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Dengue infection is caused by the dengue virus (DENV) and is transmitted to humans by infected female Aedes aegypti and Aedes albopictus mosquitoes. There are nearly 100 million new dengue cases yearly in more than 120 countries, with a five-fold increase in incidence over the past four decades. While many patients experience a mild illness, a subset suffer from severe disease, which can be fatal. Dysregulated immune responses are central to the pathogenesis of dengue, and haematologic manifestations are a prominent feature of severe disease. While thrombocytopaenia and coagulopathy are major causes of bleeding in severe dengue, leucocyte abnormalities are emerging as important markers of prognosis. In this review, we provide our perspective on the clinical aspects and pathophysiology of haematologic manifestations in dengue. We also discuss the key gaps in our current practice and areas to be addressed by future research. [ABSTRACT FROM AUTHOR]

Cyclic thrombocytopenia (CTP) is a rare disease characterized by the oscillations seen in the platelet count of the patients. The pathomechanism of the disease is poorly understood, several pathological processes have been implied in the background of CTP. In our current study, we aimed to thoroughly investigate the case of a 41-year-old female patient with a 22-year history of CTP. Wide-ranging laboratory testing, histological analyses and genetic investigations were carried out to investigate all the defects and alterations of physiological pathways described in the background of CTP to date. Bone marrow biopsy showed normal hemopoiesis with the abundance of megakaryocytes, some of which displayed hypolobulated nuclei. T-cell receptor rearrangement studies showed a polyclonal pattern with no indication of a monoclonal cell population. Flow cytometric assessment of the platelets revealed large number of immature platelets and decreased expression of glycoprotein IIb and IIIa at platelet zenith. Increased expression of glycoprotein IIb, IIIa and glycoprotein Ib-IX complex was observed at the nadir of the cycle. Whole exome sequencing revealed a heterozygous missense variant of uncertain significance in the SERPINC1 gene, which has been associated with hereditary antithrombin deficiency. The screening of autoantibodies did not reveal signs of autoreactive processes, and no thyroid dysfunction was found. Furthermore, synchronization with the menstrual cycle could not be concluded based on our patient’s case. With our results we contribute to the very limited data known about the long-term course of the disease and provide valuable insights into the genetic architecture of CTP.

Open in new tab Download slide OBJECTIVES Preoperative intravenous epoprostenol therapy can cause thrombocytopaenia, which may increase the risk of perioperative bleeding during lung transplantation. This study aimed to determine whether lung transplantation can be safely performed in patients with epoprostenol-induced thrombocytopaenia. METHODS From June 2008 to July 2022, we performed 37 lung transplants in patients with pulmonary arterial hypertension (PAH), including idiopathic PAH (n  = 26), congenital heart disease-associated PAH (n  = 7), pulmonary veno-occlusive disease (n  = 3) and peripheral pulmonary artery stenosis (n  = 1) at our institution. Of these, 26 patients received intravenous epoprostenol therapy (EPO group), whereas 11 patients were treated with no epoprostenol (no-EPO group). We retrospectively analysed the preoperative and postoperative platelet counts and post-transplant outcomes in each group. RESULTS Preoperative platelet counts were relatively lower in the EPO group than in the no-EPO group (median EPO: 127 000 vs no-EPO: 176 000/μl). However, blood loss during surgery was similar between the 2 groups (EPO: 2473 ml vs no-EPO: 2615 ml). The platelet counts significantly increased over 1 month after surgery, and both groups showed similar platelet counts (EPO: 298 000 vs no-EPO: 284 000/μl). In-hospital mortality (EPO: 3.9% vs no-EPO: 18.2%) and the 3-year survival rate (EPO: 91.4% vs no-EPO: 80.8%) were similar between the 2 groups. CONCLUSIONS Patients with PAH treated with intravenous epoprostenol showed relatively lower platelet counts, which improved after lung transplantation with good post-transplant outcomes. [ABSTRACT FROM AUTHOR]

This paper presents the case of 59-year-old patient who presented to the clinic with weakness, shortness of breath at rest, fever, and dry cough. Based on laboratory tests and physical examination, the patient was diagnosed with pneumonia. On the third day of hospitalization the patient presented resting, burning pain in the chest. Electrocardiogram (ECG) showed signs of STEMI. The percutaneous coronary intervention (PCI) attempt was not therapeutically successful, and the patient received heparin. Progressive thrombocytopaenia was found after myocardial infarction. Based on this, an assumption of heparin-induced thrombocytopaenia was made. Any clinical suspicion of heparin-induced thrombocytopaenia requires that treatment should not be withheld pending the result. This paper pays attention to this problem.

Background The co-existence of Sjögren's syndrome and aortic stenosis (AS) is infrequent, and there lack cases of transcatheter aortic valve replacement (TAVR) for these patients with detailed management decision-making. Case summary We report a case of a female patient who had AS and Sjögren's syndrome with leukopaenia and thrombocytopaenia. To overcome co-existing hyper-coagulation and high thrombogenesis risk, difficult lifetime valve management, and high infection risk, we performed TAVR with 3D printing and formulated antithrombotic and antibiotic schemes. Conclusion This case provided a successful experience of TAVR in patients with Sjögren's syndrome. Long-term follow-up will be conducted, and optimization of the therapeutic regimen requires further exploration. [ABSTRACT FROM AUTHOR]

Background: The effectiveness, safety, and cost of vancomycin and linezolid for managing gram-positive bacterial infections in Kuwait are unknown. This study assessed the effectiveness, safety, and cost of vancomycin, teicoplanin and linezolid for managing gram-positive bacterial infections in Kuwait. Research design and methods: This retrospective study included adult patients who were prescribed antibiotics (vancomycin, teicoplanin, and linezolid) for the treatment of gram-positive infections at five hospitals in Kuwait. Descriptive statistics were used to assess the effectiveness and safety outcomes. A cost analysis was performed on the patients hospitalised for gram-positive infections. Results: Among 116 patients, 42.2 % (n = 49) received glycopeptides (vancomycin [n = 45] and teicoplanin [n = 4]) or linezolid (n = 67). Clinical cure was achieved in 100 patients without significant intergroup differences (p = 0.34). Thrombocytopenia and acute kidney injury occurred in 19 and 20 patients (p = 0.82 and 0.96), respectively, and their incidence was similar with all the studied agents. The average cost per patient was USD 983.70. The estimated total direct medical costs were USD 894,570.6, the cost was highest for linezolid (USD 469,682.30) and vancomycin (USD 370,342.5), and lowest for teicoplanin (USD 20,799.9). Conclusions: Glycopeptides and linezolid were highly effective. Linezolid was the most frequently prescribed agent; its effectiveness and safety were similar according to the antibiotic class. However, treatment with linezolid and vancomycin were associated with considerable costs.

