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1.  Intrahospital transport of critically ill patients (excluding newborns) recommendations of the Société de Réanimation de Langue Française (SRLF), the Société Française d'Anesthésie et de Réanimation (SFAR), and the Société Française de Médecine d'Urgence (SFMU) 
Critically ill adult patients often require multiple examinations in the hospital and need transport from one department to another, or even between hospitals. However, to date, no guidelines exist regarding optimum practices for transport of these fragile patients. We present recommendations for intrahospital transport of critically ill patients, excluding newborns, developed by an expert group of the French-Language Society of Intensive Care (Société de Réanimation de Langue Française (SRLF), the Société Française d’Anesthésie et de Réanimation (SFAR), and the Société Française de Médecine d’Urgence (SFMU). The recommendations cover five fields of application: epidemiology of adverse events; equipment, monitoring, and maintenance; preparation of patient before transport; human resources and training for caregivers involved in transport processes; and guidelines for planning, structure, and traceability of transport processes.
PMCID: PMC3395853  PMID: 22304940
intrahospital transport; critical care; adults
2.  Management by the intensivist of gastrointestinal bleeding in adults and children 
Intensivists are regularly confronted with the question of gastrointestinal bleeding. To date, the latest international recommendations regarding prevention and treatment for gastrointestinal bleeding lack a specific approach to the critically ill patients. We present recommendations for management by the intensivist of gastrointestinal bleeding in adults and children, developed with the GRADE system by an experts group of the French-Language Society of Intensive Care (Société de Réanimation de Langue Française (SRLF), with the participation of the French Language Group of Paediatric Intensive Care and Emergencies (GFRUP), the French Society of Emergency Medicine (SFMU), the French Society of Gastroenterology (SNFGE), and the French Society of Digestive Endoscopy (SFED). The recommendations cover five fields of application: management of gastrointestinal bleeding before endoscopic diagnosis, treatment of upper gastrointestinal bleeding unrelated to portal hypertension, treatment of upper gastrointestinal bleeding related to portal hypertension, management of presumed lower gastrointestinal bleeding, and prevention of upper gastrointestinal bleeding in intensive care.
PMCID: PMC3526517  PMID: 23140348
Gastrointestinal bleeding; Intensive care; Ulcer; Gastric/esophageal varices; Recommendations
3.  From randomized trials to the clinic: is it time to implement individual lung-cancer screening in clinical practice? A multidisciplinary statement from French experts on behalf of the french intergroup (IFCT) and the groupe d'Oncologie de langue française (GOLF) 
Annals of Oncology  2012;24(3):586-597.
Despite advances in cancer therapy, mortality is still high except in early-stage tumors, and screening remains a challenge. The randomized National Lung Screening Trial (NLST), comparing annual low-dose computed tomography (LDCT) and chest X-rays, revealed a 20% decrease in lung-cancer-specific mortality. These results raised numerous questions. The French intergroup for thoracic oncology and the French-speaking oncology group convened an expert group to provide a coherent outlook on screening modalities in France.
A literature review was carried out and transmitted to the expert group, which was divided into three workshops to tackle specific questions, with responses presented in a plenary session. A writing committee drafted this article.
The multidisciplinary group favored individual screening in France, when carried out as outlined in this article and after informing subjects of the benefits and risks. The target population involves subjects aged 55–74 years, who are smokers or have a 30 pack-year smoking history. Subjects should be informed about the benefits of quitting. Screening should involve LDCT scanning with specific modalities. Criteria for CT positivity and management algorithms for positive examinations are given.
Individual screening requires rigorous assessment and precise research in order to potentially develop a lung-cancer screening policy.
PMCID: PMC3574545  PMID: 23136229
low-dose CT scan; lung cancer; lung nodule; screening; tobacco
4.  Are the GFRUP's recommendations for withholding or withdrawing treatments in critically ill children applicable? Results of a two‐year survey 
Journal of Medical Ethics  2007;33(3):128-133.
To evaluate feasibility of the guidelines of the Groupe Francophone de Réanimation et Urgence Pédiatriques (French‐speaking group of paediatric intensive and emergency care; GFRUP) for limitation of treatments in the paediatric intensive care unit (PICU).
A 2‐year prospective survey.
A 12‐bed PICU at the Hôpital Jeanne de Flandre, Lille, France.
Were included when limitation of treatments was expected.
Of 967 children admitted, 55 were included with a 2‐day median delay. They were younger than others (24 v 60 months), had a higher paediatric risk of mortality (PRISM) score (14 v 4), and a higher paediatric overall performance category (POPC) score at admission (2 v 1); all p<0.002. 34 (50% of total deaths) children died. A limitation decision was made without meeting for 7 children who died: 6 received do‐not‐resuscitate orders (DNROs) and 1 received withholding decision. Decision‐making meetings were organised for 31 children, and the following decisions were made: 12 DNROs (6 deaths and 6 survivals), 4 withholding (1 death and 3 survivals), with 14 withdrawing (14 deaths) and 1 continuing treatment (survival). After limitation, 21 (31% of total deaths) children died and 10 survived (POPC score 4). 13 procedures were interrupted because of death and 11 because of clinical improvement (POPC score 4). Parents' opinions were obtained after 4 family conferences (for a total of 110 min), 3 days after inclusion. The first meeting was planned for 6 days after inclusion and held on the 7th day after inclusion; 80% of parents were immediately informed of the decision, which was implemented after half a day.
GFRUPs procedure was applicable in most cases. The main difficulties were anticipating the correct date for the meeting and involving nurses in the procedure. Children for whom the procedure was interrupted because of clinical improvement and who survived in poor condition without a formal decision pointed out the need for medical criteria for questioning, which should systematically lead to a formal decision‐making process.
