摘要
Background: Heparin-induced thrombocytopenia (HIT) is a relatively common and life-threatening complication of exposure to heparin products, occurring in approximately 0.1% to 5% of patients across various clinical settings. Patients with end-stage renal disease, particularly those undergoing dialysis, are considered a special population in terms of frequent exposure to heparin products.Type I HIT is characterized by a transient and mild decrease in platelet count shortly after the initiation of heparin therapy. This non-immune-mediated process is not associated with any clinical manifestations, and platelet levels typically normalize after discontinuation of heparin. In contrast, Type II HIT is an immune-mediated condition caused by the development of antibodies against complexes of heparin and platelet factor 4 (PF4). These antibody/PF4/heparin complexes bind to platelets via the FcγRIIA receptor and cause platelet activation, leading to platelet activation and subsequent venous or arterial thromboembolism. Type II HIT typically manifests 5-10 days after heparin initiation, although it can occur immediately in patients with recent heparin exposure (within the past 100 days). Thrombocytopenia is usually moderately severe, with a greater than 30–50% decline from baseline in platelet count, less than 100×109/L and results in a prothrombotic state. The platelet counts generally recover within 5 to 10 days after heparin withdrawn.
When HIT is suspected, all heparin exposure must be discontinued immediately. Given the high risk of arterial and venous thrombosis in these patients, alternative systemic anticoagulants such as argatroban, bivalirudin, danaparoid, or hirudin should be initiated promptly. Although nafamostat mesilate (NM) is not approved by the FDA, it is widely used in Japan and Korea as an anticoagulant. Here, we present a case of Type II HIT in which the patient was successfully transitioned to NM for anticoagulation during maintenance hemodialysis.
Method: A 78-year-old Asian woman, with a medical history of stage 5 chronic kidney disease (CKD), type 2 diabetes mellitus, hypertension, and stent graft insertion following myocardial infarction was admitted due to heart failure, hyperkalemia, and edema. She also had a history of atrial fibrillation and had been taking rivaroxaban irregularly before admission on December 24, 2021. 4 days post-admission, hemodialysis was initiated via the right internal jugular vein, with low-molecular-weight heparin (LMWH) selected as the anticoagulant. Unfractionated heparin (UFH) was used for catheter locking. Her condition improved following dialysis, and an arteriovenous fistula (AVF) was created between the left radial artery and cephalic vein on January 6, 2022. On day 11 post-admission, the patient developed acute dyspnea, hypotension, and cardiac arrest, within 10 minutes of initiating hemodialysis. She was successfully resuscitated with manual cardiopulmonary resuscitation (CPR) and oxygen therapy. An electrocardiogram (ECG) revealed controlled atrial fibrillation at a rate of 90 beats per minute. Duplex ultrasonography of the lower limbs was performed, which did not reveal any evidence of deep vein thrombosis (DVT) at that time. Subsequent echocardiography showed an ejection fraction of 53%, and a CT pulmonary angiogram ruled out major pulmonary embolism (PE). Laboratory evaluation revealed a 50% reduction in platelet count (from 158×109/L to 59×109/L) without evidence of thrombosis, which was excluded by the ultrasound results. And the D-Dimer was elevated from 1.4μg/ml to 2.43μg/ml. Prothrombin time (PT) was 11.9s and activated partial thromboplastin time (aPTT) was 33.4s. She received 2 units of platelet transfusion, but her platelet counts further dropped to 30×10?/L. Blood samples were drawn for heparin-induced thrombocytopenia (HIT) testing, including ELISA for immunoglobulin IgG, IgA, and IgM antibodies against the PF4/heparin complex (GTI-PF4 ELISA, GTI, Wis., USA), which returned negative. However, based on a 4T score of 7, HIT was clinically diagnosed.
Results:
On day 17 post-admission, anticoagulation was withheld during dialysis. However, due to the high risk of thromboembolic complications from cardiac arrhythmia and HIT, rivaroxaban was restarted at 10 mg twice daily. Concurrently, ultrasonography revealed multiple venous and arterial thrombotic events, acrocyanosis, distal ischemic limb necrosis, dialysis circuit clotting, and catheter thrombosis. The patient required two central venous catheter replacements due to vascular access thrombosis and venous thrombosis. Within 10 days of heparin discontinuation and the use of tissue plasminogen activator (tPA) for catheter locking, her platelet count increased to 67×109/L. On day 27 post-admission, argatroban was initiated for dialysis anticoagulation, while rivaroxaban (10 mg twice daily) was continued. Her platelet counts subsequently recovered to 223×109/L. On day 47 post-admission, argatroban was discontinued, and the dose of rivaroxaban was reduced to 10 mg daily due to mucosal bleeding, bright red blood per rectum, and an elevated INR. During the SARS-CoV-2 pandemic, the patient was transferred to another hospital on day 90 post-admission. Due to a shortage of argatroban, NM (dissolved in 5% glucose and injected at a dose of 25 mg per hour) was the anticoagulant during hemodialysis. Nearly one year after initiating hemodialysis, rivaroxaban was discontinued following ultrasonographic confirmation of no further venous thrombosis. During weekly outpatient follow-ups, her platelet count remained within the normal range, and her dialysis flow rate was maintained at 200–220 mL/min.
Conclusion: This case highlights the importance of clinical diagnosis in HIT, even with negative laboratory tests, and demonstrates the efficacy of NM as an alternative anticoagulant in resource-limited settings. Further studies are needed to clarify heparin rechallenge safety and identify causative agents in patients exposed to multiple heparin products.
