensive care unit admission and duration of neonatal intensive care unit stay, respiratory distress and intubation, thrombocytopenia, hyperbilirubinemia, intraventricular hemorrhage and neonatal death. Stepwise regression analysis including gestational age at birth, birth weight and NRBC count demonstrated that in growth-restricted fetuses, NRBC count was the strongest predictor of neonatal intraventricular hemorrhage, neonatal respiratory distress and neonatal death. An elevated NRBC count independently predicts adverse perinatal outcome in growth-restricted fetuses. Copyright 2000 S. Karger AG, Basel.

Therapeutic Amenorrhea in Patients at Risk for Thrombocytopenia

PubMed Central

Martin-Johnston, Meredith K.; Okoji, Olanma Y.; Armstrong, Alicia

2016-01-01

To examine the need for and evaluate the method of menses suppression in women at risk for thrombocytopenia. A systematic review of the published literature in MEDLINE using the search terms thrombocytopenia, menorrhagia, therapeutic amenorrhea, progestin intrauterine device, combination oral contraceptive—extended and cyclic, gonadotropin releasing hormone agonist, danazol, and progestins. There are an increased number of reproductive age women at risk for thrombocytopenia who would benefit from menses suppression. A number of effective medical regimens are available. In patients who fail medical therapy, endometrial ablation appears to be effective in women with thrombocytopenia. As a result of the increased number of women at risk for thrombocytopenia, there is a need for therapeutic amenorrhea. The type of regimen selected depends upon the patients need for contraception and the ability to tolerate estrogen-containing medications. For women who fail medical therapy, there are surgical options, which are associated with less morbidity than hysterectomy. PMID:18492296

Heparin-induced thrombocytopenia

PubMed Central

2017-01-01

Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin. Pathogenic antibodies to PF4/heparin bind and activate cellular FcγRIIA on platelets and monocytes to propagate a hypercoagulable state culminating in life-threatening thrombosis. It is now recognized that anti-PF4/heparin antibodies develop commonly after heparin exposure, but only a subset of sensitized patients progress to life-threatening complications of thrombocytopenia and thrombosis. Recent scientific developments have clarified mechanisms underlying PF4/heparin immunogenicity, disease susceptibility, and clinical manifestations of disease. Insights from clinical and laboratory findings have also been recently harnessed for disease prevention. This review will summarize our current understanding of HIT by reviewing pathogenesis, essential clinical and laboratory features, and management. PMID:28416511

How do we approach thrombocytopenia in critically ill patients?

PubMed

Thachil, Jecko; Warkentin, Theodore E

2017-04-01

A low platelet count is a frequently encountered haematological abnormality in patients treated in intensive treatment units (ITUs). Although severe thrombocytopenia (platelet count <20 × 10 9 /l) can be associated with bleeding, even moderate-degree thrombocytopenia is associated with organ failure and adverse prognosis. The aetiology for thrombocytopenia in ITU is often multifactorial and correcting one aetiology may not normalise the low platelet count. The classical view for thrombocytopenia in this setting is consumption associated with thrombin-mediated platelet activation, but other concepts, including platelet adhesion to endothelial cells and leucocytes, platelet aggregation by increased von Willebrand factor release, red cell damage and histone release, and platelet destruction by the complement system, have recently been described. The management of severe thrombocytopenia is platelet transfusion in the presence of active bleeding or invasive procedure, but the risk-benefit of prophylactic platelet transfusions in this setting is uncertain. In this review, the incidence and mechanisms of thrombocytopenia in patients with ITU, its prognostic significance and the impact on organ function is discussed. A practical approach based on the authors' experience is described to guide management of a critically ill patient who develops thrombocytopenia. © 2016 John Wiley & Sons Ltd.

Identifying drugs that cause acute thrombocytopenia: an analysis using 3 distinct methods

PubMed Central

Reese, Jessica A.; Li, Xiaoning; Hauben, Manfred; Aster, Richard H.; Bougie, Daniel W.; Curtis, Brian R.; George, James N.

2010-01-01

Drug-induced immune thrombocytopenia (DITP) is often suspected in patients with acute thrombocytopenia unexplained by other causes, but documenting that a drug is the cause of thrombocytopenia can be challenging. To provide a resource for diagnosis of DITP and for drug safety surveillance, we analyzed 3 distinct methods for identifying drugs that may cause thrombocytopenia. (1) Published case reports of DITP have described 253 drugs suspected of causing thrombocytopenia; using defined clinical criteria, 87 (34%) were identified with evidence that the drug caused thrombocytopenia. (2) Serum samples from patients with suspected DITP were tested for 202 drugs; drug-dependent, platelet-reactive antibodies were identified for 67 drugs (33%). (3) The Food and Drug Administration's Adverse Event Reporting System database was searched for drugs associated with thrombocytopenia by use of data mining algorithms; 1444 drugs had at least 1 report associated with thrombocytopenia, and 573 (40%) drugs demonstrated a statistically distinctive reporting association with thrombocytopenia. Among 1468 drugs suspected of causing thrombocytopenia, 102 were evaluated by all 3 methods, and 23 of these 102 drugs had evidence for an association with thrombocytopenia by all 3 methods. Multiple methods, each with a distinct perspective, can contribute to the identification of drugs that can cause thrombocytopenia. PMID:20530792

Safe fetal platelet genotyping: new developments.

PubMed

Le Toriellec, Emilie; Chenet, Christophe; Kaplan, Cecile

2013-08-01

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is due to maternal alloimmunization against fetal platelet (PLT) antigens. Antenatal management strategies have been developed to avoid complications such as intracranial hemorrhage. The aim of this study was to set up two reliable, noninvasive fetal genotyping assays to determine the fetal risk in pregnancies in which the father is heterozygous for the offending antigen. This study focused on human PLT antigen (HPA)-1, the most frequently implicated antigen in FNAIT in Caucasians. Two assays based on cell-free fetal DNA extracted from maternal blood samples and on real-time polymerase chain reaction (QPCR) were developed: an allele-specific QPCR specifically targeting the polymorphic sequence in HPA-1 and the study of the variation in the high-resolution melting curve of amplicons containing the polymorphic region. All results from the 49 samples obtained from 29 pregnant women were consistent with expectations. Six women were compatible with their fetuses (three HPA-1aa women and three HPA-1bb women), 41 HPA-1bb women were incompatible with their fetuses, as were two HPA-1aa women. Two fetal PLT genotyping assays on maternal blood samples proved to be reliable as of 15 weeks of gestation, thereby avoiding invasive techniques such as amniocentesis. © 2012 American Association of Blood Banks.

Brain ultrasound findings in neonates treated with intrauterine transfusion for fetal anaemia.

PubMed

Leijser, Lara M; Vos, Nikki; Walther, Frans J; van Wezel-Meijler, Gerda

2012-09-01

The main causes of severe fetal anaemia are red-cell allo-immunization, parvo B19 virus infection and feto-maternal haemorrhage. Treatment consists of intrauterine transfusion (IUT). Neuro-imaging studies in surviving neonates treated with IUT are scarce. To assess if neonates treated with IUT for fetal anaemia are at risk for cerebral injury, report the incidence and severity of brain ultrasound (US) abnormalities and explore the relation between brain US findings and perinatal parameters and neurological outcome. Brain US scans of neonates born alive between 2001 and 2008 with at least one IUT were retrospectively reviewed and classified as normal, mildly or moderately/severely abnormal. Incidences of abnormalities were calculated for full-term and preterm neonates. Presence and severity of abnormalities were related to clinical and IUT related parameters and to neurological outcome around 2 years of age (adverse: moderate or severe disability; favourable: normal or mild disability). A total of 127 neonates (82 born preterm) were included. Median number of IUTs was 3 (range 1-6) and of brain US 2 (1-6). Median gestational age and weight at birth were 36.6 (26.0-41.1) weeks and 2870 (1040-3950)g. In 72/127 (57%) neonates ≥1 abnormality was seen on brain US, classified as moderate/severe in 30/127 (24%). Neurological outcome was adverse in 5 infants. Presence of brain US abnormalities was not significantly related to any of the perinatal parameters or to neurological outcome. Neonates undergoing IUT for fetal anaemia are at high risk of brain injury. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Retrospective analysis of patients with thrombocytopenia after patent ductus arteriosus interventional occlusion].

PubMed

Liao, Qi-wei; Zhang, Wei-hua; Guang, Xue-feng; Lu, Yi-bing

2013-03-01

To explore the risk factors of patent ductus arteriosus (PDA) patients with thrombocytopenia after PDA interventional occlusion. Thrombocytopenia occurred in 14 out of 350 patients underwent PDA occlusion. Age, gender, body weight, PDA size, occluder size, mean pulmonary arterial pressure, the dose of heparin, the manufacturer of occluder, residual shunt after operation were analyzed. The recovery time of different grades of thrombocytopenia was observed. Multivariate logistic regression showed that the PDA size (OR = 2.238, P < 0.05), the dose of heparin (OR = 3.247, P < 0.05), residual shunt after operation (OR = 1.912, P < 0.01) were the independent risk factors of thrombocytopenia after PDA occlusion. The recovery time of mild thrombocytopenia was (7 ± 2) days without treatment. The recovery time of moderate thrombocytopenia was (12 ± 4) days with glucocorticoids treatment. The recovery time of severe thrombocytopenia was (21 ± 7) days with platelet transfusion. The occluder size, dose of heparin, residual shunt are the independent risk factors of thrombocytopenia after PDA interventional occlusion. Recover time of thrombocytopenia after PDA interventional occlusion is closely related to the severity of thrombocytopenia.

Red blood cell alloimmunization in transfused patients in sub-Saharan Africa: A systematic review and meta-analysis.

PubMed

Ngoma, Alain M; Mutombo, Paulin B; Ikeda, Kazuhiko; Nollet, Kenneth E; Natukunda, Bernard; Ohto, Hitoshi

2016-04-01

Previous studies of Sub-Saharan Africans show significant alloimmunization to red blood cell (RBC) antigens, but country-specific data are limited. Thus, the aim of this study was to estimate, by meta-analysis, the overall proportion of red blood cell alloantibodies among transfused patients. We systematically searched Medline, Embase, and the Africa-Wide Information database to identify relevant studies in any language. Case reports, comments, letters, conference abstracts, editorials, and review articles were excluded. Of the 269 potentially relevant articles, 11 studies fulfilled our selection criteria. Overall proportions of alloimmunization were 6.7 (95% CI: 5.7, 7.8) per 100 transfused patients. With regard to antibody specificity, among clinically significant antibodies, anti-E ranked as the most common, followed by anti-K, anti-C and anti-D. Meta-analysis of available literature quantifies and qualifies the clinical challenge of RBC alloimmunization among transfused patients in Sub-Saharan Africa. These results should drive policy decisions in favour of routine testing of RBC antigens and irregular antibodies for transfused patients as a standard of care throughout Sub-Saharan Africa. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chicken pox associated thrombocytopenia in adults.

PubMed

Ali, Nadir; Anwar, Masood; Majeed, Irfan; Tariq, Waheed Uz Zaman

2006-04-01

To determine the frequency and magnitude of thrombocytopenia associated with chicken pox in adults. Observational descriptive study. Combined Military Hospital, Attock, from July 2003 to June 2004. All patients of age 15 years and above with history of fever, followed by appearance of the typical vesicular chicken pox rash, were inducted after informed consent. Two milliliters of whole blood was collected on day 1 of admission, and blood counts were performed. Patients were admitted and given 800 mg oral acyclovir, 5 times/day, for 7 days, in addition to symptomatic treatment. Patients were followed till 8 weeks. A total of 410 patients of chicken pox were received, out of which 270 were included. Age of patients ranged between 15 and 40 years with median age of 21 years. Platelet count on the day of admission ranged between 29 x 10(9)/L to 513 x 10(9)/L, mean platelet count 178 x 10(9)/L. Platelet count < 150 x 10(9)/L was detected in 80/270 (30%) patients. Platelet count in thrombocytopenia patients was from 29 x 10(9)/L to 149 x 10(9)/L with mean 121 x 10(9)/L. Thrombocytopenia recovered within 02 weeks in 78/80 (97%) patients. In 2 patients, thrombocytopenia recovered in 3 weeks. None of the patients developed purpuric spots, ecchymosis or bleeding manifestations. Thrombocytopenia in chicken pox is a common entity. Platelet count remains above 25 x 10(9) /L, which is usually not associated with bleeding manifestations. None of the patients in this series developed purpura. No specific pattern of total leukocyte counts was predictive of the progression or regression in platelet count.

Does famotidine induce thrombocytopenia in neurosurgical patients?

PubMed

Ecker, Robert D; Wijdicks, Eelco F M; Wix, Kelly; McClelland, Robyn

2004-10-01

The incidence of thrombocytopenia in neurosurgical patients prescribed famotidine is unknown. Using hospital records of neurosurgery patients treated between July 2001 and July 2002, a retrospective cohort study was performed comparing platelet counts in patients treated with famotidine with a similar group of patients who were not prescribed an H2 antagonist. Patients were excluded if: 1) platelets were less than 150,000 prior to famotidine administration; 2) pre-drug and post-drug platelets were not drawn; 3) they were concurrently taking a potential thrombocytopenic inducing drug; or 4) disseminated intravascular coagulation, thrombocytopenic purpura, or any other confounding hematologic disorder developed. Seventeen of 50 (34%) patients on famotidine developed thrombocytopenia compared with 11 of 98 (11.2%) of those untreated (P = 0.002). In this retrospective study, neurosurgical patients on famotidine developed thrombocytopenia statistically significantly more often than those untreated. Although no clinically significant sequelae developed as a result of the thrombocytopenia, if these findings are confirmed by a prospective study, proton pump inhibitors and sucralfate, with their similar efficacy, may be a better choice for gastrointestinal prophylaxis in neurosurgical patients.

Reduced MHC Alloimmunization and Partial Tolerance Protection With Pathogen Reduction Of Whole Blood

PubMed Central

Jackman, Rachael P.; Muench, Marcus O.; Inglis, Heather; Heitman, John W.; Marschner, Susanne; Goodrich, Raymond P.; Norris, Philip J.

2017-01-01

BACKGROUND Allogeneic blood transfusion can result in an immune response against major histocompatibility complex (MHC) antigens, potentially complicating future transfusions or transplants. We have previously shown that pathogen reduction of platelet-rich plasma (PRP) with riboflavin and UV light (UV+R) can prevent alloimmunization in mice. A similar pathogen reduction treatment is currently under development for the treatment of whole blood using riboflavin and a higher dose of UV light. We sought to determine the effectiveness of this treatment in prevention of alloimmunization. STUDY DESIGN AND METHODS BALB/c mice were transfused with untreated or UV+R treated allogeneic C57Bl/6 whole blood with or without leukoreduction. Mice were evaluated for donor specific antibodies and ex vivo splenocyte cytokine responses, as well as for changes in the frequency of regulatory T (Treg) cells. RESULTS UV+R treatment blocked cytokine priming and reduced anti-MHC alloantibody responses to transfused whole blood. Leukoreduction reduced alloantibody levels in both the untreated and UV+R groups. Mice transfused with UV+R treated whole blood had reduced alloantibody and cytokine responses when subsequently transfused with untreated blood from the same donor type. This reduction in responses was not associated with increased Treg cells. CONCLUSIONS Pathogen reduction of whole blood with UV+R significantly reduces, but does not eliminate the alloimmune response. Exposure to UV+R treated whole blood transfusion does appear to induce tolerance to alloantigens resulting in reduced anti-MHC alloantibody and cytokine responses to subsequent exposures to the same alloantigens. This tolerance does not appear to be driven by an increase in Treg cells. PMID:27859333

Recent advances in transfusions in neonates/infants

PubMed Central

Goel, Ruchika; Josephson, Cassandra D.

2018-01-01

Transfusions of red blood cells (RBCs), platelets, and plasma are critical therapies for infants and neonates (particularly preterm neonates) in the neonatal intensive care unit, who are the most frequently transfused subpopulation across all ages. Although traditionally a significant gap has existed between the blood utilization and the evidence base essential to adequately guide transfusion practices in infants and neonates, pediatric transfusion medicine is evolving from infancy and gradually coming of age. It is entering an exciting era with recognition as an independent discipline, a new and evolving high-quality evidence base for transfusion practices, novel technologies and therapeutics, and national/international collaborative research, educational, and clinical efforts. Triggers and thresholds for red cell transfusion are accumulating evidence with current phase III clinical trials. Ongoing trials and studies of platelet and plasma transfusions in neonates are anticipated to provide high-quality evidence in years to come. This article aims to summarize the most current evidence-based practices regarding blood component therapy in neonates. Data on the use of specific components (RBCs, plasma, and platelets) are provided. We attempt to define thresholds for anemia, thrombocytopenia, and abnormal coagulation profile in neonates to highlight the difficulties in having a specific cutoff value in neonates and preterm infants. Indications for transfusion of specific products, transfusion thresholds, and current practices and guidelines are provided, and possible adverse outcomes and complications are discussed. Finally, the critical research knowledge gaps in these practices as well as ongoing and future research areas are discussed. In an era of personalized medicine, neonatal transfusion decisions guided by a strong evidence base must be the overarching goal, and this underlies all of the strategic initiatives in pediatric and neonatal transfusion research

[Role of anti c-mpl antibody in systemic lupus erythematosus with thrombocytopenia].

PubMed

Yang, Tuo; Huang, Ci Bo; Lai, Bei; Zhao, Li Ke; Chen, Ying Juan; Zhao, Yue Tao; Zhang, Chun Mei; Zeng, Xiao Feng

2012-04-18

To determine whether anti-thrompoietin receptor (TPO-R, c-mpl) antibody contributes to thrombocytopenia in systemic lupus erytematosus (SLE) and explore the pathogenic role of this antibody. Sera from 24 SLE patients with thrombocytopenia, 27 SLE patients having normal platelet counts with a history of thrombocytopenia, 18 SLE patients with neither thrombocytopenia nor post thrombocytopenia and 18 healthy controls were collected. Anti c-mpl antibodies were detected by an indirected ELISA assay. The serum TPO levels were measured by an ELISA assay. Clinical findings, autoantibody profiles, and SLEDAI were evaluated. Serum anti c-mpl antibodies were detected in 18.8% of the SLE patientis. The frequency of this antibody in SLE with thrombocytopenia, SLE with a history of thrombocytopenia and SLE without thrombocytopenia were of no difference (P=0.600). In the patients with anti c-mpl antibodies, their platelet counts were decreased(P=0.025) and serum TPO levels elevated(P=0.038) than those in the patients without, while there were no differences between the two groups in C3, C4, ESR, CRP level, the frequency of ANA, dsDNA, ANCA and SLEDAI. Anti c-mpl antibody contributes to SLE-associated thrombocytopenia by functionally blocking an interaction between thrombopoietin and c-mpl, which might inhibit TPO-dependent megakaryocyte proliferation and differentiation.

Alarmins and Their Receptors as Modulators and Indicators of Alloimmune Responses.

PubMed

Matta, B M; Reichenbach, D K; Blazar, B R; Turnquist, H R

2017-02-01

Cell damage and death releases alarmins, self-derived immunomodulatory molecules that recruit and activate the immune system. Unfortunately, numerous processes critical to the transplantation of allogeneic materials result in the destruction of donor and recipient cells and may trigger alarmin release. Alarmins, often described as damage-associated molecular patterns, together with exogenous pathogen-associated molecular patterns, are potent orchestrators of immune responses; however, the precise role that alarmins play in alloimmune responses remains relatively undefined. We examined evolving concepts regarding how alarmins affect solid organ and allogeneic hematopoietic cell transplantation outcomes and the mechanisms by which self molecules are released. We describe how, once released, alarmins may act alone or in conjunction with nonself materials to contribute to cytokine networks controlling alloimmune responses and their intensity. It is becoming recognized that this class of molecules has pleotropic functions, and certain alarmins can promote both inflammatory and regulatory responses in transplant models. Emerging evidence indicates that alarmins and their receptors may be promising transplantation biomarkers. Developing the therapeutic ability to support alarmin regulatory mechanisms and the predictive value of alarmin pathway biomarkers for early intervention may provide opportunities to benefit graft recipients. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Immune Thrombocytopenia as a Consequence of Rocky Mountain Spotted Fever.

PubMed

Baldeo, Cherisse; Seegobin, Karan; Zuberi, Lara

2017-01-01

Primary immune thrombocytopenia (ITP) - also called idiopathic thrombocytopenic purpura or immune thrombocytopenic purpura - is an acquired thrombocytopenia caused by autoantibodies against platelet antigens. It is one of the more common causes of thrombocytopenia in otherwise asymptomatic adults. Rocky Mountain spotted fever (RMSF) is a potentially lethal, but curable, tick-borne disease. We present a case of ITP that was triggered by RMSF.

Risk of maternal alloimmunization in Southern Pakistan - a study in a cohort of 1000 pregnant women.

PubMed

Karim, Farheen; Moiz, Bushra; Kamran, Nausheen

2015-02-01

Haemolytic disease of the fetus and the newborn [HDFN] is caused by incompatibility of maternal and fetal erythrocytes. Red blood cell alloimmunization is a well-known cause of HDFN. Due to heterogeneity of populations, the spectrum of alloimmunization varies around the world. This study aimed to determine the frequency of alloimmunization in pregnant women and to determine the risk of HDFN in our population. This was a descriptive study conducted at Aga Khan University Hospital Karachi. Blood type and red cell antibody screening was determined on every pregnant woman at her first antenatal visit. Red cell antibody identification was performed on positive screening results. A total of 1000 pregnant females including 633 (63.3%) multigravida were studied. Blood type B was predominant (n = 374 or 37.4%) and D negative was observed in 136 women (13.6%). No red cell antibody was detected in 982 females (98.2%). 20 red cell antibodies were detected in 18 women (1.8%). The incidence of non-anti-D was 16/1000 [1.6%] in all pregnant females. The non-anti-D alloantibodies included anti-M (n = 3; 15%), anti-Lewis(a) (n = 3; 15%), anti C ( n = 1; 5%), anti-E (n = 1; 5%), anti-e (n = 1; 5%), anti-Lewis(b) (n = 1; 5%) and nonspecific antibodies (n = 6; 30%). The incidence of anti-D was 4/136 or 2.9% in D negative blood type. After excluding prior sensitization due to blood transfusions, risk remained was 2.2%. Antibodies of clinical significance were identified in 9 (0.9%) females. In our cohort, frequency of red cell alloimmunization during pregnancy was 1. 8% out of which 0.9% were clinically significant antibodies posing a risk for HDFN. Despite prenatal and post natal prophylaxis, risk of sensitization with D antigen in D negative women was high at 2.2%. We recommend that all pregnant women should be screened for irregular antibodies irrespective of the rhesus type. Copyright © 2014 Elsevier Ltd. All rights reserved.

Life-Threatening Thrombocytopenia Following Intravenous Contrast Media Infusion

PubMed Central

Kim, Minjeong; Park, Jisun

2018-01-01

Radiocontrast media-induced acute severe thrombocytopenia is a very rare complication and potentially life-threatening. Here, we report the case of a 63-year-old male patient with severe acute thrombocytopenia following first exposure to intravenous non-ionic contrast media without immediate allergic reactions. His platelet count dropped from 107000/µL to 2000/µL after six hours of radiocontrast infusion. After administration of corticosteroid and transfusion of platelet concentrates, the platelet count returned gradually to normal within 5 days. To the best of our knowledge, non-ionic contrast media-induced isolated acute severe thrombocytopenia following no signs or symptoms of immediate allergic reaction has never been described. PMID:29214792

NxStage dialysis system-associated thrombocytopenia: a report of two cases.

PubMed

Sekkarie, Mohamed; Waldron, Michelle; Reynolds, Texas

2016-01-01

Thrombocytopenia in hemodialysis patients has recently been reported to be commonly caused by electron-beam sterilization of dialysis filters. We report the occurrence of thrombocytopenia in the first two patients of a newly established home hemodialysis program. The 2 patients switched from conventional hemodialysis using polysulfone electron-beam sterilized dialyzers to a NxStage system, which uses gamma sterilized polyehersulfone dialyzers incorporated into a drop-in cartridge. The thrombocytopenia resolved after return to conventional dialysis in both patients and recurred upon rechallenge in the patient who opted to retry NxStage. This is the first report of thrombocytopenia with the NxStage system according to the authors’ knowledge. Dialysis-associated thrombocytopenia pathophysiology and clinical significance are not well understood and warrant additional investigations.

Intravenous gammaglobulin treatment for immune thrombocytopenia associated with infectious mononucleosis.

PubMed

Cyran, E M; Rowe, J M; Bloom, R E

1991-10-01

Severe thrombocytopenia is an uncommon (incidence less than 1%) but serious complication of infectious mononucleosis. Corticosteroids have been used for therapy with variable responses reported. Five consecutive patients with infectious mononucleosis-related severe thrombocytopenia were treated with intravenous gammaglobulin (IVIG) at a dose of 400 mg/kg/day for 2-5 days. All patients appear to have had an immunologic or consumptive etiology for their thrombocytopenia as determined by increased marrow megakaryocytes. All patients were initially treated with oral prednisone 1 mg/kg/day. Due to the relatively slow response to prednisone (platelet count less than 20,000/microliters on the 8th to 13th hospital day) or increased bleeding symptoms, IVIG was initiated. Four of the five patients rapidly developed significant increases in their platelet counts (range 44,000/microliters to 97,000/microliters). Two of these responses were sustained and two relapses occurred (while on continued steroid therapy) which again responded to booster doses of IVIG at similar doses. IVIG has been previously shown to be effective in treating patients with idiopathic thrombocytopenia purpura. Historically, patients with infectious mononucleosis-related severe thrombocytopenia often are refractory to corticosteroid therapy and our limited experience suggests that IVIG may also be effective in infectious mononucleosis-related severe thrombocytopenia.

Life-Threatening Thrombocytopenia Following Intravenous Contrast Media Infusion.

PubMed

Park, Mihwa; Kim, Minjeong; Park, Jisun; Cho, Jinhyun

2018-01-01

Radiocontrast media-induced acute severe thrombocytopenia is a very rare complication and potentially life-threatening. Here, we report the case of a 63-year-old male patient with severe acute thrombocytopenia following first exposure to intravenous non-ionic contrast media without immediate allergic reactions. His platelet count dropped from 107000/μL to 2000/μL after six hours of radiocontrast infusion. After administration of corticosteroid and transfusion of platelet concentrates, the platelet count returned gradually to normal within 5 days. To the best of our knowledge, non-ionic contrast media-induced isolated acute severe thrombocytopenia following no signs or symptoms of immediate allergic reaction has never been described. © Copyright: Yonsei University College of Medicine 2018.

Hepatopathy-thrombocytopenia syndrome after actinomycin-D therapy: treatment with defibrotide.

PubMed

Martín-Lázaro, Juan F; Palanca, Daniel; Garcia-Iñiguez, Juan P; Madurga, Paula; Carboné, Ana

2013-02-01

We report a case of administration compassionate use defibrotide in a 13-year-old girl with Sinusoidal Obstructive Syndrome and thrombocytopenia, also known as Hepatopathy--Thrombocytopenia Syndrome (HTS) during chemotherapy for Wilms' tumor.

Heparin-Induced Thrombocytopenia with Associated Thrombosis in Children after the Fontan Operation

PubMed Central

Porcelli, Rosalia; Moskowitz, Bonnie C.; Cetta, Frank; Graham, Lynn C.; Godwin, John E.; Eidem, Benjamin W.; Prechel, M. Margaret; Walenga, Jeanine M.

2003-01-01

Heparin-induced thrombocytopenia is a widely recognized clinical disorder. The spectrum of disease ranges from clinically insignificant to severe thrombosis (heparin-induced thrombocytopenia with associated thrombosis). Overall, thrombosis occurs in approximately 33% of adults diagnosed with heparin-induced thrombocytopenia and has been associated with high morbidity and mortality rates. Diagnostic testing for this disorder is not standard in children with thrombocytopenia who are receiving heparin, despite the fact that children with congenital heart disease may be exposed to heparin frequently. There are few reported cases of heparin-induced thrombocytopenia with associated thrombosis in children; herein, we describe the cases of 2 children who developed this disorder after undergoing a Fontan operation. (Tex Heart Inst J 2003;30:58–61) PMID:12638673

Prevalence of cirrhosis in patients with thrombocytopenia who receive bone marrow biopsy.

PubMed

Sheikh, Muhammad Y; Raoufi, Rahim; Atla, Pradeep R; Riaz, Muhammad; Oberer, Chad; Moffett, Michael J

2012-01-01

Thrombocytopenia is a common finding in patients with cirrhosis and may lead to unnecessary referral for bone marrow (BM) biopsy. To date, the prevalence of cirrhosis in patients with thrombocytopenia who receive BM biopsy is largely unknown. Between fiscal years 2006-2010, 744 patients (≥18 years) who underwent BM biopsies for thrombocytopenia at our hospital were identified retrospectively. 541 patients were excluded who had hematologic malignancies and received chemotherapy. Remaining 203 patients with predominant isolated thrombocytopenia were included in the study. Of 203 patients, 136 (67%) had a normal and 67 (33%) had an abnormal BM examination. Prevalence of cirrhosis in the study population was 35% (95% CI: 28.4-41.9). 51% patients with normal BM were found to have cirrhosis compared to 3% of patients with abnormal BM exam (P < 0.0001). Common causes of cirrhosis were nonalcoholic steatohepatitis (NASH) (47%), followed by alcohol and Hepatitis C virus infection. Idiopathic thrombocytopenia and myelodysplastic syndrome were most frequent causes of thrombocytopenia in patients without cirrhosis. Patients with NASH had higher body mass index (BMI) (33.4 vs. 25.8, P < 0.001) and lower MELD scores (11.1 vs. 16, P = 0.028) when compared to non-NASH patients with cirrhosis. Approximately, one third (35%) of patients with cirrhosis induced thrombocytopenia may undergo unwarranted BM biopsies. Clinical diagnosis of cirrhosis is still a challenge for many physicians, particularly with underlying NASH. We propose cirrhosis to be the prime cause of isolated thrombocytopenia.

Quinine-induced thrombocytopenia following intravenous use of heroin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Christie, D.J.; Walker, R.H.; Kolins, M.D.

1983-06-01

Profound thrombocytopenia developed in a 22-year-old man after intravenous use of heroin. A high-titer, quinine-dependent, platelet-specific antibody was detected in his serum using lysis of normal platelets labeled with chromium 51 and an electroimmunoassay for measurement of platelet-associated IgG. The antibody was specific for quinine and failed to react with platelets in the presence of quinidine hydrochloride or two structural analogues of heroin. Quinine, a common adulterant found in heroin, was detected in the patient's blood and urine. On the basis of these observations, the patient was judged to have quinine-induced immunologic thrombocytopenia. To our knowledge, this report is themore » first to confirm that quinine used as an adulterant can induce immunologic thrombocytopenia following an injection of heroin.« less

Relationship Among Viremia/Viral Infection, Alloimmunity, and Nutritional Parameters in the First Year After Pediatric Kidney Transplantation.

PubMed

Ettenger, R; Chin, H; Kesler, K; Bridges, N; Grimm, P; Reed, E F; Sarwal, M; Sibley, R; Tsai, E; Warshaw, B; Kirk, A D

2017-06-01

The Immune Development in Pediatric Transplantation (IMPACT) study was conducted to evaluate relationships among alloimmunity, protective immunity, immune development, physical parameters, and clinical outcome in children undergoing kidney transplantation. We prospectively evaluated biopsy-proven acute rejection (BPAR), de novo donor-specific antibody (dnDSA) formation, viremia, viral infection, T cell immunophenotyping, and body mass index (BMI)/weight Z scores in the first year posttransplantation in 106 pediatric kidney transplant recipients. Outcomes were excellent with no deaths and 98% graft survival. Rejection and dnDSAs occurred in 24% and 22%, respectively. Pretransplant cytomegalovirus (CMV) and Epstein-Barr virus (EBV) serologies and subsequent viremia were unrelated to BPAR or dnDSA. Viremia occurred in 73% of children (EBV, 34%; CMV, 23%; BMK viremia, 23%; and JC virus, 21%). Memory lymphocyte phenotype at baseline was not predictive of alloimmune complications. Patients who developed viral infection had lower weight (-2.1) (p = 0.028) and BMI (-1.2) (p = 0.048) Z scores at transplantation. The weight difference persisted to 12 months compared with patients without infection (p = 0.038). These data indicate that there is a high prevalence of viral disease after pediatric kidney transplantation, and underweight status at transplantation appears to be a risk factor for subsequent viral infection. The occurrence of viremia/viral infection is not associated with alloimmune events. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Controlling the burn and fueling the fire: defining the role for the alarmin interleukin-33 in alloimmunity.

PubMed

Liu, Quan; Turnquist, Heth R

2016-02-01

The purpose of this review is to provide a general update on recent developments in the immunobiology of IL-33 and IL-33-targeted immune cells. We also discuss emerging concepts regarding the potential role IL-33 appears to play in altering alloimmune responses mediating host-versus-graft and graft-versus-host alloresponses. Stromal cells and leukocytes display regulated expression of IL-33 and may actively or passively secrete this pleotropic cytokine. Type 2 innate lymphoid cells and a large proportion of tissue resident regulatory T cells (Treg) express membrane-bound suppressor of tumorigenicity 2 (ST2), the IL-33 receptor. Although Treg are appreciated suppressors of the inflammatory function of immune cells, both type 2 innate lymphoid cells and tissue resident Treg could play key roles in tissue repair and homeostasis. The functions of IL-33 in transplantation are poorly understood. However, like other disease models, the functions of IL-33 in alloimmunity appear to be quite pleiotropic. IL-33 is associated with immune regulation and graft protection in cardiac transplant settings. Yet, it is highly proinflammatory and stimulates lethal graft-versus-host disease through its capacity to stimulate type 1 immunity. Intensive studies on IL-33/ST2 signaling pathways and ST2 cell populations in solid organ and cell transplantation are warranted. A better understanding of this important pathway will provide promising therapeutic targets controlling pathogenic alloimmune responses, as well as potentially facilitating the function of regulatory and reparative immune cells posttransplantation.

Enterovirus infection in febrile neonates: A hospital-based prospective cohort study.

PubMed

Lv, Xiao-Qing; Qian, Ling-He; Wu, Tai; Yuan, Tian-Ming

2016-08-01

This study aims to investigate clinical characteristics and microbiological results and to assess the predictors for enterovirus infection in febrile neonates. A prospective cohort study was conducted on 334 febrile patients (age: 0.33-28 days) in 2011-2012 years. Enterovirus RNA was detected by reverse transcription polymerase chain reaction on faeces or cerebrospinal fluid (CSF). Clinical characteristics were compared, and non-conditional logistic regression analysis was performed to determine independent predictors for enterovirus infection. There were 131 episodes of neonatal enterovirus infection (39.22%). Forty-eight (36.64%) developed respiratory symptoms, 69 (52.67%) had diarrhoea, 22 (16.79%) had poor feeding and 34 (25.95%) had rash. Eighteen (13.74%) had lower platelet counts, and CSF specimens were positive for enterovirus RNA in 44.27% (58/131) whose CSF revealed a mean white blood cell counts of 100.38 ± 147.97 cells/mm(3) (range: 2-668 cells/mm(3) ). The positivity of stool 38.92% (130/334) was significantly higher than that of CSF specimens 26.24% (58/221) for enterovirus RNA (P < 0.01). By logistic regression analysis, the following independently predicted enterovirus infection: abnormal CSF test (odds ratio (OR): 12.426, 95% confidence interval (CI): 5.633-27.413), thrombocytopenia (OR: 3.647, 95% CI: 1.312-10.136), duration of fever >3.25 (d) (OR: 2.293, 95% CI: 1.279-4.113), highest temperature >38.35 (°C) (OR: 2.094, 95% CI: 1.342-4.123) and negative bacterial culture (OR: 5.073, 95% CI: 1.504-17.114). Our data indicated that enteroviruses should be routinely considered in the differential diagnosis of febrile neonates. The factors, which may predict the risk of neonatal enterovirus infection, were abnormal CSF test, thrombocytopenia, duration of fever >3.25 (d), highest temperature >38.35 (°C) and negative bacterial culture. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

Is Thrombocytopenia an Early Prognostic Marker in Septic Shock?

PubMed

Thiery-Antier, Nadiejda; Binquet, Christine; Vinault, Sandrine; Meziani, Ferhat; Boisramé-Helms, Julie; Quenot, Jean-Pierre

2016-04-01

To assess whether early thrombocytopenia during septic shock is associated with an increased risk of death at day 28 and to identify risk factors associated with a low platelet count. Prospective, multicenter, observational cohort study. Fourteen ICUs from 10 French university teaching and nonacademic hospitals. Consecutive adult patients with septic shock admitted between November 2009 and September 2011 were eligible. None. Of the 1,495 eligible patients, 1,486 (99.4%) were included. Simplified Acute Physiology Score II score of greater than or equal to 56, immunosuppression, age of more than 65 years, cirrhosis, bacteremia (p ≤ 0.001 for each), and urinary sepsis (p = 0.005) were globally associated with an increased risk of thrombocytopenia within the first 24 hours following the onset of septic shock. Survival at day 28 estimated by the Kaplan-Meier method was lower in patients with thrombocytopenia and decreased with thrombocytopenia severity. By multivariate Cox regression, a platelet count of less than or equal to 100,000/mm3 was independently associated with a significantly increased risk of death within the 28 days following septic shock onset. The risk of death increased with the severity of thrombocytopenia (hazard ratio, 1.65; 95% CI, 1.31-2.08 for a platelet count below 50,000/mm3 vs > 150,000/mm3; p < 0.0001). This is the first study to investigate thrombocytopenia within the first 24 hours of septic shock onset as a prognostic marker of survival at day 28 in a large cohort of ICU patients. Measuring platelet count is inexpensive and easily feasible for the physician in routine practice, and thus, it could represent an easy "alert system" among patients in septic shock.

Prevalence of Cirrhosis in Patients with Thrombocytopenia Who Receive Bone Marrow Biopsy

PubMed Central

Sheikh, Muhammad Y.; Raoufi, Rahim; Atla, Pradeep R.; Riaz, Muhammad; Oberer, Chad; Moffett, Michael J.

2012-01-01

Background/Aim: Thrombocytopenia is a common finding in patients with cirrhosis and may lead to unnecessary referral for bone marrow (BM) biopsy. To date, the prevalence of cirrhosis in patients with thrombocytopenia who receive BM biopsy is largely unknown. Materials and Methods: Between fiscal years 2006-2010, 744 patients (≥18 years) who underwent BM biopsies for thrombocytopenia at our hospital were identified retrospectively. 541 patients were excluded who had hematologic malignancies and received chemotherapy. Remaining 203 patients with predominant isolated thrombocytopenia were included in the study. Results: Of 203 patients, 136 (67%) had a normal and 67 (33%) had an abnormal BM examination. Prevalence of cirrhosis in the study population was 35% (95% CI: 28.4-41.9). 51% patients with normal BM were found to have cirrhosis compared to 3% of patients with abnormal BM exam (P < 0.0001). Common causes of cirrhosis were nonalcoholic steatohepatitis (NASH) (47%), followed by alcohol and Hepatitis C virus infection. Idiopathic thrombocytopenia and myelodysplastic syndrome were most frequent causes of thrombocytopenia in patients without cirrhosis. Patients with NASH had higher body mass index (BMI) (33.4 vs. 25.8, P < 0.001) and lower MELD scores (11.1 vs. 16, P = 0.028) when compared to non-NASH patients with cirrhosis. Conclusion: Approximately, one third (35%) of patients with cirrhosis induced thrombocytopenia may undergo unwarranted BM biopsies. Clinical diagnosis of cirrhosis is still a challenge for many physicians, particularly with underlying NASH. We propose cirrhosis to be the prime cause of isolated thrombocytopenia. PMID:22824769

Red Cell Alloimmunization In Multitransfused Thalassaemia Major Patients.

PubMed

Moeen, Shazia; Farooq, Nazish; Irshad, Romana; Ashfaq, Muhammad; Farooq, Umer; Idris, Muhammad

2018-01-01

Lifelong transfusions are life savers for thalassaemia patients but are associated with many complications. Alloimmunization is a major problem for blood banks. Antigens of foreign red blood cells induce the formation of antibodies in patients suffering from thalassaemia. The purpose of this study was to examine the frequency of red cell alloantibodies and to express the type of these antibodies in thalassaemia patients. Patients that have received multiple transfusions were included in this study. Those with the positive Coombs test (DAT) results were excluded from the study and remaining patients were screened for antibodies. A panel of known blood group antigens was used for the patients who had a positive antibody screening test because they had alloantibodies in their serum. First, three cell panel was applied. If the screen was positive then eleven cell panels was used to identify the specific antibody. Both the cell panels were applied at room-temperature, liss (low ionic strength saline) and coombs phase. Three hundred & two patients were selected out of which 65.6% (n=198) were males and 34.4% (n=104) females. Patient's age ranged from 1.5 years to 26 years ±5.40 years. All of the patients were given regular red cell transfusion at 2-4 weeks interval. They were given non leukodepleted transfusions. It is not the practice in any thalassaemia Centre in Pakistan to give phenotypically matched blood for Kell, Kidd, Duffy or any other minor group antigens to patients on regular blood transfusion. Alloimmunization was positive in 12 (4.0%) of the 302 patients studied. Male were 66.67% (n=8) and female were 33.33% (n=4). Samples of these positive patients were further tested to determine specificity of alloantibodies. Anti Cw was most common, detected in 4 out of 12 (1.3%) patients. Anti K, k, S and Lua were detected in 2 out of 12 (0.7%) each. Thalassemia major patients on regular blood transfusions can develop red cell alloantibodies. Detailed pretransfusion

To B or not to B cells-mediate a healthy start to life.

PubMed

Nguyen, T G; Ward, C M; Morris, J M

2013-02-01

Maternal immune responses during pregnancy are critical in programming the future health of a newborn. The maternal immune system is required to accommodate fetal immune tolerance as well as to provide a protective defence against infections for the immunocompromised mother and her baby during gestation and lactation. Natural immunity and antibody production by maternal B cells play a significant role in providing such immunoprotection. However, aberrations in the B cell compartment as a consequence of maternal autoimmunity can pose serious risks to both the mother and her baby. Despite their potential implication in shaping pregnancy outcomes, the role of B cells in human pregnancy has been poorly studied. This review focuses on the role of B cells and the implications of B cell depletion therapy in pregnancy. It highlights the evidence of an association between aberrant B cell compartment and obstetric conditions. It also alludes to the potential mechanisms that amplify these B cell aberrances and thereby contribute to exacerbation of some maternal autoimmune conditions and poor neonatal outcomes. Clinical and experimental evidence suggests strongly that maternal autoantibodies contribute directly to the pathologies of obstetric and neonatal conditions that have significant implications for the lifelong health of a newborn. The evidence for clinical benefit and safety of B cell depletion therapies in pregnancy is reviewed, and an argument is mounted for further clinical evaluation of B cell-targeted therapies in high-risk pregnancy, with an emphasis on improving neonatal outcomes and prevention of neonatal conditions such as congenital heart block and fetal/neonatal alloimmune thrombocytopenia. © 2012 British Society for Immunology.

Clinical and pathogenic features of ETV6-related thrombocytopenia with predisposition to acute lymphoblastic leukemia

PubMed Central

Melazzini, Federica; Palombo, Flavia; Balduini, Alessandra; De Rocco, Daniela; Marconi, Caterina; Noris, Patrizia; Gnan, Chiara; Pippucci, Tommaso; Bozzi, Valeria; Faleschini, Michela; Barozzi, Serena; Doubek, Michael; Di Buduo, Christian A.; Kozubik, Katerina Stano; Radova, Lenka; Loffredo, Giuseppe; Pospisilova, Sarka; Alfano, Caterina; Seri, Marco; Balduini, Carlo L.; Pecci, Alessandro; Savoia, Anna

2016-01-01

ETV6-related thrombocytopenia is an autosomal dominant thrombocytopenia that has been recently identified in a few families and has been suspected to predispose to hematologic malignancies. To gain further information on this disorder, we searched for ETV6 mutations in the 130 families with inherited thrombocytopenia of unknown origin from our cohort of 274 consecutive pedigrees with familial thrombocytopenia. We identified 20 patients with ETV6-related thrombocytopenia from seven pedigrees. They have five different ETV6 variants, including three novel mutations affecting the highly conserved E26 transformation-specific domain. The relative frequency of ETV6-related thrombocytopenia was 2.6% in the whole case series and 4.6% among the families with known forms of inherited thrombocytopenia. The degree of thrombocytopenia and bleeding tendency of the patients with ETV6-related thrombocytopenia were mild, but four subjects developed B-cell acute lymphoblastic leukemia during childhood, resulting in a significantly higher incidence of this condition compared to that in the general population. Clinical and laboratory findings did not identify any particular defects that could lead to the suspicion of this disorder from the routine diagnostic workup. However, at variance with most inherited thrombocytopenias, platelets were not enlarged. In vitro studies revealed that the maturation of the patients’ megakaryocytes was defective and that the patients have impaired proplatelet formation. Moreover, platelets from patients with ETV6-related thrombocytopenia have reduced ability to spread on fibrinogen. Since the dominant thrombocytopenias due to mutations in RUNX1 and ANKRD26 are also characterized by normal platelet size and predispose to hematologic malignancies, we suggest that screening for ETV6, RUNX1 and ANKRD26 mutations should be performed in all subjects with autosomal dominant thrombocytopenia and normal platelet size. PMID:27365488

Pre- and Post-Transfusion Alloimmunization in Dogs Characterized by 2 Antiglobulin-Enhanced Cross-match Tests.

PubMed

Goy-Thollot, I; Giger, U; Boisvineau, C; Perrin, R; Guidetti, M; Chaprier, B; Barthélemy, A; Pouzot-Nevoret, C; Canard, B

2017-09-01

When dogs are transfused, blood compatibility testing varies widely but may include dog erythrocyte antigen (DEA) 1 typing and rarely cross-matching. Prospective study to examine naturally occurring alloantibodies against red blood cells (RBCs) and alloimmunization by transfusion using 2 antiglobulin-enhanced cross-match tests. Eighty client-owned anemic, 72 donor, and 7 control dogs. All dogs were typed for DEA 1 and some also for DEA 4 and DEA 7. Major cross-match tests with canine antiglobulin-enhanced immunochromatographic strip and gel columns were performed 26-129 days post-transfusion (median, 39 days); some dogs had an additional early evaluation 11-22 days post-transfusion (median, 16 days). Plasma from alloimmunized recipients was cross-matched against RBCs from 34 donor and control dogs. The 2 cross-match methods gave entirely concordant results. All 126 pretransfusion cross-match results for the 80 anemic recipients were compatible, but 54 dogs died or were lost to follow up. Among the 26 recipients with follow-up, 1 dog accidently received DEA 1-mismatched blood and became cross-match-incompatible post-transfusion. Eleven of the 25 DEA 1-matched recipients (44%) became incompatible against other RBC antigens. No naturally occurring anti-DEA 7 alloantibodies were detected in DEA 7- dogs. The antiglobulin-enhanced immunochromatographic strip cross-match and laboratory gel column techniques identified no naturally occurring alloantibodies against RBC antigens, but a high degree of post-transfusion alloimmunization in dogs. Cross-matching is warranted in any dog that has been previously transfused independent of initial DEA 1 typing and cross-matching results before the first transfusion event. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

A Term Infant of Neonatal Toxic Shock Syndrome-Like Exanthematous Disease Complicated with Hemophagocytic Syndrome.

PubMed

Kaga, Akimune; Watanabe, Hiroshi; Miyabayashi, Hiroki; Metoki, Takaya; Kitaoka, Setsuko; Kumaki, Satoru

2016-10-01

Neonatal toxic shock syndrome-like exanthematous disease (NTED) is a newly recognized neonatal infectious disease, caused by the superantigen toxic shock syndrome toxin-1 (TSST-1). TSST-1 is mainly produced by methicillin-resistant Staphylococcus aureus, and the immune responses to TSST-1 are known to cause toxic shock syndrome, a life-threatening infectious disease. The clinical symptoms of NTED are skin rash, fever, and thrombocytopenia, but severe thrombocytopenia is rare in term infants with NTED. Although the cause of NTED is the same as that of toxic shock syndrome, the clinical symptoms of NTED are milder than toxic shock syndrome. The mild phenotype of NTED has been explained by selectively elevated serum levels of anti-inflammatory cytokine interleukin (IL)-10, which suppress immune responses to TSST-1. In the present study, we report a term female infant of NTED complicated with hemophagocytic syndrome (HPS). HPS is characterized by systemic inflammation and hemophagocytosis, caused by uncontrolled activation of T cells and macrophages. The serum IL-10 level of the patient at 4 days of age was relatively low (67 pg/mL) for NTED but still higher than normal controls (< 2.0 pg/mL). The patient also showed severe thrombocytopenia. We speculate that the serum IL-10 level of the patient was enough to supress immune responses to TSST-1, thereby resulting in NTED, but not enough to suppress the onset of HPS. This is the first reported case of NTED complicated with HPS. If a physician encounters an NTED patient with severe cytopenia, microscopic examination of peripheral blood smear should be carried out to exclude HPS.

Diabetes mellitus increases severity of thrombocytopenia in dengue-infected patients.

PubMed

Chen, Chung-Yuan; Lee, Mei-Yueh; Lin, Kun-Der; Hsu, Wei-Hao; Lee, Yaun-Jinn; Hsiao, Pi-Jung; Shin, Shyi-Jang

2015-02-10

Diabetes mellitus is known to exacerbate bacterial infection, but its effect on the severity of viral infection has not been well studied. The severity of thrombocytopenia is an indicator of the severity of dengue virus infection. We investigated whether diabetes is associated with thrombocytopenia in dengue-infected patients. We studied clinical characteristics of 644 patients with dengue infection at a university hospital during the epidemic on 1 June 2002 to 31 December 2002 in Taiwan. Platelet counts and biochemical data were compared between patients with and without diabetes. Potential risk factors associated with thrombocytopenia were explored using regression analyses. Dengue-infected patients with diabetes had lower platelet counts than patients without diabetes during the first three days (54.54±51.69 vs. 86.58±63.4 (p≤0.001), 43.98±44.09 vs. 64.52±45.06 (p=0.002), 43.86±35.75 vs. 62.72±51.2 (p=0.012)). Diabetes mellitus, death, dengue shock syndrome (DSS) and dengue hemorrhagic fever (DHF) and increased glutamic-pyruvate transaminase (GPT) levels were significantly associated with lower platelet counts during the first day of hospitalization for dengue fever with regression β of -13.981 (95% confidence interval (CI) -27.587, -0.374), -26.847 (95% CI -37.562, -16.132), and 0.054 (95% CI 0.015, 0.094) respectively. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in dengue patients with or without diabetes with regression β of -2.947 (p=0.004), 2.801 (p=0.005), and -3.568 (p≤0.001), respectively. Diabetic patients with dengue had a higher rate of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) than non-diabetic patients. They also had lower blood albumin, were older, and higher triglyceride levels. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in dengue patients. Dengue patients with diabetes tended to have more severe

The role of carboxyhemoglobin measured with CO-oximetry in the detection of hemolysis in newborns with ABO alloimmunization.

PubMed

Lozar-Krivec, Jana; Bratanic, Borut; Paro-Panjan, Darja

2016-01-01

To evaluate carboxyhemoglobin (COHb) values measured with a CO-oximeter (Roche-cobas b 221) in jaundiced newborns with or without hemolysis and healthy controls in order to assess whether COHb measurement determined with a CO-oximeter could be used as an indicator of hemolysis in newborns with ABO alloimmunization. A total of 86 term newborn infants were prospectively studied. The study cohort consisted of three subgroups: 18 infants with ABO HDN, 21 infants with hyperbilirubinemia without hemolytic disease who required phototherapy, and 47 healthy controls. The COHb, bilirubin, and Hb levels were measured. The three subgroups did not differ significantly with respect to birth weight, gestational age, gender, Apgar score, or mode of delivery. The ABO HDN infants had significantly higher COHb values than the healthy controls (median 2.4% versus 1.3%, p < 0.0005) and the group with hyperbilirubinemia without hemolytic disease (median 2.4% versus 1.3%, p < 0.0005), although the infants with hyperbilirubinemia without hemolytic disease did not have significantly higher COHb values compared with the healthy controls. The cut-off value of 1.7% COHb had 72% sensitivity and 97% specificity for confirming hemolysis in ABO alloimmunization. Our data show that COHb values determined with CO-oximeters are higher in newborns with hemolysis than in those without hemolysis. COHb measured with CO-oximeters could be used to confirm hemolysis in infants with ABO alloimmunization.

Relapsed hydroxychloroquine induced thrombocytopenia in a systemic lupus erythematosus patient.

PubMed

Antón Vázquez, Vanesa; Pascual, Luis; Corominas, Héctor; Giménez Torrecilla, Isabel

Hydroxychloroquine is used in the long-term therapy of systemic lupus erythematosus (SLE). Although considered to be a safe treatment, side effects have been documented. An uncommon side effect is thrombocytopenia. In order to establish the diagnosis of thrombocytopenia secondary to Hydroxychloroquine, non-pharmacological causes must be ruled out and it is necessary to determine a recurrence after re-exposure to the drug. We present one case of severe thrombocytopenia occurring in a patient with SLE undergoing treatment with Hydroxychloroquine. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Immune thrombocytopenia associated with malaria: a case report.

PubMed

Miloudi, Mouhcine; Sbaai, Mohammed; Fatihi, Jamal

2017-10-01

The association of immune thrombocytopenic with malaria is a rare event. We describ the case of a young soldier who, after returning from Central Africa, presented a fever associated with petechial purpura and gingivorrhagia, hemogram showed deep thrombocytopenia and macrocytic normochrome anemia, thick peripheral blood smears confirmed the diagnosis of Plasmodium falciparum malaria, the patient was treated with quinine, but deep thrombocytopenia and hemorrhagic manifestations persisted, the patient then underwent corticosteroid therapy, with favorable evolution and progressive normalization of platelets.

CRISPR/Cas9-mediated conversion of human platelet alloantigen allotypes

PubMed Central

Zhang, Nanyan; Zhi, Huiying; Curtis, Brian R.; Rao, Sridhar; Jobaliya, Chintan; Poncz, Mortimer; French, Deborah L.

2016-01-01

Human platelet alloantigens (HPAs) reside on functionally important platelet membrane glycoproteins and are caused by single nucleotide polymorphisms in the genes that encode them. Antibodies that form against HPAs are responsible for several clinically important alloimmune bleeding disorders, including fetal and neonatal alloimmune thrombocytopenia and posttransfusion purpura. The HPA-1a/HPA-1b alloantigen system, also known as the PlA1/PlA2 polymorphism, is the most frequently implicated HPA among whites, and a single Leu33Pro amino acid polymorphism within the integrin β3 subunit is responsible for generating the HPA-1a/HPA-1b alloantigenic epitopes. HPA-1b/b platelets, like those bearing other low-frequency platelet-specific alloantigens, are relatively rare in the population and difficult to obtain for purposes of transfusion therapy and diagnostic testing. We used CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9) gene-editing technology to transform Leu33+ megakaryocytelike DAMI cells and induced pluripotent stem cells (iPSCs) to the Pro33 allotype. CD41+ megakaryocyte progenitors derived from these cells expressed the HPA-1b (PlA2) alloantigenic epitope, as reported by diagnostic NciI restriction enzyme digestion, DNA sequencing, and western blot analysis using HPA-1b–specific human maternal alloantisera. Application of CRISPR/Cas9 technology to genetically edit this and other clinically-important HPAs holds great potential for production of designer platelets for diagnostic, investigative, and, ultimately, therapeutic use. PMID:26634302

Identification of anti-HPA-1a allo-antibodies using IgG platelet antibody detection and crossmatch system assay with Galileo Echo.

PubMed

Di Cristofaro, Julie; Frassati, Coralie; Montagnie, Rolande; Basire, Agnes; Merieux, Yves; Picard, Christophe

2015-01-01

Fetal/neonatal allo-immune thrombocytopenia is the most frequent and the most dangerous clinical condition involving anti-human platelet antigens (HPA)-1a allo-antibodies. Anti-HPA-1a allo-immunization requires rapid and accurate diagnosis to determine appropriate treatment. The Capture-P Ready-Screen assay (C-PRS) is a new qualitative immunoassay to detect IgG anti-human leukocyte antigen (HLA) and anti-HPA allo-antibodies. The aim of this study is to assess the identification of anti-HPA-1a allo-antibodies using the C-PRS assay, associated with HLA class I stripping reagents, on the automated benchtop analyzer Galileo Echo. Forty-nine sera were analyzed: without anti-HLA class I or anti-HPA allo-antibodies, with anti-HLA class I allo-antibodies, with anti-HPA-1a allo-antibodies, among which with anti-HLA class I allo-antibodies. None of the samples without allo-antibodies were reactive. Only anti-HLA antibodies, detected by cytotoxicity-dependent complement and not by Luminex, remained positive before and after stripping reagents. Of the 13 samples, anti-HPA-1a allo-antibodies that were correctly identified before and after incubation with HLA assassin reagent were 70% and 85%, respectively. Anti-glycoprotein auto-antibodies and anti-HLA allo-antibodies do not interfere with the detection of anti-HPA-1a antibodies. This preliminary study indicates that further improvement of the test will be helpful in developing a clinically useful assay in the future.

Childhood immune thrombocytopenia: Clinical presentation and management

PubMed Central

2012-01-01

Immune thrombocytopenia (ITP) is an acquired hematological disorder that is developed secondary to the production of auto-antibodies against platelets leading to isolated thrombocytopenia, in the absence of other causes of thrombocytopenia such as drugs, infections, malignancy, or other autoimmune diseases [1–6]. ITP commonly affects children between one and seven years of age. Severe life threatening bleeding is rare (0.2–0.9%) [7–12]. Childhood primary ITP usually runs a benign, self-limiting course, with or without treatment. Complete remission occurs within six months from diagnosis, commonly within 6–12 weeks, in the majority of children with the diagnosis of ITP. However, 20–30% of children will continue to have persistent low platelets count with bleeding symptoms beyond six months from diagnosis [4, 12–18]. The diagnosis of ITP in children is essentially one of exclusion. The child is usually one to seven years old, develops skin bruises, petechiae, or mucosal bleeding, who is otherwise healthy and having no lymphadenopathy or organomegally. Full blood count reveals isolated thrombocytopenia with normal hemoglobin (Hb) level, white blood count (WBC) and normal peripheral blood smear. Initial management options for newly diagnosed childhood ITP include; observation only, the use of intravenous immunoglobulin (IVIG), steroids, anti-D immunoglobulin, each alone or in combination [6, 19.] Children who develop chronic ITP may benefit from splenectomy [19, 20–24]. Rituximab, a chimeric monoclonal antibody (anti-CD20), may lead to complete remission, and defers the need for splenectomy [25–27]. Recently, the thrombopoietin (TPO) agonists (Romiplostim and Eltrombopag) produced very good response in adult and pediatric patients with severe chronic ITP [28–30]. PMID:27493327

Natural history of severe thrombocytopenia in infectious mononucleosis

PubMed Central

Wong, Su Yong; Bennett, Bruce

1982-01-01

The natural history of severe thrombocytopenia in two patients with infectious mononucleosis (minimum platelet counts under 10 × 109 and 17 × 109/l respectively) is described. In both, the platelet count rose rapidly and spontaneously, reaching approximately 100 × 109/l on the seventh day. Bleeding symptoms were also transient and never life-threatening. The possibility of very rapid spontaneous recovery from severe thrombocytopenia must be borne in mind in assessing the effect of any drug in the management of this complication of infectious mononucleosis. PMID:7111109

Management of Thrombocytopenia in Chronic Liver Disease: Focus on Pharmacotherapeutic Strategies.

PubMed

Maan, Raoel; de Knegt, Robert J; Veldt, Bart J

2015-11-01

Thrombocytopenia (platelet count <150 × 10(9)/L) often complicates chronic liver disease, impeding optimal management of these patients. The prevalence of this manifestation ranges from 6% among non-cirrhotic patients with chronic liver disease to 70% among patients with liver cirrhosis. It has also been shown that the severity of liver disease is associated with both prevalence and level of thrombocytopenia. Its development is often multifactorial, although thrombopoietin is thought to be a major factor. The discovery of and ability to clone thrombopoietin led to new treatment opportunities for this clinical manifestation. This review discusses data on the three most important thrombopoietin receptor agonists: eltrombopag, avatrombopag, and romiplostim. Currently, only eltrombopag is approved for usage among patients with thrombocytopenia and chronic hepatitis C virus infection in order to initiate and maintain interferon-based antiviral treatment. Nevertheless, the optimal management of hematologic abnormalities among patients with chronic liver disease, and its risk for bleeding complications, is still a matter of discussion. Thrombocytopenia definitely contributes to hemostatic defects but is often counterbalanced by the enhanced presence of procoagulant factors. Therefore, a thorough assessment of the patient's risk for thrombotic events is essential when the use of thrombopoietin receptor agonists is considered among patients with chronic liver disease and thrombocytopenia.

Acute disseminated encephalomyelitis and thrombocytopenia following Epstein-Barr virus infection.

PubMed

Saeed, Muhammad; Dabbagh, Omar; Al-Muhaizae, Muhammad; Dhalaan, Hesham; Chedrawi, Aziza

2014-11-01

Epstein-Barr Virus (EBV) causes a broad spectrum of disease in humans with several clinical syndromes and is ubiquitous, infecting more than 95% of the world's population. Central Nervous System (CNS) disease alone associated with Epstein-Barr virus rarely occurs in previously healthy individuals. Systemic viral illness in children and complications are rare, but may occur. In few cases, it is associated with a variety of CNS and hematological complications like acute disseminated encephalomyelitis, transverse myelitis, neuropsychiatric syndrome, GBS, autoimmune thrombocytopenia and hemolytic anemia and they usually respond to immunotherapy. We report previously healthy boy, who presented with left sided weakness, headache and thrombocytopenia following EBV infection. The thrombocytopenia was resistant to intravenous immunoglobulin and methylprednisolone but responded well to Rituximab.

Thrombocytopenia associated with vaccination of a dog with a modified-live paramyxovirus vaccine.

PubMed

McAnulty, J F; Rudd, R G

1985-06-01

Thrombocytopenia (10,000/mm3), with hematochezia and melena, appeared in a dog 8 days after it was given modified-live canine distemper, virus vaccine and persisted for approximately 5 days. Clinical investigation discounted other possible causes of thrombocytopenia; the condition was considered to be associated with vaccination. The problem spontaneously resolved. The appearance of thrombocytopenia after modified-live canine distemper virus vaccination is not unknown and may assume a severe form. This condition may be mistaken for idiopathic thrombocytopenia of immune origin, and in other instances, it may contribute significantly to surgical risk if concurrent coagulation disorders are present. Administration of levamisole HCl may alleviate the decrease in platelet count in affected animals.

Thrombocytopenia after liver transplantation: Should we care?

PubMed Central

Takahashi, Kazuhiro; Nagai, Shunji; Safwan, Mohamed; Liang, Chen; Ohkohchi, Nobuhiro

2018-01-01

Transient thrombocytopenia is a common phenomenon after liver transplantation. After liver transplantation (LT), platelet count decreases and reaches a nadir on postoperative days 3-5, with an average reduction in platelet counts of 60%; platelet count recovers to preoperative levels approximately two weeks after LT. The putative mechanisms include haemodilution, decreased platelet production, increased sequestration, medications, infections, thrombosis, or combination of these processes. However, the precise mechanisms remain unclear. The role of platelets in liver transplantation has been highlighted in recent years, and particular attention has been given to their effects beyond hemostasis and thrombosis. Previous studies have demonstrated that perioperative thrombocytopenia causes poor graft regeneration, increases the incidence of postoperative morbidity, and deteriorates the graft and decreases patient survival in both the short and long term after liver transplantation. Platelet therapies to increase perioperative platelet counts, such as thrombopoietin, thrombopoietin receptor agonist, platelet transfusion, splenectomy, and intravenous immunoglobulin treatment might have a potential for improving graft survival, however clinical trials are lacking. Further studies are warranted to detect direct evidence on whether thrombocytopenia is the cause or result of poor-graft function and postoperative complications, and to determine who needs platelet therapies in order to prevent postoperative complications and thus improve post-transplant outcomes. PMID:29632420

Thrombocytopenia after aortic valve replacement with freedom solo bioprosthesis: a propensity study.

PubMed

Piccardo, Alessandro; Rusinaru, Dan; Petitprez, Benoit; Marticho, Paul; Vaida, Ioana; Tribouilloy, Christophe; Caus, Thierry

2010-05-01

The incidence of postoperative thrombocytopenia after aortic valve replacement with the Freedom Solo bioprosthesis remains unclear. This propensity-matched study was carried out to evaluate the incidence and clinical impact of thrombocytopenia in patients receiving the Freedom Solo bioprosthesis. Patients who underwent aortic valve replacement with a Freedom Solo or Carpentier-Edwards Perimount pericardial prosthesis at our institution between 2006 and 2008 were screened retrospectively. Exclusion criteria included double valve replacement, redo surgery, and active endocarditis. Two hundred six patients were considered eligible for this analysis. Using propensity scores 36 matched pairs of patients with a Freedom Solo or Perimount bioprosthesis were obtained. The primary end point was the occurrence of postoperative thrombocytopenia. Secondary end points were postoperative thromboembolic or hemorrhagic events and 30-day mortality. Before matching, severe thrombocytopenia (<30 x 10(9) platelets/L) occurred in 22% of patients with a Freedom Solo bioprosthesis and 1% with a Perimount bioprosthesis (p < 0.0001), thromboembolic or hemorrhagic events occurred in 3% and 2%, respectively (p = 0.37), and 30-day mortality was 4% and 6%, respectively (p = 0.48). Multivariate analysis identified preoperative platelet count (p = 0.01) and Freedom Solo (p < 0.0001) as independent risk factors for severe postoperative thrombocytopenia. After matching, severe thrombocytopenia occurred in 25% and 3% of patients with Freedom Solo and Perimount bioprostheses, respectively (p < 0.0001), thromboembolic or hemorrhagic events occurred in 0%, and 30-day mortality was 3% and 6%, respectively (p = 0.99). The risk of thrombocytopenia was high after Freedom Solo implantation. However, this complication was not related to any deleterious events in our study population. Copyright (c) 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Mechanisms of Thrombocytopenia During Septic Shock: A Multiplex Cluster Analysis of Endogenous Sepsis Mediators.

PubMed

Bedet, Alexandre; Razazi, Keyvan; Boissier, Florence; Surenaud, Mathieu; Hue, Sophie; Giraudier, Stéphane; Brun-Buisson, Christian; Mekontso Dessap, Armand

2018-06-01

Thrombocytopenia is a common feature of sepsis and may involve various mechanisms often related to the inflammatory response. This study aimed at evaluating factors associated with thrombocytopenia during human septic shock. In particular, we used a multiplex analysis to assess the role of endogenous sepsis mediators. Prospective, observational study. Thrombocytopenia was defined as an absolute platelet count <100 G/L or a 50% relative decrease in platelet count during the first week of septic shock. Plasma concentrations of 27 endogenous mediators involved in sepsis and platelet pathophysiology were assessed at day-1 using a multi-analyte Milliplex human cytokine kit. Patients with underlying diseases at risk of thrombocytopenia (hematological malignancies, chemotherapy, cirrhosis, and chronic heart failure) were excluded. Thrombocytopenia occurred in 33 (55%) of 60 patients assessed. Patients with thrombocytopenia were more prone to present with extrapulmonary infections and bacteremia. Disseminated intravascular coagulation was frequent (81%) in these patients. Unbiased hierarchical clustering identified five different clusters of sepsis mediators, including one with markers of platelet activation (e.g., thrombospondin-1) positively associated with platelet count, one with markers of inflammation (e.g., tumor necrosis factor alpha and heat shock protein 70), and endothelial dysfunction (e.g., intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) negatively associated with platelet count, and another involving growth factors of thrombopoiesis (e.g., thrombopoietin), also negatively associated with platelet count. Surrogates of hemodilution (e.g., hypoprotidemia and higher fluid balance) were also associated with thrombocytopenia. Multiple mechanisms seemed involved in thrombocytopenia during septic shock, including endothelial dysfunction/coagulopathy, hemodilution, and altered thrombopoiesis.