PMCID: PMC2598266  PMID: 17329379
5.  Pseudo (Platelet-type) von Willebrand disease in pregnancy: a case report 
Pseudo (platelet-type)-von Willebrand disease is a rare autosomal dominant bleeding disorder caused by an abnormal function of the glycoprotein lb protein; the receptor for von Willebrand factor. This leads to an increased removal of VWF multimers from the circulation as well as platelets and this results in a bleeding diathesis. Worldwide, less than 50 patients are reported with platelet type von Willebrand disease (PT-VWD).
Case presentation
We describe the management of platelet type von Willebrand disease in pregnancy of a 26 year old Caucasian primigravida. The initial diagnosis was made earlier following a significant haemorrhage post tonsillectomy several years prior to pregnancy. The patient was managed under a multidisciplinary team which included obstetricians, haematologists, anaesthetists and neonatologists. Care plans were made for the ante- natal, intra-partum and post-partum periods in partnership with the patient. The patient’s platelet count levels dropped significantly during the antenatal period. This necessitated the active exclusion of other causes of thrombocytopenia in pregnancy. A vaginal delivery was desired and plans were made for induction of labour at 38 weeks of gestation with platelet cover in view of the progressive fall of the platelet count. The patient however went into spontaneous labour on the day of induction. She was transfused two units of platelets before delivery. She had an unassisted vaginal delivery of a healthy baby. The successful antenatal counselling has encouraged the diagnosis of the same condition in her mother and sister. We found this to be a particularly interesting case as well as challenging to manage due to its rarity. Psuedo von Willebrand disease in pregnancy can be confused with a number of other differential diagnoses, such as gestational thrombocutopenia, idiopathatic thrombocytopenia, thrombotic thrombocytopenic purpura and pre-eclampsia; all need consideration during investigations even in a case such as this where the diagnosis of platelet type von Willebrand disease was known before pregnancy.
Management of pseudo von Willebrand disease in pregnancy involves the co-operation of multidisciplinary teams, regular monitoring of platelet levels and factor VIII and replacement as appropriate. This case report highlights this rare condition and the need to exclude all the other differential diagnoses of thrombocytopenia in pregnant women with thrombocytopenia.
PMCID: PMC3558368  PMID: 23327637
Von Willebrand; Platelet type; Thrombocytopenia; Pregnancy
6.  Thrombocytopenia in neonates and the risk of intraventricular hemorrhage: a retrospective cohort study 
BMC Pediatrics  2011;11:16.
The overall prevalence of thrombocytopenia in neonates admitted to neonatal intensive care units ranges from 22 to 35%. There are only a few small studies that outline the relationship between the severity of thrombocytopenia and the risk of bleeding. This makes it difficult to form an evidence-based threshold for platelet transfusions in neonatal patients. The aim of this study was to determine the prevalence of thrombocytopenia in a tertiary neonatal intensive care unit and to study the relation between thrombocytopenia and the risk of intraventricular hemorrhage (IVH).
We performed a retrospective cohort study of all patients with thrombocytopenia admitted to our neonatal tertiary care nursery between January 2006 and December 2008. Patients were divided into 4 groups according to the severity of thrombocytopenia: mild (100-149 × 109/L), moderate (50-99 × 109/L), severe (30-49 × 109/L) or very severe (< 30 × 109/L). The primary outcome was IVH ≥ grade 2. Pearson's chi-squared and Fischer's exact tests were used for categorical data. ANOVA, logistic regression analysis and multivariate linear regression were used for comparisons between groups and for confounding factors.
The prevalence of thrombocytopenia was 27% (422/1569). Risk of IVH ≥ grade 2 was 12% (48/411) in neonates with versus 5% (40/844) in neonates without thrombocytopenia (p < 0.01). After multivariate linear regression analysis, risk of IVH ≥ grade 2 in the subgroups of thrombocytopenic infants was not significantly different (p = 0.3).
After logistic regression analysis the difference in mortality rate in neonates with and without thrombocytopenia was not significant (p = 0.4). Similarly, we found no difference in mortality rate in the subgroups of neonates with thrombocytopenia (p = 0.7).
Although IVH ≥ grade 2 occurs more often in neonates with thrombocytopenia, this relation is independent of the severity of thrombocytopenia. Prospective studies should be conducted to assess the true risk of hemorrhage depending on underlying conditions. Randomized controlled trials are urgently needed to determine a safe lower threshold for platelet transfusions.
PMCID: PMC3045959  PMID: 21314921
7.  Platelet counts and outcome in the pediatric intensive care unit 
Thrombocytopenia is commonly observed in critically ill patients. This study was undertaken to evaluate the variation in platelet counts and the risk factors associated with thrombocytopenia and mortality in pediatric intensive care patients. In addition, prognostic value of platelet counts for outcome in pediatric intensive care unit was studied.
Study Design:
Prospective, observational cohort analysis.
8- bedded pediatric intensive care unit of a tertiary care teaching hospital.
All consecutively admitted patients (n=138) staying in the pediatric intensive care unit (PICU) for at least 48h over a 7 months period were studied.
Measurements and Main Results:
Thrombocytopenia was defined as platelet counts <150.0/nL. Median 1st day Pediatric Risk of Mortality Score (PRISM) was 5 (range 0-30) and median ICU stay was 4 days (range 2-98 days). Twenty five percent patients had at least one episode of thrombocytopenia during the stay. Twenty percent of these patients had thrombocytopenia on admission and rest (80%) developed it during the PICU stay. Seventy one percent (19) of the patients developed thrombocytopenia by fourth day of admission. Patients with PICU acquired thrombocytopenia had statistically significant lower baseline, nadir and 4th day platelet counts and a significantly higher drop in platelet counts (56% vs. 6% P<0.001) as compared to non thrombocytopenic patients. PRISM score, long PICU stay, sepsis, coagulopathy, and creatinine levels were significantly associated with occurrence of thrombocytopenia. Patients with thrombocytopenia had higher probability of bleeding (34% vs. 15%, P=0.01). Higher platelet counts on admission were associated with significantly reduced risk of thrombocytopenia (P=0.00) Baseline, nadir and day-4 platelet counts, presence of thrombocytopenia on admission, sepsis, coagulopathy and a higher mean PRISM score on univariate analysis were significantly associated with mortality. Leucopenia or leucocytosis, thrombocytopenia and coagulopathy were found to significantly affect outcome. Drop in platelet counts was found to have slightly higher discriminative value for mortality prediction than PRISM on the ROC curve. The survivors had higher platelet counts throughout the PICU stay and after an initial fall in platelet counts in the PICU showed a significantly higher rise in the platelet counts in the following days than the non-survivors.
