---
title: "Heparin-induced thrombocytopenia during therapeutic plasma exchange in neuromyelitis optica: singl"
id: "frontiers-in-immunology-17-case-report-confirmed-and-suspected-heparin-induced-thrombocytopenia-during"
canonical_url: "https://medichelpline.com/clinical-feed/frontiers-in-immunology-17-case-report-confirmed-and-suspected-heparin-induced-thrombocytopenia-during"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "Frontiers in Immunology"
source_url: "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1884839"
published_at: "2026-09-14T00:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Heparin-induced thrombocytopenia during therapeutic plasma exchange in neuromyelitis optica: singl
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/frontiers-in-immunology-17-case-report-confirmed-and-suspected-heparin-induced-thrombocytopenia-during
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** Frontiers in Immunology
- **Source URL:** [Original Journal Publication](https://www.frontiersin.org/articles/10.3389/fimmu.2026.1884839)
- **Published At:** 2026-09-14T00:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- Source article title indicates a single-centre case series reporting both confirmed and suspected **heparin-induced thrombocytopenia** (HIT) occurring during **therapeutic plasma exchange** (TPE) for patients with **neuromyelitis optica spectrum disorder** (NMOSD). - The article type is a case report / single-centre case series published in Frontiers in Immunology; no patient-level data are available in the provided source extract. - The provided source content contains only website navigation and metadata; the body text, including methods, patient numbers, timing, diagnostic criteria, laboratory tests, anticoagulation protocols, clinical outcomes, and management decisions, was not included in the source material supplied for this rewrite. - Because the full article content was not present in the source excerpt, specific findings (number of confirmed vs suspected HIT cases, platelet trajectories, PF4/heparin antibody results, functional testing, anticoagulant alternatives used, bleeding or thrombotic events, or follow-up) cannot be reported and were not inferred. - Key elements that are missing and could be relevant to clinical readers include: case definitions and diagnostic criteria for HIT, TPE procedural details (access type, heparin use for catheter patency or systemic anticoagulation), timing of platelet count decline relative to heparin exposure, laboratory confirmation methods, therapeutic changes after suspected HIT, and patient outcomes. - Readers are advised to consult the full Frontiers in Immunology article for complete methods, case descriptions, diagnostic testing, management, and authors’ conclusions because those details were not available in the excerpt used here.
## Clinical Analysis & Structured Key Points
Frontiers | Case Report: Confirmed and suspected heparin-induced thrombocytopenia during therapeutic plasma exchange in neuromyelitis optica spectrum disorder: a single-centre case series CASE REPORT article Front. Immunol. , 14 September 2026 Sec. Autoimmune Disorders Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1884839 Published in Frontiers in Immunology Autoimmune Disorders 7 impact factor 11.3 citescore Part of a Research Topic Underecognized Issues in Women with Demyelinating Disorders Submission open 4044 views 2 articles Editor & Reviewers Edited by N S Natalia Szejko Reviewed by J M José Miguel Valdés J C JUANJUAN CHEN Outline Figures and Tables Figure 1 View in article Figure 2 View in article Figure 3 View in article Table 1 Patients with NMOSD treated with TPE (n=24). View in article Table 2 Patient characteristics. View in article CASE REPORT article Front. Immunol. , 14 September 2026 Sec. Autoimmune Disorders Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1884839 Case Report: Confirmed and suspected heparin-induced thrombocytopenia during therapeutic plasma exchange in neuromyelitis optica spectrum disorder: a single-centre case series A P Aleksandra Podlecka-Piętowska † * J R Joanna Rychter † K S Kinga Sujkowska B Z Beata Zakrzewska-Pniewska M N Monika Nojszewska Department of Neurology, Medical University of Warsaw, Warsaw, Poland Article metrics View details Abstract Neuromyelitis optica spectrum disorder (NMOSD) is a B-cell–mediated autoimmune disease associated with aquaporin-4 (AQP4-IgG) antibodies in which patients may require anticoagulation, including heparin for venous thromboembolism prophylaxis, thereby exposing