Frequency, clinical, and laboratory findings of platelet secretion disorders in patients referred to the specialized coagulation laboratory of the Iranian Blood Transfusion Organization.

OBJECTIVES: Platelet secretion disorders (PSDs) are a subgroup of platelet function disorders (PFDs) caused by defects in the content or release of platelet granules. These patients have a variable degree of mucocutaneous bleeding tendency. The diagnostic facilities of PSDs are imitated in Iran, even in specialized coagulation laboratories. The present study aims to estimate the frequency of PSDs among patients referred to the Iranian Blood Transfusion Organization (IBTO). METHODS: The research population includes all patients referred to the specialized coagulation laboratory of IBTO and requested platelet function and von Willebrand testing by their physicians. They were recruited between May 2022 and October 2022 if they were not diagnosed as having procoagulant defects, von Willebrand disease (VWD), Glanzmann thrombasthenia (GT), Bernard-Soulier syndrome (BSS), and platelet count <100 × 10 9 (except in the syndromic forms). Patients with a defect in response to at least two agonists in Light transmission aggregometry (LTA), one agonist in the ATP-secretion study, and/or impairment in the expression of CD62P are considered PSDs. RESULTS: Among 121 cases referred to our center over 6 months, 40 patients fulfilled the inclusion and exclusion criteria. Ten patients were diagnosed with PSDs. Six were classified as δ-platelet secretion disorders (δ-PSD), two α-platelet secretion disorders (α-PSD), and two αδ-platelet secretion disorders (αδ-PSD). CONCLUSIONS: The prevalence of PSDs in our population study was 25% (10/40), which seems highly prevalent. Therefore, expanding laboratory approaches to platelet function defects is necessary as a routine in our country.

Prevalence, burden and treatment effects of vaginal bleeding in women with (suspected) congenital platelet disorders throughout life: a cross-sectional study.

Congenital platelet disorders (CPDs) are rare bleeding disorders that are associated with mucocutaneous bleeds. However, data on vaginal bleeding in women with CPDs are scarce. A set of generic and bleeding-specific questionnaires were used to evaluate the prevalence of vaginal bleeding, its impact on quality of life (QoL) and sexual functioning and the consequences for pregnancy, miscarriage and delivery in a cohort of women who were referred for diagnostic evaluation for CPDs. A total of 78 women included in the study were either diagnosed with a CPD (n = 35) or were clinically suspected of a CPD (n = 43). Heavy menstrual bleeding (HMB) was reported by a large proportion of women, which mainly started at menarche. In all, 76% of women received any kind of HMB treatment, often leading to surgical prodecures. HMB was shown to have a high impact on QoL, which improved upon treatment. Even though women reported that vaginal bleeding affects sexuality, this topic is not frequently discussed with physicians. Heavy blood loss frequently occurred after miscarriage/delivery, often requiring treatment. Women with (suspected) CPDs frequently encounter HMB, negatively impacting daily life and sexual functioning. Together with peripartum bleeding, these data highlight the burden of vaginal bleeding in CPDs and importance of adequate treatment.

Trastornos plaquetarios hereditarios poco frecuentes: patología molecular y aspectos diagnósticos / Infrequent hereditary platelets disorders: molecular pathology and diagnostic aspects

Introducción: Las plaquetas tienen una función clave en la hemostasia primaria a través de cuatro mecanismos fundamentales: adhesión, agregación, secreción y actividad procoagulante, todos controlados genéticamente por más de 50 genes asociados que han sido identificados. Las manifestaciones clínicas en las alteraciones hereditarias de las plaquetas suelen ser variables; aunque estas alteraciones de la coagulación suelen presentarse con una trombocitopenia notoria, también pueden exhibir trombocitopatías, en las cuales la capacidad hemostática de las plaquetas resulta afectada sin variar su número. Por tanto, existen gran variedad de manifestaciones fenotípicas y mutaciones en relación con la función plaquetaria, algunas de las cuales se explicarán más adelante. Objetivo: Realizar revisión práctica sobre mutaciones plaquetarias hereditarias de baja incidencia y destacar la importancia de su conocimiento, correcto diagnóstico, y tratamiento precoz. Métodos: Se realizó revisión literaria en inglés y españolen MEDLINE, EMBASE, Lilacs y ScienceDirect desde mayo 2019 hasta abril 2020, con el uso de combinación de palabras clave y términos MeSH relacionados con trombastenia, genética médica, hemostasis, agregación plaquetaria, trombopoyesis. Se efectuó análisis y resumen de la bibliografía revisada. Conclusión: Entre las alteraciones hereditarias de las plaquetas se pueden encontrar defectos en todos los mecanismos en que participan; sin embargo, la confirmación diagnóstica sigue siendo complicada por el tiempo y el costo que representa lo que ocasiona diagnósticos inadecuados que impactan en el manejo clínico y la evolución(AU)