Thrombocytopenia is common in PICU. Patients requiring cardiopulmonary resuscitation or with circulatory shock, coagulopathy, sepsis and with more severe disease have higher risk of developing thrombocytopenia. Thrombocytopenic patients have a higher risk of bleeding. Drop in platelet counts >27% and thrombocytopenia were independently related to mortality. Serial measurements of platelet counts are better predictors of pediatric intensive care outcome than one-time values. Any drop in platelet counts even without thrombocytopenia needs an urgent and extensive evaluation.
PMCID: PMC2738316  PMID: 19742257
Coagulopathy; mortality; pediatric intensive care; platelets; prognosis; thrombocytopenia
8.  Thrombocytopenia and Associated Factors in Neonates Admitted to NICU during Years 2010_2011 
Thrombocytopenia is the most common hematological abnormality which is encountered in the neonatal intensive care unit (NICU). The incidence in neonates varies greatly, depending upon the population studies. According to the frequency of thrombocytopenia and its complications and because of lack of such research in Iran, this study was performed on neonates admitted to Shahid Sadughi NICU during years 2011-2012.
Materials and Methods
In a retrospective study, 350 neonates who were admitted to NICU were enrolled in the study. They were categorized to three groups regarding platelet count: mild, moderate and severe thrombocytopenia. Incidence of thrombocytopenia was determined and contribution of variables such as sex, gestational age, intrauterine growth retardation, asphyxia, sepsis, necrotizing enterocolitis, blood group, placental insufficiency in Gestational Diabetes Mellitus (GDM) and hypertension (HTN) were analyzed.
Neonatal thrombocytopenia was found in 100(28.5%) of 350 subjects, consisted of 75.3% early onset and 24.7% late onset, which most of them (96.5%) had mild and moderate thrombocytopenia, and just 3.5% had developed severe thrombocytopenia. Thrombocytopenia was associated with sepsis, intrauterine growth retardation sepsis, asphyxia, GDM, maternal hypertension and prematurity. There was no relation between occurrence of thrombocytopenia and gender.
 The incidence of neonatal thrombocytopenia was 28.5 %. Significant maternal risk factors that lead to thrombocytopenia were HTN and preeclampsia, while risk factors of neonates were asphyxia, sepsis and Intera Uterus Growth Retardation.
PMCID: PMC3915438  PMID: 24575265
Thrombocytopenia; Intensive Care Units; Neonatal; Incidence
9.  Hypoxia as a Predisposing Factor for the Development of Early Onset Neonatal Thrombocytopenia 
Journal of Clinical Neonatology  2012;1(3):131-134.
Thrombocytopenia in hypoxic neonates admitted in NICU is a morbid condition encountered very commonly. Early-onset thrombocytopenia (<72 h) is most commonly associated with fetomaternal conditions complicated by placental insufficiency and/or fetal hypoxia. Chronic intrauterine hypoxia is the most frequent cause of early-onset thrombocytopenia in preterm neonates.
In this study incidence and clinical impact of early thrombocytopenia in hypoxic neonates was investigated.
Setting and Design:
Neonatal intensive care unit of a tertiary level hospital attached to a medical college in Central India. A cross-sectional, observational hospital based study in hypoxic neonates for development of thrombocytopenia.
Materials and Methods:
603 hypoxic newborns were evaluated for development of thrombocytopenia. 155 (25.07%) developed thrombocytopenia and were the cases. Non thrombocytopenic babies 448 (74.29%) served as controls. The two groups were compared for birth weight, sex ratio, gestational age, severity of asphyxia, platelet counts and mortality rate.
Statistical Analysis:
Descriptive statistics of continuous variable were expressed in mean and SD. P value less than or equal to 0.05 were statistically significant.
Results and Conclusions:
We found thrombocytopenia to be associated with male gender, prematurity and low birth weight. Most babies had mild to moderate thrombocytopenia. Mortality was higher in preterm thrombocytopenic babies as compared to term. We suggest screening for thrombocytopenia in all asphyxiated newborns, as hypoxia can lead to neonatal thrombocytopenia.
PMCID: PMC3762028  PMID: 24027708
Neonate; birth asphyxia; hypoxia; thrombocytopenia; platelet count
10.  Gestational thrombocytopenia among pregnant Ghanaian women 
Thrombocytopenia is a common problem during pregnancy that is not frequently detected and as a result is often inappropriately managed. The obvious concern with thrombocytopenia during pregnancy is the risk of significant bleeding at the time of delivery. This study was designed to determine the prevalence of gestational thrombocytopenia in pregnant women reporting for ante-natal care at a Ghanaian primary health care centre.
Platelet count was evaluated in 300 blood samples from pregnant women and 100 non pregnant female blood donors. The platelet counts were performed using Sysmex KX-21N automated hematology analyzer. The study design was cross sectional. Proportions were analyzed for statistical significance with the Chi square, Odds ratio was also calculated
The prevalence of thrombocytopenia in pregnant women in this study was 15.3% compared with 4% in controls. This was statistically significant with a P value of 0.003. Odds ratio was 4.31 (95% CI: 1.52-12.04). Most cases of thrombocytopenia were mild (76%), only 4% of the women with thrombocytopenia had severe thrombocytopenia.