them to a risk of heparin-induced thrombocytopenia (HIT), an immune-mediated complication caused by antibodies directed against PF4–heparin complexes. Whether anti-AQP4–mediated autoimmunity contributes to susceptibility to anti-PF4/heparin immune responses warrants further investigation. Four cases of suspected or confirmed HIT in patients with NMOSD are presented, together with a review of the current literature. In our NMOSD cohort (n=90), 24 patients underwent therapeutic plasma exchange (TPE), among whom HIT was suspected in four cases (16,7% suspected and 8.3% immunoassay positive). These findings underscore the need for vigilance regarding HIT and thromboembolic complications in NMOSD patients undergoing relapse treatment with TPE. Strategies for the safe continuation of TPE using non-heparin anticoagulation and considerations for outpatient management are also addressed. Awareness of this potential association may facilitate earlier recognition and appropriate management in clinical practice. 1 Introduction Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy characterised by demyelinating lesions predominantly affecting the optic nerves, spinal cord, and brainstem. Serum aquaporin-4 (AQP4)-IgG antibodies play a central pathogenic role and are present in most patients ( 1 ). The prevalence of NMOSD is estimated to range from approximately 0.5 to 4 per 100,000, with a marked female predominance (female-to-male ratio of about 9:1). Current diagnostic criteria are based on the 2015 consensus by Wingerchuk et al. ( 2 ), although updated recommendations have been proposed at the 2025 ECTRIMS Congress ( 3 ). As these late-breaking guidelines remain preliminary, the 2015 IPND criteria remain the current diagnostic standard. Immunosuppressive and immunotherapeutic strategies are recommended to prevent relapses that can result in severe disability ( 4 ). Anticoagulation is often required during the course of NMOSD, particularly for venous thromboembolism prophylaxis and during therapeutic plasma exchange (TPE) performed for relapse treatment ( 5 ). However, exposure to heparin carries a risk of heparin-induced thrombocytopenia (HIT), an immune-mediated adverse reaction caused by antibodies directed against platelet factor 4–heparin complexes (anti-PF4/heparin Abs) ( 6 ). HIT is associated with both venous and arterial thrombosis and can be life-threatening. This article describes the co-occurrence of two rare conditions, NMOSD and HIT, in the context of the available literature. Between 2019 and 2025, four cases of confirmed or probable HIT were identified among patients with NMOSD treated at the Department of Neurology, Medical University of Warsaw. 2 Methods A retrospective analysis was performed of patients with NMOSD (n=90) treated at our institution between 2019 and 2025. Patients were identified from a prospectively maintained institutional database approved by the Bioethics Committee of the Medical University of Warsaw. Among the 24 patients who underwent TPE for NMOSD relapse treatment, four cases of suspected or confirmed HIT were identified and included in this study. Clinical data, including demographic characteristics, NMOSD therapies, heparin exposure, TPE procedures, platelet count dynamics monitored systematically at regular intervals (with assessments performed on alternate days), HIT diagnostic evaluation, management, and clinical outcomes, were retrospectively collected and analysed. TPE was performed by membrane filtration using unfractionated heparin (UFH) for circuit anticoagulation (5,000 IU intravenous bolus followed by a continuous infusion of 2,000 IU/h). Albumin (50 mL/kg body weight) was used as the replacement fluid. Five to seven TPE sessions were initially planned on alternate days, with the final number and timing determined by the patient’s clinical condition. Following suspected HIT in Case 4, TPE was switched to centrifugal apheresis using citrate anticoagulation. The timing of TPE procedures is shown in Figures 1 – 3 . Figure 1 Case 2: the trend of platelet count during hospitalization. TPE marked with blue arrows. Day 0 aligns with the first heparin exposure. Figure 2 Case 3: the trend of platelet count during hospitalization. TPE marked with pink arrows. Day 0 aligns with the first heparin exposure. Figure 3 Case 4: The trend of platelet count during hospitalization. TPE marked with yellow arrows. Day 0 aligns with the first heparin exposure. Patients with suspected HIT underwent haematological consultation, and the pretest probability of HIT was assessed using the 4Ts score. Those with an intermediate or high 4Ts score underwent anti-PF4/heparin Abs testing. Anti-PF4/heparin IgG Abs were measured using a commercially available ELISA (Immucor, USA). According to the manufacturer’s instructions, an optical density (OD) value >0.4 was considered positive. Positive immunoassay results were obtained in Cases 2 and 3. Written informed consent was obtained from the patient for publication of this case report. 