A Network Meta-Analysis of Two Doses of Recombinant Human Thrombopoietin for Treating Sepsis-Related Thrombocytopenia.

Previous studies suggest that sepsis remains a common critical illness with a global incidence of 31.5 million. The aim of this study was to evaluate the comparative therapeutic value of recombinant human thrombopoietin (rhTPO) in treating sepsis patients with thrombocytopenia. We conducted a comprehensive electronic search of PubMed, EMBASE, the Cochrane Library, and CNKI from its inception through December 31, 2021. Thirteen randomized controlled trials (RCTs) involving 963 patients were included. Network meta-analyses showed that rhTPO 300 U/kg/day and rhTPO 15000 U/day significantly increased the platelet (PLT) levels on the 7th day and decreased the requirement of transfusion of red blood cells (RBCs), plasma, and PLT compared with IVIG and NAT. SUCRA showed that rhTPO 300 U/kg/day ranked first in terms of 28-day mortality (85.5%) and transfusion, including RBC (88.7%), plasma (89.6%), and PLT (95.2%), while rhTPO 15000 U/day ranked first for the length of the intensive care unit (ICU) stay (95.9%) and PLT level at day 7 (91.6%). rhTPO 300 U/kg/day may be the optimal dose to reduce 28-day mortality and transfusion requirements. However, rhTPO 15000 U/day may be the optimal dose for shortening the ICU stay and increasing the PLT level on the 7th day. However, additional studies to further validate our findings are needed.

Platelet Deficiency Represents a Modifiable Risk Factor for Periprosthetic Joint Infection in a Preclinical Mouse Model.

BACKGROUND: Well known for their hemostatic function, platelets are increasingly becoming recognized as important immunomodulators. The purpose of the present study was to assess the impact of platelet depletion on antimicrobial host defense in a mouse model of periprosthetic joint infection (PJI). METHODS: Thrombocytopenia (TCP) was induced in C57BL/6 mice with use of a selective antibody against platelet CD41 (anti-CD41). Whole blood from pre-treated mice was incubated with Staphylococcus aureus to assess antimicrobial efficacy with use of bioluminescent imaging, quantitative histological staining, and colony forming unit (CFU) quantification. In parallel, untreated heterologous platelets were added to TCP blood to assess potential rescue of antimicrobial efficacy. In vivo, TCP and control mice underwent placement of a titanium implant in the femur inoculated with bioluminescent Xen36 S. aureus. Longitudinal bioluminescent imaging was performed postoperatively to quantify the evolution of bacterial burden, which was confirmed via assessment of S. aureus CFUs on the implant and in peri-implant tissue on postoperative day (POD) 28. RESULTS: Anti-CD41 treatment resulted in significant dose-dependent reductions in platelet count. Ex vivo, platelet-depleted whole blood demonstrated significantly less bacterial reduction than control blood. These outcomes were reversed with the addition of untreated rescue platelets. In vivo, infection burden was significantly higher in TCP mice and was inversely correlated with preoperative platelet count (r2 = 0.63, p = 0.037). Likewise, CFU quantification on POD28 was associated with increased bacterial proliferation and severity of periprosthetic infection in TCP mice compared with controls. CONCLUSIONS: Thrombocytopenia resulted in an increased bacterial burden both ex vivo and in vivo in a mouse model of PJI. CLINICAL RELEVANCE: In orthopaedic patients, deficiencies in platelet quantity or function represent an easily modifiable risk factor for PJI.

Hepatic Campylobacter jejuni infection in patients with Castleman-Kojima disease (idiopathic multicentric Castleman disease with thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO) syndrome).

