Thrombocytopenia, characterized by a platelet count less than 150 × 10^9/L, is a frequently encountered hematologic abnormality in pregnancy, observed in approximately 7-12% of all pregnant individuals. While gestational thrombocytopenia is the most common cause and is often benign, other underlying causes, such as immune thrombocytopenia (ITP), pre-eclampsia-related conditions like HELLP syndrome, and thrombotic microangiopathies (e.g., TTP, HUS, AFLP), may carry significant maternal and fetal risks. The current review aims to provide a comprehensive overview of thrombocytopenia during pregnancy, with emphasis on its differential diagnosis, clinical presentation, diagnostic workup, and management strategies. Particular focus is placed on conditions requiring urgent intervention, including thrombotic microangiopathies. We conducted a narrative review of published literature, consensus guidelines, and registry data. Emphasis was placed on clinical applicability, trimester-wise drug safety, and proposed diagnostic algorithms. Tables summarize platelet thresholds for delivery, transfusion indications, and drug safety profiles. The review reiterates that the causes of thrombocytopenia during pregnancy range from benign to potentially life-threatening. Gestational thrombocytopenia remains the most common etiology, typically requiring no intervention. In contrast, ITP and thrombotic microangiopathies often necessitate immunosuppressive therapy or plasma exchange. Differentiation is aided by clinical history, timing of onset, and accompanying systemic features. This review helps conclude that early recognition, appropriate triaging, and multidisciplinary coordination are essential to improve maternal and neonatal outcomes. Wherever feasible, therapeutic decisions must be individualized, balancing maternal benefit with fetal safety. Tables and figures should guide the clinician in applying evidence-based decisions across diverse clinical scenarios.

Management of Immunosuppression-Induced Thrombotic Microangiopathy in Heart Transplant Recipient: A Case Report

Finding the etiology of membranoproliferative glomerulonephritis.

Narsoplimab (narsoplimab-wuug; YARTEMLEA®) is a recombinant human immunoglobulin G4 monoclonal antibody targeted against mannan-binding lectin-associated serine protease2 (MASP-2) being developed by Omeros Corporation initially for the treatment of haematopoietic stem cell transplantation (HCT)-associated thrombotic microangiopathy (TA-TMA). MASP-2 inhibition by narsoplimab is thought to provide benefit in patients with TA-TMA by decreasing or preventing lectin complement pathway-mediated cellular injury. In December 2025, narsoplimab received its first approval, in the USA, for the treatment of adult and paediatric patients aged ≥ 2years with TA-TMA. Additionally, a Marketing Authorisation Application for narsoplimab for the treatment of TA-TMA is currently under regulatory review in the EU. This article summarises the milestones in the development of narsoplimab leading to this first approval for TA-TMA.

Early Post-Transplant Complement-Mediated Thrombotic Microangiopathy in a Patient with Short Telomere Syndrome

Pregnancy induces vascular, coagulation, and immune alterations that predispose to thrombotic microangiopathy (TMA). Within this spectrum-preeclampsia/ hemolysis, elevated liver enzymes, and low platelets syndrome (HELLP) and complement-mediated TMA (CM-TMA)-overlapping features complicate diagnosis, whereas management and prognosis diverge. A 39-year-old woman developed severe hypertension at 35weeks' gestation, underwent emergency cesarean section for preeclampsia, and subsequently became anuric. She had schistocytic hemolysis, thrombocytopenia, elevated lactate dehydrogenase (LDH), and transaminitis. One plasma exchange, hemodialysis, and supportive care were provided; urine output recovered and dialysis ceased. Atypical complement tests results persisted for ~ 1month (undetectable serum CH50 with elevated C3/C4), with normal functional assays and no pathogenic variants in complement-regulatory genes. On subsequent testing with Ethylenediaminetetraacetic acid (EDTA) plasma, preserved at - 80°C, showed a normal CH50, suggesting that ex vivo complement activation may have contributed to the low serum CH50. In the acute setting,HELLP versus CM-TMA remained indeterminate, so management was guided by the clinical trajectory: brief plasma exchange during TTP evaluation, close monitoring, and deferral of complement inhibition as platelets, LDH, and urine output improved. This case supports a "trend-first" approach to peripartum TMA, and underscores ex vivo complement activation as a key pitfall when interpreting complement assays in the peripartum setting.