3 Case reports 3.1 Case 1 A 44-year-old woman with seropositive NMOSD diagnosed in July 2019 was transferred to our unit in August 2019 due to steroid-refractory relapse with spastic paraplegia, sensory impairment, and urinary retention (EDSS 7.0). Clinical deterioration was associated with thoracic spinal cord lesions on magnetic resonance imaging (MRI). Laboratory tests were unremarkable at admission. Due to progressive sphincter dysfunction, seven TPE sessions were initiated on alternate days. During hospitalisation, the platelet count decreased from 389 × 10 9 /L at admission to a nadir of 58 × 10 9 /L, representing an 85% decrease. The 4Ts score was estimated at 5–7, depending on the timing of platelet nadir, which could not be precisely determined; anti-PF4/heparin antibody status was unavailable, and these data are therefore not presented in the Figures. Ultrasound confirmed deep vein thrombosis of the right lower limb. Following suspicion of HIT, heparin was discontinued, TPE was suspended, and fondaparinux (7.5 mg once daily) was initiated. Platelet count recovered to 329 × 10 9 /L by the time of discharge. Due to suspected HIT, the patient was subsequently transitioned to rivaroxaban 20 mg once daily and remains under outpatient care at a vascular diseases clinic. During follow-up, the patient reported gradual clinical improvement, with EDSS decreasing to 6.5 after relapse treatment. Since 2019, the patient has remained on rituximab with sustained clinical remission (current EDSS 5.0) and continues rivaroxaban due to previous lower-limb venous thromboembolism. Anti-PF4/heparin IgG status was not reassessed during follow-up. 3.2 Case 2 In July 2021, a 53-year-old woman with seropositive NMOSD diagnosed in 2016 was admitted due to a steroid-refractory relapse characterised by upper limb paresthesias, severe lower limb weakness, and vomiting (EDSS 8.5). MRI revealed new demyelinating lesions in the brain and cervical spinal cord. Five TPE sessions were initiated on alternate days. Admission laboratory tests were unremarkable. From the initiation of TPE, platelet counts progressively decreased from 175 × 10 9 /L at admission, reaching a nadir of 14 × 10 9 /L on day 10 of heparin, representing a 92% decrease from baseline ( Figure 1 ). Ultrasound demonstrated asymptomatic deep vein thrombosis in the left lower limb and an asymptomatic thrombus in the right internal jugular vein. Chest computed tomography (CT) revealed an asymptomatic peripheral pulmonary embolism. The 4Ts score was 7, indicating a high probability of HIT. Anti-PF4/heparin Abs testing was performed on day 8 of heparin exposure, with a positive anti-PF4/heparin IgG ELISA result. Anticoagulation was subsequently switched to fondaparinux 7.5 mg once daily. TPE was discontinued after five sessions (EDSS 7.0 after relapse treatment). Following initiation of fondaparinux, platelet counts normalised within 16 days, reaching 247 × 10 9 /L at discharge, without clinical complications. The patient was subsequently transitioned to apixaban 5 mg twice daily and remains under the care of our department; she remains on immunosuppressive treatment with rituximab. The patient showed significant neurological improvement, with independent ambulation and current EDSS 5.0. She reported improvement in both physical and emotional well-being after initiation of appropriate treatment. Due to previous pulmonary embolism and venous thromboembolism, long-term anticoagulation with apixaban 2.5 mg twice daily was continued after completion of the therapeutic phase (5 mg twice daily). 