Castleman-Kojima disease, also known as idiopathic multicentric Castleman disease with TAFRO syndrome (iMCD-TAFRO), is a recently recognized systemic inflammatory disorder with a characteristic series of clinical symptoms, including thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O). Patients with iMCD-TAFRO often develop severe abdominal pain, elevated alkaline phosphatase levels, and systemic inflammation, but the etiological factors are unknown. To investigate the potential role of bacterial infection in the pathogenesis of iMCD-TAFRO, we performed polymerase chain reaction (PCR) for the bacterial 16S rRNA gene with DNA extracted from liver specimens of three patients with iMCD-TAFRO, four patients with amyotrophic lateral sclerosis, and seven patients with inflammatory conditions. Sequencing of the PCR product showed 99% DNA sequence identity with Campylobacter jejuni in all three patients with iMCD-TAFRO and in two patients with inflammatory conditions. Immunohistochemical and electron microscopy analyses could not identify C. jejuni in patients with iMCD-TAFRO. The findings indicated that C. jejuni infection is not the pathological cause of iMCD-TAFRO; however, this ubiquitous bacterium may play a role in uncontrolled systemic hypercytokinemia, possibly through the development of cross-reactive autoantibodies.

Fatal case of TAFRO syndrome associated with over-immunosuppression: a case report and review of the literature.

TAFRO syndrome is a novel disease concept characterized by Thrombocytopenia, Anasarca, myeloFibrosis, Renal dysfunction, Organomegaly, multiple lymphadenopathy and a histopathological pattern of atypical Castleman's disease. A 58-year-old man was diagnosed as TAFRO syndrome by clinical and histopathological findings. After receiving intensive immunosuppressive therapy, his thrombocytopenia and anasarca had not improved. He developed complications such as methicillin-resistant Staphylococcus aureus sepsis, gastrointestinal bleeding, peritonitis caused by Stenotrophomonas maltophilia, gastrointestinal perforation, and disseminated candidiasis resulting in death. Autopsy revealed disseminated candidiasis and hemophagocytic lymphohistiocytosis, with no evidence of TAFRO syndrome. During treatment, we regarded his lasting thrombocytopenia and anasarca as insufficient control of TAFRO syndrome. However, the autopsy revealed that thrombocytopenia was caused by secondary hemophagocytic lymphohistiocytosis caused by over-immunosuppression. We reviewed the published literature to identify indicators of adequate treatment, which suggested improvement of platelet count and anasarca several weeks after initial therapy. This indicated that we could not depend on the platelet count and anasarca in acute medical care after initial treatment. We should treat TAFRO syndrome based on patients' clinical status and obviate the risk of treatment-related complications caused by over-immunosuppression.

Molecular detection of vector borne pathogens in anemic and thrombocytopenic dogs in southern Brazil / Detecção molecular de patógenos transmitidos por vetores em cães anemicos e trombocitopenicos no Sul do Brasil

Abstract Arthropod-borne pathogens are medically important because of their ability to cause diseases in their hosts. The purpose of this study was to detect the occurrence of Ehrlichia spp., piroplasmids and Hepatozoon spp. in dogs with anemia and thrombocytopenia in southern Brazil. EDTA-whole blood was collected from 75 domestic dogs presenting anemia or/and thrombocytopenia from Guarapuava, state of Paraná, Brazil. DNA samples were subjected to conventional PCR assays for Ehrlichia spp. (dsb), piroplasmids (18S rRNA) and Hepatozoon spp. (18S rRNA), followed by sequencing and phylogenetic analyses. Among the 75 dogs, one (1.33%) was positive for Hepatozoon sp. and six (8%) were positive for piroplasmids in 18S rRNA cPCR assays. None of the dogs showed positive results in Ehrlichia spp.-cPCR targeting dsb gene. The phylogenetic analyses revealed that three piroplasm sequences were clustered with Rangellia vitalii, while one sequence was grouped with B. vogeli. The only sequence obtained from Hepatozoon spp.-PCR protocol was pooled with H. canis. Therefore, there is urgent need for differential molecular diagnosis of the two piroplasm species cited as etiological agents in clinical cases of canine hemoparasitic diseases, given the higher pathogenic potential of R. vitalii than of B. vogeli.