A distinct plasmablast and naïve B-cell phenotype in primary immune thrombocytopenia

PubMed Central

Flint, Shaun M.; Gibson, Adele; Lucas, Geoff; Nandigam, Raghava; Taylor, Louise; Provan, Drew; Newland, Adrian C.; Savage, Caroline O.; Henderson, Robert B.

2016-01-01

Primary immune thrombocytopenia is an autoimmune disorder in which platelet destruction is a consequence of both B- and T-cell dysregulation. Flow cytometry was used to further characterize the B- and T-cell compartments in a cross-sectional cohort of 26 immune thrombocytopenia patients including antiplatelet antibody positive (n=14) and negative (n=12) patients exposed to a range of therapies, and a cohort of matched healthy volunteers. Markers for B-cell activating factor and its receptors, relevant B-cell activation markers (CD95 and CD21) and markers for CD4+ T-cell subsets, including circulating T-follicular helper-like cells, were included. Our results indicate that an expanded population of CD95+ naïve B cells correlated with disease activity in immune thrombocytopenia patients regardless of treatment status. A population of CD21-naïve B cells was specifically expanded in autoantibody-positive immune thrombocytopenia patients. Furthermore, the B-cell maturation antigen, a receptor for B-cell activating factor, was consistently and strongly up-regulated on plasmablasts from immune thrombocytopenia patients. These observations have parallels in other autoantibody-mediated diseases and suggest that loss of peripheral tolerance in naïve B cells may be an important component of immune thrombocytopenia pathogenesis. Moreover, the B-cell maturation antigen represents a potential target for plasma cell directed therapies in immune thrombocytopenia. PMID:26969086

A distinct plasmablast and naïve B-cell phenotype in primary immune thrombocytopenia.

PubMed

Flint, Shaun M; Gibson, Adele; Lucas, Geoff; Nandigam, Raghava; Taylor, Louise; Provan, Drew; Newland, Adrian C; Savage, Caroline O; Henderson, Robert B

2016-06-01

Primary immune thrombocytopenia is an autoimmune disorder in which platelet destruction is a consequence of both B- and T-cell dysregulation. Flow cytometry was used to further characterize the B- and T-cell compartments in a cross-sectional cohort of 26 immune thrombocytopenia patients including antiplatelet antibody positive (n=14) and negative (n=12) patients exposed to a range of therapies, and a cohort of matched healthy volunteers. Markers for B-cell activating factor and its receptors, relevant B-cell activation markers (CD95 and CD21) and markers for CD4(+) T-cell subsets, including circulating T-follicular helper-like cells, were included. Our results indicate that an expanded population of CD95(+) naïve B cells correlated with disease activity in immune thrombocytopenia patients regardless of treatment status. A population of CD21-naïve B cells was specifically expanded in autoantibody-positive immune thrombocytopenia patients. Furthermore, the B-cell maturation antigen, a receptor for B-cell activating factor, was consistently and strongly up-regulated on plasmablasts from immune thrombocytopenia patients. These observations have parallels in other autoantibody-mediated diseases and suggest that loss of peripheral tolerance in naïve B cells may be an important component of immune thrombocytopenia pathogenesis. Moreover, the B-cell maturation antigen represents a potential target for plasma cell directed therapies in immune thrombocytopenia. Copyright© Ferrata Storti Foundation.

Vancomycin-induced thrombocytopenia in a 60-year-old man: a case report.

PubMed

Shah, Ravish A; Musthaq, Adnan; Khardori, Nancy

2009-06-26

Vancomycin, a glycopeptide antibiotic, is used to treat resistant gram-positive infections. There has been a 10- to 20-fold increase in its use over the past 25 years. Although ototoxicity and nephrotoxicity are well known side effects of vancomycin, it can also induce platelet reactive antibodies leading to life-threatening thrombocytopenia. Vancomycin is often clinically overlooked as a cause of thrombocytopenia, especially in a scenario of sepsis or when there is use of heparin. We report a proven case of vancomycin-induced thrombocytopenia and its reversal after discontinuation of vancomycin. A 60-year-old man with a history of hypertension, congestive heart failure and dyslipidemia was admitted for a right shoulder rotator cuff tear. He underwent right-shoulder arthroscopy and rotator cuff repair. About three weeks later, he developed pain, swelling and purulent drainage from his right shoulder. Arthroscopic irrigation and drainage was then performed. Intraoperative fluid revealed the presence of Methicillin susceptible Staphylococcus aureus, vancomycin-sensitive Enterococcus spp. and Serratia marcescens. The patient had no known allergies. After reviewing his antimicrobial susceptibility, he was started on vancomycin 1500 mgs intravenously every 12 hours (to treat both Staphylococcus aureus and Enterococcus spp) and ciprofloxacin 750 mgs by oral induction every 12 hours. The patient's condition improved following antibiotic treatment. He was discharged and allowed to go home on IV vancomycin and oral ciprofloxacin. The patient's platelet count on the day of starting vancomycin therapy was 253 x 10(3)/mm(3). At weeks one, two and three, the counts were 231 x 10(3)/mm(3), 272 x 10(3)/mm and 6 x 103/mm(3), respectively. The patient was admitted for further work-up of the thrombocytopenia. He was later shown to have vancomycin-induced platelet-reactive antibodies, causing significant thrombocytopenia, and then reversal after his vancomycin medication was

Persistent immune thrombocytopenia heralds the diagnosis of Mycobacterium chimaera prosthetic valve endocarditis.

PubMed

Sacco, Keith A; Burton, M Caroline

2017-01-01

A 63 year old female was admitted for investigation of worsening renal insufficiency. During hospitalization she developed persistent immune thrombocytopenia refractory to supportive or immunosuppressive treatment. She was diagnosed with Mycobacterium chimaera prosthetic valve endocarditis and thrombocytopenia resolved with anti-mycobacterial therapy.

Platelet Immunology in China: Research and Clinical Applications.

PubMed

Wu, Guoguang; Zhou, Yan; Li, Lilan; Zhong, Zhoulin; Li, Hengchong; Li, Haiyan; Yu, Mei; Shen, Weidong; Ni, Heyu

2017-04-01

Immunization against human platelet alloantigens (HPAs) is associated with a number of clinical complications. The detection and identification of clinically relevant platelet antibodies are important for the diagnosis and management of patients affected with immune-mediated thrombocytopenias. Human platelet alloantigen frequencies and the characteristics of antiplatelet antibodies vary widely between ethnic groups. Since 2008, the importance of platelet immunology in the field of transfusion medicine has gained greater recognition by clinical laboratories in China. Laboratories in China have established and improved methods for platelet antibody detection and HPA genotyping techniques, which are used for the diagnosis of alloimmune platelet disorders in clinic and research environments. Research has revealed the frequencies of HPA alleles in different Chinese ethnic groups and compared the differences in HPA gene frequencies between the Chinese Han and other ethnic groups of the world. Production of anti-CD36 isoantibodies is an important risk factor for immune-mediated thrombocytopenia in the Chinese population. Advances in research and clinical application of platelet immunology have significantly improved the clinical diagnosis, treatment including transfusion support, and prevention of alloimmune platelet disorders in the Chinese population. Copyright © 2017. Published by Elsevier Inc.

Enoxaparin can be used safely in patients with severe thrombocytopenia due to intensive chemotherapy regimens.

PubMed

Herishanu, Yair; Misgav, Mudi; Kirgner, Ilya; Ben-Tal, Ofira; Eldor, Amiram; Naparstek, Ella

2004-07-01

Treatment with intensive chemotherapy regimens is frequently complicated by severe thrombocytopenia. During the period of severe thrombocytopenia, anticoagulant treatment is not uncommonly indicated for thromboembolic events or thromboprophylaxis in these patients. We report 10 hematological patients treated with intensive chemotherapy protocols that were anticoagulated with enoxaparin for catheter related central venous thrombosis and thromboprophylaxis. During the period of severe thrombocytopenia the dosages of enoxaparin were reduced and no major bleeding occurred. Based on our experience we suggest that reduced dosages of low molecular weight heparins may be used relatively safely during transient severe thrombocytopenia.

Eltrombopag Use in Thrombocytopenia for Endoscopic Submucosal Dissection of a Gastric Carcinoid

PubMed Central

Kaltenbach, Tonya; Martin, Beth; Rouse, Robert V.; Soetikno, Roy

2014-01-01

Severe thrombocytopenia is a contraindication for therapeutic endoscopy due to the risk of bleeding. Platelet transfusions can temporarily increase platelet count, but are difficult to administer in the 2 weeks following endoscopic resection, during which the patient is at high risk for delayed bleeding. We present the use of a novel thrombopoietin receptor agonist, eltrombopag, to sustain platelet levels for the safe and complete endoscopic submucosal dissection of a gastric carcinoid in a patient with severe thrombocytopenia due to cirrhosis and idiopathic thrombocytopenic purpura. We performed complete and safe endoscopic removal of a gastric carcinoid after correcting the thrombocytopenia. PMID:26157896

A Novel Clinically Relevant Strategy to Abrogate Autoimmunity and Regulate Alloimmunity in NOD Mice

PubMed Central

Vergani, Andrea; D'Addio, Francesca; Jurewicz, Mollie; Petrelli, Alessandra; Watanabe, Toshihiko; Liu, Kaifeng; Law, Kenneth; Schuetz, Christian; Carvello, Michele; Orsenigo, Elena; Deng, Shaoping; Rodig, Scott J.; Ansari, Javeed M.; Staudacher, Carlo; Abdi, Reza; Williams, John; Markmann, James; Atkinson, Mark; Sayegh, Mohamed H.; Fiorina, Paolo

2010-01-01

OBJECTIVE To investigate a new clinically relevant immunoregulatory strategy based on treatment with murine Thymoglobulin mATG Genzyme and CTLA4-Ig in NOD mice to prevent allo- and autoimmune activation using a stringent model of islet transplantation and diabetes reversal. RESEARCH DESIGN AND METHODS Using allogeneic islet transplantation models as well as NOD mice with recent onset type 1 diabetes, we addressed the therapeutic efficacy and immunomodulatory mechanisms associated with a new immunoregulatory protocol based on prolonged low-dose mATG plus CTLA4-Ig. RESULTS BALB/c islets transplanted into hyperglycemic NOD mice under prolonged mATG+CTLA4-Ig treatment showed a pronounced delay in allograft rejection compared with untreated mice (mean survival time: 54 vs. 8 days, P < 0.0001). Immunologic analysis of mice receiving transplants revealed a complete abrogation of autoimmune responses and severe downregulation of alloimmunity in response to treatment. The striking effect on autoimmunity was confirmed by 100% diabetes reversal in newly hyperglycemic NOD mice and 100% indefinite survival of syngeneic islet transplantation (NOD.SCID into NOD mice). CONCLUSIONS The capacity to regulate alloimmunity and to abrogate the autoimmune response in NOD mice in different settings confirmed that prolonged mATG+CTLA4-Ig treatment is a clinically relevant strategy to translate to humans with type 1 diabetes. PMID:20805386

Life-threatening haematuria caused by vancomycin-induced thrombocytopenia

PubMed Central

Lobo, Niyati; Ejiofor, Kandi; Thurairaja, Ramesh; Khan, Muhammad Shamim

2015-01-01

Thrombocytopenia is a rare side effect of vancomycin, an antibiotic that is often used to treat Gram-positive bacterial infections. A 67-year-old man developed bilateral pulmonary emboli and hospital-acquired pneumonia following left ureteric reimplantation. He was anticoagulated with rivaroxaban and started on intravenous vancomycin and gentamicin for treatment of pneumonia. After five doses of vancomycin, his platelet count dropped to a nadir of 0×109/L (baseline: 314×109/L) manifesting as visible heavy haematuria and haemodynamic instability due to excessive blood loss. Reversal of the thrombocytopenia was achieved with intravenous immunoglobulin, methylprednisolone and continuous platelet transfusions. PMID:25716041

Heparin-induced thrombocytopenia

PubMed Central

Shaikh, Nissar

2011-01-01

In the last 7 decades heparin has remained the most commonly used anticoagulant. Its use is increasing, mainly due to the increase in the number of vascular interventions and aging population. The most feared complication of heparin use is heparin-induced thrombocytopenia (HIT). HIT is a clinicopathologic hypercoagulable, procoagulant prothrombotic condition in patients on heparin therapy, and decrease in platelet count by 50% or to less than 100,000, from 5 to 14 days of therapy. This prothrombotic hypercoagulable state in HIT patient is due to the combined effect of various factors, such as platelet activation, mainly the formation of PF4/heparin/IgG complex, stimulation of the intrinsic factor, and loss of anticoagulant effect of heparin. Diagnosis of HIT is done by clinical condition, heparin use, and timing of thrombocytopenia, and it is confirmed by either serotonin release assay or ELISA assay. Complications of HIT are venous/arterial thrombosis, skin gangrene, and acute platelet activation syndrome. Stopping heparin is the basic initial treatment, and Direct Thrombin Inhibitors (DTI) are medication of choice in these patients. A few routine but essential procedures performed by using heparin are hemodialysis, Percutaneous Coronary Intervention, and Cardiopulmonary Bypass; but it cannot be used if a patient develops HIT. HIT patients with unstable angina, thromboembolism, or indwelling devices, such as valve replacement or intraaortic balloon pump, will require alternative anticoagulation therapy. HIT can be prevented significantly by keeping heparin therapy shorter, avoiding bovine heparin, using low-molecular weight heparin, and stopping heparin use for flush and heparin lock. PMID:21633576

Severe thrombocytopenia in a child with typhoid fever: a case report.

PubMed

Al Reesi, Mohammed; Stephens, Glenn; McMullan, Brendan

2016-11-30

Although thrombocytopenia is common in typhoid fever, its course, response to treatment, and need for specific therapies such as platelet transfusion are not well characterized. We report a case of typhoid fever in a 4-year-old Asian male returned traveler, admitted with prolonged fever and found to have severe thrombocytopenia (platelets 16 × 10 9 /L). Despite appropriate antibiotic therapy, his platelet recovery was slow, but did not lead to complications and he did not require platelet transfusion. There is no consensus in the medical literature guiding the optimal management of severe thrombocytopenia in typhoid fever, but it may improve with conservative management, as in our case. The epidemiology and management of this condition merits further research to guide clinical practice.

Bleeding prevalence and transfusion requirement in patients with thrombocytopenia in the emergency department.

PubMed

Turvani, Fabrizio; Pigozzi, Luca; Barutta, Letizia; Pivetta, Emanuele; Pizzolato, Elisa; Morello, Fulvio; Battista, Stefania; Moiraghi, Corrado; Montrucchio, Giuseppe; Lupia, Enrico

2014-10-01

Thrombocytopenia is the most common coagulation disorder in critically ill patients. No studies have investigated the epidemiology and clinical impact of this condition in emergency department (ED) patients. We aimed to investigate epidemiological features, incidence of bleeding, and diagnostic and therapeutic requirements of patients with thrombocytopenia admitted to the ED. We performed a retrospective observational study enrolling all patients admitted to the medical-surgical ED of the "Città della Salute e della Scienza di Torino" Hospital with a platelet count <150×10(9) PLTs/L, during four non-consecutive months. There were no exclusion criteria. The study included 1218 patients. The percentage of patients with severe (<50×10(9) PLTs/L) or very severe (<20×10(9) PLTs/L) thrombocytopenia was about 12%. Thrombocytopenia associated with liver cirrhosis was the most represented etiology. On the contrary, the most frequent cause in patients with newly recognized low platelet count was disseminated intravascular coagulation/sepsis. The incidence of bleeding and hypovolemia, as well as the need of transfusional support and mechanical, surgical or endoscopic hemostasis progressively increased with the severity of thrombocytopenia. Our results suggest that the detection of a platelet count lower than 50×10(9) PLTs/L may help to identify patients with higher bleeding risk in the ED setting. Additional studies are required to evaluate whether, in this setting, thrombocytopenia may represent an independent risk factor for bleeding episodes and increased mortality.

[New developments in spastic unilateral cerebral palsy].

PubMed

Chabrier, S; Roubertie, A; Allard, D; Bonhomme, C; Gautheron, V

2010-01-01

Hemiplegic (or spastic unilateral) cerebral palsy accounts for about 30% of all cases of cerebral palsy. With a population prevalence of 0.6 per 1000 live births, it is the most common type of cerebral palsy among term-born children and the second most common type after diplegia among preterm infants. Many types of prenatal and perinatal brain injury can lead to congenital hemiplegia and brain MRI is the most useful tool to classify them with accuracy and to provide early prognostic information. Perinatal arterial ischemic stroke thus appears as the leading cause in term infants, whereas encephalopathy of prematurity is the most common cause in premature babies. Other causes include brain malformations, neonatal sinovenous thrombosis, parenchymal hemorrhage (for example due to coagulopathy or alloimmune thrombocytopenia) and the more recently described familial forms of porencephaly associated with mutations in the COL4A1 gene. In adjunction with pharmacologic treatment (botulinium neurotoxin injection), new evidence-based rehabilitational interventions, such as constraint-induced movement therapy and mirror therapy, are increasingly being used.

Immediate transient thrombocytopenia at the time of alemtuzumab infusion in multiple sclerosis.

PubMed

Ranganathan, Usha; Kaunzner, Ulrike; Foster, Stacyann; Vartanian, Timothy; Perumal, Jai S

2018-04-01

Alemtuzumab is a monoclonal antibody approved for relapsing-remitting multiple sclerosis (RRMS). Although Immune thrombocytopenia (ITP) has been reported as a secondary autoimmune phenomenon following alemtuzumab infusion, immediate thrombocytopenia during the infusion has not been reported. We report transient, reversible, self-limiting acute-onset thrombocytopenia during the first course with alemtuzumab. In total, 3 of 22 paitents developed mild self-limited bruising associated with a drop in platelet count from their baseline during the intial 5-day course of alemtuzumab. Upon chart review, all 22 patients who received alemtuzumab developed an immediate mostly asymptomatic drop in platelet count which returned to normal within 2 months post-infusion.

[Perforated neonatal appendicitis in a preterm newborn].

PubMed

Vakrilova, L; Georgiev, Tz; Hitrova, St; Slancheva, B

2014-01-01

Abstract: Appendicitis is common in paediatric surgical praxis, but extremely rare in newborn infants. We report a premature male newborn from a twin pregnancy with gestational age of 31(+4) weeks, birth-weight 1580g, who underwent a laparotomy because of perforation. The baby was admitted to NICU after birth with transitory respiratory failure and early onset neonatal sepsis. MS-Staphylococcus epidermidis was isolated from blood culture, gastric contents and all peripheral specimens, C-reactive protein values were elevated after birth and significantly increased before surgery; thrombocytopenia and mild anemia were found. The control blood culture showed Candida albicans. At day 25 after birth life threatening deterioration occurred: feculent vomiting, progressing distension and palpable rigidity of the abdomen, absence of peristalsis, respiratory distress. Abdominal radiograph showed significantly distension of the intestines, air liquid levels, and discrete signs of pneumoperitoneum. The baby was transferred to the surgery with the diagnosis NEC with perforation. Appendicitis acuta gangrenosa perforativa and peritonitis fibrinopurulenta totalis were found intra-operatively but without signs of NEC. Appendectomy and sanitation of the abdominal cavity were carried out. The histological result confirmed gangrenous perforative appendicitis and purulent necrotic peritonitis. The postoperative course was unremarkable. The boy was transferred to the neonatology on day 33 of life and discharged home 12 days later. Despite of the low incidence of neonatal appendicitis, it should be taken into consideration if unclear abdominal symptoms occur in the neonatal period. Early surgical intervention contribute to a reduction of potential complications.

A Case Report of Drug-Induced Thrombocytopenia after Living Donor Liver Transplantation

PubMed Central

ARAI, KEISUKE; KURAMITSU, KAORI; FUKUMOTO, TAKUMI; KIDO, MASAHIRO; TAKEBE, ATSUSHI; TANAKA, MOTOFUMI; KINOSHITA, HISOKA; AJIKI, TETSUO; TOYAMA, HIROCHIKA; ASARI, SADAKI; GOTO, TADAHIRO; KU, YONSON

2016-01-01

There are few descriptions of severe thrombocytopenia during the early postoperative period after liver transplantation, and these have not been fully documented in the literature. Here, we report a case of drug-induced thrombocytopenia requiring transfusion of blood products after living donor liver transplantation. We determined that this was not caused by the interferon-free anti-viral therapy but by tacrolimus A 61-year-old woman with hepatitis C-related cirrhosis and hepatorenal syndrome underwent living donor liver transplantation using a left lobe graft from her son. After transplantation, immunosuppression consisted of tacrolimus and steroid. Seven weeks after transplantation, interferon-free therapy with daclatasvir and asunaprevir was started. Thirteen days thereafter, hepatitis C virus tested negative. However, the platelet count had begun to gradually decrease just before starting anti-viral therapy. Daclatasvir and asunaprevir were stopped because this was suspected to be a side-effect of these drugs, but the patient nonetheless went on to develop severe thrombocytopenia (platelet count 17,000/μL), which needed transfusions. Now suspecting tacrolimus as the inducer of this side effect, we changed to cyclosporin, after which the platelet count gradually recovered. Viral markers were still not detectable up to 2 months after discontinuation of the antiviral drugs. We conclude that when severe thrombocytopenia occurs, possible drug-induced thrombocytopenia as well as other disorders must be investigated. PMID:27492209

The contribution of mouse models to the understanding of constitutional thrombocytopenia.

PubMed

Léon, Catherine; Dupuis, Arnaud; Gachet, Christian; Lanza, François

2016-08-01

Constitutional thrombocytopenias result from platelet production abnormalities of hereditary origin. Long misdiagnosed and poorly studied, knowledge about these rare diseases has increased considerably over the last twenty years due to improved technology for the identification of mutations, as well as an improvement in obtaining megakaryocyte culture from patient hematopoietic stem cells. Simultaneously, the manipulation of mouse genes (transgenesis, total or conditional inactivation, introduction of point mutations, random chemical mutagenesis) have helped to generate disease models that have contributed greatly to deciphering patient clinical and laboratory features. Most of the thrombocytopenias for which the mutated genes have been identified now have a murine model counterpart. This review focuses on the contribution that these mouse models have brought to the understanding of hereditary thrombocytopenias with respect to what was known in humans. Animal models have either i) provided novel information on the molecular and cellular pathways that were missing from the patient studies; ii) improved our understanding of the mechanisms of thrombocytopoiesis; iii) been instrumental in structure-function studies of the mutated gene products; and iv) been an invaluable tool as preclinical models to test new drugs or develop gene therapies. At present, the genetic determinants of thrombocytopenia remain unknown in almost half of all cases. Currently available high-speed sequencing techniques will identify new candidate genes, which will in turn allow the generation of murine models to confirm and further study the abnormal phenotype. In a complementary manner, programs of random mutagenesis in mice should also identify new candidate genes involved in thrombocytopenia. Copyright© Ferrata Storti Foundation.

CRISPR/Cas9-mediated conversion of human platelet alloantigen allotypes.

PubMed

Zhang, Nanyan; Zhi, Huiying; Curtis, Brian R; Rao, Sridhar; Jobaliya, Chintan; Poncz, Mortimer; French, Deborah L; Newman, Peter J

2016-02-11

Human platelet alloantigens (HPAs) reside on functionally important platelet membrane glycoproteins and are caused by single nucleotide polymorphisms in the genes that encode them. Antibodies that form against HPAs are responsible for several clinically important alloimmune bleeding disorders, including fetal and neonatal alloimmune thrombocytopenia and posttransfusion purpura. The HPA-1a/HPA-1b alloantigen system, also known as the Pl(A1)/Pl(A2) polymorphism, is the most frequently implicated HPA among whites, and a single Leu33Pro amino acid polymorphism within the integrin β3 subunit is responsible for generating the HPA-1a/HPA-1b alloantigenic epitopes. HPA-1b/b platelets, like those bearing other low-frequency platelet-specific alloantigens, are relatively rare in the population and difficult to obtain for purposes of transfusion therapy and diagnostic testing. We used CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9) gene-editing technology to transform Leu33 (+) megakaryocytelike DAMI cells and induced pluripotent stem cells (iPSCs) to the Pro33 allotype. CD41(+) megakaryocyte progenitors derived from these cells expressed the HPA-1b (Pl(A2)) alloantigenic epitope, as reported by diagnostic NciI restriction enzyme digestion, DNA sequencing, and western blot analysis using HPA-1b-specific human maternal alloantisera. Application of CRISPR/Cas9 technology to genetically edit this and other clinically-important HPAs holds great potential for production of designer platelets for diagnostic, investigative, and, ultimately, therapeutic use. © 2016 by The American Society of Hematology.

Romiplostim for Immune Thrombocytopenia in Neuroblastoma Patients Receiving Chemotherapy.

PubMed

Fassel, Hannah; Bussel, James B; Roberts, Stephen S; Modak, Shakeel

2018-04-20

Thrombocytopenia, a serious complication of myelosuppressive chemotherapy in cancer patients, is managed with platelet transfusions until recovery of platelet counts. However, children receiving chemotherapy can rarely develop immune thrombocytopenia (ITP) that is refractory to transfused platelets. This limits the ability to achieve adequate platelet counts and administer further myelosuppressive chemotherapy safely, especially if first-line ITP therapy is ineffective. We report 2 cases of intravenous immunoglobulin refractory ITP in children receiving chemotherapy for high-risk neuroblastoma. ITP was successfully treated with the thrombopoietin-receptor-agonist romiplostim, allowing safe and timely continuation of antineuroblastoma therapies in these high-risk patients.

Resolution of Dialyzer Membrane-Associated Thrombocytopenia with Use of Cellulose Triacetate Membrane: A Case Report

PubMed Central

Olafiranye, Feyisayo; Kyaw, Win; Olafiranye, Oladipupo

2011-01-01

Blood and dialyzer membrane interaction can cause significant thrombocytopenia through the activation of complement system. The extent of this interaction determines the biocompatibility of the membrane. Although the newer synthetic membranes have been shown to have better biocompatibility profile than the cellulose-based membranes, little is known about the difference in biocompatibility between synthetic membrane and modified cellulose membrane. Herein, we report a case of a patient on hemodialysis who developed dialyzer-membrane-related thrombocytopenia with use of synthetic membrane (F200NR polysulfone). The diagnosis of dialyzer membrane-associated thrombocytopenia was suspected by the trend of platelet count before and after dialysis, and the absence of other possible causes of thrombocytopenia. We observed significant improvement in platelet count when the membrane was changed to modified cellulose membrane (cellulose triacetate). In patients at high risk for thrombocytopenia, the modified cellulose membrane could be a better alternative to the standard synthetic membranes during hemodialysis. PMID:21547252

Safety of milrinone use in neonatal intensive care units

PubMed Central

Samiee-Zafarghandy, Samira; Raman, Sudha R.; van den Anker, John N.; McHutchison, Kerstin; Hornik, Christoph P.; Clark, Reese H.; Smith, P. Brian

2014-01-01

Background Milrinone use in the neonatal intensive care unit has increased over the last 10 years despite a paucity of published safety data in infants. We sought to determine the safety of milrinone therapy among infants in the neonatal intensive care unit. Methods We conducted a retrospective data analysis, identifying all infants exposed to milrinone discharged from 322 neonatal intensive care units managed by the Pediatrix Medical Group from 1997–2010. We identified adverse events (AEs) during milrinone exposure. The unit of observation for clinical AEs was the first course of milrinone and for laboratory AEs was an infant-day of exposure to milrinone. Results Overall, 1446 of 716,821 (0.2%) infants received milrinone for a total of 6894 infant-days. The proportion of infants exposed to milrinone increased from 0 in 1997 to 4/1000 infant cases in 2010. Persistent pulmonary hypertension (40%) was the most commonly reported diagnosis at the start of milrinone administration. Overall, 606/1446 (42%) of infants had at least 1 clinical AE recorded during milrinone therapy. Hypotension requiring pressors and thrombocytopenia (<100,000/mm3) were the most commonly reported clinical and laboratory AEs, respectively. Death was reported in 8% of infants during the first course of milrinone therapy. Conclusion Among infants hospitalized in the neonatal intensive care unit, there was an increase in the use of milrinone over the past 13 years. The safety, dosing, and efficacy of milrinone in infants should be determined in prospective clinical trials. PMID:25460254

Safety of milrinone use in neonatal intensive care units.

PubMed

Samiee-Zafarghandy, Samira; Raman, Sudha R; van den Anker, John N; McHutchison, Kerstin; Hornik, Christoph P; Clark, Reese H; Brian Smith, P

2015-01-01

Milrinone use in the neonatal intensive care unit has increased over the last 10 years despite a paucity of published safety data in infants. We sought to determine the safety of milrinone therapy among infants in the neonatal intensive care unit. We conducted a retrospective data analysis, identifying all infants who were exposed to milrinone and discharged from 322 neonatal intensive care units managed by the Pediatrix Medical Group from 1997-2010. We identified adverse events (AEs) during milrinone exposure. The unit of observation for clinical AEs was the first course of milrinone and for laboratory AEs it was an infant-day of exposure to milrinone. Overall, 1446 of 716,821 (0.2%) infants received milrinone for a total of 6894 infant-days. The proportion of infants exposed to milrinone increased from 0 in 1997 to 4/1000 infant cases in 2010. Persistent pulmonary hypertension (40%) was the most commonly reported diagnosis at the start of milrinone administration. Overall, 606/1446 (42%) of infants had at least 1 clinical AE recorded during milrinone therapy. Hypotension requiring pressors and thrombocytopenia (<100,000/mm(3)) were the most commonly reported clinical and laboratory AEs, respectively. Death was reported in 8% of infants during the first course of milrinone therapy. Among infants hospitalized in the neonatal intensive care unit, there was an increase in the use of milrinone over the past 13 years. The safety, dosing, and efficacy of milrinone in infants should be determined in prospective clinical trials. Copyright © 2014 Elsevier Ltd. All rights reserved.

The use of antifibrinolytics in pediatric patients with hypoproliferative thrombocytopenia.

PubMed

Delaney, Meghan; Matthews, Dana C; Gernsheimer, Terry B

2017-12-01

Despite the use of evidence-based platelet transfusion therapy during periods of hypoproliferative thrombocytopenia, a large proportion of pediatric hematology/oncology patients continue to suffer from clinically significant bleeding. Antifibrinolytic (AF) drugs have been shown in certain surgical and trauma settings to decrease bleeding, blood transfusion, and improve survival. We conducted a retrospective assessment of the safety of using AF drugs in pediatric patients with hypoproliferative thrombocytopenia at our center as well as the impact on bleeding occurrence and severity. © 2017 Wiley Periodicals, Inc.

Severe thrombocytopenia as a complication of acute Epstein-Barr virus infection.

PubMed

Likic, Robert; Kuzmanic, Dusko

2004-01-31

Severe thrombocytopenia is an extremely rare complication of acute Epstein-Barr virus (EBV) infection. EBV infection usually causes hematological abnormalities, mainly atypical lymphocytosis, which is a feature of infectious mononucleosis, and uncomplicated cases often present with mild decreases in platelet counts. Our otherwise healthy, 21-year-old male Caucasian patient had thrombocytopenia and bleeding diathesis with platelet counts of 8 x 10(9)/L without other signs and symptoms of infectious mononucleosis. We commenced treatment with intravenous methylprednisolone before the acute EBV infection was serologically confirmed. Platelet counts initially rose and then fell after we stopped administrating corticosteroids. Repeated administration of methylprednisolone was followed by full recovery of the platelet count and normalization of formerly elevated transaminases. EBV infection may happen in children, adolescents and adults and this differential diagnosis should be considered in every patient presenting with acute thrombocytopenia.

Acute megakaryoblastic leukemia after transient myeloproliferative disorder with clonal karyotype evolution in a phenotypically normal neonate.

PubMed

Polski, Jacek M; Galambos, Csaba; Gale, Gordon B; Dunphy, Cherie H; Evans, H Lance; Batanian, Jacqueline R

2002-01-01

We report a case of transient myeloproliferative disorder (TMD) in a neonate without features of Down syndrome (DS) with clonal karyotype evolution, after apparent spontaneous resolution of TMD, but eventually progressing to acute megakaryoblastic leukemia (AMKL). The patient had petechiae, thrombocytopenia, and blastemia. Trisomy 21 with a satellited Y chromosome (Yqs) was found in proliferating blasts. A stimulated peripheral blood culture confirmed the constitutional origin of the Yqs, but did not reveal the presence of any trisomic 21 cell. By the age of 3 months, clonal chromosome evolution in the form of an interstitial deletion of the long-arm of chromosome 13 [del(13)(q13q31)] was detected along with trisomy 21 in unstimulated bone marrow cultures. However, remission was achieved without treatment at the age of 4 months. Trisomy 21 and del(13)(q13q31) were not identified in either cytogenetics or fluorescence in situ hybridization studies at that time. The child was asymptomatic until the age of 20 months when anemia and thrombocytopenia prompted a bone marrow biopsy, revealing changes consistent with AMKL. The remission proceeded by clonal karyotype evolution in a neonate with TMD demonstrates that clonal karyotype evolution does not indicate an immediately progressive disease. However, the development of AMKL after TMD in this case illustrates the increased risk for leukemia in TMD cases, even without DS. The gradual clonal evolution of the blasts in our patient suggests that "multiple hits" oncogenesis applies to TMD progression to acute leukemia.

Fetal thrombocytopenia in pregnancies with fetal human parvovirus-B19 infection.

PubMed

Melamed, Nir; Whittle, Wendy; Kelly, Edmond N; Windrim, Rory; Seaward, P Gareth R; Keunen, Johannes; Keating, Sarah; Ryan, Greg

2015-06-01

Fetal infection with human parvovirus B19 (hParvo-B19) has been associated mainly with fetal anemia, although data regarding other fetal hematologic effects are limited. Our aim was to assess the rate and consequences of severe fetal thrombocytopenia after fetal hParvo-B19 infection. We conducted a retrospective study of pregnancies that were complicated by fetal hParvo-B19 infection that underwent fetal blood sampling (FBS). The characteristics and outcomes of fetuses with severe thrombocytopenia (<50 × 10(9)/L) were compared with those of fetuses with a platelet concentration of ≥50 × 10(9)/L (control fetuses). Fetuses in whom 3 FBSs were performed (n = 4) were analyzed to assess the natural history of platelet levels after fetal hParvo-B19 infection. A total of 37 pregnancies that were affected by fetal hParvo-B19 infection were identified. Of the 29 cases that underwent FBS and had information regarding fetal platelets, 11 cases (38%) were complicated by severe fetal thrombocytopenia. Severely thrombocytopenic fetuses were characterized by a lower hemoglobin concentration (2.6 ± 0.9 g/dL vs 5.5 ± 3.6 g/dL; P = .01), lower reticulocyte count (9.1% ± 2.8% vs 17.3% ± 10.6%; P = .02), and lower gestational age at the time of diagnosis (21.4 ± 3.1 wk vs 23.6 ± 2.2 wk; P = .03). Both the fetal death rate within 48 hours of FBS (27.3% vs 0%; P = .02) and the risk of prematurity (100.0% vs 13.3%; P < .001) were higher in fetuses with severe thrombocytopenia. Fetal thrombocytopenia was more common during the second trimester but, in some cases, persisted into the third trimester. Intrauterine transfusion (IUT) of red blood cells resulted in a further mean decrease of 40.1% ± 31.0% in fetal platelet concentration. Severe fetal thrombocytopenia is relatively common after fetal hParvo-B19 infection, can be further worsened by IUT, and may be associated with an increased risk of procedure-related fetal loss after either FBS or IUT. Copyright © 2015. Published by

[Infectious mononucleosis and severe thrombocytopenia].

PubMed

Lucas Sendra, R; Velilla Antolín, D; Mares Diago, F J; Plaza Miranda, M A; Navarro Ortega, D

2012-09-01

Infectious mononucleosis by Epstein-Barr virus is usually a benign self-limiting disease. We present two cases admitted in the same week, with suspected co-infection by other viruses (cytomegalovirus and human herpes virus 6), which showed severe thrombocytopenia in the acute phase of the disease. The progress and treatment were different in each case. Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Ultrasonography-guided central venous catheterisation in haematological patients with severe thrombocytopenia

PubMed Central

Napolitano, Mariasanta; Malato, Alessandra; Raffaele, Francesco; Palazzolo, Manuela; Iacono, Giorgio Lo; Pinna, Roberto; Geraci, Girolamo; Modica, Giuseppe; Saccullo, Giorgia; Siragusa, Sergio; Cajozzo, Massimo

2013-01-01

Background Cannulation of the internal jugular vein (CVC) is a blind surface landmark-guided technique that could be potentially dangerous in patients with very low platelet counts. In such patients, ultrasonography (US)-guided CVC may be a valid approach. There is a lack of published data on the efficacy and safety of urgent US-guided CVC performed in haematological patients with severe thrombocytopenia. Materials and methods We retrospectively studied the safety of urgent CVC procedures in haematological patients including those with severe thrombocytopenia (platelet count <30×109/L). From January 1999 to June 2009, 431 CVC insertional procedures in 431 consecutive patients were evaluated. Patients were included in the study if they had a haematological disorder and required urgent CVC insertion. Patients were placed in Trendelenburg's position, an 18-gauge needle and guide-wire were advanced under real-time US guidance into the last part of the internal jugular vein; central venous cannulation of the internal jugular vein was performed using the Seldinger technique in all the procedures. Major and minor procedure-related complications were recorded. Results All 431 patients studied had haematological disorders: 39 had severe thrombocytopenia, refractory to platelet transfusion (group 1), while 392 did not have severe thrombocytopenia (group 2). The general characteristics of the patients in the two groups differed only for platelet count. The average time taken to perform the procedure was 4 minutes. Success rates were 97.4% and 97.9% in group 1 and group 2, respectively. No major complications occurred in either group. Discussion US-guided CVC is a safe and effective approach in haematological patients with severe thrombocytopenia requiring urgent cannulation for life support, plasma-exchange, chemotherapy and transfusion. PMID:23399356

Acute intracranial hemorrhage secondary to thrombocytopenia: CT appearances unaffected by absence of clot retraction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pierce, J.N.; Taber, K.H.; Hayman, L.A.

To describe the in vivo CT appearance of acute intracerebral blood clots formed from anemic platelet-depleted blood. Three patients with intracerebral hemorrhage secondary only to thrombocytopenia were examined with CT within 2 1/2 hours after the onset of clinical symptoms. There were no unusual CT features found in the intracerebral hemorrhages of patients with only thrombocytopenia. Specifically, a hyperdense zone(s) surrounded by areas of decreased density was identified. Clot retraction (which cannot occur in patients with severe thrombocytopenia) is not necessary for the CT appearance of acute intracerebral hemorrhage. 22 refs., 3 figs., 1 tab.

Treatment of heparin-induced thrombocytopenia with drotrecogin alfa (activated).

PubMed

Rubeiz, George J; Marrone, Christopher M; Leclerc, Jacques R

2006-03-01

A patient was administered drotrecogin alfa (activated) in addition to the standard of care for presumed severe sepsis and circulatory shock. Heparin-induced thrombocytopenia (HIT) and hepatic and splenic thromboses complicated her clinical course. Because drotrecogin alfa (activated) treatment is associated with improvement in thrombotic manifestations and thrombocytopenia, it was continued as the sole antithrombotic agent after the HIT became apparent. This approach was chosen despite the patient's severe hepatic and renal dysfunction, which made the use of direct thrombin inhibitors unfavorable. She survived with a reasonable outcome and salvage of her limbs. Although this case suggests a potential role of drotrecogin alfa (activated) in the management of HIT, systematic evaluation of its efficacy in this situation is warranted.

Cardiopulmonary bypass with bivalirudin in type II heparin-induced thrombocytopenia.

PubMed

Clayton, Stephanie B; Acsell, Jeffrey R; Crumbley, Arthur J; Uber, Walter E

2004-12-01

Cardiopulmonary bypass in patients with type II heparin induced-thrombocytopenia poses significant challenges. Inadequate pharmacokinetic profiles, monitoring, reversibility, and availability often limit alternative anticoagulation strategies. Bivalirudin, a semisynthetic direct thrombin inhibitor, was recently approved for use in patients undergoing percutaneous coronary interventions. Its unique properties, including a relatively short half-life, an anticoagulation effect that closely correlates with activated clotting time, and an alternate metabolic pathway for elimination, make bivalirudin an attractive agent for cardiopulmonary bypass in patients with type II heparin induced-thrombocytopenia. We report our experience using bivalirudin in 2 patients undergoing coronary artery bypass grafting.

Immune thrombocytopenia after bee venom therapy: a case report.

PubMed

Abdulsalam, Mohammad Adel; Ebrahim, Bader Esmael; Abdulsalam, Ahmad Jasem

2016-03-25

Immune thrombocytopenia (ITP) is a hematological disorder with an isolated decrease in number of circulating platelets. Bee venom therapy (BVT) is a form of alternative medicine. It is still being practiced in the Middle East and other parts of Asia. In BVT, acupuncture points are used to inject diluted bee venom into the body. The pharmacological basis behind BVT is not fully understood. However, it has been used to treat various medical conditions such as arthritis and low back pain. On the other hand there have been a number of reported complications of BVT use such as ITP. We present a case report on ITP after BVT. A 61 year old lady presented with gum bleeding and ecchymosis and found to have isolated thrombocytopenia (platelet count of 9 × 10(9)/L) after receiving four direct bee sting sessions. There was no evidence of any other risk factors of ITP. Bee venom components and toxicity may be associated with thrombocytopenia as a complication. Further research is needed to postulate guidelines and protocol for BVT. In the meantime, monitoring of the practice of BVT should be made, with an emphasis on patient education regarding the safety profile and associated risks compared to the gained benefits.

Health-related quality of life in children with newly diagnosed immune thrombocytopenia

PubMed Central

Heitink-Pollé, Katja M.J.; Haverman, Lotte; Annink, Kim V.; Schep, Sarah J.; de Haas, Masja; Bruin, Marrie C.A.

2014-01-01

Despite its generally transient and benign course, childhood immune thrombocytopenia has a large impact on health-related quality of life. Recently published guidelines state that quality of life should be taken into account while making decisions on management in childhood immune thrombocytopenia. We, therefore, assessed health-related quality of life in children with newly diagnosed immune thrombocytopenia in a prospective multicenter study. One hundred and seven children aged 6 months-16 years (mean age 5.57 years) were included. We used Pediatric Quality of Life Inventory™ and Kids’ ITP Tools questionnaires at diagnosis and during standardized follow-up. Scores on the Pediatric Quality of Life Inventory™ Core Scales were compared with those of healthy children. Relationships between health-related quality of life scores and treatment modality, bleeding tendency and course of the disease were examined. Kids’ ITP Tools proxy reports and parent self-reports showed significant higher health-related quality of life scores in children who recovered than in children with persistent immune thrombocytopenia (at 3 months: Kids’ ITP Tools parent self-report score 80.85 for recovered patients (n=69) versus 58.98 for patients with persistent disease (n=21), P<0.001). No significant differences in health-related quality of life were found between children with mild or moderate bleeding or between children who received intravenous immunoglobulin or children who were carefully observed. In conclusion, health-related quality of life of children with newly diagnosed immune thrombocytopenia is not influenced by treatment modality or bleeding severity, but only by clinical course of the disease. (Dutch Trial Register identifier: NTR TC1563) PMID:24951468

Heparin-Induced Thrombocytopenia in Contemporary Cardiac Surgical Practice and Experience With a Protocol for Early Identification.

PubMed

Sun, Xiumei; Hill, Peter C; Taylor-PaneK, Sharon L; Corso, Paul J; Lindsay, Joseph

2016-01-15

This analysis was designed to (1) examine the impact of heparin-induced thrombocytopenia (HIT) on contemporary cardiac surgical practice and (2) describe the results of a protocol designed for early identification of the presence of the immune mechanisms involved. Consecutive patients who underwent cardiac surgery were screened postoperatively for thrombocytopenia. Patients with thrombocytopenia were tested for antiplatelet factor 4 (PF4)/heparin antibodies by ELISA and clinical evidence of thrombosis sought. Demographics, co-morbidities, operative details, and outcomes were abstracted from the departmental registry. Of 14,415 consecutive patients undergoing cardiac surgery, 1,849 patients (13%) had thrombocytopenia. Of them, 277 patients (15%) had PF4/heparin antibodies and 76 patients (4%) had both antibodies and clinical thrombosis. Antibodies were more frequent: (1) in women (p = 0.01), (2) in patients with an increased body mass index (p <0.01), and (3) in patients with clinical heart failure before surgery (p <0.01). Thirty-day mortality was greatest among the 76 patients with the triad of thrombocytopenia, antibodies, and clinical thrombosis (30%). Of the 1,849 patients with thrombocytopenia, the presence of PF4/heparin antibodies was an independent predictor of 30-day mortality (odds ratio 2.09, 95% CI 1.46 to 2.49; p <0.001). HIT remains an infrequent but very serious complication of heparin therapy in contemporary cardiac surgical practice. The possibility that the presence of HIT antibodies in patients with thrombocytopenia independently increases operative mortality deserves further study. Copyright © 2016 Elsevier Inc. All rights reserved.

Prevalence of thrombocytopenia among pregnant women attending antenatal care service at Gondar University Teaching Hospital in 2014, northwest Ethiopia.

PubMed

Asrie, Fikir; Enawgaw, Bamlaku; Getaneh, Zegeye

2017-01-01

Thrombocytopenia is a common hematologic abnormality during pregnancy. Pregnant women with thrombocytopenia have a higher risk of bleeding excessively during or after childbirth, particularly if they need to have a cesarean section or other surgical intervention during pregnancy, labor or in the puerperium. The main aim of this study was to determine the prevalence of thrombocytopenia among pregnant women attending antenatal care service at Gondar University Hospital, northwest Ethiopia. A cross-sectional study was used to assess the prevalence of thrombocytopenia among pregnant women attending antenatal care service at Gondar University Hospital from January to April 2015. A total of 217 pregnant women were included in the study and a structured pretested questionnaire was used to obtain sociodemographic information, nutritional factors, obstetrics and gynecological factors, history and clinical condition. Blood samples were collected for platelet count and other platelet parameters, which were determined by using SysmexKX 21 automation. The data were entered to Epi info version 6 software and analyzed using SPSS version 20 software. Bivariable and multivariable statistical analyses were used to evaluate the effect of independent variable over the dependent variable. A p -value of <0.05 was considered as statistically significant. A total of 217 women receiving antenatal care service at Gondar University Hospital participated in the study. Thrombocytopenia among 19 pregnant women showed a prevalence of 8.8%. The mean ± standard deviation platelet count was 238.85×10 9 /L (±74.57). Thrombocytopenia was significantly associated with patients who lived rurally (crude odds ratio =4.3, 95% confidence interval 1.48-12.76). The prevalence of thrombocytopenia was 8.8% predominantly with mild type of thrombocytopenia. Thrombocytopenia was higher among pregnant women who lived rurally. Therefore, health care providers should screen routinely for thrombocytopenia to avoid

Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects

PubMed Central

Johnson, Ben; Lowe, Gillian C.; Futterer, Jane; Lordkipanidzé, Marie; MacDonald, David; Simpson, Michael A.; Sanchez-Guiú, Isabel; Drake, Sian; Bem, Danai; Leo, Vincenzo; Fletcher, Sarah J.; Dawood, Ban; Rivera, José; Allsup, David; Biss, Tina; Bolton-Maggs, Paula HB; Collins, Peter; Curry, Nicola; Grimley, Charlotte; James, Beki; Makris, Mike; Motwani, Jayashree; Pavord, Sue; Talks, Katherine; Thachil, Jecko; Wilde, Jonathan; Williams, Mike; Harrison, Paul; Gissen, Paul; Mundell, Stuart; Mumford, Andrew; Daly, Martina E.; Watson, Steve P.; Morgan, Neil V.

2016-01-01

Inherited thrombocytopenias are a heterogeneous group of disorders characterized by abnormally low platelet counts which can be associated with abnormal bleeding. Next-generation sequencing has previously been employed in these disorders for the confirmation of suspected genetic abnormalities, and more recently in the discovery of novel disease-causing genes. However its full potential has not yet been exploited. Over the past 6 years we have sequenced the exomes from 55 patients, including 37 index cases and 18 additional family members, all of whom were recruited to the UK Genotyping and Phenotyping of Platelets study. All patients had inherited or sustained thrombocytopenia of unknown etiology with platelet counts varying from 11×109/L to 186×109/L. Of the 51 patients phenotypically tested, 37 (73%), had an additional secondary qualitative platelet defect. Using whole exome sequencing analysis we have identified “pathogenic” or “likely pathogenic” variants in 46% (17/37) of our index patients with thrombocytopenia. In addition, we report variants of uncertain significance in 12 index cases, including novel candidate genetic variants in previously unreported genes in four index cases. These results demonstrate that whole exome sequencing is an efficient method for elucidating potential pathogenic genetic variants in inherited thrombocytopenia. Whole exome sequencing also has the added benefit of discovering potentially pathogenic genetic variants for further study in novel genes not previously implicated in inherited thrombocytopenia. PMID:27479822

Alloimmune Responses of Humanized Mice to Human Pluripotent Stem Cell Therapeutics.

PubMed

Kooreman, Nigel G; de Almeida, Patricia E; Stack, Jonathan P; Nelakanti, Raman V; Diecke, Sebastian; Shao, Ning-Yi; Swijnenburg, Rutger-Jan; Sanchez-Freire, Veronica; Matsa, Elena; Liu, Chun; Connolly, Andrew J; Hamming, Jaap F; Quax, Paul H A; Brehm, Michael A; Greiner, Dale L; Shultz, Leonard D; Wu, Joseph C

2017-08-22

There is growing interest in using embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) derivatives for tissue regeneration. However, an increased understanding of human immune responses to stem cell-derived allografts is necessary for maintaining long-term graft persistence. To model this alloimmunity, humanized mice engrafted with human hematopoietic and immune cells could prove to be useful. In this study, an in-depth analysis of graft-infiltrating human lymphocytes and splenocytes revealed that humanized mice incompletely model human immune responses toward allogeneic stem cells and their derivatives. Furthermore, using an "allogenized" mouse model, we show the feasibility of reconstituting immunodeficient mice with a functional mouse immune system and describe a key role of innate immune cells in the rejection of mouse stem cell allografts. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

A cross-sectional study of leukopenia and thrombocytopenia among Chinese adults with newly diagnosed HIV/AIDS.

PubMed

Shen, Yinzhong; Wang, Jiangrong; Wang, Zhenyan; Shen, Jiayin; Tangkai Qi; Song, Wei; Tang, Yang; Liu, Li; Zhang, Renfang; Zeng, Yi; Lu, Hongzhou

2015-04-01

We conducted a cross-sectional study to determine the prevalence and risk factors of leukopenia and thrombocytopenia among Chinese adults with newly diagnosed HIV/AIDS. One thousand nine hundred and forty-eight newly diagnosed HIV-infected patients were enrolled between 2009 and 2010. Serum samples obtained from each individual were collected for complete blood count. Factors associated with the presence of leukopenia and thrombocytopenia were analyzed by multiple logistic regression. The overall prevalence of leukopenia and of thrombocytopenia was 33.2% and 15.6%, respectively. The prevalence of leukopenia was higher among females than among males (39.4% versus 31.2%). The prevalence of leukopenia increased with decreasing CD4 count (8.2%, 26.5%, 33.4%, and 41.5% among patients with CD4 count of ≥ 350, 200-349, 50-199, and < 50 cells/mm3 respectively). The prevalence of thrombocytopenia also showed an increasing trend with decreasing CD4 count (5.8%, 12.2%, 17.8%, and 17.5% among patients with CD4 count of ≥ 350, 200-349, 50-199, and < 50 cells/mm3, respectively). Logistic analysis showed that female sex, lower CD4 count, and Han ethnicity were significantly associated with an increased risk of leukopenia, and that lower CD4 count, and HIV transmission by blood were significantly associated with an increased risk of thrombocytopenia. The study reflects that leukopenia and thrombocytopenia are common among Chinese adults with newly diagnosed HIV/AIDS; and lower CD4 count is associated with an increased risk of both leukopenia and thrombocytopenia. We propose that a routine assessment of these parameters is necessary for timely and adequate clinical management.

Clinical outcome of critically ill patients with thrombocytopenia and hypophosphatemia in the early stage of sepsis.

PubMed

Brotfain, Evgeni; Schwartz, Andrei; Boniel, Avi; Koyfman, Leonid; Boyko, Matthew; Kutz, Ruslan; Klein, Moti

2016-01-01

Hypophosphatemia and thrombocytopenia may both be independent risk factors for the development of multiple organ failure and correlate well with the severity of sepsis. In the present study we wanted to analyze the potential clinical role and prognostic significance of both early hypophosphatemia and thrombocytopenia on clinical outcomes of critically ill ICU patients with severe sepsis. We analyzed the clinical data, including the outcome of critically ill ICU patients with severe sepsis who presented during a 5 year period with early hypophosphatemia and thrombocytopenia.This study was retrospective and single centre. All clinical and laboratory data was collected from the patients' ICU and hospital electronic records. All laboratory measurements were done on admission and during the ICU stay. The included patients were distributed into one of three study groups based on the presence of hypophosphatemia and/or thrombocytopenia during the first 24 hours of admission to the ICU: group 1 - early hypophosphatemia; group 2 - early hypophosphatemia and thrombocytopenia and group 3 - early thrombocytopenia. The ICU mortality rate was significantly higher in groups 2 and 3 (25.9% and 22% vs. 9.3%, respectively, P = 0.034). An APACHE II > 27, a TISS > 25 following the first 24 hours of ICU stay , an age higher than 70, male gender and total parenteral nutrition were independent predictors of ICU and hospital mortality in this study population. It may be considered that hypophosphatemia and thrombocytopenia in the early stage of sepsis, even when severe and coexisting, reflect the degree of initial illness severity of sepsis. However, further investigations need to be done for a better understanding of the potential clinical role of these features in the septic critically ill population.

Thrombocytopenia is associated with an increased risk of cancer during treated HIV disease.

PubMed

Borges, Álvaro H; Lundgren, Jens D; Ridolfo, Annalisa; Katlama, Christine; Antunes, Francisco; Grzeszczuk, Anna; Blaxhult, Anders; Mitsura, Viktar M; Doroana, Manuela; Battegay, Manuel; Gargalianos, Panagiotis; Mocroft, Amanda

2014-11-13

To assess the relationship between platelet counts and risk of AIDS and non-AIDS-defining events. Prospective cohort. EuroSIDA patients with at least one platelet count were followed from baseline (first platelet ≥ 1 January 2005) until last visit or death. Multivariate Poisson regression was used to assess the relationship between current platelet counts and the incidence of non-AIDS-defining (pancreatitis, end-stage liver/renal disease, cancer, cardiovascular disease) and AIDS-defining events. There were 62 898 person-years of follow-up (PYFU) among 12 279 patients, including 1168 non-AIDS-defining events [crude incidence 18.6/1000 PYFU, 95% confidence interval (CI) 17.5-19.6] and 735 AIDS-defining events (crude incidence 11.7/1000 PYFU, 95% CI 10.8-12.5). Patients with thrombocytopenia (platelet count ≤100 × 10/l) had a slightly increased incidence of AIDS-defining events [adjusted incidence rate ratio (aIRR) 1.42, 95% CI 1.07-1.86], when compared to those with platelet counts 101-200 × 10/l, whereas the incidence of non-AIDS-defining events was more than two-fold higher (aIRR 2.66, 95% CI 2.17-3.26). Among non-AIDS-defining events, the adjusted incidence of cancer (aIRR 2.20, 95% CI 1.61-3.01), but not cardiovascular disease (aIRR 0.66, 95% CI 0.32-1.34), was significantly higher in patients with thrombocytopenia. The association between thrombocytopenia and cancer remained unaltered in sensitivity analyses requiring repeated platelet counts to confirm thrombocytopenia and lagging platelets by 1 year prior to clinical events. Patients with thrombocytopenia had increased incidence of AIDS-defining and non-AIDS-defining events, but the association with the latter, in particular cancer, was stronger. Future studies should investigate whether the pathophysiological processes underlying thrombocytopenia are associated with the development of cancer during treated HIV disease.

Thrombocytopenia and Platelet Dysfunction in Acute Tropical Infectious Diseases.

PubMed

Hapsari Putri, Indri; Tunjungputri, Rahajeng N; De Groot, Philip G; van der Ven, Andre J; de Mast, Quirijn

2018-06-18

Thrombocytopenia is a well-known manifestation of acute tropical infectious diseases. The role of platelets in infections has received much attention recently because of their emerging activities in modulation of inflammatory responses, host defense, and vascular integrity. However, while many studies have addressed thrombocytopenia in tropical infections, abnormalities in platelet function have been largely overlooked. This is an important research gap, as platelet dysfunction may contribute to the bleeding tendency that characterizes some tropical infections. The development of novel platelet function assays that can be used in thrombocytopenic conditions (e.g., flow cytometry assays) has contributed to important new insights in recent years. In this review, the importance of platelets in tropical infections is discussed with special emphasis on the underlying mechanisms and consequences of thrombocytopenia and platelet dysfunction in these infections. Special attention is paid to malaria, a disease characterized by microvascular obstruction in which bleeding is rare, and to infections in which bleeding is common, such as dengue, other viral hemorrhagic fevers, and the bacterial infection leptospirosis. Given the importance of platelet function abnormalities in these infections, the development of affordable assays for monitoring of platelet function in low-resource countries, as well as pharmacologic interventions to prevent or reverse platelet function abnormalities, might improve clinical care and the prognosis of these infections. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Intratumoral consumption of indium-111-labeled platelets in a child with splenic hemangioma and thrombocytopenia.

PubMed

Pampin, C; Devillers, A; Treguier, C; Fremond, B; Moisan, A; Goasguen, J; Le Gall, E

2000-01-01

The authors report Kasabach-Merritt syndrome (KMS) in a patient with thrombocytopenia and splenic hemangioma. A 13-month-old boy with a history of anemia, thrombocytopenia, and abdominal mass was admitted to the hospital. The scintigraphic studies showed that a large mass contiguous to the spleen was responsible for the platelet uptake. After partial splenectomy, the platelet count returned to normal. This report of KMS in a child with splenic hemangioma suggests that the scintigraphic studies are mandatory to confirm diagnosis. Indium-111-labeled platelets are useful in identifying hemangiomatous sequestration of platelets in patients with thrombocytopenia.

Immune thrombocytopenia: No longer ‘idiopathic’

PubMed Central

McCRAE, KEITH

2012-01-01

Immune thrombocytopenia (ITP) is a common hematologic disorder. Its pathogenesis involves both accelerated platelet destruction and impaired platelet production. First-line agents are usually effective initially but do not provide long-term responses. Splenectomy remains an effective long-term therapy, as does rituximab (Rituxan) in a subset of patients. Thrombopoietic agents offer a new alternative, although their place in the overall management of ITP remains uncertain. PMID:21632906

Effect of thrombocytopenia on outcomes following treatment with either enoxaparin or unfractionated heparin in patients presenting with acute coronary syndromes.

PubMed

Yeh, Robert W; Wiviott, Stephen D; Giugliano, Robert P; Morrow, David A; Shui, Amy; Qin, Jie; Scirica, Benjamin; Bradner, James E; Jang, Ik-Kyung; Gibson, C Michael; Antman, Elliott M

2007-12-15

Thrombocytopenia is associated with an increased risk for adverse cardiac events and bleeding in patients presenting with acute coronary syndromes (ACS) treated with unfractionated heparin (UFH). Enoxaparin has been shown to improve outcomes in ACS; however, its effect on the development of thrombocytopenia in this population is not well documented. This study was conducted to examine the incidence and clinical importance of thrombocytopenia in patients presenting with non-ST-elevation ACS randomized to treatment with enoxaparin or UFH. Thrombocytopenia was defined as a platelet count <100 x 10(9)/L or a >50% decrease from baseline. Thrombocytopenia developed in a total of 93 of 3,910 patients during the follow-up period of 14 days; the incidence was similar between study arms. The development of thrombocytopenia was associated with more frequent death, nonfatal myocardial infarction, and urgent revascularization during the study period (odds ratio 2.96, p = 0.001). This association was independent of assignment to treatment with enoxaparin or UFH (p for interaction = 0.47). Major bleeding was also more common in patients with thrombocytopenia regardless of treatment. In conclusion, thrombocytopenia is a significant correlate of adverse events in patients presenting with non-ST-elevation ACS treated with either enoxaparin or UFH.

Oral Exposure to Phytomonas serpens Attenuates Thrombocytopenia and Leukopenia during Acute Infection with Trypanosoma cruzi

PubMed Central

da Silva, Rosiane V.; Malvezi, Aparecida D.; Augusto, Leonardo da Silva; Kian, Danielle; Tatakihara, Vera Lúcia H.; Yamauchi, Lucy M.; Yamada-Ogatta, Sueli F.; Rizzo, Luiz V.; Schenkman, Sergio; Pinge-Filho, Phileno

2013-01-01

Mice infected with Trypanosoma cruzi, the agent of Chagas disease, rapidly develop anemia and thrombocytopenia. These effects are partially promoted by the parasite trans-sialidase (TS), which is shed in the blood and depletes sialic acid from the platelets, inducing accelerated platelet clearance and causing thrombocytopenia during the acute phase of disease. Here, we demonstrate that oral immunization of C57BL/6 mice with Phytomonas serpens, a phytoflagellate parasite that shares common antigens with T. cruzi but has no TS activity, reduces parasite burden and prevents thrombocytopenia and leukopenia. Immunization also reduces platelet loss after intraperitoneal injection of TS. In addition, passive transfer of immune sera raised in mice against P. serpens prevented platelet clearance. Thus, oral exposure to P. serpens attenuates the progression of thrombocytopenia induced by TS from T. cruzi. These findings are not only important for the understanding of the pathogenesis of T. cruzi infection but also for developing novel approaches of intervention in Chagas disease. PMID:23844182

Oral exposure to Phytomonas serpens attenuates thrombocytopenia and leukopenia during acute infection with Trypanosoma cruzi.

PubMed

da Silva, Rosiane V; Malvezi, Aparecida D; Augusto, Leonardo da Silva; Kian, Danielle; Tatakihara, Vera Lúcia H; Yamauchi, Lucy M; Yamada-Ogatta, Sueli F; Rizzo, Luiz V; Schenkman, Sergio; Pinge-Filho, Phileno

2013-01-01

Mice infected with Trypanosoma cruzi, the agent of Chagas disease, rapidly develop anemia and thrombocytopenia. These effects are partially promoted by the parasite trans-sialidase (TS), which is shed in the blood and depletes sialic acid from the platelets, inducing accelerated platelet clearance and causing thrombocytopenia during the acute phase of disease. Here, we demonstrate that oral immunization of C57BL/6 mice with Phytomonas serpens, a phytoflagellate parasite that shares common antigens with T. cruzi but has no TS activity, reduces parasite burden and prevents thrombocytopenia and leukopenia. Immunization also reduces platelet loss after intraperitoneal injection of TS. In addition, passive transfer of immune sera raised in mice against P. serpens prevented platelet clearance. Thus, oral exposure to P. serpens attenuates the progression of thrombocytopenia induced by TS from T. cruzi. These findings are not only important for the understanding of the pathogenesis of T. cruzi infection but also for developing novel approaches of intervention in Chagas disease.

Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects.

PubMed

Johnson, Ben; Lowe, Gillian C; Futterer, Jane; Lordkipanidzé, Marie; MacDonald, David; Simpson, Michael A; Sanchez-Guiú, Isabel; Drake, Sian; Bem, Danai; Leo, Vincenzo; Fletcher, Sarah J; Dawood, Ban; Rivera, José; Allsup, David; Biss, Tina; Bolton-Maggs, Paula Hb; Collins, Peter; Curry, Nicola; Grimley, Charlotte; James, Beki; Makris, Mike; Motwani, Jayashree; Pavord, Sue; Talks, Katherine; Thachil, Jecko; Wilde, Jonathan; Williams, Mike; Harrison, Paul; Gissen, Paul; Mundell, Stuart; Mumford, Andrew; Daly, Martina E; Watson, Steve P; Morgan, Neil V

2016-10-01

Inherited thrombocytopenias are a heterogeneous group of disorders characterized by abnormally low platelet counts which can be associated with abnormal bleeding. Next-generation sequencing has previously been employed in these disorders for the confirmation of suspected genetic abnormalities, and more recently in the discovery of novel disease-causing genes. However its full potential has not yet been exploited. Over the past 6 years we have sequenced the exomes from 55 patients, including 37 index cases and 18 additional family members, all of whom were recruited to the UK Genotyping and Phenotyping of Platelets study. All patients had inherited or sustained thrombocytopenia of unknown etiology with platelet counts varying from 11×10 9 /L to 186×10 9 /L. Of the 51 patients phenotypically tested, 37 (73%), had an additional secondary qualitative platelet defect. Using whole exome sequencing analysis we have identified "pathogenic" or "likely pathogenic" variants in 46% (17/37) of our index patients with thrombocytopenia. In addition, we report variants of uncertain significance in 12 index cases, including novel candidate genetic variants in previously unreported genes in four index cases. These results demonstrate that whole exome sequencing is an efficient method for elucidating potential pathogenic genetic variants in inherited thrombocytopenia. Whole exome sequencing also has the added benefit of discovering potentially pathogenic genetic variants for further study in novel genes not previously implicated in inherited thrombocytopenia. Copyright© Ferrata Storti Foundation.

Bone marrow morphology and disease progression in congenital thrombocytopenia: a detailed clinicopathologic and genetic study of eight cases.

PubMed

Tsang, Hamilton C; Bussel, James B; Mathew, Susan; Liu, Yen-Chun; Imahiyerobo, Allison A; Orazi, Attilio; Geyer, Julia T

2017-04-01

Patients with congenital thrombocytopenia have an increased risk of developing myeloid neoplasms. In these cases, the morphologic distinction between disease at baseline and at progression is challenging. This report analyzes clinicopathologic features of congenital thrombocytopenia with long-term follow-up at one referral center. Records from the last 20 years were searched for cases of congenital thrombocytopenia with bone marrow biopsies and peripheral blood smears. The clinical, morphologic, immunophenotypic, and molecular features were analyzed. Six adult and two pediatric patients were identified (six male, two female). Age range at first biopsy was 1-47 (median, 31) years. Underlying diseases included thrombocytopenia-absent radius syndrome, congenital thrombocytopenia with radial-ulnar synostosis, MYH9-related disorder, shortened telomere syndrome, congenital thrombocytopenia with ANKRD26 mutation, and familial platelet disorder with predisposition to acute myeloid leukemia. Four patients had myelodysplastic/myeloproliferative neoplasm-like marrow changes such as hypercellularity, increased myeloid to erythroid ratio, numerous micromegakaryocytes (highlighted by CD42b), and marrow fibrosis. Two patients had marrow hypoplasia and two had unremarkable marrow morphology. Three patients-all in the myelodysplastic/myeloproliferative neoplasm-like group-developed disease progression characterized by erythroid and myeloid dysplasia, elevated bone marrow blasts, and new cytogenetic abnormalities. Unlike non-familial myeloid neoplasms, congenital thrombocytopenia patients in the myelodysplastic/myeloproliferative neoplasm-like group had a long and indolent clinical course (average age at disease progression, 47 years). In summary, three distinct morphologic types of congenital thrombocytopenia were identified: a hyperplastic myelodysplastic/myeloproliferative neoplasm-like group, a hypoplastic bone marrow failure-like group, and a group with relatively normal marrow

Antiplatelet drug induced isolated profound thrombocytopenia in interventional cardiology: a review based on individual case reports.