The frequency of thrombocytopenia in this study was higher than that reported from more developed parts of the world. This may be due to undetected malaria infection in our patients. Pregnant women should be routinely screened for thrombocytopenia. Those found to be thrombocytopenic should have both thick and thin blood films done to exclude the presence of malaria parasites.
PMCID: PMC3415055  PMID: 22891092
Pregnancy; thrombocytopenia; Ghana; women; malaria
11.  The Potential of Antimicrobials to Induce Thrombocytopenia in Critically Ill Patients: Data from a Randomized Controlled Trial 
PLoS ONE  2013;8(11):e81477.
Antimicrobial-induced thrombocytopenia is frequently described in the literature among critically ill patients. Several antimicrobials have been implicated, although experimental evidence to demonstrate causality is limited. We report, using a randomized trial, the potential of antimicrobials to induce thrombocytopenia.
Randomized trial allocated patients to antimicrobial treatment according to standard- of-care (SOC group) or drug-escalation in case of procalcitonin increases (high-exposure group). Patients were followed until death or day 28. Thrombocytopenia defined as absolute (platelet count ≤100x109/L) or relative (≥20% decrease in platelet count). Analyses were performed in the two randomized groups and as a merged cohort.
Of the 1147 patients with platelet data available, 18% had absolute thrombocytopenia within the first 24 hours after admission to intensive care unit and additional 17% developed this complication during follow-up; 57% developed relative thrombocytopenia during follow-up. Absolute and relative thrombocytopenia day 1-4 was associated with increased mortality (HR: 1.67 [95% CI: 1.30 to 2.14]; 1.71 [95% CI: 1.30 to 2.30], P<0.0001, respectively). Patients in the high-exposure group received more antimicrobials including piperacillin/tazobactam, meropenem and ciprofloxacin compared with the SOC group, whereas cefuroxime was used more frequently in the SOC group (p<0.05). Risk of absolute and relative thrombocytopenia (RR: 0.9 [0.7-1.3], p=0.7439; 1.2 [1.0-1.4], p=0.06; respectively), as well as absolute platelet count (daily difference, high-exposure vs. SOC -1.7 [-3.8-0.5], p=0.14) was comparable between groups. In observational analyses, use of ciprofloxacin and piperacillin/tazobactam predicted risk of relative thrombocytopenia (vs. cefuroxime, RR: 2.08 [1.48-2.92]; 1.44 [1.10-1.89], respectively), however only ciprofloxacin were associated with a reduction in absolute platelet count (p=0.0005).
High exposure to broad-spectrum antimicrobials does not result in a reduction in thrombocytopenia in critically ill patients. However, single use of ciprofloxacin, and less so piperacillin/tazobactam, may contribute to a lower platelet count.
Trial Registration NCT00271752
PMCID: PMC3842947  PMID: 24312305
12.  Mechanisms and etiologies of thrombocytopenia in the intensive care unit: impact of extensive investigations 
Thrombocytopenia is common in the intensive care unit. Potential mechanisms and etiologies behind this phenomenon are multiple and often entangled. We assessed the effect of a systematic approach, using routinely available tests, on the proportion of patients in whom the mechanism (primary objective) and etiology (secondary objective) of thrombocytopenia in a mixed intensive care unit (ICU) could be identified.
Before-and-after study of all patients with thrombocytopenia was used. ‘Before’ group had no intervention. New standard operating procedures for thrombocytopenia management were introduced. In the ‘After’ group, bone marrow aspiration; determination of fibrinogen dosage, prothrombin time, factor V, D-dimers; assay of fibrin monomers, ferritin, triglycerides, lactic acid dehydrogenase, aspartate transaminase, alanine aminotransferase, vitamin B12, folates, reticulocytes, haptoglobin, and bilirubin were performed.
In the Before group (n = 20), the mechanism (central, peripheral, or mixed) was identified in 10 % versus 83% in After group (n = 23) (p < 0.001) (48% peripheral, 35% mixed). Before intervention, ≥1 etiology was identified in 15% versus 95.7% in the After group (p < 0.001).
Systematic and extensive investigation using routine tests highlights the mechanisms and etiology of thrombocytopenia in most cases.
PMCID: PMC4273722  PMID: 25593741
Thrombocytopenia; Intensive care unit; Bone marrow aspiration
13.  Sedation in French intensive care units: a survey of clinical practice 
Sedation is used frequently for patients in intensive care units who require mechanical ventilation, but oversedation is one of the main side effects. Different strategies have been proposed to prevent oversedation. The extent to which these strategies have been adopted by intensivists is unknown.
We developed a six-section questionnaire that covered the drugs used, modalities of drug administration, use of sedation scales and procedural pain scales, use of written local procedures, and targeted objectives of consciousness. In November 2011, the questionnaire was sent to 1,078 intensivists identified from the French ICU Society (SRLF) database.
The questionnaire was returned by 195 intensivists (response rate 18.1%), representing 135 of the 282 ICUs (47.8%) listed in the French ICU society (SRLF) database. The analysis showed that midazolam and sufentanil are the most frequently used hypnotics and opioids, respectively, administered in continuous intravenous (IV) infusions. IV boluses of hypnotics without subsequent continuous IV infusion are used occasionally (in <25% of patients) by 65% of intensivists. Anxiolytic benzodiazepines (e.g., clorazepam, alprazolam), hydroxyzine, and typical neuroleptics, via either an enteral or IV route, are used occasionally by two thirds of respondents. The existence of a written, local sedation management procedure in the ICU is reported by 55% of respondents, 54% of whom declare that they use it routinely. Written local sedation procedures mainly rely on titration of continuous IV hypnotics (90% of the sedation procedures); less frequently, sedation procedures describe alternative approaches to prevent oversedation, including daily interruption of continuous IV hypnotic infusion, hypnotic boluses with no subsequent continuous IV infusion, or the use of nonhypnotic drugs. Among the responding intensivists, 98% consider eye opening, either spontaneously or after light physical stimulation, a reasonable target consciousness level in patients with no severe respiratory failure or intracranial hypertension.
