Description of therapeutic strategies in severe systemic lupus erythematosus-associated immune thrombocytopenia: a retrospective cohort study of response and relapse.

OBJECTIVES: To describe the response and relapse of severe thrombocytopenia in patients with systemic lupus erythematosus (SLE) with different treatments. METHOD: We performed a retrospective cohort study, which included SLE patients who were hospitalized for thrombocytopenia of less than 30,000/µL platelets, from January 2012 to December 2021. Demographic and clinical information was obtained from clinical records. Kaplan-Meier and logrank test were performed. RESULTS: Forty-seven patients, mostly women (83%) with a median age of 31 years, were included in the study. Eight patients (17%) relapsed within a median period of 35.7 weeks. Initial acute treatment with prednisone at 1 mg/kg/day was as effective as glucocorticoid pulses. However, induction treatment with cyclophosphamide (CYC) had the lowest remission rate (43%, p = 0.034). There was no significant difference in relapse-free survival (RFS) among the acute glucocorticoid treatments. CYC induction was associated with lower RFS compared to rituximab (RTX) (CYC 43.6 weeks vs. RTX 51.8 weeks, p = 0.040) or azathioprine (AZA) (CYC 43.6 weeks vs. AZA 51.2 weeks, p = 0.024). Administration of antimalarials was associated with longer RFS (51.6 weeks vs. 45.0 weeks, p = 0.021). Factors such as antiphospholipid syndrome, IgG anti-ß2 glycoprotein I positivity, renal and additional hematologic SLE activity during follow-up significantly reduced RFS. CONCLUSIONS: Despite similar response of acute glucocorticoid regimens, induction therapy with AZA or RTX resulted in a longer RFS compared to CYC. Adding an antimalarial also improved RFS. Our study provides evidence that may help develop better treatment strategies for severe thrombocytopenia in SLE patients. Key Points • Induction therapy with azathioprine or rituximab provided longer relapse-free survival in SLE thrombocytopenia compared with cyclophosphamide. • Antimalarial administration was associated with longer relapse-free survival in SLE thrombocytopenia. • Antiphospholipid syndrome, IgG anti-ß2 glycoprotein I positivity, as well as renal and additional hematologic SLE activity during follow-up, decreased relapse-free survival.

The meaning of non-criteria clinical manifestations in a real-life primary antiphospholipid syndrome cohort.

OBJECTIVES: We aimed to evaluate the prevalence of non-criteria clinical features in patients with primary antiphospholipid syndrome (APS), and to assess their relationship to thrombosis and damage. METHODS: We retrospectively included 177 primary APS patients, and/or patients who only achieved the serological Sydney criteria but had thrombocytopenia and/or haemolytic anaemia. We registered demographics, serology, treatment, thrombotic/obstetric manifestations and non-criteria clinical manifestations (cutaneous, haematologic, renal, heart valve disease, and neurological). We scored the DIAPS and a modified SLICC index. We used logistic regression and reported OR with 95% CI. RESULTS: 78% were women with a median follow-up of 6.7 years. Thrombosis was found in 74% of patients, 29.3% had obstetric features, and 64% had non-criteria clinical manifestations. The frequency of the non-criteria clinical manifestation was: haematologic 40.1%, cutaneous 20.9%, neurologic 18%, cardiac 5% and renal 4.5%. Non-criteria features were associated with LA (OR 2.3, 95% 1.03-5.1) and prednisone use (OR 8.2, 95% CI 1.7-39.3). A DIAPS score ≥1 was associated with thrombosis (OR 53.1, 95% CI 17.8-15.2), prednisone use (OR 0.27, CI 95% 0.09-0.83) and neurological involvement (OR 6.4, 95% CI 1.05-39.8); whereas a modified SLICC ≥ 1 with thrombosis (OR 10.2; IC 95% 4.43-26.1), neurological involvement (OR 6.4, 95%CI 1.05-39.8), obstetric features (OR 0.32 CI 95% 0.12-0,81) and cutaneous features (OR 5.3, CI 95% 1.4-19), especially livedo reticularis (OR 5.45; IC 95% 1.49-19.8). CONCLUSIONS: Non-criteria clinical manifestations are common and associated with LA. Among them, neurologic involvement and the presence of livedo were associated with damage accrual.

Are accessory spleen screening and resection in refractory immune cytopenia an effective strategy or a waste of resources?