Thrombosis associated with thrombocytopaenia is an apparent paradox that is present across a wide spectrum of disorders. While thrombocytopaenia has been a controversial clinical classification criterion for APS, as initial reports failed to demonstrate a relation between low platelet count with other clinical or laboratory manifestations of the syndrome, recent data highlight the association between mild–moderate thrombocytopaenia and the risk of thrombosis. Although aPL antibodies may induce platelet activation in vitro , additional stimuli may contribute to their activation in vivo , among which are reactive oxygen and nitrogen species and lipid peroxidation products, which are elevated in patients with APS; an excess of the same stimuli may induce megakaryocyte and platelet apoptosis that leads to decreased platelet production and increased destruction, resulting ultimately in thrombocytopaenia. Herein we provide a novel plausible framework involving free radicals that could add to the understanding of the thrombocytopaenia–thrombosis paradox in APS. [ABSTRACT FROM AUTHOR]

In response to the ongoing COVID-19 pandemic, pharmaceutical companies have been able to rapidly develop and distribute effective vaccines. Despite some common, minor, local, and systemic adverse effects following vaccination, there is also, in rare cases, a potential for the development of anti-platelet factor 4 antibodies, resulting in platelet activation and aggregation leading to potentially life-threatening thrombosis. Vaccine-induced immune thrombocytopaenia (VITT) is a rare immune response following administration of adenoviral vector vaccines against severe acute respiratory coronavirus 2 (SARS-CoV-2) such as ChAdOx1 nCoV-19 AstraZeneca – Oxford and Ad26.COV2. S Johnson & Johnson. Since the discovery of the syndrome, the mortality rate has decreased by 90%. Therefore, in this paper, data including epidemiology and pathophysiology of the syndrome, followed by the diagnosis criteria and management options, were collected. The authors believe that spreading knowledge further among primary care physicians and other healthcare professionals will lead to better VITT treatment outcomes.

Background: The role of platelets in the immune response against influenza has been raised, and a diagnostic or prognostic value of platelet parameter abnormalities, including platelet count (PLT), or mean platelet volume (MPV), has been suggested. The study aimed to analyze the prognostic value of platelet parameters in children hospitalized due to laboratory-confirmed influenza. Methods: We retrospectively verified the platelet parameters (PLT, MPV, MPV/PLT, and PLT/lymphocyte ratio regarding the influenza complications (acute otitis media, pneumonia, and lower respiratory tract infection—LRTI), and the clinical course (antibiotic treatment, tertiary care transfer, and death). Results: An abnormal PLT was observed in 84 out of 489 laboratory-confirmed cases (17.2%, 44 thrombocytopaenia cases, and 40 thrombocytoses). Patients' age correlated negatively with PLT (rho = −0.46) and positively with MPV/PLT (rho = 0.44), while MPV was not age-dependent. The abnormal PLT correlated with increased odds of complications (OR = 1.67), including LRTI (OR = 1.89). Thrombocytosis was related to increased odds of LRTI (OR = 3.64), and radiologically/ultrasound-confirmed pneumonia (OR = 2.15), mostly in children aged under 1 year (OR = 4.22 and OR = 3.79, respectively). Thrombocytopaenia was related to antibiotic use (OR = 2.41) and longer hospital stays (OR = 3.03). A lowered MPV predicted a tertiary care transfer (AUC = 0.77), while MPV/PLT was the most versatile parameter in predicting LRTI (AUC = 0.7 in <1 yo), pneumonia (AUC = 0.68 in <1 yo), and antibiotic treatment (AUC = 0.66 in 1–2 yo and AUC = 0.6 in 2–5 yo). Conclusions: Platelet parameters, including PLT count abnormalities and MPV/PLT ratio, are related to the increased odds of complications and a more severe disease course, and may add important data in assessing pediatric influenza patients, but should be interpreted cautiously due to age-related specificities. [ABSTRACT FROM AUTHOR]

Introduction: Dengue fever is one of the most common vectorborne infections worldwide and is now endemic in Kerala. Knowledge about changing clinical presentation of dengue fever is important for timely diagnosis and appropriate management. Aim: To document changing trends in clinical presentation and course of illness among patients admitted with dengue fever in Kerala, India. Materials and Methods: This hospital-based, retrospective, observational study was conducted at Government Medical College and Hospital, Kannur, Kerala, India, from September 2021 to June 2022. The patients with dengue fever, presented in seasonal epidemic of the year 2019 was compared to similar patients presented during the year 2014. Data regarding clinical presentation, duration of hospital stay, complications and haematological parameters of the study population was collected using prevalidated questionnaire. Descriptive data were expressed in frequency, percentage, mean and standard deviation. Continuous and discrete variables were compared by Welch's t-test, whereas categorical variables were compared using Pearson's Chi-square test. Results: Out of the total 184 patients studied, 91 were from 2014 and 93 from 2019. The major presenting complaints were fever, body aches, headache, nausea and vomiting, arthralgia, and retroorbital pain incidence of which were similar in both the study years. Patients admitted in 2019 have shorter duration of fever (5.78 vs 6.79 days), earlier onset of severe thrombocytopaenia (6.62 vs 7.27 days) and delayed onset of complications (5.56 vs 3.6 days) compared to those admitted in 2014. They also had higher incidence of thrombocytopaenia (70.97% vs 54.94%) and complications (49.46% vs 14.29%) during the course of their illness. Conclusion: The study indicates towards a significant shift in clinical presentation of dengue fever in Kerala which may influence the admission and monitoring protocol of dengue fever patients in the years to come. [ABSTRACT FROM AUTHOR]

The current global platelet supply is often insufficient to meet all the transfusion needs of patients, in particular for those with alloimmune thrombocytopenia. To address this issue, we have developed a strategy employing a combination of approaches to achieve more efficient production of functional megakaryocytes (MKs) and platelets collected from cord blood (CB)-derived CD34+ hematopoietic cells. This strategy is based on ex-vivo expansion and differentiation of MKs in the presence of bone marrow niche-mimicking mesenchymal stem cells (MSCs), together with two other key components: (1) To enhance MK polyploidization, we used the potent pharmacological Rhoassociated coiled-coil kinase (ROCK) inhibitor, KD045, resulting in liberation of increased numbers of functional platelets both in-vitro and in-vivo; (2) To evade HLA class I T-cell-driven killing of these expanded MKs, we employed CRISPR-Cas9-mediated b-2 microglobulin (b2M) gene knockout (KO). We found that coculturing with MSCs and MK-lineage-specific cytokines significantly increased MK expansion. This was further increased by ROCK inhibition, which induced MK polyploidization and platelet production. Additionally, ex-vivo treatment of MKs with KD045 resulted in significantly higher levels of engraftment and donor chimerism in a mouse model of thrombocytopenia. Finally, b2M KO allowed MKs to evade killing by allogeneic T-cells. Overall, our approaches offer a novel, readily translatable roadmap for producing adult donor-independent platelet products for a variety of clinical indications. [ABSTRACT FROM AUTHOR]