Introduction: Platelets have a key role in primary hemostasis through four main mechanisms: adhesion, aggregation, secretion and procoagulant activity, all of these controlled by over 50 associated genes that have been identified. Clinical signs of hereditary platelets alterations are usually variable; even though these disorders of hemostasis generally course with a notorious thrombocytopenia, they also might have thrombocytopathies, in which the hemostatic capacity of platelets is affected without altering its number. According to this, there's a great variety of phenotypic manifestations and mutations that affect platelet function, some of these will be explained later on. Objective: To make a practical review of hereditary platelets mutations that have low incidence in population and to highlight the importance of knowing about them, how to diagnose them and early treatment. Methods: A review of literature in both Spanish and English, was done based on MEDLINE, EMBASE, Lilacs and ScienceDirect, during May 2019 and April 2020 using key words and MeSH terms such as thrombasthenia, medical genetics, hemostasis, platelets aggregation, thromopoiesis. Then, an analysis and summary of the reviewed bibliography was carried out. Conclusion: Among the hereditary alterations of platelets, many defects can be found in every mechanism involved; however, diagnostic confirmation is still complicated due to time and cost, causing inaccurate diagnoses that impact on clinic management and evolution(AU)

Distribution of CD36 deficiency in different Chinese ethnic groups.

BACKGROUND: CD36 is a multifunctional receptor in cells that plays a role in important cellular processes including immune regulation. Evidence indicates that mutations in the CD36 gene are associated with malaria. Moreover, studies on the frequency of CD36 deficiency have been conducted in specific provinces of China. However, the frequency of CD36 deficiency may differ among various ethnic populations. In this study, we analyzed the frequency of CD36 deficiency among seven different provinces and minorities in China. METHODS AND MATERIALS: In this study, 5313 samples were randomly collected from seven provinces in China. CD36 deficiency on platelets and monocytes was determined via flow cytometry using a monoclonal antibody (mAb) against CD36. DNA sequencing analysis was performed to identify mutations associated with CD36 deficiency. RESULTS: The frequency of CD36 deficiency among individuals from different provinces (n = 7) was 1.60%, comprising 0.38% of type-I deficiency and 1.22% of type-II deficiency. The distribution among provinces ranged from 0.81% to 1.99%. The largest ethnic group, Han, showed a lower frequency of deficiency than ethnic minorities (1.30% versus 2.37%). The most common mutations found in our overall cohort were 329-330delAC and 1228-1239delATTGTGCCTATT. Significant high frequencies of CD36 deficiency were detected in two ethnic minorities, Zhuang (3.69%) and BuYi (3.05%), living in southern China. CONCLUSIONS: Through an analysis of a large cohort, we determined the frequencies of CD36 deficiency among different Chinese ethnic groups. A high frequency of type-I deficiency was found in certain minorities living in southern China, which is known to be vulnerable to malaria epidemics. These findings may help us understand the phenotypic consequences of CD36-deficient alleles associated with malaria.

Screening for Platelet Dysfunction and Use of Prophylactic Tranexamic Acid in Patients Undergoing Deep Brain Stimulation: A Retrospective Analysis of Incidence and Outcome of Intracranial Hemorrhage.