PubMed

Höchtl, Thomas; Pachinger, Linda; Unger, Gerhard; Geppert, Alexander; Wojta, Johann; Harenberg, Job; Huber, Kurt

2007-08-01

A combination antithrombotic and antiplatelet therapy with clopidogrel, aspirin, glycoprotein IIb/IIIa receptor inhibitors and heparins is routinely used as adjunct therapy in patients undergoing percutaneous coronary intervention (PCI). As all substances inhibit platelet function, bleeding and thrombocytopenia may occur. We report on three patients who developed isolated profound thrombocytopenia (platelet count of < 20,000/mm(3)) within 24 h after initiation of combination antiplatelet and antithrombotic therapy during a 1 year observation period in 443 consecutive patients undergoing PCI and stent implantation. The data from our cardiology unit revealed an incidence of an isolated profound thrombocytopenia in 0.7% of all patients on combination antithrombotic therapy and in 1.5% of patients with GPIIb/IIIa-blockers. In all three cases with isolated profound thrombocytopenia GPIIb/IIIa-blockers were found to be the causative agents. Negative results of HIT-assays excluded heparin induced thrombocytopenia type II. Despite the extremely low platelet count no severe bleeding was observed and in all cases platelet counts normalized within 3-4 days without specific interventions except discontinuation of the responsible agent. These findings are discussed in conjunct with an overview of the recent literature.

Spontaneous heparin-induced thrombocytopenia presenting as bilateral adrenal hemorrhages and pulmonary embolism after total knee arthroplasty.

PubMed

Elshoury, Amro; Khedr, Maha; Abousayed, Mostafa M; Mehdi, Syed

2015-09-01

Heparin-induced thrombocytopenia syndrome is an acquired potentially life-threatening prothrombotic disorder caused by antibodies that recognize complexes of platelet factor 4 bound to heparin or heparin-like molecules. It typically occurs after exposure to unfractionated heparin, to a lesser extent after exposure to low-molecular-weight heparins, and rarely after exposure to fondaparinux. Herein, we report the case of a 48-year-old woman who developed severe thrombocytopenia, bilateral pulmonary embolism, and bilateral adrenal hemorrhages after total knee arthroplasty without evidence of heparin exposure. Antibodies to the heparin-platelet factor 4 complex and serotonin-release assay were positive. Spontaneous heparin-induced thrombocytopenia syndrome should be considered in patients with unexplained thrombocytopenia after knee replacement surgery even without heparin exposure, and a high index of suspicion for adrenal hemorrhage is needed in patients with fever, abdominal pain, and shock.

Unusual presentation of a severely ill patient having severe fever with thrombocytopenia syndrome: a case report.

PubMed

Kaneko, Masahiko; Maruta, Masaki; Shikata, Hisaharu; Asou, Kengo; Shinomiya, Hiroto; Suzuki, Tadaki; Hasegawa, Hideki; Shimojima, Masayuki; Saijo, Masayuki

2017-02-03

Severe fever with thrombocytopenia syndrome is an emerging infectious disease caused by a novel phlebovirus belonging to the family Bunyaviridate. Emergence of encephalitis/encephalopathy during severe fever with thrombocytopenia syndrome progression has been identified as a major risk factor associated with a poor prognosis. Here we report the case of a severely ill patient with severe fever with thrombocytopenia syndrome virus-associated encephalitis/encephalopathy characterized by a lesion of the splenium, which resolved later. A 56-year-old Japanese man presented with fever and diarrhea, followed by dysarthria. Diffusion-weighted magnetic resonance imaging demonstrated high signal intensity in the splenium of the corpus callosum. The severe fever with thrombocytopenia syndrome virus genome was detected in our patient's serum, and the clinical course was characterized by convulsion, stupor, and hemorrhagic manifestations, with disseminated intravascular coagulation and hemophagocytic lymphohistiocytosis. Supportive therapy not including administration of corticosteroids led to gradual improvement of the clinical and laboratory findings, and magnetic resonance imaging demonstrated resolution of the splenial lesion. The serum severe fever with thrombocytopenia syndrome viral copy number, which was determined with the quantitative reverse-transcription polymerase chain reaction, rapidly decreased despite the severe clinical course. Our patient's overall condition improved, allowing him to be eventually discharged. Patients with encephalitis/encephalopathy due to severe fever with thrombocytopenia syndrome virus infection may have a favorable outcome, even if they exhibit splenial lesions and a severe clinical course; monitoring the serum viral load may be of value for prediction of outcome and potentially enables the avoidance of corticosteroids to intentionally cause opportunistic infection.

Recent advances in the diagnosis and treatment of heparin-induced thrombocytopenia

PubMed Central

Bakchoul, Tamam

2012-01-01

Heparin-induced thrombocytopenia (HIT) is a drug-mediated, prothrombotic disorder caused by immunization against platelet factor 4 (PF4) after complex formation with heparin or other polyanions. After their binding to PF4/heparin complexes on the platelet surface, HIT antibodies are capable of intravascular platelet activation by cross-linking Fcγ receptor IIA leading to a platelet count decrease and/or thrombosis. Diagnosis of HIT is often difficult. This, and the low specificity of the commercially available immunoassays, leads currently to substantial overdiagnosis of HIT. Timing of onset, the moderate nature of thrombocytopenia, and the common concurrence of thrombosis are very important factors, which help to differentiate HIT from other potential causes of thrombocytopenia. A combination of a clinical pretest scoring system and laboratory investigation is usually necessary to diagnose HIT. Although HIT is considered to be a rare complication of heparin treatment, the very high number of hospital inpatients, and increasingly also hospital outpatients receiving heparin, still result in a considerable number of patients developing HIT. If HIT occurs, potentially devastating complications such as life-threatening thrombosis make it one of the most serious adverse drug reactions. If HIT is strongly suspected, all heparin must be stopped and an alternative nonheparin anticoagulant started at a therapeutic dose to prevent thromboembolic complications. However, the nonheparin alternative anticoagulants bear a considerable bleeding risk, especially if given to patients with thrombocytopenia due to other reasons than HIT. While established drugs for HIT are disappearing from the market (lepirudin, danaparoid), bivalirudin, fondaparinux and potentially the new anticoagulants such as dabigatran, rivaroxaban and apixaban provide new treatment options. PMID:23606934

[Analysis of clinical characteristics of the 12 cases of neonatal dengue fever in Guangzhou in 2014 and literatures review].

PubMed

Tan, Limei; Wang, Junping; Zeng, Fansen; Zhang, Yong; Fang, Chunxiao; Nie, Chuan; Xu, Yi; Yang, Jie

2015-12-01

To explore the clinical manifestations and laboratory examination characteristics of neonatal dengue fever. A retrospective analysis of 12 cases of neonatal dengue fever treated in the Guangdong Women and Children's Hospital and Guangzhou Women and Children's Medical Center was conducted, and related literature was reviewed. Twelve cases of neonatal dengue fever included 9 males and 3 females; their age was 30 min after birth to 29 d, the age of onset was 30 min-24 d. (1) CLINICAL FEATURES: fever was present in 11 cases, rash in 6 cases, bleeding in 1 case, jaundice in 5 cases, cough in 1 case, coagulopathy in 2 cases. (2) Mothers' perinatal conditions: 7 mothers were confirmed to have dengue fever, 2 mothers had suspected dengue fever, and in 3 mothers the dengue fever was excluded. Eight mothers prenatally had fever. (3) LABORATORY TESTS: Thrombocytopenia was found in 11 cases (19×10(9)-156×10(9)/L), activated partial thromboplastin time prolonged in 11 cases (44.0-89.8 s), fibrinogen decreased in 5 cases (1.17-3.02 g/L), aspartate aminotransferase (AST) increased in 5 cases (28-78 U/L), creatine kinase (CK-MB) increased in 4 cases (13-86 U/L), hypokalemia in 1 case (2.8-5.1 mmol/L ), C- reactive protein (CRP) increased in 6 cases (0.04-46.05 mg/L). (4) Treatment and prognosis: platelet transfusion was used in 2 cases, anti-infective therapy was given to 6 cases, intravenous gamma globulin treatment was used in 5 cases, hospitalization was 4-17 d, 10 cases were cured, 2 cases were discharged after condition was improved. Literature search was performed with "neonatal dengue" as keywords at Wanfang, Weipu, and CNKI, no relevant reports were found. Pubmed search was done with "neonatal dengue" and "case report" as keywords, 15 reports were retrieved during 1990 and 2014, which reported 30 cases, all acquired the disease via vertical transmission; the main clinical manifestations were fever, rash, petechiae, anemia, jaundice, tachycardia, and hepatomegaly

Immunologic findings, thrombocytopenia and disease activity in lupus nephritis.

PubMed Central

Clark, W. F.; Linton, A. L.; Cordy, P. E.; Keown, P. E.; Lohmann, R. C.; Lindsay, R. M.

1978-01-01

Twenty patients with nephritis due to systemic lupus erythematosus were followed up for a mean of 34 months after renal biopsy with serial determinations of total serum complement and C3 and C4 concentrations, binding of deoxyribonucleic acid (DNA), antinuclear antibody pattern and platelet count. There were 25 episodes of nonhematologic observed disease activity in 16 of the 20 patients; elevated DNA binding and thrombocytopenia correlated well with these episodes. The mean platelet count during episodes of observed disease activity was 96 +/- 42 X 10(9)/L, which was significantly different from the mean count of 248 +/- 90 X 10(9)/L during disease quiescence. The proportion of false-positive results with the immunologic tests varied from 25% to 67% and with platelet counts it was 11%. It is suggested that thrombocytopenia may be a simple and accurate index of disease activity in lupus nephritis. PMID:350367

Steroid-induced femoral head osteonecrosis in immune thrombocytopenia treatment with osteochondral autograft transplantation.

PubMed

Fotopoulos, Vasileios Ch; Mouzopoulos, George; Floros, Themistoklis; Tzurbakis, Matthaios

2015-09-01

Osteonecrosis of the femoral head is a devastating complication of steroid administration and has rarely been observed in the treatment of immune thrombocytopenia. The treatment of osteochondral defects in advanced stages of avascular necrosis (AVN), characterized by collapse of the subchondral bone, remains an unsolved burden in orthopedic surgery. In this report, we present a case of a 19-year-old female that was admitted in the Emergency Department with walking disability and painful hip joint movement due to steroid-induced femoral head osteonecrosis. Two years before she was diagnosed with immune thrombocytopenia, for which she received pulse steroid therapy with high dose of dexamethasone and underwent a splenectomy. This case report is the first to describe the use of osteochondral autograft transplantation as a treatment of steroid-induced AVN of the femoral head due to immune thrombocytopenia at the age of 19 years with very good clinical and radiological results 3 years postoperatively.

Fatal thrombocytopenia: A rare case with possible explanation

PubMed Central

Barik, Ramachandra; Patnaik, A. N.; Gulati, A. S.

2012-01-01

A 22 year old male presented with breathlessness on exertion, ecchymosis, jaundice and features of worsening right heart failure for the last fifteen days. On physical examination, he had a mid diastolic murmur in the tricuspid area and an ejection systolic murmur in the pulmonary area. Bone marrow histopathology report showed an increased in megakaryocytes count. Routine investigations reports were normal. Echocardiography and computerized tomography (CT) revealed a single mobile large intra cardiac mass originating from the right atrium and causing dynamic obstruction of the right ventricular inflow and outflow tract. Associated fatal thrombocytopenia did not respond to intravenous steroids or platelet transfusion. Patient could not be operated because of very low platelet count, and died during hospital stay before excision biopsy could be done. Pathological autopsy was not done. This is a rare case, as the fatal thrombocytopenia observed here was the result of mechanical effects like frictional and shear force, which can be attributed to the physical presence of a large intra cardiac mass resulting in obstruction to flow. PMID:22629036

Fatal thrombocytopenia: A rare case with possible explanation.

PubMed

Barik, Ramachandra; Patnaik, A N; Gulati, A S

2012-04-01

A 22 year old male presented with breathlessness on exertion, ecchymosis, jaundice and features of worsening right heart failure for the last fifteen days. On physical examination, he had a mid diastolic murmur in the tricuspid area and an ejection systolic murmur in the pulmonary area. Bone marrow histopathology report showed an increased in megakaryocytes count. Routine investigations reports were normal. Echocardiography and computerized tomography (CT) revealed a single mobile large intra cardiac mass originating from the right atrium and causing dynamic obstruction of the right ventricular inflow and outflow tract. Associated fatal thrombocytopenia did not respond to intravenous steroids or platelet transfusion. Patient could not be operated because of very low platelet count, and died during hospital stay before excision biopsy could be done. Pathological autopsy was not done. This is a rare case, as the fatal thrombocytopenia observed here was the result of mechanical effects like frictional and shear force, which can be attributed to the physical presence of a large intra cardiac mass resulting in obstruction to flow.

CXCL4-platelet factor 4, heparin-induced thrombocytopenia and cancer.

PubMed

Sandset, Per Morten

2012-04-01

Platelet factor 4 (CXCL4-PF4) is a chemokine that binds to and neutralizes heparin and other negatively charged proteoglycans, but is also involved in angiogenesis and cancer development. In some patients exposed to heparin, antibodies are generated against the CXCL-PF4/heparin complex that may activate platelets and coagulation and lead to thrombocytopenia and arterial or venous thrombosis, a condition commonly named heparin induced thrombocytopenia (HIT). HIT has been investigated in numerous clinical settings, but there is limited data on the epidemiology and phenotype of HIT in cancer patients. The present review describes the role of CXCL4-PF4 in cancer, the immunobiology, clinical presentation and diagnosis of HIT, and the specific problems faced in cancer patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

Providing ABO-identical platelets and cryoprecipitate to (almost) all patients: approach, logistics, and associated decreases in transfusion reaction and red blood cell alloimmunization incidence.

PubMed

Henrichs, Kelly F; Howk, Nedda; Masel, Debra S; Thayer, Mark; Refaai, Majed A; Kirkley, Scott A; Heal, Joanna M; Blumberg, Neil

2012-03-01

There are multiple benefits to transfusing only ABO-identical blood components. Historically our institution routinely transfused ABO-nonidentical platelets (PLTs) and cryoprecipitate to surgical patients. In April 2005, we implemented a policy of transfusing only ABO-identical components whenever feasible, regardless of outdating or logistic considerations. Technical staff closely monitored product usage and adjusted blood center orders based on recent utilization and planned transfusions. When unable to provide ABO-identical PLTs, ABO-compatible PLTs were washed to remove incompatible plasma. Data on outdating were collected for 18 months before and after implementation. We compared transfusion reaction and red blood cell (RBC) alloimmunization incidence for 4 years preceding (2001-2004) and subsequent (2006-2009) to implementation. In the year after implementation, only 11 of 410 surgical patients received ABO-nonidentical PLTs (2.7%). There was a 5.6% increase in outdating of PLTs. Transfusing ABO-identical components was associated with significant reductions in febrile (-46%; 8.0 to 4.3 per 10,000 components; p < 0.0001) and allergic transfusion reactions (-23%; from 7.0 to 5.4 per 10,000 components; p = 0.025). A progressive reduction in de novo RBC alloimmunization incidence also occurred (-50% by 2009; p = 0.03). Providing ABO-identical PLTs to almost all patients was feasible in our setting by changing ordering and inventorying procedures and making the ABO-identical policy a staff priority. Unexpected and striking reductions in febrile and allergic reactions and RBC alloimmunization were observed, of uncertain causal relationship to this ABO policy change, which will require further study. © 2011 American Association of Blood Banks.

Hematological characteristics in neonates with twin anemia-polycythemia sequence (TAPS).

PubMed

Lopriore, E; Slaghekke, F; Oepkes, D; Middeldorp, J M; Vandenbussche, F P H A; Walther, F J

2010-03-01

To evaluate the neonatal hematological features of monochorionic twins with twin anemia-polycythemia sequence (TAPS) and to determine the additional diagnostic value of reticulocyte count measurement. A cohort of consecutive monochorionic twins with TAPS (n = 19) was included in the study and each twin pair was compared with two monochorionic twin pairs (n = 38) unaffected by TAPS or twin-twin transfusion syndrome (TTTS), matched for gestational age at birth. We measured full blood counts on day 1 and determined the incidence of anemia, polycythemia, reticulocytosis and thrombocytopenia. Median inter-twin hemoglobin (Hb) difference in monochorionic twins with and without TAPS was 13.7 g/dL and 2.4 g/dL, respectively (p < 0.01). Median inter-twin reticulocyte count ratio in twins with and without TAPS was 3.1 and 1.0, respectively (p < 0.01). Thrombocytopenia (platelet count < 150 x 10(9)/L) occurred more often in the TAPS group than in the control group, 45% (17/38) versus 11% (11/38), respectively (p < 0.01). In the TAPS group, mean platelet count was significantly lower in recipients than in donors, 133 x 10(9)/L versus 218 x 10(9)/L, respectively (p < 0.01). TAPS twins have a large inter-twin Hb difference in combination with a large inter-twin reticulocyte count ratio. Recipients are more often thrombocytopenic than donors, probably due to polycythemia. Copyright (c) 2010 John Wiley & Sons, Ltd.

C-reactive protein enhances IgG-mediated phagocyte responses and thrombocytopenia.

PubMed

Kapur, Rick; Heitink-Pollé, Katja M J; Porcelijn, Leendert; Bentlage, Arthur E H; Bruin, Marrie C A; Visser, Remco; Roos, Dirk; Schasfoort, Richard B M; de Haas, Masja; van der Schoot, C Ellen; Vidarsson, Gestur

2015-03-12

Immune-mediated platelet destruction is most frequently caused by allo- or autoantibodies via Fcγ receptor-dependent phagocytosis. Disease severity can be predicted neither by antibody isotype nor by titer, indicating that other factors play a role. Here we show that the acute phase protein C-reactive protein (CRP), a ligand for Fc receptors on phagocytes, enhances antibody-mediated platelet destruction by human phagocytes in vitro and in vivo in mice. Without antiplatelet antibodies, CRP was found to be inert toward platelets, but it bound to phosphorylcholine exposed after oxidation triggered by antiplatelet antibodies, thereby enhancing platelet phagocytosis. CRP levels were significantly elevated in patients with allo- and autoantibody-mediated thrombocytopenias compared with healthy controls. Within a week, intravenous immunoglobulin treatment in children with newly diagnosed immune thrombocytopenia led to significant decrease of CRP levels, increased platelet numbers, and clinically decreased bleeding severity. Furthermore, the higher the level of CRP at diagnosis, the longer it took before stable platelet counts were reached. These data suggest that CRP amplifies antibody-mediated platelet destruction and may in part explain the aggravation of thrombocytopenia on infections. Hence, targeting CRP could offer new therapeutic opportunities for these patients. © 2015 by The American Society of Hematology.

Pathogenesis of emerging severe fever with thrombocytopenia syndrome virus in C57/BL6 mouse model

PubMed Central

Jin, Cong; Liang, Mifang; Ning, Junyu; Gu, Wen; Jiang, Hong; Wu, Wei; Zhang, Fushun; Zhang, Quanfu; Zhu, Hua; Chen, Ting; Han, Ying; Zhang, Weilun; Zhang, Shuo; Wang, Qin; Sun, Lina; Liu, Qinzhi; Wang, Tao; Wei, Qiang; Wang, Shiwen; Deng, Ying; Qin, Chuan; Li, Dexin

2012-01-01

The discovery of an emerging viral disease, severe fever with thrombocytopenia syndrome (SFTS), caused by SFTS virus (SFTSV), has prompted the need to understand pathogenesis of SFTSV. We are unique in establishing an infectious model of SFTS in C57/BL6 mice, resulting in hallmark symptoms of thrombocytopenia and leukocytopenia. Viral RNA and histopathological changes were identified in the spleen, liver, and kidney. However, viral replication was only found in the spleen, which suggested the spleen to be the principle target organ of SFTSV. Moreover, the number of macrophages and platelets were largely increased in the spleen, and SFTSV colocalized with platelets in cytoplasm of macrophages in the red pulp of the spleen. In vitro cellular assays further revealed that SFTSV adhered to mouse platelets and facilitated the phagocytosis of platelets by mouse primary macrophages, which in combination with in vivo findings, suggests that SFTSV-induced thrombocytopenia is caused by clearance of circulating virus-bound platelets by splenic macrophages. Thus, this study has elucidated the pathogenic mechanisms of thrombocytopenia in a mouse model resembling human SFTS disease. PMID:22665769

Maternal serum uric acid level and maternal and neonatal complications in preeclamptic women: A cross-sectional study.

PubMed

Asgharnia, Maryam; Mirblouk, Fariba; Kazemi, Soudabeh; Pourmarzi, Davood; Mahdipour Keivani, Mina; Dalil Heirati, Seyedeh Fatemeh

2017-09-01

Preeclampsia is associated with maternal and neonatal complications. It has been indicated that increased uric acid might have a predictive role on preeclampsia. We aimed to investigate the relationship between the level of uric acid with maternal and neonatal complications in women with preeclampsia. In this cross-sectional study, 160 singleton preeclamptic women at more than 28 wk gestational age were included. Hemoglobin, hematocrit, platelet count, liver and uric acid tests, and maternal and neonatal complications were assessed. The severity of preeclampsia, placental abruption, preterm labor, thrombocytopenia, elevated alanine aminotransferase and aspartate aminotransferase (ALT and AST), HELLP syndrome, eclampsia and required hospitalization in the ICU was considered as the maternal complication. Fetal complications were: small for gestational age (SGA), intrauterine fetal death, hospitalization in the neonatal intensive care unit, and Apgar score <7 at five minutes. Of our participants, 38 women had severe preeclampsia (23.8%). The mean level of uric acid in women with severe preeclampsia was significantly higher than non-severe preeclampsia (p=0.031), also in those with an abnormal liver test (p=0.009). The mean level of uric acid in women with preterm delivery was significantly higher than women with term delivery (p=0.0001). Also, the level of uric acid had no effect on neonatal hospitalization in neonate invasive care unit. Based on logistic regression, the incidence of severe preeclampsia not affected by decreased or increased serum levels of uric acid. With higher level of uric acid in server preeclampsia we can expected more complications such as hepatic dysfunction and preterm delivery. Thus serum uric acid measurement can be helpful marker for severe preeclampsia.

Severe Hemolytic Jaundice in a Neonate with a Novel COL4A1 Mutation.

PubMed

Tomotaki, Seiichi; Mizumoto, Hiroshi; Hamabata, Takayuki; Kumakura, Akira; Shiota, Mitsutaka; Arai, Hiroshi; Haginoya, Kazuhiro; Hata, Daisuke

2016-12-01

We report our experience with a preterm infant with severe hemolytic jaundice who required exchange transfusion just after birth. The patient was negative for alloimmune hemolysis as a result of maternal-fetal blood type incompatibility, and tests for inherited defects in erythrocyte metabolism, membrane function, and hemoglobin synthesis were normal. We also performed a bone marrow examination, but could not identify the cause of hemolysis. The patient had several other complications, including porencephaly, epilepsy, elevated serum levels of creatine kinase, and persistent microscopic hematuria. Later, we detected a genetic mutation in COL4A1, which was recently found to be associated with hemolytic anemia. We therefore believe that all of the patient's clinical features, including hemolytic anemia, were due to the mutation in COL4A1. Genetic testing for COL4A1 mutations is recommended in neonates who exhibit hemolytic disease of unknown etiology, especially when other complications compatible with COL4A1-related disorders are present. Copyright © 2014. Published by Elsevier B.V.

Safety and efficacy of cryopreserved autologous platelet concentrates in HLA-alloimmunized patients with hematologic malignancies.

PubMed

Gerber, Bernhard; Alberio, Lorenzo; Rochat, Sophie; Stenner, Frank; Manz, Markus G; Buser, Andy; Schanz, Urs; Stussi, Georg

2016-10-01

Curative chemotherapy approaches in patients with malignancies and platelet (PLT) transfusion refractoriness due to alloimmunization may be hampered by the lack of suitable PLT donors. For these patients, transfusion of cryopreserved autologous PLTs is an option, but is time- and resource-consuming. We aimed at further simplifying this process. A retrospective single-center analysis was conducted on the transfusion of cryopreserved autologous PLTs in nine female alloimmunized, PLT transfusion-refractory patients treated for acute leukemia (n = 8) and non-Hodgkin's lymphoma (n = 1). No additional processing was used before transfusion, and most notably, washing and centrifugation steps were omitted. Clinical efficacy and safety, as well as a flow cytometric assessment of structural and functional PLT changes, were analyzed. A total of 40 autologous PLT concentrates were thawed at bedside and transfused a median of 32 (range, 9 to 994) days after cryopreservation. No major bleeds and no severe dimethyl sulfoxide toxicity were observed. The median PLT count increments did not differ 1 and 18 to 24 hours after transfusion and reached 6 × 10 9 /L (interquartile range [IQR], 3 × 10 9 -7.5 × 10 9 /L) and 6 × 10 9 /L (IQR, 2.5 × 10 9 -9.5 × 10 9 /L), respectively. Cryopreservation resulted in partial activation of one-third of the PLTs. In vitro stimulation with strong agonists induced additional full activation of cryopreserved PLTs: median, 55% (IQR, 42%-60%) after thrombin and 39% (IQR, 36%-39%) after convulxin. The transfusion of cryopreserved autologous PLTs is feasible and safe. Despite the cryopreservation process, PLT functionality is partially maintained. © 2016 AABB.

T-cell-dependent immunity and thrombocytopenia in rats infected with Plasmodium chabaudi.

PubMed Central

Watier, H; Verwaerde, C; Landau, I; Werner, E; Fontaine, J; Capron, A; Auriault, C

1992-01-01

Normal, splenectomized, and athymic Fischer rats were infected with Plasmodium chabaudi. In normal rat infections, acute-phase infection resolved rapidly and completely. In splenectomized rats, infection resulted in high parasitemia and ultimately death. In nude rats, parasite growth was reduced compared with normal rats, and a persistent parasitemia (between 20 and 45%) was observed for several months. Complete resolution of the infection was achieved after adoptive transfer of T lymphocytes, even when transfer occurred during the course of infection. These results indicated that an acquired, T-lymphocyte-dependent immunity was necessary for the complete recovery observed in normal rats. In normal rats, thrombocytopenia and splenomegaly occurred during infection. By contrast, in nude rats, both of these pathological manifestations were only observed after thymus grafting. Thrombocytopenia was also absent in the splenectomized animals. Despite an increase in platelet-associated immunoglobulin levels during the infection, thrombocytopenia was not transferred by injection of infected rat serum to normal recipients. It has been concluded that the nude rat infection can be regarded as a novel and useful model for studying the T-cell-dependent effector and pathological mechanisms and to investigate the anti-P. chabaudi immune response. PMID:1729178

Human platelet antigen genotypes in Turkish and Caucasian blood donors in Germany.

PubMed

Hauck-Dlimi, B; Hammon, K; Eckstein, R; Ott, S; Zimmermann, R; Dengler, T; Ringwald, J

2012-09-01

Exposition to allogenic human platelet antigens (HPAs) can lead to antibody formation causing neonatal alloimmune thrombocytopenia (NAIT), post-transfusion purpura or platelet (PLT) transfusion refractoriness. The frequencies of HPA differ between ethnical groups which could be associated with different potential alloimmunization risk. The Turkish population is the largest ethnic minority group living in Germany. However, no data are available about the HPA frequency among Turkish population. We compared the frequency of HPA between Caucasian and Turkish blood donors. DNA from blood samples of 119 Caucasian and 117 Turkish blood donors was isolated. The genotype of HPA-1, -2, -3 -4, -5 and -15 was determined using a commercialized polymerase chain reaction kit with sequence-specific primers. In Turkish blood donors, the gene frequencies of HPA-1a/1b, -2a/2b, -3a/3b, -4a/4b, -5a/5b and -15a/15b were 0.863/0.137, 0.868/0.133, 0.607/0.393, 0.996/0.004, 0.893/0.107 and 0.474/0.256, respectively. In Caucasians, we observed 0.798/0.202, 0.908/0.092, 0.567/0.432, 1.000/0.000, 0.916/0.084 and 0.517/0.483 for HPA-1a/1b, -2a/2b, -3a/3b, -4a/4b, -5a/5b and -15a/15b, respectively. No statistically significant difference between genotypes in these populations could be observed. Due to the similar distribution of HPA genotypes in both ethnical groups, no increased risk of NAIT for children of mixed couples or of post-transfusion purpura or PLT transfusion refractoriness secondary to antibodies to HPAs for recipients of PLT concentrates from blood donors of the other ethnicity is given. © 2012 John Wiley & Sons A/S.

Pentadecapeptide BPC 157 Reduces Bleeding and Thrombocytopenia after Amputation in Rats Treated with Heparin, Warfarin, L-NAME and L-Arginine.

PubMed

Stupnisek, Mirjana; Kokot, Antonio; Drmic, Domagoj; Hrelec Patrlj, Masa; Zenko Sever, Anita; Kolenc, Danijela; Radic, Bozo; Suran, Jelena; Bojic, Davor; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag

2015-01-01

BPC 157 is a stable gastric pentadecapeptide recently implicated with a role in hemostasis. While NO is largely implicated in hemostatic mechanisms, in tail-amputation-models under heparin- and warfarin-administration, both the NO-synthase (NOS)-blocker, L-NAME (prothrombotic) and the NOS-substrate L-arginine (antithrombotic), were little investigated. Objective. To investigate the effect of L-NAME and L-arginine on hemostatic parameters, and to reveal the effects of BPC 157 on the L-NAME- and L-arginine-induced hemostatic actions under different pathological condition: tail amputation without or with anticoagulants, heparin or warfarin. Tail amputation, and/or i.v.-heparin (10 mg/kg), i.g.-warfarin (1.5 mg/kg/day for 3 days) were used in rats. Treatment includes BPC 157, L-NAME, L-arginine, per se and their combination. After (tail) amputation, with or without i.v.-heparin or i.g.-warfarin, BPC 157 (10 μg/kg, 10 ng/kg, i.p., i.v. (heparin), 10 μg/kg i.g. (warfarin)) always reduced bleeding time and/or haemorrhage and counteracted thrombocytopenia. As for L-NAME and/or L-arginine, we noted: L-arginine (100 mg/kg i.p.)-rats: more bleeding, less/no thrombocytopenia; L-NAME (5 mg/kg i.p.)-rats: less bleeding (amputation only), but present thrombocytopenia; L-NAME+L-arginine-rats also exhibited thrombocytopenia: L-NAME counteracted L-arginine-increased bleeding, L-arginine did not counteract L-NAME-thrombocytopenia. All animals receiving BPC 157 in addition (BPC 157 μg+L-NAME; BPC 157 μg+L-arginine, BPC 157 μg+L-NAME+L-arginine), exhibited decreased haemorrhage and markedly counteracted thrombocytopenia. L-NAME (thrombocytopenia), L-arginine (increased haemorrhage) counteraction and BPC 157 (decreased haemorrhage, counteracted thrombocytopenia) with rescue against two different anticoagulants, implicate a BPC 157 modulatory and balancing role with rescued NO-hemostatic mechanisms.

Should herbs take all the blame? Causality assessment of a serious thrombocytopenia event.

PubMed

Lai, Jung-Nien; Hsieh, Shu-Ching; Chen, Pau-Chung; Chen, Huey-Jen; Wang, Jung-Der

2010-11-01

With the increasing use of herbal medicines, the causality assessment of adverse drug-related reactions becomes more complicated because of the concomitant use of herbs and conventional medications. Epidemiological causal inference can be a central feature of such judgment but may be insufficient. Other scientific considerations include study design, bias, confounding, and measurement issues. The approach of this study is to establish an active safety surveillance system for finished herbal products (FHPs) and to review each adverse event regularly. A single case of serious thrombocytopenia was found in 136 subjects taking FHPs on a clinical trial for 12 weeks, for which the cause was sought. Because at the end of the first month the patient's platelet counts were normal and the thrombocytopenia developed after the co-medication with conventional drugs, it was suspected that the thrombocytopenia might not be attributed to the use of FHP. This report summarizes the criteria of causality assessment under mixed use of herbs and conventional medicine and recommends a feasible process for careful evaluation of adverse drug reactions related to all herbal medicine.

A novel canine model of immune thrombocytopenia: Has ITP gone to the dogs?

PubMed Central

LeVine, Dana N; Birkenheuer, Adam J; Brooks, Marjory B; Nordone, Shila K; Bellinger, Dwight A; Jones, Sam L; Fischer, Thomas H; Oglesbee, Stephen E; Frey, Kahlina; Brinson, Nicole S; Peters, Allison Pazandak; Marr, Henry S; Motsinger-Reif, Alison; Gudbrandsdottir, Sif; Bussel, James B; Key, Nigel S

2014-01-01

Summary Canine immune thrombocytopenia (ITP) is analogous to human ITP, with similar platelet counts and heterogeneity in bleeding phenotype among affected individuals. With a goal of ultimately investigating this bleeding heterogeneity, a canine model of antibody-mediated ITP was developed. Infusion of healthy dogs with 2F9, a murine IgG2a monoclonal antibody to the canine platelet glycoprotein GPIIb (a common target of autoantibodies in ITP) resulted in profound, dose-dependent thrombocytopenia. Model dogs developed variable bleeding phenotypes, e.g. petechiae and haematuria, despite similar degrees of thrombocytopenia. 2F9 infusion was not associated with systemic inflammation, consumptive coagulopathy, or impairment of platelet function. Unexpectedly however, evaluation of cytokine profiles led to the identification of platelets as a potential source of serum interleukin-8 (IL8) in dogs. This finding was confirmed in humans with ITP, suggesting that platelet IL8 may be a previously unrecognized modulator of platelet-neutrophil crosstalk. The utility of this model will allow future study of bleeding phenotypic heterogeneity including the role of neutrophils and endothelial cells in ITP. PMID:25039744

An enzyme-linked immunosorbent assay for the evaluation of thrombocytopenia induced by heparin.

PubMed

Howe, S E; Lynch, D M

1985-05-01

Five patients with heparin-associated thrombocytopenia (HAT) were evaluated by platelet aggregation and quantitation of immunoglobulin binding to intact target platelets in both the presence and absence of heparin. These patients developed thrombocytopenia (12,000 to 70,000 platelets/microliter) 7 to 15 days and embolic and hemorrhagic complications 9 to 15 days after the initiation of heparin therapy. Platelet aggregation after the addition of heparin was demonstrated in two of four HAT serum samples, whereas normal serum samples showed no significant platelet aggregation. The five HAT serum samples showed normal to elevated baseline serum platelet-bindable immunoglobulin (SPBIg) with a range of 4.3 to 11.4 fg/platelet (normal less than or equal to 1.0 to 6.5 fg/platelet). When HAT sera were incubated with target platelets and heparin (5 U/ml), the SPBIg increased to 8.5 to 37.5 fg/platelet, a mean increase of 148% in the presence of heparin. Normal and control serum samples (from 10 normal laboratory volunteers, nine patients without thrombocytopenia receiving heparin, nine patients with autoimmune thrombocytopenic purpura, and nine patients with nonimmune thrombocytopenia not receiving heparin) showed only a slight increase in SPBIg of 0 to 2.8 fg/platelet above baseline, a mean increase of 15% after heparin incubation with the serum samples. The measurement of SPBIg of washed platelets incubated with test serum samples in the presence and absence of heparin is potentially a specific and sensitive in vitro test for the diagnosis of HAT and may prove more sensitive than platelet aggregation studies with heparin.

Therapeutic management of neonatal hemochromatosis: report of four cases and literature review.

PubMed

Annagür, Ali; Altunhan, Hüseyin; Yüksekkaya, Hasan Ali; Örs, Rahmi

2011-10-01

Neonatal hemochromatosis (NH) is a rare disease of iron metabolism that starts at intrauterine period causing liver failure and extrahepatic siderozis. The etiology of NH has not been understood exactly, yet it is accepted that a maternofetal alloimmune disorder that leads to liver failure in fetus causes the illness. The prognosis of NH is generally bad and death is inevitable if left untreated. The efficiency of chelation-antioxidant coctail used in medical treatment is between 10% and 20% and these patients frequently need liver transplantation. In our study, we presented four newborn cases diagnosed as NH and treated medically. Of the four patients, one died of pulmonary hemorrhage and another died of multiorgan failure in the first week of hospitalization. The other two patients' clinical status and laboratory parameters recovered with medical treatment. However, since liver transplantation was not carried out, one of these patients died at the age of two and a half months and the other at eighth month due to sepsis. In this study, we would like to emphasize the importance of early liver transplantation in patients recovered with medical treatment.

Interleukin-12 (IL-12)-driven alloimmune responses in vitro and in vivo: requirement for beta1 subunit of the IL-12 receptor.

PubMed

Piccotti, J R; Li, K; Chan, S Y; Eichwald, E J; Bishop, D K

1999-06-15

Interleukin-12 (IL-12) mediates its biologic activities via binding high-affinity receptors on T and natural killer cells. Although emphasis has been placed on the requirement for IL-12Rbeta2 in IL-12 bioactivity, the role of IL-12Rbeta1 is less well defined. The current study evaluated the effects of exogenous IL-12 on alloantigen-specific immune responses and determined the requirement for IL-12Rbeta1 in IL-12-mediated alloimmunity. The mouse heterotopic cardiac transplant model was employed to evaluate the effects of IL-12 on alloantigen-specific immune responses in vivo. In addition, IFN-gamma production in mixed lymphocyte cultures (MLC) supplemented with IL-12 was measured to assess the effects of IL-12 on Th1 function in vitro. Mice deficient in IL-12Rbeta1 (IL-12Rbeta1-/-) were used to determine the requirement for this receptor component in IL-12-driven alloimmune responses. Addition of IL-12 to MLC consisting of wild-type splenocytes enhanced alloantigen-specific proliferative responses and Th1 development. In contrast, IL-12 did not alter these in vitro immune parameters in IL-12Rbeta1-/- MLC. Treatment of wild-type cardiac allograft recipients with IL-12 resulted in high concentrations of serum interferon-gamma (IFN-gamma) and a 10-fold increase in IFN-gamma production by recipient splenocytes after restimulation in vitro. However, this fulminate Th1 response did not accelerate allograft rejection. Importantly, IL-12 had no effect on serum IFN-gamma or in vivo priming of Thl in IL-12Rbeta1-/- recipients. Finally, administration of IL-12 to WT allograft recipients resulted in a bimodal alloantibody response: antibody production was suppressed at high doses of IL-12, and enhanced at lower doses. IL-12 markedly enhances alloantigen-specific immune function; however, these exaggerated Th1-driven responses do not culminate in accelerated allograft rejection. Further, these data indicate that IL-12Rbeta1 is essential for the enhancement of both in vitro and

[Thrombocytopenia induced by type II heparin and myocardial infarct: 2 case reports].

PubMed

Antonijević, Nabojsa; Stanojević, Milica; Perunicić, Jovan; Djokić, Milan; Miković, Danijla; Kovac, Mirjana; Miljić, Predrag; Milosević, Rajko; Terzić, Branka; Vasiljević, Zorana

2004-01-01

Heparin-induced thrombocytopenia (HIT) type II is an acquired thrombophylic state and life-threatening immune complication of a heparin treatment mainly clinically manifested by marked thrombocytopenia, frequently by arterial and venous thrombosis, and sometimes by skin changes. Functional assay as heparin aggregation test and 14C-serotonin release assays are used in diagnostics as well as antigen assays of which detection tests for heparin-platelet factor 4 antibodies are most frequently used. Considering the fact that there is no single reliable assays for HIT II detection available, sometimes it is necessary to combine both of the above-mentioned types of assays. We present the case of a 57-year-old patient with an acute anterior myocardial infarction with cardiac insufficiency of III and IV degree according to Killip, recurrent ventricular fibrillation and diabetes mellitus type II developing thrombocytopenia to 37 x 10(9)/l accompanied with typical skin changes. The diagnosis was confirmed by the heparin aggregation test. The second patient aged 70 undergoing the treatment for anteroseptal myocardial infarction and reinfarction of the inferior wall complicated by a cardiogenic shock and acute right bundle branch block developed thrombocytopenia 59 x 10(9)/l on the third day of the heparin therapy, with the remark that he had received a heparin therapy during the first infarction as well. Antibodies against heparin-platelet factor 4 were detected by particle gel ID-HPF4 immuno-assay. In both patients, the disease had a lethal outcome despite all then available therapeutic measures applied. Further on we discuss advantages of certain types of tests, a therapy doctrine, need for urgent therapeutic measures, inclusive of the administration of antithrombins, avoidance of harmful procedures like low-molecular-weight heparins administration and prophylactic platelet transfusion as well as preventive measures.

Thrombocytopenia Is Associated with Acute Respiratory Distress Syndrome Mortality: An International Study

PubMed Central

Duan, Meili; Li, Gang; Wang, Shupeng; Li, Wenxiong; Zhu, Zhaozhong; Wei, Yongyue; Christiani, David C.; Li, Ang; Zhu, Xi

2014-01-01

Background Early detection of the Acute Respiratory Distress Syndrome (ARDS) has the potential to improvethe prognosis of critically ill patients admitted to the intensive care unit (ICU). However, no reliable biomarkers are currently available for accurate early detection of ARDS in patients with predisposing conditions. Objectives This study examined risk factors and biomarkers for ARDS development and mortality in two prospective cohort studies. Methods We examined clinical risk factors for ARDS in a cohort of 178 patients in Beijing, China who were admitted to the ICU and were at high risk for ARDS. Identified biomarkers were then replicated in a second cohort of1,878 patients in Boston, USA. Results Of 178 patients recruited from participating hospitals in Beijing, 75 developed ARDS. After multivariate adjustment, sepsis (odds ratio [OR]:5.58, 95% CI: 1.70–18.3), pulmonary injury (OR: 3.22; 95% CI: 1.60–6.47), and thrombocytopenia, defined as platelet count <80×103/µL, (OR: 2.67; 95% CI: 1.27–5.62)were significantly associated with increased risk of developing ARDS. Thrombocytopenia was also associated with increased mortality in patients who developed ARDS (adjusted hazard ratio [AHR]: 1.38, 95% CI: 1.07–1.57) but not in those who did not develop ARDS(AHR: 1.25, 95% CI: 0.96–1.62). The presence of both thrombocytopenia and ARDS substantially increased 60-daymortality. Sensitivity analyses showed that a platelet count of <100×103/µLin combination with ARDS provide the highest prognostic value for mortality. These associations were replicated in the cohort of US patients. Conclusions This study of ICU patients in both China and US showed that thrombocytopenia is associated with an increased risk of ARDS and platelet count in combination with ARDS had a high predictive value for patient mortality. PMID:24732309

Refractory immune thrombocytopenia successfully treated with high-dose vitamin D supplementation and hydroxychloroquine: two case reports

PubMed Central

2013-01-01

Introduction Immune thrombocytopenic purpura is thought to be characterized by an immune response against the host’s own platelets. If the thrombocytopenia is severe, patients are initially treated with high-dose steroids. Other more toxic second line treatments are considered if steroids fail. Here, we report the case of two patients in whom conventional treatment was unsuccessful but who responded to hydroxychloroquine and high-dose vitamin D replacement therapy. To the best of our knowledge, this is the first description of successful treatment for immune thrombocytopenia with high-dose vitamin D and hydroxychloroquine. Case presentation Case 1: We report the case of a 79-year-old Caucasian man who presented with high titer antinuclear antibodies, positive anti-SSA/Ro autoantibodies and clinically was felt to have an overlap of systemic lupus erythematosus and/or Sjögren’s syndrome with profound life-threatening thrombocytopenia. There was no evidence of underlying malignancy. The patient’s platelet count significantly increased with vitamin D and hydroxychloroquine treatment, but upon vitamin D discontinuation his platelet levels plummeted. Hydroxychloroquine therapy was maintained throughout treatment. With reinstitution of high-dose vitamin D therapy, platelet counts were restored to normal levels. Case 2: We also report the case of an 87-year-old Caucasian woman who presented with high titer antinuclear antibodies, positive anti-SSA/Ro autoantibodies and was felt to have an overlap of systemic lupus erythematosus and/or Sjögren’s syndrome with immune thrombocytopenia; she also had severely low levels of 25-hydroxy vitamin D (17ng/mL). There was no evidence of underlying malignancy. She responded to high-dose vitamin D replacement and hydroxychloroquine treatment, thereby alleviating the need for high-dose steroid treatment. She remains in remission while taking vitamin D, hydroxychloroquine and very low-dose prednisone. No untoward side effects

Immune Thrombocytopenia in Two Unrelated Fanconi Anemia Patients – A Mere Coincidence?

PubMed Central

Karastaneva, Anna; Lanz, Sofia; Wawer, Angela; Behrends, Uta; Schindler, Detlev; Dietrich, Ralf; Burdach, Stefan; Urban, Christian; Benesch, Martin; Seidel, Markus G.

2015-01-01

Thrombocytopenia and pancytopenia, occurring in patients with Fanconi anemia (FA), are interpreted either as progression to bone marrow failure or as developing myelodysplasia. On the other hand, immune thrombocytopenia (ITP) represents an acquired and often self-limiting benign hematologic disorder, associated with peripheral, immune-mediated, platelet destruction requiring different management modalities than those used in congenital bone marrow failure syndromes, including FA. Here, we describe the clinical course of two independent FA patients with atypical – namely immune – thrombocytopenia. While in one patient belonging to complementation group FA-A, the ITP started at 17 months of age and showed a chronically persisting course with severe purpura, responding well to intravenous immunoglobulins (IVIG) and later also danazol, a synthetic androgen, the other patient (of complementation group FA-D2) had a self-limiting course that resolved after one administration of IVIG. No cytogenetic aberrations or bone marrow abnormalities other than FA-typical mild dysplasia were detected. Our data show that acute and chronic ITP may occur in FA patients and impose individual diagnostic and therapeutic challenges in this rare congenital bone marrow failure/tumor predisposition syndrome. The management and a potential context of immune pathogenesis with the underlying marrow disorder are discussed. PMID:26106590

Fetal hydrops and other variables associated with the fetal hematocrit decrease after the first intrauterine transfusion for red cell alloimmunization.

PubMed

Lobato, Gustavo; Soncini, Cristina Silveira

2008-01-01

To evaluate the influence of fetal hydrops and other variables on fetal hematocrit (Hct) decrease after the first intrauterine transfusion (IUT) in alloimmunized pregnancies. From 1996 to 2006, the data of all alloimmunized pregnancies submitted to IUT were assessed. Exclusion criteria included: fetuses submitted to intraperitoneal transfusion; pregnancies complicated by other fetal abnormalities; pregnancies submitted to only one IUT, and cases in which posttransfusion or pretransfusion blood samples were not obtained. Linear regression models were implemented to assess the relationship between the rate of Hct fall after the first IUT and the following variables: fetal hydrops; antibody titer; gestational age at the first IUT; number of days between the first and second IUT; pretransfusion and posttransfusion fetal Hct values. Fifty fetuses fulfilled the study criteria. The fetal Hct decrease after the first IUT was 1.21 (range 0.18-2.3) %/day. The variables independently associated with the fetal Hct drop after the first IUT were the fetal hydrops (p = 0.000), the pretransfusion fetal Hct (p = 0.001) and the posttransfusion fetal Hct (p = 0.016). Fetal hydrops, pretransfusion fetal Hct and posttransfusion fetal Hct seem to influence the fetal Hct decrease between the first and second IUT. These findings may be helpful for estimating the rate of fetal Hct drop and programming the following IUT. Copyright 2008 S. Karger AG, Basel.

Pentadecapeptide BPC 157 Reduces Bleeding and Thrombocytopenia after Amputation in Rats Treated with Heparin, Warfarin, L-NAME and L-Arginine

PubMed Central

Stupnisek, Mirjana; Kokot, Antonio; Drmic, Domagoj; Hrelec Patrlj, Masa; Zenko Sever, Anita; Kolenc, Danijela; Radic, Bozo; Suran, Jelena; Bojic, Davor; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag

2015-01-01

Background BPC 157 is a stable gastric pentadecapeptide recently implicated with a role in hemostasis. While NO is largely implicated in hemostatic mechanisms, in tail-amputation-models under heparin- and warfarin-administration, both the NO-synthase (NOS)-blocker, L-NAME (prothrombotic) and the NOS-substrate L-arginine (antithrombotic), were little investigated. Objective. To investigate the effect of L-NAME and L-arginine on hemostatic parameters, and to reveal the effects of BPC 157 on the L-NAME- and L-arginine-induced hemostatic actions under different pathological condition: tail amputation without or with anticoagulants, heparin or warfarin. Methods Tail amputation, and/or i.v.-heparin (10 mg/kg), i.g.-warfarin (1.5 mg/kg/day for 3 days) were used in rats. Treatment includes BPC 157, L-NAME, L-arginine, per se and their combination. Results After (tail) amputation, with or without i.v.-heparin or i.g.-warfarin, BPC 157 (10 μg/kg, 10 ng/kg, i.p., i.v. (heparin), 10 μg/kg i.g. (warfarin)) always reduced bleeding time and/or haemorrhage and counteracted thrombocytopenia. As for L-NAME and/or L-arginine, we noted: L-arginine (100 mg/kg i.p.)–rats: more bleeding, less/no thrombocytopenia; L-NAME (5 mg/kg i.p.)-rats: less bleeding (amputation only), but present thrombocytopenia; L-NAME+L-arginine-rats also exhibited thrombocytopenia: L-NAME counteracted L-arginine-increased bleeding, L-arginine did not counteract L-NAME-thrombocytopenia. All animals receiving BPC 157 in addition (BPC 157μg+L-NAME; BPC 157μg+L-arginine, BPC 157μg+L-NAME+L-arginine), exhibited decreased haemorrhage and markedly counteracted thrombocytopenia. Conclusions L-NAME (thrombocytopenia), L-arginine (increased haemorrhage) counteraction and BPC 157 (decreased haemorrhage, counteracted thrombocytopenia) with rescue against two different anticoagulants, implicate a BPC 157 modulatory and balancing role with rescued NO-hemostatic mechanisms. PMID:25897838

Severe neonatal cytomegalovirus infection: about a case

PubMed Central

El Hasbaoui, Brahim; Bousselamti, Amal; Redouani, Mohammed Amine; Barkat, Amina

2017-01-01

Maternofoetal infection with Cytomegalovirus (CMV) is the most common congenital infection and a leading cause of mental retardation and sensori-neural hearing loss. Population-based studies indicate that at least 0.5% of all infants born alive have CMV of whom approximately 10% have clinically evident symptomsat birth. The Justification of systematic screening for foetal CMV infection is still controversial and is not recommended in most developed countries. This is mainly justified by the paucity of antenatal prognostic factors and the lack of established intrauterine treatment when foetal infection has been diagnosed. In case of congenital CMV infection, infants can be symptomatic or asymptomatic at birth. Mortality for such infants can reach 30%, and survivors can have mental retardation, sensorineural hearing loss, chorioretinitis, and other significant medical problems. A newborn symptomatic is defined by the existence of clinical and / or biological signs and / or neonatal imaging, the most frequent clinical signs are: hepatosplenomegaly (60%), microcephaly (53%), jaundice (67%), petechiae (76%), at least one neurological abnormality (68%). The frequency of biological abnormalities is as follows: increase in transaminases (83%), thrombocytopenia (77%), hyperbilirubinemia (69%), haemolysis (51%), hyperproteinorrachy (46%). The abnormalities of neonatal imaging are present in 70% of symptomatic newborns; intracerebral calcifications are the most frequent abnormalities. We report a case of newborn who presented a congenital infection by CMV, evoked on the intrauterine growth retardation, organs of the reticulo endothelial and haematological system were reached while nervous system was spared, and CMV PCR was very positive. indicating an antiviral treatment for 6weeks based on ganciclovir. PMID:28904689

[Congenital syphilis: presenting as septic shock alter the neonatal period].

PubMed

Arriagada, Daniela; Donoso, Alejandro; Cruces, Pablo; Díaz, Franco

2012-10-01

Clinical spectrum of congenital syphilis ranges from asymptomatic infection to fulminant sepsis. Treponema pallidum is acquired crossing the placenta from the mother to the fetus during maternal spirochetemia or through direct contact of the child with an infected lesion at delivery. We report a 27 days-old previously healthy girl diagnosed with congenital syphilis. Her mother had an unremarkable previous history, adequate obstetric care and negative prenatal screening test for syphilis. The patient was brought to the ER due to development of skin lesions and fever in the last 24 h. She was admitted to pediatric ICU lethargic and poorly responsive, with hepa-tosplenomegaly and perioral, palmoplantar erythematous desquamative scaly lesions. Laboratory data revealed anemia, leukocytosis, thrombocytopenia and C-reactive protein of 183 mg/l. Soon after admission she developed septic shock with leukocytosis up to 45,800/mm3 and exacerbation of thrombocytopenia, hypoalbuminemia and metabolic acidosis. Congenital syphilis was diagnosed at the second day of admission with VDRL titers of 1:128 in serum and 1:8 in cerebrospinal fluid. Maternal serum VDRL was positive with titers of 1:32. The patient was treated with penicillin for three weeks with adequate clinical and laboratory response. Congenital syphilis is a life threatening infection, but cannot always be diagnosed at birth. Health care workers must be aware of the difficulties in obtaining a definitive diagnosis and must have a high index of suspicion, considering the possible errors of prenatal serology and the diverse possible clinical presentations, including neonatal sepsis during the first month of life.

A novel assay for the detection of anti-human platelet antigen antibodies (HPA-1a) based on peptide aptamer technology

PubMed Central

Thibaut, Julien; Mérieux, Yves; Rigal, Dominique; Gillet, Germain

2012-01-01

Background Neonatal alloimmune thrombocytopenia is mostly due to the presence of maternal antibodies against the fetal platelet antigen HPA-1a on the platelet integrin GPIIb-IIIa. Accurate detection of anti-HPA-1a antibodies in the mother is, therefore, critical. Current diagnostic assays rely on the availability of pools of human platelets that vary according to donors and blood centers. There is still no satisfactory standardization of these assays. Design and Methods Peptide aptamer was used to detect and identify HPA-1a-specific antibodies in human serum that do not require human platelets. A peptide aptamer library was screened using an anti-HPA-1a human monoclonal antibody as a bait to isolate an aptamer that mimics the human platelet antigen HPA-1a. Results This is the first report in platelet immunology of the use of a peptide aptamer for diagnostic purposes. This assay gives better results than the MAIPA currently in use, detecting around 90% of the expected alloantibodies. Conclusions This assay could help define a standard for the quantitation of anti-HPA antibodies. This report also demonstrates that peptide aptamers can potentially detect a variety of biomarkers in body fluids; this is of particular interest for diagnostic purposes. PMID:22133781

Mitoquinone restores platelet production in irradiation-induced thrombocytopenia

PubMed Central

Ramsey, Haley; Zhang, Qi; Wu, Mei X.

2014-01-01

Myelodysplastic syndromes (MDS) are hallmarked by cytopenia and dysplasia of hematopoietic cells, often accompanied by mitochondrial dysfunction and increases of reactive oxygen species (ROS) within affected cells. However, it is not known whether the increase in ROS production is an instigator or a byproduct of the disease. The present investigation shows that mice lacking immediate early responsive gene X-1 (IEX-1) exhibit lineage specific increases in ROS production and abnormal cytology upon radiation in blood cell types commonly identified in MDS. These affected cell lineages chiefly have the bone marrow as a primary site of differentiation and maturation, while cells with extramedullary differentiation and maturation like B- and T-cells remain unaffected. Increased ROS production is likely to contribute significantly to irradiation-induced thrombocytopenia in the absence of IEX-1 as demonstrated by effective reversal of the disorder after mitoquinone (MitoQ) treatment, a mitochondria-specific antioxidant. MitoQ reduced intracellular ROS production within megakaryocytes and platelets. It also normalized mitochondrial membrane potential and superoxide production in platelets in irradiated, IEX-1 deficient mice. The lineage-specific effects of mitochondrial ROS may help us understand the etiology of thrombocytopenia in association with MDS in a subgroup of the patients. PMID:25025394

Thrombocytopenia in the first 24 hours after birth and incidence of patent ductus arteriosus.

PubMed

Sallmon, Hannes; Weber, Sven C; Hüning, Britta; Stein, Anja; Horn, Peter A; Metze, Boris C; Dame, Christof; Bührer, Christoph; Felderhoff-Müser, Ursula; Hansmann, Georg; Koehne, Petra

2012-09-01

Experimental studies suggest that platelet-triggered ductal sealing is critically involved in definite ductus arteriosus closure. Whether thrombocytopenia contributes to persistently patent ductus arteriosus (PDA) in humans is controversial. This was a retrospective study of 1350 very low birth weight (VLBW; <1500 g) infants, including 592 extremely low birth weight (ELBW; <1000 g) infants. All infants who had a platelet count in the first 24 hours after birth and an echocardiogram performed on day of life 4 to 5 were included. The incidence of thrombocytopenia was analyzed in infants with and without PDA, and in those who did or did not undergo PDA intervention. The impact of thrombocytopenia, gestational age, birth weight, gender, and sepsis on PDA was determined by receiver operating characteristic curve, odds ratio, and regression analyses. Platelet numbers within the first 24 hours after birth did not differ between VLBW/ELBW infants with and without spontaneous ductal closure. Platelet numbers were not associated with subsequent PDA treatment. Low platelet counts were not related to failure of pharma-cologic PDA treatment and the need for subsequent surgical ligation. Lower gestational age or birth weight, male gender, and sepsis were linked to the presence of PDA in VLBW infants on day of life 4 to 5. Thrombocytopenia in the first 24 hours after birth was not associated with PDA in this largest VLBW/ELBW infant cohort studied to date. Impaired platelet function, due to immaturity and critical illness, rather than platelet number, might play a role in ductus arteriosus patency.

Primary biliary cirrhosis-specific antimitochondrial antibodies in neonatal haemochromatosis.

PubMed

Smyk, Daniel S; Mytilinaiou, Maria G; Grammatikopoulos, Tassos; Knisely, A S; Mieli-Vergani, Giorgina; Bogdanos, Dimitrios P; Vergani, Diego

2013-01-01

Neonatal hemochromatosis (NH) is characterised by severe liver injury and extrahepatic siderosis sparing the reticuloendothelial system. Its aetiology is obscure, although it has been proposed as an alloimmune disease, resulting from immunological reaction to self-antigens (alloantigens) which the body recognizes as foreign. We studied an infant with NH and his mother whose sera contained antimitochondrial antibody (AMA), the hallmark of primary biliary cirrhosis (PBC). To investigate the origin of AMA in the infant, we studied isotype distributions in serum from the mother and infant. Serum samples were obtained at diagnosis of NH, after liver transplantation (LT; age 1 month), and over the ensuing 17 months. At NH diagnosis, infant and maternal serum contained AMA of the IgG isotype, predominantly of the G3 and G1 subclasses. AMA strongly reacted against the pyruvate dehydrogenase complex E2 subunit (PDC-E2), the major PBC-specific AMA autoantigen. Anti-PDC-E2 responses in both infant and mother declined over time, being present 2 months after LT (mother and child) and absent 10 months later (mother) and 17 months later (child). The association of maternally transferred IgG1 and IgG3 subclass AMA with the appearance of liver damage in an infant with NH may suggest a causal link between antibody and liver damage.

Alloimmune responses and atherosclerotic disease after kidney transplantation.

PubMed

Ducloux, Didier; Courivaud, Cécile; Bamoulid, Jamal; Bisaccia, Vincent; Roubiou, Caroline; Crepin, Thomas; Gaugler, Béatrice; Laheurte, Caroline; Rebibou, Jean-Michel; Chalopin, Jean-Marc; Saas, Philippe

2015-01-01

Chronic exposure to exogenous antigens causes accumulation of proinflammatory CD57(+)CD28(-) hyperactivated CD8(+) T cells that may promote atherosclerosis. We hypothesized that persistent alloimmune responses may induce immune activation and contribute to posttransplant atherosclerosis. This hypothesis was tested in a single-center cohort of 577 kidney transplant patients. Propensity score analysis was performed to address potential confounding variables by indication. Immune exhaustion was studied in subcohort of 103 patients. Five hundred seventy-seven consecutive renal transplant recipients were included. Seventy-seven atherosclerotic events (AE) (12.3%) occurred during a mean follow-up of 7 years. The cumulative incidence of AE increased with the number of human leukocyte antigen (HLA) mismatches (18%, 10%, and 5% in patients with 5-6, 3-4, and 0-2 mismatches, respectively; P=0.012). Human leukocyte antigen mismatch number (hazards ratio, 1.35; 95% confidence interval, 1.10-1.66, for each supplementary mismatch; P=0.005) was an independent risk factor for AE. In the propensity score match analysis, having received a well-matched kidney conferred a reduced risk of AE (hazards ratio, 0.22; 95% confidence interval, 0.05-0.95; P=0.044). We observed a significant correlation between HLA mismatch numbers and circulating CD57(+)CD28(-) CD8(+) T cells (R=0.31; P=0.017). These CD8(+) T cells were more frequent in patients with more HLA mismatches (P<0.0001). Overall, our results suggest that chronic allogeneic stimulation participates to accelerated atherosclerosis observed after transplantation.

Platelet transfusions in cancer patients with hypoproliferative thrombocytopenia in the intensive care unit.

PubMed

Habr, Bassem; Charpentier, Julien; Champigneulle, Benoît; Dechartres, Agnès; Daviaud, Fabrice; Geri, Guillaume; Cariou, Alain; Chiche, Jean-Daniel; Mira, Jean-Paul; Pène, Frédéric

2015-12-01

Thrombocytopenia is a frequent finding in critically ill cancer patients for whom indications of platelet transfusions are unclear. We herein addressed the current practices in platelet transfusion and the risk of bleeding in cancer patients with hypoproliferative thrombocytopenia in the intensive care unit (ICU). A retrospective monocenter study over a 7-year period was conducted in a medical ICU. Adult patients with malignancies and hypoproliferative thrombocytopenia, and who received at least one platelet concentrate during their ICU stay, were included. 296 patients were included and received a total of 904 platelet transfusions, for prophylactic indications in 300 (33.2 %) episodes, for securing an invasive procedure in 257 (28.4 %), and for treatment of minor to major bleeding manifestations in 347 (38.4 %). Most prophylactic transfusions (80 %) were performed at platelet count thresholds below 10-20 × 10(9)/L. Platelet increments were generally low in all three indications, 10 (interquartile range 2-25), 11 (2-25), and 8 (0-21) × 10(9)/L, respectively. A total of 97 major ICU-acquired bleeding events occurred in 40 patients. About half of those bleeding episodes (54.7 %) occurred at platelet counts below 20 × 10(9)/L. However, neither low admission platelet count nor low nadir platelet counts were predictive of ICU-acquired bleeding. The in-ICU mortality rate tended to be higher in patients with severe ICU-acquired bleeding events (50 vs. 36 %). Most prophylactic platelet transfusions were given using thresholds of 10-20 × 10(9)/L in critically ill thrombocytopenic cancer patients. The individual risk of ICU-acquired severe bleeding appears hardly predictable with the depth of thrombocytopenia.

The Safety of Acupuncture in Patients with Cancer Therapy–Related Thrombocytopenia

PubMed Central

Cybularz, Paul A.; Brothers, Karen; Singh, Gurneet M.; Feingold, Jennifer L.; Niesley, Michelle L.

2015-01-01

Abstract Background: Acceptance of acupuncture as an efficacious integrative modality for oncology-related side-effect management is rapidly expanding. It is imperative that guidelines regarding safe treatment supported by clinical experience are established. Oncology patients frequently experience thrombocytopenia as a side-effect of chemotherapy or radiation. However, safety data for acupuncture in adult patients with cancer who are thrombocytopenic is lacking. Materials and Methods: The medical records of 684 patients who received acupuncture treatments in an established acupuncture program at a private cancer treatment hospital were reviewed for adverse events occurring within the context of thrombocytopenia. Results: Of 2135 visits eligible for evaluation, 98 individual acupuncture visits occurred in patients with platelet counts <100,000/μL, including nine visits in which platelet counts were <50,000/μL. No adverse events of increased bruising or bleeding were noted. Medications and nutritional supplements or botanicals that may influence coagulation were also tabulated, with no apparent adverse events in this patient population. Conclusions: Discrepancies in the literature highlight the need to create cohesive safety guidelines backed by clinical research, specifically for groups at higher risk for adverse events. The preliminary evidence put forth in this study lays the foundation that supports the notion that acupuncture can be used safely with a high-need oncology population within an integrated model of care. In this descriptive retrospective case series of adult oncology patients with thrombocytopenia, no adverse events of increased bruising or bleeding were documented. Prospective trials are needed to confirm these initial observations. PMID:26401193

Obstacles in the diagnostics and therapy of heparin-induced thrombocytopenia.

PubMed

Antonijević, Nebojsa M; Radovanović, Nebojsa; Obradović, Slobodan; Vucelić, Dragica; Stojanović, Bojan; Miković, Danijela; Kovac, Mirjana; Kocica, Tina; Tadić, Svetlana; Antonijević, Irina; Drasković, Snezana; Djordjević, Valentina; Calija, Branko; Perunicić, Jovan; Vasiljević, Zorana

2010-01-01

An immune-mediated, severe, acquired prothrombotic disorder, heparin-induced thrombocytopenia type II (HIT II) occurs in 0.5-5% of patients exposed to unfractionated heparin longer than 5-7 days. Arterial and venous thromboses are induced by HIT II in about 35-50% of patients. Typical death rate for HIT is about 29%, while 21% of HIT patients result in amputation of a limb. The trend towards the occurrence of HIT due to the administration of low molecular weight heparins (LMWH) taking ever conspicuous place in the standard venous thromboembolism (VTE) prophylaxis has been more frequently observed recently. It is considered that LMWH may cause HIT II in about 0.25-1%. The need for further modification of HIPA assays with LMWH has been imposed in the HIT laboratory diagnostics, heretofore overburdened with complexity. There are several constantly opposing problems arising in HIT laboratory diagnostics, one of which is that in a certain number of patients immunologic assays detect nonpathogenic antibodies (mainly IgM or IgA heparin-PF4 antibodies) while, on the other hand, the occurrence of HIT pathogenetically mediated by minor antigens (neutrophil-activating peptide 2 or interleukin 8) may be neglected in certain cases. The following factors play an important role in the interpretation of each laboratory HIT assays performed: 1. correlation with HIT clinical probability test, the best known of which is 4T'score, 2. the interpretation of the laboratory findings dependent on the time of the thrombocytopenia onset, as well as 3. the sensitivity and specificity of each test respectively. The HIT diagnostics in the presence of other comorbid states which may also induce thrombocytopenia, more precisely known as pseudo HIT (cancer, sepsis, disseminated intravascular coagulation, pulmonary embolism, antiphospholipid syndrome, etc), represents a specific clinical problem.

