Should HLA and HPA-matched platelet transfusions for patients with Glanzmann Thrombasthenia or Bernard-Soulier syndrome be standardized care? A Dutch survey and recommendations.

BACKGROUND: Glanzmann thrombasthenia (GT) and Bernard-Soulier syndrome (BSS) patients require frequent platelet transfusions and hence have an increased risk for alloimmunization against donor Human Leukocyte Antigens (HLA) when no HLA-matching is performed. Knowing that Human Platelet Antigens (HPA) are located on the platelet glycoproteins that can be absent in these patients, preventive HPA-matching may also be considered. Uniform recommendations on this topic lack in transfusion guidelines making standard practice unclear, therefore, we aimed to provide a framework for matched platelet transfusions. STUDY DESIGN AND METHODS: We conducted a targeted literature search and a national survey of Dutch (pediatric) hematologists from July to September 2021. RESULTS: We found 20 articles describing platelet transfusion policies in 483 GT-patients and 29 BSS-patients, both adults and children. Twenty surveys were returned for full analysis. All responders treated patients with platelet disorders, including GT (n = 36 reported) and BSS (n = 29 reported). Of respondents, 75% estimated the risk of antibody formation as "likely" for HLA and 65% for HPA. Formation of HLA antibodies was reported in 5 GT and in 5 BSS-patients, including one child. Fifteen respondents gave preventive HLA-matched platelets in elective setting (75%). Three respondents additionally matched for HPA in GT-patients (15%). Main argument for matched platelet transfusions was preventing alloimmunization to safeguard the effectivity of 'random' donor-platelets in acute settings. CONCLUSION: Elective HLA-matching for GT and BSS-patients is already conducted by most Dutch (pediatric) hematologists. HPA-matching is mainly applied when HPA-antibodies are formed. Based on the current literature and the survey, recommendations are proposed.

Use of crushed tranexamic acid tablets in water for paediatric patients with bleeding disorders.

BACKGROUND: Ε-Aminocaproic acid oral solution (EACA OS) is the only commercially available antifibrinolytic for patients who cannot swallow tablets. Insurance denials and high costs remain barriers to its use. OBJECTIVES: To determine the safety and efficacy of crushed tranexamic acid tablets in water (cTXAw) for children with bleeding disorders. METHODS: We retrospectively reviewed records of children (<10 years) with bleeding disorders who received cTXAw or EACA OS from 1 December 2018, through 31 July 2022, at Mayo Clinic (Rochester, Minnesota). Bleeding outcomes were defined according to ISTH criteria. RESULTS: Thirty-two patients were included (median age, 3 years; male, n = 23). Diagnoses were VWD (n = 17), haemophilia (n = 5), FVII deficiency (n = 3), inherited platelet disorder (n = 4), ITP (n = 2), and combined FV and FVII deficiencies (n = 1). Thirty-two courses of cTXAw (monotherapy 24/32; mean duration 6 days) and fifteen courses of EACA (monotherapy 12/15; mean duration 5 days) were administered. No surgical procedures (n = 28) were complicated by bleeding. Of the 19 bleeding events, 16 had effective haemostasis, two had no reported outcome, and one had no response. cTXAw and EACA were equally effective in preventing and treating bleeding (p value > .1). No patients had adverse effects. Eight of 19 patients (42%) who were initially prescribed EACA OS did not receive it because of cost or insurance denial. The estimated average wholesale price of one treatment was $94 for cTXAw and $905 for EACA OS. CONCLUSIONS: CTXAw appears to be an effective, safe, and low-cost alternative option to EACA OS for young children with bleeding disorders.

ISTH bleeding assessment tool and platelet function analyzer in children with mild inherited platelet function disorders.