Resumo Agentes transmitidos por artrópodes têm grande importância na medicina veterinária devido à sua capacidade de causar doenças graves em seus hospedeiros. O presente estudo objetivou investigar a ocorrência de três patógenos transmitidos por vetores, Ehrlichia canis, Rangelia vitalii e Hepatozoon canis, em cães na região sul do Brasil. Foram coletadas amostras de sangue total de 75 cães domésticos que apresentavam anemia e/ou trombocitopenia, em Guarapuava, Paraná, Brasil. As amostras de DNA foram submetidas à técnica de PCR convencional para E. canis (dsb), piroplasmídeos (18S rRNA) e Hepatozoon spp. (18S rRNA), seguida de sequenciamento e análises filogenéticas. Das 75 amostras, uma (1,33%) foi positiva para Hepatozoon spp. e seis (8%) foram positivas para Babesia spp. Nenhuma amostra mostrou resultados positivos para Ehrlichia spp. utilizando a detecção pelo gene dsb. As análises filogenéticas revelaram que três sequências obtidas foram agrupadas no mesmo clado que R. vitalii , enquanto uma foi agrupada juntamente com B. vogeli. A única sequência obtida pelo protocolo de PCR para Hepatozoon spp. foi agrupada juntamente com H. canis. Assim, é justificada necessidade de diferenciação das espécies de piroplasmas, através do diagnóstico molecular, como agentes etiológicos nos casos clínicos de hemoparasitose canina, considerando o potencial patogênico de R. vitalii quando comparado à B. vogeli.

Hematochezia and thrombocytopenia in a 3-day-old infant: Congenital adenoviral infection.

Neonatal adenovirus infection is infrequent, but in most cases the outcome of the infection is fatal. In this case report we describe the hospital course of a 3 day old newborn patient presenting with bloody stools and thrombocytopenia that remained clinically stable and had a benign course following Adenovirus 40/41 infection detected in stool. Neonatal adenovirus infection should be considered in the differential diagnosis of neonatal sepsis and pneumonia but also in patients that present with hematochezia, thrombocytopenia and/or other less specific signs and symptoms of viral illness.

A Case Report and Literature Review of Scrub Typhus With Acute Abdomen and Septic Shock in a Child-The Role of Leukocytoclastic Vasculitis and Granulysin.

Scrub typhus is becoming a clinically important cause of acute undifferentiated febrile illness in Taiwan. The incubation period is between 6 and 21 days after exposure. It is transmitted by chiggers (larva of trombiculid mite) in long grasses and in dirt-floor homes, with infection characterized by a flu-like illness of fever, headache, and myalgia lasting approximately 1 week. It has various systemic manifestations, including GI symptoms. In some, the illness progresses to multiorgan dysfunction syndrome and death. We report on a 13-year-old boy who lived in Taipei City and who had initially tentative diagnosis of acute pyrexia of unknown origin with high fever up to 40.3°C for 1 week, but later had thrombocytopenia and diffuse abdominal pain with peritoneal sign suspected acute appendicitis. During the clinical course, septic shock and disseminated intravascular coagulopathy (DIC) were noted. There were skin rash in his trunk and extremities and an eschar with black crust surrounded by a scaling erythematous rim on his right buttock. In addition, we got the information of his travel history in Green Island and Orchid Island for 10 days.With the correct antibiotics, vancomycin, meropenem, and doxycycline, the patient was getting better and corresponding with high level of granulysin and tumor necrosis factor-alpha. The diagnosis of scrub typhus was confirmed by the biopsy of eschar and high quantitative real-time polymerase chain reaction values of Orientia tsutsugamushi (16sRNA and 56 kDa) tested by Centers for Disease Control and Prevention, Taiwan. Histopathological findings of the eschar revealed the leukocytoclastic vasculitis, crust and thrombus formation with many gram-negative microorganisms, O. tsutsugamushi demonstrated by 47 kDa monoclonal antibody immunohistochemical stain and electromicroscopy. OUTCOMES: After the careful selection of appropriate antibiotics including meropenem, vancomycin, and doxycycline, he recovered and was subsequently discharged 7 days after admission. LESSON SUBSECTIONS: This case highlights that scrub typhus infection can mimic acute abdomen and septic shock with DIC. This rare presentation of acute abdomen and septic shock with thrombocytopenia and DIC caused by scrub typhus should remind physicians to be alert to the possibility of acute abdomen and febrile illness resulting from scrub typhus.