The current global platelet supply is often insufficient to meet all the transfusion needs of patients, in particular for those with alloimmune thrombocytopenia. To address this issue, we have developed a strategy employing a combination of approaches to achieve more efficient production of functional megakaryocytes (MKs) and platelets collected from cord blood (CB)-derived CD34+ hematopoietic cells. This strategy is based on ex-vivo expansion and differentiation of MKs in the presence of bone marrow niche-mimicking mesenchymal stem cells (MSCs), together with two other key components: (1) To enhance MK polyploidization, we used the potent pharmacological Rho-associated coiled-coil kinase (ROCK) inhibitor, KD045, resulting in liberation of increased numbers of functional platelets both in-vitro and in-vivo; (2) To evade HLA class I T-cell-driven killing of these expanded MKs, we employed CRISPR-Cas9-mediated β-2 microglobulin (β2M) gene knockout (KO). We found that coculturing with MSCs and MK-lineage-specific cytokines significantly increased MK expansion. This was further increased by ROCK inhibition, which induced MK polyploidization and platelet production. Additionally, ex-vivo treatment of MKs with KD045 resulted in significantly higher levels of engraftment and donor chimerism in a mouse model of thrombocytopenia. Finally, β2M KO allowed MKs to evade killing by allogeneic T-cells. Overall, our approaches offer a novel, readily translatable roadmap for producing adult donor-independent platelet products for a variety of clinical indications.

Summary: Fedratinib, an oral Janus kinase‐2 (JAK2) inhibitor, is approved for patients with myelofibrosis (MF) and platelet counts ≥50 × 109/l, based on outcomes from the phase 3, placebo‐controlled JAKARTA trial in JAK‐inhibitor‐naïve MF, and the phase 2, single‐arm JAKARTA2 trial in patients previously treated with ruxolitinib. We evaluated the efficacy and safety of fedratinib 400 mg/day in patients with baseline platelet counts 50 to <100 × 109/l ("Low‐Platelets" cohorts), including 14/96 patients (15%) in JAKARTA and 33/97 (34%) in JAKARTA2. At 24 weeks, spleen response rates were not significantly different between the Low‐Platelets cohort and patients with baseline platelet counts ≥100 × 109/l ("High‐Platelets" cohort), in JAKARTA (36% vs. 49%, respectively; p = 0.37) or JAKARTA2 (36% vs. 28%; p = 0.41). Symptom response rates were also not statistically different between the Low‐ and High‐Platelets cohorts. Fedratinib was generally well‐tolerated in both platelet‐count cohorts. New or worsening thrombocytopaenia was more frequent in the Low‐Platelets (44%) versus the High‐Platelets (9%) cohort, but no serious thrombocytopaenia events occurred. Thrombocytopaenia was typically managed with dose modifications; only 3/48 Low‐Platelets patients discontinued fedratinib due to thrombocytopaenia. These data indicate that fedratinib 400 mg/day is safe and effective in patients with MF and low pretreatment platelet counts, and no initial fedratinib dose adjustment is required for these patients. [ABSTRACT FROM AUTHOR]

We present a case of cryptogenic elevation of aspartate aminotransferase (AST) activity. AST is an enzyme found in many tissues, so the serum activity of this enzyme may be elevated in various diseases. If there is an isolated increase in AST, we are therefore faced with a diagnostic challenge and many diseases must be ruled out. When most diseases have been ruled out with a high probability, it is referred to as a cryptogenic increase in AST activity. Some studies have shown that part of this increase can be explained by macroenzymes, more specifically by macro - AST. In the case presented, we also suspected that the increased AST activity was due to macro - AST. As the determination of macro - AST is not possible in the laboratory of the University Clinical Centre Ljubljana, it has not been possible to confirm or refute the diagnosis.

Introduction: Fever and thrombocytopenia, often presenting features of malaria, are also the hallmarks of dengue infections. This study examines the degree and duration of thrombocytopenia in imported malaria infections in Sri Lanka and the extent to which this could provide a false trail in favor of a dengue diagnosis. Methods: The data of all confirmed malaria cases reported in Sri Lanka from 2017 to 2019 were extracted from the national malaria database. These included detailed histories, the time to malaria diagnosis, platelet counts, and in 2019, the trail of diagnostic procedures. Results: Over the 3 years, 158 malaria cases (157 imported and one introduced) were reported. Platelet counts were available in 90.5% (n = 143) of patients among whom 86% (n = 123) showed a thrombocytopenia (

Antiphospholipid antibody syndrome (APS) is an autoimmune disease with clinical symptoms such as recurrent arterial/venous thrombosis, pregnancy morbidities and thrombocytopaenia. Antiphospholipid antibodies are suggested to be involved in the pathological condition of APS. Therefore, belimumab (BLM), which reduces autoantibody production from B cells, is expected to be effective in the treatment of APS. We report a case of a 63-years-old woman with APS with refractory thrombocytopaenia. Her thrombocytopaenia did not respond to antithrombotic therapy and immunosuppressive treatment including corticosteroids and rituximab but improved with BLM. This is the first report of an APS-induced thrombocytopaenia treated successfully with BLM. BLM should be an effective treatment for APS-related thrombocytopaenia. [ABSTRACT FROM AUTHOR]

Aims: The association of renal function and linezolid‐induced thrombocytopaenia (LIT) remains controversial. We performed a meta‐analysis to determine whether impaired renal function is associated with an increased LIT risk. Methods: We conducted a systematic search of PubMed, EMBASE and the Cochrane Library from inception to February 2021 for eligible studies evaluating the relationship between renal function and LIT. Indicators of renal function included renal impairment (RI), severe RI, haemodialysis status, creatinine clearance rate (Ccr) and estimated glomerular filtration rate (eGFR). Unadjusted and adjusted estimates and 95% confidence intervals (CIs) were calculated separately using a random‐effect model. Results: A total of 24 studies with 3580 patients were included in the meta‐analysis. RI patients had an increased LIT risk compared to non‐RI patients in both the unadjusted (OR 3.54; 95% CI 2.27, 5.54; I2 = 77.7%) and adjusted analyses (OR 2.51; 95% CI 1.82, 3.45; I2 = 17.9%). This association persisted in the subset of studies involving only patients receiving a fixed conventional dose (600 mg every 12 h) and other subgroup analyses by ethnicity, sample size and study quality. Moreover, the LIT risk was significantly higher in patients with severe RI and haemodialysis than in patients without severe RI and haemodialysis. The eGFR and Ccr were significantly lower in LIT patients than in non‐LIT patients. Conclusions: Impaired renal function is associated with an increased risk of LIT. A reduced linezolid dose may be considered in RI patients at a low risk of treatment failure, ideally guided by therapeutic drug monitoring. [ABSTRACT FROM AUTHOR]