OBJECTIVES: To evaluate the diagnostic performance of platelet function analyzer (PFA) and The International Society on Thrombosis and Hemostasis bleeding-assessment-tool (ISTH-BAT) in detecting mild inherited platelet function disorders (IPFDs) in children with suspected bleeding disorders. METHODS: Prospective single-center diagnostic study including consecutive patients <18 years with suspected bleeding disorder and performing a standardized workup for platelet function defects including ISTH-BAT, PFA, platelet aggregation testing, blood smear-based immunofluorescence, and next-generation sequencing-based genetic screening for IPFDs. RESULTS: We studied 97 patients, of which 34 von Willebrand disease (VWD, 22 type-1, 11 type-2), 29 IPFDs (including delta-/alpha-storage pool disease, Glanzmann thrombasthenia, Hermansky-Pudlak syndrome) and 34 with no diagnosis. In a model combining PFA-adenosine diphosphate (ADP), PFA-epinephrine (EPI), and ISTH-BAT overall performance to diagnose IPFDs was low with area under the curves of 0.56 (95% CI 0.44, 0.69) compared with 0.84 (95% CI 0.76, 0.92) for VWD. Correlation of PFA-EPI/-ADP and ISTH-BAT was low with 0.25/0.39 Spearman's correlation coefficients. PFA were significantly prolonged in patients with VWD and Glanzmann thrombasthenia. ISTH-BAT-scores were only positive in severe bleeding disorders, but not in children with mild IPFDs or VWD. CONCLUSION: Neither ISTH-BAT nor PFA or the combination of both help diagnosing mild IPFDs in children. PFA is suited to exclude severe IPFDs or VWD and is in this regard superior to ISTH-BAT in children.

Multicolor flow cytometry in clinical samples for platelet signaling assessment.

Background: Availability of multichannel cytometers and specific commercial antibodies makes flow cytometry a new option to simultaneously assess multiple intracellular platelet signaling pathways for clinical purposes, in small volume of blood or low platelet count. Objectives: To describe a multicolor flow cytometry with fluorescent barcoding technique for screening signaling pathways downstream membrane receptors of major platelet agonists (adenosine diphosphate, thrombin, thromboxane, and collagen). Methods: By comparison with immunoblotting, we first selected the target phosphoproteins, AKT, P38MAPK, LIMK, and SPL76; the times of stimulation; and phosphoflow barcoding conditions. We then performed a clinical study on whole blood of patients without evidence of blood platelet disorder on standard biological screening, consulting for trivial or occasionally provoked bleeds without familial antecedent (bleeding of unknown origin, n = 23) or type-1 von Willebrand disease (n = 9). In addition, we included a small group of patients with definite platelet disorders (Glanzmann thrombasthenia, δ-storage pool deficiency, and immune glycoprotein VI-related disease with granule secretion defect). Results: The range, kinetics, and distribution of fluorescence intensity were established for each agonist-target protein combination. Principal component analysis indicates a correlation in response to a target phosphoprotein (AKT and P38MAPK) to different agonists but no correlation in the response of different target phosphoproteins to the same agonist. The heterogeneity of individual responses in the whole population displayed was analyzed using clustering algorithm. Patients with platelet storage pool deficiency were positioned as lowest responders on the heatmap. Conclusion: In complement of functional tests, this study introduces a new approach for rapid platelet signaling profiling in clinical practice.

Prothrombin consumption as an indicator of hemorrhagic phenotype in mild platelet function disorders.

BACKGROUND: The bleeding risk of patients with mild platelet function disorders is difficult to assess and their phenotype remains ill-explored. AIM: This study was designed to establish a comprehensive biological phenotype of patients with mild platelet function disorders. METHODS: Twenty patients were included with persistent abnormal light transmission aggregometry (LTA). The ISTH bleeding assessment tool (ISTH-BAT) was assessed to identify laboratory analyses associated with an abnormal hemorrhagic score. RESULTS: The majority of patients had defects that might affect Gαi protein signaling pathways or minor abnormalities. No LTA nor flow cytometry parameters were associated with an above-normal hemorrhagic score. However, prothrombin consumption, which corresponds to the ratio of serum residual factor II to plasma residual factor II, was significantly higher (p = .006) in the abnormal ISTH-BAT group (mean = 14%, SD = 6) compared with the normal ISTH-BAT group (mean = 8%, SD 4). Prothrombin consumption was significantly associated with ISTH-BAT score (r = .5287, IC 95% 0.0986-0.7924, p = .0165). CONCLUSION: In this group of patients, there was an association between a pathological bleeding score and increased prothrombin consumption. This test could be used as an additional indicator of platelet function abnormality liable to be related to bleeding risk.