Splenectomy remains an effective treatment for refractory immune cytopenia (RIC), which encompasses immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Accessory spleens (AS) have been described without identifying specific risk factors. We retrospectively analyzed patients with RIC after splenectomy who underwent splenic scintigraphy (SS) at our institution. Seventy-one patients were included. Sixty-two patients had ITP, five had AIHA, and four had Evans syndrome. Seventy-five percent (n = 53) were women. Eleven patients (15.5%) had an AS detected by SS. A complete response (CR) to first-line steroids (odds ratio (OR) 5.75, 95% confidence interval (CI) 1.37-24.14, p = 0.017) and the absence of Howell-Jolly bodies (HJB) in peripheral blood smear (PBS) (OR 11.37, 95% CI 2.70-47.85, p = 0.001) were found to be risk factors. Patients with both elements had a higher rate of AS (83.3%) when compared to those with one or no factors (p < 0.001). Eight patients (73%) underwent an accessory splenectomy: seven (87.5%) achieved a CR, and none had perioperative complications. The presence of HJB in PBS changed from 25 to 87.5% after accessory splenectomy. We recommend the search for an AS via SS in patients with RIC due to ITP, who had a CR to corticosteroids and the absence of HJB in PBS. Accessory splenectomy is a safe and effective procedure.

Risk Factors of Thrombocytopenia After Cardiac Surgery with Cardiopulmonary Bypass.

INTRODUCTION: Postoperative thrombocytopenia is common in cardiac surgery with cardiopulmonary bypass, and its risk factors are unclear. METHODS: This retrospective study enrolled 3,175 adult patients undergoing valve surgeries with cardiopulmonary bypass from January 1, 2017 to December 30, 2018 in our institute. Postoperative thrombocytopenia was defined as the first postoperative platelet count below the 10th quantile in all the enrolled patients. Outcomes between patients with and without postoperative thrombocytopenia were compared. The primary outcome was in-hospital mortality. Risk factors of postoperative thrombocytopenia were assessed by logistic regression analysis. RESULTS: The 10th quantile of all enrolled patients (75×109/L) was defined as the threshold for postoperative thrombocytopenia. In-hospital mortality was comparable between thrombocytopenia and non-thrombocytopenia groups (0.9% vs. 0.6%, P=0.434). Patients in the thrombocytopenia group had higher rate of postoperative blood transfusion (5.9% vs. 3.2%, P=0.014), more chest drainage volume (735 [550-1080] vs. 560 [430-730] ml, P<0.001), and higher incidence of acute kidney injury (12.3% vs. 4.2%, P<0.001). Age > 60 years (odds ratio [OR] 2.25, 95% confidence interval [CI] 1.345-3.765, P=0.002], preoperative thrombocytopenia (OR 18.671, 95% CI 13.649-25.542, P<0.001), and cardiopulmonary bypass time (OR 1.088, 95% CI 1.059-1.117, P<0.001) were positively independently associated with postoperative thrombocytopenia. Body surface area (BSA) (OR 0.247, 95% CI 0.114-0.538, P<0.001) and isolated mitral valve surgery (OR 0.475, 95% CI 0.294-0.77) were negatively independently associated with postoperative thrombocytopenia. CONCLUSION: Positive predictors for thrombocytopenia after valve surgery included age > 60 years, small BSA, preoperative thrombocytopenia, and cardiopulmonary bypass time. BSA and isolated mitral valve surgery were negative predictors.

Trombocitopenia inmune trombótica inducida por Vacuna / Vaccine-induced thrombotic immune thrombocytopenia