A Severe Case of Murine Typhus Presenting With Anemia and Severe Thrombocytopenia.

We discuss a child with severe thrombocytopenia and mild anemia admitted to the Hematology service who quickly deteriorated to a life-threatening state. However, once rickettsial disease was considered in the differential diagnosis and empiric doxycycline begun, she quickly and fully recovered. A diagnostic panel, including Rickettsia typhi serology, confirmed the diagnosis of murine typhus but this occurred weeks after she had recovered. Given the potential severity of rickettsial diseases and the ease of modern travel across geographic borders, hematology-oncology providers everywhere must consider rickettsial diseases in their differential diagnosis of critically ill children and begin empiric therapy with doxycycline promptly.

Prevalence of selected rickettsial infections in cats in Southern Germany.

Prevalence of Anaplasma, Ehrlichia, Neorickettsia, and Wolbachia DNA in blood of 479 cats collected in different veterinary clinics in Southern Germany was determined using a previously published conventional PCR using 16S-23S intergenic spacer primers (5' CTG GGG ACT ACG GTC GCA AGA C 3' - forward; 5' CTC CAG TTT ATC ACT GGA AGT T 3' - reverse). Purified amplicons were sequenced to confirm genus and species. Associations between rickettsial infections, and feline immunodeficiency virus (FIV), as well as feline leukemia virus (FeLV) status were evaluated. Rickettsial prevalence was 0.4% (2/479; CI: 0.01-1.62%). In the two infected cats, Anaplasma phagocytophilum DNA was amplified. These cats came from different environment and had outdoor access. Both were ill with many of their problems likely related to other diseases. However, one cat had neutrophilia with left shift and the other thrombocytopenia potentially caused by their A. phagocytophilum infection. There was no significant difference in the FIV and FeLV status between A. phagocytophilum-negative and -positive cats. A. phagocytophilum can cause infection in cats in Southern Germany, and appropriate tick control is recommended.

Whipple's in the valleys: a case of Whipple's with thrombocytopenia and endocarditis.

INTRODUCTION: This case report details the second described case of Whipple's disease-related thrombocytopenia in the medical literature. Whipple's disease is a rare multisystem infection caused by the actinomycete Tropheryma whipplei, first described by George Whipple in 1907. The key clinical manifestations are weight loss, diarrhoea and malabsorption, but arthralgia and endocarditis are also well described. CASE PRESENTATION: A 62-year-old Caucasian female presented with weight loss, anaemia and behavioural changes but denied any abdominal symptoms. Thrombocytopenia subsequently developed rapidly. Bone marrow examination showed abundant megakaryocytes in keeping with peripheral platelet sequestration. In addition, there was significant polyclonal plasmacytosis. She was also found to have a 1.6 cm tricuspid vegetation. The diagnosis was confirmed by presence of foamy macrophages on duodenal biopsy, positive periodic acid-Schiff staining and visualisation of T whipplei actinomycetes on electron microscopy. Tissue PCR performed mid-treatment showed traces of T whipplei DNA. The infection was treated with a 2-week intravenous course of ceftriaxone followed by 12 months of oral co-trimoxazole. The thrombocytopenia and anaemia resolved rapidly with antibiotic therapy, her behaviour returned to normal and she remains clinically well. CONCLUSIONS: This report confirms the association of thrombocytopenia with Whipple's disease, likely due to peripheral platelet sequestration, which resolves rapidly with treatment. In patients with a long history of unintended weight loss, Whipple's disease is a rare but important differential diagnosis as it is ultimately fatal if left untreated.

Helicobacter pylori infection is not correlated with subclinical thrombocytopenia: a cross-sectional study.