Clinical Cytometry for Platelets and Platelet Disorders.

Clinical flow cytometry tests for inherited and acquired platelet disorders are useful diagnostic tools but are not widely available. Flow cytometric methods are available to detect inherited glycoprotein deficiencies, granule release (secretion defects), drug-induced thrombocytopenias, presence of antiplatelet antibodies, and pharmacodynamic inhibition by antiplatelet agents. New tests take advantage of advanced multicolor cytometers and allow identification of novel platelet subsets by high-dimensional immunophenotyping. Studies are needed to evaluate the value of these new tests for diagnosis and monitoring of therapy in patients with platelet disorders.

Validation of immunofluorescence analysis of blood smears in patients with inherited platelet disorders.

BACKGROUND: Inherited platelet disorders (IPDs) are rare diseases characterized by reduced blood platelet counts and/or impaired platelet function. Recognizing IPDs is advisable but often challenging. The diagnostic tools include clinical evaluation, platelet function tests, and molecular analyses. Demonstration of a pathogenic genetic variant confirms IPDs. We established a method to assess the platelet phenotype on blood smears using immunofluorescence microscopy as a diagnostic tool for IPDs. OBJECTIVES: The aim of the present study was to validate immunofluorescence microscopy as a screening tool for IPDs in comparison with genetic screening. METHODS: We performed a blinded comparison between the diagnosis made using immunofluorescence microscopy on blood smears and genetic findings in a cohort of 43 families affected with 20 different genetically confirmed IPDs. In total, 76% of the cases had inherited thrombocytopenia. RESULTS: Immunofluorescence correctly predicted the underlying IPD in the vast majority of patients with 1 of 9 IPDs for which the typical morphologic pattern is known. Thirty of the 43 enrolled families (70%) were affected by 1 of these 9 IPDs. For the other 11 forms of IPD, we describe alterations of platelet structure in 9 disorders and normal findings in 2 disorders. CONCLUSION: Immunofluorescence microscopy on blood smears is an effective screening tool for 9 forms of IPD, which include the most frequent forms of inherited thrombocytopenia. Using this approach, typical changes in the phenotype may also be identified for other rare IPDs.

Mitochondrial Dysfunction in Trauma-Related Coagulopathy: Is There Causality? Study Protocol for a Prospective Observational Study.

Hemorrhage control often poses a great challenge for clinicians due to trauma-induced coagulopathy (TIC). The pathogenesis of TIC is not completely revealed; however, growing evidence attributes a central role to altered platelet biology. The activation of thrombocytes and subsequent clot formation are highly energetic processes being tied to mitochondrial activity, and the inhibition of the electron transport chain (ETC) impedes on thrombogenesis, suggesting the potential role of mitochondria in TIC. Our present study protocol provides a guide to quantitatively characterize the derangements of mitochondrial functions in TIC. One hundred eleven severely injured (injury severity score ≥16), bleeding trauma patients with an age of 18 or greater will be included in this prospective observational study. Patients receiving oral antiplatelet agents including cyclooxygenase-1 or adenosine diphosphate receptor inhibitors (aspirin, clopidogrel, prasugrel, and ticagrelor) will be excluded from the final analysis. Hemorrhage will be confirmed and assessed with computer tomography. Conventional laboratory markers of hemostasis such as prothrombin time and international normalized ratio will be measured and rotational thromboelastometry (ROTEM) will be performed directly upon patient arrival. Platelets will be isolated from venous blood samples and subjected to high-resolution fluororespirometry (Oxygraph-2k, Oroboros Instruments, Innsbruck, Austria) to evaluate the efficacy of mitochondrial respiration. Oxidative phosphorylation (OxPhos), coupling of the ETC, mitochondrial superoxide formation, mitochondrial membrane potential changes, and extramitochondrial Ca2+-movement will be recorded. The association between OxPhos capacity of platelet mitochondria and numerical parameters of ROTEM aggregometry will constitute our primary outcome. The relation between OxPhos capacity and results of viscoelastic assays and conventional markers of hemostasis will serve as secondary outcomes. The association of the OxPhos capacity of platelet mitochondria upon patient arrival to the need for massive blood transfusion and 24-h mortality will constitute our tertiary outcomes. Mitochondrial dysfunction and its importance in TIC are yet to be assessed for the deeper understanding of this common, life-threatening condition. Disclosure of mitochondria-mediated processes in thrombocytes may reveal new therapeutic targets in the management of hemorrhaging trauma patients, thereby leading to a reduction of potentially preventable mortality. The present protocol was registered to ClinicalTrials.gov on 12 August 2021, under the reference number NCT05004844.