¿QUÉ ES LA TROMBOCITOPENIA INMUNE TROMBÓTICA INDUCIDA POR VACUNAS?: La trombocitopenia trombótica inmunitaria inducida por vacunas (VITT, por sus siglas en inglés) se define como un síndrome clínico caracterizado por todas las anomalías de laboratorio y radiológicas descritas a continuación que ocurren en individuos de 4 a 30 días después de la vacunación con Ad26.COV2 (Johnson & Johnson) o ChAdOx1 nCoV-19(Oxford-A. Zeneca). Ambas vacunas comparten la misma plataforma viral recombinante de adenovirus tipo 26 de chimpancé no replicativo. ¿CON QUE FRECUENCIA APARECE ESTE SÍNDROME?: La incidencia de este cuadro de trombosis (VITT) se estima en 14,2 por millón de dosis (1,42/100.000). Se han reportado 419 casos de eventos tromboembólicos con trombocitopenia simultánea en el resumen semanal del MHRA (Medicines and Healthcare products Regulatory Agency) publicado el 22 de septiembre del 2021. 3 Cabe mencionar que el riesgo de Trombosis venosa central y periférica posterior a la infección por Covid-19 es significativamente superior, ( 42,8 y 392,3 millón habitantes, respectivamente) representando un riesgo mayor. ¿EXISTE RELACIÓN CON TROMBOFILIA u OTRAS CONDICIONES COMO ESTAR ANTICOAGULADO QUE DETERMINAN CONTRAINDICACIÓN PARA RECIBIR ESTAS VACUNAS?: Los casos descriptos y su fisiopatología no se relacionan con el antecedente de trombofilia o eventos tromboembólicos previos. Est evento nuevo parece ocurrir por un mecanismo inmune gatillado por el vector viral. Por lo tanto, estos pacientes no deberían presentar mayor riesgo de un evento trombótico por la vacuna y deben recibir la vacuna para COVID-19, aún la del laboratorio Astra Zeneca disponible en el país. Esta sugerencia está sustentada por la CoNaSeVa6 .Tampoco el hecho de estar previamente anticoagulado con anticoagulantes orales debido a un evento trombótico venoso o como profilaxis de trombo-embolismo de origen cardio-embólico determina ninguna contraindicación para cualquiera de las vacunas y se pueden administrar enforma intramuscular en el músculo deltoides sin riesgo. ¿QUÉ CONDUCTA SE PUEDE RECOMENDAR A LOS EQUIPOS DE SALUD SEGÚN LA EVIDENCIA DISPONIBLE?: El NICE de Reino Unido ha emitido una recomendación estableciendo que debido a que la trombocitopenia trombótica inmunitaria inducida por vacunas ( VITT) es una afección nueva, hay "evidencia limitada disponible para informar el manejo clínico, la identificación y el manejo de la afección está evolucionando rápidamente a medida que la definición de caso se vuelve más clara." 8 . Ha publicado una guía en un entorno de actualización continua (MagiCAPP)9 que a la fecha de este informe establece pautas muy acotadas en el tratamiento del cuadro, como el uso de anticoagulantes no heparínicos (orales directos); intervenciones más complejas (transfusión, uso de fibrinógeno) requieren considerar en todo momento la condición basal del paciente y el contexto de atención del mismo (complejidad asistencial). La CONASEVA recomienda la consulta con especialista y la no administración de plaquetas. Además, el Ministerio de Salud de Mendoza indica que todo evento caracterizado de este tipo debe ser informado como Evento adverso de manera inmediata en las fichas de notificación disponibles en cada establecimiento.

Involvement of von Willebrand factor and botrocetin in the thrombocytopenia induced by Bothrops jararaca snake venom.

Patients bitten by snakes consistently manifest a bleeding tendency, in which thrombocytopenia, consumption coagulopathy, mucous bleeding, and, more rarely, thrombotic microangiopathy, are observed. Von Willebrand factor (VWF) is required for primary hemostasis, and some venom proteins, such as botrocetin (a C-type lectin-like protein) and snake venom metalloproteinases (SVMP), disturb the normal interaction between platelets and VWF, possibly contributing to snakebite-induced bleedings. To understand the relationship among plasma VWF, platelets, botrocetin and SVMP from Bothrops jararaca snake venom (BjV) in the development of thrombocytopenia, we used (a) Wistar rats injected s.c. with BjV preincubated with anti-botrocetin antibodies (ABA) and/or Na2-EDTA (a SVMP inhibitor), and (b) VWF knockout mice (Vwf-/-) injected with BjV. Under all conditions, BjV induced a rapid and intense thrombocytopenia. In rats, BjV alone reduced the levels of VWF:Ag, VWF:CB, high molecular weight multimers of VWF, ADAMTS13 activity, and factor VIII. Moreover, VWF:Ag levels in rats that received BjV preincubated with Na2-EDTA and/or ABA tended to recover faster. In mice, BjV caused thrombocytopenia in both Vwf-/- and C57BL/6 (background control) strains, and VWF:Ag levels tended to decrease in C57BL/6, demonstrating that thrombocytopenia was independent of the presence of plasma VWF. These findings showed that botrocetin present in BjV failed to affect the extent or the time course of thrombocytopenia induced by envenomation, but it contributed to decrease the levels and function of plasma VWF. Thus, VWF alterations during B. jararaca envenomation are an ancillary event, and not the main mechanism leading to decreased platelet counts.