INTRODUCTION: The rate of intracranial hemorrhage (ICH) after deep brain stimulation (DBS) is between 1.5 and 6.1%, with prolonged deficits occurring in 0.4-2.5% of the patients. This retrospective study investigates whether the prophylactic administration of tranexamic acid (TA) to patients with abnormal platelet function detected preoperatively by platelet function analyzer (PFA) lowered the risk for an ICH event. METHODS: We performed a systematic review of the medical records of 485 consecutively admitted patients who underwent bilateral DBS surgery in a single-center university hospital setting between 2009 and 2018. The cohort was split into two groups. In one group, preoperative PFA screening was performed (n = 156, patients recruited from 2014 to 2018), and TA was administered if platelet function was abnormal. No preoperative PFA was performed in the second group (n = 359, patients recruited from 2009 to 2013). Both cohorts were analyzed for the occurrence of ICH, defined by (i) detection of ICH in routine postoperative magnetic resonance/computed tomography imaging or (ii) in non-routine imaging for the onset of new neurological symptoms. RESULTS: Fourteen of the 156 screened patients (9%) showed reproducible PFA-100 closure abnormalities (3 with von Willebrand disease, 11 with no identifiable cause of platelet dysfunction). Two of the 156 patients (1.3%) in this cohort revealed an ICH on imaging, 1 of whom (0.6%) exhibited a prolonged neurological deficit as a result of ICH. In the cohort without platelet testing, 11 of the 329 patients (3.3%) demonstrated ICH on imaging, of whom 5 (1.5%) suffered from a prolonged neurological deficit. CONCLUSION: In this retrospective study, the screening and the administration of TA appeared to lower the risk of an ICH by 1.8%. One patient with von Willebrand disease suffered an ICH despite TA treatment. A prospective study is needed to clarify the impact of platelet testing and TA administration on the of incidence ICH.

Primary Thrombophilia in Mexico XIII: Localization of the Thrombotic Events in Mexican Mestizos With the Sticky Platelet Syndrome.

The sticky platelet syndrome (SPS) is a common cause of both arterial and venous thrombosis, being a dominant autosomal disease with qualitative platelet alterations and familial occurrence. It is characterized by platelet hyperreactivity with increased platelet aggregability in response to low concentrations of platelet agonists: epinephrine, adenosine diphosphate, or both. The clinical manifestations involve venous or arterial thrombosis, recurrent pregnancy loss, and fetal growth retardation. To analyze the localization of the thrombotic episodes in a cohort of Mexican mestizo patients with SPS. Between 1992 and 2016, 86 Mexican mestizo patients with SPS as the single thrombophilic condition were prospectively identified; all of them had a history of thrombosis. There were 15 males and 71 females. The thrombotic episodes were arterial in 26 cases and venous in 60 (70%). Arterial thrombosis was mainly pulmonary thromboembolism, whereas venous thromboses were identified most frequently in the lower limbs. Mexican mestizo population with SPS is mainly female; the type I of the condition is the most frequent; both arterial and venous thrombosis can occur, and they are mainly pulmonary embolism and lower limbs venous thrombosis, respectively.

The association between platelet dysfunction and adverse outcomes in cardiac surgical patients.

Haemostatic activation during cardiopulmonary bypass is associated with prothrombotic complications. Although it is not possible to detect and quantify haemostatic activation directly, platelet dysfunction, as measured with point-of-care-assays, may be a useful surrogate. In this study, we assessed the association between cardiopulmonary bypass-associated platelet dysfunction and adverse outcomes in 3010 cardiac surgical patients. Platelet dysfunction, as measured near the end of the rewarming phase of cardiopulmonary bypass, was calculated as the proportion of non-functional platelets after activation with collagen. Logistic regression and multivariable analyses were applied to assess the relationship between platelet dysfunction and a composite of in-hospital death; myocardial infarction; stroke; deep vein thrombosis or pulmonary embolism; and acute kidney injury (greater than a two-fold increase in creatinine). The outcome occurred in 251 (8%) of 3010 patients. The median (IQR [range]) percentage platelet dysfunction was less for those without the outcome as compared with those with the outcome; 14% (8-28% [1-99%]) vs. 19% (11-45% [2-98%]), p < 0.001. After risk adjustment, platelet dysfunction was independently associated with the composite outcome (p < 0.001), such that for each 1% increase in platelet dysfunction there was an approximately 1% increase in the composite outcome (OR 1.012; 95%CI 1.006-1.018). This exploratory study suggests that cardiopulmonary bypass-associated platelet dysfunction has prognostic value and may be a useful clinical measure of haemostatic activation in cardiac surgery.

