Toxoplasma gondii infection in cats is mostly subclinical. Systemic disease usually occurs in immunocompromised individuals. This report describes an unusual systemic toxoplasmosis, presenting as parasitic arthritis in an adult 14-year-old neutered male indoor domestic shorthair cat, with no identifiable cause of immunosuppression, and referred for lethargy, anorexia, and fever. Laboratory abnormalities included non-regenerative anemia, thrombocytopenia, increased serum amyloid A concentration, and polyclonal hypergammaglobulinemia. With persistent discomfort on palpation of the pelvic region and hind limb joints, synovial fluid was aspirated from the left carpus, elbow, and tarsus, and cytological analysis supported inflammatory polyarthritis. Additionally, the elbow joint fluid showed free crescent-shaped organisms, morphologically resemblingT. gondii tachyzoites. Serum anti-T. gondii IgG titer was initially 1:256 (cut-off titer, 1:50), although this was insufficient to confirm active infection. Whole-blood T. gondii polymerase chain reaction (PCR) was negative. The cat markedly improved with amoxicillin-clavulanate, enrofloxacin, clindamycin and supportive treatment. Two weeks later, serum anti-T. gondii IgG titer increased fourfold (1:1024), confirming seroconversion and active systemic toxoplasmosis. The infection likely triggered secondary immune-mediated thrombocytopenia (sIMT) and hemophagocytic syndrome, which improved following antibiotic therapy. T. gondii-associated immune thrombocytopenic purpura is reported in humans, but to our knowledge, never in cats. This case highlights the diagnostic value of synovial fluid cytology and seroconversion in feline systemic toxoplasmosis. Negative blood PCR test should not exclude active infection. Toxoplasmosis should be considered in cats presenting with fever of unknown origin, polyarthritis, or unexplained hyperglobulinemia, regardless of the immune status or lifestyle.

BackgroundImmune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia and increased bleeding risk. Although first-line therapies such as corticosteroids and intravenous immunoglobulin provide initial benefit, many patients relapse or develop refractory disease. Romiplostim, a thrombopoietin receptor agonist, has emerged as an effective second-line therapy; however, evidence comparing its efficacy and safety with placebo across both pediatric and adult populations remains limited.MethodsA systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted following PRISMA guidelines (PROSPERO: CRD420261357179). PubMed, Scopus, Cochrane Library, and Google Scholar were searched up to March 2026. RCTs comparing romiplostim with placebo in ITP patients were included. A random-effects model was used to calculate mean differences (MD) and risk ratios (RR) with 95% confidence intervals (CI). Risk of bias was assessed using the Cochrane RoB 2 tool. Certainty of evidence was evaluated using the GRADE approach.ResultsNine RCTs (n=748) were included. Romiplostim significantly increased platelet counts at week 2 (MD 25.71; 95% CI 9.41-42.02), week 4 (MD 42.74; 95% CI 26.82-58.66), week 6 (MD 50.42; 95% CI 33.87-66.97), and week 8 (MD 49.14; 95% CI 20.45-77.83), with larger effects in adults. Platelet response rates were significantly higher with romiplostim (RR 6.10). The proportion achieving ≥20×10[9]/L increase improved (RR 3.23), and the need for rescue therapy decreased (RR 0.49). Adverse events were comparable between groups, with slight increases in myalgia and rash.ConclusionRomiplostim is an effective and well-tolerated therapy for ITP, significantly improving platelet outcomes and reducing rescue therapy requirements without major safety concerns.

BackgroundImmune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening autoimmune condition driven by severe ADAMTS13 deficiency. Therapeutic plasma exchange (TPE) is the traditional cornerstone of acute therapy, as it clears autoantibodies and replenishes functional ADAMTS13. However, caplacizumab-an anti-von Willebrand factor nanobody that rapidly blocks platelet-von Willebrand factor interactions-has raised the possibility of safely omitting TPE in carefully selected patients.ObjectiveTo review the biological rationale, current clinical evidence, patient-selection criteria, safety profile, and practical implementation of utilizing caplacizumab for iTTP treatment without relying on plasma exchange.MethodsA comprehensive narrative review was conducted. It analyzed published case reports, case series, registry data, comparative cohort studies, and guideline-relevant literature focusing on TPE-free or TPE-sparing caplacizumab-based regimens for iTTP.ResultsEvidence has evolved from isolated, necessity-driven cases to robust multicenter comparative data. Caplacizumab-based, TPE-free treatment combined with immunosuppression consistently drives rapid platelet recovery, typically within three to five days. Large comparative cohorts demonstrate that clinical response, exacerbation rates, refractoriness, and mortality are similar to conventional TPE-based therapies. Furthermore, the TPE-free approach offers the benefits of shorter hospital stays and reduced intensive care utilization. However, a subset of patients with inadequate initial platelet responses or complex comorbidities still required rescue TPE.ConclusionTPE-free caplacizumab therapy is a promising, highly targeted strategy, though it should not replace standard therapy outside experienced centers. Safe implementation demands confirmed iTTP, clinical stability, immediate caplacizumab availability, rigorous ADAMTS13 monitoring, adequate immunosuppression, and predefined thresholds for rescue TPE.