Trombocitopenia neonatal: Revisión. II. Trombocitopenias no inmunes; transfusión de plaquetas / Neonatal thrombocytopenia: A review.II. Non-immune thrombocytopenia; platelet transfusion

Las trombocitopenias de causa no inmunológica son ocasionadas por múltiples patologías; las más frecuentes son las debidas a infecciones extra- o intrauterinas y las secundarias a otras patologías involucradas en la interrelación niño-placenta-madre. En este segundo artículo, se enumeran sus causas y se describen en detalle las distintas patologías. La transfusión de plaquetas es ampliamente utilizada en neonatología, tanto para tratamiento como para profilaxis de hemorragias. Sin embargo, no hay aún consenso generalizado sobre el umbral de recuento plaquetario conveniente para indicar la transfusión ni sobre sus reales indicaciones. Se comentan artículos recientes sobre las distintas estrategias propuestas. Se enfatiza la discusión sobre los múltiples efectos adversos de las transfusiones de plaquetas, cuyo conocimiento está cambiando el paradigma relativo a sus indicaciones, lo que sugiere que se debe aplicar una política mucho más restrictiva al respect

Non-immune thrombocytopenia is caused by multiple pathologies; the most common causes are extra- or intrauterine infections, whereas secondary cases result from other pathologies involved in the fetal-placental-maternal interface. This second article lists its causes and provides details of the different pathologies. Platelet transfusion is widely used in neonatology, both as treatment and as bleeding prophylaxis. However, there is no general consensus about the platelet count threshold that is convenient to indicate a transfusion or actual indications. Recent articles are commented regarding the different proposed strategies. The emphasis is on discussing the multiple adverse effects of platelet transfusions because knowledge about them is changing the paradigm for indications, suggesting that a much more restrictive policy is required

Ruxolitinib for Severe COVID-19-Related Hyperinflammation in Nonresponders to Steroids.

INTRODUCTION: Currently, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is a major public health problem worldwide. Although most patients present a mild infection, effective strategies are required for patients who develop the severe disease. Anti-inflammatory treatment with JAK inhibitors has been considered in SARS-CoV-2. METHODS: In this study, we presented our experience in a group of severe SARS-CoV-2 Chilean patients. This prospective study was performed on consecutive patients presenting severe respiratory failure owing to COVID-19 or high-risk clinical condition associated with SARS-CoV-2, and who were treated with ruxolitinib for management of associated inflammation. Overall, 18 patients presenting SARS-CoV-2 viral-induced hyperinflammation were treated with ruxolitinib, with 16 patients previously treated with steroids, 4 with tocilizumab, and 3 with both treatments. RESULTS: Ten patients evolved with favorable response, including 7 patients admitted with severe respiratory failure (PaFi less than 200 mm Hg in high-flow nasal cannula), presenting complete regression of hyperinflammation, regression of the lung lesions, and subsequent discharge. In the remaining 8 patients, 25% showed reduced inflammation, but early discharge was not achieved owing to the slow evolution of respiratory failure. Unfortunately, 3 patients demonstrated a severe respiratory failure. The early initiation of ruxolitinib was found to be associated with better clinical evolution (p < 0.005). CONCLUSION: In this study, ruxolitinib resolved hyperinflammatory state in 55% of the patients, regardless of the previous steroid or tocilizumab therapy. Unfortunately, few patients demonstrated severe evolution despite ruxolitinib therapy. Notably, the treatment starting time appears to play an important role in achieving good outcomes. Further validation in randomized controlled trials is crucial.

Diagnosis and management of coronavirus disease-associated immune thrombocytopenia: a case series.

Data on health problems and fatal complications associated with coronavirus disease (COVID-19) have consistently been reported. Although immune thrombocytopenia has been associated with multiple viral infections, only few studies have shown its association with COVID-19. Here, we have reported a case series of two cases pertaining to patients diagnosed with COVID-19-associated immune thrombocytopenia, elaborating on the clinical course, management, and response to treatment.

Signos de alarma en pacientes con paludismo importado por Plasmodium falciparum / Warning signs in patients with imported Plasmodium falciparum malaria

Introducción: El paludismo es una enfermedad febril aguda potencialmente mortal causada por parásitos que se transmiten al ser humano por la picadura de mosquitos del género Anopheles. De los 214 millones de casos de paludismo registrados en 2016, la mayoría de ellos se producen en niños menores de cinco años en África subsahariana. La mortalidad está dada por la presencia de sus complicaciones que deben ser detectadas y tratadas precozmente. Objetivo: Identificar la presencia de signos de alarma, y determinar su relación con otras variables clínicas y de laboratorio. Métodos: Se realizó un estudio descriptivo de 47 pacientes adultos con paludismo por Plasmodium falciparum importado, ingresados en el Departamento de Medicina del Instituto de Medicina Tropical Pedro Kourí, desde enero de 2016 a diciembre de 2018. Los datos fueron procesados en una base de datos en Microsoft Excel y luego analizados en el programa estadístico SPSS 11,5. Resultados: Predominaron los pacientes del sexo masculino, con una media de edad de 35,9 años. Fue significativa la relación existente entre los signos de alarma y la severidad del cuadro clínico, la hiperparasitemia, el supuesto estado no inmune de los pacientes, trombocitopenia y la demora en el ingreso. La respuesta al tratamiento es excelente con los esquemas combinados utilizados a base de quinina. Conclusiones: Los signos de alarma, dentro de los cuales podemos incluir la trombocitopenia, constituyen elementos importantes para poder prevenir futuras complicaciones(AU)