Platelet function tests: A 5-year audit of platelet function tests done for bleeding disorders in a tertiary care center of a developing country.

INTRODUCTION: The platelet function disorders remain largely undiagnosed or incompletely diagnosed in developing nations due to lack of availability of tests like lumiaggregometry, granule release assay or molecular testing. We performed a retrospective analysis of all the platelet function test (PFT) carried out in past 5 years by Light transmission aggregometery (LTA) using a panel of agonist. The indications and the test results were analyzed by two hematopathologist with the aim to look into the present diagnostic facilities or lack of it for correct diagnosis. This is essential for better management and genetic counselling. MATERIALS AND METHODS: The PFT was performed both on patients and healthy unrelated age specific controls by light transmission aggregometry on Chronolog platelet aggregometer using platelet rich plasma. The panel of agonists included ADP (10µm/l and 2.0 µm/l), epinephrine (10.0 µm/l), collagen (2µg/ml), arachidonic acid (0.75 mM) and ristocetin (1.25 mg/ml & 0.25 mg/l). RESULTS: The 5 years records of 110 cases were audited, 101 of these were tested for clinical bleeding , 35 adults and 66 children. The adults included 29 women and 6 men, 17 to 82 years of age. The children were 16 years to 3 months of age, 30 girls and 36 boys. Platelet function test abnormality was found in 31.6% (32/101) cases ,a majority remained undiagnosed of these about 21% had clinically significant bleeding.The cases diagnosed included Glanzmann Thromboasthenia-11 , von Willebrand Disease-6, Bernard Soulier'syndrome-1, storage pool disorder-6, mild defect of Epinephrine-3, isolated defect with collagen in1. CONCLUSION: An epidemiologically large proportion of platelet function disorders amongst people living in developing nations remain undiagnosed. This lacunae needs to be highlighted and addressed on larger scale. The options available are to increase the available armamentarium of tests or international collaboration with a specialized laboratory to aid in complete diagnosis.

Clinical Course and Outcome of Childhood Acquired Platelet Dysfunction with Eosinophilia.

Acquired platelet dysfunction with eosinophilia (APDE) is a syndrome which manifests as a transient state of platelet dysfunction in the presence of eosinophilia. The aim of this work was to study the clinical course and outcomes of children diagnosed with APDE. The hospital records of children with APDE were retrospectively reviewed and a total of 69 children were included. The mean (standard deviation) age at diagnosis was 6.9 (3.1) years. All of the patients presented with ecchymoses on the extremities, body, and face. None had serious bleeding symptoms. Platelet counts were within the normal range but all of the patients had abnormal platelet morphology by light microscopy. Parasitic infestation was found in 38% and most (87%) were treated with antiparasitic drugs. The median time from the onset of symptoms to remission was 2.6 months (95% CI 1.8-3.1). The overall complete remission rates at 3, 6, and 12 months were 61, 90, and 94%, respectively, with a median follow-up time after remission of 14.0 months (interquartile range 6.0-30.8). Neither univariate nor multivariate analysis indicated any statistically significant determinants for remission time. In our study, APDE was transient with spontaneous remission, no serious bleeding manifestations, and had a benign clinical course.

Patterns of bruising in preschool children with inherited bleeding disorders: a longitudinal study.

