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.

Bronchoalveolar lavage fluid analysis and mortality risk in systemic lupus erythematosus patients with pneumonia and respiratory failure.

BACKGROUND: Our aim was to characterize etiologic diagnoses obtained from bronchoalveolar lavage fluid (BALF) and blood specimens, and to identify risk factors for mortality in systemic lupus erythematosus (SLE) patients with pneumonia and respiratory failure. METHODS: We conducted a retrospective analysis of SLE patients with pneumonia and respiratory failure. Clinical characteristics, laboratory profiles, and microbiology in BALF and blood samples were evaluated. We performed univariable analyses to identify mortality risk factors. RESULTS: All 24 patients (F:M = 21:3, median age 46.5 years; disease duration 11 years) received mechanical ventilation (median duration: 11 days). Pathogens identified in BALF included Pneumocystis jiroveci (12 patients [50%]), cytomegalovirus (CMV, 7 patients [29.2%]), and bacteria (11 patients [45.8%]). Thirteen patients (54.2%) yielded pathogens in blood (CMV in 8 patients [33.3%] and Escherichia coli in 5 patients [20.8%]). Eight developed septic shock, and 9 died within 30 days. Univariable analysis identified thrombocytopenia (odds ratio [OR]: 8.0, 95% confidence interval [CI]: 1.23-52.25), bacteremia within 30 days before or after endotracheal intubation (OR: 8.0, 95% CI: 1.23-52.5), and P. jiroveci pneumonia (PJP, OR: 7.0, 95% CI: 1.04-46.95) as risk factors for 30-day mortality. Kaplan-Meier analysis confirmed an increased risk of 30-day mortality with thrombocytopenia and bacteremia. CONCLUSION: There are high prevalence rates of PJP and CMV infections as evidenced by BALF analyses in SLE patients with pneumonia and respiratory failure. BALF analysis can facilitate rescue therapy per pathogen. Thrombocytopenia, bacteremia, and PJP in SLE patients can increase their 30-day mortality, so warrant early and aggressive treatments.

Rare case of severe rhabdomyolysis secondary to human granulocytic anaplasmosis.

Anaplasma phagocytophilum (AP) is the causative agent of human granulocytic anaplasmosis (HGA), a tick-borne illness with highest incidence in north-eastern regions of the United States. This condition presents with vague constitutional symptoms and has been associated with laboratory derangements such as leukopenia, thrombocytopenia and transaminitis1. Rhabdomyolysis, however, is not one of these associations. We report a case of confirmed HGA associated with severe rhabdomyolysis, where no other cause was identified. The etiology of rhabdomyolysis secondary to AP infection is still unknown. A presumptive diagnosis of HGA can be made in the presence of fever, non-specific symptoms such as myalgias, laboratory derangements such as leukopenia and thrombocytopenia in an individual residing in an endemic area3. Serological confirmation should not delay treatment, given the rapid progression of this dangerous infection. Rhabdomyolysis should also be considered as part of supporting data in the diagnostic consideration for HGA.

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.

Clinical Utility of Platelet Count as a Prognostic Marker for Melioidosis.

Thromobocytopenia predicts mortality in patients with melioidosis in Thailand. We analyzed platelet counts in two large cohorts of melioidosis patients in tropical northern Australia to assess utility in a different clinical setting. Admission platelet counts were compared between subgroups of patients with different clinical outcomes. Patients with more severe disease (indicated by bacteremia, septic shock, and death) had significantly lower platelet counts than those with less severe disease. Logistic regression analysis was carried out for potential predictors of mortality among various clinical parameters, and platelet count was shown to be an independent predictor of mortality. Furthermore, in patients critically ill with melioidosis, an increasing platelet count after admission was associated with a significantly greater chance of survival. However, given that most patients with severe disease still had platelet counts within the normal range, platelet count is not a useful biomarker for predicting the severity of melioidosis in a clinical context.

Murine Typhus: A Life-Threatening Presentation of a Case in Galveston, Texas.

BACKGROUND Murine typhus is a rare bacterial infection caused by Rickettsia typhi, which is transmitted from rodents to humans through the infected Xenopsylla cheopis flea. The disease presentation is often non-specific, leading to unnecessary tests, and a delay in diagnosis and treatment. CASE REPORT A report is presented of a 22-year-old, previously healthy man, who presented with several symptoms and signs that increased in severity, requiring admission to the medical intensive care unit (MICU). After an extensive bacterial and viral laboratory workup, IgM and IgG titers confirmed the diagnosis of murine typhus due to infection by Rickettsia typhi. The patient was treated with doxycycline, which resulted in significant clinical improvement. CONCLUSIONS Murine typhus can present with a characteristic triad of fever, headache, and rash but also with other symptoms and signs and can vary in severity. Given its increasing prevalence in coastal cities, awareness of this infection and early diagnosis and treatment with doxycycline can reduce patient morbidity.

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.

Molecular detection of vector borne pathogens in anemic and thrombocytopenic dogs in southern Brazil.

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.

Platelet activation and prothrombotic properties in a mouse model of peritoneal sepsis.