Introduction: Malaria is an acute potentially fatal febrile disease caused by parasites transmitted to humans through the bite of mosquitoes from the genus Anopheles. Most of the 214 million malaria cases reported in the year 2016 were children aged under five years from Sub-Saharan Africa. Mortality is due to the presence of complications which should be detected and treated timely. Objective: Identify the presence of warning signs and determine their relationship to other clinical and laboratory variables. Methods: A descriptive study was conducted of 47 adult patients with imported Plasmodium falciparum malaria admitted to the Medicine Department of Pedro Kourí Tropical Medicine Institute from January 2016 to December 2018. The data obtained were processed in a Microsoft Excel database and then analyzed with the statistical software SPSS 11.5. Results: Male patients prevailed, with a mean age of 35.9 years. A significant relationship was found between warning signs and severity of the clinical status, hyperparasitemia, the supposed non-immune status of patients, thrombocytopenia and admission delay. An excellent response was obtained to treatment with combined quinine-based schemes. Conclusions: Warning signs, among them thrombocytopenia, are important to prevent future complications(AU)

Diagnosis and management of coronavirus disease-associated immune thrombocytopenia: a case series

Abstract Data on health problems and fatal complications associated with coronavirus disease (COVID-19) have consistently been reported. Although immune thrombocytopenia has been associated with multiple viral infections, only few studies have shown its association with COVID-19. Here, we have reported a case series of two cases pertaining to patients diagnosed with COVID-19-associated immune thrombocytopenia, elaborating on the clinical course, management, and response to treatment.

Cov-hep study: heparin in standard anticoagulation based on citrate for continuous veno-venous hemodialysis in patients with COVID-19: a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: The primary objective is to test if heparin added to a standard regional anticoagulation protocol based on citrate is able to reduce dialysis circuit losses by clotting without increasing the risk of thrombocytopenia or bleeding, in patients with COVID-19 with acute kidney injury requiring dialysis. TRIAL DESIGN: Randomized, parallel-group, open-label trial, with two arms (ratio 1:1) comparing different continuous renal replacement therapy anticoagulation strategies. PARTICIPANTS: Eligibility conditions: All ICU patients of University of Sao Paulo General Hospital (Hospital das Clínicas), Brazil will be screened for eligibility conditions. Adults (> 18 years old) with confirmed COVID-19 and acute kidney injury requiring dialysis with agreement between ICU and nephrology teams for the introduction of renal continuous replacement therapy in daily ICU rounds. Continuous renal replacement therapy will be prescribed by consulting nephrologists based on standard clinical guidelines, including acute kidney injury with hemodynamic instability plus hyperkalemia, severe acidosis, volume overload, respiratory distress, multiorgan failure or some combination of these factors. DATA COLLECTION: Patients demographics and associated clinical data and comorbidities will be recorded at ICU entry. Demographic information will include the patient's age, sex, and admission dates. Clinical data comprise comorbidities, APACHE 2, SAPS 3, need for mechanical ventilation, and use of vasopressor drugs. Physiological data collected by the day of CRRT start will be vital signs, the arterial oxygen tension/fraction of inspired oxygen (PaO2/FiO2) index, and serum creatinine, blood urea nitrogen, bilirubin, hemoglobin, hematocrit, platelets, white blood cell count levels and Peak D-dimer levels. Patients will be analyzed for the first 72h of CRRT, and they will be evaluated regarding clinical variables, filter patency and any adverse events that could be related to the anticoagulation choice, as bleeding (mild or major) or low platelets counts (<100.000 ui/uL) during treatment period. Mild and major bleeding will be defined by hemorrhagic event without clinical impact or hemoglobin (Hb) fall lesser than 1g/dL and hemorrhagic event with clinical impact or Hb fall higher than 1g/dL, respectively. EXCLUSION CRITERIA: Hypersensitivity to any of the substances going to be used in the study (Citric acid dextrosol 2.2% and unfractionated heparin); Previous diagnosis of coagulopathy or thrombophilia; Contraindication to the use of unfractionated heparin; Risk of citrate poisoning - (Lactate> 30 mg/dL, international normalized ratio > 2.5, Total bilirubin> 15 mg/dL); Pregnancy; Patients unlikely to survive for more than 24 hours. The trial is being undertaken at the University of Sao Paulo General Hospital (Hospital das Clinicas), Brazil. INTERVENTION AND COMPARATOR: Group A (control) - Patients on continuous renal replacement therapy (blood flow 150 ml/min, dose of 30 mL/Kg/h) receiving anticoagulation with sodium citrate at 4 mmol/L Group B (experiment): Patients on continuous hemodialysis (blood flow 150 mL/min, dose of 30 mL/Kg/h) receiving anticoagulation with sodium citrate at 4 mmol/L associated with unfractionated heparin at 10 U/Kg/h. MAIN OUTCOMES: The percentage of clotted dialyzers within 72 hours in each of the studied groups (Primary outcome) Secondary outcomes: Number of dialyzers used in the first 72 hours of dialysis protocol, Mortality in the first 72 h of dialysis protocol, Bleeding events (Major or minor) in the first 72 h of dialysis protocol, Thrombocytopenia (less than 50.000 platelets) proportion in the first 72 h of dialysis protocol, Dialysis efficiency (Urea sieving) - variation in urea sieving between the first, second and third days of dialysis protocol, Continuous renal replacement therapy pressures (Arterial, Venous, dialysate and pre-filter pressure) in the first 72 h of dialysis protocol, in-hospital mortality. RANDOMIZATION: RedCap→ randomization - 2 blocks randomization by D-dimer level (5000ng/dL cut-off) and catheter site (Right Internal Jugular versus other sites) with 1:1 allocation ratio. BLINDING (MASKING): No blinding - Open label format NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Total number of patients 90 (45 per group) TRIAL STATUS: Trial version 2.0 - ongoing recruitment. First recruitment: June 29, 2020 Estimated date for last recruitment: December 31, 2020 TRIAL REGISTRATION: Responsible Party: University of Sao Paulo General Hospital (Hospital das Clinicas) ClinicalTrials.gov Identifier: NCT04487990 , registered July 27, 2020, ReBec www.ensaiosclinicos.gov.br/rg/RBR-45kf9p/ Other Study ID Numbers: U1111-1252-0194 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1) In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Acquired hemophagocytic lymphohistiocytosis as initial manifestation of multiple myeloma: A case report and literature review.