OBJECTIVE: The extent that inherited bleeding disorders affect; number, size and location of bruises in young children <6 years. DESIGN: Prospective, longitudinal, observational study. SETTING: Community. PATIENTS: 105 children with bleeding disorders, were compared with 328 without a bleeding disorder and classified by mobility: premobile (non-rolling/rolling over/sitting), early mobile (crawling/cruising) and walking and by disease severity: severe bleeding disorder factor VIII/IX/XI <1 IU/dL or type 3 von Willebrand disease. INTERVENTIONS: Number, size and location of bruises recorded in each child weekly for up to 12 weeks. OUTCOMES: The interventions were compared between children with severe and mild/moderate bleeding disorders and those without bleeding disorders. Multiple collections for individual children were analysed by multilevel modelling. RESULTS: Children with bleeding disorders had more and larger bruises, especially when premobile. Compared with premobile children without a bleeding disorder; the modelled ratio of means (95% CI) for number of bruises/collection was 31.82 (8.39 to 65.42) for severe bleeding disorders and 5.15 (1.23 to 11.17) for mild/moderate, and was 1.81 (1.13 to 2.23) for size of bruises. Children with bleeding disorders rarely had bruises on the ears, neck, cheeks, eyes or genitalia. CONCLUSIONS: Children with bleeding disorder have more and larger bruises at all developmental stages. The differences were greatest in premobile children. In this age group for children with unexplained bruising, it is essential that coagulation studies are done early to avoid the erroneous diagnosis of physical abuse when the child actually has a serious bleeding disorder, however a blood test compatible with a mild/moderate bleeding disorder cannot be assumed to be the cause of bruising.

Spectrum of clinical and genetic features of patients with inherited platelet disorder with suspected predisposition to hematological malignancies: a nationwide survey in Japan.

BACKGROUND: Inherited thrombocytopenia (IT) contains several forms of familial thrombocytopenia and some of them have propensity to hematological malignancies. The etiological and genetic features of this heterogeneous syndrome have not yet been elucidated. PATIENTS AND METHODS: We conducted a nationwide survey to collect clinical information and samples from patients with familial thrombocytopenia and/or hematological malignancies in order to obtain a comprehensive understanding of IT. RESULTS: Among the 43 pedigrees with clinical samples, RUNX1 mutations were identified in 8 pedigrees (18.6%). While MYH9 and ANKRD26 mutations were identified in 2 and 1 pedigrees, respectively, no gene mutations were detected in the remaining 32 pedigrees from a panel of previously reported pathogenetic mutations. Clinical data were comparable between FPD/AML and non-FPD/AML probands. CONCLUSIONS: Our study clarified that it is unexpectedly difficult to diagnose FPD/AML based on clinical information alone, and thus, genetic testing is strongly recommended. Our survey also identified some pedigrees with a strong family history of myelodysplastic syndromes of unknown origin. Additionally, there were 14 pedigrees in which three or more members were affected by immune thrombocytopenia (ITP), and a computer-aided simulation suggested that such a distribution almost never happens by coincidence, which implicates a genetic predisposition to ITP.

A whole genome approach to platelet and bleeding disorders.

The sequencing of hundreds of thousands of human exomes and hundreds of thousands of whole genomes is providing a progressively accurate and complete catalogue of human genetic variation. The initial studies to use genome wide data to help understand platelet disorders performed genome wide association studies to identify loci linked to variations in blood cell parameters. These studies used normal variation to find corresponding genetic variation. We next wished to investigate the genetic basis of bleeding disorders which may also provide a key to novel genes regulating platelet and haemostatic functions. The BRIDGE consortium (www.bridgestudy.org) is funded by the NIHR and brings together 13 rare disease gene discovery projects. The aim of these projects is to investigate as yet undiagnosed rare inherited diseases and identify the underlying mutational basis. We have used a cluster analysis based on the Human Phenotype Ontology in combination with next generation sequencing techniques to help identify patients with similar phenotypes which we hypothesise will arise from defects in the same gene. Preliminary results validate the clustering approach and have also resulted in a number of novel genes important for normal and pathogenic platelet physiology.

Genetic variations of CD36 and low platelet CD36 expression - a risk factor for lipemic plasma donation in Taiwanese apheresis donors.