Manejo de la trombastenia de Glanzmann durante el embarazo: reporte de un caso y revisión de la literatura / Management of Glanzmann's thrombasthenia during pregnancy: a case report and literature review

Resumen Objetivo: Reportar el caso de una paciente con trombastenia de Glanzmann que recibe manejo con transfusión de plaquetas con factor VII activado y realizar una revisión de la literatura referente al tratamiento y el pronóstico de esta patología durante la gestación. Método: Se presenta el caso de una paciente de 27 años con trombastenia de Glanzmann y embarazo de 33 semanas, con cesárea al término sin complicaciones. Se realizó una búsqueda en las bases de datos Medline vía PubMed, Lilacs, SciELO y ScienceDirect; se incluyeron reportes de caso, series de casos y revisiones bibliográficas hasta 2021. Resultados: Se encontraron 21 artículos, con 23 casos reportados. Los embarazos se presentaron entre la tercera y la cuarta décadas de la vida, siendo la mayoría pacientes con anticuerpos frente a antígenos plaquetarios (43,4% de los casos). El principal manejo fue con transfusión plaquetaria. Conclusiones: La trombastenia de Glanzmann durante el embarazo es infrecuente y se asocia a eventos hemorrágicos. La presencia de anticuerpos frente a antígenos plaquetarios condiciona el manejo con mayor riesgo de complicaciones perinatales. No tiene un enfoque terapéutico unificado, siendo el de elección la transfusión de plaquetas y como segunda línea el factor VII activado.

Abstract Objective: To report the case of a patient with Glanzmann's thrombasthenia who receives management with platelet transfusion with activated factor VII and a literature review regarding the treatment and prognosis of this pathology during pregnancy. Method: We present the case of a 27 year old patient with Glanzmann's thrombasthenia and a 33-week pregnancy, with a cesarean section at term without complications. Medline databases were searched via PubMed, Lilacs, SciELO and ScienceDirect; case reports, case series and bibliographic reviews were included until 2021. Results: A total of 21 articles were found, with 23 reported cases; the pregnancies occurred between the third and fourth decades of life, the majority being patients with anti-platelet antigen antibodies in 43.4% of the cases. The main management was with platelet transfusion. Conclusions: Glanzmann's thrombasthenia during pregnancy is rare and is associated with hemorrhagic events. The presence of anti-platelet antigen antibodies conditions management with a higher risk of perinatal complications. It does not have a unified therapeutic approach, with platelet transfusion being the management of choice and activated factor VII as second line.

[Thrombosis with Thrombocytopenia Syndrome following adenovirus vector-based vaccines to prevent COVID-19: epidemiology and clinical presentation in Spain]. / Síndrome de Trombosis con Trombocitopenia asociado a vacunas de adenovirus frente a la COVID-19: epidemiología y presentación clínica de la serie española.