Ceftazidime-induced thrombocytopenia.

PubMed

Domingo-Chiva, E; Díaz-Rangel, M; Monsalve-Naharro, J Á; Cuesta-Montero, P; Catalá-Ripoll, J V; García-Martínez, E M

2017-12-01

Ceftazidime is an antibiotic belonging to the group of third generation cephalosporins, frequently used in clinical practice for its broad antibacterial spectrum. A case report is presented on a 78-year-old man who entered the intensive care unit due to respiratory failure secondary to nosocomial pneumonia in the postoperative period of a laparoscopic hepatic bisegmentectomy for a hepatocarcinoma. It required invasive mechanical ventilation and was treated with ceftazidime, developing a progressive decrease in platelet count after the onset of this drug and after re-exposure to it, not coinciding with the introduction of other drugs. The adverse reaction was reported to the Spanish pharmacosurveillance system and according to the Naranjo algorithm the causal relationship was probable. Since no case of ceftazidime-induced thrombocytopenia was found in the literature, we consider knowledge of it relevant as an adverse effect to be taken into account given its potential severity, especially when it cannot be explained by other causes. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Effects of pegylated recombinant human megakaryocyte growth and development factor on thrombocytopenia induced by a new myelosuppressive chemotherapy regimen in mice.

PubMed

Akahori, H; Shibuya, K; Ozai, M; Ida, M; Kabaya, K; Kato, T; Miyazaki, H

1996-11-01

Thrombopoietin, the endogenous c-Mpl ligand, is a novel lineage-specific hematopoietic factor that plays a pivotal role in the regulation of megakaryocytopoiesis and thrombopoiesis. In this study, we examined the effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), a truncated molecule of recombinant human c-Mpl ligand derivatized with polyethylene glycol, on myelosuppressive chemotherapy-induced thrombocytopenia in mice. We developed a new murine model of thrombocytopenia induced by i.v. injections of mitomycin C (MMC) for two consecutive days. In control mice, platelet counts began to decrease on day 6, reached a nadir of less than 5% of basal level on day 14, and could not recover to basal level by day 26. Administration of PEG-rHuMGDF greatly enhanced recovery of the number of megakaryocyte progenitor cells and the megakaryocytes in bone marrow, and markedly reduced the severity of thrombocytopenia; it also accelerated platelet recovery in a dose-dependent manner in myelosuppressed mice. Mice receiving consecutive administration of higher doses of PEG-rHuMGDF showed no thrombocytopenia but rather had platelet counts being increased over basal level. Although absolute neutrophil counts and red cell counts also were decreased following MMC treatment, administration of PEG-rHuMGDF also improved neutropenia and anemia. Administration of PEG-rHuMGDF on alternate days or once a week after chemotherapy was almost as effective as consecutive administration in improving thrombocytopenia. Combined administration of PEG-rHuMGDF and rHuG-CSF had an additive effect on improvement of thrombocytopenia and neutropenia. These results suggest that PEG-rHuMGDF is a therapeutically effective agent in the treatment of thrombocytopenia associated with chemotherapy.

Role of molecular mimicry to HIV-1 peptides in HIV-1–related immunologic thrombocytopenia

PubMed Central

Li, Zongdong; Nardi, Michael A.; Karpatkin, Simon

2005-01-01

Patients with early HIV-1 infection develop an autoimmune thrombocytopenia in which antibody is directed against an immunodominant epitope of the β3 (glycoprotein IIIa [GPIIIa]) integrin, GPIIIa49-66. This antibody induces thrombocytopenia by a novel complement-independent mechanism in which platelets are fragmented by antibody-induced generation of H2O2 derived from the interaction of platelet nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and 12-lipoxygenase. To examine whether sharing of epitope between host and parasite may be responsible for this immunodominant epitope, we screened for antibody-reactive peptides capable of inhibiting platelet lysis and oxidation in vitro, using a filamentous phage display 7-mer peptide library. Fourteen of these phage-peptide clones were identified. Five shared close sequence similarity with GPIIIa49-66, as expected. Ten were molecular mimics with close sequence similarity to HIV-1 proteins nef, gag, env, and pol. Seven were synthesized as 10-mers from their known HIV-1 sequence and found to inhibit anti–GPIIIa49-66–induced platelet oxidation/fragmentation in vitro. Three rabbit antibodies raised against these peptides induced platelet oxidation/fragmentation in vitro and thrombocytopenia in vivo when passively transferred into mice. One of the peptides shared a known epitope region with HIV-1 protein nef and was derived from a variant region of the protein. These data provide strong support for molecular mimicry in HIV-1-immunologic thrombocytopenia within polymorphic regions of HIV-1 proteins. A known epitope of nef is particularly incriminated. PMID:15774614

Heparin-induced thrombocytopenia (HIT) in pediatric cardiac surgery: an emerging cause of morbidity and mortality.

PubMed

Alsoufi, Bahaaldin; Boshkov, Lynn K; Kirby, Aileen; Ibsen, Laura; Dower, Nancy; Shen, Irving; Ungerleider, Ross

2004-01-01

Unfractionated heparin (UFH) is immunogenic, and heparin-dependent antibodies can be demonstrated 5 to 10 days postoperatively in 25% to 50% of adult postcardiac surgery patients. In a minority of these cases (1% to 3% if UFH is continued longer than 1 week) these antibodies strongly activate platelets, causing thrombocytopenia and massive thrombin generation (HIT syndrome). HIT is an intensely procoagulant disorder, and in adult cardiac surgery patients carries both significant thrombotic morbidity (38% to 81%) and mortality (28%). Despite the ubiquitous use of UFH in pediatric intensive care units, and the repeated and sustained exposures to UFH in neonates and young children with congenital heart disease, HIT has been infrequently recognized and reported in this patient population. However, emerging experience at our institution and elsewhere suggests that HIT is significantly under-recognized in pediatric congenital heart disease patients, and may in fact have an incidence and associated thrombotic morbidity and mortality in this patient group comparable to that seen in adult cardiac surgery patients. This article will review HIT in pediatric patients with congenital heart disease and emphasize the special challenges posed in clinical recognition, laboratory diagnosis, and treatment of HIT in this patient group. We will also outline our experience with the off-label use of the direct thrombin inhibitor, argatroban, in pediatric patients with HIT.

PEG-rHuMGDF ameliorates thrombocytopenia in carboplatin-treated rats without inducing myelofibrosis.

PubMed

Ide, Y; Harada, K; Imai, A; Yanagida, M

1999-08-01

We examined the effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on carboplatin-induced thrombocytopenia in rats. The focus was on whether myelofibrosis is associated with the PEG-rHuMGDF treatment in this chemotherapy model. After a single injection of carboplatin, rats received subcutaneous PEG-rHuMGDF at pharmacologic doses (1,3, or 30 micrograms/kg) or a vehicle daily for 7 days. PEG-rHuMGDF at more than 3 micrograms/kg ameliorated the thrombocytopenia at day 10. Histologically, no myelofibrosis was detected in the rats treated with PEG-rHuMGDF or vehicle. Subsequently, PEG-rHuMGDF at a suprapharmacologic dose (100 micrograms/kg) was subcutaneously administered to normal and to carboplatin-treated rats daily for 7 days. Histological analysis revealed that the treatment with PEG-rHuMGDF induced myelofibrosis in the normal rats but not in the carboplatin-treated rats. Additionally, the transforming growth factor-beta 1 (TGF-beta 1) levels in the extracellular fluid and the whole extract of the bone marrow were increased to a much lesser degree in the carboplatin-treated rats compared to the normal rats. These findings suggest that PEG-rHuMGDF is effective for carboplatin-induced thrombocytopenia. Proper control of platelet counts and TGF-beta 1 levels is essential so that myelofibrosis is not induced in clinical use.

The Effect of Chronic Kidney Disease on T Cell Alloimmunity

PubMed Central

Winterberg, Pamela D.; Ford, Mandy L.

2017-01-01

Purpose of review Altered differentiation and activation of T cell subsets occur in patients with CKD, but the impact on graft rejection and protective immunity during transplantation are not fully understood. Recent findings Patients with CKD have decreased frequency of naïve T cells, accumulation of activated, terminally differentiated memory cells, and skewed regulatory versus T helper 17 ratio. Naïve and memory T cell subsets do not appear to improve following kidney transplantation. Retained thymic output is associated with acute rejection, while naïve lymphopenia and accumulation of CD8+TEMRA cells correlate with long-term graft dysfunction. CD28null memory cells accumulate during CKD and appear to confer protection against acute rejection under standard immunosuppression and possibly co-stimulation blockade. T cells bearing CD57 are also increased in patients with CKD and may underlie rejection during co-stimulation blockade. Summary The mechanisms by which CKD alters the differentiation and activation status of T cell subsets is poorly understood. Further research is also needed to understand which cell populations mediate rejection under various immunosuppressive regimens. To date, there is little use of animal models of organ failure in transplant immunology research. CKD mouse models may help identify novel pathways and targets to better control alloimmunity in post-transplant. PMID:27926546

Heparin-induced thrombocytopenia and heart operation: management with tedelparin.

PubMed

Altés, A; Martino, R; Gari, M; Cámara, M L; Garín, R; Casas, J I; Fontcuberta, J

1995-02-01

Anticoagulation for cardiopulmonary bypass in the infrequent clinical setting of thrombocytopenia associated with the use of unfractionated heparin is a very serious problem. We describe a case in which a low-molecular-weight heparin (tedelparin) was selected for this purpose based on a platelet aggregation test, permitting adequate anticoagulation during cardiopulmonary bypass for valve replacement. This case report might help establish an adequate anticoagulation protocol when faced with a patient suffering from this condition.

PF4/heparin antibody testing and treatment of heparin-induced thrombocytopenia in the intensive care unit.

PubMed

Wanat, Matthew; Fitousis, Kalliopi; Hall, Jeff; Rice, Lawrence

2013-06-01

The diagnosis of heparin-induced thrombocytopenia (HIT) may be challenging in critically ill patients, as heparin exposures are ubiquitous, and thrombocytopenia is common. Unwarranted ordering and incorrect interpretation of heparin antibody tests can expose a patient to adverse drug events and imposes a significant economic burden on our health care system. A prospective, observational study was performed over 4 months on all adult patients located in 5 intensive care units, with a heparin antibody test ordered. A platelet factor 4/heparin enzyme-linked immunosorbent assay (ELISA) test was ordered in 131 patients. In total, 110 patients had a low 4Ts score (0-3), and of these 103 had a negative ELISA result. In patients with a low 4Ts score, 0 (0%) of 110 had an optical density value >1.0. One hundred twenty-nine patients (98%) had another possible cause of thrombocytopenia identified. In critically ill patients, low 4Ts scores indicate a low probability of HIT, and heparin antibody testing in these patients is not useful.

Differential roles of fibrinogen and von Willebrand factor on clot formation and platelet adhesion in reconstituted and immune thrombocytopenia.

PubMed

Misgav, Mudi; Shenkman, Boris; Budnik, Ivan; Einav, Yulia; Martinowitz, Uri

2011-05-01

Bleeding tendencies in immune thrombocytopenia (ITP) do not always correlate with the number of platelets, suggesting platelet function variation. We used a model of normal whole blood thrombocytopenia to compare platelet function and other hemostatic variables with ITP patients. We further investigated the effect of in vitro spiking with von Willebrand factor (vWF) and fibrinogen on platelet function and hemostatic variables. The Cone and Plate(let) Analyzer was used to measure platelet adhesion (surface coverage [SC], %) and aggregation (average size, μm(2)) under defined shear rate (1200 s(-1)). Rotational thromboelastometry was used to determine variables of clot formation triggered by CaCl(2) and tissue factor. In both the model of thrombocytopenia as well as in ITP, the SC and to some extent the average size were correlated to the platelet number over a range of 5 to 80 × 10(6)/mL. The results obtained for most ITP samples were within the boundaries of the lower and upper limits set by the whole blood model of thrombocytopenia. The addition of 2 U/mL vWF (Haemate-P) to whole blood (calculated to plasma volume) results in an increase in the SC and average size without affecting clot formation. Spiking with fibrinogen (100 and 300 mg/dL) did not affect platelet deposition but improved clot formation. Using a model of whole blood thrombocytopenia enables us to establish reference variables for the Cone and Plate(let) Analyzer and rotational thromboelastometry and to assess platelet function and clot formation in the presence of severe thrombocytopenia. We demonstrated that in most cases of ITP, platelet function is comparable to normal platelets. This work also suggests that vWF and fibrinogen differentially affect primary and secondary hemostasis and therefore both may perform a function in the bleeding phenotype and possibly may be considered for treatment in patients with ITP. © 2011 International Anesthesia Research Society

Pathophysiology of HIV related thrombocytopenia: an analysis of 41 patients.

PubMed Central

Domínguez, A; Gamallo, G; Garcia, R; Lopez-Pastor, A; Peña, J M; Vazquez, J J

1994-01-01

AIM--To analyse the pathogenic mechanism of HIV related thrombocytopenia. METHODS--Forty one patients with thrombocytopenia and HIV-1 infection were investigated over two years. Anticardiolipin antibodies were measured using an enzyme linked immunosorbent assay and antiplatelet antibodies were measured using an immunocapture technique. Tests for VDRL, C3 and C4, antinuclear antibodies and rheumatoid factor were also carried out in all patients and 80 control subjects (HIV-1 positive but non-thrombocytopenic). Indiumoxine labelled platelets were transfused in 13 patients. P24 antigen were also measured in 12 bone marrow aspirates. RESULTS--Antiplatelet antibodies and circulating immune complexes were found exclusively in the thrombocytopenic group; values for antiplatelet antibodies and circulating immune complexes were both higher in homosexual and bisexual patients. Three kinds of pattern were observed using 111 In-labelled platelets: splenic (n = 10); hepatic (n = 2); and destruction of bone marrow in just one case. The two most influential factors in the sequestration pattern were antiplatelet antibodies in the splenic uptake and circulating immune complexes in the hepatic and marrow sequestration. All patients, except three, had decreased platelet recovery. In those patients with a CD4 lymphocyte count of less than 200 x 10(6) cells/l the recovery was clearly greater (53%) than in patients who had more than 200 x 10(6) /l (28%). Finally, in seven of the 12 patients who were chosen for immunohistochemical study, p24 antigen was detected in the megakaryocytes, verifying that HIV-1 infects such cells. CONCLUSIONS--The pathogenic mechanism of HIV related thrombocytopenia is probably multifaceted. Antiplatelet antibodies and circulating immune complexes would cause peripheral destruction in the spleen, liver, and bone marrow, in that order; and, on the other hand, there would be an ineffective immune thrombopoiesis and direct infection of the megakaryocytes which

Lameness associated with tarsal haemarthrosis as the sole clinical sign of idiopathic immune-mediated thrombocytopenia in a dog.

PubMed

Walton, M B; Mardell, E; Spoor, M; Innes, J

2014-01-01

A four-year-old, male Cocker Spaniel was presented for investigation of pelvic limb stiffness. There was palpable effusion of both tarsi, and analysis of synovial fluid from these joints indicated previous haemorrhage. After further investigation a diagnosis of idiopathic immune-mediated thrombocytopenia was made. The dog responded to treatment with prednisolone and azathioprine. To the authors' knowledge, this is the first reported case of confirmed haemarthrosis as the sole presenting clinical sign for canine idiopathic immune-mediated thrombocytopenia.

Levofloxacin-Induced Acute Immune-Mediated Thrombocytopenia of Rapid-Onset.

PubMed

Shih, Andrew W; Lam, Andy S; Warkentin, Theodore E

2018-04-01

Drug-induced immune thrombocytopenia (D-ITP) typically occurs after the patient has been receiving the implicated drug for at least 1 week, due to newly forming drug-dependent antibodies ("typical-onset" D-ITP). A "rapid-onset" form of D-ITP can occur when previous sensitization has occurred, where antibodies have thus already been formed, and a precipitous platelet count fall occurs upon reexposure. Typical-onset D-ITP has been reported after levofloxacin, but the rapid-onset form with a well-documented previous exposure has not been described. We report a 76-year-old male treated with levofloxacin for acute exacerbation of chronic obstructive pulmonary disease. After a single 750 mg oral dose of levofloxacin, his platelet count fell from 187 to 5 × 10 9 /L (nadir) over 4 days. Other causes of thrombocytopenia were ruled out. He had received a previous course of levofloxacin 6 months earlier. Discontinuation of levofloxacin and treatment with intravenous immunoglobulin and dexamethasone resulted in platelet count recovery. Levofloxacin-dependent antibodies were not detectable, consistent with the known low sensitivity of laboratory tests for drug-dependent antibodies, presumably indicating antibodies against levofloxacin metabolites, as is indirectly supported by the abrupt but relatively slow platelet count decline observed. This case illustrates a rapid-onset presentation of levofloxacin-induced D-ITP in the setting of previous drug exposure.

Platelets are versatile cells: New discoveries in hemostasis, thrombosis, immune responses, tumor metastasis and beyond.

PubMed

Xu, Xiaohong Ruby; Zhang, Dan; Oswald, Brigitta Elaine; Carrim, Naadiya; Wang, Xiaozhong; Hou, Yan; Zhang, Qing; Lavalle, Christopher; McKeown, Thomas; Marshall, Alexandra H; Ni, Heyu

2016-12-01

Platelets are small anucleate blood cells generated from megakaryocytes in the bone marrow and cleared in the reticuloendothelial system. At the site of vascular injury, platelet adhesion, activation and aggregation constitute the first wave of hemostasis. Blood coagulation, which is initiated by the intrinsic or extrinsic coagulation cascades, is the second wave of hemostasis. Activated platelets can also provide negatively-charged surfaces that harbor coagulation factors and markedly potentiate cell-based thrombin generation. Recently, deposition of plasma fibronectin, and likely other plasma proteins, onto the injured vessel wall has been identified as a new "protein wave of hemostasis" that may occur even earlier than the first wave of hemostasis, platelet accumulation. Although no experimental evidence currently exists, it is conceivable that platelets may also contribute to this protein wave of hemostasis by releasing their granule fibronectin and other proteins that may facilitate fibronectin self- and non-self-assembly on the vessel wall. Thus, platelets may contribute to all three waves of hemostasis and are central players in this critical physiological process to prevent bleeding. Low platelet counts in blood caused by enhanced platelet clearance and/or impaired platelet production are usually associated with hemorrhage. Auto- and allo-immune thrombocytopenias such as idiopathic thrombocytopenic purpura and fetal and neonatal alloimmune thrombocytopenia may cause life-threatening bleeding such as intracranial hemorrhage. When triggered under pathological conditions such as rupture of an atherosclerotic plaque, excessive platelet activation and aggregation may result in thrombosis and vessel occlusion. This may lead to myocardial infarction or ischemic stroke, the major causes of mortality and morbidity worldwide. Platelets are also involved in deep vein thrombosis and thromboembolism, another leading cause of mortality. Although fibrinogen has been

Neonatal Death

MedlinePlus

... Home > Complications & Loss > Loss & grief > Neonatal death Neonatal death E-mail to a friend Please fill in ... cope with your baby’s death. What is neonatal death? Neonatal death is when a baby dies in ...

Heparin-induced thrombocytopenia in the critically ill: interpreting the 4Ts test in a randomized trial.

PubMed

Crowther, Mark; Cook, Deborah; Guyatt, Gordon; Zytaruk, Nicole; McDonald, Ellen; Williamson, David; Albert, Martin; Dodek, Peter; Finfer, Simon; Vallance, Shirley; Heels-Ansdell, Diane; McIntyre, Lauralyn; Mehta, Sangeeta; Lamontagne, Francois; Muscedere, John; Jacka, Michael; Lesur, Olivier; Kutsiogiannis, Jim; Friedrich, Jan; Klinger, James R; Qushmaq, Ismael; Burry, Lisa; Khwaja, Kosar; Sheppard, Jo-Ann; Warkentin, Theodore E

2014-06-01

Thrombocytopenia occurs in 20% to 45% of critically ill medical-surgical patients. The 4Ts heparin-induced thrombocytopenia (HIT) score (with 4 domains: Thrombocytopenia, Timing of thrombocytopenia, Thrombosis and oTher reason[s] for thrombocytopenia) might reliably identify patients at low risk for HIT. Interobserver agreement on 4Ts scoring is uncertain in this setting. To evaluate whether a published clinical prediction rule (the "4Ts score") reliably rules out HIT in "low-risk" intensive care unit (ICU) patients as assessed by research coordinators (who prospectively scored) and 2 adjudicators (who scored retrospectively) during an international heparin thromboprophylaxis trial (PROTECT, NCT00182143). Of 3746 medical-surgical ICU patients in PROTECT, 794 met the enrollment criteria for this HIT substudy. Enrollment was predicated on one of the following occurring in ICU: platelets less than 50×10(9)/L, platelets decreased to 50% of ICU admission value (if admission value<100×10(9)/L), any venous thrombosis, or if HIT was otherwise clinically suspected. Independently, 4Ts scores were completed in real time by research coordinators blinded to study drug and laboratory HIT results, and retrospectively by 2 adjudicators blinded to study drug, laboratory HIT results, and research coordinators' scores; the adjudicators arrived at consensus in all cases. Of the 763 patients, 474 had a central or local laboratory HIT test performed and had 4Ts scoring by adjudicators; 432 were scored by trained research coordinators. Heparin-induced thrombocytopenia was defined by a centrally performed positive serotonin release assay (SRA). Of the 474 patients with central adjudication, 407 (85.9%) had a 4Ts score of 3 or lower, conferring a low pretest probability (PTP) of HIT; of these, 6 (1.5% [95% confidence interval, 0.7%-3.2%) had a positive SRA. Fifty-nine (12.4%) had a moderate PTP (4Ts score of 4-5); of these, 4 (6.8%) had a positive SRA. Eight patients had a high PTP (4Ts

Modulation of alloimmune response by commensal gut microbiota and potential new avenues to influence the outcome of allogeneic transplantation by modification of the 'gut culture'.

PubMed

Kanangat, S

2017-02-01

Host defence response against microbial infections was the foundation for the Science of Immunology. Now, we know the mechanisms of such host defence which include innate immune responses that is generally nonspecific but effective in many cases and lead to more specific responses called adaptive immune response. The gene loci of class I, II and III of the major histocompatibility complex (MHC) play a major role in directing the adaptive immune responses by presenting processed antigens to T and B cells to induce appropriate antigen-specific cellular and or humoral immune responses. In humans, these are commonly referred to as human leucocyte antigens class I/II-HLA I/II). The class III region, the gamma region in the MHC complex, is mostly associated with regulation of immune responses along with genes associated with complement activation. The adaptive immune responses are orchestrated by T and B cells that are tuned to respond to antigens that are normally foreign to the body, because these cells are educated to avoid self-antigens by a process of thymic education and selection of the T cells that are mostly non-self-reactive which also helps the B cells in eliciting specific immune responses to non-self-antigens. A by-product of this is the ability of the T and B cells to elicit strong immune responses to foreign HLA/MHC (alloimmune response), which developed into the field of histocompatibility testing for allogeneic transplantation of stem cells and organs. Now, we are beginning to learn that such alloimmune responses can be influenced by the microbiota that symbiotically live in our body especially on the mucosal surfaces and on the skin. This review deals with new and emerging data on how the commensal mucosal and skin microbiota influence the immune homeostasis, and how manipulating the commensal microbiota of the mucosa and skin could influence the survival and long-term functions of the allografts. Also, alterations of the microbiota by the inevitable

Management and outcomes of neonates with down syndrome admitted to neonatal units.

PubMed

Mann, Jake P; Statnikov, Eugene; Modi, Neena; Johnson, Nik; Springett, Anna; Morris, Joan K

2016-06-01

Neonates with Down syndrome have an increased risk of being admitted to a neonatal unit compared with unaffected neonates. We aimed to estimate the proportion of neonates with Down syndrome admitted to a neonatal unit and compare their management and outcomes with other neonatal admissions. Case-control study of neonates born from 2009 to 2011 admitted to 122 NHS Neonatal Units in England using data from the National Down Syndrome Cytogenetic Register and the National Neonatal Research Database. For each neonate with Down syndrome, three neonates admitted to the same unit in the same month and born at the same gestation were identified. Forty-six percent of neonates with Down syndrome were admitted to a neonatal unit. Boys were more likely to be admitted than girls (odds ratio = 1.7; 95% confidence interval, 1.4-2.0). Neonates with Down syndrome required more intensive or high dependency care compared with unaffected neonates (37% vs. 27%. p < 0.01) and stayed in neonatal units for longer (11 days vs. 5 days, p < 0.01). A total of 31% of neonates with Down syndrome required respiratory support compared with 22% (p < 0.001) of unaffected neonates, and 11% were discharged requiring oxygen supplementation compared with 3% (p < 0.001) of unaffected neonates. A total of 3% of neonates with Down syndrome died in a neonatal unit compared with 1% (p = 0.01) of unaffected neonates. Neonates with Down syndrome are more likely than unaffected neonates to be admitted to a neonatal unit, have a prolonged stay, and be discharged home on supplemental oxygen. Birth Defects Research (Part A) 106:468-474, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Further examination of various administration protocols of pegylated recombinant human megakaryocyte growth and development factor on thrombocytopenia in myelosuppressed mice.

PubMed

Akahori, H; Ozai, M; Ida, M; Shibuya, K; Kato, T; Miyazaki, H

1998-02-01

Thrombopoietin (TPO) is the recently isolated lineage-dominant hematopoietic factor that plays a pivotal role in the regulation of megakaryocytopoiesis and thrombopoiesis. In vivo studies have shown that daily multiple injections of pegylated human megakaryocyte growth and development factor (PEG-rHuMGDF), a truncated molecule related to human TPO, modified with polyethylene glycol, greatly improve thrombocytopenia and in most cases anemia and neutropenia in myelosuppressed animal models. In this study, we further examined various administration protocols of PEG-rHuMGDF on thrombocytopenia in mice treated with a combination of irradiation and carboplatin. After the myelosuppressive treatment on Day 0, mice received the same amount of PEG-rHuMGDF beginning on Day 1 by a single, 3 times (on alternate days), or 7 day daily administration. A single injection of PEG-rHuMGDF significantly reduced the severity and duration of thrombocytopenia and anemia with a concomitant accelerated recovery of megakaryocytic and erythroid progenitors in the bone marrow, similar to the 2 other administration protocols. As the start of a single injection of PEG-rHuMGDF was delayed, its therapeutic effects were attenuated. These results indicate that an administration of PEG-rHuMGDF at an earlier time after the myelosuppressive treatment is necessary to improve thrombocytopenia and anemia.

Severe Fever with Thrombocytopenia Syndrome in Patients Suspected of Having Scrub Typhus.

PubMed

Wi, Yu Mi; Woo, Hye In; Park, Dahee; Lee, Keun Hwa; Kang, Cheol-In; Chung, Doo Ryeon; Peck, Kyong Ran; Song, Jae-Hoon

2016-11-01

To determine prevalence of severe fever with thrombocytopenia syndrome in South Korea, we examined serum samples from patients with fever and insect bite history in scrub typhus-endemic areas. During the 2013 scrub typhus season, prevalence of this syndrome among patients suspected of having scrub typhus was high (23.0%), suggesting possible co-infection.

Oral surgery in a patient with cirrhosis and thrombocytopenia: a case report.

PubMed

Patel, Seena; Perry, Maureen Munnelly; Spolarich, Ann Eshenaur

2016-01-01

While most oral surgical procedures can be safely performed in an outpatient setting, certain medical conditions may present a higher chance of postoperative complications. In particular, those predisposing the patient to bleeding abnormalities pose a potential risk when performing such treatments. The authors report a case involving full-mouth extractions in a patient with cirrhosis and thrombocytopenia after obtaining a platelet transfusion. A 62-year-old Caucasian female presented to a university special care dental clinic requiring extractions. Her pertinent medical history was remarkable for cirrhosis and thrombocytopenia, with a platelet count of 32,000/uL. Upon medical consultation, the patient was appointed for a prophylactic platelet transfusion. The surgery was rendered uneventfully, and the patient achieved adequate hemostasis without hospitalization. Patients with cirrhosis pose a potential bleeding risk with dental surgical procedures. Pre-operative medical consultation, review of pertinent laboratory values, and prophylactic platelet transfusion allow these patients to be managed safely in an outpatient setting. © 2015 Special Care Dentistry Association and Wiley Periodicals, Inc.

CD32a antibodies induce thrombocytopenia and type II hypersensitivity reactions in FCGR2A mice

PubMed Central

Robles-Carrillo, Liza; Davila, Monica; Brodie, Meghan; Desai, Hina; Rivera-Amaya, Mildred; Francis, John L.; Amirkhosravi, Ali

2015-01-01

The CD32a immunoglobulin G (IgG) receptor (Fcγ receptor IIa) is a potential therapeutic target for diseases in which IgG immune complexes (ICs) mediate inflammation, such as heparin-induced thrombocytopenia, rheumatoid arthritis, and systemic lupus erythematosus. Monoclonal antibodies (mAbs) are a promising strategy for treating such diseases. However, IV.3, perhaps the best characterized CD32a-blocking mAb, was recently shown to induce anaphylaxis in immunocompromised “3KO” mice. This anaphylactic reaction required a human CD32a transgene because mice lack an equivalent of this gene. The finding that IV.3 induces anaphylaxis in CD32a-transgenic mice was surprising because IV.3 had long been thought to lack the intrinsic capacity to trigger cellular activation via CD32a. Such an anaphylactic reaction would also limit potential therapeutic applications of IV.3. In the present study, we examine the molecular mechanisms by which IV.3 induces anaphylaxis. We now report that IV.3 induces anaphylaxis in immunocompetent CD32a-transgenic “FCGR2A” mice, along with the novel finding that IV.3 and 2 other well-characterized CD32a-blocking mAbs, AT-10 and MDE-8, also induce severe thrombocytopenia in FCGR2A mice. Using recombinant variants of these same mAbs, we show that IgG “Fc” effector function is necessary for the induction of anaphylaxis and thrombocytopenia in FCGR2A mice. Variants of these mAbs lacking the capacity to activate mouse IgG receptors not only failed to induce anaphylaxis or thrombocytopenia, but also very potently protected FCGR2A mice from near lethal doses of IgG ICs. Our findings show that effector-deficient IV.3, AT-10, and MDE-8 are promising candidates for developing therapeutic mAbs to treat CD32a-mediated diseases. PMID:26396093

Neutropenia in the Newborn

PubMed Central

Maheshwari, Akhil

2013-01-01

PURPOSE OF REVIEW Review normal blood neutrophil concentrations and the clinical approach to neutropenia in the neonatal period. A literature search on neonatal neutropenia was performed using the databases PubMed, EMBASE, and Scopus and the electronic archive of abstracts presented at the annual meetings of the Pediatric Academic Societies. RECENT FINDINGS This review summarizes current knowledge on the causes of neutropenia in premature and critically-ill neonates, focusing on common causes such as maternal hypertension, neonatal sepsis, twin-twin transfusion, alloimmunization, and hemolytic disease. The article provides a rational approach to diagnosis and treatment of neonatal neutropenia, including current evidence on the role of recombinant hematopoietic growth factors. SUMMARY Neutrophil counts should be carefully evaluated in premature and critically-ill neonates. Although neutropenia is usually benign and runs a self-limited course in most neonates, it can be prolonged and constitute a serious deficiency in antimicrobial defense in some infants. PMID:24322487

Immune thrombocytopenia with multi-organ dysfunction syndrome as a rare presentation of scrub typhus: a case report.

PubMed

Ittyachen, Abraham M; Abraham, Saramma P; Krishnamoorthy, Smitha; Vijayan, Anuroopa; Kokkat, Jayamohan

2017-10-06

Scrub typhus is an acute infectious illness caused by Orientia tsutsugamushi. It is endemic to a part of the world known as the "tsutsugamushi triangle". Humans are accidental hosts in this zoonotic disease. About a third of patients admitted with scrub typhus have evidence of multi-organ dysfunction. Multi-organ dysfunction secondary to scrub typhus carries a high mortality rate. We report a 65-year old lady who was admitted in a Tertiary Care Center in the state of Kerala in India, with 7 day history of fever, myalgia and reduced urine output. Head to foot examination revealed the presence of an eschar on her chest. One week prior to the onset of her illness she had gone trekking through a hilly forest area. She was clinically suspected to have scrub typhus, which was later confirmed with laboratory tests. She developed multi-organ dysfunction syndrome secondary to this illness. Though there was an improvement in the multi-organ dysfunction, thrombocytopenia alone failed to improve. Bone marrow study was done which was suggestive of immune thrombocytopenia. Patient was given a course of steroids with which the thrombocytopenia improved. Failure of platelet count to normalize even after there has been a general improvement of other markers of multi-organ dysfunction in scrub typhus should prompt the clinician to consider other potential causes of thrombocytopenia. An unusual finding as this calls for further research to understand the molecular mechanisms behind such an event. Further, considering the close similarity in clinical presentation of several tropical illnesses, meticulous history taking and a detailed physical examination needs to be emphasized.

Dialyzer-related Thrombocytopenia due to a Polysulfone Membrane.

PubMed

Kobari, Eri; Terawaki, Hiroyuki; Takahashi, Yasuhito; Kusano, Yuki; Sakurai, Kaoru; Matsunaga, Keiko; Fukushima, Naotaro; Suzuki, Sawako; Tanaka, Ken-Ichi; Hayashi, Yoshimitsu; Watanabe, Tsuyoshi; Nakayama, Masaaki

2016-01-01

A 72-year-old Japanese woman was admitted to our hospital with rapidly progressive glomerulonephritis associated with anti-glomerular basement membrane antibody. Hemodialysis (HD) therapy was initiated on the day of admission using a biocompatible polysulfone (PS) membrane. Her platelet count (PLT; ×10(4)/μL) decreased gradually from 58.7 (day 1) to 5.8 (day 25). Considering the possibility of dialyzer-related thrombocytopenia (DRT), we measured her PLT count before and after the HD session on day 72, which revealed a dramatic decrease of 7.5 to 4.3. This finding suggested that the PS dialyzer caused PLT depletion. After discontinuation of the PS dialyzer, DRT was resolved.

Neonatal Hyperglycemia due to Transient Neonatal Diabetes Mellitus in Puerto Rico

PubMed Central

Fargas-Berríos, N.; García-Fragoso, L.; García-García, I.; Valcárcel, M.

2015-01-01

Neonatal hyperglycemia is a metabolic disorder found in the neonatal intensive care units. Neonatal diabetes mellitus (NDM) is a very uncommon cause of hyperglycemia in the newborn, occurring in 1 in every 400,000 births. There are two subtypes of neonatal diabetes mellitus: permanent neonatal diabetes mellitus (PNDM) and transient neonatal diabetes mellitus (TNDM). We describe a term, small for gestational age, female neonate with transient neonatal diabetes mellitus who presented with poor feeding tolerance and vomiting associated with hyperglycemia (385 mg/dL), glycosuria, and metabolic acidosis within the first 12 hours of life. The neonate was treated with intravenous insulin, obtaining a slight control of hyperglycemia. An adequate glycemia was achieved at 5 weeks of life. The molecular studies showed complete loss of maternal methylation at the TND differentially methylated region on chromosome 6q24. The etiology of this neonate's hyperglycemia was a hypomethylation of the maternal TND locus. A rare cause of neonatal diabetes mellitus must be considered if a neonate presents refractory hyperglycemia. To our knowledge, this is the first case reported in Puerto Rico of transient neonatal mellitus due to the uncommon mechanism of maternal hypomethylation of the TND locus. Its prevalence in Puerto Rico is unknown. PMID:26576310

Neonatal Hyperglycemia due to Transient Neonatal Diabetes Mellitus in Puerto Rico.

PubMed

Fargas-Berríos, N; García-Fragoso, L; García-García, I; Valcárcel, M

2015-01-01

Neonatal hyperglycemia is a metabolic disorder found in the neonatal intensive care units. Neonatal diabetes mellitus (NDM) is a very uncommon cause of hyperglycemia in the newborn, occurring in 1 in every 400,000 births. There are two subtypes of neonatal diabetes mellitus: permanent neonatal diabetes mellitus (PNDM) and transient neonatal diabetes mellitus (TNDM). We describe a term, small for gestational age, female neonate with transient neonatal diabetes mellitus who presented with poor feeding tolerance and vomiting associated with hyperglycemia (385 mg/dL), glycosuria, and metabolic acidosis within the first 12 hours of life. The neonate was treated with intravenous insulin, obtaining a slight control of hyperglycemia. An adequate glycemia was achieved at 5 weeks of life. The molecular studies showed complete loss of maternal methylation at the TND differentially methylated region on chromosome 6q24. The etiology of this neonate's hyperglycemia was a hypomethylation of the maternal TND locus. A rare cause of neonatal diabetes mellitus must be considered if a neonate presents refractory hyperglycemia. To our knowledge, this is the first case reported in Puerto Rico of transient neonatal mellitus due to the uncommon mechanism of maternal hypomethylation of the TND locus. Its prevalence in Puerto Rico is unknown.

Prevalence of thrombocytopenia before and after initiation of HAART among HIV infected patients at black lion specialized hospital, Addis Ababa, Ethiopia: a cross sectional study.

PubMed

Woldeamanuel, Gashaw Garedew; Wondimu, Diresibachew Haile

2018-01-01

Hematological abnormalities are common in HIV positive patients. Of these, thrombocytopenia is a known complication which has been associated with a variety of bleeding disorders. However, its magnitude and related factors have not been well-characterized in the era of highly active antiretroviral therapy (HAART) in Ethiopia. Therefore, this study aimed to assess the prevalence of thrombocytopenia before and after initiation of HAART among HIV positive patients attending Black Lion Specialized Hospital, Addis Ababa, Ethiopia. A cross sectional study was conducted from February to April 2017 in Black Lion Specialized Hospital, Addis Ababa, Ethiopia. A total of 176 patients on HAART were selected using simple random sampling techniques. Socio-demographic and clinical characteristics of the study patients were collected using structured questionnaire. Measurements of platelet counts and CD4 + T cell counts were made using Sysmex XT 2000i hematology analyzer and BD FACS Count CD4 analyzer, respectively. Statistical analysis of the data (Paired T- test and binary logistic regression) was done using SPSS version 20. P -value < 0.05 was considered as statistically significant. A total of 176 patients (Age > 18 years old) were enrolled in this study and had a mean age of 40.08 ± 9.38 years. There was significant increase in the mean values of platelet counts (218.44 ± 106.6 × 10 3 /μl vs 273.65 ± 83.8 × 10 3 /μl, p  < 0.001) after six months of HAART initiation compared to the baseline. Prevalence of thrombocytopenia before and after HAART initiation was 25 and 5.7% respectively. HIV patients whose CD4 counts < 200 Cells/μl were more likely to have thrombocytopenia than HIV patients whose CD4 count ≥350 Cells/μl. However, it was not statistically associated with prevalence of thrombocytopenia. This study has shown that the prevalence of thrombocytopenia after HAART initiation was decreased significantly. Based on our results

Reporting an outbreak of Candida pelliculosa fungemia in a neonatal intensive care unit.

PubMed

Lin, Hsiao-Chuan; Lin, Hsiang-Yu; Su, Bai-Hong; Ho, Mao-Wang; Ho, Cheng-Mao; Lee, Ching-Yi; Lin, Ming-Hsia; Hsieh, Hsin-Yang; Lin, Hung-Chih; Li, Tsai-Chung; Hwang, Kao-Pin; Lu, Jang-Jih

2013-12-01

Fungemia in preterm infants is associated with high mortality and morbidity. This study reports an outbreak of unusual fungemia in a tertiary neonatal intensive care unit (NICU). Ten Candida pelliculosa bloodstream isolates were identified from six infants hospitalized in the NICU from February to March 2009. Environmental study was performed, and genetic relatedness among the 10 clinical isolates of C pelliculosa and six control C pelliculosa strains was characterized by randomly amplified polymorphic DNA assay. In vitro susceptibility of isolates to six antifungal agents was analyzed by broth microdilution method. Amphotericin B was given to infected infants and prophylactic fluconazole was prescribed to the other noninfected extremely low birth weight infants during the outbreak. Thrombocytopenia (platelet counts <100×10(9)/L) was the early laboratory finding in four infants. One of six patients died, making overall mortality 17%. Fluconazole, voriconazole, amphotericin B, and micafungin provided good antifungal activity. Cultures from the environment and hands of caregivers were all negative. Molecular studies indicated the outbreak as caused by a single strain. The outbreak was controlled by strict hand washing, cohort infected patients, confined physicians and nurses to take care of patients, prophylactic fluconazole to uninfected neonates, and proper management of human milk. The study demonstrated the clinical importance of emerged non-albicans Candida species in NICU. For unusual pathogen isolated from immunocompromised hosts, more attention should be paid to monitor the possibility of an outbreak. Copyright © 2012. Published by Elsevier B.V.

Congenital amegakaryocytic thrombocytopenia iPS cells exhibit defective MPL-mediated signaling

PubMed Central

Hirata, Shinji; Takayama, Naoya; Jono-Ohnishi, Ryoko; Endo, Hiroshi; Nakamura, Sou; Dohda, Takeaki; Nishi, Masanori; Hamazaki, Yuhei; Ishii, Ei-ichi; Kaneko, Shin; Otsu, Makoto; Nakauchi, Hiromitsu; Kunishima, Shinji; Eto, Koji

2013-01-01

Congenital amegakaryocytic thrombocytopenia (CAMT) is caused by the loss of thrombopoietin receptor–mediated (MPL-mediated) signaling, which causes severe pancytopenia leading to bone marrow failure with onset of thrombocytopenia and anemia prior to leukopenia. Because Mpl–/– mice do not exhibit the human disease phenotype, we used an in vitro disease tracing system with induced pluripotent stem cells (iPSCs) derived from a CAMT patient (CAMT iPSCs) and normal iPSCs to investigate the role of MPL signaling in hematopoiesis. We found that MPL signaling is essential for maintenance of the CD34+ multipotent hematopoietic progenitor (MPP) population and development of the CD41+GPA+ megakaryocyte-erythrocyte progenitor (MEP) population, and its role in the fate decision leading differentiation toward megakaryopoiesis or erythropoiesis differs considerably between normal and CAMT cells. Surprisingly, complimentary transduction of MPL into normal or CAMT iPSCs using a retroviral vector showed that MPL overexpression promoted erythropoiesis in normal CD34+ hematopoietic progenitor cells (HPCs), but impaired erythropoiesis and increased aberrant megakaryocyte production in CAMT iPSC–derived CD34+ HPCs, reflecting a difference in the expression of the transcription factor FLI1. These results demonstrate that impaired transcriptional regulation of the MPL signaling that normally governs megakaryopoiesis and erythropoiesis underlies CAMT. PMID:23908116

Congenital amegakaryocytic thrombocytopenia iPS cells exhibit defective MPL-mediated signaling.

PubMed

Hirata, Shinji; Takayama, Naoya; Jono-Ohnishi, Ryoko; Endo, Hiroshi; Nakamura, Sou; Dohda, Takeaki; Nishi, Masanori; Hamazaki, Yuhei; Ishii, Ei-ichi; Kaneko, Shin; Otsu, Makoto; Nakauchi, Hiromitsu; Kunishima, Shinji; Eto, Koji

2013-09-01

Congenital amegakaryocytic thrombocytopenia (CAMT) is caused by the loss of thrombopoietin receptor-mediated (MPL-mediated) signaling, which causes severe pancytopenia leading to bone marrow failure with onset of thrombocytopenia and anemia prior to leukopenia. Because Mpl(-/-) mice do not exhibit the human disease phenotype, we used an in vitro disease tracing system with induced pluripotent stem cells (iPSCs) derived from a CAMT patient (CAMT iPSCs) and normal iPSCs to investigate the role of MPL signaling in hematopoiesis. We found that MPL signaling is essential for maintenance of the CD34+ multipotent hematopoietic progenitor (MPP) population and development of the CD41+GPA+ megakaryocyte-erythrocyte progenitor (MEP) population, and its role in the fate decision leading differentiation toward megakaryopoiesis or erythropoiesis differs considerably between normal and CAMT cells. Surprisingly, complimentary transduction of MPL into normal or CAMT iPSCs using a retroviral vector showed that MPL overexpression promoted erythropoiesis in normal CD34+ hematopoietic progenitor cells (HPCs), but impaired erythropoiesis and increased aberrant megakaryocyte production in CAMT iPSC-derived CD34+ HPCs, reflecting a difference in the expression of the transcription factor FLI1. These results demonstrate that impaired transcriptional regulation of the MPL signaling that normally governs megakaryopoiesis and erythropoiesis underlies CAMT.

Recurrent coagulopathy and thrombocytopenia in children treated with crotalidae polyvalent immune fab: a case series.

PubMed

Miller, Alexander D; Young, Michael C; DeMott, Megan C; Ly, Binh T; Clark, Richard F

2010-08-01

Recurrent signs and symptoms after initial treatment and control of coagulopathy and thrombocytopenia after American pit viper (crotaline) envenomations have been previously described in patients treated with Crotalidae polyvalent immune Fab antivenom (FabAV). The significance and necessity of treatment of these recurrent abnormalities are uncertain. Our goal was to further characterize recurrent coagulopathy or thrombocytopenia in pediatric patients. All cases presenting to our Toxicology Consult Service, which covers 6 hospitals in a metropolitan area, from May 2007 to April 2008 with recurrent coagulopathy after initial control with FabAV were included and retrospectively reviewed. Four cases of pediatric patients are presented who presented with recurrent coagulopathy and/or thrombocytopenia after initial control with FabAV. The patients were all treated with delayed administration of FabAV with variable results. Blood products administered without concurrent FabAV were of limited use. The laboratory abnormalities took up to 18 days to resolve in one case. One patient developed hemodynamically significant spontaneous bleeding. The cases presented here suggest administration of FabAV may correct delayed coagulopathy associated with crotaline envenomations. The first 3 cases illustrate that in the face of severe derangements in laboratory values, most envenomated patients treated with FabAV do not develop significant bleeding. These cases may respond to additional antivenom alone. However, case 4 illustrates that hemodynamically significant spontaneous bleeding can occur. Until more data are available, readministration of FabAV is a reasonable first-line therapy for delayed coagulopathy associated with crotaline envenomations.

Haemolytic disease of the fetus and newborn.

PubMed

de Haas, M; Thurik, F F; Koelewijn, J M; van der Schoot, C E

2015-08-01

Haemolytic Disease of the Fetus and Newborn (HDFN) is caused by maternal alloimmunization against red blood cell antigens. In severe cases, HDFN may lead to fetal anaemia with a risk for fetal death and to severe forms of neonatal hyperbilirubinaemia with a risk for kernicterus. Most severe cases are caused by anti-D, despite the introduction of antental and postnatal anti-D immunoglobulin prophylaxis. In general, red blood cell antibody screening programmes are aimed to detect maternal alloimmunization early in pregnancy to facilitate the identification of high-risk cases to timely start antenatal and postnatal treatment. In this review, an overview of the clinical relevance of red cell alloantibodies in relation to occurrence of HDFN and recent views on prevention, screening and treatment options of HDFN are provided. © 2015 International Society of Blood Transfusion.

Chinese guidelines for treatment of adult primary immune thrombocytopenia.

PubMed

Liu, Xin-Guang; Bai, Xiao-Chuan; Chen, Fang-Ping; Cheng, Yun-Feng; Dai, Ke-Sheng; Fang, Mei-Yun; Feng, Jian-Ming; Gong, Yu-Ping; Guo, Tao; Guo, Xin-Hong; Han, Yue; Hong, Luo-Jia; Hu, Yu; Hua, Bao-Lai; Huang, Rui-Bing; Li, Yan; Peng, Jun; Shu, Mi-Mi; Sun, Jing; Sun, Pei-Yan; Sun, Yu-Qian; Wang, Chun-Sen; Wang, Shu-Jie; Wang, Xiao-Min; Wu, Cong-Ming; Wu, Wen-Man; Yan, Zhen-Yu; Yang, Feng-E; Yang, Lin-Hua; Yang, Ren-Chi; Yang, Tong-Hua; Ye, Xu; Zhang, Guang-Sen; Zhang, Lei; Zheng, Chang-Cheng; Zhou, Hu; Zhou, Min; Zhou, Rong-Fu; Zhou, Ze-Ping; Zhu, Hong-Li; Zhu, Tie-Nan; Hou, Ming

2018-06-01

Primary immune thrombocytopenia (ITP) is a bleeding disorder commonly encountered in clinical practice. The International Working Group (IWG) on ITP has published several landmark papers on terminology, definitions, outcome criteria, bleeding assessment, diagnosis, and management of ITP. The Chinese consensus reports for diagnosis and management of adult ITP have been updated to the 4th edition. Based on current consensus positions and new emerging clinical evidence, the thrombosis and hemostasis group of the Chinese Society of Hematology issued Chinese guidelines for management of adult ITP, which aim to provide evidence-based recommendations for clinical decision making.

Parvovirus B19-triggered Acute Hemolytic Anemia and Thrombocytopenia in a Child with Evans Syndrome.

PubMed

Zikidou, Panagiota; Grapsa, Anastassia; Bezirgiannidou, Zoe; Chatzimichael, Athanassios; Mantadakis, Elpis

2018-01-01

Human parvovirus B19 (HPV-B19) is the etiologic agent of erythema infectiosum, of transient aplastic crises in individuals with underlying chronic hemolytic disorders, and of chronic pure red cell aplasia in immunocompromised individuals. We describe a 14-year-old girl with long-standing Evans syndrome, who presented with severe anemia, reticulocytopenia and thrombocytopenia. A bone marrow aspirate revealed severe erythroid hypoplasia along with the presence of giant pronormoblasts, while serological studies and real-time PCR of whole blood were positive for acute parvovirus B19 infection. The patient was initially managed with corticosteroids, but both cytopenias resolved only after administration of intravenous gamma globulin 0.8g/kg. Acute parvovirus B19 infection should be suspected in patients with immunologic diseases, who present reticulocytopenic hemolytic anemia and thrombocytopenia. In this setting, intravenous gamma globulin is effective for both cytopenias.

Management of Platelet Transfusion Therapy in Patients With Blood Cancer or Treatment-Induced Thrombocytopenia

ClinicalTrials.gov

2018-02-15

Acute Biphenotypic Leukemia; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; B-Cell Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Hematologic and Lymphocytic Disorder; Hematopoietic Cell Transplantation Recipient; Myelodysplastic Syndrome; Primary Myelofibrosis; Secondary Myelofibrosis; T-Cell Non-Hodgkin Lymphoma; Thrombocytopenia; Venous Thromboembolism

Seroprevalence of Severe Fever with Thrombocytopenia Syndrome Virus Antibodies in Rural Areas, South Korea

PubMed Central

Han, Mi Ah; Kim, Choon-Mee; Yun, Na Ra; Park, Sun-Whan; Han, Myung Guk; Lee, Won-Ja

2018-01-01

We investigated 1,228 residents of 3 rural areas in South Korea and determined that 50 (4.1%) were positive for severe fever with thrombocytopenia syndrome virus antibodies. Fever and gastrointestinal symptoms in the previous 3 years and career duration were associated with virus seropositivity. PMID:29664384

Neonatal gastric perforation.

PubMed

Kuremu, R T; Hadley, G P; Wiersma, R

2004-01-01

Gastric perforation in neonates is a catastrophe associated with high morbidity. Most are due to underlying primary pathology. To review the management of gastric perforation in neonates in Kwa Zulu-Natal, South Africa. Retrospective study of consecutive complete data sets of neonates presenting with gastric perforation. Department of Paediatric Surgery, Nelson R. Mandela School of Medicine, University of Natal, Durban, South Africa. Eight neonates treated for gastric perforation between January 1998 and April 2003. Morbidity and mortality. There was an equal number of males and females. Median birth weight was 2.0 kg with a range of 1.4 to 3.2 kg. Five of the eight neonates were premature. Primary pathologies were associated with perforation in seven of the eight neonates. Prematurity, low birth weight and pneumonia were contributing factors to the poor outcome. Sepsis was a complication in seven of the eight neonates leading to their death (88% mortality). Active perinatal management, early treatment of primary pathologies, and protection of the stomach against distension in neonates at risk are essential in the management of neonatal gastric perforation.

Neonatal Hypoglycemia.

PubMed

Thompson-Branch, Alecia; Havranek, Thomas

2017-04-01

Lower blood glucose values are common in the healthy neonate immediately after birth as compared to older infants, children, and adults. These transiently lower glucose values improve and reach normal ranges within hours after birth. Such transitional hypoglycemia is common in the healthy newborn. A minority of neonates experience a more prolonged and severe hypoglycemia, usually associated with specific risk factors and possibly a congenital hypoglycemia syndrome. Despite the lack of a specific blood glucose value that defines hypoglycemia, concern for substantial neurologic morbidity in the neonatal population has led to the generation of guidelines by both the American Academy of Pediatrics (AAP) and the Pediatric Endocrine Society (PES). Similarities between the 2 guidelines include recognition that the transitional form of neonatal hypoglycemia likely resolves within 48 hours after birth and that hypoglycemia that persists beyond that duration may be pathologic. One major difference between the 2 sets of guidelines is the goal blood glucose value in the neonate. This article reviews transitional and pathologic hypoglycemia in the neonate and presents a framework for understanding the nuances of the AAP and PES guidelines for neonatal hypoglycemia. © American Academy of Pediatrics, 2017. All rights reserved.

Neonatal hypertension.

PubMed

Sharma, Deepak; Farahbakhsh, Nazanin; Shastri, Sweta; Sharma, Pradeep

2017-03-01

Neonatal hypertension (HT) is a frequently under reported condition and is seen uncommonly in the intensive care unit. Neonatal HT has defined arbitrarily as blood pressure more than 2 standard deviations above the base as per the age or defined as systolic BP more than 95% for infants of similar size, gestational age and postnatal age. It has been diagnosed long back but still is the least studied field in neonatology. There is still lack of universally accepted normotensive data for neonates as per gestational age, weight and post-natal age. Neonatal HT is an important morbidity that needs timely detection and appropriate management, as it can lead to devastating short-term effect on various organs and also poor long-term adverse outcomes. There is no consensus yet about the treatment guidelines and majority of treatment protocols are based on the expert opinion. Neonate with HT should be evaluated in detail starting from antenatal, perinatal, post-natal history, and drug intake by neonate and mother. This review article covers multiple aspects of neonatal hypertension like definition, normotensive data, various etiologies and methods of BP measurement, clinical features, diagnosis and management.

Effect of Carica papaya Leaf Extract Capsule on Platelet Count in Patients of Dengue Fever with Thrombocytopenia.

PubMed

Gadhwal, Ajeet Kumar; Ankit, B S; Chahar, Chitresh; Tantia, Pankaj; Sirohi, P; Agrawal, R P

2016-06-01

Thrombocytopenia in dengue fever is a common and serious complication. However, no specific treatment is available for dengue fever induced thrombocytopenia. In few countries (Pakistan, Malaysia, Sri Lanka and other Asian countries) the leaf extract of Carica papaya has been effectively used for thrombocytopenia. So, the study is planned to access effect of Carica papaya leaf extract on platelet count in dengue fever patients. All participants were randomised into two groups, study group and control group; the study group was given papaya leaf extract capsule of 500 mg once daily and routine supportive treatment for consecutive five days. The controls were given only routine supportive treatment. Daily complete blood counts, platelet counts and haematocrit level, liver function test, renal function test of both groups were observed. On the first day platelet count of study group and control group was (59.82±18.63, 61.06±20.03 thousands, p value 0.36). On the 2nd day platelet count of both study and control groups was not significantly different (61.67±19.46 and 59.93±19.52 thousands, p value 0.20) but on 3rd day platelet count of study group was significantly higher than control group (82.96±16.72, 66.45±17.36 thousands, p value < 0.01). On 4th and 5th day platelet count of study group (122.43±19.36 and 112.47±17.49 thousands respectively) was also significantly higher than the control group (88.75±21.65 and 102.59±19.35 thousands) (p value < 0.01). On 7th day platelet count of study group and control group were not significantly different (124.47±12.35 and 122.46±19.76 thousands respectively, p value 0.08). Average hospitalization period of study group v/s control group was 3.65±0.97 v/s 5.42±0.98 days (p value < 0.01). Average platelet transfusion requirement in study group was significantly less than control group (0.685 units per patient v/s 1.19 units per patient) (p value <0.01). It is concluded that Carica papaya leaf extract increases the

Utility of the immature platelet fraction in pediatric immune thrombocytopenia: Differentiating from bone marrow failure and predicting bleeding risk.

PubMed

McDonnell, Alicia; Bride, Karen L; Lim, Derick; Paessler, Michele; Witmer, Char M; Lambert, Michele P

2018-02-01

Differentiating childhood immune thrombocytopenia (ITP) from other cause of thrombocytopenia remains a diagnosis of exclusion. Additionally factors that predict bleeding risk for those patients with ITP are currently not well understood. Previous small studies have suggested that immature platelet fraction (IPF) may differentiate ITP from other causes of thrombocytopenia and in combination with other factors may predict bleeding risk. We performed a retrospective chart review of thrombocytopenic patients with an IPF measured between November 1, 2013 and July 1, 2015. Patients were between 2 months and 21 years of age with a platelet count <50 × 10 9 /l. Each patient chart was reviewed for final diagnosis and bleeding symptoms. A bleeding severity score was retrospectively assigned. Two hundred seventy two patients met inclusion criteria, 97 with ITP, 11 with bone marrow failure (BMF), 126 with malignancy, and 38 with other causes of thrombocytopenia. An IPF > 5.2% differentiated ITP from BMF with 93% sensitivity and 91% specificity. Absolute immature platelet number (AIPN) was significantly lower in ITP patients with severe to life-threatening hemorrhage than those without, despite similar platelet counts. On multivariate analysis, an IPF < 10.4% was confirmed as an independent predictor of bleeding risk at platelet counts <10 × 10 9 /l in patients with ITP. IPF measurement alone has utility in both the diagnosis of ITP and identifying patients at increased risk of hemorrhage. Further study is required to understand the pathophysiological differences of ITP patients with lower IPF/AIPN. © 2017 Wiley Periodicals, Inc.

Antibodies against Severe Fever with Thrombocytopenia Syndrome Virus in Healthy Persons, China, 2013

PubMed Central

Zhang, Lei; Sun, Jimin; Yan, Jie; Lv, Huakun; Chai, Chengliang; Sun, Yi; Shao, Bin; Jiang, Jianmin; Chen, Zhiping

2014-01-01

In June 2013, a subclinical infection with severe fever with thrombocytopenia syndrome virus (SFTSV) was detected in Zhejiang Province, China, prompting seroprevalence studies in 6 districts within the province. Of 986 healthy persons tested, 71 had IgG antibodies against SFTSV. This finding suggests that most natural infections with SFTSV are mild or subclinical. PMID:25061813

The trans-sialidase from Trypanosoma cruzi induces thrombocytopenia during acute Chagas' disease by reducing the platelet sialic acid contents.

PubMed

Tribulatti, María Virginia; Mucci, Juan; Van Rooijen, Nico; Leguizamón, María Susana; Campetella, Oscar

2005-01-01

Strong thrombocytopenia is observed during acute infection with Trypanosoma cruzi, the parasitic protozoan agent of American trypanosomiasis or Chagas' disease. The parasite sheds trans-sialidase, an enzyme able to mobilize the sialyl residues on cell surfaces, which is distributed in blood and is a virulence factor. Since the sialic acid content on the platelet surface is crucial for determining the half-life of platelets in blood, we examined the possible involvement of the parasite-derived enzyme in thrombocytopenia induction. We found that a single intravenous injection of trans-sialidase into naive mice reduced the platelet count by 50%, a transient effect that lasted as long as the enzyme remained in the blood. CD43(-/-) mice were affected to a similar extent. When green fluorescent protein-expressing platelets were treated in vitro with trans-sialidase, their sialic acid content was reduced together with their life span, as determined after transfusion into naive animals. No apparent deleterious effect on the bone marrow was observed. A central role for Kupffer cells in the clearance of trans-sialidase-altered platelets was revealed after phagocyte depletion by administration of clodronate-containing liposomes and splenectomy. Consistent with this, parasite strains known to exhibit more trans-sialidase activity induced heavier thrombocytopenia. Finally, the passive transfer of a trans-sialidase-neutralizing monoclonal antibody to infected animals prevented the clearance of transfused platelets. Results reported here strongly support the hypothesis that the trans-sialidase is the virulence factor that, after depleting the sialic acid content of platelets, induces the accelerated clearance of the platelets that leads to the thrombocytopenia observed during acute Chagas' disease.

Women's attitude towards routine human platelet antigen-screening in pregnancy.

PubMed

Winkelhorst, Dian; Loeff, Rosanne M; van den Akker-Van Marle, M Elske; de Haas, Masja; Oepkes, Dick

2017-08-01

Fetal and neonatal alloimmune thrombocytopenia is a potentially life-threatening disease with excellent preventative treatment available for subsequent pregnancies. To prevent index cases, the effectiveness of a population-based screening program has been suggested repeatedly. Therefore, we aimed to evaluate women's attitude towards possible future human platelet antigen-screening in pregnancy. We performed a cross-sectional questionnaire study among healthy pregnant women receiving prenatal care in one of seven participating midwifery practices. Attitude was assessed using a questionnaire based on the validated Multidimensional Measurement of Informed Choice model, containing questions assessing knowledge, attitude and intention to participate. A total of 143 of the 220 women (65%) completed and returned the questionnaire. A positive attitude towards human platelet antigen-screening was expressed by 91% of participants, of which 94% was based on sufficient knowledge. Attitude was more likely to be negatively influenced by the opinion that screening can be frightening. Informed choices were made in 87% and occurred significantly less in women from non-European origin, 89% in European women vs. 60% in non-European women (p = 0.03). Pregnant women in the Netherlands expressed a positive attitude towards human platelet antigen-screening in pregnancy. We therefore expect a high rate of informed uptake when human platelet antigen-screening is implemented. In future counseling on human platelet antigen-screening, ethnicity and possible anxiety associated with a screening test need to be specifically addressed. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

Congenital amegakaryocytic thrombocytopenia in three siblings: molecular analysis of atypical clinical presentation.

PubMed

Gandhi, Manish J; Pendergrass, Thomas W; Cummings, Carrie C; Ihara, Kenji; Blau, C Anthony; Drachman, Jonathan G

2005-10-01

An 11-year-old girl, presenting with fatigue and bruising, was found to be profoundly pancytopenic. Bone marrow exam and clinical evaluation were consistent with aplastic anemia. Family members were studied as potential stem cell donors, revealing that both younger siblings displayed significant thrombocytopenia, whereas both parents had normal blood counts. We evaluated this pedigree to understand the unusually late presentation of congenital amegakaryocytic thrombocytopenia (CAMT). The coding region and the intron/exon junctions of MPL were sequenced from each family member. Vectors representing each of the mutations were constructed and tested for the ability to support growth of Baf3/Mpl(mutant) cells. All three siblings had elevated thrombopoietin levels. Analysis of genomic DNA demonstrated that each parent had mutations/polymorphisms in a single MPL allele and that each child was a compound heterozygote, having inherited both abnormal alleles. The maternal allele encoded a mutation of the donor splice-junction at the exon-3/intron-3 boundary. A mini-gene construct encoding normal vs mutant versions of the intron-3 donor-site demonstrated that physiologic splicing was significantly reduced in the mutant construct. Mutations that incompletely eliminate Mpl expression/function may result in delayed diagnosis of CAMT and confusion with aplastic anemia.

Heparin-induced thrombocytopenia: real-world issues.

PubMed

Linkins, Lori-Ann; Warkentin, Theodore E

2011-09-01

Heparin-induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by platelet-activating antibodies. HIT sera often activate platelets without needing heparin-such heparin-"independent" platelet activation can be associated with HIT beginning or worsening despite stopping heparin ("delayed-onset HIT"). We address important issues in HIT diagnosis and therapy, using a recent cohort of HIT patients to illustrate influences of heparin type; triggers for HIT investigation; serological features of heparin-independent platelet activation; and treatment. In our cohort of recent HIT cases ( N = 13), low-molecular-weight heparin (dalteparin) was a common causative agent ( N = 8, 62%); most patients were diagnosed after HIT-thrombosis had occurred; and danaparoid was the most frequently selected treatment. Heparin-independent platelet activation was common (7/13 [54%]) and predicted slower platelet count recovery (>1 week) among evaluable patients (5/5 vs 1/6; P = 0.015). In our experience with argatroban-treated patients, HIT-associated consumptive coagulopathy confounds anticoagulant monitoring. Our observations provide guidance on practical aspects of HIT diagnosis and management. Thieme Medical Publishers.

Primary anti-phospholipid antibody syndrome causing recurrent venous thrombosis and thrombocytopenia in a patient with Addison's disease.

PubMed

Elebrashy, Ibrahim; Yousief, Elham; Saif, Aasem

2014-12-01

We report a case of Addison's disease presenting with recurrent deep venous thrombosis and thrombocytopenia and proved to have primary anti-phospholipid antibody syndrome. The case report highlights the shared autoimmune nature of both diseases.

Advancing Neurologic Care in the Neonatal Intensive Care Unit with a Neonatal Neurologist

PubMed Central

Mulkey, Sarah B.; Swearingen, Christopher J.

2014-01-01

Neonatal neurology is a growing sub-specialty area. Given the considerable amount of neurologic problems present in the neonatal intensive care unit, a neurologist with expertise in neonates is becoming more important. We sought to evaluate the change in neurologic care in the neonatal intensive care unit at our tertiary care hospital by having a dedicated neonatal neurologist. The period post-neonatal neurologist showed a greater number of neurology consultations (P<0.001), number of neurology encounters per patient (P<0.001), a wider variety of diagnoses seen, and an increase in the use of video-electroencephalography (P=0.022), compared to the pre-neonatal neurologist period. The neonatologists expressed appreciation for having a dedicated neurologist available. Standardized protocols for treating hypoxic-ischemic encephalopathy and neonatal seizures were also developed. Overall, by having a neonatal neurologist, neurology became part of the multi-disciplinary team providing focused neurologic care to newborns. PMID:23271754

Bim regulates alloimmune-mediated vascular injury through effects on T-cell activation and death.

PubMed

von Rossum, Anna; Enns, Winnie; Shi, Yu P; MacEwan, Grace E; Malekesmaeli, Mehrnoush; Brinkman, Ryan; Choy, Jonathan C

2014-06-01

Bim is a proapoptotic Bcl-2 protein known to downregulate immune responses and to also be required for antigen-induced T-cell activation. However, it is not known how the effect of Bim on these offsetting processes determines the outcome of allogeneic immune responses. We have defined the role of Bim in regulating alloantigen-driven T-cell responses in a model of vascular rejection. Bim was required for proliferation of CD4 and CD8 T cells, and for interleukin-2 production, in T cells stimulated with alloantigen in vitro. Moreover, a partial reduction in Bim expression was sufficient to attenuate T-cell activation, whereas a complete elimination of Bim was required to prevent CD4 T-cell death in response to cytokine withdrawl. When alloimmune-mediated vascular rejection was examined using an aortic interposition model, there was significantly less intimal thickening in Bim(+/-), but not Bim(-/-), graft recipients. T-cell proliferation in response to allograft arteries was significantly reduced in both Bim(+/-) and Bim(-/-) mice, but cell death was attenuated only in Bim(-/-) animals. Bim controls both T-cell activation and death in response to alloantigen stimulation. These processes act cooperatively to determine the outcome of immune responses in allograft arteries. © 2014 American Heart Association, Inc.