We present the case of a 48-year-old woman with human epidermal growth factor receptor 2- and hormone receptor-positive left early breast cancer who developed severe thrombocytopaenia and moderate liver dysfunction after administration of trastuzumab emtansine as an adjuvant therapy. Briefly, she experienced grade 2 subcutaneous bleeding, decreased platelet count (18,000/µL), and elevated aspartate aminotransferase/alanine aminotransferase levels (254/193 IU), resulting in admission to the emergency room. Although thrombocytopaenia is a well-known adverse event associated with trastuzumab emtansine, we observed it immediately after trastuzumab emtansine administration in our patient. Based on the literature survey, we hypothesised that trastuzumab emtansine may have affected mature platelets in our patient. In addition, moderate hepatotoxicity may be partially explained based on the pharmacological mechanisms of trastuzumab emtansine action involving microtubule disorganisation in hepatocytes via cytoskeleton-associated protein 5 on the cell surface by emtansine. We discuss the mechanism of the development of thrombocytopaenia and liver dysfunction., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: KM received an honorarium from Nippon-Kayaku, Eisai and AbbVie for his presentation, and received compensation of travel fees to conferences held by AbbVie. The Department of Hospital Pharmaceutics, School of Pharmacy, Showa University received research grants from Daiichi Sankyo, Taiho, Mochida, Takeda, Nippon Kayaku, Ono, Bayer and Shionogi. MK received an honorarium from Nippon Kayaku, Eli Lilly Japan, Daiichi Sankyo, Taiho and Chugai for his presentation. TS received an honorarium from Daiichi Sankyo, Astra Zeneca, Pfizer, Nipro, Nichi-Iko, Nippon Kayaku, Meiji Seika Pharma and Sandoz K.K. for his presentation. The Department of Hospital Pharmaceuticals received a contracted research fee for another research from Ono. Department of Appropriate Medication Therapy Management, School of Pharmacy, Showa University received research grants from Daiichi Sankyo. SAT received an honorarium from Astra Zeneca, Eli Lilly Japan, MSD, Pfizer, Daiichi Sankyo, Eizai, Shimadzu, Fuji Film Medical, GE health care Japan, Exact Science, Medtronic, Taiho, Bayer, Shionogi, Nippon-Kayaku, Kyowa-Kirin, Sawai and Chugai for her presentation., (© The Author(s) 2024.)

TAFRO syndrome, a rare disease characterised by thrombocytopaenia, anasarca, fever, reticulin fibrosis, and organomegaly, is thought to be caused by hypercytokinaemia. It is a heterogeneous clinical entity, and a recent comprehensive international definition defined TAFRO syndrome with lymph node histopathology consistent with idiopathic multicentric Castleman disease (iMCD) as iMCD-TAFRO. Herein, we present a rare case of iMCD-TAFRO following coronavirus disease 2019 (COVID-19) infection. A 62-year-old Japanese woman, initially diagnosed with COVID-19, developed a persistent fever and fluid retention, prompting the diagnosis of iMCD-TAFRO. Following the initiation of prednisolone and cyclosporine, her symptoms gradually resolved. Therefore, we discuss the potential pathophysiological link between COVID-19 and iMCD-TAFRO, emphasising the role of cytokine storms. This case report highlights the importance of recognising the spectrum of inflammatory states after COVID-19 and differentiating iMCD-TAFRO after COVID-19 from the COVID-19 cytokine storm syndrome., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Purpose: Partial splenic endovascular embolization (PSEE) could be an option for patients with thrombocytopaenia (TCP). We selected a group of 22 patients diagnosed with refractory TCP to undergo PSEE, and we followed them for detailed analysis. Material and methods: Twenty-two patients aged 27-75 years (mean 46.5 ± 3.5 years) underwent PSEE, and 5 participants underwent a second PSEE due to the lack of effectiveness after the first procedure. A total of 27 PSEEs were performed. A semi-quantitative scale was used to assess the severity of the post-embolization syndrome. The percentage of spleen parenchyma excluded from circulation was 30-70%. We used the mixture of Histoacryl N-butyl cyanoacrylate glue and Lipiodol in 10 cases, spirals in 10 cases, and polyvinyl alcohol in 7 cases, for the embolization. Results: The mean value of platelet count (PLT) before procedure increased from 22.0 ± 15.0 to 87.7 ± 67.9 (p < 0.05) in a mean period of 194 days. In 2 cases severe post-embolization syndrome was observed. Closure less than 50% of the spleen circulation was associated with poorly expressed post-embolization symptoms. Serious complications occurred in 1 patient (3.5%). A strong positive correlation (r = 0.8, p < 0.05) was found between C-reactive protein (CRP) and the severity of post-embolization syndrome. Increased symptoms of post-embolization syndrome were also associated with a significant increase in hospitalization time – 27.0 vs. 7.2 days (r = 0.66, p < 0.05). Conclusions: Partial endovascular embolization of the spleen (PSEE) may be a valuable therapeutic option for patients with refractory TCP. PSEE is a safe method with a low complication rate. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES Platelet count reduction is a common but not fully understood phenomenon after aortic valve replacement (AVR) with bioprosthesis implantation. The aim of the present study was to investigate the occurrence and the clinical impact of platelet count reduction in patients receiving the Perceval bioprosthesis compared to those receiving standard sutured stented bioprosthetic aortic valve in a randomized, controlled AVR study. METHODS PERceval Sutureless Implant versus STandard Aortic Valve Replacement is a prospective, randomized, adaptive, open-label trial. Patients were randomized (March 2016–September 2018) to AVR with a sutureless or stented valve. Ad hoc analyses have been performed to evaluate the occurrence of platelet count reduction and the clinical impact of the platelet variations in the 2 groups. RESULTS The Perceval group showed a higher platelet reduction than the control group (46% vs 32%). The phenomenon was transient in both groups, with a slow recovery of the platelet count by hospital discharge. No differences were observed between groups regarding need of transfusions, blood loss, major bleeding and stroke events. CONCLUSIONS The Perceval sutureless aortic bioprosthesis implantation is associated with higher rate of transient platelet reduction as compared to stented bioprostheses for AVR. However, the platelet count reduction is transient and the decline does not affect the patient's clinical outcomes. Current explanations for this phenomenon are speculative, and further investigations are required to elucidate it. Clinical trial registration number NCT02673697—ClinicalTrials.gov—4 February 2016. [ABSTRACT FROM AUTHOR]