Severe Class III Lupus Nephritis With Concurrent Thrombotic Microangiopathy and Suspected Atypical Hemolytic Uremic Syndrome Requiring Complement Blockade: A Complex Multisystem Presentation

Multiple myeloma (MM) is a prevalent hematological malignancy, with proteasome inhibitors (PIs) playing a crucial role in its therapeutic management. Although PIs are generally well-tolerated and associated with relatively mild side effects, recent evidence has increasingly drawn attention to proteasome inhibitor-related thrombotic microangiopathy (PI-related TMA). Here, we report two cases with high clinical suspicion for PI-related TMA, highlighting the diagnostic process and subsequent management strategies. Clinical suspicion of PI-related TMA prompted the discontinuation of the offending agent and consideration of plasma exchange therapy, which proved beneficial in selected patients. These case reports further facilitate a detailed discussion regarding the underlying pathogenic mechanisms and potential therapeutic approaches for PI-related TMA in MM. PI-related TMA is a rare but life-threatening complication in MM. Early recognition and prompt discontinuation of the offending drug are critical. Plasma exchange and eculizumab may be considered in selected cases.

We report a 33-year-old woman with systemic lupus erythematosus (SLE) who developed fulminant multiorgan ischemic manifestations and hematologic abnormalities. She presented with persistent fever, newly developed painful fingertip cyanosis, and acute kidney injury. Laboratory tests showed severe thrombocytopenia, hemolytic anemia with fragmented red blood cells, positive direct and indirect Coombs tests, hypocomplementemia, and positivity for multiple autoantibodies, including a triple-positive antiphospholipid antibody profile. Within the first week of hospitalization, in addition to digital ischemia, she developed multiple cerebral infarctions and acalculous cholecystitis, findings consistent with catastrophic antiphospholipid syndrome (APS). Unexpectedly, the activity of a disintegrin and metalloproteinase with thrombospondin type 1 motifs member 13 (ADAMTS13) was severely reduced to 5%, whereas ADAMTS13 inhibitor was not detected by the Bethesda assay. There was no past medical or family history suggestive of congenital thrombotic thrombocytopenic purpura. After treatment with high-dose glucocorticoids and nine sessions of plasma exchange (PE), abdominal pain resolved and digital ischemia improved, accompanied by improvement in hematologic and renal abnormalities and disappearance of fragmented red blood cells. Subsequently, ADAMTS13 activity normalized to 63% and remained stable after completion of PE. Later, non-inhibitory anti-ADAMTS13 autoantibodies were detected by enzyme-linked immunosorbent assay in a stored serum sample obtained on admission. ADAMTS13 deficiency due to non-inhibitory anti-ADAMTS13 autoantibodies may modify the complications of SLE and APS by promoting thrombotic microangiopathy.

Multisystem inflammatory syndrome in children (MIS-C) represents a severe postinfectious hyperinflammatory condition following SARS-CoV-2 infection. Despite extensive clinical characterization, histopathologic data-especially from pre-mortem pediatric biopsies-remain scarce. We report a 9-month-old male infant with confirmed SARS-CoV-2 infection and rapid multiorgan failure. Pre-mortem incisional biopsies from the myocardium, lung, and pleura revealed degenerative myocyte changes, endothelial swelling, and fibrin-platelet microthrombi consistent with thrombotic microangiopathy. Immunohistochemistry demonstrated mild CD3+ T-cell-predominant infiltrates and focal SARS-CoV-2 antigen positivity confined to alveolar and bronchiolar epithelium, while myocardial and pleural tissues were negative. These findings highlight early morphologic correlates of immune-mediated vascular injury in MIS-C, characterized by endothelial dysfunction, microvascular inflammation, and T-cell-driven immunopathology in the absence of direct viral cytopathy. This case provides rare pre-mortem evidence of immune-thrombotic endotheliopathy in an infant, bridging clinical and histologic manifestations of pediatric SARS-CoV-2-associated hyperinflammatory disease.