BACKGROUND: We describe the epidemiological and clinical characteristics of thrombosis with thrombocytopenia syndrome (TTS) cases reported in Spain. METHODS: We included all venous or arterial thrombosis with thrombocytopenia following adenovirus vector-based vaccines (AstraZeneca or Janssen) to prevent COVID-19 disease between February 1st and September 26th, 2021. We describe the crude rate and the standardized morbidity ratio. We assessed the predictors of mortality. RESULTS: Sixty-one cases were reported and 45 fulfilled eligibility criteria, 82% women. The crude TTS rate was 4/1,000,000 doses and 14-15/1,000,000 doses between 30-49 years. The number of observed cases of cerebral venous thrombosis was 6-18 higher than the expected in patients younger than 49 years. Symptoms started 10 (interquartile range (IQR): 7-14) days after vaccination. Eighty percent (95% confidence interval (CI): 65-90%) had thrombocytopenia at the time of the emergency department visit, and 65% (95% CI: 49-78%) had D-dimer >2000 ng/mL. Patients had multiple location thrombosis in 36% and fatal outcome in 24% cases. A platelet nadir <50,000 /µL (odds ratio (OR): 7.4; CI 95%: 1.2-47.5) and intracranial hemorrhage (OR: 7.9; IC95%: 1.3-47.0) were associated with fatal outcome. CONCLUSION: TTS must be suspected in patients with symptoms 10 days after vaccination and thrombocytopenia and/or D-dimer increase.

Platelet function testing: Current practice among clinical centres in Northern Europe.

INTRODUCTION: Platelet function tests are used to screen and diagnose patients with possible inherited platelet function defects (IPFD). Some acquired platelet dysfunction may be caused by certain drugs or comorbidities, which need to be excluded before testing. AIMS: To identify current practice among centres performing platelet function tests in Northern Europe. METHODS: A total of 14 clinical centres from Sweden (six), Finland (two), Denmark (two), Norway (one), Estonia (two) and Iceland (one) completed the survey questionnaire, the population capture area of about 29.5 million. RESULTS: Six of the 14 (42.8%) centres providing platelet function assessment represent comprehensive treatment centres (EUHANET status). A Bleeding score (BS) or ISTH bleeding assessment tool (ISTH BAT score) is evaluated in 11/14 (78.6%) centres and family history in all. Five/14 centres (35.7%) use structured preanalytical patient instructions, and 10/14 (71.4%) recorded questionnaire on the preassessment of avoidance of any drugs or natural products affecting platelet functions. Preliminary investigations of screening tests of coagulation are performed in 10/14 (71.4%), while in 4/14 (28.6%), the diagnostic work-up of IPFD and von Willebrand disease (VWD) is performed simultaneously. The work-up of IPFD includes peripheral blood smear in 10/14 (71.4%), platelet aggregometry in all, flow cytometry in 10/14 (71.4%) and Platelet Function Analysis (PFA) in 3/11 (28.6%). Molecular genetic diagnosis is available in 7/14 (50%) centres. CONCLUSIONS: The considerable variability in the current practice illustrates the need for harmonization between the Northern European centres according to the international registers (i.e. EUHASS) and IPFD guidelines (ISTH, EHA).

Diagnosis of rare bleeding disorders.

Rare bleeding disorders result in significant morbidity but are globally underdiagnosed. Advances in genomic testing and specialist laboratory assays have greatly increased the diagnostic armamentarium. This has resulted in the discovery of new genetic causes for rare diseases and a better understanding of the underlying molecular pathology.

High-power laser for periodontal surgery in a patient with glanzmann thrombasthenia / Laser de alta potência para cirurgia periodontal em paciente com trombastenia de glanzmann

Background: Glanzmann thrombasthenia (GT) is a rare autosomal recessive disorder characterized by platelet function impairment. Considering that the oral cavity is highly vascularized and performing some local hemostatic maneuvers may be difficult, GT patients are at high risk for hemorrhage related to invasive oral procedures. This study aimed to present an alternative method for periodontal surgery in a young GT patient. Case Report: A 15-year-old female GT patient with a recent history of excessive bleeding following dental surgeries was referred to a public dental center, presenting gingival hyperplasia. The procedure was performed using a high-power laser (HPL), and except for local anesthesia with epinephrine, no further hemostatic agent was necessary. Conclusion: According to the case, the HPL seems to be an efficient tool for preventing perioperative bleeding in GT patients submitted to minor oral surgeries(AU)