This real-world, observational study aimed to assess and compare the clinical efficacy and safety of eltrombopag with recombinant human thrombopoietin (rhTPO) in the treatment of chemotherapy induced thrombocytopenia (CIT) in patients with lymphoma. One hundred and fifty-three patients who experienced grade 3 or 4 thrombocytopenia after chemotherapy for lymphoma were enrolled, 51 of which were treated with eltrombopag, 50 with rhTPO, and 52 patients with no drug treatment were served as the control group. The lowest platelet level and mean platelet counts at Day 5, Day 7, and Day 10 were significantly higher in both the eltrombopag group (P=.041,.003,.000,.000) and rhTPO group (P=.005,.005,.000,.000) than the control, but there was no difference between treatment with eltrombopag and rhTPO. Similarly, days required for the recovery of platelet counts to ≥50×109/L and ≥75×109/L were not different between the two treatment groups but significantly higher than the control group (P

Currently, blood donors in Ghana are not screened for malaria parasites. Therefore, this study assessed platelet thrombogenicity in blood donors infected asymptomatically with Plasmodium falciparum and the relationship between tumour necrosis factor alpha (TNF-α), 8-iso-prostaglandin F2α oxidative stress biomarker (8-iso-PG2α), C-reactive protein (hs-CRP) and D-dimer, and platelet thrombogenes levels. Haematology analyser was used to enumerate platelet count and platelet indices in 80 P. falciparum infected blood donors and 160 matched non-infected controls. Replicate serum levels of von Willebrand Factor (vWF), platelet factor 4 (PF4), P-selectin thrombogenic factors as well as TNF-α and 8-iso-PG2α were determined using enzyme immuno-assay while high sensitive hs-CRP and D-dimer concentrations were determined by fluorescent immunoassay. The geometric mean of parasite density in malaria infected donors was 1784 parasites/µL (505-2478 parasites/µL). This led to significant increase in the mean levels of 8-iso-PG2α, hs-CRP, TNF-α and D-dimer. However, PF4, P-selectin were significantly lower in infected donors while vWF levels did not differ significantly among the groups even though lower levels were observed in the infected donors. Significant direct relationship existed between both P-selectin and PF4 and platelet count, and plateletcrit and platelet large cell ratio whereas these thrombogenic factors varied inversely to 8-iso-PG2α, TNF-α and hs-CRP. Relative thrombocytopaenia was associated with significant reduction in P-selectin and platelet factor 4 levels together with increased 8-iso-PG2α, hs-CRP, TNF-α and D-dimer levels. Taken together, it is recommended that all P. falciparum infected blood donors should be deferred. [ABSTRACT FROM AUTHOR]

Introduction: Fever and thrombocytopenia, often presenting features of malaria, are also the hallmarks of dengue infections. This study examines the degree and duration of thrombocytopenia in imported malaria infections in Sri Lanka and the extent to which this could provide a false trail in favor of a dengue diagnosis. Methods: The data of all confirmed malaria cases reported in Sri Lanka from 2017 to 2019 were extracted from the national malaria database. These included detailed histories, the time to malaria diagnosis, platelet counts, and in 2019, the trail of diagnostic procedures. Results: Over the 3 years, 158 malaria cases (157 imported and one introduced) were reported. Platelet counts were available in 90.5% (n = 143) of patients among whom 86% (n = 123) showed a thrombocytopenia (<150,000 cells/μl) and in nearly a third (n = 52) a severe thrombocytopenia (<50,000 cells/μl). Only 30% of patients (n = 48) were diagnosed with malaria within 3 days of the onset of symptoms, while in 37% (n = 58) it took 7 or more days. Platelet counts where significantly higher in patients who had symptoms for 7 days or more compared to those who had symptoms for <7 days (χ2 = 6.888, P = 0.009). Dengue fever was suspected first in 30% (n = 16) of the total malaria patients reported in 2019. Conclusions: Low platelet counts could delay suspecting and testing for malaria. Eliciting a history of travel to a malaria-endemic country could provide an important and discerning clue to suspect and test for malaria in such patients. [ABSTRACT FROM AUTHOR]

This real-world, observational study aimed to assess and compare the clinical efficacy and safety of eltrombopag with recombinant human thrombopoietin (rhTPO) in the treatment of chemotherapy induced thrombocytopenia (CIT) in patients with lymphoma. One hundred and fifty-three patients who experienced grade 3 or 4 thrombocytopenia after chemotherapy for lymphoma were enrolled, 51 of which were treated with eltrombopag, 50 with rhTPO, and 52 patients with no drug treatment were served as the control group. The lowest platelet level and mean platelet counts at Day 5, Day 7, and Day 10 were significantly higher in both the eltrombopag group (P=.041,.003,.000,.000) and rhTPO group (P=.005,.005,.000,.000) than the control, but there was no difference between treatment with eltrombopag and rhTPO. Similarly, days required for the recovery of platelet counts to ≥50×109/L and ≥75×109/L were not different between the two treatment groups but significantly higher than the control group (P <.05). Rates of bleeding and platelet transfusion were all significantly reduced in patients treated with eltrombopag (P=.031,.032) or rhTPO (P=.017,.009) when compared to the control. Treatment-related adverse events (AEs) were reported in 7 (13.7%) and 6 (12.0%) patients in the eltrombopag and rhTPO groups, respectively, all being mild and transient in nature. In conclusion, both eltrombopag and rhTPO were effective and safe in the treatment of thrombocytopenia after chemotherapy for lymphoma. [ABSTRACT FROM AUTHOR]

Abstract Background Carica papaya (CP) extract is becoming popular as an unlicensed herbal remedy purported to hasten recovery in dengue infection, mostly based on observations that it may increase platelet counts. This systematic review and meta-analysis aims to critically analyze the evidence from controlled clinical trials on the efficacy and safety of CP extract in the treatment of dengue infection. Methods PubMed, LILACS and Google Scholar were searched for randomized or non-randomized trials enrolling patients with suspected or confirmed dengue where CP extract was compared, as a treatment measure, against standard treatment. Recovery of platelet counts as well as other clinical indicators of favourable outcome (duration of hospital stay, prevention of plasma leakage, life threatening complications, and mortality) were assessed. Results Nine studies (India-6, Pakistan-1, Indonesia-1, Malaysia-1) met the inclusion criteria. Seven studies showed an increase in platelet counts in patients receiving CP extract, while one study showed no significant difference between the two groups, and direct comparison was not possible in the remaining study. Serious adverse events were not reported. CP extract may reduce the duration of hospital stay (mean difference − 1.98 days, 95% confidence interval − 1.83 to − 2.12, 3 studies, 580 participants, low quality evidence), and cause improvement in mean platelet counts between the first and fifth day of treatment (mean difference 35.45, 95% confidence interval 23.74 to 47.15, 3 studies, 129 participants, low quality evidence). No evidence was available regarding other clinical outcomes. Conclusions The clinical value of improvement in platelet count or early discharge is unclear in the absence of more robust indicators of favourable clinical outcome. Current evidence is insufficient to comment on the role of CP extract in dengue. There is a need for further well designed clinical trials examining the effect of CP on platelet counts, plasma leakage, other serious manifestations of dengue, and mortality, with clearly defined outcome measures.