Despite a low individual response rate, the respondents to our survey represent almost half of the ICUs in the French SRLF database. The presence of a written local sedation procedure, a cornerstone of preventing oversedation, is reported by only half of respondents; when present, it is used in for a limited number of patients. Sedation procedures mainly rely on titration of continuous IV hypnotics, but other strategies to limit oversedation also are included in sedation procedures. French intensivists no longer consider severely altered consciousness a sedation objective for most patients.
PMCID: PMC3751696  PMID: 23937955
Sedation; Midazolam; Propofol; Opioids; Intensive care unit; Mechanical ventilation; Practice survey; Oversedation
14.  A novel acquired inv(2)(p23.3q24.3) with concurrent submicroscopic deletions at 2p23.3, 2p22.1, 2q24.3 and 1p13.2 in a patient with chronic thrombocytopenia and anemia 
Thrombocytopenia can result from a wide range of conditions and may be determined by multiple mechanisms. It can be due to a reduced platelet production or an increased destruction of platelets. Increased destruction is seen in conditions such as disseminated intravascular coagulation (DIC) and thrombotic microangiopathies, whereas decreased production is seen in bone marrow (BM) failure syndromes such as aplastic anemia, myelodysplastic syndromes, and chemotherapy-induced thrombocytopenia. In BM failure syndromes thrombocytopenia is often accompanied by anemia and/or leucopenia. Recognition of the cause of thrombocytopenia is often crucial for correct management of patients.
Case presentation
Here, we report on a 71 year-old male caucasian with thrombocytopenia since six years, and a recent development of anemia. At the time of progression with anemia a bone marrow sampling was done to examine for a possible causative myeloid malignancy. The morphological examination was normal whereas immunophenotyping by flowcytometry could not exclude myelodysplasia. Cytogenetic analysis by G-banding revealed a pericentric inversion of chromosome 2 in 23 out of 25 analyzed metaphases. The inversion was further characterized by molecular cytogenetics and high-resolution oligo-based array-CGH analysis. Together the analyses demonstrated a 141.8 Mb pericentric inversion, inv(2)(p23.3q24.3), and concurrent submicroscopic deletions in 2p23.3, 2p22.1, 2q24.3 and 1p13.2 between 0.6-1.9 Mb in size. Locus-specific FISH analyses confirmed all deletions and the pericentric inversion of chromosome 2. The chromosomal abnormalities were present in 87% of the bone marrow cells whereas analysis of a skin biopsy revealed a normal male karyotype as well as a normal array-CGH result. These findings demonstrate that the identified abnormalities were acquired.
To the best of our knowledge, this is the first report of chronic thrombocytopenia and anemia associated with acquired inv(2)(p23.3q24.3) as a sole cytogenetic abnormality together with concurrent submicroscopic deletions at 2p23.3, 2p22.1, 2q24.3 and 1p13.2.
Electronic supplementary material
The online version of this article (doi:10.1186/s13039-015-0113-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4316802  PMID: 25653716
Thrombocytopenia; Anemia; Chromosome 2; Inversion; Microdeletion; aCGH
15.  Comparative evaluation of thrombocytopenia in adult patients receiving linezolid or glycopeptides in a respiratory intensive care unit 
Linezolid is an oxazolidinone antibiotic agent, active against gram-positive bacteria that are resistant to traditional antibiotics, including glycopeptides. Linezolid is generally well tolerated, but has been associated with hematologic adverse effects such as thrombocytopenia. The primary objective of this study was to compare the incidence of thrombocytopenia between patients receiving linezolid or glycopeptides in different age groups. The secondary objective was to assess the association between the time-to-event and occurrence of thrombocytopenia. This retrospective study reviewed the medical records of patients who were treated with linezolid or glycopeptides (vancomycin or teicoplanin) between January 2010 and June 2013 in a respiratory intensive care unit. Data were extracted from the patients’ electronic medical records, which were obtained from a central database in the hospital, and multivariate analyses were performed. In total, the study included 225 patients who received linezolid or glycopeptides. The cumulative probability of thrombocytopenia was higher in the patients receiving linezolid than in those receiving glycopeptides (P<0.05), however the cumulative probability of thrombocytopenia did not differ significantly between patients receiving linezolid or glycopeptides in the subgroup whose age was <65 years (P>0.05). With a treatment duration of ≥7 days, the incidence of thrombocytopenia and the mean platelet count reduction in the patients receiving linezolid was significantly higher than in those receiving glycopeptides (P<0.05). No significant difference was identified in the mean platelet counts between the patients receiving linezolid and those receiving glycopeptides. In conclusion, it was identified that patients in a respiratory intensive care unit, aged ≥65 years or with a treatment duration of ≥7 days who were treated with linezolid were more likely to develop thrombocytopenia than patients of the same subgroup who were treated with glycopeptides.
PMCID: PMC3881040  PMID: 24396434
thrombocytopenia; linezolid; glycopeptides
16.  Extracorporeal life support for patients with acute respiratory distress syndrome: report of a Consensus Conference 
The influenza H1N1 epidemics in 2009 led a substantial number of people to develop severe acute respiratory distress syndrome and refractory hypoxemia. In these patients, extracorporeal membrane oxygenation was used as rescue oxygenation therapy. Several randomized clinical trials and observational studies suggested that extracorporeal membrane oxygenation associated with protective mechanical ventilation could improve outcome, but its efficacy remains uncertain. Organized by the Société de Réanimation de Langue Française (SRLF) in conjunction with the Société Française d’Anesthésie et de Réanimation (SFAR), the Société de Pneumologie de Langue Française (SPLF), the Groupe Francophone de Réanimation et d’Urgences Pédiatriques (GFRUP), the Société Française de Perfusion (SOFRAPERF), the Société Française de Chirurgie Thoracique et Cardiovasculaire (SFCTV) et the Sociedad Española de Medecina Intensiva Critica y Unidades Coronarias (SEMICYUC), a Consensus Conference was held in December 2013 and a jury of 13 members wrote 65 recommendations to answer the five following questions regarding the place of extracorporeal life support for patients with acute respiratory distress syndrome: 1) What are the available techniques?; 2) Which patients could benefit from extracorporeal life support?; 3) How to perform extracorporeal life support?; 4) How and when to stop extracorporeal life support?; 5) Which organization should be recommended? To write the recommendations, evidence-based medicine (GRADE method), expert panel opinions, and shared decisions taken by all the thirteen members of the jury of the Consensus Conference were taken into account.