In a small percentage of patients with immune thrombocytopenia (ITP), H. pylori eradication has a positive effect on platelet counts. Whether H. pylori infection is associated with a lower thrombocyte count in persons without clinical ITP is unknown. We performed a cross-sectional study to compare thrombocyte count between H. pylori infected (n=108) and H. pylori non-infected patients (n=600) who underwent a diagnostic gastroscopy. The mean thrombocyte count in H. pylori negative patients was 257 × 10(9)/l, in H. pylori positive patients 252 × 10(9)/l (mean difference 5 × 10(9)/l, 95% CI: -23 to 14). Subgroup analysis did not show significant differences either. In the patient group without apparent comorbidity, there were no subjects with thrombocyte counts <120. In 36 H. pylori positive patients in whom data post-eradication was available, platelet counts pre- and post-eradication were similar. In conclusion, this study could not demonstrate a lower thrombocyte count in H. pylori infected patients or in subgroups of H. pylori infected patients compared to non-infected subjects.

Association between Helicobacter pylori and liver-to-spleen ratio: a randomized-controlled single-blind study.

BACKGROUND AND AIM: Helicobacter pylori infection is reported to be associated with some extragastrointestinal manifestations, such as hematological diseases (thrombocytopenia, anemia), obesity, and fatty liver disease. The length or the volume ratio of liver to spleen was suggested to be changed in some hematological and hepatobiliary disorders. We hypothesized that the liver-to-spleen ratio may be affected in H. pylori-positive patients. In this respect, we aimed to evaluate the effect of H. pylori infection on the liver-to-spleen ratio and platelet indices. METHOD: A total of 174 patients with functional dyspepsia were included in the study. Patients were divided into group 1 (H. pylori-positive gastritis) (n=95) and group 2 (H. pylori negative, control group) (n=79). Liver, spleen length measurement, and liver steatosis scores were performed by ultrasonography by the same physicians who were blinded to the H. pylori results. Blood count values including the platelet count and the mean platelet volume (MPV) were compared between the two groups. BMI was also evaluated as a potential confounding factor for fatty liver. RESULTS: The liver-to-spleen ratio, platelet-to-spleen ratio, MPV-to-spleen ratio, and the MPV-to-liver ratio were significantly lower in the H. pylori-positive group compared with the H. pylori-negative group (P<0.001, <0.001, <0.001, and 0.038, respectively). Fatty liver was significantly more frequent in H. pylori-positive patients. CONCLUSION: Liver-to-spleen ratio and the MPV-to-spleen ratio are important indices in the pathogenesis of H. pylori-linked liver and spleen manifestations, and thrombocytopenia.

Immunomodulatory and protective roles of quorum-sensing signaling molecules N-acyl homoserine lactones during infection of mice with Aeromonas hydrophila.

Aeromonas hydrophila leads to both intestinal and extraintestinal infections in animals and humans, and the underlying mechanisms leading to mortality are largely unknown. By using a septicemic mouse model of infection, we showed that animals challenged with A. hydrophila die because of kidney and liver damage, hypoglycemia, and thrombocytopenia. Pretreatment of animals with quorum-sensing-associated signaling molecules N-acyl homoserine lactones (AHLs), such as butanoyl and hexanoyl homoserine lactones (C(4)- and C(6)-HSLs), as well as N-3-oxododecanoyl (3-oxo-C(12))-HSL, prevented clinical sequelae, resulting in increased survivability of mice. Since little is known as to how different AHLs modulate the immune response during infection, we treated mice with the above AHLs prior to lethal A. hydrophila infection. When we compared results in such animals to those in controls, the treated animals exhibited a significantly reduced bacterial load in the blood and other mouse organs, as well as various levels of cytokines/chemokines. Importantly, neutrophil numbers were significantly elevated in the blood of C(6)-HSL-treated mice compared to those in animals given phosphate-buffered saline and then infected with the bacteria. These findings coincided with the fact that neutropenic animals were more susceptible to A. hydrophila infection than normal mice. Our data suggested that neutrophils quickly cleared bacteria by either phagocytosis or possibly another mechanism(s) during infection. In a parallel study, we indeed showed that other predominant immune cells inflicted during A. hydrophila infections, such as murine macrophages, when they were pretreated with AHLs, rapidly phagocytosed bacteria, whereas untreated cells phagocytosed fewer bacteria. This study is the first to report that AHL pretreatment modulates the innate immune response in mice and enhances their survivability during A. hydrophila infection.