Laboratory Testing Protocols for Heparin-Induced Thrombocytopenia (HIT) Testing.

PubMed

Lau, Kun Kan Edwin; Mohammed, Soma; Pasalic, Leonardo; Favaloro, Emmanuel J

2017-01-01

Heparin-induced thrombocytopenia (HIT) represents a significant high morbidity complication of heparin therapy. The clinicopathological diagnosis of HIT remains challenging for many reasons; thus, laboratory testing represents an important component of an accurate diagnosis. Although there are many assays available to assess HIT, these essentially fall into two categories-(a) immunological assays, and (b) functional assays. The current chapter presents protocols for several HIT assays, being those that are most commonly performed in laboratory practice and have the widest geographic distribution. These comprise a manual lateral flow-based system (STiC), a fully automated latex immunoturbidimetric assay, a fully automated chemiluminescent assay (CLIA), light transmission aggregation (LTA), and whole blood aggregation (Multiplate).

A case report of neonatal diabetes due to neonatal hemochromatosis.

PubMed

Cetinkaya, Semra; Kunak, Benal; Kara, Cengiz; Demirçeken, Fulya; Yarali, Neşe; Polat, Emine; Aycan, Zehra

2010-05-01

A 6-week-old girl, the first child of non-consanguineous parents, was admitted to the hospital for evaluation of vomiting. She was small for gestational age (1500 g). On admission, she weighed 1830 g, and appeared dehydrated. The blood glucose was 880 mg/dL. Insulin and C-peptide levels were <1 microIU/ml and 0.1 pmol/L, respectively. Antibodies of diabetes were negative. The serum triglyceride level was markedly elevated (5322 mg/dL). After a few days of insulin therapy, the triglyceride levels dramatically decreased, but cholestasis persisted. A liver biopsy revealed diffuse iron deposition and the diagnosis of neonatal hemochromatosis was established. In neonatal hemochromatosis, diabetes may occur as a result of iron deposition in the pancreas. The coexistence of neonatal diabetes secondary to neonatal hemochromatosis with a fatal course during the infancy period has not been previously reported. In this report, an infant with neonatal diabetes secondary to neonatal hemochromatosis is presented as the first case in the literature involving the coexistence of these two conditions.

United Kingdom immune thrombocytopenia registry: retrospective evaluation of bone marrow fibrosis in adult patients with primary immune thrombocytopenia and correlation with clinical findings.

PubMed

Rizvi, Hasan; Butler, Tom; Calaminici, Mariarita; Doobaree, Indraraj U; Nandigam, Raghava C; Bennett, Dimitri; Provan, Drew; Newland, Adrian C

2015-05-01

Fibrosis has been reported in some patients with immune thrombocytopenia (ITP) treated with thrombopoietin receptor agonists (TPO-RA). However, fibrosis has also been reported in patients with various stages of ITP, who were TPO-RA treatment-naïve. In our study, we looked for fibrosis in bone marrow trephine biopsies taken at initial diagnosis from 32 adult patients with ITP. Ten of the 32 evaluated samples (31·25%) showed increased reticulin (Grade 1-2 on Bauermeister scale and Grade 0-1 on the European Consensus scale), which showed a positive correlation with ethnicity (0·3%) but did not correlate with disease severity, any clinical features or co-morbidities. © 2015 John Wiley & Sons Ltd.

PDGFRα promoter polymorphisms and expression patterns influence risk of development of imatinib-induced thrombocytopenia in chronic myeloid leukemia: A study from India.

PubMed

Guru, Sameer Ahmad; Mir, Rashid; Bhat, Musadiq; Najar, Imtiyaz; Zuberi, Mariyam; Sumi, Mamta; Masroor, Mirza; Gupta, Naresh; Saxena, Alpana

2017-10-01

Platelet-derived growth factor receptor has been implicated in many malignant and non-malignant diseases. Platelet-derived growth factor receptor-α is a tyrosine kinase and a side target for imatinib, a revolutionary drug for the treatment of chronic myeloid leukemia that has dramatically improved the survival of chronic myeloid leukemia patients. Given the importance of platelet-derived growth factor receptor in platelet development and its inhibition by imatinib, it was intriguing to analyze the role of platelet-derived growth factor receptor-α in relation to imatinib treatment in the development of imatinib-induced thrombocytopenia in chronic myeloid leukemia patients. We hypothesized that two known functional polymorphisms, +68GA insertion/deletion and -909C/A, in the promoter region of the platelet-derived growth factor receptor-α gene may affect the susceptibility of chronic myeloid leukemia patients receiving imatinib treatment to the development of thrombocytopenia. A case-control study was conducted among a cohort of chronic myeloid leukemia patients admitted to the Lok Nayak Hospital, New Delhi, India. A set of 100 patients of chronic myeloid leukemia in chronic phase and 100 age- and sex-matched healthy controls were studied. After initiation of imatinib treatment, the hematological response of chronic myeloid leukemia patients was monitored regularly for 2 years, in which the development of thrombocytopenia was the primary end point. Platelet-derived growth factor receptor-α promoter polymorphisms +68GA ins/del and -909C/A were studied by allele-specific polymerase chain reaction. Platelet-derived growth factor receptor-α messenger RNA expression was evaluated by quantitative real-time polymerase chain reaction. The messenger RNA expression results were expressed as 2 -Δct ± standard deviation. The distribution of +68GA ins/del promoter polymorphism genotypes differed significantly between the thrombocytopenic and non-thrombocytopenic chronic

Maternal or neonatal infection: association with neonatal encephalopathy outcomes

PubMed Central

Jenster, Meike; Bonifacio, Sonia L.; Ruel, Theodore; Rogers, Elizabeth E.; Tam, Emily W.; Partridge, John Colin; Barkovich, A. James; Ferriero, Donna M.; Glass, Hannah C.

2014-01-01

Background Perinatal infection may potentiate brain injury among children born preterm. The objective of this study was to examine whether maternal and/or neonatal infection are associated with adverse outcomes among term neonates with encephalopathy. Methods Cohort study of 258 term newborns with encephalopathy whose clinical records were examined for signs of maternal infection (chorioamnionitis) and infant infection (sepsis). Multivariate regression was used to assess associations between infection, pattern and severity of injury on neonatal MRI, as well as neurodevelopment at 30 months (neuromotor exam, or Bayley Scales of Infant Development II MDI <70 or Bayley III cognitive score <85). Results Chorioamnionitis was associated with lower risk of moderate-severe brain injury (adjusted OR 0.3; 95% CI 0.1–0.7, P=0.004), and adverse cognitive outcome in children when compared to no chorioamnionitis. Children with signs of neonatal sepsis were more likely to exhibit watershed predominant injury than those without (P=0.007). Conclusions Among neonates with encephalopathy, chorioamnionitis was associated with a lower risk of brain injury and adverse outcomes, whereas signs of neonatal sepsis carried an elevated risk. The etiology of encephalopathy and timing of infection and its associated inflammatory response may influence whether infection potentiates or mitigates injury in term newborns. PMID:24713817

Mechanism Underlying Linezolid-induced Thrombocytopenia in a Chronic Kidney Failure Mouse Model

PubMed Central

Nishijo, Nao; Tsuji, Yasuhiro; Matsunaga, Kazuhisa; Kutsukake, Masahiko; Okazaki, Fumiyasu; Fukumori, Shiro; Kasai, Hidefumi; Hiraki, Yoichi; Sakamaki, Ippei; Yamamoto, Yoshihiro; Karube, Yoshiharu; To, Hideto

2017-01-01

Objective: To investigate the relationship between renal function and linezolid (LZD)-induced thrombocytopenia and elucidate the underlying mechanism using a chronic renal disease (CRD) mouse model. Materials and Methods: CRD was induced in 5-week-old male Institute of Cancer Research (ICR) mice by 5/6 nephrectomy. After this procedure, LZD (25 and 100 mg/kg) was administered intraperitoneally once every day for 28 days. Platelet counts, white blood cell (WBC) counts, and hematocrit (HCT) levels were measured every 7 days. 2-14C-thymidine (0.185 MBq) was administrated intravenously to LZD-administered mice to evaluate the thymidine uptake ability of bone marrow. Results: Platelet counts were significantly lower in the LZD-administered CRD group than in the LZD-nonadministered groups at 14, 21, and 28 days (P < 0.05); however, these changes were not observed in LZD-administered mice with normal renal function, regardless of the duration of LZD administration. No significant changes were observed in WBC counts or HCT levels in any LZD-administered CRD mouse. Moreover, radioactive levels in bone marrow were not significantly different in each group. Conclusions: These results indicate that LZD-induced decreases in platelet counts were enhanced by renal impairment in vivo, suggesting that LZD-induced thrombocytopenia is not caused by nonimmune-mediated bone marrow suppression. PMID:28405130

Neonatal hypocalcemia, neonatal seizures, and intellectual disability in 22q11.2 deletion syndrome

PubMed Central

Cheung, Evelyn Ning Man; George, Susan R.; Andrade, Danielle M.; Chow, Eva W. C.; Silversides, Candice K.; Bassett, Anne S.

2015-01-01

Purpose Hypocalcemia is a common endocrinological condition in 22q11.2 deletion syndrome. Neonatal hypocalcemia may affect neurodevelopment. We hypothesized that neonatal hypocalcemia would be associated with rare, more severe forms of intellectual disability in 22q11.2 deletion syndrome. Methods We used a logistic regression model to investigate potential predictors of intellectual disability severity, including neonatal hypocalcemia, neonatal seizures, and complex congenital heart disease, e.g., interrupted aortic arch, in 149 adults with 22q11.2 deletion syndrome. Ten subjects had moderate-to-severe intellectual disability. Results The model was highly significant (P < 0.0001), showing neonatal seizures (P = 0.0018) and neonatal hypocalcemia (P = 0.047) to be significant predictors of a more severe level of intellectual disability. Neonatal seizures were significantly associated with neonatal hypocalcemia in the entire sample (P < 0.0001), regardless of intellectual level. There was no evidence for the association of moderate- to-severe intellectual disability with other factors such as major structural brain malformations in this sample. Conclusion The results suggest that neonatal seizures may increase the risk for more severe intellectual deficits in 22q11.2 deletion syndrome, likely mediated by neonatal hypocalcemia. Neonatal hypocalcemia often remains unrecognized until the postseizure period, when damage to neurons may already have occurred. These findings support the importance of early recognition and treatment of neonatal hypocalcemia and potentially neonatal screening for 22q11.2 deletions. PMID:23765047

Fetal and neonatal thyrotoxicosis

PubMed Central

Batra, Chandar Mohan

2013-01-01

Fetal thyrotoxicosis is a rare disease occurring in 1 out of 70 pregnancies with Grave's disease or in 1 out of 4000-50,000 deliveries. The mortality is 12-20%, usually from heart failure, but other complications are tracheal compression, infections and thrombocytopenia. It results from transfer of thyroid stimulating immunoglobulins from mother to fetus through the placenta. This transplacental transfer begins around 20th week of pregnancy and reaches its maximum by 30th week. These autoantibodies bind to the fetal thyroid stimulating hormone (TSH) receptors and increase the secretion of the thyroid hormones. The mother has an active autoimmune thyroid disease or has been treated for it in the past. She may be absolutely euthyroid due to past treatment by drugs, surgery or radioiodine ablation, but still have active TSH receptor stimulating autoantibodies, which can cause fetal thyrotoxicosis. The other features of this disease are fetal tachycardia, fetal goiter and history of spontaneous abortions and findings of goiter, ascites, craniosyntosis, fetal growth retardation, maceration and hydrops at fetal autopsy. If untreated, this disease can result in intrauterine death. The treatment for this disease consists of giving carbimazole to the mother, which is transferred through the placenta to the fetus. The dose of carbimazole is titrated with the fetal heart rate. If the mother becomes hypothyroid due to carbimazole, thyroxine is added taking advantage of the fact that very little of thyroxine is transferred across the placenta. Neonatal thyrotoxicosis patients are very sick and require emergency treatment. The goal of the treatment is to normalize thyroid functions as quickly as possible, to avoid iatrogenic hypothyroidism while providing management and supportive therapy for the infant's specific signs and symptoms. PMID:24251220

Neonatal sepsis

MedlinePlus

... BE. Perinatal viral infections. In Martin RJ, Fanaroff AA, Walsh MC, eds. Fanaroff and Martin's Neonatal-Perinatal ... K. Postnatal bacterial infections. In Martin RJ, Fanaroff AA, Walsh MC, eds. Fanaroff and Martin's Neonatal-Perinatal ...

Thrombotic thrombocytopenic purpura or immune thrombocytopenia in a sickle cell/β+-thalassemia patient: a rare and challenging condition.

PubMed

Vlachaki, Efthymia; Agapidou, Aleka; Neokleous, Nikolaos; Adamidou, Despoina; Vetsiou, Evaggelia; Boura, Panagiota

2014-10-01

The diagnosis of thrombotic thrombocytopenic purpura is one of the possible diagnosis when a patient is admitted with unexpected micro-angiopathic hemolytic anemia and thrombocytopenia. The combination of sickle cell/β(+)-thalassemia and thrombotic thrombocytopenic purpura is rare and triggering. This article describes the poor outcome of a patient with sickle cell/β(+)-thalassemia presenting with gingival bleeding, severe thrombocytopenia and anemia. The patient had normal renal function, no neurological deficit and he was initially treated as immune thrombocytopenic purpura. He eventually died due to multi-organ failure and brain hemorrhage even though he had started plasma exchange sessions. The co-existence of thrombotic thrombocytopenic purpura and sickle cell anemia is making the diagnosis of the former difficult. Early and rapid intervention is critical to the outcome. Copyright © 2014 Elsevier Ltd. All rights reserved.

Maternal or neonatal infection: association with neonatal encephalopathy outcomes.

PubMed

Jenster, Meike; Bonifacio, Sonia L; Ruel, Theodore; Rogers, Elizabeth E; Tam, Emily W; Partridge, John Colin; Barkovich, Anthony James; Ferriero, Donna M; Glass, Hannah C

2014-07-01

Perinatal infection may potentiate brain injury among children born preterm. The objective of this study was to examine whether maternal and/or neonatal infection are associated with adverse outcomes among term neonates with encephalopathy. This study is a cohort study of 258 term newborns with encephalopathy whose clinical records were examined for signs of maternal infection (chorioamnionitis) and infant infection (sepsis). Multivariate regression was used to assess associations between infection, pattern, and severity of injury on neonatal magnetic resonance imaging, as well as neurodevelopment at 30 mo (neuromotor examination, or Bayley Scales of Infant Development, second edition mental development index <70 or Bayley Scales of Infant Development, third edition cognitive score <85). Chorioamnionitis was associated with lower risk of moderate-severe brain injury (adjusted odds ratio: 0.3; 95% confidence interval: 0.1-0.7; P = 0.004) and adverse cognitive outcome in children when compared with no chorioamnionitis. Children with signs of neonatal sepsis were more likely to exhibit watershed predominant injury than those without (P = 0.007). Among neonates with encephalopathy, chorioamnionitis was associated with a lower risk of brain injury and adverse outcomes, whereas signs of neonatal sepsis carried an elevated risk. The etiology of encephalopathy and timing of infection and its associated inflammatory response may influence whether infection potentiates or mitigates injury in term newborns.

Utility of Targeted Neonatal Echocardiography in the Management of Neonatal Illness.

PubMed

Harabor, Andrei; Soraisham, Amuchou Singh

2015-07-01

To describe the impact of targeted neonatal echocardiography on management of neonatal illness in a tertiary perinatal center neonatal intensive care unit (NICU). We conducted a retrospective analysis of consecutive targeted neonatal echocardiographic studies that were performed over an 18-month period in a regional perinatal center NICU in Canada. All studies were performed with a cardiovascular ultrasound machine and transducer and read on a workstation with storage and analysis software. Reporting was done on a standardized document, and any management change resulting from targeted neonatal echocardiography was documented. A total of 303 consecutive targeted neonatal echocardiographic studies were performed on 129 neonates. The mean gestational age ± SD was 27.8 ± 4.3 weeks (range, 23-41 weeks), and the mean birth weight ± SD was 1196 ± 197 g (range, 490- 4500 g). The median number of studies per neonate was 2 (range, 1-8), with most repeated studies for a patent ductus arteriosus (PDA). The most common indication for echocardiography was assessment of a PDA (52.1%), followed by early global hemodynamic assessment of very low birth weight (16.2%) and pulmonary hypertension (12.2%). Of the 303 studies, 126 (41.5%) resulted in management changes. The contribution to management was significantly related to the timing of echocardiography. Around half of the echocardiographic examinations during first the week of life resulted in management changes, compared to 22% of studies after 1 week of age (P = .002). Patent ductus arteriosus management accounted for almost half of the interventions. Targeted neonatal echocardiography is a valuable tool in the NICU and can contribute substantially to hemodynamic management in the first week of life, PDA management in the first 2 weeks of life, and cases of hypotension or shock at any time during the hospital stay. © 2015 by the American Institute of Ultrasound in Medicine.

Chickens treated with a nitric oxide inhibitor became more resistant to Plasmodium gallinaceum infection due to reduced anemia, thrombocytopenia and inflammation

PubMed Central

2013-01-01

Malaria is a serious infectious disease caused by parasites of the Plasmodium genus that affect different vertebrate hosts. Severe malaria leads to host death and involves different pathophysiological phenomena such as anemia, thrombocytopenia and inflammation. Nitric oxide (NO) is an important effector molecule in this disease, but little is known about its role in avian malaria models. Plasmodium gallinaceum- infected chickens were treated with aminoguanidine (AG), an inhibitor of inducible nitric oxide synthase, to observe the role of NO in the pathogenesis of this avian model. AG increased the survival of chickens, but also induced higher parasitemia. Treated chickens demonstrated reduced anemia and thrombocytopenia. Moreover, erythrocytes at different stages of maturation, heterophils, monocytes and thrombocytes were infected by Plasmodium gallinaceum and animals presented a generalized leucopenia. Activated leukocytes and thrombocytes with elongated double nuclei were observed in chickens with higher parasitemia; however, eosinophils were not involved in the infection. AG reduced levels of hemozoin in the spleen and liver, indicating lower inflammation. Taken together, the results suggest that AG reduced anemia, thrombocytopenia and inflammation, explaining the greater survival rate of the treated chickens. PMID:23398940

Use of Fondaparinux Off-Label or Approved Anticoagulants for Management of Heparin-Induced Thrombocytopenia.

PubMed

Schindewolf, Marc; Steindl, Julia; Beyer-Westendorf, Jan; Schellong, Sebastian; Dohmen, Pascal Maria; Brachmann, Johannes; Madlener, Katharina; Pötzsch, Bernd; Klamroth, Robert; Hankowitz, Johannes; Banik, Norbert; Eberle, Sonja; Müller, Markus Michael; Kropff, Stefan; Lindhoff-Last, Edelgard

2017-11-28

Life-threatening heparin-induced thrombocytopenia (HIT) is treated with the alternative nonheparin anticoagulants argatroban, lepirudin, or danaparoid. Frequently, the pentasaccharide fondaparinux is used off-label. The authors sought to investigate the safety and efficacy of the different anticoagulants for treating HIT. In a national, multicenter registry study, hospitalized patients who were diagnosed with HIT, an at least intermediate clinical HIT-risk (4Ts score ≥4 points), and received treatment with ≥1 dose of the aforementioned anticoagulants were included. Main outcome measures were the incidences of HIT-specific complications (thromboembolic venous/arterial events, amputations, recurrent/persistent thrombocytopenia, skin lesions) and bleedings. Of 195 patients, 46 (23.6%), 4 (2.1%), 61 (31.3%), and 84 (43.1%) had been treated first-line with argatroban, lepirudin, danaparoid, and fondaparinux, respectively. The composite endpoint of HIT-specific complications (thromboembolic events, amputation, skin necrosis) occurred in 11.7% of patients treated with approved alternative anticoagulation and in 0.0% of fondaparinux-treated patients. The all-cause in-hospital mortality rates were 14.4% during approved alternative anticoagulation and 0.0% during fondaparinux treatment. Bleeding complications occurred in alternatively anticoagulated patients and in fondaparinux-treated patients in 6.3% and 4.8%, respectively. Post hoc analysis of clinical and laboratory features confirmed "true" HIT in at least 74 of 195 (38.0%) patients; 35 of 74 (47.3%) were treated with fondaparinux. Fondaparinux is effective and safe in suspected acute HIT; no HIT-specific complications occurred in the fondaparinux-treated patients, even among those with a high clinical HIT probability. Further data from randomized controlled trials are urgently needed because lepirudin was recalled from the market; danaparoid access has been limited and is not approved in the United States; and

[Neonatal transport characteristics].

PubMed

Baleine, Julien Frédéric; Fournier-Favre, Patricia; Fabre, Agnès

2016-01-01

Neonatal transport is necessary where a neonate is transferred between two care units. It provides all the skills of a dedicated team, representing a real mobile neonatal intensive care unit. Informing and involving the families is essential during this transport, which can be a source of stress for the child and its family. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Bim Regulates Alloimmune-Mediated Vascular Injury Through Effects on T Cell Activation and Death

PubMed Central

von Rossum, Anna; Enns, Winnie; Shi, Yu P.; MacEwan, Grace E.; Malekesmaeli, Mehrnoush; Brinkman, Ryan; Choy, Jonathan C.

2014-01-01

Objective Bim is a pro-apoptotic Bcl-2 protein known to down-regulate immune responses and to also be required for antigen-induced T cell activation. However, it is not known how the effect of Bim on these offsetting processes determines the outcome of allogeneic immune responses. We have defined the role of Bim in regulating alloantigen-driven T cell responses in a model of vascular rejection. Approach and Results Bim was required for proliferation of CD4 and CD8 T cells, and for IL-2 production, in T cells stimulated with alloantigen in vitro. Moreover, a partial reduction in Bim expression was sufficient to attenuate T cell activation whereas a complete elimination of Bim was required to prevent CD4 T cell death in response to cytokine withdrawl. When alloimmune-mediated vascular rejection was examined using an aortic interposition model, there was significantly less intimal thickening in Bim+/−, but not Bim−/−, graft recipients. T cell proliferation in response to allograft arteries was significantly reduced in both Bim+/− and Bim−/− mice, but cell death was attenuated only in Bim−/− animals. Conclusions Bim controls both T cell activation and death in response to alloantigen stimulation. These processes act cooperatively to determine the outcome of immune responses in allograft arteries. PMID:24700126

Management of neonatal abstinence syndrome in neonates born to opioid maintained women.

PubMed

Ebner, Nina; Rohrmeister, Klaudia; Winklbaur, Bernadette; Baewert, Andjela; Jagsch, Reinhold; Peternell, Alexandra; Thau, Kenneth; Fischer, Gabriele

2007-03-16

Neonates born to opioid-maintained mothers are at risk of developing neonatal abstinence syndrome (NAS), which often requires pharmacological treatment. This study examined the effect of opioid maintenance treatment on the incidence and timing of NAS, and compared two different NAS treatments (phenobarbital versus morphine hydrochloride). Fifty-three neonates born to opioid-maintained mothers were included in this study. The mothers received methadone (n=22), slow-release oral morphine (n=17) or buprenorphine (n=14) throughout pregnancy. Irrespective of maintenance treatment, all neonates showed APGAR scores comparable to infants of non-opioid dependent mothers. No difference was found between the three maintenance groups regarding neonatal weight, length or head circumference. Sixty percent (n=32) of neonates required treatment for NAS [68% in the methadone-maintained group (n=15), 82% in the morphine-maintained group (n=14), and 21% in the buprenorphine-maintained group (n=3)]. The mean duration from birth to requirement of NAS treatment was 33 h for the morphine-maintained group, 34 h for the buprenorphine-maintained group and 58 h for the methadone-maintained group. In neonates requiring NAS treatment, those receiving morphine required a significantly shorter mean duration of treatment (9.9 days) versus those treated with phenobarbital (17.7 days). Results suggest that morphine hydrochloride is preferable for neonates suffering NAS due to opioid withdrawal.

Neonatal fluid management.

PubMed

Murat, Isabelle; Humblot, Alexis; Girault, Laure; Piana, Federica

2010-09-01

Perioperative fluid management in paediatrics has been the subject of many controversies in recent years, but fluid management in the neonatal period has not been considered in most reviews and guidelines. The literature regarding neonatal fluid management mainly appears in the paediatric textbooks and few recent data are available, except for resuscitation and fluid loading during shock and major surgery. In the context of anaesthesia, many neonates requiring surgery within the first month of life have organ malformation and/or dysfunction. This article aims at reviewing basic physiological considerations important for neonatal fluid management and mainly focusses on fluid maintenance and replacement during surgery.

[Heparin-induced thrombocytopenia type II (HIT II) : A medical-economic view].

PubMed

Riedel, R; Schmieder, A; Koster, A; Kim, S; Baumgarten, G; Schewe, J C

2017-05-01

In the context of inpatient and increasingly ambulatory thrombosis prophylaxis, heparins have been recognised as standard therapy for decades. In addition to the therapeutic benefit, therapy with heparins also entails the risk of undesirable side effects, such as bleeding and thrombocytopenia. Heparin-induced thrombocytopenia (HIT II) is deemed a serious side effect. In the following work, HIT II is subjected to a medico-economic consideration (treatment, pharmaceuticals, subsequent costs due to possible complications) and, with regard to a possible HIT II prophylaxis, aspects of increasingly respected patient safety are also considered. In the context of a literature search the active ingredients argatroban and danaparoid, which are approved for HIT II treatment, were evaluated. HIT II - especially in combination with thromboembolic complications - represents a medical-economic burden for the hospital. Although this is only an orientation guide, it shows that HIT II syndrome is not adequately cost-covered by the G‑DRG system. An early thrombosis prophylaxis with argatroban/danaparoid for HIT II risk patients should therefore be taken into account for medical-related as well as patient safety-relevant aspects. According to experience, the pharmaceutical supply for these medically needed products (anticoagulants) should be ensured for reasons of patient safety. The risk of an immunological response to heparin therapy is known. Within the context of increased patient safety, thrombosis prophylaxis should be issued with a risk-adjusted prophylaxis.

Neonatal pain

PubMed Central

Walker, Suellen M

2014-01-01

Effective management of procedural and postoperative pain in neonates is required to minimize acute physiological and behavioral distress and may also improve acute and long-term outcomes. Painful stimuli activate nociceptive pathways, from the periphery to the cortex, in neonates and behavioral responses form the basis for validated pain assessment tools. However, there is an increasing awareness of the need to not only reduce acute behavioral responses to pain in neonates, but also to protect the developing nervous system from persistent sensitization of pain pathways and potential damaging effects of altered neural activity on central nervous system development. Analgesic requirements are influenced by age-related changes in both pharmacokinetic and pharmacodynamic response, and increasing data are available to guide safe and effective dosing with opioids and paracetamol. Regional analgesic techniques provide effective perioperative analgesia, but higher complication rates in neonates emphasize the importance of monitoring and choice of the most appropriate drug and dose. There have been significant improvements in the understanding and management of neonatal pain, but additional research evidence will further reduce the need to extrapolate data from older age groups. Translation into improved clinical care will continue to depend on an integrated approach to implementation that encompasses assessment and titration against individual response, education and training, and audit and feedback. PMID:24330444

Mild thrombocytopenia as presenting symptom of type 1 Gauchers's disease.

PubMed

Müzes, G; Pitlik, E; Somogyi, A; Tulassay, Z

2001-06-01

A young woman was examined for a mild thrombocytopenia which was present for some months. No signs of bleeding had so far occurred. Physical examination was normal except for a moderately enlarged spleen. Laboratory investigations showed a low platelet count. There was no evidence of an autoimmune or hematologic disease. Bone narrow aspirate indicated Gaucher's-like cells raising the suspicion of Gaucher's disease. This was further supported by electron microscopic demonstration of Gaucher's bodies in crista biopsy specimens. However, the definitive diagnosis was obtained by verifying deficient lysosomal glucosylceramide-beta-D-glucosidase activity in peripheral blood leukocytes. Upon the absence of neurologic involvement the patient was typical for the adult-onset or type 1 form of Gaucher's disease.

Design of the rivaroxaban for heparin-induced thrombocytopenia study.

PubMed

Linkins, Lori-Ann; Warkentin, Theodore E; Pai, Menaka; Shivakumar, Sudeep; Manji, Rizwan A; Wells, Philip S; Crowther, Mark A

2014-11-01

Rivaroxaban is an ideal potential candidate for treatment of heparin-induced thrombocytopenia (HIT) because it is administered orally by fixed dosing, requires no laboratory monitoring and is effective in the treatment of venous and arterial thromboembolism in other settings. The Rivaroxaban for HIT study is a prospective, multicentre, single-arm, cohort study evaluating the incidence of new symptomatic venous and arterial thromboembolism in patients with suspected or confirmed HIT who are treated with rivaroxaban. Methodological challenges faced in the design of this study include heterogeneity of the patient population, differences in the baseline risk of thrombosis and bleeding dependent on whether HIT is confirmed or just suspected, and heterogeneity in laboratory confirmation of HIT. The rationale for how these challenges were addressed and the final design of the Rivaroxaban for HIT study is reviewed.

Low-level light treatment ameliorates immune thrombocytopenia

NASA Astrophysics Data System (ADS)

Yang, Jingke; Zhang, Qi; Wu, Mei X.

2017-02-01

Immune thrombocytopenia (ITP) is an immune-mediated acquired bleeding disorder characterized by abnormally low platelet counts. We reported here the ability of low-level light treatment (LLLT) to alleviate ITP in mice. The treatment is based on noninvasive whole body illumination 30 min a day for a few consecutive days by near infrared light (830 nm) transmitted by an array of light-emitting diodes (LEDs). LLLT significantly lifted the nadir of platelet counts and restored tail bleeding time when applied to two passive ITP models induced by anti-CD41 antibody. The anti-platelet antibody hindered megakaryocyte differentiation from the progenitors, impaired proplatelet and platelet formation, and induced apoptosis of platelets. These adverse effects of anti-CD41 antibody were all mitigated by LLLT to varying degrees, owing to its ability to enhance mitochondrial biogenesis and activity in megakaryocytes and preserve mitochondrial functions in platelets in the presence of the antibody. The observations argue not only for contribution of mitochondrial stress to the pathology of ITP, but also clinical potentials of LLLT as a safe, simple, and cost-effective modality of ITP.

Neonatal hearing screening in a neonatal intensive care unit using distortion-product otoacoustic emissions.

PubMed

Chiong, Charlotte M; Llanes, Erasmo Gonzalo Dv; Tirona-Remulla, Agnes N; Calaquian, Christopher Malorre E; Reyes-Quintos, Maria-Rina T

2003-01-01

To determine pass and refer rates, and identify risk factors relating to refer responses, in neonates screened using distortion-product otoacoustic emissions (DPOAEs). A total of 435 neonates admitted to the neonatal intensive care unit (NICU) of the Philippine General Hospital between May and October 2000 were screened using DPOAEs within 48 h of admission. The male:female ratio in the sample was 1.05. In total, 56% of neonates were born preterm, the mean birthweight was 2,428.39 +/- 710.39 g and 8.9% weighed < 1,500 g. In total, 47.9% were delivered by Caesarian section and 44.9% were delivered vaginally. Almost 14% of neonates had 1-min Apgar scores of < 6, and 4% had 5-min Apgar scores of < 7. Approximately 95% of neonates had a poor perinatal history. Using pediatric aging it was noted that 46% of these neonates were born preterm. and 30.4% were small for gestational age. At least one neonatal disease was found in 42% of neonates, whilst 95.7% had to be given medication. The bilateral refer rate was 29.1%. Two-by-two analysis of risk factors for hearing loss and DPOAE measurements showed that only male sex seemed to have a significant association with a refer response. Neonates weighing < 1,500 g at birth showed a marginally significant association with a refer response (p = 0.07). All other neonates showed no crude association with DPOAE measurements. These preliminary data show that a high proportion of NICU patients may have poor outer hair cell function, and thus poor hearing. In order to develop an effective neonatal hearing screening program, further studies of prevalence and risk factors should be pursued in the same setting.

Differences in the profile of neonatal abstinence syndrome signs in methadone- versus buprenorphine-exposed neonates

PubMed Central

Gaalema, Diann E.; Scott, Teresa Linares; Heil, Sarah H.; Coyle, Mara G.; Kaltenbach, Karol; Badger, Gary J.; Arria, Amelia M.; Stine, Susan M.; Martin, Peter R.; Jones, Hendrée E.

2014-01-01

Aims To compare the profile of signs of neonatal abstinence syndrome (NAS) in methadone- versus buprenorphine-exposed infants. Design, setting and participants Secondary analysis of NAS data from a multi-site, double-blind, double-dummy, flexible-dosing, randomized clinical trial. Data from a total of 129 neonates born to opioid-dependent women who had been assigned to receive methadone or buprenorphine treatment during pregnancy were examined. Measurements For 10 days after delivery, neonates (methadone = 72, buprenorphine = 57) were assessed regularly using a 19-item modified Finnegan scale. Data from neonates who required pharmacological treatment (methadone = 41, buprenorphine = 27) were included up to the time treatment was initiated. The incidence and mean severity of the total NAS score and each individual sign of NAS were calculated and compared between medication conditions, as was the median time until morphine treatment initiation among treated infants in each condition. Findings Two NAS signs (undisturbed tremors and hyperactive Moro reflex) were observed significantly more frequently in methadone-exposed neonates and three (nasal stuffiness, sneezing, loose stools) were observed more frequently in buprenorphine-exposed neonates. Mean severity scores on the total NAS score and five individual signs (disturbed and undisturbed tremors, hyperactive Moro reflex, excessive irritability, failure to thrive) were significantly higher among methadone-exposed neonates, while sneezing was higher among buprenorphine-exposed neonates. Among treated neonates, methadone-exposed infants required treatment significantly earlier than buprenorphine-exposed infants (36 versus 59 hours postnatal, respectively). Conclusions The profile of neonatal abstinence syndrome differs in methadone- versus buprenorphine-exposed neonates, with significant differences in incidence, severity and treatment initiation time. Overall, methadone-exposed neonates have a more severe neonatal

Severe Clinical Course in a Patient with Congenital Amegakaryocytic Thrombocytopenia Due to a Missense Mutation of the c-MPL Gene.

PubMed

Ok Bozkaya, İkbal; Yaralı, Neşe; Işık, Pamir; Ünsal Saç, Rukiye; Tavil, Betül; Tunç, Bahattin

2015-06-01

Congenital amegakaryocytic thrombocytopenia (CAMT) generally begins at birth with severe thrombocytopenia and progresses to pancytopenia. It is caused by mutations in the thrombopoietin receptor gene, the myeloproliferative leukemia virus oncogene (c-MPL). The association between CAMT and c-MPL mutation type has been reported in the literature. Patients with CAMT have been categorized according to their clinical symptoms caused by different mutations. Missense mutations of c-MPL have been classified as type II and these patients have delayed onset of bone marrow failure compared to type I patients. Here we present a girl with severe clinical course of CAMT II having a missense mutation in exon 4 of the c-MPL gene who was admitted to our hospital with intracranial hemorrhage during the newborn period.

Desialylation is a mechanism of Fc-independent platelet clearance and a therapeutic target in immune thrombocytopenia

PubMed Central

Li, June; van der Wal, Dianne E.; Zhu, Guangheng; Xu, Miao; Yougbare, Issaka; Ma, Li; Vadasz, Brian; Carrim, Naadiya; Grozovsky, Renata; Ruan, Min; Zhu, Lingyan; Zeng, Qingshu; Tao, Lili; Zhai, Zhi-min; Peng, Jun; Hou, Ming; Leytin, Valery; Freedman, John; Hoffmeister, Karin M.; Ni, Heyu

2015-01-01

Immune thrombocytopenia (ITP) is a common bleeding disorder caused primarily by autoantibodies against platelet GPIIbIIIa and/or the GPIb complex. Current theory suggests that antibody-mediated platelet destruction occurs in the spleen, via macrophages through Fc–FcγR interactions. However, we and others have demonstrated that anti-GPIbα (but not GPIIbIIIa)-mediated ITP is often refractory to therapies targeting FcγR pathways. Here, we generate mouse anti-mouse monoclonal antibodies (mAbs) that recognize GPIbα and GPIIbIIIa of different species. Utilizing these unique mAbs and human ITP plasma, we find that anti-GPIbα, but not anti-GPIIbIIIa antibodies, induces Fc-independent platelet activation, sialidase neuraminidase-1 translocation and desialylation. This leads to platelet clearance in the liver via hepatocyte Ashwell–Morell receptors, which is fundamentally different from the classical Fc–FcγR-dependent macrophage phagocytosis. Importantly, sialidase inhibitors ameliorate anti-GPIbα-mediated thrombocytopenia in mice. These findings shed light on Fc-independent cytopenias, designating desialylation as a potential diagnostic biomarker and therapeutic target in the treatment of refractory ITP. PMID:26185093

Socioeconomic factors and adolescent pregnancy outcomes: distinctions between neonatal and post-neonatal deaths?

PubMed Central

Markovitz, Barry P; Cook, Rebeka; Flick, Louise H; Leet, Terry L

2005-01-01

Background Young maternal age has long been associated with higher infant mortality rates, but the role of socioeconomic factors in this association has been controversial. We sought to investigate the relationships between infant mortality (distinguishing neonatal from post-neonatal deaths), socioeconomic status and maternal age in a large, retrospective cohort study. Methods We conducted a population-based cohort study using linked birth-death certificate data for Missouri residents during 1997–1999. Infant mortality rates for all singleton births to adolescent women (12–17 years, n = 10,131; 18–19 years, n = 18,954) were compared to those for older women (20–35 years, n = 28,899). Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for all potential associations. Results The risk of infant (OR 1.95, CI 1.54–2.48), neonatal (1.69, 1.24–2.31) and post-neonatal mortality (2.47, 1.70–3.59) were significantly higher for younger adolescent (12–17 years) than older (20–34 years) mothers. After adjusting for race, marital status, age-appropriate education level, parity, smoking status, prenatal care utilization, and poverty status (indicated by participation in WIC, food stamps or Medicaid), the risk of post-neonatal mortality (1.73, 1.14–2.64) but not neonatal mortality (1.43, 0.98–2.08) remained significant for younger adolescent mothers. There were no differences in neonatal or post-neonatal mortality risks for older adolescent (18–19 years) mothers. Conclusion Socioeconomic factors may largely explain the increased neonatal mortality risk among younger adolescent mothers but not the increase in post-neonatal mortality risk. PMID:16042801

[Neonatal diabetes mellitus].

PubMed

Gurgel, Lucimary C; Moisés, Regina S

2008-03-01

Neonatal diabetes is a rare condition characterized by hyperglycemia, requiring insulin treatment, diagnosed within the first months of life. The disorder may be either transient, resolving in infancy or early childhood with possible relapse later, or permanent in which case lifelong treatment is necessary. Both conditions are genetically heterogeneous; however, the majority of the cases of transient neonatal diabetes are due to abnormalities of an imprinted region of chromosome 6q24. For permanent neonatal diabetes, the most common causes are heterozygous activating mutations of KCNJ11, the gene encoding the Kir6.2 sub-unit of the ATP-sensitive potassium channel. In this article we discuss the clinical features of neonatal diabetes, the underlying genetic defects and the therapeutic implications.

Application of vincristine-loaded platelet therapy in three dogs with refractory immune-mediated thrombocytopenia

PubMed Central

Park, Hyung-Jin; Kim, Ja-Won; Song, Kun-Ho

2015-01-01

Three dogs presented with refractory immune-mediated thrombocytopenia (IMT). All patients failed to respond to prednisone, which is considered a mainstay of immunosuppressive therapy. Vincristine-loaded platelets (VLPs), which act selectively on mononuclear phagocytes,were introduced. After the VLPs were transfused, two dogs responded quickly withimproved clinical signs while the third dogwith recurrent IMT was euthanized due to its deteriorating condition. This case report describesthe efficacy of VLP therapy in refractory IMT patients. PMID:25269722

Glucocorticoid-dependent hypoadrenocorticism with thrombocytopenia and neutropenia mimicking sepsis in a Labrador retriever dog

PubMed Central

Snead, Elisabeth; Vargo, Cheryl; Myers, Sherry

2011-01-01

Glucocorticoid-deficient hypoadrenocorticism (GDH) with immune-mediated-neutropenia (IMN) and -thrombocytopenia (IMT) were diagnosed in a 3-year-old Labrador retriever dog. Glucocorticoid-deficient hypoadrenocorticism is rare and diagnostically challenging as clinical signs and laboratory abnormalities are often nonspecific. Immune-mediated cytopenias and other autoimmune disorders, as part of an autoimmune polyglandular syndrome have been reported with hypoadrenocorticism in humans. This is the first reported case of hypoadrenocorticism and bicytopenia in a dog. PMID:22467971

Estimation of the incidence of severe fever with thrombocytopenia syndrome in high endemic areas in China: an inpatient-based retrospective study.

PubMed

Huang, Xiaoxia; Wang, Shiwen; Wang, Xianjun; Lyu, Yong; Jiang, Mei; Chen, Deying; Li, Kaichun; Liu, Jingyu; Xie, Shaoyu; Lyu, Tao; Sun, Jie; Xu, Pengpeng; Cao, Minghua; Liang, Mifang; Li, Dexin

2018-02-05

Severe fever with thrombocytopenia syndrome (SFTS) is a severe viral disease caused by SFTSV. It is important to estimate the rate of missed SFTS diagnosis and to further understand the actual incidence in high endemic areas in China. This study was conducted in two high SFTS endemic provinces in 2015. Patients hospitalized in 2014 or within 1 year before investigation were selected after considering their clinical manifestations, specifically, fever, platelet, and white blood cell. During retrospective investigation, sera were collected to detect SFTSV antibodies to assess SFTSV infection. To further understand SFTSV infection, acute phase sera were detected; SFTSV infection rate among a healthy population was also investigated to determine the basic infection level. In total, 246 hospitalized cases were included, including 83 cases (33.7%) with fever, thrombocytopenia and leukopenia, 38 cases (15.4%) with fever and thrombocytopenia but without leukopenia, and 125 cases (50.8%) without fever but with thrombocytopenia and leukopenia. In total, 13 patients (5.3%) were SFTSV IgM antibody-positive, 48 (19.5%) were IgG-positive. Of the 13 IgM-positive cases, 11 (84.6%) were IgG-positive (9 with titres ≥1:400). Seropositive rates of antibodies were high (8.4% for IgM and 30.1% for IgG) in patients with fever, thrombocytopenia and leukopenia. Furthermore, among IgG-positive cases in this group, 76% (19/25) of patients' IgG antibody titres were ≥1:400. Additionally, 28 of 246 cases were initially diagnosed with suspected SFTS and were then excluded, and 218 patients were never diagnosed with SFTS; the seropositive rates of IgM and IgG in these two groups were 25% and 67.9% and 2.8% and 13.3%, respectively. These rates were 64.3% and 21.4% in 14 sera collected during acute phase of the 28 cases mentioned above. Seropositive rate of SFTSV IgG was only 1.3% in the patient-matched healthy group, and no IgM antibody was detected. A preliminary estimate of 8.3% of SFTS

Neonatal streptococcal infections.

PubMed Central

Parker, M. T.

1977-01-01

Most serious neonatal streptococcal infections are caused by group-B streptococci. The pattern of serious group-B neonatal disease in Britain resembles that described in other countries; both "early-onset" and "late-onset" forms are seen, but reliable incidence rates have not yet been determined. Serological-type III strains predominate in neonatal meningitis in Britain, but not so markedly as in some parts of the U.S.A. A deficiency of group-II strains in meningitis is, however, apparent in both countries. Present information about the carriage of group-B streptococci suggests that antibiotic prophylaxis administered to mothers or infants is unlikely to reduce greatly the frequency of "early-onset" disease. The continuous presence of a suitable chemical disinfectant in the vagina during labour might be more effective. Insufficient is known about the epidemiology of "late-onset" neonatal disease for rational preventive measures to be designed. More information is required about the postnatal acquisition of group-B streptococci by neonates and its sources, and about passive transfer of type-specific antibody from the mother to her child. PMID:339212

Tactile stimulation during neonatal transition and its effect on vital parameters in neonates during neonatal transition.

PubMed

Baik-Schneditz, Nariae; Urlesberger, Berndt; Schwaberger, Bernhard; Mileder, Lukas; Schmölzer, Georg; Avian, Alexander; Pichler, Gerhard

2018-06-01

This study analysed tactile stimulation during neonatal transition and resuscitation in preterm and term neonates born by Caesarean delivery. It examined the frequency, location and body region, duration and possible effects of stimulation on heart rate and arterial oxygen saturation (SpO 2 ). Two independent investigators analysed video recordings of tactile stimulation on term and preterm neonates during neonatal transition from January 2012 to December 2014. They were recorded during a prospective observational study and randomised controlled trial at a tertiary centre, the Medical University of Graz, Austria. SpO 2 and heart rate were continuously recorded. Data on the frequency, body region and duration of stimulation were collected. To investigate the possible effects of stimulation, SpO 2 and heart rate were compared before and after stimulation. Term infants received tactile stimulation more than once, and it tended to start later, last longer and be applied in more locations than in preterm infants. Only preterm infants showed a significant increase in SpO 2 after stimulation and heart rates did not show any significant changes in either group. Tactile stimulation was applied in different ways to preterm and term infants during neonatal transition and SpO 2 showed a significant increase in preterm infants. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

The Incidence of Allergic Disorders in First Degree Relatives of Neonates with Transient Tachypnea of Neonate

PubMed Central

Basiri, Behnaz; Ghaeeni, Mehdi

2015-01-01

Background The role of maternal allergic disorders to increase the risk of Transient Tachypnea of Neonate (TTN) in neonates remained unclear. We determined the incidence of allergic disorders in first degree relatives of neonates suffered from TTN to clear role of these allergic disorders to predispose TTN in neonates. Materials and Methods In a cross-sectional study carried out at Fatemieh hospital between September 2010 and September 2011, all consecutive neonates with the diagnosis of TTN were included into the study. Those neonates were not treated after 5 days of hospitalization were excluded. Baseline information with regard to the history of allergic diseases among first degree relatives of neonates were charted from family members using a structured questionnaire at enrolment by interviewing and examination if required. Results The two groups were matched for baseline data including neonate gender, birth weight, and type of delivery. In the TTN group, one of first degree relatives (2.9%) suffered from bronchial asthma and two of them (5.7) had atopic dermatitis. In total, allergic diseases was revealed in 8.6% of first degree relatives of neonates with TTN. Besides, none of the first degree relatives of neonates in healthy neonates group experienced bronchial asthma or atopic dermatitis. Allergic rhinitis was not also found in the relatives of the two study neonates groups. Comparing incidence of allergic diseases in first degree relatives of neonates in TTN and healthy groups showed no significant difference (8.6% in TTN group versus 0.0% in healthy group, p = 0.076). Conclusion Our study showed that the incidence of allergic disorders in first degree relatives of neonates suffered from TTN is higher than healthy newborns, but these differences are not statistically significant. PMID:26436012

Management of immune thrombocytopenia: Korean experts recommendation in 2017.

PubMed

Jang, Jun Ho; Kim, Ji Yoon; Mun, Yeung-Chul; Bang, Soo-Mee; Lim, Yeon Jung; Shin, Dong-Yeop; Choi, Young Bae; Yhim, Ho-Young; Lee, Jong Wook; Kook, Hoon

2017-12-01

Management options for patients with immune thrombocytopenia (ITP) have evolved substantially over the past decades. The American Society of Hematology published a treatment guideline for clinicians referring to the management of ITP in 2011. This evidence-based practice guideline for ITP enables the appropriate treatment of a larger proportion of patients and the maintenance of normal platelet counts. Korean authority operates a unified mandatory national health insurance system. Even though we have a uniform standard guideline enforced by insurance reimbursement, there are several unsolved issues in real practice in ITP treatment. To optimize the management of Korean ITP patients, the Korean Society of Hematology Aplastic Anemia Working Party (KSHAAWP) reviewed the consensus and the Korean data on the clinical practices of ITP therapy. Here, we report a Korean expert recommendation guide for the management of ITP.

Drug Labeling and Exposure in Neonates

PubMed Central

Laughon, Matthew M.; Avant, Debbie; Tripathi, Nidhi; Hornik, Christoph P.; Cohen-Wolkowiez, Michael; Clark, Reese H.; Smith, P. Brian; Rodriguez, William

2014-01-01

Importance Federal legislation has led to a notable increase in pediatric studies submitted to the Food and Drug Administration (FDA), resulting in new pediatric information in product labeling. However, approximately 50% of drug labels still have insufficient information on safety, efficacy, or dosing in children. Neonatal information in labeling is even scarcer because neonates comprise a vulnerable subpopulation for which end point development is lagging and studies are more challenging. Objective To quantify progress made in neonatal studies and neonatal information in product labeling as result of recent legislation. Design 1. Cohort of neonatal drug studies; and 2. Cohort of infants exposed to these drugs.. Setting 1. Neonatal drug studies: FDA website; 2. National review: infants admitted to a neonatal intensive care unit (NICU) Participants 1) We identified drug studies between 1997 and 2010 that included neonates as a result of pediatric legislation using information available on the FDA website. We determined what studies were published in the medical literature, the legislation responsible for the studies, and the resulting neonatal labeling changes. 2) We then examined the use of these drugs in neonates admitted to 290 NICUs (the Pediatrix Data Warehouse) in the United States from 2005–2010. Exposures Infants exposed to a drug studied in neonates as identified by the FDA website Main outcome measures Number of drug studies with neonates and rate of exposure per 1000 admission among infants admitted to a NICU Results In a review of the FDA databases, we identified 28 drugs studied in neonates and 24 related labeling changes. Forty-one studies encompassed the 28 drugs, and 31 (76%) of these were published. Eleven (46%) of the 24 neonatal labeling changes established safety and effectiveness. In a review of a cohort of 446,335 hospitalized infants, we identified 399 drugs used and 1,525,739 drug exposures in the first 28 postnatal days. Thirteen (46%) of

Efficacy of DHMEQ, a NF-κB inhibitor, in islet transplantation: II. Induction DHMEQ treatment ameliorates subsequent alloimmune responses and permits long-term islet allograft acceptance.

PubMed

Watanabe, Masaaki; Yamashita, Kenichiro; Kamachi, Hirofumi; Kuraya, Daisuke; Koshizuka, Yasuyuki; Shibasaki, Susumu; Asahi, Yoh; Ono, Hitoshi; Emoto, Shin; Ogura, Masaomi; Yoshida, Tadashi; Ozaki, Michitaka; Umezawa, Kazuo; Matsushita, Michiaki; Todo, Satoru

2013-09-15

Long-term graft deterioration remains a major obstacle in the success of pancreatic islet transplantation (PITx). Antigen-independent inflammatory and innate immune responses strengthen subsequent antigen-dependent immunity; further, activation of nuclear factor (NF)-κB plays a key role during these responses. In this study, we tested our hypothesis that, by the inhibition of NF-κB activation, the suppression of these early responses after PITx could facilitate graft acceptance. Full major histocompatibility complex (MHC)-mismatched BALB/c (H-2) mice islets were transplanted into streptozotocin-induced diabetic C57BL/6 (B6: H-2) mice. The NF-κB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) was administered for either 3 or 14 days after PITx. To some PITx recipients, tacrolimus was also administered. Islet allograft survival, alloimmune responses, and in vitro effects of DHMEQ on dendritic cells (DCs) were assessed. With a vehicle treatment, 600 islet allografts were promptly rejected after PITx. In contrast, 3-day treatment with DHMEQ, followed by 2-week treatment with tacrolimus, allowed permanent acceptance of islet allografts. The endogenous danger-signaling molecule high mobility group complex 1 (HMGB1) was elevated in sera shortly after PITx, whereas DHMEQ administration abolished this elevation. DHMEQ suppressed HMGB1-driven cellular activation and proinflammatory cytokine secretion in mouse bone marrow-derived DCs and significantly reduced the capacity of DCs to prime allogeneic T-cell proliferation in vitro. Finally, the DHMEQ plus tacrolimus regimen reverted the diabetic state with only 300 islet allografts. Inhibition of NF-κB activation by DHMEQ shortly after PITx suppresses HMGB1, which activates DCs and strengthens the magnitude of alloimmune responses; this permits long-term islet allograft acceptance, even in case of fewer islet allografts.

Developments in neonatal care and nursing responses.

PubMed

Healy, Patricia; Fallon, Anne

This article reviews the origins and evolution of neonatology and considers the role of the neonatal nurse within this specialty. Neonatal nurses are a vital part of the neonatal team that provides care for sick babies. The nursing care required by sick babies and their families on a neonatal unit can be variable and complex. The past century has seen significant changes in the role of the neonatal nurse. This has come about through dramatic technological developments on neonatal units, an increased understanding of neonatal physiology and pathology, changes in the education of neonatal nurses, and active and ongoing clinical research within the specialty. The resulting significant advances in neonatal care, including that provided by neonatal nurses, have made a crucial and steadfast contribution to marked improvements in neonatal outcomes.

Application of vincristine-loaded platelet therapy in three dogs with refractory immune-mediated thrombocytopenia.

PubMed

Park, Hyung-Jin; Kim, Ja-Won; Song, Kun-Ho; Seo, Kyoung-Won

2015-01-01

Three dogs presented with refractory immune-mediated thrombocytopenia (IMT). All patients failed to respond to prednisone, which is considered a mainstay of immunosuppressive therapy. Vincristine-loaded platelets (VLPs), which act selectively on mononuclear phagocytes,were introduced. After the VLPs were transfused, two dogs responded quickly with improved clinical signs while the third dog with recurrent IMT was euthanized due to its deteriorating condition. This case report describes the efficacy of VLP therapy in refractory IMT patients.

Human Herpesvirus 6 Infection Presenting as an Acute Febrile Illness Associated with Thrombocytopenia and Leukopenia

PubMed Central

Avšič-Županc, Tatjana; Uršič, Tina; Petrovec, Miroslav

2016-01-01

We present an infant with acute fever, thrombocytopenia, and leukopenia, coming from an endemic region for tick-borne encephalitis, human granulocytic anaplasmosis, and hantavirus infection. The primary human herpesvirus 6 infection was diagnosed by seroconversion of specific IgM and IgG and by identification of viral DNA in the acute patient's serum. The patient did not show skin rash suggestive of exanthema subitum during the course of illness. PMID:27980872

Drug labeling and exposure in neonates.

PubMed

Laughon, Matthew M; Avant, Debbie; Tripathi, Nidhi; Hornik, Christoph P; Cohen-Wolkowiez, Michael; Clark, Reese H; Smith, P Brian; Rodriguez, William

2014-02-01

Federal legislation has led to a notable increase in pediatric studies submitted to the Food and Drug Administration (FDA), resulting in new pediatric information in product labeling. However, approximately 50% of drug labels still have insufficient information on safety, efficacy, or dosing in children. Neonatal information in labeling is even scarcer because neonates comprise a vulnerable subpopulation for which end-point development is lagging and studies are more challenging. To quantify progress made in neonatal studies and neonatal information in product labeling as a result of recent legislation. We identified a cohort of drug studies between 1997 and 2010 that included neonates as a result of pediatric legislation using information available on the FDA website. We determined what studies were published in the medical literature, the legislation responsible for the studies, and the resulting neonatal labeling changes. We then examined the use of these drugs in a cohort of neonates admitted to 290 neonatal intensive care units (NICUs) (the Pediatrix Data Warehouse) in the United States from 2005 to 2010. Infants exposed to a drug studied in neonates as identified by the FDA website. Number of drug studies with neonates and rate of exposure per 1000 admissions among infants admitted to an NICU. In a review of the FDA databases, we identified 28 drugs studied in neonates and 24 related labeling changes. Forty-one studies encompassed the 28 drugs, and 31 (76%) of these were published. Eleven (46%) of the 24 neonatal labeling changes established safety and effectiveness. In a review of a cohort of 446,335 hospitalized infants, we identified 399 drugs used and 1,525,739 drug exposures in the first 28 postnatal days. Thirteen (46%) of the 28 drugs studied in neonates were not used in NICUs; 8 (29%) were used in fewer than 60 neonates. Of the drugs studied, ranitidine was used most often (15,627 neonates, 35 exposures per 1000 admissions). Few drug labeling changes

Neonatal pulmonary physiology.

PubMed

Davis, Ryan P; Mychaliska, George B

2013-11-01

Managing pulmonary issues faced by both term and preterm infants remains a challenge to the practicing pediatric surgeon. An understanding of normal fetal and neonatal pulmonary development and physiology is the cornerstone for understanding the pathophysiology and treatment of many congenital and acquired problems in the neonate. Progression through the phases of lung development and the transition to postnatal life requires a symphony of complex and overlapping events to work in concert for smooth and successful transition to occur. Pulmonary physiology and oxygen transport in the neonate are similar to older children; however, there are critical differences that are important to take into consideration when treating the youngest of patients. Our understanding of fetal and neonatal pulmonary physiology continues to evolve as the molecular and cellular events governing these processes are better understood. This deeper understanding has helped to facilitate groundbreaking research, leading to improved technology and treatment of term and preterm infants. As therapeutics and research continue to advance, a review of neonatal pulmonary physiology is essential to assist the clinician with his/her management of the wide variety of challenging congenital and acquired pulmonary disease. © 2013 Published by Elsevier Inc.

Interventions to reduce neonatal mortality from neonatal tetanus in low and middle income countries--a systematic review.

PubMed

Khan, Adeel Ahmed; Zahidie, Aysha; Rabbani, Fauziah

2013-04-09

In 1988, WHO estimated around 787,000 newborns deaths due to neonatal tetanus. Despite few success stories majority of the Low and Middle Income Countries (LMICs) are still struggling to reduce neonatal mortality due to neonatal tetanus. We conducted a systematic review to understand the interventions that have had a substantial effect on reducing neonatal mortality rate due to neonatal tetanus in LMICs and come up with feasible recommendations for decreasing neonatal tetanus in the Pakistani setting. We systemically reviewed the published literature (Pubmed and Pubget databases) to identify appropriate interventions for reducing tetanus related neonatal mortality. A total of 26 out of 30 studies were shortlisted for preliminary screening after removing overlapping information. Key words used were "neonatal tetanus, neonatal mortality, tetanus toxoid women". Of these twenty-six studies, 20 were excluded. The pre-defined exclusion criteria was (i) strategies and interventions to reduce mortality among neonates not described (ii) no abstract/author (4 studies) (iii) not freely accessible online (1 study) (iv) conducted in high income countries (2 studies) and (v) not directly related to neonatal tetanus mortality and tetanus toxoid immunization (5). Finally six studies which met the eligibility criteria were entered in the pre-designed data extraction form and five were selected for commentary as they were directly linked with neonatal tetanus reduction. Interventions that were identified to reduce neonatal mortality in LMICs were: a) vaccination of women of child bearing age (married and unmarried both) with tetanus toxoid b) community based interventions i.e. tetanus toxoid immunization for all mothers; clean and skilled care at delivery; newborn resuscitation; exclusive breastfeeding; umbilical cord care and management of infections in newborns c) supplementary immunization (in addition to regular EPI program) d) safer delivery practices. The key intervention to

Perioperative use of iloprost in cardiac surgery patients diagnosed with heparin-induced thrombocytopenia-reactive antibodies or with true HIT (HIT-reactive antibodies plus thrombocytopenia): An 11-year experience.

PubMed

Palatianos, George; Michalis, Alkiviadis; Alivizatos, Petros; Lacoumenda, Stavroula; Geroulanos, Stefanos; Karabinis, Andreas; Iliopoulou, Eugenia; Soufla, Giannoula; Kanthou, Chryso; Khoury, Mazen; Sfyrakis, Petros; Stavridis, George; Astras, George; Vassili, Maria; Antzaka, Christina; Marathias, Katerina; Kriaras, Ioannis; Tasouli, Androniki; Papadopoulos, Kyrillos; Katafygioti, Marina; Matoula, Nikoletta; Angelidis, Antonios; Melissari, Euthemia

2015-07-01

Thrombocytopenia and thromboembolism(s) may develop in heparin immune-mediated thrombocytopenia (HIT) patients after reexposure to heparin. At the Onassis Cardiac Surgery Center, 530 out of 17,000 patients requiring heart surgery over an 11-year period underwent preoperative HIT assessment by ELISA and a three-point heparin-induced platelet aggregation assay (HIPAG). The screening identified 110 patients with HIT-reactive antibodies, out of which 46 were also thrombocytopenic (true HIT). Cardiac surgery was performed in HIT-positive patients under heparin anticoagulation and iloprost infusion. A control group of 118 HIT-negative patients received heparin but no iloprost during surgery. For the first 20 patients, the dose of iloprost diminishing the HIPAG test to ≤5% was determined prior to surgery by in vitro titration using the patients' own plasma and donor platelets. In parallel, the iloprost "target dose" was also established for each patient intraoperatively, but before heparin administration. Iloprost was infused initially at 3 ng/kg/mL and further adjusted intraoperatively, until ex vivo aggregation reached ≤5%. As a close correlation was observed between the "target dose" identified before surgery and that established intraoperatively, the remaining 90 patients were administered iloprost starting at the presurgery identified "target dose." This process significantly reduced the number of intraoperative HIPAG reassessments needed to determine the iloprost target dose, and reduced surgical time, while maintaining similar primary clinical outcomes to controls. Therefore, infusion of iloprost throughout surgery, under continuous titration, allows cardiac surgery to be undertaken safely using heparin, while avoiding life-threatening iloprost-induced hypotension in patients diagnosed with HIT-reactive antibodies or true HIT. © 2015 Wiley Periodicals, Inc.

Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia

PubMed Central

Lee-Sherick, Alisa B.; Callaghan, Michael; Noris, Patrizia; Savoia, Anna; Rajpurkar, Madhvi; Jones, Kenneth; Gowan, Katherine; Balduini, Carlo; Pecci, Alessandro; Gnan, Chiara; De Rocco, Daniela; Doubek, Michael; Li, Ling; Lu, Lily; Leung, Richard; Landolt-Marticorena, Carolina; Hunger, Stephen; Heller, Paula; Gutierrez-Hartmann, Arthur; Xiayuan, Liang; Pluthero, Fred G.; Rowley, Jesse W.; Weyrich, Andrew S.

2015-01-01

Some familial platelet disorders are associated with predisposition to leukemia, myelodysplastic syndrome (MDS) or dyserythropoietic anemia.1,2 We identified a family with autosomal dominant thrombocytopenia, high erythrocyte mean corpuscular volume (MCV) and two occurrences of B-cell precursor acute lymphoblastic leukemia (ALL). Whole exome sequencing identified a heterozygous single nucleotide change in ETV6 (Ets Variant Gene 6), c.641C>T, encoding a p.Pro214Leu substitution in the central domain, segregating with thrombocytopenia and elevated MCV. A screen of 23 families with similar phenotype found two with ETV6 mutations. One family had the p.Pro214Leu mutation and one individual with ALL. The other family had a c.1252A>G transition producing a p.Arg418Gly substitution in the DNA binding domain, with alternative splicing and exon-skipping. Functional characterization of these mutations showed aberrant cellular localization of mutant and endogenous ETV6, decreased transcriptional repression and altered megakaryocyte maturation. Our findings underscore a key role for ETV6 in platelet formation and leukemia predisposition. PMID:25807284

Low-level light treatment ameliorates immune thrombocytopenia

PubMed Central

Yang, Jingke; Zhang, Qi; Li, Peiyu; Dong, Tingting; Wu, Mei X.

2016-01-01

Immune thrombocytopenia (ITP) is an immune-mediated acquired bleeding disorder characterized by abnormally low platelet counts. We reported here the ability of low-level light treatment (LLLT) to alleviate ITP in mice. The treatment is based on noninvasive whole body illumination 30 min a day for a few consecutive days by near infrared light (830 nm) transmitted by an array of light-emitting diodes (LEDs). LLLT significantly lifted the nadir of platelet counts and restored tail bleeding time when applied to two passive ITP models induced by anti-CD41 antibody. The anti-platelet antibody hindered megakaryocyte differentiation from the progenitors, impaired proplatelet and platelet formation, and induced apoptosis of platelets. These adverse effects of anti-CD41 antibody were all mitigated by LLLT to varying degrees, owing to its ability to enhance mitochondrial biogenesis and activity in megakaryocytes and preserve mitochondrial functions in platelets in the presence of the antibody. The observations argue not only for contribution of mitochondrial stress to the pathology of ITP, but also clinical potentials of LLLT as a safe, simple, and cost-effective modality of ITP. PMID:27901126

Blocking neutrophil diapedesis prevents hemorrhage during thrombocytopenia

PubMed Central

Hillgruber, Carina; Pöppelmann, Birgit; Weishaupt, Carsten; Steingräber, Annika Kathrin; Wessel, Florian; Berdel, Wolfgang E.; Gessner, J. Engelbert; Ho-Tin-Noé, Benoît

2015-01-01

Spontaneous organ hemorrhage is the major complication in thrombocytopenia with a potential fatal outcome. However, the exact mechanisms regulating vascular integrity are still unknown. Here, we demonstrate that neutrophils recruited to inflammatory sites are the cellular culprits inducing thrombocytopenic tissue hemorrhage. Exposure of thrombocytopenic mice to UVB light provokes cutaneous petechial bleeding. This phenomenon is also observed in immune-thrombocytopenic patients when tested for UVB tolerance. Mechanistically, we show, analyzing several inflammatory models, that it is neutrophil diapedesis through the endothelial barrier that is responsible for the bleeding defect. First, bleeding is triggered by neutrophil-mediated mechanisms, which act downstream of capturing, adhesion, and crawling on the blood vessel wall and require Gαi signaling in neutrophils. Second, mutating Y731 in the cytoplasmic tail of VE-cadherin, known to selectively affect leukocyte diapedesis, but not the induction of vascular permeability, attenuates bleeding. Third, and in line with this, simply destabilizing endothelial junctions by histamine did not trigger bleeding. We conclude that specifically targeting neutrophil diapedesis through the endothelial barrier may represent a new therapeutic avenue to prevent fatal bleeding in immune-thrombocytopenic patients. PMID:26169941

Neonatal Informatics: Transforming Neonatal Care Through Translational Bioinformatics

PubMed Central

Palma, Jonathan P.; Benitz, William E.; Tarczy-Hornoch, Peter; Butte, Atul J.; Longhurst, Christopher A.

2012-01-01

The future of neonatal informatics will be driven by the availability of increasingly vast amounts of clinical and genetic data. The field of translational bioinformatics is concerned with linking and learning from these data and applying new findings to clinical care to transform the data into proactive, predictive, preventive, and participatory health. As a result of advances in translational informatics, the care of neonates will become more data driven, evidence based, and personalized. PMID:22924023

Development of fulminant Type 1 diabetes with thrombocytopenia after influenza vaccination: a case report.