Introdução: A trombastenia de Glanzmann (TG) é uma doença autossômica recessiva rara caracterizada por comprometimento da função plaquetária. Tendo em vista que a cavidade oral é altamente vascularizada e a realização de algumas manobras hemostáticas locais pode ser difícil, pacientes com TG apresentam alto risco de hemorragia relacionada a procedimentos orais invasivos. Este artigo teve como objetivo apresentar uma técnica alternativa para cirurgia periodontal em um paciente jovem com TG. Relato de Caso: Paciente com TG, sexo feminino, 15 anos, com história recente de sangramento excessivo relacionado a cirurgias odontológicas prévias, foi encaminhada a um centro odontológico público apresentando hiperplasia gengival. O procedimento de remoção foi realizado com laser de alta potência e, com exceção da anestesia local com epinefrina, nenhum outro agente hemostático foi necessário. Conclusão: De acordo com o caso, o laser de alta potência parece ser uma ferramenta eficiente na prevenção de sangramento perioperatório em pacientes com TG submetidos a pequenas cirurgias orais(AU)

Hematomas en un lactante de 3 meses. La importancia del diagnóstico diferencial / Bruising in a 3-month-old infant. The importance of differential diagnosis

Introducción: el motivo de consulta en Pediatría puede o no estar relacionado con patología subyacente importante, la exploración física exhaustiva en busca de signos de alarma es fundamental. Caso clínico: presentamos el caso de un lactante de 3 meses en el que durante una visita a nuestro servicio de urgencias se detectaron hematomas. Con la sospecha inicial de un posible maltrato, se realizaron varios estudios y el diagnóstico final fue el de tromboastenia de Glanzmann. Discusión: la tromboastenia de Glanzmann es un trastorno hereditario de la función plaquetaria. Se trata de una enfermedad muy poco frecuente de herencia autosómica recesiva. El hemograma y las pruebas de coagulación básicas son normales y el diagnóstico se realiza mediante análisis de pruebas de función plaquetaria y agregometría por transmisión de luz. Conclusiones: la presencia de hematomas en un lactante de corta edad constituye siempre un motivo de investigación. Aunque por su incidencia el maltrato infantil constituye una de las principales causas, no debemos olvidar que se trata de un diagnóstico de exclusión, por lo que deberán descartarse otras patologías en función de los signos y síntomas que presente el paciente (AU)

Introduction: the presenting complaint in a paediatric visit may or not be related to an important underlying disease, so performing an exhaustive physical examination in search of warning signs is essential.Clinical case: we present the case of a 3-month-old infant in whom little bruises in thorax were detected during a visit to our emergency room. Several tests were performed to assess the initial suspicion of physical child abuse, after which the final diagnosis was Glanzmann thrombasthenia.Discussion: Glanzmann thrombasthenia is an inherited platelet function disorder. It is a rare disorder with autosomal recessive inheritance. Complete blood count and basic coagulation tests are normal, and the diagnosis is performed by platelet function testing and light transmission aggregometry.Conclusions: the presence of bruises in infants is always a reason for investigation. Although, given its frequency, child abuse is one of the leading causes, we must not forget that it is a diagnosis of exclusion. Therefore, other pathologies should be ruled out based on the presenting signs and symptoms. (AU)

Concurrencia entre el síndrome de Guillain-Barré y púrpura trombocitopénica inmune posiblemente inducidos por COVID-19 prolongado / Concurrence between Guillain-Barré syndrome and immune thrombocytopenic purpura possibly induced by long COVID-19

RESUMEN Durante la infección aguda por el SARVS-CoV-2 se produce una desregulación del sistema inmune que puede durar hasta ocho meses después de controlado el cuadro agudo. Esto, sumado a otros factores, posiblemente este asociado con un aumento del riesgo de aparición y concurrencia de enfermedades autoinmunes. La aparición simultanea del síndrome de Guillain-Barré (SGB) y púrpura trombocitopénica (PTI) se ha reportado poco en la literatura, y el SGB raramente se asocia con otra enfermedad autoinmune. Presentamos el caso de un varón que luego de un mes de tener un cuadro agudo de COVID-19 moderado, presentó concurrentemente SGB y PTI con respuesta adecuada al tratamiento.