Chronic liver disease increases the risk of linezolid-related thrombocytopenia in methicillin-resistant Staphylococcus aureus-infected patients after digestive surgery.

Linezolid is an effective antibiotic for treatment of infections caused by resistant Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). However, thrombocytopenia has been reported in a certain proportion of patients receiving linezolid treatment. We investigated the risk factors for linezolid-related thrombocytopenia in MRSA-infected patients after digestive surgery. Forty-three patients who were treated with linezolid for postoperative MRSA infection were enrolled. We compared the characteristics of the patients who developed thrombocytopenia during linezolid therapy with those of the patients who did not. Thrombocytopenia was defined as a platelet ratio (post/pre-treatment with linezolid) of < 0.7. Twenty-one (48.8%) patients developed thrombocytopenia. In univariate analysis, long treatment duration, high pre-treatment levels of total-bilirubin and transaminases, and the coexistence of chronic liver disease (CLD) were found to be significant risk factors for development of thrombocytopenia. Other factors, for example pre-treatment platelet count, serum creatinine and albumin levels, and previous hepatic resection were not associated with thrombocytopenia. In the multivariate regression analysis, only CLD remained as an independent factor associated with thrombocytopenia. In addition, thrombocytopenia was more common among patients with indocyanine green retention at 15 min (ICG-R15) of more than 10% than in those with an ICG-R15 of 10% or less. Our results suggest that patients with CLD are at high risk of developing linezolid-related thrombocytopenia. Therefore, they should be targeted for more intense platelet count monitoring during linezolid therapy.

Invasive Candida albicans infection mimicking leukemia in a neonate.

Congenital leukemia is rare, and is frequently diagnosed as a form of acute myeloid leukemia at, or immediately after birth. Some infections, viral in particular, can mimic clinical signs and/or laboratory findings of congenital leukemia. This is the first documented case of candidemia resembling leukemia.

Helicobacter pylori infection and thrombocytopenia: A single-institution experience in Mexico / Infección por Helicobacter pylori y trombocitopenia: Experiencia en una sola institución mexicana

The association between gastrointestinal H. pylori infection and thrombocytopenia was studied in a single institution in Mexico, over a 5-year period. In 99 individuals with H. pylori infection, the prevalence of thrombocytopenia was 14%, whereas in 23 consecutive patients with chronic refractory thrombocytopenic purpura, the prevalence of H. pylori infection was 60%, this figure being similar to that informed in the general population of Mexico (66%); the association between thrombocytopenia and H. pylori infection was not significant. In 14 patients who were found to have both thrombocytopenia and H. pylori infection, eradication treatment was given and the platelet count recovered in three. It is not still clear if detection of H. pylori infection should be routinely included in the initial workup of chronic thrombocytopenia.

Se investigó la asociación entre infección del tubo digestivo por H. pylori y trombocitopenia en una sola institución en México, en un periodo de cinco años. En 99 individuos infectados por H. pylori, la prevalencia de trombocitopenia fue de 14%; por otro lado, en 23 pacientes consecutivos con púrpura trombocitopénica crónica refractaria, la prevalencia de infección por H. pylori fue de 60%, cifra similar a la descrita para la población general de nuestro país, de alrededor de 66%; en consecuencia, la asociación entre trombocitopenia e infección por H. pylori no fue significativa. En 14 pacientes en quienes coexistieron púrpura trombocitopénica e infección por H. pylori, se administró tratamiento de erradicación de la bacteria y la cuenta de plaquetas se normalizó en tres. Los datos apoyan otras publicaciones que muestran falta de asociación entre estas variables y son insuficientes para recomendar si es prudente o no investigar la infección por H. pylori en el estudio inicial de todos los pacientes con púrpura trombocitopénica.