PubMed

Yasuda, H; Nagata, M; Moriyama, H; Kobayashi, H; Akisaki, T; Ueda, H; Hara, K; Yokono, K

2012-01-01

Fulminant Type 1 diabetes was originally reported as idiopathic Type 1 diabetes. Involvement of viral infections in the pathogenesis of fulminant T1D has been suggested, but the development of fulminant Type 1 diabetes after influenza vaccination has not been reported. We report a case of fulminant Type 1 diabetes with thrombocytopenia following influenza vaccination. A 54-year-old man was admitted to hospital with hyperglycaemia and diabetic ketosis. Seven days before admission, he received a seasonal influenza vaccine for the prevention of influenza infection. On admission, blood glucose was 29 mmol/L and HbA1c 40 mmol/mol (5.9%). Fasting and 2-h C-peptide immunoreactivity were <0.0333 nmol/L and 0.0999 nmol/L, respectively. Anti-GAD and anti-IA-2 antibodies were negative, so no autoimmunity seemed to participate in the etiology. ELISPOT assay also showed no association with T cell-mediated autoimmunity. HLA genotypes were consistent with susceptibility to fulminant Type 1 diabetes. After the abrupt onset of diabetes, he showed mild thrombocytopenia, which has been observed for approximately 5 years after diabetes development. This is the first description of fulminant Type 1 diabetes after influenza vaccination. Our observation raises the possibility that influenza vaccination might trigger this condition via the TLR7 pathway. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

Neonates need tailored drug formulations.

PubMed

Allegaert, Karel

2013-02-08

Drugs are very strong tools used to improve outcome in neonates. Despite this fact and in contrast to tailored perfusion equipment, incubators or ventilators for neonates, we still commonly use drug formulations initially developed for adults. We would like to make the point that drug formulations given to neonates need to be tailored for this age group. Besides the obvious need to search for active compounds that take the pathophysiology of the newborn into account, this includes the dosage and formulation. The dosage or concentration should facilitate the administration of low amounts and be flexible since clearance is lower in neonates with additional extensive between-individual variability. Formulations need to be tailored for dosage variability in the low ranges and also to the clinical characteristics of neonates. A specific focus of interest during neonatal drug development therefore is a need to quantify and limit excipient exposure based on the available knowledge of their safety or toxicity. Until such tailored vials and formulations become available, compounding practices for drug formulations in neonates should be evaluated to guarantee the correct dosing, product stability and safety.

[Anaesthetic implications in a pregnant patient with an extreme thrombocytopenia due to a May-Hegglin anomaly: general o regional anaesthesia?].

PubMed

García Vallejo, G; Cabellos, M; Kabiri, M; Fraile, J R; Cuesta, J

2014-10-01

The May-Hegglin anomaly is an inherited disorder, so uncommon that the incidence is still unknown. It is characterized by macro-thrombocytopenia with normal platelet function and cytoplasmic inclusion bodies in granulocytes. The case is reported of a 28-year-old primiparous patient who had an urgent caesarean section due to failed induction of labour. The patient had no history of abnormal bleeding. Other causes of thrombocytopenia or platelet dysfunction, such as preeclampsia, HELLP syndrome, or placental abruption, were ruled out. The platelet count prior to surgery was 20,900/mm(3) with normal platelet function. General anaesthesia was performed. No excessive bleeding occurred and a platelet transfusion was not needed. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

Interventions to reduce neonatal mortality from neonatal tetanus in low and middle income countries - a systematic review

PubMed Central

2013-01-01

Background In 1988, WHO estimated around 787,000 newborns deaths due to neonatal tetanus. Despite few success stories majority of the Low and Middle Income Countries (LMICs) are still struggling to reduce neonatal mortality due to neonatal tetanus. We conducted a systematic review to understand the interventions that have had a substantial effect on reducing neonatal mortality rate due to neonatal tetanus in LMICs and come up with feasible recommendations for decreasing neonatal tetanus in the Pakistani setting. Methods We systemically reviewed the published literature (Pubmed and Pubget databases) to identify appropriate interventions for reducing tetanus related neonatal mortality. A total of 26 out of 30 studies were shortlisted for preliminary screening after removing overlapping information. Key words used were “neonatal tetanus, neonatal mortality, tetanus toxoid women”. Of these twenty-six studies, 20 were excluded. The pre-defined exclusion criteria was (i) strategies and interventions to reduce mortality among neonates not described (ii) no abstract/author (4 studies) (iii) not freely accessible online (1 study) (iv) conducted in high income countries (2 studies) and (v) not directly related to neonatal tetanus mortality and tetanus toxoid immunization (5). Finally six studies which met the eligibility criteria were entered in the pre-designed data extraction form and five were selected for commentary as they were directly linked with neonatal tetanus reduction. Results Interventions that were identified to reduce neonatal mortality in LMICs were: a) vaccination of women of child bearing age (married and unmarried both) with tetanus toxoid b) community based interventions i.e. tetanus toxoid immunization for all mothers; clean and skilled care at delivery; newborn resuscitation; exclusive breastfeeding; umbilical cord care and management of infections in newborns c) supplementary immunization (in addition to regular EPI program) d) safer delivery

Neonatal Vaccination: Challenges and Intervention Strategies.

PubMed

Morris, Matthew C; Surendran, Naveen

2016-01-01

While vaccines have been tremendously successful in reducing the incidence of serious infectious diseases, newborns remain particularly vulnerable in the first few months of their life to life-threatening infections. A number of challenges exist to neonatal vaccination. However, recent advances in the understanding of neonatal immunology offer insights to overcome many of those challenges. This review will present an overview of the features of neonatal immunity which make vaccination difficult, survey the mechanisms of action of available vaccine adjuvants with respect to the unique features of neonatal immunity, and propose a possible mechanism contributing to the inability of neonates to generate protective immune responses to vaccines. We surveyed recent published findings on the challenges to neonatal vaccination and possible intervention strategies including the use of novel vaccine adjuvants to develop efficacious neonatal vaccines. Challenges in the vaccination of neonates include interference from maternal antibody and excessive skewing towards Th2 immunity, which can be counteracted by the use of proper adjuvants. Synergistic stimulation of multiple Toll-like receptors by incorporating well-defined agonist-adjuvant combinations to vaccines is a promising strategy to ensure a protective vaccine response in neonates. © 2016 S. Karger AG, Basel.

Clinical and laboratory characteristics of neonatal hypocalcemia

PubMed Central

Cho, Won Im; Yu, Hyeoh Won; Shin, Choong Ho; Yang, Sei Won; Choi, Chang Won; Kim, Beyong Il

2015-01-01

Purpose To describe the clinical characteristics of full-term neonates with hypocalcemia and to suggest factors associated with neonatal hypocalcemia Methods The medical records of full-term neonates with hypocalcemia were reviewed. Hypocalcemia was defined as an ionized calcium (iCa) concentration of <4 mg/dL. Parathyroid hormone (PTH) insufficiency was defined as a serum PTH level of <60 pg/mL or a serum phosphorus level higher than the serum calcium level in the presence of hypocalcemia. Results Fifty-three neonates were enrolled. The median age at diagnosis of hypocalcemia was 3 days. In all the neonates, formula feeding predominance was observed. Thirty-eight neonates (69.8%) were compatible with PTH insufficiency. The number of formula-fed neonates was significantly higher than that of breast-fed patients among neonates with PTH insufficiency (P=0.017). Intact PTH was negatively correlated with serum phosphorus levels. Twelve out of 14 neonates (85.7%) had 25-hydroxy vitamin D (25OHD) levels <20 ng/mL and 9 neonates (64.3%) had 25OHD levels <10 ng/mL. Twenty-one neonates had hypocalcemic tetany. The serum calcium and iCa concentrations of neonates with tetany were 4.2-8.3 mg/dL and 1.85-3.88 mg/dL, respectively. Three neonates showed symptomatic hypocalcemia with calcium levels over 7.5 mg/dL. Among the 16 neonates who underwent electroencephalography (EEG), 12 had abnormalities, which normalized after 1-2 months. Conclusion Formula milk feeding, PTH insufficiency and low serum vitamin D concentration are associated with the development of neonatal hypocalcemia. Symptoms such as tetany and QT interval prolongation can develop in relatively mild hypocalcemia. Moreover, transient neonatal hypocalcemia can cause transient EEG abnormalities. PMID:26191512

45 CFR 46.205 - Research involving neonates.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false Research involving neonates. 46.205 Section 46.205... SUBJECTS Additional Protections for Pregnant Women, Human Fetuses and Neonates Involved in Research § 46.205 Research involving neonates. (a) Neonates of uncertain viability and nonviable neonates may be...

2-O, 3-O desulfated heparin mitigates murine chemotherapy- and radiation-induced thrombocytopenia

PubMed Central

Tkaczynski, Elizabeth; Arulselvan, Abinaya; Tkaczynski, John; Avery, Stephen; Xiao, Liqing; Torok-Storb, Beverly; Abrams, Kraig; Rao, Narayanam V.; Johnson, Gregory; Poncz, Mortimer

2018-01-01

Thrombocytopenia is a significant complication of chemotherapy and radiation therapy. Platelet factor 4 (PF4; CXCL4) is a negative paracrine of megakaryopoiesis. We have shown that PF4 levels are inversely related to steady-state platelet counts, and to the duration and severity of chemotherapy- and radiation-induced thrombocytopenia (CIT and RIT, respectively). Murine studies suggest that blocking the effect of PF4 improves megakaryopoiesis, raising nadir platelet counts and shortening the time to platelet count recovery. We examined the ability of 2-O, 3-O desulfated heparin (ODSH), a heparin variant with little anticoagulant effects, to neutralize PF4’s effects on megakaryopoiesis. Using megakaryocyte colony assays and liquid cultures, we show that ODSH restored megakaryocyte proliferation in PF4-treated Cxcl4−/− murine and human CD34+-derived megakaryocyte cultures (17.4% megakaryocyte colonies, P < .01 compared with PF4). In murine CIT and RIT models, ODSH, started 24 hours after injury, was examined for the effect on hematopoietic recovery demonstrating higher platelet count nadirs (9% ± 5% treated vs 4% ± 4% control) and significantly improved survival in treated animals (73% treated vs 36% control survival). Treatment with ODSH was able to reduce intramedullary free PF4 concentrations by immunohistochemical analysis. In summary, ODSH mitigated CIT and RIT in mice by neutralizing the intramedullary negative paracrine PF4. ODSH, already in clinical trials in humans as an adjuvant to chemotherapy, may be an important, clinically relevant therapeutic for CIT and RIT. PMID:29599195

Neonatal head injuries

PubMed Central

Graham, C.; O'Toole, S.; Haddock, G.

2000-01-01

A retrospective case note review of head injuries in neonates admitted to the Neonatal Surgical Unit in Glasgow between 1990 and 1996 (n=25) was carried out. Most injuries were caused by a fall (68%) and resulted in scalp haematomata and associated skull fractures in the majority of patients. Three neonates were involved in high speed road traffic accidents, and these infants all had intracranial pathology identified by computed tomography. Isolated skull fractures were common and did not appear to be associated with any neurological deficit. Non-accidental injury was uncommon in this age group. Outcome was excellent in the majority of patients (92%). PMID:11005402

Gut microbial colonisation in premature neonates predicts neonatal sepsis

PubMed Central

Madan, Juliette C; Salari, Richard Cowper; Saxena, Deepti; Davidson, Lisa; O’Toole, George A; Moore, Jason H; Sogin, Mitchell L; Foster, James A; Edwards, William H; Palumbo, Paul; Hibberd, Patricia L

2013-01-01

Background Neonatal sepsis due to intestinal bacterial translocation is a major cause of morbidity and mortality. Understanding microbial colonisation of the gut in prematurity may predict risk of sepsis to guide future strategies to manipulate the microbiome. Methods Prospective longitudinal study of premature infants. Stool samples were obtained weekly. DNA was extracted and the V6 hypervariable region of 16S rRNA was amplified followed by high throughput pyrosequencing, comparing subjects with and without sepsis. Results Six neonates were 24–27 weeks gestation at birth and had 18 samples analysed. Two subjects had no sepsis during the study period, two developed late-onset culture-positive sepsis and two had culture-negative systemic inflammation. 324 350 sequences were obtained. The meconium was not sterile and had predominance of Lactobacillus, Staphylococcus and Enterobacteriales. Overall, infants who developed sepsis began life with low microbial diversity, and acquired a predominance of Staphylococcus, while healthy infants had more diversity and predominance of Clostridium, Klebsiella and Veillonella. Conclusions In very low birth weight infants, the authors found that meconium is not sterile and is less diverse from birth in infants who will develop late-onset sepsis. Empiric, prolonged antibiotics profoundly decrease microbial diversity and promote a microbiota that is associated not only with neonatal sepsis, but the predominant pathogen previously identified in the microbiome. Our data suggest that there may be a ‘healthy microbiome’ present in extremely premature neonates that may ameliorate risk of sepsis. More research is needed to determine whether altered antibiotics, probiotics or other novel therapies can re-establish a healthy microbiome in neonates. PMID:22562869

Species-Specific Involvement of Integrin αIIbβ3 in a Monoclonal Antibody CH12 Triggers Off-Target Thrombocytopenia in Cynomolgus Monkeys.

PubMed

Zhang, Yiting; Sun, Jianhua; Tan, Minjia; Liu, Yongzhen; Li, Qian; Jiang, Hua; Wang, Huamao; Li, Zonghai; Wan, Wei; Jiang, Hualiang; Lu, Henglei; Wang, Bingshun; Ren, Jin; Gong, Likun

2018-04-07

CH12 is a novel humanized monoclonal antibody against epidermal growth factor receptor variant III (EGFRvIII) for cancer treatment. Unfortunately, in pre-clinical safety evaluation studies, acute thrombocytopenia was observed after administration of CH12 in cynomolgus monkeys, but not rats. More importantly, in vitro experiments found that CH12 can bind and activate platelets in cynomolgus monkey, but not human peripheral blood samples. Cynomolgus monkey-specific thrombocytopenia has been reported previously; however, the underlying mechanism remains unclear. Here, we first showed that CH12 induced thrombocytopenia in cynomolgus monkeys through off-target platelet binding and activation, resulting in platelet destruction. We subsequently found that integrin αIIbβ3 (which is expressed on platelets) contributed to this off-target toxicity. Furthermore, three-dimensional structural modeling of the αIIbβ3 molecules in cynomolgus monkeys, humans, and rats suggested that an additional unique loop exists in the ligand-binding pocket of the αIIb subunit in cynomolgus monkeys, which may explain why CH12 binds to platelets only in cynomolgus monkeys. Moreover, this study supported the hypothesis that the minor differences between cynomolgus monkeys and humans can confuse human risk assessments and suggests that species differences can help the prediction of human risks and avoid losses in drug development. Copyright © 2018. Published by Elsevier Inc.

Achieving a satisfactory clinical and biochemical response in antiphospholipid syndrome and severe thrombocytopenia with rituximab: two case reports.

PubMed

Gamoudi, Donia; Cutajar, Melanie; Gamoudi, Nadia; Camilleri, David James; Gatt, Alex

2017-06-01

In AP syndrome (APS) with severe thrombocytopenia, rituximab represents a unique drug which can balance the effect of bleeding and thrombosis. By reducing the production of autoantibodies, rituximab can simultaneously raise the platelets and reduce the chance of thrombosis by suppressing APL antibodies. Rituximab can supersede splenectomy as second-line therapy in similar patients.

[Neonatal tumours and congenital malformations].

PubMed

Berbel Tornero, O; Ortega García, J A; Ferrís i Tortajada, J; García Castell, J; Donat i Colomer, J; Soldin, O P; Fuster Soler, J L

2008-06-01

The association between pediatric cancer and congenital abnormalities is well known but, there is no exclusive data on the neonatal period and the underlying etiopathogenic mechanisms are unknown. First, to analyze the frequency of neonatal tumours associated with congenital abnormalities; and second, to comment on the likely etiopathogenic hypotheses of a relationship between neonatal tumours and congenital abnormalities. Historical series of neonatal tumours from La Fe University Children's Hospital in Valencia (Spain), from January 1990 to December 1999. Histological varieties of neonatal tumours and associated congenital abnormalities were described. A systematic review of the last 25 years was carried out using Medline, Cancerlit, Index Citation Science and Embase. The search profile used was the combination of "neonatal/congenital-tumors/cancer/neoplasms" and "congenital malformations/birth defects". 72 neonatal tumours were identified (2.8% of all pediatric cancers diagnosed in our hospital) and in 15 cases (20.8%) there was some associated malformation, disease or syndrome. The association between congenital abnormalities and neonatal tumours were: a) angiomas in three patients: two patients with congenital heart disease with a choanal stenosis, laryngomalacia; b) neuroblastomas in two patients: horseshoe kidney with vertebral anomalies and other with congenital heart disease; c) teratomas in two patients: one with cleft palate with vertebral anomalies and other with metatarsal varus; d) one tumour of the central nervous system with Bochdaleck hernia; e) heart tumours in four patients with tuberous sclerosis; f) acute leukaemia in one patient with Down syndrome and congenital heart disease; g) kidney tumour in one case with triventricular hydrocephaly, and h) adrenocortical tumour: hemihypertrophy. The publications included the tumours diagnosed in different pediatric periods and without unified criteria to classify the congenital abnormalities. Little data

Multidrug-resistant organisms in neonatal sepsis in two tertiary neonatal ICUs, Egypt.

PubMed

Awad, Hesham A; Mohamed, Maha H; Badran, Nabil F; Mohsen, Manal; Abd-Elrhman, Al-Sayed A

2016-03-01

Neonatal sepsis remains a serious problem in any neonatal intensive care unit (NICU). Bacterial organisms have developed increased resistance to commonly used antibiotics. Because not enough data are available from Egypt, the aim of the present study was to determine the causative bacteria and the level of their resistance to commonly used antibiotics in tertiary NICUs in Cairo, Egypt. A 3.5-year retrospective study was carried out at NICUs of the Children's Hospital of Ain Shams University and that of El-Hussein Hospital, Al-Azhar University, Egypt. Records of neonates were reviewed. All neonates with culture-proven sepsis were included in the study. Almost one-third of the admitted neonates (33.4%) were diagnosed as having neonatal sepsis, 32.25% of them culture-proven. Early/late onset sepsis was found in 35.4 and 64.6%, respectively. Gram-negative/gram-positive bacteria was found in 68 to 25.6%. Fungal infection was detected in 9% of the isolates. Escherichia coli was the main pathogen isolated in both early-onset sepsis (41.2%) and late-onset sepsis (24.5%). Overall, 77% of the isolates were multidrug-resistant (60% of gram-positive bacteria and 83.4% of gram-negative bacteria). Nearly 80% (79%) of mortality was caused by multidrug-resistant organisms. Gram-positive and gram-negative bacteria showed high resistance against commonly used antibiotics such as ampicillin, amoxicillin, cefotaxime, ceftriaxone, and gentamicin. There is an alarming increase in antibiotic resistance to the commonly used antibiotics. Continuous surveillance for antibiotic susceptibility is needed to ensure proper empirical therapy. Improvement of infection control practices, avoidance of irrational use of antibiotics, and revision of the protocols are mandatory in the prevention of neonatal sepsis.

Safety and Efficacy of a Single Dose of Anti-D (WinRho®) in Severe Thrombocytopenia Secondary to Dengue Virus Infection

PubMed Central

Pannu, Ashok Kumar; Bhalla, Ashish; Singhal, Mayank; Suri, Vikas; Shafiq, Nusrat; Varma, Subhash

2017-01-01

Objective: To evaluate the efficacy of a single intravenous (IV) dose of anti-D in severe thrombocytopenia (<20,000) due to dengue virus (DEV) infection. Materials and Methods: An open label, investigator-initiated, randomized interventional study was conducted that included thirty dengue patients (all positive for IgM enzyme-linked immunosorbent assay) with severe thrombocytopenia (<20,000/mm3). Patients were randomized to receive anti-D (50 μg/kg single IV dose) plus supportive therapy or supportive therapy alone. Results: The rate of rise in platelet count was significantly high in the intervention group at 24, 36, and 48 h. At the end of 48 h, 60% patients in the intervention group achieved a platelet count of ≥50,000/mm3 as compared to 6.7% in the control group (P = 0.0019). The requirement of the platelet concentrate infusion in the control group was significantly higher, i.e. 342 ml (±193) as compared to the intervention group requiring only 187 ml (±79). The intervention group showed a significant improvement in bleeding manifestations in all the patients by 24 h in Grade 2 bleed (P = 0.032) and by 48 h in Grade 1 bleed (P = 0.014). Conclusions: Severe thrombocytopenia (≤20,000/mm3) secondary to DEV infection was rapidly and safely reversed by administration of a single dose of 50 μg/kg (250 IU/kg) anti-D IV. PMID:28250602

Epidemiological and Clinical Features of Severe Fever with Thrombocytopenia Syndrome in Japan, 2013-2014.

PubMed

Kato, Hirofumi; Yamagishi, Takuya; Shimada, Tomoe; Matsui, Tamano; Shimojima, Masayuki; Saijo, Masayuki; Oishi, Kazunori

2016-01-01

Although severe fever with thrombocytopenia syndrome (SFTS) was first reported from Japan in 2013, the precise clinical features and the risk factors for SFTS have not been fully investigated in Japan. Ninety-six cases of severe fever with thrombocytopenia syndrome (SFTS) were notified through the national surveillance system between April 2013 and September 2014 in Japan. All cases were from western Japan, and 82 cases (85%) had an onset between April and August. A retrospective observational study of the notified SFTS cases was conducted to identify the clinical features and laboratory findings during the same period. Of 96 notified cases, 49 (51%) were included in this study. Most case-patients were of advanced age (median age 78 years) and were retired or unemployed, or farmers. These case-patients had a history of outdoor activity within 2 weeks before the onset of illness. The median serum C-reactive protein concentration was slightly elevated at admission. Fungal infections such as invasive aspergilosis were found in 10% of these case-patients. Hemophagocytosis was observed in 15 of the 18 case-patients (83%) whose bone marrow samples were available. Fifteen cases were fatal, giving a case-fatality proportion of 31%. The proportion of neurological abnormalities and serum concentrations of lactate dehydrogenase and aspartate aminotransferase were significantly higher in the fatal cases than in the nonfatal cases during hospitalization. Appearance of neurological abnormality may be useful for predicting the prognosis in SFTS patients.

Weight loss, leukopenia and thrombocytopenia associated with sustained virologic response to Hepatitis C treatment

PubMed Central

Suwantarat, Nuntra; Tice, Alan D.; Khawcharoenporn, Thana; Chow, Dominic C.

2010-01-01

OBJECTIVE: To identify apparent adverse effects of treatment of chronic hepatitis C and their relationship to sustained virologic response (SVR). METHODS: A retrospective study was conducted of all Hepatitis C virus (HCV)-infected patients treated with pegylated interferon and ribavirin in an academic ambulatory infectious disease practice. Clinical and laboratory characteristics were compared between patients with SVR and without SVR. RESULTS: Fifty-four patients completed therapy with the overall SVR rate of 76%. SVR was associated with genotype non-1 (P=0.01), weight loss more than 5 kilograms (P=0.04), end of treatment leukopenia (P=0.02) and thrombocytopenia (P=0.05). In multivariate analysis, SVR was significant associated with HCV genotype non-1 (Adjusted Odd Ratio [AOR] 15.22; CI 1.55 to 149.72; P=0.02), weight loss more than 5 kilograms, (AOR 5.74; CI 1.24 to 26.32; P=0.04), and end of treatment white blood cell count level less than 3 X 103 cells/µl (AOR 9.09; CI 1.59 to 52.63; P=0.02). Thrombocytopenia was not significant after adjustment. Other factors including age, gender, ethnicity, injection drug use, viral load, anemia, alanine transaminase level, and liver histology did not reach statistical significance. CONCLUSION: Besides non-1 genotype, SVR was found to be independently associated with weight loss during therapy, and leukopenia at the end of HCV treatment. These correlations suggest continuation of therapy despite adverse effects, may be of benefit. PMID:20107528

Thrombocytopenia induced by the histone deacetylase inhibitor abexinostat involves p53-dependent and -independent mechanisms.

PubMed

Ali, A; Bluteau, O; Messaoudi, K; Palazzo, A; Boukour, S; Lordier, L; Lecluse, Y; Rameau, P; Kraus-Berthier, L; Jacquet-Bescond, A; Lelièvre, H; Depil, S; Dessen, P; Solary, E; Raslova, H; Vainchenker, W; Plo, I; Debili, N

2013-07-25

Abexinostat is a pan histone deacetylase inhibitor (HDACi) that demonstrates efficacy in malignancy treatment. Like other HDACi, this drug induces a profound thrombocytopenia whose mechanism is only partially understood. We have analyzed its effect at doses reached in patient plasma on in vitro megakaryopoiesis derived from human CD34(+) cells. When added at day 0 in culture, abexinostat inhibited CFU-MK growth, megakaryocyte (MK) proliferation and differentiation. These effects required only a short incubation period. Decreased proliferation was due to induction of apoptosis and was not related to a defect in TPO/MPL/JAK2/STAT signaling. When added later (day 8), the compound induced a dose-dependent decrease (up to 10-fold) in proplatelet (PPT) formation. Gene profiling from MK revealed a silencing in the expression of DNA repair genes with a marked RAD51 decrease at protein level. DNA double-strand breaks were increased as attested by elevated γH2AX phosphorylation level. Moreover, ATM was phosphorylated leading to p53 stabilization and increased BAX and p21 expression. The use of a p53 shRNA rescued apoptosis, and only partially the defect in PPT formation. These results suggest that HDACi induces a thrombocytopenia by a p53-dependent mechanism along MK differentiation and a p53-dependent and -independent mechanism for PPT formation.

Maternal and neonatal tetanus

PubMed Central

Thwaites, C Louise; Beeching, Nicholas J; Newton, Charles R

2017-01-01

Maternal and neonatal tetanus is still a substantial but preventable cause of mortality in many developing countries. Case fatality from these diseases remains high and treatment is limited by scarcity of resources and effective drug treatments. The Maternal and Neonatal Tetanus Elimination Initiative, launched by WHO and its partners, has made substantial progress in eliminating maternal and neonatal tetanus. Sustained emphasis on improvement of vaccination coverage, birth hygiene, and surveillance, with specific approaches in high-risk areas, has meant that the incidence of the disease continues to fall. Despite this progress, an estimated 58 000 neonates and an unknown number of mothers die every year from tetanus. As of June, 2014, 24 countries are still to eliminate the disease. Maintenance of elimination needs ongoing vaccination programmes and improved public health infrastructure. PMID:25149223

The kinetics of unmatched and HLA-matched 111in-labelled homologous platelets in recipients with chronic marrow hypoplasia and anti-platelet immunity.

PubMed

Peters, A M; Porter, J B; Saverymuttu, S H; Malik, F; Zuiable, A; Lavender, J P; Schwarz, G; Lewis, S M; Gordon-Smith, E C

1985-05-01

The kinetics of homologous platelets, labelled in plasma with 111In-tropolonate, have been studied in five recipients with chronic marrow hypoplasia and severe thrombocytopenia, who were refractory to platelet transfusions as a result of alloimmunization. Mean platelet life span (MPLS), recovery, plasma 111In level and splenic and hepatic uptake kinetics were studied on two occasions, one using HLA-matched platelets and the other unmatched platelets. In each case, recovery of labelled platelets at 1 h post-injection and MPLS improved with HLA matching, although this improvement was highly variable. Only two of the five subjects would have derived any significant benefit from HLA-matched as compared with unmatched platelet transfusions. It was concluded that the need exists for additional cross-matching procedures, possibly related to platelet specific antigens, in patients who remain refractory to platelet transfusion.

Oral Lesions in Neonates

PubMed Central

Rao, Roopa S; Majumdar, Barnali; Jafer, Mohammed; Maralingannavar, Mahesh; Sukumaran, Anil

2016-01-01

ABSTRACT Oral lesions in neonates represent a wide range of diseases often creating apprehension and anxiety among parents. Early examination and prompt diagnosis can aid in prudent management and serve as baseline against the future course of the disease. The present review aims to enlist and describe the diagnostic features of commonly encountered oral lesions in neonates. How to cite this article: Patil S, Rao RS, Majumdar B, Jafer M, Maralingannavar M, Sukumaran A. Oral Lesions in Neonates. Int J Clin Pediatr Dent 2016;9(2):131-138. PMID:27365934

Congenital hypoplastic bone marrow failure associated with a de novo partial deletion of the MECOM gene at 3q26.2.

PubMed

Kjeldsen, Eigil; Veigaard, Christopher; Aggerholm, Anni; Hasle, Henrik

2018-05-20

Congenital hypoplastic bone marrow failure is a rare condition in neonates. The genetics and mechanisms behind are largely obscure. Here we characterize a neonate presenting with congenital thrombocytopenia and anemia. During the first 2-4 weeks after birth the neonate developed severe neutropenia while the lymphoid lineages were unaffected. The neonate was without dysmorphic signs. A de novo mono-allelic constitutional microdeletion of 175.1 kb at 3q26.2 affecting exon 2 of MECOM, involving MDS1 but not EVI1, was identified as the only copy number alteration by oligo-based array-CGH analysis. Expression analysis showed profoundly reduced expression of multiple MECOM transcripts in the bone marrow cells. Whole exome sequencing detected no pathogenic mutations in genes known to be associated with inherited bone marrow failure syndromes. The patient was successfully treated with hematopoietic stem cell transplantation at 5 months of age. Interstitial deletions encompassing the 3q26.2 region are very rare. A literature search revealed two previous cases with microdeletions involving this region, and the cases were associated with congenital thrombocytopenia and anemia, but unaffected lymphopoiesis. Together these data indicate that MECOM may be important for normal myeloid hematopoiesis in humans but dispensable for lymphoid differentiation. We suggest that partial deletion in MECOM may be a primary event associated with congenital pancytopenia. Copyright © 2018 Elsevier B.V. All rights reserved.

Determinants of neonatal mortality in Indonesia.

PubMed

Titaley, Christiana R; Dibley, Michael J; Agho, Kingsley; Roberts, Christine L; Hall, John

2008-07-09

Neonatal mortality accounts for almost 40 per cent of under-five child mortality, globally. An understanding of the factors related to neonatal mortality is important to guide the development of focused and evidence-based health interventions to prevent neonatal deaths. This study aimed to identify the determinants of neonatal mortality in Indonesia, for a nationally representative sample of births from 1997 to 2002. The data source for the analysis was the 2002-2003 Indonesia Demographic and Health Survey from which survival information of 15,952 singleton live-born infants born between 1997 and 2002 was examined. Multilevel logistic regression using a hierarchical approach was performed to analyze the factors associated with neonatal deaths, using community, socio-economic status and proximate determinants. At the community level, the odds of neonatal death was significantly higher for infants from East Java (OR = 5.01, p = 0.00), and for North, Central and Southeast Sulawesi and Gorontalo combined (OR = 3.17, p = 0.03) compared to the lowest neonatal mortality regions of Bali, South Sulawesi and Jambi provinces. A progressive reduction in the odds was found as the percentage of deliveries assisted by trained delivery attendants in the cluster increased. The odds of neonatal death were higher for infants born to both mother and father who were employed (OR = 1.84, p = 0.00) and for infants born to father who were unemployed (OR = 2.99, p = 0.02). The odds were also higher for higher rank infants with a short birth interval (OR = 2.82, p = 0.00), male infants (OR = 1.49, p = 0.01), smaller than average-sized infants (OR = 2.80, p = 0.00), and infant's whose mother had a history of delivery complications (OR = 1.81, p = 0.00). Infants receiving any postnatal care were significantly protected from neonatal death (OR = 0.63, p = 0.03). Public health interventions directed at reducing neonatal death should address community, household and individual level factors

The effect of high risk pregnancy on duration of neonatal stay in neonatal intensive care unit.

PubMed

Afrasiabi, Narges; Mohagheghi, Parisa; Kalani, Majid; Mohades, Gholam; Farahani, Zahra

2014-08-01

High risk pregnancies increase the risk of neonatal mortality and morbidity. In order to identify the influence of pregnancy complications on the period of neonatal stay in Neonatal Intensive Care Units (NICUs), an analysis has been carried out in our center. In a cross-sectional-descriptive analytical study, the data including NICU length of stay was gathered from 526 medical records of neonates. We also assessed their maternal complications such as premature rapture of membranes (PROM), urinary tract infection (UTI), preeclampsia, oligohydramnios, and twin/triplet pregnancy. Finally we analyzed the relation between variables by SPSS statistics software version 19. The level of significance was considered P<0.05. 37 of 526 neonatal medical records were excluded. Of the 489 babies hospitalized in NICU for 1 to 54 days; 28.42% born were preterm, 308 with birth weight <2500 gram and 170 with birth weight between 2500 and 4000 gram. There was a significant relation between length of neonatal NICU stay and maternal PROM (P=0.001), preeclampsia (P=0.01), UTI (P=0.02), multiple gestation (P=0.03), and oligohydramnios (P=0.003). We found a positive correlation between numbers of gestation and length of NICU stay (P=0.03). A positive correlation existed between neonatal complication and length of NICU stay (P<0.001). By increasing maternal health level and prenatal care services, neonatal outcome can be improved and length of stay in NICUs decreased.

Neonatal hypoglycemia.

PubMed

Adamkin, David H

2017-02-01

A consistent definition for neonatal hypoglycemia in the first 48 h of life continues to elude us. Enhanced understanding of metabolic disturbances and genetic disorders that underlie alterations in postnatal glucose homeostasis has added useful information to understanding transitional hypoglycemia. This growth in knowledge still has not led to what we need to know: "How low is too low and for how long?" This article reviews the current state of understanding of neonatal hypoglycemia and how different approaches reach different "expert" opinions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Specialist teams for neonatal transport to neonatal intensive care units for prevention of morbidity and mortality.

PubMed

Chang, Alvin S M; Berry, Andrew; Jones, Lisa J; Sivasangari, Subramaniam

2015-10-28

Maternal antenatal transfers provide better neonatal outcomes. However, there will inevitably be some infants who require acute transport to a neonatal intensive care unit (NICU). Because of this, many institutions develop services to provide neonatal transport by specially trained health personnel. However, few studies report on relevant clinical outcomes in infants requiring transport to NICU. To determine the effects of specialist transport teams compared with non-specialist transport teams on the risk of neonatal mortality and morbidity among high-risk newborn infants requiring transport to neonatal intensive care. We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 7), MEDLINE (1966 to 31 July 2015), EMBASE (1980 to 31 July 2015), CINAHL (1982 to 31 July 2015), conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. randomised, quasi-randomised or cluster randomised controlled trials. neonates requiring transport to a neonatal intensive care unit. transport by a specialist team compared to a non-specialist team. any of the following outcomes - death; adverse events during transport leading to respiratory compromise; and condition on admission to the neonatal intensive care unit. The methodological quality of the trials was assessed using the information provided in the studies and by personal communication with the author. Data on relevant outcomes were extracted and the effect size estimated and reported as risk ratio (RR), risk difference (RD), number needed to treat for an additional beneficial outcome (NNTB) or number needed to treat for an additional harmful outcome (NNTH) and mean difference (MD) for continuous outcomes. Data from cluster randomised trials were not combined for analysis. One trial met the inclusion criteria of this review but was considered ineligible owing to

Impact of neonatal resuscitation trainings on neonatal and perinatal mortality: a systematic review and meta-analysis

PubMed Central

Patel, Archana; Kurhe, Kunal; Bhargava, Savita; Bang, Akash

2017-01-01

Background Training of birth attendants in neonatal resuscitation is likely to reduce birth asphyxia and neonatal mortality. We performed a systematic review and meta-analysis to assess the impact of neonatal resuscitation training (NRT) programme in reducing stillbirths, neonatal mortality, and perinatal mortality Methods We considered studies where any NRT was provided to healthcare personnel involved in delivery process and handling of newborns. We searched MEDLINE, CENTRAL, ERIC and other electronic databases. We also searched ongoing trials and bibliographies of the retrieved articles, and contacted experts for unpublished work. We undertook screening of studies and assessment of risk of bias in duplicates. We performed review according to Cochrane Handbook. We assessed the quality of evidence using the GRADE approach. Results We included 20 trials with 1 653 805 births in this meta-analysis. The meta-analysis of NRT versus control shows that NRT decreases the risk of all stillbirths by 21% (RR 0.79, 95% CI 0.44 to 1.41), 7-day neonatal mortality by 47% (RR 0.53, 95% CI 0.38 to 0.73), 28-day neonatal mortality by 50% (RR 0.50, 95% CI 0.37 to 0.68) and perinatal mortality by 37% (RR 0.63, 95% CI 0.42 to 0.94). The meta-analysis of pre-NRT versus post-NRT showed that post-NRT decreased the risk of all stillbirths by 12% (RR 0.88, 95% CI 0.83 to 0.94), fresh stillbirths by 26% (RR 0.74, 95% CI 0.61 to 0.90), 1-day neonatal mortality by 42% (RR 0.58, 95% CI 0.42 to 0.82), 7-day neonatal mortality by 18% (RR 0.82, 95% CI 0.73 to 0.93), 28-day neonatal mortality by 14% (RR 0.86, 95% CI 0.65 to 1.13) and perinatal mortality by 18% (RR 0.82, 95% CI 0.74 to 0.91). Conclusions Findings of this review show that implementation of NRT improves neonatal and perinatal mortality. Further good quality randomised controlled trials addressing the role of NRT for improving neonatal and perinatal outcomes may be warranted. Trial registration number PROSPERO

Role of massage therapy on reduction of neonatal hyperbilirubinemia in term and preterm neonates: a review of clinical trials.

PubMed

Garg, Bhawan Deep; Kabra, Nandkishor S; Balasubramanian, Haribalakrishna

2017-09-13

Neonatal hyperbilirubinemia (NNH) is one of the leading causes of admissions in nursery throughout the world. It affects approximately 2.4-15% of neonates during the first 2 weeks of life. To evaluate the role of massage therapy for reduction of NNH in both term and preterm neonates. The literature search was done for various randomized control trials (RCTs) by searching the Cochrane Library, PubMed, and EMBASE. This review included total of 10 RCTs (two in preterm neonates and eight in term neonates) that fulfilled inclusion criteria. In most of the trials, Field massage was given. Six out of eight trials reported reduction in bilirubin levels in term neonates. However, only one trial (out of two) reported significant reduction in bilirubin levels in preterm neonates. Both trials in preterm neonates and most of the trials in term neonates (five trials) reported increased stool frequencies. Role of massage therapy in the management of NNH is supported by the current evidence. However, due to limitations of the trials, current evidences are not sufficient to use massage therapy for the management of NNH in routine practice.

Indirect neonatal hyperbilirubinemia in hospitalized neonates on the Thai-Myanmar border: a review of neonatal medical records from 2009 to 2014.

PubMed

Thielemans, L; Trip-Hoving, M; Landier, J; Turner, C; Prins, T J; Wouda, E M N; Hanboonkunupakarn, B; Po, C; Beau, C; Mu, M; Hannay, T; Nosten, F; Van Overmeire, B; McGready, R; Carrara, V I

2018-06-12

Indirect neonatal hyperbilirubinemia (INH) is a common neonatal disorder worldwide which can remain benign if prompt management is available. However there is a higher morbidity and mortality risk in settings with limited access to diagnosis and care. The manuscript describes the characteristics of neonates with INH, the burden of severe INH and identifies factors associated with severity in a resource-constrained setting. We conducted a retrospective evaluation of anonymized records of neonates hospitalized on the Thai-Myanmar border. INH was defined according to the National Institute for Health and Care Excellence guidelines as 'moderate' if at least one serum bilirubin (SBR) value exceeded the phototherapy threshold and as 'severe' if above the exchange transfusion threshold. Out of 2980 records reviewed, 1580 (53%) had INH within the first 14 days of life. INH was moderate in 87% (1368/1580) and severe in 13% (212/1580). From 2009 to 2011, the proportion of severe INH decreased from 37 to 15% and the mortality dropped from 10% (8/82) to 2% (7/449) coinciding with the implementation of standardized guidelines and light-emitting diode (LED) phototherapy. Severe INH was associated with: prematurity (< 32 weeks, Adjusted Odds Ratio (AOR) 3.3; 95% CI 1.6-6.6 and 32 to 37 weeks, AOR 2.2; 95% CI 1.6-3.1), Glucose-6-phosphate dehydrogenase deficiency (G6PD) (AOR 2.3; 95% CI 1.6-3.3), potential ABO incompatibility (AOR 1.5; 95% CI 1.0-2.2) and late presentation (AOR 1.8; 95% CI 1.3-2.6). The risk of developing severe INH and INH-related mortality significantly increased with each additional risk factor. INH is an important cause of neonatal hospitalization on the Thai-Myanmar border. Risk factors for severity were similar to previous reports from Asia. Implementing standardized guidelines and appropriate treatment was successful in reducing mortality and severity. Accessing to basic neonatal care including SBR testing, LED phototherapy and G6PD screening can

The prevalence of neonatal jaundice and risk factors in healthy term neonates at National District Hospital in Bloemfontein

PubMed Central

2018-01-01

Background Neonatal jaundice affects one in two infants globally. The jaundice is the result of an accumulation of bilirubin as foetal haemoglobin is metabolised by the immature liver. High serum levels of bilirubin result in lethargy, poor feeding and kernicterus of the infant. Aim The main aim of this article was to determine the prevalence of neonatal jaundice and secondly to explore its risk factors in healthy term neonates. Setting Maternity ward, National District Hospital, Bloemfontein, South Africa. Methods In this cross-sectional study, mothers and infants were conveniently sampled after delivery and before discharge. The mothers were interviewed and their case records were reviewed for risk factors for neonatal jaundice and the clinical appearance and bilirubin levels of the infants were measured with a non-invasive transcutaneous bilirubin meter. Results A total of 96 mother-infant pairs were included in the study. The prevalence of neonatal jaundice was 55.2%; however, only 10% of black babies who were diagnosed with jaundice appeared clinically jaundiced. Normal vaginal delivery was the only risk factor associated with neonatal jaundice. Black race and maternal smoking were not protective against neonatal jaundice as in some other studies. Conclusion More than half (55.2%) of healthy term neonates developed neonatal jaundice. As it is difficult to clinically diagnose neonatal jaundice in darker pigmented babies, it is recommended that the bilirubin level of all babies should be checked with a non-invasive bilirubin meter before discharge from hospital or maternity unit as well as during the first clinic visit on day 3 after birth.

Screening for G6PD Deficiency Among Neonates with Neonatal Jaundice Admitted to Tertiary Care Center: A Need in Disguise.

PubMed

Kumar, Kishwer; Sohaila, Arjumand; Tikmani, Shiyam Sunder; Khan, Iqtidar Ahmed; Zafar, Anila

2015-08-01

This study was conducted to determine the association of Glucose-6-Phosphate Dehydrogenase (G-6-PD) deficiency among neonates admitted with jaundice at the neonatal intensive care unit, well baby nursery and neonatal step down nursery of the Aga Khan University Hospital, Karachi, Pakistan, from January to June 2010. A total of 205 neonates following the selection criteria were included. All selected neonates have their venous blood drawn, saved in EDTA bottle and sent to laboratory of The Aga Khan University Hospital (AKUH). The laboratory results of whether G-6-PD deficiency was present or not was recorded in the proforma. G-6-PD was deficient in 19 neonates (9.3%). All neonates were male.

Heparin Induced Thrombocytopenia and Re-Thrombosis Associated with Warfarin and Fondaparinux in a Child

PubMed Central

Maurer, Scott H.; Wilimas, Judith A.; Wang, Winfred C.; Reiss, Ulrike M.

2016-01-01

An 11 year-old female developed heparin induced thrombocytopenia (HIT) with thrombosis during therapy for lower extremity deep vein thrombosis and pulmonary embolism. Transition from bivalirudin, a direct thrombin inhibitor (DTI), to warfarin resulted in extensive re-thrombosis, and fondaparinux therapy similarly failed. She was then treated with argatroban, and transitioned successfully to warfarin after nine weeks. The risk of re-thrombosis was ultimately reduced by allowing time for the thrombogenic potential to abate. The argatroban/warfarin transition was monitored with chromogenic factor X levels. This case highlights several difficult problems in pediatric thrombosis. PMID:19415734

Epidemiological and Clinical Features of Severe Fever with Thrombocytopenia Syndrome in Japan, 2013–2014

PubMed Central

Shimada, Tomoe; Matsui, Tamano; Shimojima, Masayuki; Saijo, Masayuki; Oishi, Kazunori

2016-01-01

Although severe fever with thrombocytopenia syndrome (SFTS) was first reported from Japan in 2013, the precise clinical features and the risk factors for SFTS have not been fully investigated in Japan. Ninety-six cases of severe fever with thrombocytopenia syndrome (SFTS) were notified through the national surveillance system between April 2013 and September 2014 in Japan. All cases were from western Japan, and 82 cases (85%) had an onset between April and August. A retrospective observational study of the notified SFTS cases was conducted to identify the clinical features and laboratory findings during the same period. Of 96 notified cases, 49 (51%) were included in this study. Most case-patients were of advanced age (median age 78 years) and were retired or unemployed, or farmers. These case-patients had a history of outdoor activity within 2 weeks before the onset of illness. The median serum C-reactive protein concentration was slightly elevated at admission. Fungal infections such as invasive aspergilosis were found in 10% of these case-patients. Hemophagocytosis was observed in 15 of the 18 case-patients (83%) whose bone marrow samples were available. Fifteen cases were fatal, giving a case-fatality proportion of 31%. The proportion of neurological abnormalities and serum concentrations of lactate dehydrogenase and aspartate aminotransferase were significantly higher in the fatal cases than in the nonfatal cases during hospitalization. Appearance of neurological abnormality may be useful for predicting the prognosis in SFTS patients. PMID:27776187

Bartter syndrome: presentation in an extremely premature neonate.

PubMed

Flores, F X; Ojeda, F J; Calhoun, D A

2013-08-01

Reports of Bartter syndrome in premature neonates are rare. We describe the presentation and clinical course of a neonate born at 25.6 weeks estimated gestational age with polyuria, hyponatremia, hypokalemia and hypercalciuria ,who was diagnosed with neonatal Bartter syndrome. The evaluation, diagnosis and management of neonatal Bartter syndrome in this premature neonate are discussed.

Trends in neonatal and post-neonatal tetanus admissions at a Nigerian teaching hospital.

PubMed

Oyedeji, Olusola Adetunji; Fadero, Francis; Joel-Medewase, Victor; Elemile, Peter; Oyedeji, Gabriel Ademola

2012-12-15

Tetanus accounts for high morbidity and case fatality rates in developing countries. This study therefore aimed to identify reasons for the persistence of this disease. Paediatric admissions at Ladoke Akintola University Teaching Hospital between 1 January 2006 and 31 December 2008 diagnosed with tetanus were studied. Data was analyzed with SPSS 18 and statistical significance was set at p < 0.05. Of the total 1,681 paediatric admissions, 30 (1.8%) had tetanus. Of the 878 neonatal admissions, 8 (0.9%) had tetanus, while 22 (2.7%) of the total 803 post-neonatal admissions had tetanus. Neonatal tetanus admissions were significantly higher in 2006 compared to 2007 and 2008 (7 [2.3%] versus 1 [0.2%] [χ²= 7.50, P=0.01]). Of the eight mothers whose neonates had tetanus, seven did not receive tetanus toxoids in pregnancy and five (62.5%) were secondary school dropouts. Post-neonatal tetanus cases admitted in the years 2006, 2007, and 2008 were 4, 12, and 6 children respectively. Most of these 22 children did not receive tetanus toxoid immunization in their first year of life. None of the 22 children received booster doses of tetanus toxoids after their first years of life. Mothers at risk of their babies having tetanus, such as secondary school dropouts, must be identified antenatally and vaccinated with tetanus toxiod. Their babies should also receive good care post-delivery. Completion of routine tetanus toxoid schedule in the first year and booster doses in the post-neonatal age should be ensured.

Determinants of neonatal mortality in Indonesia

PubMed Central

Titaley, Christiana R; Dibley, Michael J; Agho, Kingsley; Roberts, Christine L; Hall, John

2008-01-01

Background Neonatal mortality accounts for almost 40 per cent of under-five child mortality, globally. An understanding of the factors related to neonatal mortality is important to guide the development of focused and evidence-based health interventions to prevent neonatal deaths. This study aimed to identify the determinants of neonatal mortality in Indonesia, for a nationally representative sample of births from 1997 to 2002. Methods The data source for the analysis was the 2002–2003 Indonesia Demographic and Health Survey from which survival information of 15,952 singleton live-born infants born between 1997 and 2002 was examined. Multilevel logistic regression using a hierarchical approach was performed to analyze the factors associated with neonatal deaths, using community, socio-economic status and proximate determinants. Results At the community level, the odds of neonatal death was significantly higher for infants from East Java (OR = 5.01, p = 0.00), and for North, Central and Southeast Sulawesi and Gorontalo combined (OR = 3.17, p = 0.03) compared to the lowest neonatal mortality regions of Bali, South Sulawesi and Jambi provinces. A progressive reduction in the odds was found as the percentage of deliveries assisted by trained delivery attendants in the cluster increased. The odds of neonatal death were higher for infants born to both mother and father who were employed (OR = 1.84, p = 0.00) and for infants born to father who were unemployed (OR = 2.99, p = 0.02). The odds were also higher for higher rank infants with a short birth interval (OR = 2.82, p = 0.00), male infants (OR = 1.49, p = 0.01), smaller than average-sized infants (OR = 2.80, p = 0.00), and infant's whose mother had a history of delivery complications (OR = 1.81, p = 0.00). Infants receiving any postnatal care were significantly protected from neonatal death (OR = 0.63, p = 0.03). Conclusion Public health interventions directed at reducing neonatal death should address community

21 CFR 880.5400 - Neonatal incubator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Neonatal incubator. 880.5400 Section 880.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... § 880.5400 Neonatal incubator. (a) Identification. A neonatal incubator is a device consisting of a...

Inhibition of Megakaryocyte Differentiation by Antibody-Drug Conjugates (ADCs) is Mediated by Macropinocytosis: Implications for ADC-induced Thrombocytopenia.

PubMed

Zhao, Hui; Gulesserian, Sara; Ganesan, Sathish Kumar; Ou, Jimmy; Morrison, Karen; Zeng, Zhilan; Robles, Veronica; Snyder, Josh; Do, Lisa; Aviña, Hector; Karki, Sher; Stover, David R; Doñate, Fernando

2017-09-01

Thrombocytopenia is a common adverse event in cancer patients treated with antibody-drug conjugates (ADC), including AGS-16C3F, an ADC targeting ENPP3 (ectonucleotide pyrophosphatase/phosphodiesterase-3) and trastuzumab emtansine (T-DM1). This study aims to elucidate the mechanism of action of ADC-induced thrombocytopenia. ENPP3 expression in platelets and megakaryocytes (MK) was investigated and shown to be negative. The direct effect of AGS-16C3F on platelets was evaluated using platelet rich plasma following the expression of platelet activation markers. Effects of AGS-16C3F, T-DM1, and control ADCs on maturing megakaryocytes were evaluated in an in vitro system in which human hematopoietic stem cells (HSC) were differentiated into MKs. AGS-16C3F, like T-DM1, did not affect platelets directly, but inhibited MK differentiation by the activity of Cys-mcMMAF, its active metabolite. FcγRIIA did not appear to play an important role in ADC cytotoxicity to differentiating MKs. AGS-16C3F, cytotoxic to MKs, did not bind to FcγRIIA on MKs. Blocking the interaction of T-DM1 with FcγRIIA did not prevent the inhibition of MK differentiation and IgG1-mcMMAF was not as cytotoxic to MKs despite binding to FcγRIIA. Several lines of evidence suggest that internalization of AGS-16C3F into MKs is mediated by macropinocytosis. Macropinocytosis activity of differentiating HSCs correlated with cell sensitivity to AGS-16C3F. AGS-16C3F was colocalized with a macropinocytosis marker, dextran-Texas Red in differentiating MKs. Ethyl isopropyl amiloride (EIPA), a macropinocytosis inhibitor, blocked internalization of dextran-Texas Red and AGS-16C3F. These data support the notion that inhibition of MK differentiation via macropinocytosis-mediated internalization plays a role in ADC-induced thrombocytopenia. Mol Cancer Ther; 16(9); 1877-86. ©2017 AACR See related article by Zhao et al., p. 1866 . ©2017 American Association for Cancer Research.

Laser Photoradiation Therapy For Neonatal Jaundice

NASA Astrophysics Data System (ADS)

Hamza, Mostafa; Hamza, Mohammad

1987-04-01

This paper describes our leading experience in the clinical application of laser in the treatment of neonatal jaundice. Currently, the irradiation of jaundiced infants during neonatal life to fluorescent light is the most common treatment of neonatal hyperbilirubinemia. The authors have investigated the photodegradation of bilirubin by laser in vitro and in Gunn rats before embarking on its clinical application in the treatment of jaundice in the new born child. This work was done to study the theraputic effect of laser compared to the currently used phototherapy in the treatment of neonatal jaundice. We selected 16 full term neonates with jaundice to be the subject of this study. The neonates of the study were devided into two groups. The first group was treated with continuous phototherapy . The second group recieved photoradiation therapy with gas laser The laser used was a CW argon-ion laser tuned to oscillate at 488.0 nm wavelength. This wavelength selection was based on our previous studies on the effect of laser irradiation of Gunn rats at different wavelengths. Comparison of the results of both methods of treatment will be reported in detail. The advantages and limitations of laser photoradiation therapy for neonatal jaundice will be discussed.

The Korean Neonatal Network: An Overview

PubMed Central

Chang, Yun Sil; Park, Hyun-Young

2015-01-01

Currently, in the Republic of Korea, despite the very-low-birth rate, the birth rate and number of preterm infants are markedly increasing. Neonatal deaths and major complications mostly occur in premature infants, especially very-low-birth-weight infants (VLBWIs). VLBWIs weigh less than 1,500 g at birth and require intensive treatment in a neonatal intensive care unit (NICU). The operation of the Korean Neonatal Network (KNN) officially started on April 15, 2013, by the Korean Society of Neonatology with support from the Korea Centers for Disease Control and Prevention. The KNN is a national multicenter neonatal network based on a prospective web-based registry for VLBWIs. About 2,000 VLBWIs from 60 participating hospital NICUs are registered annually in the KNN. The KNN has built unique systems such as a web-based real-time data display on the web site and a site-visit monitoring system for data quality surveillance. The KNN should be maintained and developed further in order to generate appropriate, population-based, data-driven, health-care policies; facilitate active multicenter neonatal research, including quality improvement of neonatal care; and ultimately lead to improvement in the prognosis of high-risk newborns and subsequent reduction in health-care costs through the development of evidence-based neonatal medicine in Korea. PMID:26566355

The Korean Neonatal Network: An Overview.

PubMed

Chang, Yun Sil; Park, Hyun-Young; Park, Won Soon

2015-10-01

Currently, in the Republic of Korea, despite the very-low-birth rate, the birth rate and number of preterm infants are markedly increasing. Neonatal deaths and major complications mostly occur in premature infants, especially very-low-birth-weight infants (VLBWIs). VLBWIs weigh less than 1,500 g at birth and require intensive treatment in a neonatal intensive care unit (NICU). The operation of the Korean Neonatal Network (KNN) officially started on April 15, 2013, by the Korean Society of Neonatology with support from the Korea Centers for Disease Control and Prevention. The KNN is a national multicenter neonatal network based on a prospective web-based registry for VLBWIs. About 2,000 VLBWIs from 60 participating hospital NICUs are registered annually in the KNN. The KNN has built unique systems such as a web-based real-time data display on the web site and a site-visit monitoring system for data quality surveillance. The KNN should be maintained and developed further in order to generate appropriate, population-based, data-driven, health-care policies; facilitate active multicenter neonatal research, including quality improvement of neonatal care; and ultimately lead to improvement in the prognosis of high-risk newborns and subsequent reduction in health-care costs through the development of evidence-based neonatal medicine in Korea.

Neonatal chemical hypoglycemia in newborns from pregnancies complicated by type 2 and gestational diabetes mellitus - the importance of neonatal ponderal index.

PubMed

Ramos, Gladys A; Hanley, Alethea A; Aguayo, Jennifer; Warshak, Carri R; Kim, Jae H; Moore, Thomas R

2012-03-01

To determine the frequency and risk factors associated with neonatal chemical hypoglycemia in neonates of mothers with type 2 diabetes and gestational diabetes mellitus (GDM). A retrospective cohort study of women with type 2 diabetes or GDM and their singleton neonates. The primary outcome measure was the presence of neonatal chemical hypoglycemia (capillary plasma equivalent glucose <45 mg/dl) within 1 h of birth. Statistical methods included bivariate and multivariate analyses. 242 mother infant dyads were identified. Sixty-eight (28%) were treated with diet, 110 (46%) with glyburide, and 64 (26%) with insulin. The incidence of neonatal chemical hypoglycemia was 18% (44/242). The incidence was significantly higher in those requiring pharmacotherapy (25% vs. 3%, p < 0.001). The frequency of neonatal chemical hypoglycemia between the glyburide and insulin-treated pregnancies did not differ significantly (23% vs. 27%, p = 0.58). The frequency of neonatal chemical hypoglycemia was statistically associated with birth weight, macrosomia and ponderal index (p < 0.001). Neonatal ponderal index was the strongest predictor of hypoglycemia (adjusted Odds ratio 5.59). Neonatal chemical hypoglycemia occurs more frequently in infants from women with type 2 diabetes and GDM treated with glyburide or insulin. An increased neonatal ponderal index is a strong predictor of significant neonatal chemical hypoglycemia.

Missed Opportunities in Neonatal Deaths in Rwanda: Applying the Three Delays Model in a Cross-Sectional Analysis of Neonatal Death.

PubMed

Wilmot, Efua; Yotebieng, Marcel; Norris, Alison; Ngabo, Fidele

2017-05-01

Objective Administered in a timely manner, current evidence-based interventions could reduce neonatal deaths from infections, intrapartum injuries and complications due to prematurity. The three delays model (delay in seeking care, in arriving at a health facility, and in receiving adequate care), which has been applied to understanding maternal deaths, may be useful for understanding neonatal deaths. We assess the main causes of neonatal deaths in Rwanda and their associated delays. Methods Using a cross-sectional study design, we evaluated data from 2012 from 40 facilities in which babies were delivered. Audit committees in each facility reviewed each neonatal death in the facility and reported finding to the Ministry of Health using structured questionnaires. Information from questionnaires were centralized in an electronic database. At the end of 2012, records from 40 health facilities across Rwanda's five provinces (mainly district hospitals) were available in the database and were used for this analysis. Results Of the 1324 neonates, the major causes of death were: asphyxia and its complications (36.7%), lower respiratory tract infections (LRTI) (22.5%), and prematurity (22.4%). At least one delay was experienced by nearly three-quarters of neonates: Maternal Delay in Seeking Care 22.1%, Maternal Delay in Arrival to Care 11.2%, Maternal Delay in Adequate Care 14.2%, Neonatal Delay in Seeking Care 8.1%, Neonatal Delay in Arrival to Care 9.3%, and Neonatal Delay in Adequate Care 29.1%. Neonates with each of the main causes of death had statistically significantly increased odds of experiencing Maternal Delay in Seeking Care. Asphyxia deaths had increased odds of experiencing all three Maternal Delays. LRTI deaths had increased odds of all three Neonatal Delays. Conclusion Delays for women in seeking obstetrical care is a critical factor associated with the main causes of neonatal death in Rwanda. Improving obstetrical care quality could reduce neonatal deaths

Gene editing rescue of a novel MPL mutant associated with congenital amegakaryocytic thrombocytopenia.

PubMed

Cleyrat, Cédric; Girard, Romain; Choi, Eun H; Jeziorski, Éric; Lavabre-Bertrand, Thierry; Hermouet, Sylvie; Carillo, Serge; Wilson, Bridget S

2017-09-26

Thrombopoietin (Tpo) and its receptor (Mpl) are the principal regulators of early and late thrombopoiesis and hematopoietic stem cell maintenance. Mutations in MPL can drastically impair its function and be a contributing factor in multiple hematologic malignancies, including congenital amegakaryocytic thrombocytopenia (CAMT). CAMT is characterized by severe thrombocytopenia at birth, which progresses to bone marrow failure and pancytopenia. Here we report unique familial cases of CAMT that presented with a previously unreported MPL mutation: T814C (W272R) in the background of the activating MPL G117T (K39N or Baltimore) mutation. Confocal microscopy, proliferation and surface biotinylation assays, co-immunoprecipitation, and western blotting analysis were used to elucidate the function and trafficking of Mpl mutants. Results showed that Mpl protein bearing the W272R mutation, alone or together with the K39N mutation, lacks detectable surface expression while being strongly colocalized with the endoplasmic reticulum (ER) marker calreticulin. Both WT and K39N-mutated Mpl were found to be signaling competent, but single or double mutants bearing W272R were unresponsive to Tpo. Function of the deficient Mpl receptor could be rescued by using 2 separate approaches: (1) GRASP55 overexpression, which partially restored Tpo-induced signaling of mutant Mpl by activating an autophagy-dependent secretory pathway and thus forcing ER-trapped immature receptors to traffic to the cell surface; and (2) CRISPR-Cas9 gene editing used to repair MPL T814C mutation in transfected cell lines and primary umbilical cord blood-derived CD34 + cells. We demonstrate proof of principle for rescue of mutant Mpl function by using gene editing of primary hematopoietic stem cells, which indicates direct therapeutic applications for CAMT patients.

Gene editing rescue of a novel MPL mutant associated with congenital amegakaryocytic thrombocytopenia

PubMed Central

Girard, Romain; Choi, Eun H.; Jeziorski, Éric; Lavabre-Bertrand, Thierry; Hermouet, Sylvie; Carillo, Serge; Wilson, Bridget S.

2017-01-01

Thrombopoietin (Tpo) and its receptor (Mpl) are the principal regulators of early and late thrombopoiesis and hematopoietic stem cell maintenance. Mutations in MPL can drastically impair its function and be a contributing factor in multiple hematologic malignancies, including congenital amegakaryocytic thrombocytopenia (CAMT). CAMT is characterized by severe thrombocytopenia at birth, which progresses to bone marrow failure and pancytopenia. Here we report unique familial cases of CAMT that presented with a previously unreported MPL mutation: T814C (W272R) in the background of the activating MPL G117T (K39N or Baltimore) mutation. Confocal microscopy, proliferation and surface biotinylation assays, co-immunoprecipitation, and western blotting analysis were used to elucidate the function and trafficking of Mpl mutants. Results showed that Mpl protein bearing the W272R mutation, alone or together with the K39N mutation, lacks detectable surface expression while being strongly colocalized with the endoplasmic reticulum (ER) marker calreticulin. Both WT and K39N-mutated Mpl were found to be signaling competent, but single or double mutants bearing W272R were unresponsive to Tpo. Function of the deficient Mpl receptor could be rescued by using 2 separate approaches: (1) GRASP55 overexpression, which partially restored Tpo-induced signaling of mutant Mpl by activating an autophagy-dependent secretory pathway and thus forcing ER-trapped immature receptors to traffic to the cell surface; and (2) CRISPR-Cas9 gene editing used to repair MPL T814C mutation in transfected cell lines and primary umbilical cord blood–derived CD34+ cells. We demonstrate proof of principle for rescue of mutant Mpl function by using gene editing of primary hematopoietic stem cells, which indicates direct therapeutic applications for CAMT patients. PMID:29296828

Implementation of a rapid HIT immunoassay at a university hospital - Retrospective analysis of HIT laboratory orders in patients with thrombocytopenia.

PubMed

Black, Anne; Heimerl, Susanne; Oertli, Linnéa; Wilczek, Wolf; Greinacher, Andreas; Spannagl, Michael; Herr, Wolfgang; Hart, Christina

2017-10-01

Heparin-induced thrombocytopenia (HIT) is a rare cause of thrombocytopenia and a potentially life-threatening adverse drug reaction. Clinical overdiagnosis of HIT results in costly laboratory tests and anticoagulation. Criteria and algorithms for diagnosis are established, but their translation into clinical practice is still challenging. In a retrospective approach we studied all HIT related laboratory test requests within four years and evaluated data before (1st period, 24month) and after (2nd period, 24month) replacing particle gel immunoassay (PaGIA) and enzyme-linked immunosorbent assay (ELISA) by a chemiluminescent immunoassay (CLIA). HIT was confirmed by heparin-induced platelet activation (HIPA) test. Clinical pretest probability for HIT using an implemented simplified 4Ts score and platelet count were evaluated. Costs for laboratory tests and alternative anticoagulation were calculated. In 1850 patients with suspected HIT, 2327 laboratory orders were performed. In 87.2% of these orders an intermediate/high simplified 4Ts score was found. Thrombocytopenia was present in 87.1%. After replacing PaGIA and ELISA by CLIA the number of immunological and functional laboratory tests was reduced by 38.2%. The number of positive HIT immunoassays declined from 22.6% to 6.0%, while the number of positive HIPA tests among positive immunological tests increased by 19%. Altogether, acute HIT was confirmed in 59 patients. A decline in the use of alternative anticoagulants was observed in the 2nd period. Our study shows that in a university hospital setting HIT is well-known, but diagnosis requires a precise laboratory confirmation. Replacing PaGIA and ELISA by CLIA did not influence laboratory order behavior but results in reduced overall costs for laboratory diagnostics and alternative anticoagulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Recent advances in neonatal pharmacotherapy.

PubMed

Calhoun, Darlene A; Murthy, S Narasimha; Bryant, Bobby G; Luedtke, Sherry A; Bhatt-Mehta, Varsha

2006-04-01

To provide commentary and reviews and brief discussions in controversial or innovative recent advances in neonatal pharmacotherapy. To discuss cutting edge drug delivery systems that may become useful in neonatal drug delivery in the future. Articles were identified through searches of MEDLINE (1990-October 2005), key articles in the authors' files, and in some cases, through data generated and/or published by the author of a particular topic. Article selection and relevance to the topics under discussion was determined by individual authors. Therapeutic strategies addressed in this review include the use of hematopoietic growth factors including a simulated amniotic fluid preparation containing these growth factors for neonates with selected gastrointestinal problems, erythropoietin for neuroprotection following perinatal asphyxia, drug therapy advances in treatment of patent ductus arteriosus (PDA), evaluation of advances in transdermal drug delivery, and its potential application to neonates and advances in the treatment of persistent pulmonary hypertension (PPHN) of the newborn. Despite being over 30 years old, the practice of neonatology is as much of an art as a science. Advances in the basic science research have improved our understanding of use of pharmacologic agents in the premature and full-term neonate including drug disposition pathways. Expanding our knowledge on issues such as physiology of hematopoietic factors, the pharmacologic responses of conditions such as PDA and PPHN, and newer technologies for drug administration, as well as other pharmacologic responses in the neonate are vital in the development of safe and efficacious treatments for neonates. Many questions remain unanswered, and every clinician must make an effort to contribute to the knowledge and understanding of pharmacotherapy in this patient population.

Neonatal mortality rate and risk factors in northeast China: analysis of 5,277 neonates in 2005.