3.3 Case 3 A 64-year-old woman with seronegative NMOSD diagnosed in November 2023 was admitted due to a relapse. The initial presentation in July 2023 included acute right lower limb paresis and hypoesthesia below the Th5 level. Spinal MRI revealed longitudinally extensive transverse myelitis (LETM) from Th1 to Th3 with contrast enhancement. Serum anti-AQP4 and myelin oligodendrocyte glycoprotein antibodies (anti-MOG) were negative on fixed cell-based assays (CBA). Cerebrospinal fluid analysis was unremarkable, and infectious workup, including Borrelia testing, was negative. Chest computed tomography (CT) showed no abnormalities. Following intravenous methylprednisolone treatment, the patient achieved gradual neurological improvement, although EDSS remained unchanged (6.5 at admission and discharge). She was discharged with oral methylprednisolone tapering. After rehabilitation, significant functional improvement was observed (EDSS 3.0–3.5). In November 2023, the patient was admitted with a second relapse presenting with spastic paraparesis, hypoesthesia below T7 including the anogenital region, and urinary dysfunction (EDSS 3.5). Follow-up MRI showed a longitudinally extensive thoracic spinal cord lesion (T1–T4) with contrast enhancement and a few small demyelinating brain lesions. Anti-AQP4 and anti-MOG Abs were reassessed using a fixed CBA and remained negative; however, testing was performed during prolonged corticosteroid therapy, which may have affected sensitivity. Due to insufficient response to intravenous methylprednisolone (1000 mg/day for 10 days), five TPE sessions were initiated on alternate days. A total of 7 days after initiation of heparin anticoagulation for TPE, subconjunctival haemorrhage was observed. Platelet counts decreased from 366 × 10 9 /L at admission and 200 × 10 9 /L before heparin exposure to a nadir of 34 × 10 9 /L on day 14 of heparin (83% decrease; Figure 2 ), leading to discontinuation of TPE. HIT was suspected; the 4Ts score was 7, indicating high probability. CT angiography revealed acute left popliteal artery thrombosis. Due to severe thrombocytopenia, surgical intervention was not performed. Anticoagulation was switched to fondaparinux (5 mg once daily), and aspirin (75 mg once daily) was added after multidisciplinary haematology and vascular surgery consultation. Anti-PF4/heparin IgG ELISA performed on day 11 of heparin exposure was positive. Platelet counts recovered to 166 × 10 9 /L at discharge, and anticoagulation was continued with rivaroxaban (20 mg once daily). Neurological status improved, with EDSS remaining stable at 3.5 at discharge. Based on the clinical, radiological, and laboratory findings (negative OCB type 2, serum anti-AQP4, anti-MOG, ANA, and infectious workup), a diagnosis of seronegative NMOSD was established. Neuroimaging findings fulfilled the 2015 IPND criteria, demonstrating LETM during the first relapse (Th1–Th3) and a subsequent new LETM lesion extending from Th1 to Th4, followed by spinal cord atrophy, consistent with NMOSD. Due to the active and fulminant disease course, rituximab therapy was initiated. The patient remains under haematological and vascular surgery follow-up, and CT angiography showed progressive resolution of thromboembolic lesions. Rivaroxaban was continued until March 2025. The patient remained clinically stable, with gradual improvement in daily functioning (current EDSS 2.0). 3.4 Case 4 A 37-year-old man with seronegative NMOSD was admitted in January 2025 with right optic neuritis (EDSS 3.5). His previous relapses (2016–2018) included motor and sensory symptoms, with MRI showing cervical spinal cord lesions (multiple, confluent demyelinating lesions C2–C5 with heterogeneous contrast enhancement and mild oedema) and limited brain lesions. Cerebrospinal fluid analysis performed in 2016 demonstrated the presence of type 2 oligoclonal bands. Serum anti-AQP4 and anti-MOG Abs tested negative using fixed CBA. Differential diagnosis included multiple sclerosis (MS) and NMOSD. He had not received disease-modifying therapy due to personal preference. At admission in 2025, orbital MRI demonstrated longitudinally extensive right optic nerve enhancement, while brain MRI showed few T2-hyperintense lesions with mild corpus callosum thinning. Spinal MRI revealed confluent cervical demyelinating lesions (C2–C5) and marked atrophy. Visual evoked potentials confirmed right optic nerve dysfunction (absent response). Due to poor response to intravenous methylprednisolone (1000 mg/day for 7 days), five TPE sessions were planned on alternate days. On the day of the first TPE session, superficial venous thrombosis of the right arm was diagnosed. From the day of admission, platelet counts progressively decreased from 287 × 10 9 /L and 135 × 10 9 /L before heparin exposure to a nadir of 85 × 10 9 /L on day 6 after heparin initiation (37% decrease; Figure 3 ). Haematological assessment resulted in a 4Ts score of 5, indicating an intermediate probability of HIT. Based on this assessment, rivaroxaban was initiated, and TPE was continued using citrate anticoagulation. Anti-PF4/heparin