PMCID: PMC4046033  PMID: 24936342
Extracorporeal life support; Extracorporeal membrane oxygenation; Extracorporeal CO2 removal; Acute respiratory distress syndrome; Protective ventilation
17.  Severe heparin-induced thrombocytopenia: when the obvious is not obvious, a case report 
Thrombocytopenia commonly occurs in hospitalized patients, particularly critically ill patients. We present an exemplifying case of severe heparin-induced thrombocytopenia (HIT) in an effort to solidify its high priority in the differential diagnosis of thrombocytopenia. A 75-year-old female underwent cardiac surgery with intraaortic balloon pump (IABP) placement. A platelet count drop to 25 × 10(9)/L by the third postoperative day was attributed to the IABP, which was removed. Her thrombocytopenia remained refractory to multiple platelet transfusions over several days. Right hand cyanosis then developed, attributed to a right radial arterial catheter, which was removed. All toes and fingers then showed severe ischemic changes. Ten days after the initial platelet count drop, a critical care specialist new to the treating team suspected HIT. Heparin exposure was stopped and argatroban was initiated. A HIT antibody test was subsequently strongly positive. The patients thrombocytopenia gradually resolved. No additional thromboses occurred during a 27-day intensive care unit stay. This case underscores the need for vigilance in suspecting HIT in patients with thrombocytopenia and recent heparin exposure. To avoid catastrophic outcomes in such patients, heparin should be stopped and alternative anticoagulation should be initiated, at least until HIT is excluded.
PMCID: PMC1865550  PMID: 17470295
18.  Management of hemodynamically unstable pelvic trauma: results of the first Italian consensus conference (cooperative guidelines of the Italian Society of Surgery, the Italian Association of Hospital Surgeons, the Multi-specialist Italian Society of Young Surgeons, the Italian Society of Emergency Surgery and Trauma, the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care, the Italian Society of Orthopaedics and Traumatology, the Italian Society of Emergency Medicine, the Italian Society of Medical Radiology -Section of Vascular and Interventional Radiology- and the World Society of Emergency Surgery) 
Hemodynamically Unstable Pelvic Trauma is a major problem in blunt traumatic injury. No cosensus has been reached in literature on the optimal treatment of this condition. We present the results of the First Italian Consensus Conference on Pelvic Trauma which took place in Bergamo on April 13 2013. An extensive review of the literature has been undertaken by the Organizing Committee (OC) and forwarded to the Scientific Committee (SC) and the Panel (JP). Members of them were appointed by surgery, critical care, radiology, emergency medicine and orthopedics Italian and International societies: the Italian Society of Surgery, the Italian Association of Hospital Surgeons, the Multi-specialist Italian Society of Young Surgeons, the Italian Society of Emergency Surgery and Trauma, the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care, the Italian Society of Orthopaedics and Traumatology, the Italian Society of Emergency Medicine, the Italian Society of Medical Radiology, Section of Vascular and Interventional Radiology and the World Society of Emergency Surgery. From November 2012 to January 2013 the SC undertook the critical revision and prepared the presentation to the audience and the Panel on the day of the Conference. Then 3 recommendations were presented according to the 3 submitted questions. The Panel voted the recommendations after discussion and amendments with the audience. Later on a email debate took place until December 2013 to reach a unanimous consent. We present results on the 3 following questions: which hemodynamically unstable patient needs an extraperitoneal pelvic packing? Which hemodynamically unstable patient needs an external fixation? Which hemodynamically unstable patient needs emergent angiography? No longer angiography is considered the first therapeutic maneuver in such a patient. Preperitoneal pelvic packing and external fixation, preceded by pelvic binder have a pivotal role in the management of these patients.
Hemodynamically Unstable Pelvic Trauma is a frequent death cause among people who sustain blunt trauma. We present the results of the First Italian Consensus Conference.
PMCID: PMC3975341  PMID: 24606950
Pelvic trauma; Angiography; Preperitoneal pelvic packing; External fixation; Pelvic binder
19.  Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV-Exposed and HIV-Infected Children: Recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics 
This report updates and combines into one document earlier versions of guidelines for preventing and treating opportunistic infections (OIs) among HIV-exposed and HIV-infected children, last published in 2002 and 2004, respectively. These guidelines are intended for use by clinicians and other health-care workers providing medical care for HIV-exposed and HIV-infected children in the United States. The guidelines discuss opportunistic pathogens that occur in the United States and one that might be acquired during international travel (i.e., malaria). Topic areas covered for each OI include a brief description of the epidemiology, clinical presentation, and diagnosis of the OI in children; prevention of exposure; prevention of disease by chemoprophylaxis and/or vaccination; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment; management of treatment failure; prevention of disease recurrence; and discontinuation of secondary prophylaxis after immune reconstitution. A separate document about preventing and treating of OIs among HIV-infected adults and postpubertal adolescents (Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents) was prepared by a working group of adult HIV and infectious disease specialists.