PubMed

Sun, J; Qu, S; Zhang, C; Xiang, Z; Fu, Z; Yao, L

2014-01-01

Healthcare has dramatically improved for both mothers and neonates over the last three decades in China. However, the reported rates of morbidity and mortality vary among different regions of China, and the exact rates in Northeast China are unknown. This study aimed to determine neonatal morbidity and mortality rates and the associated risk factors in Northeast China. Neonates born in 2005 at seven hospitals in five major cities of Heilongjiang province in Northeast China were recruited. Standardized questionnaires on both the mother and neonate were conducted by trained investigators. The questions included demographic data on the mother, the mother's weight, gestational age (GA), complications during pregnancy, method of delivery, neonate's gender, weight, general health situation, and complications after delivery. Results: A total of 5,277 neonates were included, with a male to female ratio of 1.07. The incidence ofpreterm delivery was 8.7%, which was associated with an increased age of the mother, a history of preeclampsia-eclampsia, premature rupture of membranes, and intrauterine distress. Morbidity occurred in 7.0% of neonates, including hypoxic ischemic encephalopathy (2.4%), asphyxia (1.6%), pneumonia (1.6%), hyperbilirubinemia (0.5%), intracranial hemorrhage (0.5%), meconium as- piration syndrome (0.2%), and ingestion syndrome (0.2%). The overall mortality was 9.5%0. Preterm delivery, maternal history ofpreeclamp- sia-eclampsia, hypoxic ischemic encephalopathy, intracranial hemorrhage, pneumonia, asphyxia, and meconium aspiration syndrome were independent risk factors for mortality with odds ratios (95% confidence interval) of 17.42 (7.31-38.9), 12.52 (Table 3) (3.91-16.82), 10.13 (2.52-19.86), 9.77 (2.35-19.93), 4.15 (1.78-9.52), 2.18 (1.21-5.47), and 2.76 (2.11-6.32), respectively (all P<0.01). In 2005, the overall morbidity and mortality was 7.0% and 9.5%0, respectively in northeast China, and preterm delivery was the highest risk factor for neonatal

The large contribution of twins to neonatal and post-neonatal mortality in The Gambia, a 5-year prospective study.

PubMed

Miyahara, Reiko; Jasseh, Momodou; Mackenzie, Grant Austin; Bottomley, Christian; Hossain, M Jahangir; Greenwood, Brian M; D'Alessandro, Umberto; Roca, Anna

2016-03-15

A high twinning rate and an increased risk of mortality among twins contribute to the high burden of infant mortality in Africa. This study examined the contribution of twins to neonatal and post-neonatal mortality in The Gambia, and evaluated factors that contribute to the excess mortality among twins. We analysed data from the Basse Health and Demographic Surveillance System (BHDSS) collected from January 2009 to December 2013. Demographic and epidemiological variables were assessed for their association with mortality in different age groups. We included 32,436 singletons and 1083 twins in the analysis (twining rate 16.7/1000 deliveries). Twins represented 11.8 % of all neonatal deaths and 7.8 % of post-neonatal deaths. Mortality among twins was higher than in singletons [adjusted odds ratio (AOR) 4.33 (95 % CI: 3.09, 6.06) in the neonatal period and 2.61 (95 % CI: 1.85, 3.68) in the post-neonatal period]. Post-neonatal mortality among twins increased in girls (P for interaction = 0.064), being born during the dry season (P for interaction = 0.030) and lacking access to clean water (P for interaction = 0.042). Mortality among twins makes a significant contribution to the high burden of neonatal and post-neonatal mortality in The Gambia and preventive interventions targeting twins should be prioritized.

Fibrin network changes in neonates after cardiopulmonary bypass

PubMed Central

Brown, Ashley C.; Hannan, Riley; Timmins, Lucas H.; Fernandez, Janet D.; Barker, Thomas H.; Guzzetta, Nina A.

2016-01-01

Background Quantitative and qualitative differences exist between the hemostatic systems of neonates and adults, among them the presence of ‘fetal’ fibrinogen, a qualitatively dysfunctional form of fibrinogen that exists until one year of age. The consequences of ‘fetal’ fibrinogen on clot structure in neonates, particularly in the context of surgical associated bleeding, have not been well characterized. Here we examine the sequential changes in clotting components and resultant clot structure in a small sample of neonates undergoing cardiac surgery and cardiopulmonary bypass (CPB). Methods Blood samples were collected from neonates (n=10) before surgery, immediately after CPB and following the transfusion of cryoprecipitate (i.e. adult fibrinogen component). Clots were formed from patient samples or purified neonatal and adult fibrinogen. Clot structure was analyzed using confocal microscopy. Results Clots formed from plasma obtained after CPB and after transfusion were more porous than baseline clots. Analysis of clots formed from purified neonatal and adult fibrinogen, demonstrated that at equivalent fibrinogen concentrations, neonatal clots lack three-dimensional structure while adult clots were denser with significant three-dimensional structure. Clots formed from a combination of purified neonatal and adult fibrinogen were less homogenous than those formed from either purified adult or neonatal fibrinogen. Conclusions Our results confirm that significant differences exist in clot structure between neonates and adults, and that neonatal and adult fibrinogen may not integrate well. These findings suggest that differential treatment strategies for neonates should be pursued to reduce the demonstrated morbidity of blood product transfusion. PMID:26914227

Parents' experiences with neonatal home care following initial care in the neonatal intensive care unit: a phenomenological hermeneutical interview study.

PubMed

Dellenmark-Blom, Michaela; Wigert, Helena

2014-03-01

A descriptive study of parents' experiences with neonatal home care following initial care in the neonatal intensive care unit. As survival rates improve among premature and critically ill infants with an increased risk of morbidity, parents' responsibilities for neonatal care grow in scope and degree under the banner of family-centred care. Concurrent with medical advances, new questions arise about the role of parents and the experience of being provided neonatal care at home. An interview study with a phenomenological hermeneutic approach. Parents from a Swedish neonatal (n = 22) home care setting were extensively interviewed within one year of discharge. Data were collected during 2011-2012. The main theme of the findings is that parents experience neonatal home care as an inner emotional journey, from having a child to being a parent. This finding derives from three themes: the parents' experience of leaving the hospital milieu in favour of establishing independent parenthood, maturing as a parent and processing experiences during the period of neonatal intensive care. This study suggests that neonatal home care is experienced as a care structure adjusted to incorporate parents' needs following discharge from a neonatal intensive care unit. Neonatal home care appears to bridge the gap between hospital and home, supporting the family's adaptation to life in the home setting. Parents become empowered to be primary caregivers, having nurse consultants serving the needs of the whole family. Neonatal home care may therefore be understood as the implementation of family-centred care during the transition from NICU to home. © 2013 John Wiley & Sons Ltd.

An agent based architecture for high-risk neonate management at neonatal intensive care unit.

PubMed

Malak, Jaleh Shoshtarian; Safdari, Reza; Zeraati, Hojjat; Nayeri, Fatemeh Sadat; Mohammadzadeh, Niloofar; Farajollah, Seide Sedighe Seied

2018-01-01

In recent years, the use of new tools and technologies has decreased the neonatal mortality rate. Despite the positive effect of using these technologies, the decisions are complex and uncertain in critical conditions when the neonate is preterm or has a low birth weight or malformations. There is a need to automate the high-risk neonate management process by creating real-time and more precise decision support tools. To create a collaborative and real-time environment to manage neonates with critical conditions at the NICU (Neonatal Intensive Care Unit) and to overcome high-risk neonate management weaknesses by applying a multi agent based analysis and design methodology as a new solution for NICU management. This study was a basic research for medical informatics method development that was carried out in 2017. The requirement analysis was done by reviewing articles on NICU Decision Support Systems. PubMed, Science Direct, and IEEE databases were searched. Only English articles published after 1990 were included; also, a needs assessment was done by reviewing the extracted features and current processes at the NICU environment where the research was conducted. We analyzed the requirements and identified the main system roles (agents) and interactions by a comparative study of existing NICU decision support systems. The Universal Multi Agent Platform (UMAP) was applied to implement a prototype of our multi agent based high-risk neonate management architecture. Local environment agents interacted inside a container and each container interacted with external resources, including other NICU systems and consultation centers. In the NICU container, the main identified agents were reception, monitoring, NICU registry, and outcome prediction, which interacted with human agents including nurses and physicians. Managing patients at the NICU units requires online data collection, real-time collaboration, and management of many components. Multi agent systems are applied as

Neonatal tetanus associated with skin infection.

PubMed

Maharaj, M; Dungwa, N

2016-08-03

A 1-week-old infant was brought to a regional hospital with a history of recurrent seizures following lower abdominal septic skin infection. She was found to have neonatal tetanus, and a spatula test was positive. The tetanus infection was associated with a superficial skin infection, common in neonates. Treatment included sedatives (diazepam, chlorpromazine, phenobarbitone and morphine), muscle relaxants, antibiotics and ventilation in the neonatal intensive care unit. Intrathecal and intramuscular immunoglobulin were given, and the wound was treated. The infant recovered, with no seizures by the 16th day from admission, and was off the ventilator by the 18th day. This was shorter than the usual 3 - 4 weeks for neonates with tetanus at the hospital. The question arises whether tetanus immunisation should be considered in infants with skin infections, which frequently occur in the neonatal period.

Controversies in neonatal resuscitation.

PubMed

Chalkias, Athanasios; Xanthos, Theodoros; Syggelou, Angeliki; Bassareo, Pier Paolo; Iacovidou, Nicoletta

2013-10-01

Despite recent advances in perinatal medicine and in the art of neonatal resuscitation, resuscitation strategy and treatment methods in the delivery room should be individualized depending on the unique characteristics of the neonate. The constantly increasing evidence has resulted in significant treatment controversies, which need to be resolved with further clinical and experimental research.

Effect of maternal and neonatal factors on neonatal thyroid stimulating hormone: Results from a population-based prospective cohort study in China.

PubMed

Zhang, Yixin; Du, Cong; Wang, Wei; Chen, Wen; Shao, Ping; Wang, Chongdan; Leng, Junhong; Shen, Jun; Tan, Long; Zhang, Wanqi

2018-09-01

Neonatal TSH screening is effective in detecting congenital hypothyroidism and estimating iodine status in a given population, but various factors influence TSH levels. The aim of this study was to evaluate the effect of maternal and neonatal factors on neonatal TSH levels. Data were obtained from an ongoing prospective cohort study. A total of 988 pregnant women and their newborn infants participated in the study from April 2015 to May 2017 at Tianjin Maternal and Child Health Center and Tanggu Maternity Hospital in Tianjin, China. Maternal demographic information, including age, height, and parity, was recorded by questionnaire. Fasting blood and urinary samples were collected from all pregnant women. After parturition, information on gestation duration, mode of delivery, neonatal sex, neonatal TSH, neonatal birth weight, and neonatal birth height were recorded. Maternal age, maternal BMI, gestation duration, parity, and neonatal birth weight and height were significantly correlated with neonatal TSH (p < 0.05). Quantile regression revealed that maternal age, TSH, FT 4 , and gestation duration were positively correlated with neonatal TSH level. A logistic regression model identified maternal BMI, TSH, and birth height as risk factors for having neonatal TSH > 5 mIU/L (p < 0.05). Neonatal TSH levels are dynamic and may be affected by several maternal and neonatal factors including maternal age, TSH, FT 4 , and birth weight and height. Identification of these confounders is useful for assessing the status of neonatal thyroid development. STRENGTHS AND LIMITATIONS OF THIS STUDY: (1) Iodine deficiency disorder has generally been eliminated, so the median urinary iodine concentration of pregnancy is higher than 150 μg/L even in mildly or moderately iodine deficient areas. (2) Unlike many other studies, which did not consider the complexity of factors or examined only one or two variables, this study used a multivariate model to analyze the data. (3

Use of diuretics during pregnancy

PubMed Central

Al-Balas, Mosa’b; Bozzo, Pina; Einarson, Adrienne

2009-01-01

ABSTRACT QUESTION Several of my pregnant patients use diuretics for hypertension. I have heard that diuretics cannot be used in pregnancy because of the reduction of plasma volume and the potential for decreasing placental perfusion, as well as a possible diabetogenic effect. ANSWER Many studies—including a meta-analysis of almost 7000 neonates exposed to diuretics during pregnancy—did not find an increased risk of adverse effects, such as birth defects, fetal growth restriction, thrombocytopenia, or diabetes, among neonates exposed to diuretics in utero. PMID:19155365

[Care practices for neonates while setting up a neonatal unit in a university hospital].

PubMed

Pedron, Cecília Drebes; Bonilha, Ana Lúcia de Lourenzi

2008-12-01

The hospitalization process of neonates makes them vulnerable to several care practices. The aim of this study was to get to know the care practices adopted by health professionals while setting up a neonatal unit at the Hospital de Clínicas of Porto Alegre, Rio Grande do Sul, Brazil. This is a qualitative study based on the New History Theory. The study collected data from October 2006 to January 2007. Fifteen health professionals responsible for the project and/or its implementation from 1972 to 1984 provided information. The thematic data analysis highlighted the concern among health professionals of making good use of technological advances, as well as unifying scientifically-based conducts. Besides, they tried to establish routines enabling neonate's parents to stay at the bedside during the whole hospitalization period. Finally, it was inferred that the main objective of these practices was to increase the survival of neonates.

Cross-boundary rotational working for neonatal nurses.

PubMed

Kane, Tina

2007-05-01

Neonatal services in England and Wales are undergoing significant changes as a result of technological advances as well as the development of new networks. These changes have had a dramatic effect on the neonatal workforce. The skills of the available staff govern the level of activity of neonatal units: many units have had to re-evaluate the services they can safely deliver with the available workforce. This has resulted in the re-configuration of some neonatal units and changes in the dependency levels of many. Units have had to undertake reviews of the patterns of working of their staff to ensure that a skilled and competent workforce is available to provide the level of care each neonatal service requires. Shortages in some areas have meant that units have had to find new ways to retain and update skilled staff. This article describes a rotational programme developed with the aim of providing a continued clinical development pathway for neonatal nursing staff. The programme incorporates competency assessments of emergency skills and clinical and technological advances in neonatal care.

Neonatal and infantile acne vulgaris: an update.

PubMed

Serna-Tamayo, Cristian; Janniger, Camila K; Micali, Giuseppe; Schwartz, Robert A

2014-07-01

Acne may present in neonates, infants, and small children. Neonatal and infantile acne vulgaris are not considered to be rare. The presentation of acne in this patient population sometimes represents virilization and may portend later development of severe adolescent acne. Neonatal and infantile acne vulgaris must be distinguished from other cutaneous disorders seen in newborns and infants. Infantile acne tends to be more pleomorphic and inflammatory, thus requiring more vigorous therapy than neonatal acne.

Providing safe surgery for neonates in sub-Saharan Africa.

PubMed

Ameh, Emmanuel A; Ameh, Nkeiruka

2003-07-01

Advances in neonatal intensive care, total parenteral nutrition and improvements in technology have led to a greatly improved outcome of neonatal surgery in developed countries. In many parts of sub-Saharan Africa, however, neonatal surgery continues to pose wide-ranging challenges. Delivery outside hospital, delayed referral, poor transportation, and lack of appropriate personnel and facilities continue to contribute to increased morbidity and mortality in neonates, particularly under emergency situations. Antenatal supervision and hospital delivery needs to be encouraged in our communities. Adequate attention needs to be paid to providing appropriate facilities for neonatal transport and support and training of appropriate staff for neonatal surgery. Neonates with surgical problems should be adequately resuscitated before referral where necessary but surgery should not be unduly delayed. Major neonatal surgery should as much as possible be performed by those trained to operate on neonates. Appropriate research and international collaboration is necessary to improve neonatal surgical care in the environment.

Safety and Efficacy of Neonatal Vaccination

PubMed Central

Demirjian, Alicia; Levy, Ofer

2009-01-01

Newborns have an immature immune system that renders them at high risk for infection while simultaneously reducing responses to most vaccines, thereby posing challenges in protecting this vulnerable population. Nevertheless, certain vaccines, such as Bacillus Calmette Guérin (BCG) and Hepatitis B vaccine (HBV), do demonstrate safety and some efficacy at birth, providing proof of principal that certain antigen-adjuvant combinations are able to elicit protective neonatal responses. Moreover, birth is a major point of healthcare contact globally meaning that effective neonatal vaccines achieve high population penetration. Given the potentially significant benefit of vaccinating at birth, availability of a broader range of more effective neonatal vaccines is an unmet medical need and a public health priority. This review focuses on safety and efficacy of neonatal vaccination in humans as well as recent research employing novel approaches to enhance the efficacy of neonatal vaccination. PMID:19089811

Neurodiagnostic techniques in neonatal critical care.

PubMed

Chang, Taeun; du Plessis, Adre

2012-04-01

This article reviews recent advances in the neurodiagnostic tools available to clinicians practicing in neonatal critical care. The advent of induced mild hypothermia for acute neonatal hypoxic-ischemic encephalopathy in 2005 has been responsible for renewed urgency in the development of precise and reliable neonatal neurodiagnostic techniques. Traditional evaluations of bedside head ultrasounds, head computed tomography scans, and routine electroencephalograms (EEGs) have been upgraded in most tertiary pediatric centers to incorporate protocols for MRI, continuous EEG monitoring with remote bedside access, amplitude-integrated EEG, and near-infrared spectroscopy. Meanwhile, recent studies supporting the association between placental pathology and neonatal brain injury highlight the need for closer examination of the placenta in the neurodiagnostic evaluation of the acutely ill newborn. As the pursuit of more effective neuroprotection moves into the "hypothermia plus" era, the identification, evaluation, and treatment of the neurologically affected newborn in the neonatal intensive care unit has increasing significance.

Neonatal orbital abscess

PubMed Central

Al-Salem, Khalil M; Alsarayra, Fawaz A; Somkawar, Areej R

2014-01-01

Orbital complications due to ethmoiditis are rare in neonates. A case of orbital abscess due to acute ethmoiditis in a 28-day-old girl is presented. A Successful outcome was achieved following antimicrobial therapy alone; spontaneous drainage of the abscess occurred from the lower lid without the need for surgery. From this case report, we intend to emphasize on eyelid retraction as a sign of neonatal orbital abscess, and to review all the available literature of similar cases. PMID:24008806

The use of argatroban for carotid endarterectomy in heparin-induced thrombocytopenia.

PubMed

Hallman, Sarah E; Hebbar, Latha; Robison, Jay; Uber, Walter E

2005-04-01

Heparin-induced thrombocytopenia (HIT) is a major obstacle in cardiovascular surgeries. In this case report, we used argatroban, a direct thrombin inhibitor, to achieve and maintain anticoagulation for carotid endarterectomy. Unlike heparin, the direct thrombin inhibitors bind directly to thrombin, bypassing antithrombin III and the potential to precipitate HIT. A bolus of argatroban 150 microg/kg followed by an infusion of 5 microg . kg(-1) . min(-1) was used, and adequate anticoagulation was demonstrated with multiple laboratory tests (at 28 min, prothrombin time = 29.8 s, partial thromboplastin time = 69.1 s, international normalized ratio = 3.52 s, and activated clotting time = 220 s). The surgery was successful, and the patient was discharged the next day with no postoperative neurologic sequelae or other complications. We conclude that argatroban can be used safely and successfully for carotid endarterectomy in a patient with a history of HIT.

Abdominal surgery in neonatal foals.

PubMed

Bryant, James E; Gaughan, Earl M

2005-08-01

Abdominal surgery in foals under 30 days old has become more common with improved neonatal care. Early recognition of a foal at risk and better nursing care have increased the survival rates of foals that require neonatal care. The success of improved neonatal care also has increased the need for accurate diagnosis and treatment of gastrointestinal, umbilical, and bladder disorders in these foals. This chapter focuses on the early and accurate diagnosis of specific disorders that require abdominal exploratory surgery and the specific treatment considerations and prognosis for these disorders.

NEONATAL DESTRUCTION OF DOPAMINERGIC NEURONS

EPA Science Inventory

Rats treated as neonates with 6-hydroxydopamine are proposed to model the dopamine deficiency associated with Lesch-Nyhan syndrome (LNS). o understand the neurobiological basis of specific behaviors in LNS, investigations were undertaken in these neonatally lesioned rats. everal ...

Relationships among intrapartum maternal fluid intake, birth type, neonatal output, and neonatal weight loss during the first 48 hours after birth.

PubMed

Lamp, Jane M; Macke, Judi K

2010-01-01

To examine predictive relationships among intrapartum maternal fluid intake, birth type, neonatal output, and neonatal weight loss during the first 48 hours after birth. Prospective descriptive design. Women's center of a 900-bed regional acute care facility with 6,700 births per year. A convenience sample of 200 mother/neonate dyads. The Optimality Index of Murphy and Fullerton guided the inclusion and exclusion criteria to ensure healthy dyads. Data collection began in the intrapartum period and concluded with maternal/neonatal discharge. Measures included maternal intrapartum fluid intake from admission to birth, daily neonatal weight, output, and feedings. Data were analyzed via descriptive statistics, tests of significance and multiple regression. Neonatal weight loss was not significantly related to intrapartum maternal fluid intake. Strong predictors of neonatal weight loss and significant weight loss within the first 48 hours were type of feeding (p=.000) and average number of wet diapers (p=.003). Variables predictive of neonatal weight loss can facilitate identification of at-risk neonates to prevent significant weight loss. Close monitoring of the number of wet diapers in the first 48 hours and accurate daily weights at birth time can lead to early detection and preventive interventions.

Neonatal tetanus in the world today*

PubMed Central

Stanfield, J. P.; Galazka, A.

1984-01-01

Neonatal tetanus is an important cause of avoidable morbidity and mortality. In the past this disease was overlooked by the health services of many developing countries, but recently the extent and magnitude of neonatal tetanus has become clearer and shown that it is a very serious health problem in the developing countries. The results of community-based surveys show that neonatal tetanus mortality rates range from less than 5 to more than 60 per 1000 live births; these deaths represent between 23% and 72% of all neonatal deaths. The results so far suggest that this disease claims the lives of over half a million new-born children every year. All forms of tetanus, and especially neonatal tetanus, remain substantially under-reported in many countries, and routine reporting systems identify only about 2-5% of the estimated number of tetanus cases (based on the results of community surveys). More reliable and accurate estimates of the incidence and mortality from tetanus are therefore required. The elimination of neonatal tetanus is an essential and attainable goal. It may be achieved by combining two approaches: (1) increasing the immunization coverage of women of child-bearing age, and especially pregnant women, with tetanus toxoid, and (2) improving maternity care, with particular emphasis on increasing the proportions of deliveries that are attended by trained persons. Neonatal tetanus mortality should serve as an index of the quality and the extent of utilization of the maternal health services, of the impact of immunization programmes, and of the progress being made in achieving the WHO goal of “Health for All by the Year 2000”. The elimination of neonatal tetanus calls for a full commitment by governments and by other bodies, public and private, with a responsibility for the care of women and children. The occurrence of even a single case of neonatal tetanus is witness to failures in the health system, for prevention is possible through the actions of

Efficacy of combined intravenous immunoglobulins and steroids in children with primary immune thrombocytopenia and persistent bleeding symptoms.

PubMed

Parodi, Emilia; Giordano, Paola; Rivetti, Elisa; Giraudo, Maria Teresa; Ansaldi, Giulia; Davitto, Mirella; Mondino, Anna; Farruggia, Piero; Amendola, Giovanni; Matarese, Sofia M R; Rossi, Francesca; Russo, Giovanna; Ramenghi, Ugo

2014-07-01

The aim of this study was to investigate the effect of the combined administration of intravenous immunoglobulins and steroids as a second-line therapy in 34 children with primary immune thrombocytopenia and persistent, symptomatic bleeding. Combined therapy (intravenous immunoglobulins 0.4 g/kg daily on days 1 and 2, and methylprednisolone 20 mg/kg daily on days 1-3) was administered to 12 patients with newly diagnosed ITP who did not respond to the administration of a single therapy (either intravenous immunoglobulins or steroids) and to 22 children with persistent and chronic disease who required frequent administrations (i.e. more frequently than every 30 days) of either immunoglobulins or steroids (at the same standard dosages) in order to control active bleeding. A response (i.e. platelet count >50×10(9)/L and remission of active bleeding) was observed in 8/12 (67%) patients with newly diagnosed ITP. The clinical presentation of responders and non-responders did not differ apparently. Patients in the chronic/persistent phase of disease had a significantly longer median period of remission from symptoms compared with the previous longest period of remission (p=0.016). The treatment was well tolerated. Our data suggest that the combined approach described is a well-tolerated therapeutic option for children with primary immune thrombocytopenia and persistent bleeding symptoms that can be used in both emergency and/or maintenance settings.

Baby on the move: issues in neonatal transport.

PubMed

Teasdale, Debra; Hamilton, Catherine

2008-02-01

The 2003 review of UK neonatal services led to wide-ranging changes including the centralisation of intensive care into level 3 units, the geographical organisation of neonatal care into 'networks', and the setting up of dedicated network transport teams. Despite these changes, neonatal transport continues to be problematic. Approaches to neonatal transportation are not yet standardised and this presents logistical problems for staff. Risks need to be considered and managed effectively to ensure safety for all involved. Although algorithms are in use for general stabilisation of the neonates, more guidance is required for effective stabilisation and management of infants with complex/surgical conditions. Staff involved in transport need to understand how neonatal physiology may be altered during transportation. They should also consider the legal implications of neonatal transport which are likely to remain unclear until the law is challenged in some way.

Maternal and neonatal hyponatremia during labor: a case series.

PubMed

Solomon, Neta; Many, Ariel; Orbach, Rotem; Mandel, Dror; Shinar, Shiri

2018-03-12

Hyponatremia during labor and delivery may result in severe maternal and neonatal sequelae. Our aim was to describe the direct effect of hyponatremia in labor on pregnancy outcome. A case series of parturients diagnosed with hyponatremia during labor and their neonates. Clinical presentation, laboratory workup, and maternal and neonatal outcomes are presented. Four parturients and their corresponding six neonates were diagnosed with hyponatremia. Of these, two cases were caused by water intoxication and two were preeclampsia induced. While two were identified due to maternal or neonatal symptoms, two were diagnosed by routine laboratory testing. In all cases, low maternal sodium resulted in similarly low neonatal sodium. Neonatal symptoms included respiratory distress syndrome (RDS), lethargy, and jaundice. Psychogenic drinking during labor and preeclampsia may predispose to maternal hyponatremia, resulting in neonatal hyponatremia. Early recognition and treatment can prevent further maternal deterioration and adverse neonatal sequelae.

Estimation of adult and neonatal RBC lifespans in anemic neonates using RBCs labeled at several discrete biotin densities.

PubMed

Kuruvilla, Denison J; Widness, John A; Nalbant, Demet; Schmidt, Robert L; Mock, Donald M; An, Guohua; Veng-Pedersen, Peter

2017-06-01

Prior conclusions that autologous neonatal red blood cells (RBC) have substantially shorter lifespans than allogeneic adult RBCs were not based on direct comparison of autologous neonatal vs. allogeneic adult RBCs performed concurrently in the same infant. Biotin labeling of autologous neonatal RBCs and allogeneic adult donor RBCs permits concurrent direct comparison of autologous vs. allogeneic RBC lifespan. RBCs from 15 allogeneic adult donors and from 15 very-low-birth-weight (VLBW) neonates were labeled at separate biotin densities and transfused simultaneously into the 15 neonates. Two mathematical models that account for the RBC differences were employed to estimate lifespans for the two RBC populations. Mean ± SD lifespan for adult allogeneic RBC was 70.1 ± 19.1 d, which is substantially shorter than the 120 d lifespan of both autologous and adult allogeneic RBC in healthy adults. Mean ± SD lifespan for neonatal RBC was 54.2 ± 11.3 d, which is only about 30% shorter than that of the adult allogeneic RBCs. This study provides evidence that extrinsic environmental factors primarily determine RBC survival (e.g., small bore of the capillaries of neonates, rate of oxygenation/deoxygenation cycles) rather than factors intrinsic to RBC.

[Lactose intolerance in neonates with non-infectious diarrhea].

PubMed

Su, Hui-Min; Jiang, Yi; Hu, Yu-Lian; Yang, Hui; Dong, Tian-Jin

2016-04-01

To investigate the development of lactose intolerance in neonates with non-infectious diarrhea and its association with diarrhea, and to evaluate the diagnostic values of fecal pH value and urine galactose determination for neonatal lactase deficiency. Seventy hospitalized neonates who developed non-infectious diarrhea between October 2012 and June 2015 were enrolled as the diarrhea group, and 162 hospitalized neonates without non-infectious diarrhea were enrolled as the non-diarrhea group. Test paper was used to determine fecal pH value. The galactose oxidase method was used to detect urine galactose. The neonates with positive galactose oxidase were diagnosed with lactase deficiency, and those with lactase deficiency and diarrhea were diagnosed with lactose intolerance. According to the results of urine galactose detection, 69 neonates in the diarrhea group who underwent urine galactose detection were classified into lactose intolerance group (45 neonates) and lactose tolerance group (24 neonates), and their conditions after treatment were compared between the two groups. The follow-up visits were performed for neonates with diarrhea at 3 months after discharge. Fecal pH value and positive rate of urine galactose (65% vs 54%) showed no significant differences between the diarrhea and non-diarrhea groups (P>0.05). Fecal pH value showed no significant difference between the lactose intolerance and lactose tolerance groups (P>0.05), while the neonates in the lactose intolerance group had a significantly longer time to recovery of defecation than those in the lactose tolerance group (P<0.05). The incidence of lactase deficiency is high in neonates, and diarrhea due to lactose intolerance tends to occur. Determination of fecal pH value has no significance in the diagnosis of lactose intolerance in neonates with diarrhea.

Call for neonatal nursing specialization in developing countries.

PubMed

Premji, Shahirose S; Spence, Kaye; Kenner, Carole

2013-01-01

In an attempt to reach Millennium Development Goals, health facility births, which are births occurring in health centers, facilities, or institutions under the care of a skilled birth attendant, are increasing in developing countries. We examined the state of neonatal nursing care in the context of issues related to the capacity of these health facilities to provide quality care and the high facility mortality rates in those neonates admitted to hospital. Neonatal nursing as a specialty within a community-hospital-community network system is proposed as an effective scaling-up strategy to improve neonatal survival. Establishment of international competency standards for neonatal nursing together with regulatory processes with mechanisms to facilitate specialty education forms the basis for the specialty of neonatal nursing. We have identified a strategy to mobilize financial resources for the development of the specialty of neonatal nursing. Evaluation of trends in mortality and identification of process indicators will facilitate examination of the effectiveness of the introduction of the specialty of neonatal nursing as a scaling-up strategy.

Neonatal hypothermia in low-resource settings.

PubMed

Mullany, Luke C

2010-12-01

Hypothermia among newborns is considered an important contributor to neonatal morbidity and mortality in low-resource settings. However, in these settings only limited progress has been made towards understanding the risk of mortality after hypothermia, describing how this relationship is dependent on both the degree or severity of exposure and the gestational age and weight status of the baby, and implementing interventions to mitigate both exposure and the associated risk of poor outcomes. Given the centrality of averting neonatal mortality to achieving global milestones towards reductions in child mortality by 2015, recent years have seen substantial resources and efforts implemented to improve understanding of global epidemiology of neonatal health. In this article, a summary of the burden, consequences, and risk factors of neonatal hypothermia in low-resources settings is presented, with a particular focus on community-based data. Context-appropriate interventions for reducing hypothermia exposure and the role of these interventions in reducing global neonatal mortality burden are explored. Copyright © 2010 Elsevier Inc. All rights reserved.

Proteinuria and Hematuria in the Neonate

PubMed Central

Joseph, Catherine; Gattineni, Jyothsna

2016-01-01

Purpose of Review Neonatal proteinuria and hematuria while not common can have potentially devastating consequences if left undiagnosed and untreated. It is important to distinguish between inherited and acquired causes of proteinuria to initiate appropriate and timely treatment. In regards to hematuria, it is critical to identify true hematuria from pseudo-hematuria in order to balance between thorough investigation and unnecessary laboratory work up. This review provides an overview of the common causes of hematuria and proteinuria in a neonate. Recent Findings Identification of genetic mutations in nephrotic syndrome has improved our understanding of the role of various proteins that play an important role in maintaining the glomerular filtration barrier. With the advancement in our ability to provide care for extreme premature neonates, the incidence of acute kidney injury has increased in these neonates along with proteinuria and hematuria. Summary Persistent proteinuria after neonatal acute kidney injury would be of interest in regards to the risk of developing future chronic kidney disease and hypertension. PMID:26845146

Dosing antibiotics in neonates: review of the pharmacokinetic data.

PubMed

Rivera-Chaparro, Nazario D; Cohen-Wolkowiez, Michael; Greenberg, Rachel G

2017-09-01

Antibiotics are often used in neonates despite the absence of relevant dosing information in drug labels. For neonatal dosing, clinicians must extrapolate data from studies for adults and older children, who have strikingly different physiologies. As a result, dosing extrapolation can lead to increased toxicity or efficacy failures in neonates. Driven by these differences and recent legislation mandating the study of drugs in children and neonates, an increasing number of pharmacokinetic studies of antibiotics are being performed in neonates. These studies have led to new dosing recommendations with particular consideration for neonate body size and maturation. Herein, we highlight the available pharmacokinetic data for commonly used systemic antibiotics in neonates.

Neonatal hypoglycemia.

PubMed

Arya, Ved Bhushan; Senniappan, Senthil; Guemes, Maria; Hussain, Khalid

2014-01-01

Glucose is essential for cerebral metabolism. Unsurprisingly therefore, hypoglycemia may result in encephalopathy. Knowledge of the homeostatic mechanisms that maintain blood glucose concentrations within a tight range is the key for diagnosis and appropriate management of hypoglycemia. Neonatal hypoglycemia can be transient and is commonly observed in at-risk infants. A wide range of rare endocrine and metabolic disorders can present with neonatal hypoglycemia, of which congenital hyperinsulinism is responsible for the most severe form of hypoglycemia. Collection of appropriate blood samples for hormones and intermediary metabolites during an episode of hypoglycemia is critical for diagnosis and appropriate management. Prompt diagnosis with aggressive early intervention remains the mainstay of treatment to avert irreversible brain damage.

[Epidemiology of nosocomial infections in neonates].

PubMed

Lachassinne, E; Letamendia-Richard, E; Gaudelus, J

2004-03-01

Epidemiology of nosocomial infections in neonates has to be described according to our definitions (early onset GBS diseases excluded) and according to levels of care. Nosocomial risk exists in maternity departments (3% in postnatal beds), incidence rates are 7.5-12.7% or 1.3-8.5 per 1000 days in neonatal care units and 14.2% or 11.7 per 1000 days in neonatal intensive care units (NICU). Gram-positive cocci bloodstream infections are the most common nosocomial infections in NICU but viral gastroenteritis are more frequent in neonatal care units. Risk factors are low birthweight, small gestational age and intravascular catheter in NICU, and for viral nosocomial infections, visits and winter outbreaks.

Diagnosis and management of neonatal leukaemia.

PubMed

van der Linden, Marieke H; Creemers, Sara; Pieters, Rob

2012-08-01

Leukaemia in neonates (infants <1 month) is rare, whereby neonatal acute myeloid leukaemia (AML) is more frequent than neonatal acute lymphoblastic leukaemia (ALL). High mortality rates are observed, though AML has a better prognosis than ALL. Neonatal leukaemia is typically presented with hepatosplenomegaly, leukaemia cutis and/or hyperleucocytosis. Congenital infections should be ruled out before diagnosis. Rearrangement of the MLL gene is the most frequently occurring genetic aberration. Treatment includes intensive multi-agent chemotherapy, usually with age-related dose adjustments next to supportive care. Treatment intensification for ALL could be indicated in the future as the dismal prognosis is subject to high relapse rates in ALL. Copyright © 2012. Published by Elsevier Ltd.

21 CFR 880.5410 - Neonatal transport incubator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Neonatal transport incubator. 880.5410 Section 880... Devices § 880.5410 Neonatal transport incubator. (a) Identification. A neonatal transport incubator is a... kept in a controlled environment while being transported for medical care. The device may include...

21 CFR 880.5410 - Neonatal transport incubator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Neonatal transport incubator. 880.5410 Section 880... Devices § 880.5410 Neonatal transport incubator. (a) Identification. A neonatal transport incubator is a... kept in a controlled environment while being transported for medical care. The device may include...

21 CFR 880.5700 - Neonatal phototherapy unit.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Neonatal phototherapy unit. 880.5700 Section 880.5700 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Devices § 880.5700 Neonatal phototherapy unit. (a) Identification. A neonatal phototherapy unit is a...

Prediction of Neonatal Hyperthyroidism.

PubMed

Banigé, Maïa; Polak, Michel; Luton, Dominique

2018-06-01

To assess whether it is possible to identify the neonatal predictors of neonatal hyperthyroidism at the presymptomatic stage of the disease. This retrospective multicenter study in 10 maternity units was based on the medical records of all patients monitored for a pregnancy between January 1, 2007, and January 1, 2014. Among 280 000 births, 2288 medical records of women with thyroid dysfunction were selected and screened. Of these, 415 women had Graves disease and were positive for thyrotropin receptor antibody during pregnancy, and were included. A thyroid-stimulating hormone (TSH) level of less than 0.90 mIU/L between days 3 and 7 of life predicted neonatal hyperthyroidism with a sensitivity 78% (95% CI, 74%-82%) and a and specificity of 99% (95% CI, 98%-100%), a positive predictive value of 90% (95% CI, 87%-93%), a negative predictive value of 98% (95% CI, 97%-99%), and an area under the receiver operating characteristic curve of 0.99 (95% CI, 0.97-1.0). A thyrotropin receptor antibody (TRAb) elimination time was calculated using the equation: 7.28 + 2.88 × log() + 11.62 log(TRAb 2 ). All newborns with a TSH level of less than 0.90 mIU/L should be examined by a pediatrician. Using TSH, it is possible to screen for neonatal hypothyroidism and for neonatal hyperthyroidism with a TSH cutoff of 0.90 mIU/L, and this shows the relevance of our study in terms of public health. Copyright © 2018 Elsevier Inc. All rights reserved.

Neonatal physical therapy. Part I: clinical competencies and neonatal intensive care unit clinical training models.

PubMed

Sweeney, Jane K; Heriza, Carolyn B; Blanchard, Yvette

2009-01-01

To describe clinical training models, delineate clinical competencies, and outline a clinical decision-making algorithm for neonatal physical therapy. In these updated practice guidelines, advanced clinical training models, including precepted practicum and residency or fellowship training, are presented to guide practitioners in organizing mentored, competency-based preparation for neonatal care. Clinical competencies in neonatal physical therapy are outlined with advanced clinical proficiencies and knowledge areas specific to each role. An algorithm for decision making on examination, evaluation, intervention, and re-examination processes provides a framework for clinical reasoning. Because of advanced-level competency requirements and the continuous examination, evaluation, and modification of procedures during each patient contact, the intensive care unit is a restricted practice area for physical therapist assistants, physical therapist generalists, and physical therapy students. Accountable, ethical physical therapy for neonates requires advanced, competency-based training with a preceptor in the pediatric subspecialty of neonatology.

Neonatal resuscitation: advances in training and practice

PubMed Central

Sawyer, Taylor; Umoren, Rachel A; Gray, Megan M

2017-01-01

Each year in the US, some four hundred thousand newborns need help breathing when they are born. Due to the frequent need for resuscitation at birth, it is vital to have evidence-based care guidelines and to provide effective neonatal resuscitation training. Every five years, the International Liaison Committee on Resuscitation (ILCOR) reviews the science of neonatal resuscitation. In the US, the American Heart Association (AHA) develops treatment guidelines based on the ILCOR science review, and the Neonatal Resuscitation Program (NRP) translates the AHA guidelines into an educational curriculum. In this report, we review recent advances in neonatal resuscitation training and practice. We begin with a review of the new 7th edition NRP training curriculum. Then, we examine key changes to the 2015 AHA neonatal resuscitation guidelines. The four components of the NRP curriculum reviewed here include eSim®, Performance Skills Stations, Integrated Skills Station, and Simulation and Debriefing. The key changes to the AHA neonatal resuscitation guidelines reviewed include initial steps of newborn care, positive-pressure ventilation, endotracheal intubation and use of laryngeal mask, chest compressions, medications, resuscitation of preterm newborns, and ethics and end-of-life care. We hope this report provides a succinct review of recent advances in neonatal resuscitation. PMID:28096704

Risk factors for hyperbilirubinemia in breastfed term neonates.

PubMed

Chen, Ying-Juang; Chen, Wei-Chuan; Chen, Chung-Ming

2012-01-01

Increased breastfeeding was suggested as a contributing factor to significant hyperbilirubinemia. The aim of this study was to identify the risk factors associated with jaundice in exclusively breastfed term neonates. We retrospectively reviewed all consecutively live-born neonates from August 2009 to July 2010 who had complete outpatient department (OPD) follow-up at ≤14 days old. Hyperbilirubinemia was defined as a transcutaneous bilirubin (TcB) value of ≥15 mg/dl. During the study period, there were 718 deliveries, of which 152 neonates were transferred to the special care nursery or neonatal intensive care unit; 566 neonates were discharged from the nursery, and 243 neonates were excluded: 83 did not return to the OPD, 46 were older than 14 days at OPD follow-up, 44 were <37 weeks of gestational age, and 70 had been fed formula. In total, 323 neonates were enrolled and classified into the hyperbilirubinemic (114 neonates) and non-hyperbilirubinemic groups (209 neonates). The gender, gestational age, Apgar score, age at nursery discharge, birth weight, and body weight at nursery discharge and at OPD were comparable between the two groups. TcB values at nursery discharge were positively correlated with TcB values in the OPD. Infants with hyperbilirubinemia exhibited significantly greater body weight loss from birth to the OPD follow-up and significantly less body weight gain from nursery discharge to OPD follow-up. High TcB values at nursery discharge and a smaller body weight gain are associated with hyperbilirubinemia in term neonates who are exclusively breastfed.

Pediatric epilepsy following neonatal seizures symptomatic of stroke.

PubMed

Suppiej, Agnese; Mastrangelo, Massimo; Mastella, Laura; Accorsi, Patrizia; Grazian, Luisa; Casara, Gianluca; Peruzzi, Cinzia; Carpanelli, Maria Luisa; Janes, Augusta; Traverso, Annalisa; Dalla Bernardina, Bernardo

2016-01-01

Neonatal seizures are a risk factor for later epilepsy and their etiology is known to be implicated in the outcome but, little is known about this issue in the subgroup of seizures symptomatic of perinatal arterial ischemic stroke. The aim of this study was to describe the long term risk of epilepsy after electroencephalographic confirmed neonatal seizures symptomatic of perinatal arterial ischemic stroke. Fifty-five patients with electroclinical ictal data, vascular territory confirmed by neuroimaging and a minimum follow up of 3.5 years were identified from a multi-centre prospective neonatal seizures registry. Primary outcome was occurrence of post-neonatal epilepsy. The association of outcome with family history of epilepsy, gender, location of the infarct, neonatal clinical and electroencephalogram data were also studied. During a mean follow up of 8 years and 5 months, 16.4% of the patients developed post neonatal epilepsy. The mean age at first post neonatal seizure was 4 years and 2 months (range 1-10 years and 6 months). Location of the infarct was the only statistically significant risk factor (p=0.001); epilepsy was more represented in males but the difference was not statistically significant. Neonatal seizures symptomatic of perinatal arterial ischemic stroke had lower risk and later onset of post-neonatal epilepsy, compared to seizures described in the setting of other perinatal brain insults. Our data have implications for counseling to the family at discharge from neonatal intensive care unit. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

iNICU - Integrated Neonatal Care Unit: Capturing Neonatal Journey in an Intelligent Data Way.

PubMed

Singh, Harpreet; Yadav, Gautam; Mallaiah, Raghuram; Joshi, Preetha; Joshi, Vinay; Kaur, Ravneet; Bansal, Suneyna; Brahmachari, Samir K

2017-08-01

Neonatal period represents first 28 days of life, which is the most vulnerable time for a child's survival especially for the preterm babies. High neonatal mortality is a prominent and persistent problem across the globe. Non-availability of trained staff and infrastructure are the major recognized hurdles in the quality care of these neonates. Hourly progress growth charts and reports are still maintained manually by nurses along with continuous calculation of drug dosage and nutrition as per the changing weight of the baby. iNICU (integrated Neonatology Intensive Care Unit) leverages Beaglebone and Intel Edison based IoT integration with biomedical devices in NICU i.e. monitor, ventilator and blood gas machine. iNICU is hosted on IBM Softlayer based cloud computing infrastructure and map NICU workflow in Java based responsive web application to provide translational research informatics support to the clinicians. iNICU captures real time vital parameters i.e. respiration rate, heart rate, lab data and PACS amounting for millions of data points per day per child. Stream of data is sent to Apache Kafka layer which stores the same in Apache Cassandra NoSQL. iNICU also captures clinical data like feed intake, urine output, and daily assessment of child in PostgreSQL database. It acts as first Big Data hub (of both structured and unstructured data) of neonates across India offering temporal (longitudinal) data of their stay in NICU and allow clinicians in evaluating efficacy of their interventions. iNICU leverages drools based clinical rule based engine and deep learning based big data analytical model coded in R and PMML. iNICU solution aims to improve care time, fills skill gap, enable remote monitoring of neonates in rural regions, assists in identifying the early onset of disease, and reduction in neonatal mortality.

Forecast of severe fever with thrombocytopenia syndrome incidence with meteorological factors.

PubMed

Sun, Ji-Min; Lu, Liang; Liu, Ke-Ke; Yang, Jun; Wu, Hai-Xia; Liu, Qi-Yong

2018-06-01

Severe fever with thrombocytopenia syndrome (SFTS) is emerging and some studies reported that SFTS incidence was associated with meteorological factors, while no report on SFTS forecast models was reported up to date. In this study, we constructed and compared three forecast models using autoregressive integrated moving average (ARIMA) model, negative binomial regression model (NBM), and quasi-Poisson generalized additive model (GAM). The dataset from 2011 to 2015 were used for model construction and the dataset in 2016 were used for external validity assessment. All the three models fitted the SFTS cases reasonably well during the training process and forecast process, while the NBM model forecasted better than other two models. Moreover, we demonstrated that temperature and relative humidity played key roles in explaining the temporal dynamics of SFTS occurrence. Our study contributes to better understanding of SFTS dynamics and provides predictive tools for the control and prevention of SFTS. Copyright © 2018 Elsevier B.V. All rights reserved.

Chronic adult primary immune thrombocytopenia (ITP) in the Asia-Pacific region.

PubMed

Heng, Lee Lai; Caguioa, Priscilla; Chin, Ng Soo; Chiou, Tzeon-Jye; Lee, Jong Wook; Miyakawa, Yoshitaka; Tambunan, Karmel L; Chong, Beng H

2011-08-01

Patients with primary immune thrombocytopenia (ITP) from the Asia-Pacific region often exhibit characteristics distinct from those of patients from the West. Moreover, as the region itself is heterogeneous, the ITP landscape among individual Asia-Pacific countries can be diverse. The recently released international consensus report on ITP places new emphasis on ITP, but does not address the unique ITP landscape in the Asia-Pacific region, which is home to 60% of the world's population. In an attempt to characterize how the ITP landscape differs between the West and the Asia-Pacific region, an expert panel with representatives from Northeast Asia, Southeast Asia, and Australia was convened. Important differences were identified between the guidance provided in the international consensus report and experience in the Asia-Pacific region, namely diagnostic practices, incidence and approach to ITP secondary to H. pylori infection, systemic lupus erythematosus-related ITP, the use of bone marrow examination, initial treatment strategies, and the role of splenectomy, rituximab, and thrombopoietin receptor agonists.

Neonatal health in Nepal: analysis of absolute and relative inequalities and impact of current efforts to reduce neonatal mortality

PubMed Central

2013-01-01

Background Nepal has made substantial progress in reducing under-five mortality and is on track to achieve Millennium Development Goal 4, but advances in neonatal health are less encouraging. The objectives of this study were to assess relative and absolute inequalities in neonatal mortality over time, and to review experience with major programs to promote neonatal health. Methods Using four nationally representative surveys conducted in 1996, 2001, 2006 and 2011, we calculated neonatal mortality rates for Nepal and for population groups based on child sex, geographical and socio-economic variables using a true cohort log probability approach. Inequalities based on different variables and years were assessed using rate differences (rd) and rate ratios (rr); time trends in neonatal mortality were measured using the annual rate of reduction. Through literature searches and expert consultation, information on Nepalese policies and programs implemented since 1990 and directly or indirectly attempting to reduce neonatal mortality was compiled. Data on timeline, coverage and effectiveness were extracted for major programs. Results The annual rate of reduction for neonatal mortality between 1996 and 2011 (2.8 percent per annum) greatly lags behind the achievements in under-five and infant mortality, and varies across population groups. For the year 2011, stark absolute and relative inequalities in neonatal mortality exist in relation to wealth status (rd = 21.4, rr = 2.2); these are less pronounced for other measures of socio-economic status, child sex and urban–rural residence, ecological and development region. Among many efforts to promote child and maternal health, three established programs and two pilot programs emerged as particularly relevant to reducing neonatal mortality. While these were designed based on national and international evidence, information about coverage of different population groups and effectiveness is limited. Conclusion Neonatal

Neonatal health in Nepal: analysis of absolute and relative inequalities and impact of current efforts to reduce neonatal mortality.

PubMed

Paudel, Deepak; Shrestha, Ishwar B; Siebeck, Matthias; Rehfuess, Eva A

2013-12-28

Nepal has made substantial progress in reducing under-five mortality and is on track to achieve Millennium Development Goal 4, but advances in neonatal health are less encouraging. The objectives of this study were to assess relative and absolute inequalities in neonatal mortality over time, and to review experience with major programs to promote neonatal health. Using four nationally representative surveys conducted in 1996, 2001, 2006 and 2011, we calculated neonatal mortality rates for Nepal and for population groups based on child sex, geographical and socio-economic variables using a true cohort log probability approach. Inequalities based on different variables and years were assessed using rate differences (rd) and rate ratios (rr); time trends in neonatal mortality were measured using the annual rate of reduction. Through literature searches and expert consultation, information on Nepalese policies and programs implemented since 1990 and directly or indirectly attempting to reduce neonatal mortality was compiled. Data on timeline, coverage and effectiveness were extracted for major programs. The annual rate of reduction for neonatal mortality between 1996 and 2011 (2.8 percent per annum) greatly lags behind the achievements in under-five and infant mortality, and varies across population groups. For the year 2011, stark absolute and relative inequalities in neonatal mortality exist in relation to wealth status (rd = 21.4, rr = 2.2); these are less pronounced for other measures of socio-economic status, child sex and urban-rural residence, ecological and development region. Among many efforts to promote child and maternal health, three established programs and two pilot programs emerged as particularly relevant to reducing neonatal mortality. While these were designed based on national and international evidence, information about coverage of different population groups and effectiveness is limited. Neonatal mortality varies greatly by socio

Glutathione S-transferases in neonatal liver disease.

PubMed Central

Mathew, J.; Cattan, A. R.; Hall, A. G.; Hines, J. E.; Nelson, R.; Eastham, E.; Burt, A. D.

1992-01-01

AIMS: To investigate the distribution of alpha and pi class glutathione S-transferases (GST) in normal fetal, neonatal, and adult liver; and to examine changes in GST expression in neonatal liver disease. METHODS: alpha and pi class GST were immunolocalised in sections of formalin fixed liver tissue obtained from human fetuses (n = 21), neonates (n = 8), young children (n = 9) and adults (n = 10), and from neonates with extrahepatic biliary atresia (n = 15) and neonatal hepatitis (n = 12). Monospecific rabbit polyclonal antibodies were used with a peroxidase-antiperoxidase method. RESULTS: Expression of pi GST was localised predominantly within biliary epithelial cells of developing and mature bile ducts of all sizes from 16 weeks' gestation until term and in neonatal and adult liver. Coexpression of pi and alpha GST was seen in hepatocytes of developing fetal liver between 16 and 34 weeks' gestation. Although pi GST was seen in occasional hepatocytes up to six months of life, this isoenzyme was not expressed by hepatocytes in adult liver. By contrast, alpha GST continued to be expressed by hepatocytes in adult liver; this isoenzyme was also seen in some epithelial cells of large bile ducts in adult liver. No change was observed in the distribution of alpha GST in either neonatal hepatitis or extrahepatic biliary atresia. However, aberrant expression of pi GST was identified in hepatocytes of all but one case of extrahepatic biliary atresia but in only two cases of neonatal hepatitis. CONCLUSIONS: The phenotypic alterations noted in extrahepatic biliary atresia may result from the effect of cholate stasis. Evaluation of the pattern of pi and alpha GST distribution by immunohistochemical staining may provide valuable information in distinguishing between these two forms of neonatal liver disease. Images PMID:1401176

21 CFR 880.5270 - Neonatal eye pad.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Neonatal eye pad. 880.5270 Section 880.5270 Food... § 880.5270 Neonatal eye pad. (a) Identification. A neonatal eye pad is an opaque device used to cover and protect the eye of an infant during therapeutic procedures, such as phototherapy. (b...

21 CFR 880.5270 - Neonatal eye pad.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Neonatal eye pad. 880.5270 Section 880.5270 Food... § 880.5270 Neonatal eye pad. (a) Identification. A neonatal eye pad is an opaque device used to cover and protect the eye of an infant during therapeutic procedures, such as phototherapy. (b...

Acid-base disorders in critically ill neonates

PubMed Central

Lekhwani, S.; Shanker, V.; Gathwala, G.; Vaswani, N. D.

2010-01-01

Objective: To study acid–base imbalance in common pediatric diseases (such as sepsis, bronchopneumonia, diarrhea, birth-asphyxia etc.) in neonates. Design and Setting: An observational study was conducted in an emergency room of a tertiary teaching care hospital in Haryana, India. Patients and Methods: Fifty neonates (from first hour to one month) attending pediatric emergency services with various ailments. Blood gas analysis, electrolytes, plasma lactate, and plasma albumin were estimated in neonates. Results: Metabolic acidosis was the most common acid–base disorder. Hyperlactatemia was observed in more than half of such cases. Birth asphyxia was another common disorder with the highest mortality in neonates followed by bronchopneumonia and sepsis. Significant correlation between mortality and critical values of lactate was observed. Conclusion: Birth asphyxia with high-lactate levels in neonates constituted major alterations in acid–base disorders seen in an emergency room of a tertiary teaching care hospital. Plasma lactate concentration measurement provides an invaluable tool to assess type of metabolic acidosis in addition to predicting mortality in these neonates. PMID:20859489

Wideband acoustic immittance for assessing middle ear functioning for preterm neonates in the neonatal intensive care unit.

PubMed

Gouws, Nandel; Swanepoel, De Wet; De Jager, Leigh Biagio

2017-06-28

The primary aim of newborn hearing screening is to detect permanent hearing loss. Because otoacoustic emissions (OAEs) and automated auditory brainstem response (AABR) are sensitive to hearing loss, they are often used as screening tools. On the other hand, false-positive results are most often because of transient outer- and middle ear conditions. Wideband acoustic immittance (WAI), which includes physical measures known as reflectance and absorbance, has shown potential for accurate assessment of middle ear function in young infants. The main objective of this study was to determine the feasibility of WAI as a diagnostic tool for assessing middle ear functioning in preterm neonates in the neonatal intensive care unit (NICU) designed for premature and ill neonates. A further objective was to indicate the difference between the reflectance values of tones and click stimuli. Fifty-six at-risk neonates (30 male and 26 female), with a mean age at testing of 35.6 weeks (range: 32-37 weeks) and a standard deviation of 1.6 from three private hospitals, who passed both the distortion product otoacoustic emission (DPOAE) and AABR tests, were evaluated prior to discharge from the NICU. Neonates who presented with abnormal DPOAE and AABR results were excluded from the study. WAI was measured by using chirp and tone stimuli. In addition to reflectance, the reflectance area index (RAI) values were calculated. Both tone and chirp stimuli indicated high-power reflectance values below a frequency of 1.5 kHz. Median reflectance reached a minimum of 0.67 at 1 kHz - 2 kHz but increased to 0.7 below 1 kHz and 0.72 above 2 kHz for the tone stimuli. For chirp stimuli, the median reflectance reached a minimum of 0.51 at 1 kHz - 2 kHz but increased to 0.68 below 1 kHz and decreased to 0.5 above 2 kHz. A comparison between the present study and previous studies on WAI indicated a substantial variability across all frequency ranges. These WAI measurements conducted on at-risk preterm NICU

Use of cefoperazone/sulbactam in neonates.

PubMed

Ovali, Fahri; Gursoy, Tugba; Sari, Ilkay; Divrikli, Demet; Aktas, Alev

2012-02-01

Neonates are at high risk for nosocomial infections due to multidrug-resistant pathogens. The use of β-lactamase inhibitors in combination with β-lactam antibiotics broadens the antimicrobial spectrum. Cefoperazone/sulbactam is used in children but there are limited data on its usage in neonates. The purpose of the present study was therefore to evaluate the use of cefoperazone/sulbactam in the treatment of neonatal infections caused by multidrug-resistant pathogens. The records of neonates who were hospitalized and who received cefoperazone/sulbactam were reviewed. There were 90 infants who received cefoperazone/sulbactam. A pathogen could be isolated in 41 (45.6%) of the infants. In total, 17.1% of isolated pathogens were resistant to cefoperazone/sulbactam. Side-effects were seen in four of the infants. Two infants had cholestasis, one infant had neutropenia and one had superinfection with candida. Cefoperazone/sulbactam can be used in the treatment of nosocomial infections caused by multidrug-resistant pathogens in neonates. © 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.

Late-onset neonatal sepsis: recent developments

PubMed Central

Dong, Ying; Speer, Christian P

2015-01-01

The incidence of neonatal late-onset sepsis (LOS) is inversely related to the degree of maturity and varies geographically from 0.61% to 14.2% among hospitalised newborns. Epidemiological data on very low birth weight infants shows that the predominant pathogens of neonatal LOS are coagulase-negative staphylococci, followed by Gram-negative bacilli and fungi. Due to the difficulties in a prompt diagnosis of LOS and LOS-associated high risk of mortality and long-term neurodevelopmental sequelae, empirical antibiotic treatment is initiated on suspicion of LOS. However, empirical therapy is often inappropriately used with unnecessary broad-spectrum antibiotics and a prolonged duration of treatment. The increasing number of multidrug-resistant Gram-negative micro-organisms in neonatal intensive care units (NICU) worldwide is a serious concern, which requires thorough and efficient surveillance strategies and appropriate treatment regimens. Immunological strategies for preventing neonatal LOS are not supported by current evidence, and approaches, such as a strict hygiene protocol and the minimisation of invasive procedures in NICUs represent the cornerstone to reduce the burden of neonatal LOS. PMID:25425653

Neonatal Bartter Syndrome in association with congenital adrenal hyperplasia in a neonate - a rare combination.

PubMed

Hussain, Shabbir

2016-05-01

Neonatal Bartter syndrome (NBS) is an autosomal recessive renal tubulopathy characterized by hypokalaemic, hypochloraemic metabolic alkalosis associated with increased urinary loss of sodium, potassium, calcium and chloride. There is hyperreninaemia and hyperaldosteronaemia but normotension. Congenital adrenal hyperplasia (CAH), another autosomal recessive condition, may present in the neonatal period with vomiting, hypovolaemia, failure to gain weight or ambiguous genitalia. We report a case of NBS and CAH combination in a neonate. A male neonate born at term was admitted with history of recurrent vomiting and dehydration episodes. Investigations revealed electrolytes imbalance, metabolic alkalosis, raised aldosterone and renin levels suggestive of NBS. He was treated successfully and discharged. He was re-admitted with the same symptoms. Further evaluation confirmed the presence of CAH as well. We report this case because of the rarity of this combination (NBS plus CAH) and to the best of our knowledge this is the first such case report from Pakistan.

Ondansetron Pharmacokinetics in Pregnant Women and Neonates: Towards a New Treatment for Neonatal Abstinence Syndrome

PubMed Central

Elkomy, Mohammed H.; Sultan, Pervez; Carvalho, Brendan; Peltz, Gary; Wu, Manhong; Clavijo, Claudia; Galinkin, Jeffery L.; Drover, David R.

2014-01-01

Ondansetron is the drug of choice to prevent nausea in women undergoing cesarean surgery and can be used to prevent neonatal abstinence syndrome (NAS). Pharmacokinetics of ondansetron has not been characterized in pregnant women or in newborns. A nonlinear mixed-effects modeling approach was used to analyze plasma samples obtained from 20 non-pregnant and 40 pregnant women following single administration of 4 or 8 mg ondansetron, from umbilical cord blood at delivery, and from neonates after birth. The analysis indicates that: ondansetron disposition is not affected by pregnancy (p>0.05), but influenced by dose (p<0.05), and is characterized by rapid transplacental transfer and longer elimination half-life in neonates compared to their mother. A dosing regimen for prevention of NAS was designed based on the model. The regimen involves IV administration of 4 mg to the mothers shortly before cord clamping, or oral administration of 0.07 mg/kg (or equivalently 0.04 mg/kg IV) to neonates. PMID:25670522

A survey of the management of neonatal hypoglycaemia within the Australian and New Zealand Neonatal Network.

PubMed

Harris, Deborah L; Weston, Philip J; Battin, Malcolm R; Harding, Jane E

2014-10-01

Neonatal hypoglycaemia is a common problem linked to both brain damage and death. There is controversy regarding both the definition of and best treatment for neonatal hypoglycaemia. To determine current management of neonatal hypoglycaemia within the Australian and New Zealand Neonatal Network (ANZNN). Four questionnaires were sent to the Director of each of the 45 nurseries within the ANZNN. The Director was asked to complete one questionnaire and give the remaining three to other doctors involved with the management of babies with hypoglycaemia in the nursery. One hundred and eighty surveys were sent and 127 were returned (71%), including at least one from each nursery. Almost all respondents (120, 94%) reported using a protocol to treat hypoglycaemia. Only 2 (2%) reported screening all babies for neonatal hypoglycaemia, with the remainder screening babies at risk. Only 67, (53%) reported that blood glucose levels were tested on an analyser generally considered to be reliable at low levels. Most respondents (99, 78%) reported the clinical threshold for treatment was <2.6 mmol/L. However, when provided with clinical scenarios, respondents reported a variety of interventions, including no treatment. Doctors within the ANZNN are consistent about definition and screening for neonatal hypoglycaemia. However, frequently, the diagnosis is made using unreliable analysers. There is also wide variation in treatment, suggesting a lack of reliable evidence on which to base practice. © 2009 The Authors. Journal compilation © 2009 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

[Neonatal eucapnic pH at birth: Application in a cohort of 5392 neonates].

PubMed

Racinet, C; Peresse, J-F; Richalet, G; Corne, C; Ouellet, P

2016-09-01

To apply a newly concept of neonatal eucapnic pH at birth [pH euc (n)] and compare its contribution towards conventional criteria of severe metabolic acidosis. Analysis of a cohort of 5392 neonates from 2010 to 2014 in a level 1 maternity. clinical data (birth weight, gestational age, mode of delivery, APGAR score) were collected from archived files. Biological data were collected from umbilical cord blood, consisting of pH, PCO2, Base deficit, lactate. Eucapnic pH and eucapnic base deficit were calculated from pH and PCO2 with the Henderson-Hasselbalch equation applied in the Charles-Racinet diagram and/or with an Excel spreadsheet. Data set the prevalence of neonatal acidemia<7.00 to 0.62 %. The current cohort shows 32 cases of severe neonatal metabolic acidosis according to ACOG-AAP (2014) criteria and 26/29 cases according to McLennan (2015) criteria, of which 80 % were born by cesarean section or instrumental delivery. In 55 % of cases, calculated eucapnic pH at birth did not confirm the severity of metabolic acidosis based on a threshold set at 7.11. Five cases were transferred in neonatalogy only on clinical considerations of poor neonatal adaptation but not on biological consideration (pH euc<7.11 was equally distributed between transferred and non-transferred neonates, P=0.76; the same distribution was observed with the pH, P=0.20) and followed normal outcome. The pH determination provides information only on the degree of acidemia and not on respiratory and/or metabolic components. Moreover, hypercapnia always present at birth is not included in the instructions to determine a metabolic acidosis (The American College of Obstetricians and Gynecologists, 2014; MacLennan et al., 2015). The new concept of neonatal eucapnic pH at birth accounts for only the metabolic component. We feel it should fine tune indications for cerebral hypothermia and thus improve its effectiveness. From a medicolegal perspective, for cases of cerebral palsy, it often

Suprapubic Bladder Aspiration in Neonates

PubMed Central

Akierman, Albert R.

1987-01-01

Suprapubic bladder aspiration in neonates is a simple, safe, and useful technique for collection of sterile urine. The procedure can be performed in the hospital or office. Neither sedation nor local anesthetic is required. Suprapubic bladder aspiration of urine is the preferred method of collecting urine for culture in septic neonates. The technique is also indicated to verify urinary tract infection in neonates. Suprapubic bladder aspiration is contraindicated in the presence of abdominal distension or an empty bladder. Carefully and properly performed, the risk of complications should be negligible, and the success rate in obtaining urine is 90%. ImagesFigure 1Figure 2 PMID:21263980

Treatment and Prevention of Heparin-Induced Thrombocytopenia

PubMed Central

Dans, Antonio L.; Moores, Lisa K.; Bona, Robert; Davidson, Bruce L.; Schulman, Sam; Crowther, Mark

2012-01-01

Background: Heparin-induced thrombocytopenia (HIT) is an antibody-mediated adverse drug reaction that can lead to devastating thromboembolic complications, including pulmonary embolism, ischemic limb necrosis necessitating limb amputation, acute myocardial infarction, and stroke. Methods: The methods of this guideline follow the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. Results: Among the key recommendations for this article are the following: For patients receiving heparin in whom clinicians consider the risk of HIT to be > 1%, we suggest that platelet count monitoring be performed every 2 or 3 days from day 4 to day 14 (or until heparin is stopped, whichever occurs first) (Grade 2C). For patients receiving heparin in whom clinicians consider the risk of HIT to be < 1%, we suggest that platelet counts not be monitored (Grade 2C). In patients with HIT with thrombosis (HITT) or isolated HIT who have normal renal function, we suggest the use of argatroban or lepirudin or danaparoid over other nonheparin anticoagulants (Grade 2C). In patients with HITT and renal insufficiency, we suggest the use of argatroban over other nonheparin anticoagulants (Grade 2C). In patients with acute HIT or subacute HIT who require urgent cardiac surgery, we suggest the use of bivalirudin over other nonheparin anticoagulants or heparin plus antiplatelet agents (Grade 2C). Conclusions: Further studies evaluating the role of fondaparinux and the new oral anticoagulants in the treatment of HIT are needed. PMID:22315270

The financial impact of heparin-induced thrombocytopenia.

PubMed

Smythe, Maureen A; Koerber, John M; Fitzgerald, Maureen; Mattson, Joan C

2008-09-01

Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction that increases patient morbidity and mortality. The financial impact of HIT to an institution is thought to be significant. The objective of this study was to evaluate the financial impact of HIT. A case-control study was employed. Case patients were identified as newly diagnosed HIT patients. Control subjects were matched by diagnosis-related group, primary diagnosis code, primary procedure code, and hospital admission date. The financial/decision support database of the hospital was queried to identify the matched control subjects, total cost, and reimbursement. The determination of financial impact included the total profit or (total loss) and the backfill effect (ie, the lost operating margin resulting from increased length of stay). Length of stay and mortality were compared. Data from 22 case patients and 255 control subjects were analyzed. On average, HIT case patients incurred a financial loss of $14,387 per patient and an increase in length of stay of 14.5 days. When confining the analysis to only Medicare case patients (n = 17) and Medicare control subjects, case patients incurred a financial loss of $20,170 per case and an increase in length of stay of 15.8 days. Depending on the occupancy rate of the institution, additional financial loss could result from the backfill effect. Mortality was not significantly affected. For an institution that sees 50 new cases of HIT per year, the projected annual financial impact ranges from approximately $700,000 to $1 million. Institutions with high bed occupancy rates may see an additional loss from the backfill effect.

Adrenal haemorrhage due to heparin-induced thrombocytopenia.