ABSTRACT During acute SARS-CoV-2 infection, there is persistent deregulation of the immune system that can last up to 8 months after the acute condition is controlled. This, added to other factors, is possibly associated with an increased risk of the appearance and concurrence of autoimmune diseases. The simultaneous occurrence of GBS and ITP has been rarely reported in the literature, and GBS is rarely associated with another autoimmune disease. We present the case of a man who, one month after his recovery from acute moderate COVID-19, presented concurrent GBS and ITP with an adequate response to treatment.

Dialysis-related thrombocytopenia: a case report / Plaquetopenia relacionada à hemodiálise: relato de caso

Abstract Thrombocytopenia is frequently observed in hemodialysis patients, and its correct investigation and control remain a challenge. It is estimated that during the hemodialysis session there is a drop of up to 15% in the platelet count, with recovery after the end of treatment. This reduction in platelets is due to platelet adhesion and complement activation, regardless of the membrane material. Several studies with platelet surface markers demonstrate increased platelet activation and aggregation secondary to exposure to cardiopulmonary bypass. This case report describes a patient on hemodialysis who developed severe thrombocytopenia during hospitalization. Investigation and exclusion of the most common causes were carried out: heparin-related thrombocytopenia, adverse drug reaction, hypersplenism, and hematological diseases. Afterwards, the possibility of hemodialysis-related thrombocytopenia was raised, since the fall was accentuated during the sessions with partial recovery after the dialyzer change. Attention to the sterilization method and dialyzer reuse must be considered for correction. In the current case, reusing the dialyzer minimized the drop in platelet counts associated with hemodialysis.

Resumo Plaquetopenia é frequentemente observada em pacientes em hemodiálise, e sua correta investigação e controle permanecem um desafio. Estima-se que, durante a sessão de hemodiálise, ocorra queda de até 15% da contagem de plaquetas, com recuperação após o término do tratamento. Essa queda de plaquetas é decorrente de adesão plaquetária e ativação do complemento, independentemente do material da membrana. Vários estudos com marcadores de superfície plaquetária demonstram aumento da ativação e agregação plaquetária secundários à exposição à circulação extracorpórea. Este relato de caso mostra um paciente dialítico que evoluiu com plaquetopenia severa durante internação. Realizada investigação e exclusão de causas mais comuns: plaquetopenia relacionada à heparina, reação adversa a medicamentos, hiperesplenismo e doenças hematológicas, foi então aventada a possibilidade de plaquetopenia relacionada à hemodiálise após observação de que a queda se acentuava durante as sessões de hemodiálise com recuperação parcial após. Mudança do dialisador, atenção ao método de esterilização e realização do reuso devem ser consideradas para correção. No presente caso, a utilização do reuso minimizou a plaquetopenia associada a hemodiálise.

Stability and utility of flow cytometric platelet activation tests: A modality to bridge the gap between diagnostic demand and supply.

Light transmission aggregometry (LTA) is the gold standard for the diagnosis of platelet function disorders (PFDs). The requirement of customized aggregometer, large blood volume, normal platelet count and processing within 4 hours of venipuncture for LTA makes platelet function testing inaccessible to wider population. Flow cytometric platelet activation test (PACT) may overcome these limitations. This study compares the performance of PACT with LTA, characterizes diagnostic patterns of PFDs on PACT and assesses the stability of PACT beyond 4 hours of venipuncture in controls (n = 5) at different temperature conditions. LTA and PACT were performed in 121 healthy controls and 66 patients with suspected PFD. PACT had excellent agreement (kappa = 0.93) with LTA and 94.1% sensitivity, 98.5% specificity. PACT had distinct patterns in Bernard Soulier Syndrome (n = 10), Glanzmann Thrombasthenia (n = 24), δ-granule disorder (n = 7), and other PFDs (n = 12). PACT could assess platelet function in patients (14%) with thrombocytopenia/lipemia wherein LTA was inconclusive. PACT was stable up to 24 hours in samples stored/transported at 2-8◦C. The results of utility and stability are only valid for the specific markers, agonist concentrations, and conditions investigated in this paper. PACT is a useful modality for the diagnosis of PFD, especially in children, thrombocytopenia cases or in the setup where an aggregometer is not readily available.

Patient-reported outcomes in autosomal inherited bleeding disorders: A systematic literature review.