Pregnancy-related acute kidney injury is a major global health burden associated with increased maternal and fetal morbidity and mortality. Thrombotic microangiopathies (TMA) occurring in pregnancy or postpartum include severe preeclampsia/Hemolysis Elevated Liver Enzymes Low Platelets (HELLP) syndrome, atypical Hemolytic Uremic Syndrome (aHUS) and Thrombotic Thrombocytopenic Purpura (TTP). Severe acute kidney injury and progression to chronic kidney disease are particularly associated with complement-mediated thrombotic microangiopathy/atypical hemolytic uremic syndrome and may also complicate severe preeclampsia/HELLP syndrome, while renal involvement is usually less prominent in TTP. Interestingly, preeclampsia, HELLP syndrome, aHUS, TTP, lupus nephritis and antiphospholipid syndrome share common autoimmune pathogenic mechanisms, as both are characterized by exaggerated neutrophil activation and increased neutrophil extracellular traps (NETs) release, as well as complement activation. In an era of targeted therapies, the lack of treatment of preeclampsia and HELLP results from the limited understanding of the underlying pathogenetic mechanisms. Eculizumab, a C5 inhibitor that targets the complement, significantly reduced the risk of ESKD in women with pregnancy-associated aHUS, supporting the therapeutic relevance of complement modulation. In this review, we performed a narrative synthesis of established and emerging experimental, translational and clinical data on pregnancy-associated TMAs, summarizing current evidence on the interaction between neutrophil dysregulation, NET formation, complement activation and endothelial injury in pregnancy-associated thrombotic microangiopathies. A better understanding of the neutrophil-NET-complement axis may help refine diagnostic distinctions among overlapping pregnancy-associated thrombotic microangiopathies and facilitate the development of more targeted therapeutic strategies.

Thrombotic microangiopathy (TMA) is a process characterized by thrombocytopenia, microangiopathic hemolytic anemia, and end-organ injury. Malignancy-associated TMA is uncommon and may resemble primary TMA syndromes, particularly when renal dysfunction predominates and peripheral smear findings are limited. We present a case of biopsy-confirmed renal TMA in the setting of newly diagnosed metastatic squamous cell carcinoma (SCC) following significant diagnostic uncertainty. A 59-year-old man with insulin-dependent diabetes mellitus presented with worsening headache, neck pain, dysphagia, shortness of breath, poor oral intake, and significant weight loss. Initial evaluation demonstrated acute hypoxic respiratory failure, progressive renal failure, thrombocytopenia, and a newly identified right-sided neck mass. Laboratory studies showed anemia, elevated lactate dehydrogenase, low haptoglobin, and reticulocytosis, raising concern for TMA. Peripheral smear showed few schistocytes, while ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif member 13) activity was reduced but not severely deficient. Autoimmune and complement studies were unrevealing. Renal function progressively worsened, requiring initiation of hemodialysis. Renal biopsy demonstrated acute and chronic TMA with chronic vascular changes. Additional otolaryngologic evaluation confirmed invasive, moderately differentiated nonkeratinizing SCC of the uvula with metastatic cervical disease. Given the biopsy findings, lack of severe ADAMTS13 deficiency, unrevealing autoimmune workup, and overall clinical course, malignancy-associated TMA was favored over primary thrombotic thrombocytopenic purpura and other secondary causes. Renal TMA in patients with newly diagnosed malignancy may present with a broad and overlapping differential diagnosis. In this case, renal biopsy clarified this mechanism, as the limited peripheral smear findings and multiple overlapping causes of secondary TMA had posed significant diagnostic challenges.

Atypical hemolytic uremic syndrome (aHUS) is not a common thrombotic microangiopathy (TMA) characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment, often due to dysregulation of the alternative complement pathway. Bone marrow study in HUS is classically hypercellular. However, hypo-cellularity is rarely encountered. We report a case of a five-year-old boy who presented with severe pallor, thrombocytopenia, hypertension, and signs of TMA, including schistocytosis and renal impairment. Infectious and autoimmune causes were excluded. Initial management with plasma exchange and other supportive measures showed no improvement. ADAMTS13 activity was within normal limits, which excluded thrombotic thrombocytopenic purpura (TTP). Further investigations, including next-generation sequencing and anti-complement factor H (anti-CFH) antibody tests, were negative. To our surprise, bone marrow biopsy revealed markedly hypocellular marrow (10-15% cellularity), indicative of aplastic anemia. Despite escalation of therapy with steroids, intravenous immunoglobulin (IVIG), and eculizumab, the child showed no response and succumbed to a pulmonary hemorrhage. The case highlights a rare and fatal presentation of aHUS associated with bone marrow hypoplasia, an uncommon and diagnostically challenging phenotype. It underscores the need for high clinical suspicion, early bone marrow evaluation in refractory cases, and the importance of timely access to complement-targeted therapies. The coexistence of aHUS and aplastic anemia suggests a potential novel pathophysiologic overlap warranting further investigation.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is rare in children, and its pathogenesis remains incompletely understood. Current evidence suggests that complex interactions between genetic susceptibility and environmental triggers contribute to disease development. We report a case of pediatric-onset microscopic polyangiitis (MPA) preceded by recurrent cutaneous manifestations and occurring in a patient with a history of Kawasaki disease and a strong family history of autoimmune diseases. A 14-year-old boy presented with recurrent painful edematous erythema involving the palms, wrists, and dorsum of the feet. Several months later, he developed fever, arthralgia, oral aphthous ulcers, and weight loss. Urinalysis revealed hematuria and proteinuria, and serum myeloperoxidase (MPO)-ANCA levels were markedly elevated. Renal biopsy demonstrated pauci-immune crescentic glomerulonephritis, leading to the diagnosis of MPA. Remission induction therapy with corticosteroids and cyclophosphamide achieved sustained clinical remission without renal dysfunction. The patient had a history of Kawasaki disease in infancy, more than a decade before the onset of MPA. In addition, his mother had rheumatoid arthritis and myasthenia gravis, and his younger sister had immune thrombocytopenic purpura. This case raises the possibility that prior immune-mediated vascular inflammation, together with autoimmune genetic predisposition, may contribute to the later development of MPO-ANCA-associated vasculitis. Further accumulation of similar cases may help clarify the immunopathogenic relationship between Kawasaki disease and AAV.