PubMed

Ketha, Siva; Smithedajkul, Patrick; Vella, Adrian; Pruthi, Rajiv; Wysokinski, Waldemar; McBane, Robert

2013-04-01

Adrenal haemorrhage (AH) is a rare but potentially devastating complication of heparin-induced thrombocytopenia (HIT). Neither the prevalence nor the natural history of AH due to HIT are known. The objectives of this study were to identify the spectrum of AH causes, to characterise the frequency of AH due to HIT and determine the natural history of HIT-associated AH. All patients with incident adrenal haemorrhage from January 2002 through June 2012 seen at the Mayo Clinic were identified. Over this time frame, there were a total of 115 patients with AH of which 11 cases (10%; mean age 67 ± 8 years; 73% female) were associated with HIT. Of these, all but one occurred in the postoperative setting and involved both adrenal glands (89%) with acute adrenal insufficiency at the time of diagnosis. Cases were found incidentally during an evaluation for fever, shock, abdominal pain or mental status changes. All HIT patients experienced venous thrombosis at other locations including deep venous thromboses (n=14), pulmonary emboli (n= 4) and arterial thrombosis (n=2). Four patients undergoing total knee arthroplasty had "spontaneous HIT" with AH in the absence of identifiable heparin exposure. Other causes of AH included trauma (29%), sepsis (15%), antiphospholipid antibody syndrome (10%), and metastatic disease (12%). In conclusion, AH is an important but seldom recognised presumed thrombotic complication of HIT, which usually occurs in the postoperative period, especially after orthopaedic procedures. This syndrome can occur in the apparent absence of heparin exposure, especially following major joint replacement surgery.

Hypocalcemia in jaundiced neonates receiving phototherapy

PubMed Central

Khan, Mashal; Malik, Kanwal Altaf; Bai, Rekha

2016-01-01

Objective: To determine the frequency of hypocalcemia in term neonates with jaundice receiving phototherapy. Methods: This was a cross sectional study conducted at Neonatal intensive care unit, National Institute of Child Health, Karachi from 1st January 2014 to 30th December 2014. A total of 123 term neonates with jaundice of either gender managed by phototherapy were enrolled in the study. Gestational age was assessed through modified Ballard scoring. Duration of phototherapy was recorded. A sample of 3 ml of blood was sent to the laboratory for serum calcium level before initiating phototherapy and after 24 hours of continued phototherapy. All the data were recorded in the preformed proforma. Data was analyzed using SPSS version 19. P value <0.05 was taken as significant. Results: The mean age of the neonates was 8.35±6.74 days. Mean gestational age at the time of birth was 39.08±1.37 weeks. Mean duration of jaundice was 2.4±1.20 days. Mean duration of phototherapy was 1.74±0.98 days. Serum calcium level before and after 24 hours of initiating phototherapy was 8.73±0.68 mg/dl and 7.47±0.82mg/dl respectively Frequency of hypocalcemia in term jaundiced neonates receiving phototherapy were observed in 22.76% (28/123). Conclusions: The frequency of hypocalcemia is significant in the jaundiced neonates treated with phototherapy. One needs to be vigilant in dealing neonates in this context while serial monitoring for hypocalcemia and its complications should be considered in institutional policy and research priority. PMID:28083043

The Effect of Mother's Voice on Arterial Blood Sampling Induced Pain in Neonates Hospitalized in Neonate Intensive Care Unit.

PubMed

Azarmnejad, Elham; Sarhangi, Forogh; Javadi, Mahrooz; Rejeh, Nahid

2015-04-19

Due to devastating effects of pain in neonates, it is very important to ease it though safe and feasible methods. This study was to determine the effect of familiar auditory stimuli on the arterial blood sampling (ABS) induced pain in term neonates. This study was done on 30 newborns hospitalized in neonate intensive care unit (NICU) of a hospital in Tehran. Research samples were selected by using convenience sampling and randomly divided into two groups of control and test. In the test group, the recorded mothers' voices were played for the newborns before and after blood sampling procedure. Then, pain measures were recorded 10 minutes before, during and 10 minutes after blood collection based on Neonatal Infant Pain Scale (NIPS); then the pain level changes were reviewed and studied. The findings showed significant differences between the control and test groups that indicating the effect of mother's voice on reducing the pain of neonates during the ABS (p<0.005). Research findings demonstrate that mother's voice reduces ABS induced pain in the term neonates.

Neonatal screening for glucose-6-phosphate dehydrogenase deficiency.

PubMed

Pao, Mritunjay; Kulkarni, Anjali; Gupta, Vidya; Kaul, Sushma; Balan, Saroja

2005-10-01

This study was carried out to detect the incidence of erythrocytic Glucose-6 -Phosphate dehydrogenase (G-6-PD) deficiency, to compare the incidence of hyperbilirubinemia in G-6-PD deficient neonates as compared to G-6-PD normal neonates and to asses the usefulness of neonatal screening for G-6-PD deficiency. In a retrospective hospital based study 2,479 male and female neonates consecutively born at Indraprastha Apollo hospital between July 1998 to June 2003 who were screened for G-6-PD levels were evaluated for the incidence of G-6-PD deficiency. Incidence of G-6-PD deficiency was found to be 2.0%. Incidence in males was 283% and female was 1.05%. The incidence of hyperbilirubinemia was found to be 32% in G-6-PD deficient neonates which was significantly higher than the incidence of hyperbilirubinemia in neonates with normal G-6-PD, which was 12.3% (P< 0.001). Our data suggests that neonatal screening for G-6-PD deficiency is a useful test for preventing and early treatment of complications associated with it.

Non-pharmacological techniques for pain management in neonates.

PubMed

Golianu, Brenda; Krane, Elliot; Seybold, Jeannie; Almgren, Chris; Anand, K J S

2007-10-01

Significant progress in understanding the physiology, clinical correlates, and consequences of neonatal pain have resulted in greater attention to pain management during neonatal intensive care. A number of nonpharmacological therapies have been investigated, including nonnutritive sucking, with and without sucrose use, swaddling or facilitated tucking, kangaroo care, music therapy, and multi-sensorial stimulation. Although the efficacy of these approaches is clearly evident, they cannot provide analgesia for moderate or severe pain in the neonate. Further, some of these therapies cannot be effectively applied to all populations of critically ill neonates. Acupuncture, an ancient practice in Chinese medicine, has gained increasing popularity for symptom control among adults and older children. Acupuncture may provide an effective nonpharmacological approach for the treatment of pain in neonates, even moderate or severe pain, and should be considered for inclusion in a graduated multidisciplinary algorithm for neonatal pain management.

Gender-related analysis of the clinical presentation, treatment response and outcome in patients with immune thrombocytopenia.

PubMed

Andrès, Emmanuel; Mecili, Mustapha; Fothergill, Helen; Zimmer, Jacques; Vogel, Thomas; Maloisel, Frédéric

2012-09-01

Immune thrombocytopenia (idiopathic thrombocytopenic purpura [ITP]) frequently occurs in young adults, particularly women in their third or fourth decade. The female predominance suggests that sex hormones may play a role in the different aspects of ITP. In this paper, we report a gender-related analysis of patients with ITP, specifically examining the clinical manifestations, responses to treatment and overall outcomes of the patients. We included patients with "ITP" attending the departments of onco-hematology or internal medicine B (university hospital of Strasbourg, France) between 1990 and December 2010 The gender-related analysis was retrospective. We studied in 225 consecutive cases of established ITP with a follow-up period of 1.7 to 112 months The mean age of the patients was 44 years; 156 patients were female. The analysis revealed no significant statistical differences regarding patient characteristics between the female and male groups, with the exception of the following characteristics: the bleeding score, which altered in the presence of meno- and/or metrorrhagia and hematuria in female patients (P=0.03); the presence of anemia (P=0.04); and the detection of antinuclear and/or antiphospholipid antibodies (P=0.02). During the follow-up, no statistically significant difference was found regarding outcome or treatment response in relation to gender among these 225 patients (all P>0.05). Gender does not appear to affect the manifestation of immune thrombocytopenia, the outcome or response to treatment. However, further large-scale randomized trials are needed to confirm these findings. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Human platelet antigens in Burmese, Karen and north-eastern Thais.

PubMed

Phuangtham, R; Romphruk, A; Puapairoj, C; Leelayuwat, C; Romphruk, A V

2017-02-01

A comparative study of allele frequencies at HPA-1 to -6 and HPA-15 in Burmese and Karen populations as well as at HPA-15 in north-eastern Thais (NET) is presented. Human platelet antigens (HPAs) are clinically important in several immune platelet disorders, including foetal and neonatal alloimmune thrombocytopenia (FNAIT), post-transfusion purpura (PTP) and platelet transfusion refractoriness (PTR). The knowledge of antigen frequencies in a population is essential for the evaluation of patients suffering from immune-mediated platelet disorders. A total of 285 unrelated, healthy Burmese, 242 Karen and 300 NET were recruited to this study. Genotype and allele frequencies of HPA-1 to -6 and HPA-15 were defined using polymerase chain reaction sequence-specific primers (PCR-SSP) RESULTS: No individuals homozygous for HPA-1bb, -2bb, -4bb, -5bb and -6bb were detected. HPA-1a, -2a, -4a, -5a and -6a were present in all samples of Burmese and Karen origin. HPA-1b, -2b, -4b, -5b and -6b were rare in these populations. The frequencies of HPA-3a/-3b were 60·4/39·6% in Burmese and 55·8/44·2% in Karen, respectively. Frequencies of HPA-15a/-15b were 57·2/42·8% in Burmese, 52·5/47·5% in Karen and 49·8/50·2% in NET. The frequencies of HPA genotypes in our study indicates that HPA-1a, -2a, -4a, -5a and -6a are unlikely involved in FNAIT, PTP and PTR in Burmese and Karen populations. However, HPA-1b, -2b, -3a, -3b, -4b, -5b, -6b, -15a and -15b may likely stimulate alloantibodies in these populations. © 2016 British Blood Transfusion Society.

Development of a single-antigen magnetic bead assay (SAMBA) for the sensitive detection of HPA-1a alloantibodies using tag-engineered recombinant soluble β3 integrin.

PubMed

Skaik, Younis; Battermann, Anja; Hiller, Oliver; Meyer, Oliver; Figueiredo, Constanca; Salama, Abdulgabar; Blasczyk, Rainer

2013-05-31

Timely and accurate testing for human platelet antigen 1a (HPA-1a) alloantibodies is vital for clinical diagnosis of neonatal alloimmune thrombocytopenia (NAIT). Current antigen-specific assays used for the detection of HPA-1 alloantibodies are technically very complex and cumbersome for most diagnostic laboratories. Hence, we designed and applied recombinant soluble (rs) β3 integrins displaying HPA-1a or HPA-1b epitopes for the development of a single-antigen magnetic bead assay (SAMBA). Soluble HPA-1a and HPA-1b were produced recombinantly in human embryonic kidney 293 (HEK293) cells and differentially tagged. The recombinant soluble proteins were then immobilized onto paramagnetic beads and used for analysis of HPA-1 alloantibodies by enzyme-linked immunosorbent assay (ELISA). HPA-1a serum samples (n=7) from NAIT patients, inert sera and sera containing non-HPA-1a antibodies were used to evaluate the sensitivity and specificity of the SAMBA. Fusion of V5-His or GS-SBP-His tags to the rsβ3 integrins resulted in high-yield expression. SAMBA was able to detect all HPA-1a and -1b alloantibodies recognized by monoclonal antibody-specific immobilization of platelet antigens assay (MAIPA). No cross-reactions between the sera were observed. Two out of seven of the HPA-1a alloantibody-containing sera demonstrated weak to moderate reactivity in MAIPA but strong signals in SAMBA. SAMBA provides a very reliable method for the detection of HPA-1 antibodies with high specificity and sensitivity. This simple and rapid assay can be adapted for use in any routine laboratory and can be potentially adapted for use on automated systems. Copyright © 2013 Elsevier B.V. All rights reserved.

Intracranial complications of Serratia marcescens infection in neonates.

PubMed

Madide, Ayanda; Smith, Johan

2016-03-15

Even though Serratia marcescens is not one of the most common causes of infection in neonates, it is associated with grave morbidity and mortality. We describe the evolution of brain parenchymal affectation observed in association with S. marcescens infection in neonates. This retrospective case series details brain ultrasound findings of five neonates with hospital-acquired S. marcescens infection. Neonatal S. marcescens infection with or without associated meningitis can be complicated by brain parenchymal affectation, leading to cerebral abscess formation. It is recommended that all neonates with this infection should undergo neuro-imaging more than once before discharge from hospital; this can be achieved using bedside ultrasonography.

Spatial Analysis of Severe Fever with Thrombocytopenia Syndrome Virus in China Using a Geographically Weighted Logistic Regression Model

PubMed Central

Wu, Liang; Deng, Fei; Xie, Zhong; Hu, Sheng; Shen, Shu; Shi, Junming; Liu, Dan

2016-01-01

Severe fever with thrombocytopenia syndrome (SFTS) is caused by severe fever with thrombocytopenia syndrome virus (SFTSV), which has had a serious impact on public health in parts of Asia. There is no specific antiviral drug or vaccine for SFTSV and, therefore, it is important to determine the factors that influence the occurrence of SFTSV infections. This study aimed to explore the spatial associations between SFTSV infections and several potential determinants, and to predict the high-risk areas in mainland China. The analysis was carried out at the level of provinces in mainland China. The potential explanatory variables that were investigated consisted of meteorological factors (average temperature, average monthly precipitation and average relative humidity), the average proportion of rural population and the average proportion of primary industries over three years (2010–2012). We constructed a geographically weighted logistic regression (GWLR) model in order to explore the associations between the selected variables and confirmed cases of SFTSV. The study showed that: (1) meteorological factors have a strong influence on the SFTSV cover; (2) a GWLR model is suitable for exploring SFTSV cover in mainland China; (3) our findings can be used for predicting high-risk areas and highlighting when meteorological factors pose a risk in order to aid in the implementation of public health strategies. PMID:27845737

Status of Neonatal Pain Assessment and Management in Jordan.

PubMed

Abdel Razeq, Nadin M; Akuma, Akuma O; Jordan, Sue

2016-08-01

Current pain assessment and management in neonates need to be fully described before neonatal pain care can be optimized. This study's purpose was to report neonatal nurses' knowledge, existing pain assessment practice, and pharmacological pain management of neonates in Jordan. A cross-sectional descriptive study was conducted. Eighteen neonatal intensive care units in Jordan were included in the study. One hundred eighty-four neonatal nurses participated. Questionnaires were distributed by and returned to the neonatal intensive care units' managers between June and August 2014. Descriptive and inferential statistics were used to present study results. Of 240 questionnaires distributed, 184 useable responses were returned. Nurses' knowledge regarding neonates' neurological development, nociception, and need for neonatal pain management was suboptimal. The analgesics most commonly used to treat neonatal pain were acetaminophen (52%) and lidocaine (45%). Benzodiazepines, phenobarbitone, and muscles relaxants were also used. Most nurses (54%-97%) reported that pain emanating from most painful procedures was never or rarely treated. Circumcision, lumbar punctures, and chest tube insertion were assigned the highest pain scores (≥9), but were rarely accompanied by analgesia. Pain assessment scales were more likely to be used, and procedural pain was more likely to be treated, in private hospitals than public hospitals. Neonates who require special care still suffer unnecessary pain that could be avoided and managed by following best practice recommendations. Disparities between developed and developing countries in quality of neonatal pain care appear to exist. Resources for education and routine care are needed to address these discrepancies. Copyright © 2016 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Neonatal listeriosis in the UK 2004-2014.

PubMed

Sapuan, Shari; Kortsalioudaki, Christina; Anthony, Mark; Chang, John; Embleton, Nicholas D; Geethanath, Ruppa M; Gray, Jim; Greenough, Anne; Lal, Mithilesh K; Luck, Suzanne; Pattnayak, Santosh; Reynolds, Peter; Russell, Allison B; Scorrer, Timothy; Turner, Mark; Heath, Paul T; Vergnano, Stefania

2017-03-01

To define the clinical features and outcomes of neonatal listeriosis, and identify the maternal risk factors to seek scope for improvement. Neonatal listeriosis was identified prospectively from a United Kingdom neonatal infection surveillance network (neonIN) between 2004 and 2014. The participating neonatal units completed a study-specific proforma. The incidence of neonatal listeriosis was 3.4 per 100,000 live births. Of the 21 cases identified, 19 were confirmed with a median gestational age of 33 weeks and a median birth weight of 1960 g. The majority had clinical features (95%, 18/19), presented within the first 24 h (95%, 18/19), and received penicillin empirically (94%, 18/19). The neonatal case-fatality rate was 21% (24% if probable cases were included). A proportion of mothers were investigated (60%, 12/18) and diagnosed with listeriosis (58%, 7/12); 32% (6/19) were treated with antibiotics but only 33% (6/12) included penicillin. Despite its rarity and the prompt and appropriate use of antibiotics neonatal listeriosis has a high case-fatality rate. There is room for improvement in the adherence to the empiric antibiotic choice for puerperal sepsis, according to the national guidelines as this, would target listeriosis. Strategies should be in place to prevent pregnancy-associated listeriosis in higher risk population. Copyright © 2016 The British Infection Association. All rights reserved.

Prediction of initiation and duration of breast-feeding for neonates admitted to the neonatal intensive care unit.

PubMed

Lessen, Rachelle; Crivelli-Kovach, Andrea

2007-01-01

Women who desire to breast-feed their sick newborns often encounter obstacles, including insufficient support and education as well as unsupportive hospital practices. The purpose of this study was to describe maternal, neonatal, and outside influences associated with the intention, initiation, and duration of breast-feeding for women whose newborns were admitted to the neonatal intensive care unit. One hundred mothers were interviewed. Most mothers (67%) intended to breast-feed exclusively and this was significantly related to maternal characteristics such as age, education, parity, smoking and marital status, pre-breast-feeding experience, and the influences of the neonate's father and prenatal education. Seventy-eight mothers initiated pumping. Initiation was significantly related to maternal education, smoking, parity, previous breast-feeding experience, the neonate's physician, the neonate's father, and postpartum breast-feeding education. Fifty-four mothers were followed up by telephone after discharge until weaning. Thirty percent were exclusively breast-feeding at 2 weeks after discharge, and 15% were breast-feeding at 1 year. Duration of breast-feeding was significantly associated with education, marital status, ethnicity, income, assistance from nurses and lactation consultants, and feeding method along with milk type and milk volume at discharge. Increased family support, timely breast-feeding information, and a supportive neonatal intensive care unit environment are needed for women to succeed in breast-feeding their hospitalized newborns.

Efficacy of combined intravenous immunoglobulins and steroids in children with primary immune thrombocytopenia and persistent bleeding symptoms

PubMed Central

Parodi, Emilia; Giordano, Paola; Rivetti, Elisa; Giraudo, Maria Teresa; Ansaldi, Giulia; Davitto, Mirella; Mondino, Anna; Farruggia, Piero; Amendola, Giovanni; Matarese, Sofia M.R.; Rossi, Francesca; Russo, Giovanna; Ramenghi, Ugo

2014-01-01

Background The aim of this study was to investigate the effect of the combined administration of intravenous immunoglobulins and steroids as a second-line therapy in 34 children with primary immune thrombocytopenia and persistent, symptomatic bleeding. Materials and methods Combined therapy (intravenous immunoglobulins 0.4 g/kg daily on days 1 and 2, and methylprednisolone 20 mg/kg daily on days 1–3) was administered to 12 patients with newly diagnosed ITP who did not respond to the administration of a single therapy (either intravenous immunoglobulins or steroids) and to 22 children with persistent and chronic disease who required frequent administrations (i.e. more frequently than every 30 days) of either immunoglobulins or steroids (at the same standard dosages) in order to control active bleeding. Results A response (i.e. platelet count >50×109/L and remission of active bleeding) was observed in 8/12 (67%) patients with newly diagnosed ITP. The clinical presentation of responders and non-responders did not differ apparently. Patients in the chronic/persistent phase of disease had a significantly longer median period of remission from symptoms compared with the previous longest period of remission (p=0.016). The treatment was well tolerated. Discussion Our data suggest that the combined approach described is a well-tolerated therapeutic option for children with primary immune thrombocytopenia and persistent bleeding symptoms that can be used in both emergency and/or maintenance settings. PMID:24887226

Utilization of 4T score to determine the pretest probability of heparin-induced thrombocytopenia in a community hospital in upstate New York.

PubMed

Samhouri, Yazan; Telfah, Mohammad; Kouides, Ruth; Woodlock, Timothy

2016-01-01

Thrombocytopenia is common in hospitalized patients. Heparin-induced thrombocytopenia (HIT) is a life-threatening condition which can lead to extensive thrombosis. Diagnosis of HIT relies on clinical suspicion determined by 4T score and immunoassays through testing for anti-PF4/heparin antibodies. Clinical practice guidelines published by the American Society of Hematology in 2013 recommended use of the 4T score before ordering the immunoassays as a measure of pretest probability. The purpose of this study was to evaluate the utilization of 4T score before ordering anti-PF4/heparin antibodies at Unity Hospital. We did a retrospective chart review for patients who are 18 years or older, admitted to Unity Hospital between July 1, 2013, and December 31, 2014, and had anti-PF4/heparin antibodies ordered. Subjects who had prior history of HIT or had end-stage renal disease on hemodialysis were excluded. After calculating 4T score retrospectively, we calculated the proportion of patients who had 4T score documented prior to ELISA testing and proportion of ELISA tests, which were not indicated due to a 4T score less than or equal to 3 using Minitab 16. Review of 123 patients, with an average age of 69.4 years, showed that testing was indicated in 18 patients. Six subjects had positive results, and testing was indicated in all of them. 4T score was documented in three patients. This quality improvement study showed that 4T score documentation rate at Unity Hospital is 2.4%. Anti-PF4/heparin antibody testing was indicated in 14.6%. This test is being overused in thrombocytopenia work up at Unity Hospital, costing $9,345. The topic was reviewed for residents. A prompt and calculator for 4T score were added to electronic medical records before ordering the test as a step to improve high value care.

Reduced nephron endowment in the neonates of Indigenous Australian peoples.

PubMed

Kandasamy, Y; Smith, R; Wright, I M R; Lumbers, E R

2014-02-01

Rates of chronic kidney disease (CKD) among Indigenous groups in Australia exceed non-Indigenous rates eight-fold. Using kidney volume as a surrogate for nephron number, we carried out a study to determine if Indigenous neonates have a smaller kidney volume (and thus a reduced nephron number) from birth compared with non-Indigenous neonates. We recruited term and preterm neonates (<32 weeks) at a tertiary care neonatal unit over a 12 months period. Preterm neonates were assessed (renal sonography and renal function measurement) at 32 weeks corrected age (CA) and again at 38 weeks CA when blood pressure was also measured. All term neonates were assessed in the first post-natal week, including renal sonography, renal function and blood pressure measurement. The primary outcome measured was total kidney volume (TKV) and estimated glomerular filtration rate (eGFR) was a secondary outcome. Data was available for 44 preterm (11 Indigenous) and 39 term (13 Indigenous) neonates. TKV of Indigenous neonates was significantly lower at 32 weeks [12.0 (2.0) v. 15.4 (5.1) ml; P=0.03] and 38 weeks CA [18.6 (4.0) v. 22.6 (5.9) ml; P=0.04] respectively. Term Indigenous neonates also had smaller kidney volumes compared with non-Indigenous neonates. Despite a smaller kidney volume (and reduced nephron number), Indigenous neonates did not have a significantly lower eGFR. Indigenous neonates achieve similar eGFRs to Non-Indigenous neonates, presumably through a higher single nephron filtration rate. This places Indigenous neonates at a greater risk of long-term kidney damage later in life.

Malsoor Virus, a Novel Bat Phlebovirus, Is Closely Related to Severe Fever with Thrombocytopenia Syndrome Virus and Heartland Virus

PubMed Central

Yadav, P. D.; Basu, A.; Shete, A.; Patil, D. Y.; Zawar, D.; Majumdar, T. D.; Kokate, P.; Sarkale, P.; Raut, C. G.; Jadhav, S. M.

2014-01-01

During a survey in the year 2010, a novel phlebovirus was isolated from the Rousettus leschenaultii species of bats in western India. The virus was identified by electron microscopy from infected Vero E6 cells. Phylogenic analysis of the complete genome showed its close relation to severe fever with thrombocytopenia syndrome (SFTS) and Heartland viruses, which makes it imperative to further study its natural ecology and potential as a novel emerging zoonotic virus. PMID:24390329

Antioxidant treatment improves neonatal survival and prevents impaired cardiac function at adulthood following neonatal glucocorticoid therapy

PubMed Central

Niu, Youguo; Herrera, Emilio A; Evans, Rhys D; Giussani, Dino A

2013-01-01

Glucocorticoids are widely used to treat chronic lung disease in premature infants but their longer-term adverse effects on the cardiovascular system raise concerns. We reported that neonatal dexamethasone treatment in rats induced in the short term molecular indices of cardiac oxidative stress and cardiovascular tissue remodelling at weaning, and that neonatal combined antioxidant and dexamethasone treatment was protective at this time. In this study, we investigated whether such effects of neonatal dexamethasone have adverse consequences for NO bioavailability and cardiovascular function at adulthood, and whether neonatal combined antioxidant and dexamethasone treatment is protective in the adult. Newborn rat pups received daily i.p. injections of a human-relevant tapering dose of dexamethasone (D; n= 8; 0.5, 0.3, 0.1 μg g−1) or D with vitamins C and E (DCE; n= 8; 200 and 100 mg kg−1, respectively) on postnatal days 1–3 (P1–3); vitamins were continued from P4 to P6. Controls received equal volumes of vehicle from P1 to P6 (C; n= 8). A fourth group received vitamins alone (CCE; n= 8). At P100, plasma NO metabolites (NOx) was measured and isolated hearts were assessed under both Working and Langendorff preparations. Relative to controls, neonatal dexamethasone therapy increased mortality by 18% (P < 0.05). Surviving D pups at adulthood had lower plasma NOx concentrations (10.6 ± 0.8 vs. 28.0 ± 1.5 μm), an increased relative left ventricular (LV) mass (70 ± 2 vs. 63 ± 1%), enhanced LV end-diastolic pressure (14 ± 2 vs. 8 ± 1 mmHg) and these hearts failed to adapt output with increased preload (Δcardiac output: 2.9 ± 2.0 vs. 10.6 ± 1.2 ml min−1) or afterload (Δcardiac output: −5.3 ± 2.0 vs.1.4 ± 1.2 ml min−1); all P < 0.05. Combined neonatal dexamethasone with antioxidant vitamins improved postnatal survival, restored plasma NOx and protected against cardiac dysfunction at adulthood. In conclusion, neonatal dexamethasone therapy promotes

Nurses' Awareness of Preterm Neonates' Sleep in the NICU.

PubMed

Mahmoodi, Nasrin; Arbabisarjou, Azizollah; Rezaeipoor, Mahmood; Pishkar Mofrad, Zahra

2015-11-17

Fetus and neonate spend most of their time sleeping inside and outside the womb. Sleep is considered a crucial action of neonatal period similar to breathing and nutrition. It plays a key role in brain development. Today, it is shown that sleep plays a predominant role in body temperature regulation, energy saving and neuronal detoxification. Sleep is the most important behavioral state of neonates, particularly in preterm ones. Noise, light, invasive treatment and caring activities are among disturbing factors in the neonatal intensive care unit (NICU) that leave negative impacts on brain development through disturbing the sleep process. This descriptive study assessed all NICU nurses of Ali-ibn-Abitaleb hospital using the census sampling method. Demographic data was collected through a questionnaire with 10 questions about active sleep (AS) cycles, also referred to as REM, methods for inducing AS and AS specifications in neonates. The questionnaire was distributed between the nurses. After completion, data was analyzed using SPSS 16 and descriptive statistics method. According to analyses, 24%, 20%, 48% and 92% of nurses gave correct answers to questions about AS cycle, AS in neonates, the role of sleep in saving energy and ideal noise level, respectively. According to results, nurses had a low level of knowledge towards neonatal sleep. All nurses need to know the importance of sleep in preterm neonates. The main role of inducing sleep is to protect the development of the neonates' brain in the NICU. Those nurses who spend a remarkable portion of their time for caring neonates in the NICU play a significant role in neonatal sleep care.

Biochemical abnormalities in neonatal seizures.

PubMed

Sood, Arvind; Grover, Neelam; Sharma, Roshan

2003-03-01

The presence of seizure does not constitute a diagnoses but it is a symptom of an underlying central nervous system disorder due to systemic or biochemical disturbances. Biochemical disturbances occur frequently in the neonatal seizures either as an underlying cause or as an associated abnormality. In their presence, it is difficult to control seizure and there is a risk of further brain damage. Early recognition and treatment of biochemical disturbances is essential for optimal management and satisfactory long term outcome. The present study was conducted in the department of pediatrics in IGMC Shimla on 59 neonates. Biochemical abnormalities were detected in 29 (49.15%) of cases. Primary metabolic abnormalities occurred in 10(16.94%) cases of neonatal seizures, most common being hypocalcaemia followed by hypoglycemia, other metabolic abnormalities include hypomagnesaemia and hyponateremia. Biochemical abnormalities were seen in 19(38.77%) cases of non metabolic seizure in neonates. Associated metabolic abnormalities were observed more often with Hypoxic-ischemic-encephalopathy (11 out of 19) cases and hypoglycemia was most common in this group. No infant had hyponateremia, hyperkelemia or low zinc level.

Evaluation of Dry Sensors for Neonatal EEG recordings

PubMed Central

Fridman, Igor; Cordeiro, Malaika; Rais-Bahrami, Khodayar; McDonald, Neil J.; Reese, James J.; Massaro, An N.; Conry, Joan A.; Chang, Taeun; Soussou, Walid; Tsuchida, Tammy N.

2015-01-01

Introduction Neonatal seizures are a common neurologic diagnosis in Neonatal Intensive Care Units (NICUs), occurring in approximately 14,000 newborns annually in the US. While the only reliable means of detecting and treating neonatal seizures is with an EEG recording, many neonates do not get an EEG or experience delays in getting them. Barriers to obtaining neonatal EEGs include: 1) lack of skilled EEG technologists to apply conventional wet electrodes to delicate neonatal skin, 2) poor signal quality due to improper skin preparation and artifact, 3) extensive time needed to apply electrodes. Dry sensors have the potential to overcome these obstacles but have not been previously evaluated on neonates. Methods Sequential and simultaneous recordings with wet and dry sensors were performed for one hour on 27 neonates from 35-42.5 weeks postmenstrual age. Recordings were analyzed for correlation and amplitude, and were reviewed by neurophysiologists. Performance of dry sensors on simulated vernix was examined. Results Analysis of dry and wet signals showed good time-domain correlation (reaching >0.8) given the non-superimposed sensor positions, and similar power spectral density curves. Neurophysiologist reviews showed no statistically significant difference between dry and wet data on most clinically-relevant EEG background and seizure patterns. There was no skin injury after 1 hr of dry sensor recordings. In contrast to wet electrodes, impedance and electrical artifact of dry sensors were largely unaffected by simulated vernix. Conclusions Dry sensors evaluated in this study have the potential to provide high-quality, timely EEG recordings on neonates with less risk of skin injury. PMID:26562208

Evaluation of Dry Sensors for Neonatal EEG Recordings.

PubMed

Fridman, Igor; Cordeiro, Malaika; Rais-Bahrami, Khodayar; McDonald, Neil J; Reese, James J; Massaro, An N; Conry, Joan A; Chang, Taeun; Soussou, Walid; Tsuchida, Tammy N

2016-04-01

Neonatal seizures are a common neurologic diagnosis in neonatal intensive care units, occurring in approximately 14,000 newborns annually in the United States. Although the only reliable means of detecting and treating neonatal seizures is with an electroencephalography (EEG) recording, many neonates do not receive an EEG or experience delays in getting them. Barriers to obtaining neonatal EEGs include (1) lack of skilled EEG technologists to apply conventional wet electrodes to delicate neonatal skin, (2) poor signal quality because of improper skin preparation and artifact, and (3) extensive time needed to apply electrodes. Dry sensors have the potential to overcome these obstacles but have not previously been evaluated on neonates. Sequential and simultaneous recordings with wet and dry sensors were performed for 1 hour on 27 neonates from 35 to 42.5 weeks postmenstrual age. Recordings were analyzed for correlation and amplitude and were reviewed by neurophysiologists. Performance of dry sensors on simulated vernix was examined. Analysis of dry and wet signals showed good time-domain correlation (reaching >0.8), given the nonsuperimposed sensor positions and similar power spectral density curves. Neurophysiologist reviews showed no statistically significant difference between dry and wet data on most clinically relevant EEG background and seizure patterns. There was no skin injury after 1 hour of dry sensor recordings. In contrast to wet electrodes, impedance and electrical artifact of dry sensors were largely unaffected by simulated vernix. Dry sensors evaluated in this study have the potential to provide high-quality, timely EEG recordings on neonates with less risk of skin injury.

Oxidative Stress Markers Correlate with Renal Dysfunction and Thrombocytopenia in Severe Leptospirosis

PubMed Central

Araújo, Alan M.; Reis, Eliana A. G.; Athanazio, Daniel A.; Ribeiro, Guilherme S.; Hagan, José E.; Araujo, Guilherme C.; Damião, Alcineia O.; Couto, Nicolli S.; Ko, Albert I.; Noronha-Dutra, Alberto; Reis, Mitermayer G.

2014-01-01

Leptospirosis is a zoonotic disease that causes severe manifestations such as Weil's disease and pulmonary hemorrhage syndrome. The aim of this study was to evaluate whether reactive oxygen species (ROS) production and antioxidant reduced glutathione (GSH) levels are related to complications in patients hospitalized with leptospirosis. The ROS production and GSH levels were measured in blood samples of 12 patients and nine healthy controls using chemiluminescence and absorbance assays. We found that ROS production was higher and GSH levels were lower in leptospirosis patients compared with healthy individuals. Among patients, GSH depletion was correlated with thrombocytopenia and elevated serum creatinine, whereas a strong positive correlation was observed between ROS production and elevated serum potassium. Additional investigation of the biological significance of ROS production and GSH levels is warranted as they may guide the development of novel adjuvant therapies for leptospirosis targeting oxidative stress. PMID:24493675

The utility of pre-test clinical scoring for clinical diagnosis of heparin-induced thrombocytopenia in cardiac surgery patients of a tertiary care centre in north India.

PubMed

Sachan, D; Gupta, N; Agarwal, P; Chaudhary, R

2011-08-01

Heparin-induced thrombocytopenia (HIT) should be diagnosed clinically as well as by laboratory assays for timely recognition, prevention and management of complications. To evaluate the clinical utility of pre-test clinical scoring system in combination with two immunoassays for the diagnosis of HIT in cardiac surgery patients. A total of 100 consecutive patients undergoing cardiac surgery were studied. Pre-test clinical scoring was carried out in patients with thrombocytopenia and further tested by two immunoassays, i.e., Heparin platelet factor 4 (H-PF4) enzyme-linked immunosorbent assay (ELISA) and particle gel immunoassay (PaGIA). Of the 100 patients studied, 42 patients developed thrombocytopenia post-operatively. On pre-test clinical scoring, low T-score was observed in 6 patients, intermediate in 28 and high score in 8 patients, whereas 19 patients (45.2%) were positive by H-PF4 ELISA and 10 (23.8%) by PaGIA for H-PF4 antibody. The difference in the incidence of clinically significant HIT antibodies in the three categories was statistically significant. A good correlation was also observed with ELISA optical density, T-scoring and PaGIA. Pre-test clinical scoring correlates well with the development of H-PF4 antibodies which are incriminated in the causation of thrombotic complications in patients with HIT. We also propose a protocol for diagnosing patients with clinical suspicion of HIT using pre-test clinical scoring and immunoassay. © 2011 The Authors. Transfusion Medicine © 2011 British Blood Transfusion Society.

Neonatal follow-up program: Where do we stand?

PubMed Central

2012-01-01

Neonatal follow-up program (NFP) is becoming the corner stone of standard, high quality care provided to newborns at risk of future neuorodevelopmental delay. Most of the recognized neonatal intensive care units in the developed countries are adopting NFP as part of their mandatory care for the best long term outcome of high risk infants, especially very low birth weight (VLBW) infants. Unfortunately, in the developing and in underdeveloped countries, such early detection and intervention programs are rarely existing, mainly because of the lack of awareness of and exposure to such programs in spite of the increasing numbers of surviving sick newborns due to advancement in neonatal care in these countries. This is a review article to explore the Neonatal follow-up programs looking at historical development, benefts and aims, and standard requirements for successful program development that can be adopted in our countries. In conclusion, proper Neonatal follow-up programs are needed to improve neonatal outcome. Therefore all professionals working in the feld of neonatal care in developing countries should cooperate to create such programs for early detection and hence early intervention for any adverse long term outcome in high-risk newborn infants PMID:27493326

The Amelioration of Myelofibrosis with Thrombocytopenia by a JAK1/2 Inhibitor, Ruxolitinib, in a Post-polycythemia Vera Myelofibrosis Patient with a JAK2 Exon 12 Mutation.

PubMed

Ikeda, Kazuhiko; Ueda, Koki; Sano, Takahiro; Ogawa, Kazuei; Ikezoe, Takayuki; Hashimoto, Yuko; Morishita, Soji; Komatsu, Norio; Ohto, Hitoshi; Takeishi, Yasuchika

2017-01-01

Less than 5% of patients with polycythemia vera (PV) show JAK2 exon 12 mutations. Although PV patients with JAK2 exon 12 mutations are known to develop post-PV myelofibrosis (MF) as well as PV with JAK2V617F, the role of JAK inhibitors in post-PV MF patients with JAK2 exon 12 mutations remains unknown. We describe how treatment with a JAK1/2 inhibitor, ruxolitinib, led to the rapid amelioration of marrow fibrosis, erythrocytosis and thrombocytopenia in a 77-year-old man with post-PV MF who carried a JAK2 exon 12 mutation (JAK2H538QK539L). This case suggests that ruxolitinib is a treatment option for post-PV MF in patients with thrombocytopenia or JAK2 exon 12 mutations.

Hypothermia for neonatal hypoxic-ischemic encephalopathy: NICHD Neonatal Research Network contribution to the field.

PubMed

Shankaran, Seetha; Natarajan, Girija; Chalak, Lina; Pappas, Athina; McDonald, Scott A; Laptook, Abbot R

2016-10-01

In this article, we summarize the NICHD Neonatal Research Network (NRN) trial of whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy in relation to other randomized controlled trials (RCTs) of hypothermia neuroprotection. We describe the NRN secondary studies that have been published in the past 10 years evaluating clinical, genetic, biochemical, and imaging biomarkers of outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

Association of Preoperative Anemia With Postoperative Mortality in Neonates.

PubMed

Goobie, Susan M; Faraoni, David; Zurakowski, David; DiNardo, James A

2016-09-01

Neonates undergoing noncardiac surgery are at risk for adverse outcomes. Preoperative anemia is a strong independent risk factor for postoperative mortality in adults. To our knowledge, this association has not been investigated in the neonatal population. To assess the association between preoperative anemia and postoperative mortality in neonates undergoing noncardiac surgery in a large sample of US hospitals. Using data from the 2012 and 2013 pediatric databases of the American College of Surgeons National Surgical Quality Improvement Program, we conducted a retrospective study of neonates undergoing noncardiac surgery. Analysis of the data took place between June 2015 and December 2015. All neonates (0-30 days old) with a recorded preoperative hematocrit value were included. Anemia defined as hematocrit level of less than 40%. Receiver operating characteristics analysis was used to assess the association between preoperative hematocrit and mortality, and the Youden J Index was used to determine the specific hematocrit cutoff point to define anemia in the neonatal population. Demographic and postoperative outcomes variables were compared between anemic and nonanemic neonates. Univariate and multivariable logistic regression analyses were used to determine factors associated with postoperative neonatal mortality. An external validation was performed using the 2014 American College of Surgeons National Surgical Quality Improvement Program database. Neonates accounted for 2764 children (6%) in the 2012-2013 American College of Surgeons National Surgical Quality Improvement Program databases. Neonates inlcuded in the study were predominately male (64.5%), white (66.3%), and term (69.9% greater than 36 weeks' gestation) and weighed more than 2 kg (85.0%). Postoperative in-hospital mortality was 3.4% in neonates and 0.6% in all age groups (0-18 years). A preoperative hematocrit level of less than 40% was the optimal cutoff (Youden) to predict in-hospital mortality

Incidence, risk factors, and mortality of neonatal and late-onset dilated cardiomyopathy associated with cardiac neonatal lupus.

PubMed

Morel, Nathalie; Lévesque, Kateri; Maltret, Alice; Baron, Gabriel; Hamidou, Mohamed; Orquevaux, Pauline; Piette, Jean-Charles; Barriere, François; Le Bidois, Jérôme; Fermont, Laurent; Fain, Olivier; Theulin, Arnaud; Sassolas, François; Hauet, Quentin; Guettrot-Imbert, Gaëlle; Georgin-Lavialle, Sophie; Deligny, Christophe; Hachulla, Eric; Mouthon, Luc; Le Jeunne, Claire; Ravaud, Philippe; Le Mercier, Delphine; Romefort, Bénédicte; Villain, Elisabeth; Bonnet, Damien; Costedoat-Chalumeau, Nathalie

2017-12-01

Dilated cardiomyopathy (DCM), a well-known complication of cardiac neonatal lupus, is associated with high mortality rate. Its risk factors remain unclear. We analyzed occurrence of postnatal DCM among children with high-degree congenital heart block (CHB) and mothers with anti-SSA and/or anti-SSB antibodies. Among 187 neonates with CHB, 35 (18.8%, one missing data) had DCM and 22 (11.8%) died during a median follow-up of 7years [range: birth-36years]. On multivariate analysis, factors associated with postnatal DCM were in utero DCM (P=0.0199; HR=3.13 [95% CI: 1.20-8.16]), non-European origin (P=0.0052; HR=4.10 [95% CI: 1.81-9.28]) and pacemaker implantation (P=0.0013; HR=5.48 [95% CI: 1.94-15.47]). Postnatal DCM could be categorized in two subgroups: neonatal DCM (n=13, diagnosed at a median age of 0day [birth-4days]) and late-onset DCM (n=22, diagnosed at a median age of 15.2months [3.6months-22.8years]). Factors associated with neonatal DCM were in utero DCM, hydrops, endocardial fibroelastosis and pericardial effusion, whereas those associated with late-onset DCM were non-European origin, in utero mitral valve insufficiency, and pacemaker implantation. Fluorinated steroids showed no protective effect against late-onset DCM (P=0.27; HR=1.65 [95% CI: 0.63-4.25]). Probability of survival at 10years was 23.1% for newborns diagnosed neonatally with DCM, 53.9% for those who developed late-onset DCM, and 98.6% for those without DCM. Neonatal and late-onset DCM appear to be two different entities. None of the known risk factors associated with neonatal DCM predicted late-onset DCM. Long-term follow-up of cardiac function is warranted in all children with CHB. Copyright © 2017 Elsevier B.V. All rights reserved.

Fondaparinux for intra and perioperative anticoagulation in patients with heparin-induced thrombocytopenia candidates for peripheral vascular surgery: Report of 4 cases.

PubMed

Illuminati, Giulio; Calio', Francesco G; Pizzardi, Giulia; Amatucci, Chiara; Masci, Federica; Palumbo, Piergaspare

2016-01-01

Intra and perioperative anticoagulation in patients with heparin induced thrombocytopenia (HIT), candidates for peripheral vascular surgery remains a challenge, as the best alternative to heparin has not yet been established. We evaluated the off-label use of fondaparinux in four patients with HIT, undergoing peripheral vascular surgery procedures. Four patients of whom 3 men of a mean age of 66 years, with proven heparin induced thrombocytopenia (HIT) underwent two axillo-femoral bypasses, one femoro-popliteal bypass and one resection of a splenic artery aneurysm under fondaparinux. No intra or perioperative bleeding or thrombosis of new onset was observed. In the absence of a valid alternative to heparin for intra and perioperative anticoagulation in HIT, several other anticoagulants can be used in an off-label setting. However, no general consensus exist on which should be the one of choice. In this small series fondaparinux appeared to be both safe and effective. These preliminary results seem to justify the off-label use of fondaparinux for intra and perioperative anticoagulation in patients with HIT, candidates for peripheral vascular surgery interventions. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Neonatal opioid withdrawal and antenatal opioid prescribing

PubMed Central

Gomes, Tara; Camacho, Ximena; Yao, Zhan; Guttmann, Astrid; Mamdani, Muhammad M.; Juurlink, David N.; Dhalla, Irfan A.

2015-01-01

Background The incidence of neonatal opioid withdrawal is increasing in both Canada and the United States. However, the degree to which the treatment of pain with opioids, rather than the misuse of prescription opioids or heroin, contributes to the prevalence of neonatal opioid withdrawal remains unknown. Methods We conducted a retrospective, population-based, cross-sectional study between 1992 and 2011 in Ontario with 2 objectives. First, we determined the annual incidence of neonatal abstinence syndrome. Second, using data from a subset of women eligible for publicly funded prescription drugs, we determined what proportion of women who deliver an infant with neonatal abstinence syndrome were given a prescription for an opioid before and during pregnancy. Results The incidence of neonatal abstinence syndrome in Ontario increased 15-fold during the study period, from 0.28 per 1000 live births in 1992 to 4.29 per 1000 live births in 2011. During the final 5 years of the study, we identified 927 deliveries of infants with neonatal abstinence syndrome to mothers who were public drug plan beneficiaries. Of these mothers, 67% had received an opioid prescription in the 100 days preceding delivery, including 53.3% who received methadone, an increase from 28.6% in the interval spanning 1 to 2 years before delivery (p < 0.001). Prescription for nonmethadone opioids decreased from 38% to 17% (p < 0.001). Interpretation The incidence of neonatal opioid withdrawal in Ontario has increased substantially over the last 20 years. Most of the women in this cohort who delivered an infant with neonatal abstinence syndrome had received a prescription for an opioid both before and during their pregnancy. PMID:25844370

Neonatal Seizures: An Update on Mechanisms and Management

PubMed Central

Jensen, Frances E.

2010-01-01

The lifespan risk of seizures is highest in the neonatal period. Currently used therapies have limited efficacy. Although the treatment of neonatal seizures has not significantly changed in the last several decades, there has been substantial progress in understanding developmental mechanisms that influence seizure generation and responsiveness to anticonvulsants. Here we provide an overview of current approaches to the diagnosis and treatment of neonatal seizures, identifying some of the recent insights about the pathophysiology of neonatal seizures that may provide the foundation for better treatment. PMID:19944840

The sonographic features of neonatal appendicitis: A case report.

PubMed

Si, Shu-Yu; Guo, Yi-Yi; Mu, Jian-Feng; Yan, Chao-Ying

2017-11-01

Neonatal appendicitis is extremely rare, and preoperative diagnosis is challenging. This study aimed to investigate the utility of ultrasound for the diagnosis of neonatal appendicitis. Four cases of neonatal appendicitis were included in this case series. One was a female infant and the other 3 were male infants; they were aged from 10 to 17 days. Neonatal appendicitis. Four newborns in our hospital were diagnosed with neonatal appendicitis by abdominal ultrasound. Their sonographic features were summarized and compared with surgical and pathological findings. In these infants, abdominal ultrasound demonstrated ileocecal bowel dilatation, intestinal and bowel wall thickening, and localized encapsulated effusion in the right lower quadrant and the abscess area, which was assumed to surround the appendix. Ultrasound is helpful for the diagnosis of neonatal appendicitis.

Prenatal cocaine exposure and neonatal/infant outcomes.

PubMed

Cambell, Shelly

2003-01-01

Illegal drug use throughout the nation is a problem of epidemic proportion. Of particular concern is drug use among pregnant women. In most cases, these women have little hope of achieving a better life for themselves or their children. Illegal drugs, cocaine in particular, can have devastating effects on the neonate. These effects can last well into childhood and can exhibit themselves in academic, social, and family situations. Challenges for the neonatal nurse include early identification of these infants and use of available resources. This article addresses prenatal cocaine use and support services for drug-dependent women, effects of cocaine during the neonatal period, possible neonatal and infant outcomes, and implications for nursing practice.

Respiratory distress in term neonates in low-resource settings.

PubMed

Sivanandan, Sindhu; Agarwal, Ramesh; Sethi, Amanpreet

2017-08-01

Most neonatal deaths worldwide occur in low- and middle-income countries (LMICs). Respiratory distress is an important cause of neonatal morbidity and mortality. The epidemiology of respiratory distress among term neonates who constitute the vast majority of births is under reported. The scarcely available data from LMICs suggest an incidence of 1.2% to 7.2% among term live births and greater morbidity compared to that in high-income countries. Pneumonia and meconium aspiration syndrome are the predominant causes among outborn neonates, but next only to transient tachypnea among inborn neonates. Community management of neonatal sepsis/pneumonia using simplified antibiotic regimens when referral is not feasible, implementation of non-invasive ventilation, and innovative low-cost technologies to deliver respiratory therapy are important advances that have taken place in these settings. There is an urgent need to generate data on respiratory morbidities among term neonates so that the limited resources in these settings can be allocated judiciously. Copyright © 2017 Elsevier Ltd. All rights reserved.

Strategies to sustain a quality improvement initiative in neonatal resuscitation

PubMed Central

van Heerden, Carlien; Janse van Rensburg, Elsie S.

2016-01-01

Background Many neonatal deaths can be prevented globally through effective resuscitation. South Africa (SA) committed towards attaining the Millennium Development Goal 4 (MDG4) set by the World Health Organization (WHO). However, SA’s district hospitals have the highest early neonatal mortality rates. Modifiable and avoidable causes associated with patient-related, administrative and health care provider factors contribute to neonatal mortality. A quality improvement initiative in neonatal resuscitation could contribute towards decreasing neonatal mortality, thereby contributing towards the attainment of the MDG4. Aim The aim of this study was, (1) to explore and describe the existing situation regarding neonatal resuscitation in a district hospital, (2) to develop strategies to sustain a neonatal resuscitation quality improvement initiative and (3) to decrease neonatal mortality. Changes that occurred and the sustainability of strategies were evaluated. Setting A maternity section of a district hospital in South Africa. Methods The National Health Service (NHS) Sustainability Model formed the theoretical framework for the study. The Problem Resolving Action Research model was applied and the study was conducted in three cycles. Purposive sampling was used for the quantitative and qualitative aspects of data collection. Data was analysed accordingly. Results The findings indicated that the strategies formulated and implemented to address factors related to neonatal resuscitation (training, equipment and stock, staff shortages, staff attitude, neonatal transport and protocols) had probable sustainability and contributed towards a reduction in neonatal mortality in the setting. Conclusion These strategies had the probability of sustainability and could potentially improve neonatal outcomes and reduce neonatal mortality to contribute toward South Africa’s’ drive to attain the MDG4. PMID:27380840

Update on neonatal cardiopulmonary resuscitation

PubMed

2018-06-01

An update of the national recommendations on neonatal resuscitation elaborated by the Neonatal Resuscitation Work Area of the Fetal-Neonatal Studies Committee (CEFEN) of the Argentine Society of Pediatrics (SAP) is presented. These recommendations are original and in their elaboration, we have taken into account the best available evidence gathered by the International Liaison Committee on Resuscitation (ILCOR) as well as an exhaustive review of publications and discussions in the area to define controversial issues. Relevant concepts and major changes are described and analyzed. These recommendations refer to support for the transition at birth and to resuscitation of newborns, focusing on safety and effectiveness. We include a section on the importance of teamwork and its impact on results when we proceed with an adequate organization.

Maternal Risk Factors for Neonatal Necrotizing Enterocolitis

PubMed Central

March, Melissa I.; Gupta, Munish; Modest, Anna M.; Wu, Lily; Hacker, Michele R.; Martin, Camilia R.; Rana, Sarosh

2015-01-01

Objective This study aimed to investigate the relationship between maternal hypertensive disease and other risk factors and the neonatal development of necrotizing enterocolitis (NEC). Methods This was a retrospective case control study of infants with NEC from 2008 to 2012. The primary exposure of interest was maternal hypertensive disease, which has been hypothesized to put infants at risk for NEC. Other variables collected included demographics, pregnancy complications, medications, and neonatal hospital course. Data was abstracted from medical records. Results 28 cases of singleton neonates with NEC and 81 matched controls were identified and analyzed. There was no significant difference in the primary outcome. Fetuses with an antenatal diagnosis of growth restriction were more likely to develop NEC (p=0.008). Infants with NEC had lower median birth weight than infants without NEC (p=0.009). Infants with NEC had more late-onset sepsis (p=0.01) and mortality before discharge (p=0.001). Conclusions The factors identified by this case-control study that increased the risk of neonatal NEC included intrauterine growth restriction and lower neonatal birth weight. The primary exposure, hypertensive disease, did not show a significantly increased risk of neonatal NEC, however there was a nearly two-fold difference observed. Our study was underpowered to detect the observed difference. PMID:25162307

Severe fever with thrombocytopenia syndrome, an emerging tick-borne zoonosis.

PubMed

Liu, Quan; He, Biao; Huang, Si-Yang; Wei, Feng; Zhu, Xing-Quan

2014-08-01

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging haemorrhagic fever that was first described in rural areas of China. The causative agent, SFTS virus (SFTSV), is a novel phlebovirus in the Bunyaviridae family. Since the first report in 2010, SFTS has been found in 11 provinces of China, with about 2500 reported cases, and an average case-fatality rate of 7·3%. The disease was also reported in Japan and Korea in 2012; Heartland virus, another phlebovirus genetically closely related to SFTSV, was isolated from two patients in the USA. The disease has become a substantial risk to public health, not only in China, but also in other parts of the world. The virus could undergo rapid evolution by gene mutation, reassortment, and homologous recombination in tick vectors and vertebrate reservoir hosts. No specific treatment of SFTS is available, and avoiding tick bites is an important measure to prevent the infection and transmission of SFTSV. This Review provides information on the molecular characteristics and ecology of this emerging tick-borne virus and describes the epidemiology, clinical signs, pathogenesis, diagnosis, treatment, and prevention of human infection with SFTSV. Copyright © 2014 Elsevier Ltd. All rights reserved.

Subacute sclerosing panencephalitis and immune thrombocytopenia: More than a coincidence?

PubMed

Oncel, I; Saltik, S; Anlar, B

2018-02-01

Subacute sclerosing panencephalitis (SSPE) is a progressive disease caused by persistent measles virus (MV). It has an incidence of 0.4-2.0/million in Turkey. Immune thrombocytopenia (ITP) is a bleeding disorder whose estimated incidence is 4.2/100.000 person/years in the pediatric age group. We observed three cases with ITP in our cohort of 315 pediatric SSPE cases, an incidence higher than coincidentally expected in the general population. We hypothesize an association between SSPE and ITP. Our three cases had measles 1-2 years before the onset of ITP and 8-10 years before first symptoms of SSPE. A common immunogenetic background creating susceptibility to infection and autoimmunity might play a role. Alternatively, chronic antigenic stimulation by the MV leading to synthesis of cross-reacting antibodies against platelets, or treatment of ITP with immunoglobulins or steroids might affect or alter the development and manifestation of SSPE. The co-occurrence of these two disorders of viral and immune pathogenesis may draw attention to similar observations and provide clues for their mechanisms. Copyright © 2018 Elsevier Ltd. All rights reserved.

Performance of a Quantitative PCR-Based Assay and Beta-d-Glucan Detection for Diagnosis of Invasive Candidiasis in Very-Low-Birth-Weight Preterm Neonatal Patients (CANDINEO Study).

PubMed

Ramos, Jose Tomas; Villar, Sonia; Bouza, Emilio; Bergon-Sendin, Elena; Perez Rivilla, Alfredo; Collados, Caridad Tapia; Andreu, Mariano; Reyes, Candelaria Santana; Campos-Herrero, María Isolina; de Heredia, Jon López; Herrera, María Cruz López; Alonso, Paloma Anguita; Pallás-Alonso, Carmen Rosa; Cuenca-Estrella, Manuel

2017-09-01

An epidemiological, multicenter, noninterventional, observational case-control study was conducted to describe the performance of serum beta-d-glucan (BDG) and Candida PCR in blood, serum, and sterile samples for the diagnosis of invasive candidiasis (IC) in very-low-birth-weight (VLBW) preterm neonates and to compare these techniques with culture of samples from blood and other sterile sites. Seventeen centers participated in the study, and the number of episodes analyzed was 159. A total of 9 episodes of IC from 9 patients (7 confirmed and 2 probable) and 150 episodes of suspected sepsis from 117 controls were identified. The prevalence of IC was 5.7% (95% confidence interval [95% CI], 2.1 to 9.3). The mortality was significantly higher in episodes of IC (44.4%) than in the non-IC episodes (11.1%, P < 0.01). The sensitivity and specificity of the PCR performed on blood/serum samples were 87.5% and 81.6%, respectively. The sensitivity and specificity of the BDG results were lower (75.0% and 64.6%). For cases with negative culture results, the PCR and the BDG results were positive in 27 (17.4%) and 52 (33.5%) episodes, respectively. The presence of multiorgan failure, improvement with empirical antifungal therapy, thrombocytopenia, and Candida colonization were significantly associated ( P < 0.01) with PCR or BDG positivity regardless of the results of the cultures. Serum BDG analysis and Candida PCR could be used as complementary diagnostic techniques to detect IC in VLBW neonates. Copyright © 2017 Ramos et al.

Performance of a Quantitative PCR-Based Assay and Beta-d-Glucan Detection for Diagnosis of Invasive Candidiasis in Very-Low-Birth-Weight Preterm Neonatal Patients (CANDINEO Study)

PubMed Central

Ramos, Jose Tomas; Villar, Sonia; Bouza, Emilio; Bergon-Sendin, Elena; Perez Rivilla, Alfredo; Collados, Caridad Tapia; Andreu, Mariano; Reyes, Candelaria Santana; Campos-Herrero, María Isolina; de Heredia, Jon López; Herrera, María Cruz López; Alonso, Paloma Anguita; Pallás-Alonso, Carmen Rosa

2017-01-01

ABSTRACT An epidemiological, multicenter, noninterventional, observational case-control study was conducted to describe the performance of serum beta-d-glucan (BDG) and Candida PCR in blood, serum, and sterile samples for the diagnosis of invasive candidiasis (IC) in very-low-birth-weight (VLBW) preterm neonates and to compare these techniques with culture of samples from blood and other sterile sites. Seventeen centers participated in the study, and the number of episodes analyzed was 159. A total of 9 episodes of IC from 9 patients (7 confirmed and 2 probable) and 150 episodes of suspected sepsis from 117 controls were identified. The prevalence of IC was 5.7% (95% confidence interval [95% CI], 2.1 to 9.3). The mortality was significantly higher in episodes of IC (44.4%) than in the non-IC episodes (11.1%, P < 0.01). The sensitivity and specificity of the PCR performed on blood/serum samples were 87.5% and 81.6%, respectively. The sensitivity and specificity of the BDG results were lower (75.0% and 64.6%). For cases with negative culture results, the PCR and the BDG results were positive in 27 (17.4%) and 52 (33.5%) episodes, respectively. The presence of multiorgan failure, improvement with empirical antifungal therapy, thrombocytopenia, and Candida colonization were significantly associated (P < 0.01) with PCR or BDG positivity regardless of the results of the cultures. Serum BDG analysis and Candida PCR could be used as complementary diagnostic techniques to detect IC in VLBW neonates. PMID:28659321

NSs protein of severe fever with thrombocytopenia syndrome virus suppresses interferon production through different mechanism than Rift Valley fever virus.

PubMed

Zhang, S; Zheng, B; Wang, T; Li, A; Wan, J; Qu, J; Li, C H; Li, D; Liang, M

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a newly identified Phlebovirus that causes severe fever with thrombocytopenia syndrome. Our study demonstrated that SFTSV NSs functioned as IFN antagonist mainly by suppressing TBK1/IKKε-IRF3 signaling pathway. NSs interacted with and relocalized TANK-binding kinase 1 (TBK1) into NSs-induced cytoplasmic structures and this interaction could effectively inhibit downstream phosphorylation and dimerization of interferon regulatory factor 3 (IRF3), resulting in the suppression of antiviral signaling and IFN induction. Functional sites of SFTSV NSs binding with TBK1 were then studied and results showed that NSs had lost their IFN-inhibiting activity after deleting the 25 amino acids in N-terminal. Furthermore, the mechanism of Rift Valley fever virus (RVFV) NSs blocking IFN-β response were also investigated. Preliminary results showed that RVFV NSs proteins could neither interact nor co-localize with TBK1 in cytoplasm, but suppressed its expression levels, phosphorylation and dimerization of IRF3 in the subsequent steps, resulting in inhibition of the IFN-β production. Altogether, our data demonstrated the probable mechanism used by SFTSV to inhibit IFN responses which was different from RVFV and pointed toward a novel mechanism for RVFV suppressing IFN responses.

Length of stay and cost analysis of neonates undergoing surgery at a tertiary neonatal unit in England.

PubMed

Shetty, S; Kennea, N; Desai, P; Giuliani, S; Richards, J

2016-01-01

Introduction There is a lack of knowledge on the average length of stay (LOS) in neonatal units after surgical repair of common congenital anomalies. There are few if any publications reporting the activity performed by units undertaking neonatal surgery. Such activity is important for contracting arrangements, commissioning specialist services and counselling parents. The aim of this study was to describe postnatal LOS for infants admitted to a single tertiary referral neonatal unit with congenital malformations requiring surgery. Methods Data on nine conditions were collected prospectively for babies on the neonatal unit over a five-year period (2006-2011). For those transferred back to their local unit following surgery, the local unit was contacted to determine the total LOS. Only those babies who had surgery during their first admission to our unit and who survived to discharge were included in the study. Cost estimates were based on the tariffs agreed for neonatal care between our trust and the London specialised commissioning group in 2011-2012. Results The median LOS for the conditions studied was: gastroschisis 35 days (range: 19-154 days), oesophageal atresia 33 days (range: 9-133 days), congenital diaphragmatic hernia 28 days (range: 7-99 days), intestinal atresia 24 days (range: 6-168 days), Hirschsprung's disease 21 days (range: 15-36 days), sacrococcygeal teratoma 17 days (range: 12-55 days), myelomeningocoele 15.5 days (range: 8-24 days), anorectal malformation 15 days (range: 6-90 days) and exomphalos 12 days (range: 3-228 days). The total neonatal bed day costs for the median LOS ranged from £8,701 (myelomeningocoele) to £23,874 (gastroschisis). The cost of surgery was not included. Conclusions There is wide variation in LOS for the same conditions in a single neonatal unit. This can be explained by different types and severity within the same congenital anomalies, different surgeons and other clinical confounders (eg sepsis, surgical

Brazelton Neonatal Assessment for School Psychologists.

ERIC Educational Resources Information Center

Stoudt, Calvin L.

This speech addresses the "What,""Why," and "How" of Brazelton Neonatal Assessment Training for school psychologists. "What" concerns the Brazelton Neonatal Behavioral Assessment Scale, its administration, and what it assesses. Based on the best performance, the infant's score on this scale is scored in the…

[Clinical efficacy of flomoxef in neonatal bacterial infection].

PubMed

Sakata, H; Hirano, Y; Maruyama, S

1993-03-01

One hundred and seventy one neonates were treated with flomoxef (FMOX) and the clinical efficacy and safety were evaluated. The ages of the patients ranged from 0 to 28 days, and their body weights from 450 to 4300 g. Dose levels were 12.4 to 24.9 mg/kg every 8 or 12 hours for 1 to 10 days. Fifty two patients who responded to the FMOX treatment included 5 neonates with sepsis, 17 with suspected sepsis, 9 with urinary tract infections, 12 with pneumonia, 8 with intrauterine infections, and 1 with omphalitis. The other neonates could not be retrospectively diagnosed as bacterial infections. Of 52 patients, clinical results were excellent in 15, good in 34, fair in 1, and poor in 2. And the FMOX treatment was effective in 13 out of 14 patients in which causative bacteria were identified. The drug was well tolerated, but 6 neonates out of 33 over 5 days old had diarrhea. From these results, empiric treatment with FMOX against neonatal bacterial infection was as clinically useful as that of combination with ampicillin and gentamicin or cefotaxime and ampicillin in our neonatal intensive care unit. But, as this study did not include neonate with meningitis, efficacy to meningitis was not evaluated.

Pharmacokinetics of Epsilon-Aminocaproic Acid in Neonates

PubMed Central

Eaton, Michael P.; Alfieris, George M; Sweeney, Dawn M; Angona, Ronald E; Cholette, Jill M; Venuto, Charles; Anderson, Brian

2016-01-01

Background Antifibrinolytic medications such as epsilon-aminocaproic acid (EACA) are used in pediatric heart surgery to decrease surgical bleeding and transfusion. Dosing schemes for neonates are often based on adult regimens, or are simply empiric, in part due to the lack of neonatal pharmacokinetic information. We sought to determine the pharmacokinetics of EACA in neonates undergoing cardiac surgery and to devise a dosing regimen for this population. Methods Ten neonates undergoing cardiac surgery with cardiopulmonary bypass were given EACA according to standard practice, and blood was drawn at 10 time points to determine drug concentrations. Time-concentration profiles were analyzed using nonlinear mixed effects models. Parameter estimates (standardized to a 70 kg person) were used to develop a dosing regimen intended to maintain a target concentration shown to inhibit fibrinolysis in neonatal plasma (50 mg/L). Results Pharmacokinetics were described using a two compartment model plus an additional compartment for the cardiopulmonary bypass pump. First order elimination was described with a clearance of 5.07 L/h*(WT/70) 0.75. Simulation showed a dosing regimen with a loading dose of 40 mg/kg, and an infusion of 30 mg/kg/h, with a pump prime concentration of 100 mg/L maintained plasma concentrations above 50 mg/L in 90% of neonates during cardiopulmonary bypass surgery. Conclusions EACA clearance, expressed using allometry, is reduced in neonates compared to older children and adults. Loading dose and infusion dose are approximately half those required in children and adults. PMID:25723765

Neonatal Intrathoracic Stomach without Gastric Volvulus.

PubMed

Bokka, Sriharsha; Mohanty, Manoj Kumar

2016-10-01

Intrathoracic stomach is a rare and serious congenital abnormality. The anomaly may be complicated by gastric volvulus and can lead to ischemic gastric infarction in the neonate. If diagnosed antenatally, neonatal management can be planned in advance so as to reduce morbidity. This anomaly must be differentiated from the more common congenital diaphragmatic hernia, as associated pulmonary hypoplasia is common in the latter and rare with gastric herniation. We report a case of intrathoracic stomach in a neonate without volvulus, fortunately a rare entity which was managed operatively, and the child has been under regular follow-up.

[Neonatal hyperthyroidism: A sometimes challenging diagnosis].

PubMed

Couturier, C; Cneude, F; Spiteri, A; Nugues, F; Debillon, T

2017-07-01

Graves disease complicates two pregnancies out of 1000 and when it is known before pregnancy, it warrants careful monitoring of the fetus and the newborn. We report on a case of neonatal hyperthyroidism, which revealed a previously unknown maternal thyroid disease. In this situation, neonatal signs can be misinterpreted, delaying the diagnosis. Neonatal hyperthyroidism is, however, a therapeutic emergency because of the risk of cardiac and neurological complications. The neonatologist must identify thyroid disease in the absence of a maternal history in order to promptly start therapy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.