Background & Aims: Despite limitations, platelet transfusion has been used to minimise bleeding risk in patients with thrombocytopaenia. Lusutrombopag is an oral, thrombopoietin receptor agonist approved for treatment of thrombocytopaenia associated with chronic liver disease in patients undergoing planned invasive procedures. This post-hoc analysis assessed the magnitude of platelet count change based on the integrated per-protocol population from 2 similar phase III multicentre, randomised, double-blind, placebo-controlled trials. Methods: Adults with chronic liver disease-induced thrombocytopaenia and platelet count

Since the beginning of the COVID-19 pandemic, an optimal management of vulnerable patients, such as pregnant women, has been regarded as a challenge for healthcare professionals. Although thrombocytopaenia is considered a minor criterion for admission within an intensive care unit, a low platelet count has been observed in COVID-19 patients, including a pregnant woman, who developed severe pulmonary complications. Furthermore, thrombocytopaenia has been proposed as a potential biomarker in order to identify cases at high-risk complications. Nevertheless, thrombocytopaenia is a relatively frequent condition observed in pregnancy. In this context, a differential diagnosis is essential for the correct management of COVID-19 pregnant women. [ABSTRACT FROM AUTHOR]

Abstract A 72‐year‐old Japanese man was diagnosed with idiopathic pulmonary fibrosis (IPF), and treatment with nintedanib was initiated. Ten months after nintedanib treatment initiation, his serum platelet levels gradually decreased until it reached 14,000/mm2 and he was admitted to our hospital. At admission, his serum platelet‐associated immunoglobin G level was markedly increased, and bone marrow biopsy showed megakaryocytic hyperplasia. We suspended nintedanib treatment and transfused platelet concentrate. In the absence of evidence of other diseases related to thrombocytopaenia, including Helicobacter pylori infection, thrombocytopaenia was considered to have been caused by nintedanib use. After the patient received high‐dose dexamethasone therapy (20 mg/day for four days) and thrombopoietin receptor agonist, eltrombopag olamine (maximum dose: 50 mg/day), the serum platelet count gradually increased. Here, we present a rare case of symptomatic thrombocytopaenia associated with nintedanib treatment in a patient with IPF.

Abstract Background Plasmodium vivax is the most geographically widespread species among human malaria parasites. Immunopathological studies have shown that platelets are an important component of the host innate immune response against malaria infections. The objectives of this study were to quantify thrombocytopaenia in P. vivax malaria patients and to determine the associated risks of severe thrombocytopaenia in patients with vivax malaria compared to patients with P. falciparum malaria. Main body A systematic review and meta-analysis of the available literature on thrombocytopaenia in P. vivax malaria patients was undertaken. Relevant studies in health-related electronic databases were identified and reviewed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Fifty-eight observational studies (n = 29 664) were included in the current review. Severe thrombocytopaenia (

The multilocular thymic cyst (MTC) is a rare, acquired disease caused by inflammatory changes in the thymus, and is associated with autoimmune diseases. We report a case of MTC with thrombocytopaenia, which improved following surgical resection. A 45-year-old man developed thrombocytopaenia with an anterior mediastinal tumour. Thrombocytopaenia due to an autoimmune mechanism, associated with thymoma or thymus-related disease, was suspected. Pathologic analysis following thoracoscopic thymectomy confirmed MTC. The platelet level recovered postoperatively. Our findings suggested a relationship between the acquired formation of MTC and the development of autoimmune antibodies. However, further investigation is needed to obtain more information. [ABSTRACT FROM AUTHOR]

Copyright of Paediatrics & Family Medicine / Pediatria i Medycyna Rodzinna is the property of Medical Communications Sp. z o.o. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Paediatrics & Family Medicine / Pediatria i Medycyna Rodzinna is the property of Medical Communications Sp. z o.o. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: The present study aimed to investigate the prevalence and influential factors of thrombocytopaenia in systemic lupus erythematosus (SLE) patients among the Chinese population in order to provide evidence for improving the treatment and nursing of SLE patients. Methods: A retrospective analysis of 3140 SLE patients admitted to two large tertiary hospitals was conducted in Anhui, China, from 2011 to 2018. In addition, the influential factors related to SLE with thrombocytopaenia were analysed through univariate and multivariate analysis. Results: A total of 804 SLE patients had thrombocytopaenia (25.6%). The top 5 clinical manifestations of SLE inpatients were proteinuria (51.0%), lupus nephritis (45.9%), new rash (38.4%), haematuria (36.7%) and pyuria (32.2%). The incidence of neurological manifestations, oral mucosal ulceration, pleurisy, pericarditis, hyperglycaemia, leucocytopaenia, urinary casts, haematuria, pyuria and high disease activity in the thrombocytopaenia group were higher than those in the non-thrombocytopaenia group (p < 0.05). Multivariate analysis showed age (odds ratio (OR) = 1.009, p = 0.005), neurological manifestations (OR = 1.373, p = 0.048), pericarditis (OR = 1.394, p = 0.048), hyperglycaemia (OR = 1.717, p < 0.001), leucocytopaenia (OR = 2.551, p < 0.001), haematuria (OR = 1.582, p < 0.001), serum C3 level <0.85 g/L (OR = 1.525, p = 0.001), serum C4 concentration <0.10 g/L (OR = 1.287, p = 0.020), serum CRP concentration <8 ng/L (OR = 1.314, p = 0.005), prothrombin time >15.30 seconds (OR = 1.479, p = 0.032), activated partial thromboplatin time >45 seconds (OR = 1.924, p < 0.001) and thrombin time >21 seconds (OR = 1.629, p = 0.015) were associated with thrombocytopaenia. Conclusion: Thrombocytopaenia has a high prevalence in SLE patients and is related to some baseline, clinical and laboratory characteristics, affecting multiple organs and systems. [ABSTRACT FROM AUTHOR]