The guidelines were developed by a panel of specialists in pediatric HIV infection and infectious diseases (the Pediatric Opportunistic Infections Working Group) from the U.S. government and academic institutions. For each OI, a pediatric specialist with content-matter expertise reviewed the literature for new information since the last guidelines were published; they then proposed revised recommendations at a meeting at the National Institutes of Health (NIH) in June 2007. After these presentations and discussions, the guidelines underwent further revision, with review and approval by the Working Group, and final endorsement by NIH, CDC, the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA), the Pediatric Infectious Disease Society (PIDS), and the American Academy of Pediatrics (AAP). The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of the evidence supporting the recommendation so readers can ascertain how best to apply the recommendations in their practice environments.
An important mode of acquisition of OIs, as well as HIV infection among children, is from their infected mother; HIV-infected women coinfected with opportunistic pathogens might be more likely than women without HIV infection to transmit these infections to their infants. In addition, HIV-infected women or HIV-infected family members coinfected with certain opportunistic pathogens might be more likely to transmit these infections horizontally to their children, resulting in increased likelihood of primary acquisition of such infections in the young child. Therefore, infections with opportunistic pathogens might affect not just HIV-infected infants but also HIV-exposed but uninfected infants who become infected by the pathogen because of transmission from HIV-infected mothers or family members with coinfections. These guidelines for treating OIs in children therefore consider treatment of infections among all children, both HIV-infected and uninfected, born to HIV-infected women.
Additionally, HIV infection is increasingly seen among adolescents with perinatal infection now surviving into their teens and among youth with behaviorally acquired HIV infection. Although guidelines for postpubertal adolescents can be found in the adult OI guidelines, drug pharmacokinetics and response to treatment may differ for younger prepubertal or pubertal adolescents. Therefore, these guidelines also apply to treatment of HIV-infected youth who have not yet completed pubertal development.
Major changes in the guidelines include 1) greater emphasis on the importance of antiretroviral therapy for preventing and treating OIs, especially those OIs for which no specific therapy exists; 2) information about the diagnosis and management of immune reconstitution inflammatory syndromes; 3) information about managing antiretroviral therapy in children with OIs, including potential drug--drug interactions; 4) new guidance on diagnosing of HIV infection and presumptively excluding HIV infection in infants that affect the need for initiation of prophylaxis to prevent Pneumocystis jirovecii pneumonia (PCP) in neonates; 5) updated immunization recommendations for HIV-exposed and HIV-infected children, including hepatitis A, human papillomavirus, meningococcal, and rotavirus vaccines; 6) addition of sections on aspergillosis; bartonella; human herpes virus-6, −7, and −8; malaria; and progressive multifocal leukodystrophy (PML); and 7) new recommendations on discontinuation of OI prophylaxis after immune reconstitution in children. The report includes six tables pertinent to preventing and treating OIs in children and two figures describing immunization recommendations for children aged 0--6 years and 7--18 years.
Because treatment of OIs is an evolving science, and availability of new agents or clinical data on existing agents might change therapeutic options and preferences, these recommendations will be periodically updated and will be available at
PMCID: PMC2821196  PMID: 19730409
20.  Thrombocytopenia in Hypertensive Disease of Pregnancy 
Thrombocytopenia is defined as a platelet count of less than 150 × 103 μl. It is commonly diagnosed and has attracted more interest from the researchers in pregnant women during the last 20 years, especially in hypertensive pregnant women.
To assess the incidence of thrombocytopenia in hypertensive pregnant women during the third trimester of pregnancy.
Five hundred forty-four pregnant women were included in this study from a total of 10,272 admitted at the Obstetrics and Gynecology Department at Tripoli Medical Center during January–August 2007. Frequent blood pressure monitorings and full blood counts were performed in several medical follow ups. They were not known to be HBV, HCV, or HIV positive women before pregnancy, and none was reported to have evidence of HBV, HCV, or HIV upon performing HBs-Ag, anti-HCV antibody, or HIV-antigen positive tests. Data were arranged in Excel Microsoft program version 2010, and statistically analyzed by SPSS windows program version 17.
Five hundred and forty-four women were hypertensive according to WHO hypertension definition criteria. Sixty-seven women had only one reading of high blood pressure, while 39 women fulfilled HELP syndrome criteria (hemolysis elevated liver enzymes low platelet). These 39 women were excluded from the study. Therefore, only 438 pregnant women remained eligible for the study. The mean age was (32.56 ± 1.5), with their ages ranging between 18 and 49 years. Most of the included women were primigravida 179 (39 %), gravid 2, para one were 72 (16.4 %), and the rest were gravid 3 or more (42.6 %). The blood pressure was 140-160/90-110 mmHg in 365 women (83.4 %), and 73 women (16.7 %) had blood pressure readings more than 160/110 mmHg. Mean platelets count was (206.49 × 103/μl ± 3.35), and ranged between (41.0 - 449.0 × 103/μl). Thrombocytopenia (less than 150 × 103/μl) was recorded in 103 women (23.5 %). All pregnancy cases were delivered safely with no fetal complications.
Gestational thrombocytopenia (GT) is recognized as a major cause of thrombocytopenia particularly in hypertensive pregnant women during the third trimester. Careful follow up during and after pregnancy for those women is recommended.
PMCID: PMC3664679  PMID: 24431613
Pregnancy; Thrombocytopenia; Gestational hypertension; Thrombocytopenia
21.  Neonatal Thrombocytopenia after Perinatal Asphyxia Treated with Hypothermia: A Retrospective Case Control Study 
Our objective was to estimate the effect of therapeutic hypothermia on platelet count in neonates after perinatal asphyxia. We performed a retrospective case control study of all (near-) term neonates with perinatal asphyxia admitted between 2004 and 2012 to our neonatal intensive care unit. All neonates treated with therapeutic hypothermia were included in this study (hypothermia group) and compared with a historic control group of neonates with perinatal asphyxia treated before introduction of therapeutic hypothermia (2008). Primary outcome was thrombocytopenia during the first week after birth. Thrombocytopenia was found significantly more often in the hypothermia group than in the control group, 80% (43/54) versus 59% (27/46) (P = .02). The lowest mean platelet count in the hypothermia group and control group was 97 × 109/L and 125 × 109/L (P = .06), respectively, and was reached at a mean age of 4.1 days in the hypothermia group and 2.9 days in the control group (P < .001). The incidence of moderate/severe cerebral hemorrhage was 6% (3/47) in the hypothermia group versus 9% (3/35) in the control group (P = .64). In conclusion, neonates with perinatal asphyxia treated with therapeutic hypothermia are at increased risk of thrombocytopenia, without increased risk of cerebral hemorrhage.