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a condition characterized by a hyperinflammatory state and persistent macrophage activation, resulting in reactive phagocytosis of the hematopoietic elements. In children, it is usually a hereditary disorder, while in adults it is usually acquired secondary to viral infections, collagenoses, or tumors. Although accounting for 10% of hematologic malignancies, HLH is rarely associated with multiple myeloma (MM) and other plasmacytic dyscrasias. PATIENT CONCERNS: A 64-year-old Brazilian man seeked medical care with a 3-month history of intermittent fever, weight loss, night sweats, and progressive anemic symptoms. DIAGNOSIS: Total blood count showed severe bicytopenia (normocytic-normochromic anemia and thrombocytopenia), biochemical exams showed elevation of creatinine, as well as monoclonal peak in serum protein electrophoresis, high IgA dosage, and serum immunofixation with IgA kappa paraprotein. Bone marrow biopsy showed 30% of monoclonal and phenotypically anomalous plasmocytes, confirming the diagnosis of MM. Diagnosis of HLH was established by the presence of clinical and laboratory criteria: fever, splenomegaly, cytopenias, hypofibrinogenemia, hyperferritinemia, elevation of triglycerides, and several figures of erythrophagocytosis in bone marrow aspirate. INTERVENTIONS: The patient experienced pulse therapy with methylprednisolone for hemophagocytic lymphohistiocytosis, followed by initial therapy for multiple myeloma with cyclophosphamide and dexamethasone. OUTCOMES: Once the diagnosis of MM and secondary hemophagocytic syndrome was established, the patient had a rapid clinical deterioration despite the established therapeutic measures, evolving with cardiovascular failure, acute liver failure, acute disseminated intravascular coagulation, worsening renal dysfunction requiring dialysis support, respiratory dysfunction, and lowering of consciousness, characterizing rapid multiple organ dysfunction, ultimately leading to the death of the patient. INNOVATION: Here, we aimed to describe the sixth reported case of HLH associated with MM, according to cases cataloged in the PubMed database, and the first case evaluated by 18-fluordeoxyglucose positron emission tomography (18-FDG-PETCT). CONCLUSION: Our case report seeks to provide support for a better clinical and laboratory characterization of this rare paraneoplastic entity associated with MM, and aims to call the attention of hematologists and intensivists to this condition that falls within the scope of the differential diagnosis of rapid onset multiple organ failure in patients with plasmacytic neoplasms.

Haem oxygenase protects against thrombocytopaenia and malaria-associated lung injury.