IgG ELISA performed on day 6 of heparin exposure was negative (functional assays were unavailable at that time). Platelet counts recovered after discontinuation of heparin exposure during TPE, reaching 232 × 10 9 /L at discharge. Based on the clinical presentation, haematological consultation supported the diagnosis of probable HIT, and future avoidance of heparin products was recommended. During hospitalisation, anti-AQP4 and anti-MOG Abs were reassessed using fixed CBA (live CBA was unavailable in Poland) and remained negative at baseline and after 3 months of follow-up. Testing was performed during prolonged corticosteroid therapy, which may have affected assay sensitivity. The patient’s first neurological symptoms occurred in 2016, and during follow-up until 2025, MRI examinations did not demonstrate features suggestive of MS progression, including progression independent of relapse activity (PIRA) or brain atrophy, which are typical for MS. In contrast, marked spinal cord atrophy was observed following longitudinally extensive spinal cord lesions, which is consistent with the 2015 IPND criteria supporting an NMOSD diagnosis. Regarding MS-specific imaging markers, the available brain MRI data did not reveal central vein sign (CVS) or paramagnetic rim lesions (PRLs), which are increasingly recognised as supportive biomarkers of MS according to the 2024 revision of the McDonald criteria. Clinically, the patient presented with severe, treatment-refractory optic neuritis characterised by longitudinally extensive optic nerve involvement, a pattern typical of NMOSD. Neuroimaging did not reveal features suggestive of MOG-associated disease, such as optic nerve perineuritis. Additionally, visual evoked potentials demonstrated absent responses from the affected eye, supporting severe optic nerve injury. Cerebrospinal fluid analysis revealed type 2 oligoclonal bands, which, although more commonly associated with multiple sclerosis, may also be present in a subset of NMOSD patients ( 1 ). Based on the clinical, radiological, and laboratory findings, seronegative NMOSD was diagnosed, and rituximab therapy was initiated due to active disease. Follow-up care in haematology and neurology outpatient clinics was arranged; anti-PF4/heparin IgG serostatus was not reassessed. Following initiation of rituximab therapy, the patient achieved clinical stabilisation of NMOSD, with EDSS remaining at 3.5. Rivaroxaban was discontinued after 1 month of treatment based on recommendations from a haematologist and vascular surgeon. 4 Discussion HIT is a rare condition with an incidence ranging from 0.1% to 7% among hospitalised patients ( 7 ). The coexistence of NMOSD and HIT, both rare conditions, is therefore noteworthy. In our unit, 90 patients with NMOSD were followed; among 24 NMOSD patients undergoing TPE ( Table 1 ), HIT was suspected in 4 cases (16,7%) and immunoassay positive in 2 cases (8,3%). The most recent and largest directly relevant series by Lv et al. (2025) ( 8 ) reported that among 158 patients with neurological autoimmune diseases undergoing TPE, 139 developed a significant decrease in platelet count; however, only 23 patients with a continuous platelet decline and 4Ts scores ≥ 4 underwent PF4 antibody testing, and of these only 4 tested positive (2.5%). Clinical reports have suggested a possible association between inflammatory neurological diseases, such as NMOSD or MS, and an increased risk of HIT; However, the current evidence remains limited, precluding definitive conclusions ( 7 , 9 ). Table 1 Variable Without HIT suspicion (n=20) HIT suspected or confirmed (n=4) Mean age (years) 51.3 49.5 Mean disease duration (years) 8.9 6 Mean baseline EDSS 5.5 5.5 Positive AQP4-IgG serostatus (n) 16 2 Core clinical manifestation (n) • optic neuritis 18 1 • myelitis 16 3 • area postrema syndrome 9 0 Patients with NMOSD treated with TPE (n=24). Although most patients with NMOSD test positive for AQP4-IgG or MOG-IgG, there exists a subset of double-seronegative patients who share similar clinical and radiological features ( 10 ). The pathophysiology of NMOSD is likely driven by a heterogeneous inflammatory response, with the primary mechanism involving B-cell–mediated injury with AQP4-IgG binding to astrocytes, complement system activation, subsequent antibody-dependent cell-mediated cytotoxicity (ADCC), and inflammation. Given the chronic inflammation associated with this condition, it may trigger procoagulant responses ( 9 , 11 ). In standard relapse
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