BACKGROUND: New CD36 mutations are constantly being identified, although no study has specifically targeted a Taiwanese population. CD36 deficiency can result in dyslipid state and slow clearance of chylomicron. This could be linked to more frequent lipemic donations. STUDY DESIGN AND METHODS: We used flow cytometric methods to study the CD36 deficiency in 640 regular volunteer platelet apheresis donors from Taipei blood centre. The coding exons of CD36 gene were sequenced in CD36-deficient individuals, and the allele frequencies of CD36 variants were determined in the larger population by mutation-specific PCR and oligonucleotide hybridization. Visual inspection of lipemic plasma was routinely performed on samples taken before commencement of apheresis. Individuals found to have lipemic plasma are deferred until next donation. We investigated the link between positive lipemic deferral record and low platelet CD36 expression status. RESULTS: We found four donors (0·6%) with type I CD36 deficiency (both platelets and monocytes CD36(null) ) and six (1·0%) with type II CD36 deficiency (PLT: CD36(null) , monocyte: CD36(low) ). Six CD36 genetic variants were identified, two of them were novel, all but one are found exclusively in CD36(null) and CD36(low) expressors. Subjects with CD36 genetic variants also displayed deficient or reduced CD36 on monocytes. Donors with null or low PLT CD36 expression were more likely to have a lipemic deferral record than control subjects with normal PLT CD36 expression (X(2) = 27·36, odds ratio = 2·6, 95% conference interval: 1·8-3·8, P < 0·0001). CONCLUSION: Through this study, we established a donor registry to supply CD36-negative platelets for patients in need.

Poorer prognosis with ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia: a single-center case-control study.

In ethylenediaminetetraacetic acid (EDTA)-dependent pseudothrombocytopenia (PTCP), automated platelet counts are lower than actual counts because of EDTA-induced aggregation. Factors contributing to the incidence of EDTA-PTCP are unknown, and no study has assessed the prognosis of EDTA-PTCP patients. This retrospective study assessed characteristics in EDTA-PTCP patients and matched controls to determine differences in prognosis. A retrospective case-control study was designed. From the University of Tokyo Hospital database, we identified patients diagnosed with EDTA-PTCP between 2009 and 2012, and performed 1:2 case:control matching for age and sex. A control group of sex- and age-matched patients was selected at random from the same database. We investigated differences in the frequency of complications, medication history, and blood transfusion history between the groups at the time of blood collection. Prognosis was evaluated using multivariate Cox regression analysis adjusting for age, sex, autoimmune disease, liver disease, and malignant tumor. We identified 104 EDTA-PTCP patients and 208 matched controls. The median age was 69.0 years (interquartile range: 54-76), with men comprising 51%. EDTA-PTCP patients had a higher frequency of malignant tumor and a lower frequency of hypertension and diabetes than controls. After adjustment for background factors, prognosis of EDTA-PTCP patients was significantly poorer than controls (hazard ratio, 11.8; 95% confidence intervals, 2.62-53.54). In conclusion, EDTA-PTCP patients had higher mortality, and EDTA-PTCP may need to be recognized as an indicator of worse prognosis.

Functional and molecular characterization of inherited platelet disorders in the Iberian Peninsula: results from a collaborative study.

BACKGROUND: The diagnostic evaluation of inherited platelet disorders (IPDs) is complicated and time-consuming, resulting in a relevant number of undiagnosed and incorrectly classified patients. In order to evaluate the spectrum of IPDs in individuals with clinical suspicion of these disorders, and to provide a diagnostic tool to centers not having access to specific platelets studies, we established the project "Functional and Molecular Characterization of Patients with Inherited Platelet Disorders" under the scientific sponsorship of the Spanish Society of Thrombosis and Haemostasis. PATIENTS/METHODS: Subjects were patients from a prospective cohort of individuals referred for clinical suspicion of IPDs as well as healthy controls. Functional studies included light transmission aggregation, flow cytometry, and when indicated, Western-blot analysis of platelet glycoproteins, and clot retraction analysis. Genetic analysis was mainly performed by sequencing of coding regions and proximal regulatory regions of the genes of interest. RESULTS: Of the 70 cases referred for study, we functionally and molecularly characterized 12 patients with Glanzmann Thrombasthenia, 8 patients with Bernard Soulier syndrome, and 8 with other forms of IPDs. Twelve novel mutations were identified among these patients. The systematic study of patients revealed that almost one-third of patients had been previously misdiagnosed. CONCLUSIONS: Our study provides a global picture of the current limitations and access to the diagnosis of IPDs, identifies and confirms new genetic variants that cause these disorders, and emphasizes the need of creating reference centers that can help health care providers in the recognition of these defects.

Congenital cardiac lesions involving systolic flow abnormalities are associated with platelet dysfunction in children.