BACKGROUND: Malaria-triggered lung injury can occur in both severe and non-severe cases. Platelets may interact with parasitized erythrocytes, leukocytes and endothelium. These interactions can lead to microvessel obstructions and induce release of inflammatory mediators. Induction of the haem oxygenase enzyme is important in the host's response to free haem and to several other molecules generated by infectious or non-infectious diseases. In addition, an important role for the haem oxygenase-1 isotype has been demonstrated in experimental cerebral malaria and in clinical cases. Therefore, the present work aims to determine the influence of haem oxygenase in thrombocytopaenia and acute pulmonary injury during infection with Plasmodium berghei strain NK65. METHODS: C57BL/6 mice were infected with P. berghei and analysed 7-10 days post-infection. For each experiment, Cobalt Protoporphyrin IX/CoPPIX or saline were administered. Bronchoalveolar lavage fluid was used for total and differential leukocyte count and for protein measurement. Lungs were used for histological analyses or for analysis of cytokines and western blotting. The lung permeability was analysed by Evans blue dye concentration. Platelet-leukocyte aggregate formation was assayed using the flow cytometer. RESULTS: Plasmodium berghei NK65 infection generated an intense lung injury, with increased levels of inflammatory mediators, oedema, and cell migration into the lung. Plasmodium berghei infection was also accompanied by marked thrombocytopaenia and formation of platelet-leukocyte aggregates in peripheral blood. Treatment with the HO-1 inducer cobalt protoporphyrin IX (CoPPIX) modified the inflammatory response but did not affect the evolution of parasitaemia. Animals treated with CoPPIX showed an improvement in lung injury, with decreased inflammatory infiltrate in the lung parenchyma, oedema and reduced thrombocytopaenia. CONCLUSION: Data here presented suggest that treatment with CoPPIX inducer leads to less severe pulmonary lung injury and thrombocytopaenia during malaria infection, thus increasing animal survival.

Leucemia mieloide aguda y pre-eclampsia coexistente: algunas dificultades diagnósticas: a propósito de un caso / Acute myeloid leukemia and coexisting preeclampsia: some diagnosis difficulties: a case report

OBJETIVO: Remarcar la importancia de hacer un adecuado diagnóstico diferencial de la anemia y trombocitopenia en la gestante, ya que en ocasiones enmascaran cuadros tan graves como la leucemia. Presentar un caso de leucemia mieloide aguda con una preeclampsia sobreañadida y describir el proceso diagnóstico y terapéutico llevado a cabo. CASO CLÍNICO: Secundigesta, 25 años, gestante de 37 semanas, con antecedentes de preeclampsia, derivada desde atención primaria por alteración analítica y malestar general. A su llegada a urgencias el cuadro clínico es compatible con un Síndrome de HELLP. Tras el estudio del mismo se llega a la certeza de que se trata de una preeclampsia asociada a una leucemia mieloide aguda que ha simulado los parámetros analíticos de un Síndrome de HELLP. CONCLUSIONES: Es importante el adecuado estudio etiológico de la anemia y trombocitopenia en la gestación. La leucemia exige al clínico un abordaje precoz y multidisciplinar tanto diagnóstico como terapéutico.

OBJECTIVE: To emphasize on the importance of performing a precise differential diagnosis of anaemia and thrombocytopenia during pregnancy, as they can be due to important diseases as leukemia. A case of acute myeloid leukemia associated with preeclampsia is reported, describing the complexity of the diagnostic and therapeutic process. CLINICAL CASE: 25-year-old woman, gravida 2, para 1 (preeclampsia), at 36 weeks of gestation was referred to the emergency department by her primary care physician due to severe disturbance on the blood tests and general discomfort. Initially, a HELLP syndrome was suspected. However, after going in depth in the case, the final diagnosis was preeclampsia associated to acute myeloid leukemia, simulating blood parameters in HELLP syndrome. CONCLUSIONS: It is essential to study deeply and carry out a complete differential diagnosis process of anaemia and thrombocytopenia during pregnancy. Leukemia requires an early multidisciplinary management both for diagnosis and treatment.

Comprehensive treatment in severe dengue during preterm and term labor: could tocolysis be useful?