Introduction: Thrombocytopaenia and autoimmune haemolytic anaemia (AIHA) have considerable impact on prognosis in systemic lupus erythematosus (SLE). We investigated the frequencies of these haemocytopaenias, along with their associations and effect on outcome in a single-centre cohort of patients with SLE. Methods: Demographic characteristics, clinical features, autoantibody profiles, damage and mortality data were compared between patients with and without each haematological abnormality. Variables displaying significant differences between the groups were entered into logistic regression. Results: Ninety-three patients had AIHA and 215 had thrombocytopaenia. Both were associated with neuropsychiatric (NP) involvement, with each other, leucopaenia, antiphospholipid syndrome (APS) and antiphospholipid antibodies. More patients in both groups had organ damage, and their damage scores were higher. Association to NP damage was discernible. In addition, cardiovascular and renal damage and diabetes were more pronounced in patients with thrombocytopaenia. At logistic regression analysis, younger age, anticardiolipin antibody IgM positivity, leucopaenia and thrombocytopaenia were associated with AIHA whilst lupus anticoagulant activity, AIHA, leucopaenia, APS and NP involvement were associated with thrombocytopaenia. Among damage items, peripheral vascular damage, diabetes, NP damage, renal and ocular damage displayed significant associations with thrombocytopaenia, whereas none of the items did with AIHA. Patients with AIHA had significantly reduced survival rates at 10 and 20 years. Conclusions: We observed that AIHA and thrombocytopaenia were associated with severe lupus, affecting major organs and causing end organ damage. Thus, they may be considered as prognostic markers. Furthermore, AIHA and especially thrombocytopaenia may also be a marker for a subgroup of lupus patients who have or may develop APS. [ABSTRACT FROM AUTHOR]

The effectiveness, safety, and cost of vancomycin and linezolid for managing gram-positive bacterial infections in Kuwait are unknown. This study assessed the effectiveness, safety, and cost of vancomycin, teicoplanin and linezolid for managing gram-positive bacterial infections in Kuwait. This retrospective study included adult patients who were prescribed antibiotics (vancomycin, teicoplanin, and linezolid) for the treatment of gram-positive infections at five hospitals in Kuwait. Descriptive statistics were used to assess the effectiveness and safety outcomes. A cost analysis was performed on the patients hospitalised for gram-positive infections. Among 116 patients, 42.2 % (n = 49) received glycopeptides (vancomycin [n = 45] and teicoplanin [n = 4]) or linezolid (n = 67). Clinical cure was achieved in 100 patients without significant intergroup differences (p = 0.34). Thrombocytopenia and acute kidney injury occurred in 19 and 20 patients (p = 0.82 and 0.96), respectively, and their incidence was similar with all the studied agents. The average cost per patient was USD 983.70. The estimated total direct medical costs were USD 894,570.6, the cost was highest for linezolid (USD 469,682.30) and vancomycin (USD 370,342.5), and lowest for teicoplanin (USD 20,799.9). Glycopeptides and linezolid were highly effective. Linezolid was the most frequently prescribed agent; its effectiveness and safety were similar according to the antibiotic class. However, treatment with linezolid and vancomycin were associated with considerable costs. [ABSTRACT FROM AUTHOR]

Abstract Background Malaria worldwide annual reported cases range between 250 and 500 million and nearly half a million deaths are reported every year. Colombia has a vast expanse of territory with environmental and social conditions conducive to malaria transmission, which is the reason why it has second place in Latin America for the number of cases of malaria. Methods This is a retrospective, paired, case–control study that compares patients with severe malaria and malaria patients without mention of complication. Medical records of patients with confirmed malaria diagnosis were reviewed. The objective of this study was to identify factors associated with complicated malaria in three municipalities of Colombia during the period 2009–2013. Results A total sample of 180 medical records was collected, 60 corresponding to cases and 120 to controls following a 1:2 ratio. From the total sample, 88.33 % (159) of subjects were originally from Tumaco, 7.78 %, most of the patients of the study (104) were diagnosed and treated in 2013. Among the laboratory findings, the platelet count was found to have statistically significant differences between cases and controls; this was also true for total bilirubin value and transaminases. The most prevalent severity finding was clinical jaundice, followed by elevated bilirubin (25 %) and elevated transaminases (44.4 %). Thrombocytopenia was found in 11/44 cases (20 %) and only five of 60 patients (8.3 %) presented severe anaemia. The multivariate analysis showed that a platelet count

In this study, we analysed platelet count trends in infants receiving iNO treatment for PH. GLO:1XW/01feb20:bjh16301-fig-0001.jpg PHOTO (COLOR): Platelet count in infants with PH (excluding CDH or pulmonary hypoplasia) is consistent before and during iNO therapy, but increase after stopping iNO. Mechanistically, the observed post-iNO platelet increase is unlikely to be due to resolution of platelet consumption or bleeding that might have occurred during iNO therapy. [Extracted from the article]

Klippel Trenaunay Weber syndrome (KTW) is a rare disorder, which occurs, in one in 27500 live births.1 It is a congenital neuroectodermal disorder1 and is characterized by the triad of symptoms such as port wine stain, bone and soft tissue hypertrophy and varicose veins. It is also associated with arteriovenous malformation.2 Due to the complexity of this disease, it is a real challenge to the anaesthetist and the obstetrician. We report a case of a KTW syndrome patient in her first pregnancy who was transferred to us from a district general hospital for the delivery. She had all the features along with multiple vascular anomalies and thrombocytopaenia. She underwent an elective caesarean section under general anaesthesia. Her intraoperative period was uneventful. At her postoperative day one she had a sudden cardiac arrest due to massive pulmonary embolism. This case highlights the high risk of thromboembolic events in patients with KTW syndrome. [ABSTRACT FROM AUTHOR]

Alloimmune thrombocytopaenia (AIT) is caused by alloantibodies against specific platelet glycoproteins. Alloimmune thrombocytopaenic disorders include alloimmune neonatal thrombocytopaenia, posttransfusion purpura, refractoriness to platelet transfusions, passive AIT, and transplantation-associated AIT. In this review we have summarised five thrombocytopaenic syndromes caused by platelet-reactive alloantibodies. Increased awareness of these syndromes, together with the greater availability of highly specialised laboratory methods to detect and to characterise platelet-reactive alloantibodies, will lead to their more frequent diagnosis.

