We investigated the clinical characteristics and treatment outcomes of heparin-induced thrombocytopenia (HIT) following therapeutic plasma exchange (TPE) with heparin anticoagulation in patients with neurological autoimmune diseases.Clinical data were prospectively collected from 158 patients (79 males, 79 females; mean age 37.49 ± 16.95 years) with neurological autoimmune diseases who underwent TPE in the neuro-intensive care unit between January 2016 and June 2024. For patients with continuous platelet decline after TPE, the 4Ts score was determined, and platelet factor 4 (PF4) antibody tests were performed. Their platelet counts, clinical complications (thrombosis and bleeding), treatment plans, outcomes, and prognoses before and after TPE were analyzed.One hundred thirty-nine patients experienced at least one significant decrease in platelet count during TPE (average decrease 36.75 ± 19.63%), and the average 4Ts score was 3.55 ± 1.87 points. PF4 antibody testing was conducted on 23 patients with continuous platelet decline and 4Ts scores ≥ 4. Four PF4-positive patients were diagnosed with type II HIT and developed deep vein thrombosis. After heparin withdrawal, the platelet count gradually normalized after intravenous immunoglobulin (IVIG), nonheparin TPE, or argatroban/fondaparinux anticoagulant therapy (mean recovery time 8.17 ± 3.54 days). The platelet counts spontaneously recovered for the remaining 116 patients (mean recovery time 3.88 ± 2.66 days).Platelet counts should be dynamically monitored throughout TPE with heparin anticoagulation. Patients with continually decreasing platelet counts and an intermediate to high 4Ts score should be monitored for HIT. Heparin should be discontinued immediately for patients with type II HIT, and nonheparin anticoagulants, IVIG, or nonheparin TPE may be administered.© 2025 Wiley Periodicals LLC.