BACKGROUND Autoimmune hemolytic anemia (AIHA) is characterized by immune-mediated premature red blood cell destruction. Although AIHA has been reported after solid organ transplantation, it remains uncommon, and very late-onset presentations occurring decades after transplantation are rare. Both warm and cold AIHA have been reported after transplant. Reported etiologies include immune dysregulation, infections, post-transplant lymphoproliferative disorders, and medication-associated immune hemolysis, including calcineurin inhibitor-related effects. CASE REPORT A 30-year-old woman with orthotopic liver transplantation at age 9 for biliary atresia, on long-term tacrolimus, presented 21 years after transplant with exertional dyspnea and symptomatic anemia. Laboratory evaluation revealed severe anemia with biochemical evidence of hemolysis, including undetectable haptoglobin and reticulocytosis. A direct antiglobulin test was positive for IgG, confirming warm autoimmune hemolytic anemia. Antibody identification revealed a warm autoantibody, and crossmatch-compatible red blood cells were transfused without reaction. Extensive evaluation excluded gastrointestinal bleeding, infection including Epstein-Barr virus, post-transplant lymphoproliferative disorder, and thrombotic microangiopathy. She was treated with high-dose corticosteroids with partial response, followed by early rituximab due to persistent hemoglobin instability. The tacrolimus dose was modestly reduced but not discontinued. Bone marrow biopsy excluded hematolymphoid malignancy. The patient achieved complete remission with normalization of hemoglobin and hemolysis markers after 4 rituximab doses and steroid tapering. CONCLUSIONS Warm autoimmune hemolytic anemia can present decades after solid organ transplantation and should be considered in transplant recipients with unexplained anemia. Remission can be achieved with corticosteroids and early rituximab without discontinuation of tacrolimus. Further studies are needed to clarify optimal treatment strategies for late-onset post-transplant AIHA, including the role of early rituximab.

Complement activation is a consistent and predictable biological response to adeno-associated virus gene therapy, particularly after high-dose systemic administration. Early postdose laboratory changes, including mild thrombocytopenia, modest reductions in C3 and C4, and low-level elevations in complement activation markers, are commonly observed and generally reflect expected pharmacodynamic effects rather than toxicity in isolation. However, a subset of individuals progresses to complement-mediated endothelial injury and thrombotic microangiopathy, a rare but potentially severe complication. Despite increasing recognition of complement biology in gene therapy safety, laboratory monitoring practices remain inconsistent, and interpretation of complement biomarkers is often fragmented. Reliance on isolated measurements may obscure early pathologic trajectories, while functional assays are sensitive to preanalytical variability. Emerging data suggest that alternative pathway amplification governs severity across diverse initiating mechanisms and distinguishes self-limited complement activation from sustained endothelial injury. This article proposes a laboratory-centered framework that integrates complement biomarkers with hematologic and renal indices, emphasizing serial trends over isolated values. Standardized interpretation of complement testing is essential for early recognition of pathologic escalation and for maintaining patient safety as gene therapy expands across clinical settings.

Efficacy of skin microvasculature C5b-9 and MASP2 deposition in transplant-associated thrombotic microangiopathy