Background: The co-existence of Sjögren's syndrome and aortic stenosis (AS) is infrequent, and there lack cases of transcatheter aortic valve replacement (TAVR) for these patients with detailed management decision-making., Case Summary: We report a case of a female patient who had AS and Sjögren's syndrome with leukopaenia and thrombocytopaenia. To overcome co-existing hyper-coagulation and high thrombogenesis risk, difficult lifetime valve management, and high infection risk, we performed TAVR with 3D printing and formulated antithrombotic and antibiotic schemes., Conclusion: This case provided a successful experience of TAVR in patients with Sjögren's syndrome. Long-term follow-up will be conducted, and optimization of the therapeutic regimen requires further exploration., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The complement system contributes to the pathogenesis of systemic lupus erythematosus (SLE). Mannose-binding lectin (MBL) is a key molecule of the lectin pathway of complement and seems to be related to the clinical manifestations of this disease. We evaluated the serum levels of MBL and its relationship with disease onset and clinical findings in SLE patients. Serum samples were analysed in 195 patients and 145 healthy controls from southern Brazil. Patients with high MBL levels (above 2000 ng/ml) showed a significant increase in the frequency of thrombocytopaenia (p = 0.007; OR = 2.71; 95% CI = 1.32–5.55); and seizures (p = 0.034; OR = 2.61; 95% CI = 1.07–6.37). A positive correlation between disease activity and MBL levels (>2000 ng/ml; p = 0.031, rho = 0.279) as well as of MBL concentration with accumulated organ damage (p = 0.021; rho = 0.232) was observed. Our results suggest a role for MBL in the development of clinical manifestations such as thrombocytopaenia and seizures in SLE patients. These findings corroborate the participation of the lectin pathway of complement in the pathophysiologic mechanisms underlying clinical manifestations of SLE. [ABSTRACT FROM AUTHOR]

Abstract: Background: Thrombotic thrombocytopaenic purpura (TTP) is a rare illness characterised by haemolytic anaemia, thrombocytopaenia and microvascular thrombosis with a 90% mortality rate if left untreated. It is a known adverse reaction to quinine; hydroxychloroquine, as a synthetic derivative of this parent compound, may also put patients at risk of this complication. However, reports of hydroxychloroquine‐induced TTP are extremely rare in the literature. Aim: This report describes a potential association between consumption of hydroxychloroquine and the development of TTP. Clinical details: A 64‐year‐old woman presented with confusion, ataxia, fevers and chills, poor urine output and muscle weakness after receiving three doses of hydroxychloroquine for rheumatoid arthritis. Initial investigations were consistent with haemolytic anaemia, thrombocytopaenia and renal and neurological deterioration. Management and outcome: The patient's usual medications were withheld, intravenous corticosteroids were started and total plasma exchange began on day three of her admission. She remained febrile without a source of sepsis, her platelet count and haemoglobin level recovered only slightly and her brain computed tomography showed microvascular ischaemia. Poor prognosis and likely significant long‐term neurological disability led to active treatment being withdrawn on day 15 of her admission and she died the following day. Conclusion: This reaction appears similar to the presentation of quinine‐associated TTP and could evolve via a similar mechanism given the structural similarities of these molecules. This case report, sparse reports of hydroxychloroquine‐induced thrombocytopaenia and only one published case report of TTP secondary to this drug highlight a possible association between TTP and hydroxychloroquine. [ABSTRACT FROM AUTHOR]

Background: The cause and clinical significance of the transient decrease in platelet (PLT) count observed in relapsing remitting multiple sclerosis (RRMS) during alemtuzumab administration remain undefined. The aim of this study was to analyse the kinetics and clinical relevance of early onset thrombocytopaenia in alemtuzumab-treated RRMS. Methods: A total of 26 patients with RRMS were included in a longitudinal study. Blood samples were collected immediately before the first alemtuzumab infusion (D0), and after 3 days (D3), 28 days (D28) and 49 days (D49). PLT, red blood cell (RC), leucocyte and lymphocyte counts, haemoglobin (Hb) concentration and haematocrit (Htc) were measured. Patients with MS were clinically evaluated every day of drug infusion and then at D28 and D49 to verify the presence of signs or symptoms suggestive of thrombocytopaenia. Results: PLT number significantly decreased at D3 (p < 0.005) and was associated with a decrease in RC count (r: 0.53, p < 0.01), Hb (r: 0.42, p = 0.05) and Htc (r: 0.53, p < 0.01). A progressive reversion of PLT number to normal values was observed at D28 and D49. A mild thrombocytopaenia was observed in 12 patients (46.2%), 8 of which (66.6%) had PLT nadir values at D3, and 4 (33.3%) at D28. No sign or symptom suggestive of thrombocytopaenia was observed. A strong correlation between pretreatment and nadir PTL counts (r: 0.59, p < 0.005) was observed; indeed, mild thrombocytopaenia was observed more frequently in these patients with a baseline PTL count lower than 230 X 109/L (83.3% versus 42.9%, p < 0.05). Conclusions: The early PLT decrease in alemtuzumab-treated patients is transient, mild, not associated with clinically relevant events and is probably related to the cytokine-released syndrome. Notwithstanding this, our findings suggest the opportunity for PLT monitoring during infusion and in the following 2 months, since a decrease in PLT count may occur. [ABSTRACT FROM AUTHOR]

Aim Complement-mediated atypical haemolytic uraemic syndrome (aHUS) is a rare disease with high mortality and morbidity if left untreated. The diagnostic work-up is complicated and the manifestations overlap with other conditions. Therefore, we hypothesize that complement-mediated aHUS is an under diagnosed disease. Methods A cohort of 768 referrals referred to the Coagulation Unit in Malmo, Sweden, for analysis of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), 2007-2012, were retrospectively reviewed. Subjects were included on the basis of presence of haemolytic anaemia, thrombocytopaenia, renal failure and ADAMTS13 > 0.05. They were excluded if tested positive for Escherichia coli. Included subjects were categorized as 'suspected HUS' with and without potential causes and triggers. Levels of C3 and C4, presence of complement factor H (CFH)-specific antibodies and associated deficiency in complement factor H related protein 1 (CFHR1) were analyzed on frozen samples. Results In total, 134/316 (42%) unique subjects fulfilled inclusion criteria; 103 were categorized as 'suspected HUS associated with potential causes/triggers' and 31 subjects categorized as 'suspected HUS' without such association. One case of complement-mediated aHUS had been confirmed during the treatment period. Laboratory analyses performed showed that in total 78 cases had findings consistent with complement-mediated aHUS: 24 cases indicated presence of CFH-specific antibodies whereof five cases had isolated low C3 titres and six cases had deficiency of CFHR1. Additionally 54 cases indicated isolated alternative pathway consumption. Conclusion The results suggest that the presence of complement-mediated aHUS was under diagnosed in this cohort calling for improvement of diagnostic availability. [ABSTRACT FROM AUTHOR]