PMCID: PMC4158299  PMID: 25214854
22.  Hematologic Complications of Pregnancy 
Seminars in hematology  2013;50(3):222-231.
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.
PMCID: PMC3748382  PMID: 23953339
23.  Prospective observational evaluation of the particle immunofiltration anti-platelet factor 4 rapid assay in MICU patients with thrombocytopenia 
Critical Care  2013;17(4):R143.
Heparin-induced thrombocytopenia (HIT) results from antibodies to PF4/heparin complexes and clinical diagnosis is difficult. We evaluated the particle immunofiltration anti-platelet factor 4 (PIFA) rapid assay, in conjunction with a clinical risk score, in the diagnosis of HIT.
We performed a prospective observational study in all patients admitted to the medical intensive care unit (MICU) in a large academic medical center. Patients were screened daily for thrombocytopenia defined as either a platelet count that decreased by at least 33% or an absolute platelet count less than 150,000/μL. Patients with suspected HIT underwent PIFA and ELISA testing for anti-PF4/heparin antibodies. Available residual frozen sera were sent to a reference laboratory for serotonin release assay (SRA) testing.
During the study period, 340 patients were admitted to the MICU, of which 143 patients met criteria for thrombocytopenia. Forty-three patients had no evidence of recent heparin exposure. PIFA and ELISA testing were performed on 100 patients, of which 92 had samples available for SRA analysis. PIFA results were negative in 62, positive in 28 and inconclusive in 2 patients. The 4Ts score showed low to intermediate risk in 57 of the PIFA negative patients. The ELISA results were negative in 86 and positive in 6 patients. SRA testing identified 3 patients with a positive SRA test and 89 patients with a negative result. All patients with a negative PIFA result also had a negative SRA result. In the one patient deemed to have clinical HIT, the pretest probability was high (4Ts score of 6) and the anti-PF4/heparin antibody testing revealed a positive SRA, inconclusive PIFA and a negative ELISA result.
While thrombocytopenia in our population is common, the prevalence of HIT is low. The combination of a low to intermediate pretest probability with a negative PIFA test can rapidly exclude the presence of platelet activating anti-PF4/heparin antibodies and, therefore, HIT as the cause of the thrombocytopenia. Since a positive PIFA result has a low positive predictive value, a positive PIFA is not diagnostic of HIT and additional evaluation is warranted.
PMCID: PMC4056086  PMID: 23876263
heparin; thrombocytopenia; platelet factor 4; intensive care; thrombosis; clinical laboratory techniques
Seminars in hematology  2010;47(3):281-288.
Thrombocytopenia is common among sick neonates, affecting 20–35% of all patients admitted to the neonatal intensive care unit (NICU). While most cases of neonatal thrombocytopenia are mild or moderate and resolve within 7–14 days with appropriate therapy, 2.5–5% of NICU patients develop severe thrombocytopenia, sometimes lasting for several weeks and requiring >20 platelet transfusions. The availability of thrombopoietic agents offers the possibility of decreasing the number of platelet transfusions and potentially improving the outcomes of these infants. Adding thrombopoietin (TPO) mimetics to the therapeutic armamentarium of neonatologists, however, will require careful attention to the substantial developmental differences between neonates and adults in the process of megakaryocytopoiesis and in their responses to TPO. Taken together, the available data suggest that TPO mimetics will stimulate platelet production in neonates, but might do so through different mechanisms and at different doses than those established for adults. In addition, the specific groups of thrombocytopenic neonates most likely to benefit from therapy with TPO mimetics need to be defined, and the potential non-hematological effects of these agents on the developing organism need to be considered. This review summarizes our current understanding of neonatal megakaryocytopoiesis, and examines in detail the developmental factors relevant to the potential use of TPO mimetics in neonates.
PMCID: PMC2934854  PMID: 20620440
25.  Impact of a nurses' protocol-directed weaning procedure on outcomes in patients undergoing mechanical ventilation for longer than 48 hours: a prospective cohort study with a matched historical control group 
Critical Care  2005;9(2):R83-R89.
The aim of the study was to determine whether the use of a nurses' protocol-directed weaning procedure, based on the French intensive care society (SRLF) consensus recommendations, was associated with reductions in the duration of mechanical ventilation and intensive care unit (ICU) length of stay in patients requiring more than 48 hours of mechanical ventilation.
This prospective study was conducted in a university hospital ICU from January 2002 through to February 2003. A total of 104 patients who had been ventilated for more than 48 hours and were weaned from mechanical ventilation using a nurses' protocol-directed procedure (cases) were compared with a 1:1 matched historical control group who underwent conventional physician-directed weaning (between 1999 and 2001). Duration of ventilation and length of ICU stay, rate of unsuccessful extubation and rate of ventilator-associated pneumonia were compared between cases and controls.
The duration of mechanical ventilation (16.6 ± 13 days versus 22.5 ± 21 days; P = 0.02) and ICU length of stay (21.6 ± 14.3 days versus 27.6 ± 21.7 days; P = 0.02) were lower among patients who underwent the nurses' protocol-directed weaning than among control individuals. Ventilator-associated pneumonia, ventilator discontinuation failure rates and ICU mortality were similar between the two groups.
Application of the nurses' protocol-directed weaning procedure described here is safe and promotes significant outcome benefits in patients who require more than 48 hours of mechanical ventilation.
PMCID: PMC1175918  PMID: 15774054
intensive care unit; mechanical ventilation; protocol-directed weaning

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