Sepsis is associated with thrombocytopenia and microvascular thrombosis. Studies have described platelets implication in this pathology but their kinetics of activation and behavior remain poorly known. We show in a mouse model of peritonitis, the appearance of platelet-rich thrombi in organ microvessels and organ damage. Complementary methods are necessary to characterize platelet activation during sepsis as circulating soluble markers and platelet-monocyte aggregates revealed early platelet activation, while surface activation markers were detected at later stage. A microfluidic based ex-vivo thrombosis assay demonstrated that platelets from septic mice have a prothrombotic behavior at shear rate encountered in microvessels. Interestingly, we found that even though phosphoinositide-3-kinase ß-deficient platelet mice formed less thrombi in liver microcirculation, peritoneal sepsis activates a platelet alternative pathway to compensate the otherwise mandatory role of this lipid-kinase to form stable thrombi at high shear rate. Platelets are rapidly activated during sepsis. Thrombocytopenia can be attributed in part to platelet-rich thrombi formation in capillaries and platelet-leukocytes interactions. Platelets from septic mice have a prothrombotic phenotype at a shear rate encountered in arterioles. Further studies are necessary to unravel molecular mechanisms leading to this prothrombotic state of platelets in order to guide the development of future treatments of polymicrobial sepsis.

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.

Outbreak of Pichia kudriavzevii fungaemia in a neonatal intensive care unit.

PURPOSE: Fungaemia is associated with substantial morbidity and mortality in neonates admitted to neonatal intensive care units (NICUs). We report an outbreak of fungaemia in a NICU due to rare yeast, Pichia kudriavzevii (a teleomorph of Candida krusei). To the best of our knowledge, this is the first report of neonatal sepsis due to P. kudriavzevii. METHODOLOGY: Between August and September 2014, blood cultures from nine neonates diagnosed with late-onset sepsis in the NICU yielded yeast-like organisms. The molecular identification and typing of these isolates was performed by sequencing the D1/D2 region of 26S rDNA and fluorescent amplified fragment length polymorphism (FAFLP) respectively. Antifungal susceptibility was tested by broth microdilution as per the Clinical Laboratory Standards Institute (CLSI) guidelines. Sampling from environmental sources and the hands of healthcare workers (HCWs) in the NICU was performed. RESULTS: Of the nine neonates, eight were preterm and six had very low birth weight (VLBW). Thrombocytopenia was present in two neonates. Sequencing identified all the isolates as P. kudriavzevii and FAFLP showed their clonal origin. Antifungal susceptibility testing revealed the susceptibility of all isolates to the antifungals tested. Treatment with voriconazole was advised. However, only seven neonates were treated successfully and discharged after improvement, whereas two were lost for follow-up. Cultures from the environment and the hands of HCWs were negative. The outbreak was controlled by the strict implementation of infection control practices. CONCLUSION: This study emphasizes the importance of accurate identification of the aetiological agent of sepsis and vigilant monitoring for the possibility of an outbreak in NICUs.

A rare cause of acute pancreatitis: Hantavirus infection.

Hantaviruses cause potentially fatal two different systemic infectious diseases in humans named as hemorrhagic fever with renal syndrome (HFRS) and Hantavirus pulmonary syndrome. The clinical features of HFRS are hemorrhage, fever, thrombocytopenia and acute renal insufficiency frequently observed. HFRS shows distinctive clinical manifestations throughout from acute influenza-like febrile illness to shock. Although a large portion of HRFS patients present with a complaint of abdominal pain, acute pancreatitis is a rare complication of HFRS. No specific treatment protocol has been described for HRFS and supportive treatment is the basic approach. The rate of success enhanced with early diagnosis and intensive care support. Clinicians should be alert to the HFRS in patients with acute pancreatitis associated with systemic viral infection. We describe a case with HFRS who has presented with acute kidney injury, thrombocytopenia and acute pancreatitis. The patient was treated by supportive management successfully.

Thrombocytopenia in hospitalized patients with severe clostridium difficile infection.

Clostridium difficile infection (CDI) is a common cause of nosocomial diarrhea and colitis. The incidence and prognostic significance of thrombocytopenia as related to mode of acquisition (hospital vs. community), NAP1/027 strain, and disease severity has not been examined. We performed a single-institution retrospective analysis of all adult inpatients from 2013 to 2014 diagnosed with CDI during their hospitalization to document the incidence/prevalence of thrombocytopenia and associated outcomes. Severe disease was defined by a composite endpoint of inpatient death, death within 30 days of discharge, presence of septic shock, or need for colectomy during hospitalization. Of the 533 patients diagnosed with CDI, moderate thrombocytopenia (platelet count <100 × 109/L at time of CDI diagnosis) was present in 15 % of the total cohort and incident thrombocytopenia developed in 3 % of patients after admission. Thrombocytopenia was more common in hospital-acquired disease and associated with increased length of stay, but was not associated with treatment failure. Those with moderate thrombocytopenia were more likely to have severe disease, after controlling for white blood cell count, albumin, and creatinine. Moderate thrombocytopenia is associated with poor prognosis and is a potential risk stratification tool for severe CDI.

Strains of Group B streptococci from septic patients induce platelet activation via Toll-like Receptor 2.

Group B Streptococcus (GBS) causes life-threatening bacterial sepsis, especially in newborns and pregnant women. Patients suffering from sepsis often display low platelet counts, characterized by thrombocytopenia, because of platelet activation. In the present study, the roles of six GBS strains from septic patients in platelet aggregation, as well as the underlying mechanisms, were investigated. Incubation of platelets with three of the strains induced platelet aggregation, increased the secretion of cellular adhesin molecule CD62P and activation of GPIIb/IIIa. Furthermore, the GBS strains that induced platelet activation also caused an increase in the expression of Toll-like receptor (TLR) 2 in platelets. Pre-incubation of platelets with anti-TLR2 monoclonal antibody, but not anti-TLR4 monoclonal antibody, inhibited these functional responses induced by GBS. TLR2 stimulation also activated the phosphoinositide 3-kinase (PI3-K)/Akt signalling pathway in platelets, and inhibition of PI3-K significantly reduced GBS-induced platelet responses. Our results indicate that three of the GBS strains from the septic patients can trigger platelet activation by interacting with platelets, which involves the elevation of platelet TLR2 expression.