BACKGROUND: Shear stress-induced platelet dysfunction (PD) is prevalent among adults with aortic stenosis. Our aim was to determine whether abnormal platelet function was associated with specific congenital cardiac lesions in children. METHODS: The charts of 407 children who had undergone cardiopulmonary bypass and had preoperative platelet function analysis were evaluated. Patients were assigned to 1 of 11 different lesion categories. Platelet dysfunction (PD) was defined as prolonged closure time (CT) as measured with a platelet function analyzer. Odds ratio (OR) estimates for prolonged CT were calculated for each lesion category. Mean CTs were compared with Tukey-Kramer separated means testing. Analysis of variance modeling was used to determine association between hematocrit value and CT. RESULTS: CT in patients with ventricular septal defects (VSD) and right ventricular outflow tract obstruction (RVOTO) lesions was prolonged. OR analysis found that patients with VSDs (OR, 2.46) or RVOTO (OR, 2.88) had at least a 95% probability of an abnormal CT. In contrast, patients with atrial septal defect (ASD), bidirectional Glenn procedure (BDG), and pulmonary insufficiency (PI) had a reduced probability of a prolonged CT (p < 0.05). A similar pattern was seen in parametric analysis comparing mean CTs across lesion categories. A lower preoperative hematocrit value was associated with prolonged CTs across all lesion types (p < 0.05). CONCLUSIONS: PD was common in children with congenital cardiac lesions involving systolic flow abnormalities and was uncommon among children with lesions having diastolic abnormalities. Lower preoperative hematocrit values were associated with prolonged CTs, suggesting subclinical bleeding secondary to excessive platelet shearing.

Prevalence of disease and relationships between laboratory phenotype and bleeding severity in platelet primary secretion defects.

BACKGROUND: The prevalence of platelet primary secretion defects (PSD) among patients with bleeding diathesis is unknown. Moreover, there is paucity of data on the determinants of bleeding severity in PSD patients. OBJECTIVE: To determine the prevalence of PSD in patients with clinical bleeding and to study the relationships between the type of platelet defect and bleeding severity. METHODS: Data on patients referred for bleeding to the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan (Italy) in the years between 2008 and 2012 were retrieved to study the prevalence of PSD. Demographic, clinical and laboratory information on 32 patients with a diagnosis of PSD was used to compare patients with or without associated medical conditions and to investigate whether or not the type and extension of platelet defects were associated with the bleeding severity score (crude and age-normalized) or with the age at first bleeding requiring medical attention. RESULTS: The estimated prevalence of PSD among 207 patients with bleeding diathesis and bleeding severity score above 4 was 18.8% (95% confidence interval [CI]: 14.1-24.7%). Patients without associated medical conditions had earlier age of first bleeding (18 vs 45 years; difference: -27 years; 95% CI: -46 to -9 years) and different platelet functional defect patterns (Fisher's exact test of the distribution of patterns, P = 0.007) than patients with accompanying medical conditions. The type and extension of platelet defect was not associated with the severity of bleeding. CONCLUSIONS: PSD is found in approximately one fifth of patients with clinical bleeding. In patients with PSD, the type and extension of laboratory defect was not associated with bleeding severity.

An investigation of the spectrum of common and rare inherited coagulation disorders in north-eastern Iran.

BACKGROUND: Health care officials and legislators need accurate data on prevalence and numbers of individuals with bleeding disorders in order to plan and allot their budgets; the manufacturers of coagulation factors also need these data to estimate the amount of factors required to prevent scarcity of these products. MATERIALS AND METHODS: We surveyed the prevalence of haemophilia A, haemophilia B, von Willebrand's disease and rare bleeding disorders in North-Eastern Iran. The survey was done in the period from September 2009 to March 2011. Information was collected from the medical records in three major hospitals and a haemophilia centre; the patients' updated data were obtained by telephone. RESULTS: Overall in the current survey 552 patients with inherited coagulation disorders were identified and their medical records obtained. Of these, 429 (77.5%) had common bleeding disorders (haemophilia A, haemophilia B, von Willebrand's disease), 85 (15.6%) had rare bleeding disorders (deficiency of coagulation factors V, VII, X, XIII, I, XI, combined factor V and VIII deficiency) and 38 (6.9%) had platelet disorders.The commonest bleeding disorders were haemophilia A (n=287, 51.9%), haemophilia B (n=92, 16.6%), von Willebrand's disease (n=50, 9%), factor V deficiency (n=21, 3.8%), factor VII deficiency (n=19, 3.4%), factor X deficiency (n=2, 0.36%), combined factor V and VIII deficiency (n=28, 5.8%), factor XIII deficiency (n=11, 1.99%), factor XI deficiency (n=2, 0.4%), afibrinogenaemia (n=2, 0.36%) and platelet disorders (n=38, 6.9%). DISCUSSION: There is notable population of individuals with bleeding disorders in North-Eastern Iran.