Objective: There is lack of data on the management of severe dengue infection during labor. The objective of this study was to describe our experience in the management of preterm and term labor of pregnant patients with severe dengue infection and thrombocytopenia.Materials and methods: We describe patients with dengue infection confirmed by dengue serology or NS1 antigen in Cali, Colombia. All of the patients had warning or severity signs for dengue and initiated labor, either term or preterm, during their hospital stay. All had thrombocytopenia at the moment labor started. Therefore, we treated them with support management, including intravenous fluids and a tocolytic agent (either atosiban, magnesium sulfate or nifedipine). Tocolytics aimed to stop contractions until platelets were in a safe range previous to delivery. Platelets transfusions were performed if the count was less than 10,000 cells/ml and active bleeding was present. The primary outcome we evaluated was postpartum hemorrhage (defined as a loss of >500 ml following a vaginal delivery or >1000 ml after cesarean section) or maternal and neonatal morbidity and mortality.Results: We present a total of six pregnant women. The median platelet count 24 h previous to delivery was 94,000 cells/ml and after tocolysis was 132,500 cells/ml. Two patients suffered postpartum hemorrhage despite the management. Only one woman required platelet transfusion. No maternal or newborn mortality were present. Three patients were diagnosed with preeclampsia. Four patients had delivery via cesarean section. Five out of six newborns required hospitalization, three of them due to neonatal respiratory distress syndrome.Conclusion: Comprehensive treatment including fluids resuscitation and uterine inhibition in pregnant women with severe dengue in preterm or term labor could be useful. More clinical studies are required to evaluate the benefit of this intervention in tropical countries.Brief rationale: We present an original research article and literature review entitled "Comprehensive treatment in severe dengue during preterm and term labor: could tocolysis be useful?". Our article describes the clinical manifestation, laboratory findings, complications and management provided to a group of six patients that presented to the hospital with acute dengue virus infection and initiated labor while viremic and thrombocytopenic in this study.In the present study, we found that most of our patients (5 out of 6), presented with signs of severe dengue fever and all of the patients had warning signs. In this population, we decided to provide support treatment and tocolytic agents to these patients with the aim of delaying labor to allow platelet count to rise, thus reducing the odds of hemorrhagic complications. We concluded that although tocolysis is not regularly used in patients with dengue fever, our results suggest that our protocol could benefit pregnant patients with thrombocytopenia due to dengue; however, prospective studies which determine the safety and effectiveness of our intervention are needed.

Trombocitopenia por agregados plaquetarios / Thrombocytopenia by aggregated platelet: case report

Introducción: la pseudotrombocitopenia inducida por EDTA (ácido etilendiamino tetraacético) es un fenómeno de aglutinación de plaquetas que se presenta in vitro, mediado por anticuerpos anti-plaquetarios de tipo IgG, IgA o IgM dirigidos contra el complejo glucoproteínico IIb/IIIa de la membrana plaquetaria. Caso clínico: presentamos un caso clínico de una paciente de 59 años de edad sometida a recambio valvular aórtico; clínicamente con evolución favorable durante el periodo posquirúrgico, sin embargo, en estudios de control se registra trombocitopenia severa, lo que llevo a cuestionar el uso de anticoagulantes y la necesidad de transfusión de plaquetas. Al realizar estudios complementarios se encontró agregados plaquetarios en el frotis de sangre periférica, posteriormente se realizó recuento seriado de plaquetas y comparación del histograma plaquetario, catalogando el caso como pseudotrombocitopenia. Conclusión: La trombocitopenia por agregados plaquetarios es una condición de baja incidencia (0.07% a 0.1%). Se debe a la agregación de plaquetas in vitro asociada al uso de anticoagulantes, frecuentemente etilendiaminotetraacético (EDTA), en el presente caso también se asoció al uso de citrato de sodio. Este problema no se asocia a sangrado, sin embargo su desconocimiento pudo haber llevado a realizar procedimientos diagnósticos y terapéuticos innecesarios

Introduction: EDTA (ethylenediamine tetraacetic acid) ­induced by pseudothrombocytopenia is a platelet agglutination phenomenon that occurs in vitro, which are mediated by anti-platelet antibodies of the IgG, IgA or IgM type directed against the glycoprotein complex IIb / IIIa of the platelet membrane . Clinical case: This is a clinical case of a 59-yearsold patient undergoing aortic valve replacement, clinically with a favorable evolution during the postoperative period, however, in control studies, severe thrombocytopenia was recorded, which led to questioning the use of anticoagulants and the need for platelet transfusion. When carrying out complementary studies, aggregated platelet were found in the peripheral blood smear, later, a serial platelet count and comparison of the platelet histogram were performed, classifying the case as pseudotrombocytopenia. Conclusion: Thrombocytopenia due to aggregated platelet is a low incidence condition (0.07% to 0.1%). It is due to the aggregation of platelets in vitro associated with the use of anticoagulants [frequently ethylenediamine tetra acetic (EDTA)]; in the present case it was also associated with the use of sodium citrate. This problem is not associated with bleeding; however its lack of knowledge leads to unnecessary diagnostic and therapeutic procedures.