The objective of a multicentre, prospective, observational study of an eculizumab biosimilar (Elizaria®) was to analyse the efficacy and safety of long-term complement inhibitor therapy in patients with atypical haemolytic uraemic syndrome (aHUS). The study included 50 patients aged 1 to 55 years, with 42% of them under the age of 18. The patients received the eculizumab biosimilar in routine clinical practice within 56 weeks; 19 patients (38%) had been treated with eculizumab prior to enrolment, whereas 31 patients (62%) were naive to complement inhibitors. By the end of the study, an increase in platelet count of 39.48±21.7×109/L and 33.61±24.06×109/L was reported in treatment-naive and treatment-experienced patients, respectively. By the end of the study, 96% of treatment-experienced patients and 100% of treatment-naive patients had normal platelet counts. The mean LDH activity did not change significantly, with levels of 253.84±122.22 U/L registered at screening and 245.24±93.52 U/L at the end of the study. In total, 39 patients (77.6%) at Week 21 and 40 patients (80%) at Week 52 had no thrombotic microangiopathy (TMA) events. During the study, the proportion of patients with a complete TMA response increased significantly, rising to 8% (P = 0.046). The proportion of patients with an eGFR improvement of 15 mL/min/1.73 m2 and more at Week 52 was 12%. During the safety assessment, 63 adverse events not related to the investigational medicinal product were reported. Long-term complement inhibitor therapy with the eculizumab biosimilar in patients with aHUS has demonstrated a stable effect, a favourable safety profile and low immunogenicity.

Atypical hemolytic uremic syndrome (aHUS) is a rare cause of thrombotic microangiopathy (TMA). When aHUS cannot be excluded, diagnostic treatment with anti-C5 antibody agents should be considered. We report a patient with a novel heterozygous complement factor H (CFH) variant, p.Glu1198Asp (c.3594A>T), who received ravulizumab three months after disease onset. Ravulizumab was administered for relapse prevention in the chronic phase, and no recurrence of thrombotic microangiopathy was observed during the follow-up.

This narrative review examines acute and chronic kidney injury following COVID-19 infection and vaccination, discussing the mechanism of SARS-CoV-2 entry into host cells through the ACE2 receptor - highly expressed in renal tissues - facilitating the viral invasion. Viral RNA has been detected in the urine of patients infected with SARS-CoV-2, suggesting direct renal involvement. The incidence of acute kidney injuriy (AKI) among hospitalized COVID-19 patients was particularly higher in the early stages of the pandemic and largely varied by 29%-46%, depending on population studied and COVID-19 wave. Pathological findings include acute tubular injury (ATI), collapsing glomerulopathy, and focal segmental glomerulosclerosis. Major risk factors for AKI comprise older age, male sex, diabetes, hypertension, cardiovascular disease, and preexisting Chronic Kidney Disease (CKD). AKI significantly increases mortality of COVID-19 patients, particularly in advanced stages of renal failure. CKD is also associated with severe COVID-19 outcomes, including increased hospitalization, intensive care admission, and mortality. Patients with CKD show a dose-dependent relationship between disease stage and adverse patient outcomes. This review further addresses renal complications following COVID-19 vaccination, which, although rare, encompass various immune-mediated glomerular diseases. Minimal Change Disease (MCD) is most frequently reported after COVID-19 vaccination, followed by IgA nephropathy, membranous nephropathy, anti-glomerular basement membrane (anti-GBM) nephritis, and ANCA-associated vasculitis. These conditions commonly present with hematuria, proteinuria, or nephrotic syndrome, and many respond to corticosteroid or immunosuppressive therapy. Other less frequent renal complications include thrombotic microangiopathy, acute tubulointerstitial nephritis, and IgG4-related nephritis. In conclusion, both COVID-19 infection and vaccination can be associated with a spectrum of renal manifestations ranging from AKI to CKD and immune-mediated glomerulopathies. Awareness, early detection, and multidisciplinary management are essential to reduce renal morbidity and improve patient outcomes.