A longitudinal prospective study of bleeding diathesis in Egyptian pediatric patients: single-center experience.

Keeping an updated registry of bleeding disorders is crucial for planning care and documenting prevalence. We aimed to assess the prevalence of various bleeding disorders including rare inherited coagulation and platelet disorders concerning their clinico-epidemiological, diagnostic data and bleeding manifestations severity. Patients suffering from manifestations of bleeding or coagulation disorders presented to Hematology Clinic during 16 years were included and prospectively followed up. Demographics, clinical characteristics, complete blood count, bleeding, prothrombin and activated partial thromboplastin times, platelet aggregation tests and bone marrow aspiration were recorded. Overall 687 patients with bleeding disorders from total 2949 patients were identified. Inherited coagulation defects were found in 27.2%; hemophilia A (70.6%), hemophilia B (13.9%), factor I deficiency (2.3%), factor V deficiency (1.6%), factor X deficiency (4.2%), factor VII deficiency (2.6%), factor XIII deficiency (1.1%), combined factor deficiency (2.1%) and unclassified coagulation disorders in 1.6% of studied patients. Overall 72.7% had diagnosed with platelet disorders; immune thrombocytopenia was the commonest (74.8%), and inherited conditions represent (25.2%) in the following order: Glanzman's thrombasthenia (11.2%), von Willebrand disease (6.6%), Bernard-Soulier syndrome (1%) and Chediak Higashi in 0.4% and unclassified in 6%. Median age of diagnosis of coagulation and platelet disorders were 33 and 72 months. Presenting symptoms of coagulation disorders were: 25.1% post circumcision bleeding, 22.5% ecchymosis, 20.9% hemoarthrosis and 15% epistaxis. Symptoms of rare coagulation disorders were postcircumcision bleeding (20%), bleeding umbilical stump (20%), epistaxis (12%), hemoarthrosis (8%) and hematomas (4%). Presenting symptoms in rare inherited platelet disorders were purpura, ecchymosis, epistaxis and bleeding gums, respectively. Analysis of the clinico-epidemiological data of patients with bleeding disorders is a useful tool for monitoring and improving their quality of care.

Early platelet dysfunction: an unrecognized role in the acute coagulopathy of trauma.

BACKGROUND: Our aim was to determine the prevalence of platelet dysfunction using an end point of assembly into a stable thrombus after severe injury. Although the current debate on acute traumatic coagulopathy has focused on the consumption or inhibition of coagulation factors, the question of early platelet dysfunction in this setting remains unclear. STUDY DESIGN: Prospective platelet function in assembly and stability of the thrombus was determined within 30 minutes of injury using whole blood samples from trauma patients at the point of care using thrombelastography-based platelet functional analysis. RESULTS: There were 51 patients in the study. There were significant differences in the platelet response between trauma patients and healthy volunteers, such that there was impaired aggregation to these agonists. In trauma patients, the median ADP inhibition of platelet function was 86.1% (interquartile range [IQR] 38.6% to 97.7%) compared with 4.2 % (IQR 0 to 18.2%) in healthy volunteers. After trauma, the impairment of platelet function in response to arachidonic acid was 44.9% (IQR 26.6% to 59.3%) compared with 0.5% (IQR 0 to 3.02%) in volunteers (Wilcoxon nonparametric test, p < 0.0001 for both tests). CONCLUSIONS: In this study, we show that platelet dysfunction is manifest after major trauma and before substantial fluid or blood administration. These data suggest a potential role for early platelet transfusion in severely injured patients at risk for postinjury coagulopathy.