AIM: Currently, it is unknown which patient-reported outcomes are important for patients with autosomal inherited bleeding disorders. Therefore, the purpose of this study is to systematically review the available literature assessing patient-reported outcomes and their measurement methods in autosomal inherited bleeding disorders. METHODS: The Embase, Medline ALL, Web of Science Core Collection, Cochrane Central Register of Controlled Trails and Google Scholar databases were searched from inception until 14 August 2020. Studies on patient-reported outcomes in patients with von Willebrand disease, inherited platelet function disorders and coagulation factor deficiencies were included. RESULTS: Twenty-one articles met the inclusion criteria. Three studies were assessed as having poor quality, and therefore a high risk of bias. Nineteen studies had fair quality rating. Different measurements methods were used, ranging from predefined to self-developed questionnaires. The majority of included studies focused on von Willebrand disease. Patients with von Willebrand disease reported lower health-related quality of life compared to the general population. Overall, this trend was especially visible in the following domains: vitality, physical and social functioning and pain. Women with inherited bleeding disorders scored lower on health-related quality of life compared to men, especially women with heavy menstrual bleeding. Patients with joint bleeds or heavy menstrual bleeding reported an increased level of pain. CONCLUSION: Patients with autosomal inherited bleeding disorders report lower health related quality of life, especially those with joint bleeds or heavy menstrual bleeding. Numerous measurement methods are used in patients with autosomal inherited bleeding disorders, highlighting the need for studies using established, standardized measurement methods.

A Novel Likely Pathogenic Variant in the RUNX1 Gene as the Cause of Congenital Thrombocytopenia.

Introduction: Heterozygous pathogenic and likely pathogenic sequence variants in the RUNX1 (Runt-related Transcription Factor 1) gene are a common genetic cause of decreased platelet count and/or platelet dysfunction and an increased risk of developing myelodysplasia and acute myeloid leukemia. The majority of causative variants are substitutions, which rarely occur de novo. The aim of this case report is to present a patient with congenital thrombocytopenia caused by a deletion variant in exon 9 in the RUNX1 gene. Case report: A one-month-old male infant was admitted to the Clinical Hospital Center Rijeka because of anemia and thrombocytopenia verified in the course of an acute viral infection. During follow-up, he occasionally had petechiae and ecchymoses on the lower extremities after mild trauma, with no other symptoms. The patient had persistent slightly decreased values of platelets with normal morphology, but with pathological aggregation with adrenaline and adenosine diphosphate. Due to the unclear etiology of persistent mild thrombocytopenia, he was referred for genetic testing at the age of five. Genomic DNA was isolated from the patient's peripheral blood and whole-exome sequencing was performed using the next-generation sequencing method. A heterozygous frameshift variant, c.1160delG (NM_001754.4), was identified in exon 9. The variant is classified as likely pathogenic. Conclusion: To the best of our knowledge, the heterozygous variant c.1160delG in the RUNX1 gene was first described in our patient. Although pathogenic variants in the RUNX1 genes are very rare, persistently low platelet counts of unclear etiology should raise suspicion of an underlying genetic disorder.

Invasive procedures in the oral cavity of individuals with Bernard-Soulier syndrome: An integrative review.

AIM: Bernard-Soulier syndrome (BSS) is an inherited bleeding disorder characterized by macroplatelets and thrombocytopenia, prolonged bleeding time, and a prevalence of less than 1 in 1,000,000. In view of the recognition of the risk of bleeding and the management of daily surgical practice in these patients, adequate strategies are necessary to provide the safest care. This article aims to perform an integrative review of the literature on the management of invasive procedures in the oral cavity of individuals with BSS. METHOD: The PubMed/Medline and LILACS databases were searched using Boolean operators related to BSS, bleeding disorders, and oral care. RESULTS: As a result, only five articles with the main theme were included: one letter to the editor and four case reports, described chronologically as to date of publication, classification of the article, and medical/odontological measures taken. CONCLUSION: We conclude with this review the need for adequate knowledge of surgeons regarding coagulation disorders and the need to discuss and plan procedures with the hematology team, as well as the importance of the notion of management of possible complications resulting from invasive treatments in the oral cavity of patients with BSS.