There are limited real-world data regarding the safety and effectiveness of onasemnogene abeparvovec (OA; Zolgensma) infusion, a one-time gene replacement therapy, for Japanese patients with spinal muscular atrophy (SMA). We aimed to improve understanding of the real-world outcomes for OA in Japan. We report interim, 5-year results of Japanese post-marketing surveillance of OA (part of the RESTORE registry: NCT04174157). Eighty patients were registered and treated with OA (monotherapy: 30%; bridge or switch to OA: 54%). The median (min, max) age (months) was 3.0 (0, 18) at symptom onset and 10.0 (0, 24) at OA infusion. Forty patients each (50.0%) had two or three survival motor neuron 2 (SMN2) gene copies. Ten patients were identified by newborn screening. Adverse events related to OA were reported in 98.8% (serious: 26.3%; no deaths). Adverse events of special interest occurred in 92.5%, including hepatotoxicity (90.0%), transient thrombocytopenia (62.5%), cardiac adverse events (33.8%), and thrombotic microangiopathy (5.0%). Event-free survival at 3 years since OA administration was 93.0%. There was one death from disease progression. Of 39 patients with two or more developmental milestones, 64.1% achieved new developmental milestones and 15.4% maintained their milestones. Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores increased by ≥ 4 points in 81.8% (54/66). The safety profile of OA in Japanese patients with SMA mirrored that of earlier studies. In our real-world observations, patients showed gains in or maintenance of motor milestones or motor function scores that were sustained over the observation period. NCT04174157 (ClinicalTrials.gov).

Anti-glomerular basement membrane (anti-GBM) disease complicated by thrombotic microangiopathy (TMA) is rare and clinically challenging. In the setting of severe infection and active autoimmune disease, complement activation may reflect a secondary process rather than primary atypical hemolytic uremic syndrome (aHUS). Therapeutic plasma exchange (TPE) is standard therapy for anti-GBM disease, but alternative antibody removal strategies are required when TPE is not tolerated. We describe a 46-year-old female with anti-GBM disease who developed TMA with preserved ADAMTS13 activity (72.04%) and 2.3% schistocytes on peripheral smear. Soluble C5b-9 was elevated in the context of severe concurrent infection. TPE was discontinued due to intolerance (oxygen desaturation, fever, and dizziness). Seven sessions of protein A immunoadsorption (PAIA) were performed for selective antibody removal, and anti-GBM antibody levels decreased from > 400 to 20.80 RU/mL during treatment. Eculizumab was administered on Days 7, 14, and 30, for persistent complement activation. Hematologic and biochemical parameters stabilized and gradually improved during combined therapy. This case suggests that PAIA may represent a feasible alternative antibody removal strategy in anti-GBM disease intolerant to plasma exchange. In selected cases of secondary complement-mediated TMA with ongoing complement activation, short-term complement inhibition may contribute to disease stabilization; however, a definitive causal relationship cannot be established in a single case.

Hemolytic-uremic syndrome (HUS) is a thrombotic microangiopathy that is most commonly caused by infection with Shiga toxin-producing Escherichia coli (STEC-HUS). Atypical HUS (aHUS) is associated with inappropriate activation of the alternative complement pathway caused by infections, including SARS-CoV-2, malignancies, medications, or other triggering factors in genetically predisposed individuals. Assessment of the impact of the COVID-19 pandemic on epidemiology, course, complications, and outcome of HUS in children in a single tertiary nephrological center in Poland. It is a retrospective study, in which a total number of 74 pediatric patients with HUS were analyzed, including 16 cases in 5-year period before the outbreak of the COVID-19 pandemic (HUS-5) and 58 cases in 5-year period after the outbreak of the pandemic (HUS+5). A more than 3.6-fold increase in HUS cases and a 7-fold higher incidence of STEC-HUS were reported in the HUS+5 population. Strokes and persistent neurological complications were observed only in this group. 91.9% of patients presented with abnormal renal ultrasound (USG) findings at admission, and these findings improved significantly more frequently in the HUS-5 (68.75% vs 25.9%, p = 0.002) group. Mortality did not differ significantly between the 2 analyzed groups and was 6.8% for the entire population. The COVID-19 pandemic has had a significant impact on the incidence of HUS in the pediatric population. SARS-CoV-2 infection most markedly increases the risk of neurological complications but does not affect overall mortality.

TA-TMA and GVHD are distinct consequences of endothelial injury: A MIDAS consortium study.