The direct thrombin inhibitor argatroban is licensed for use in Heparin-induced thrombocytopenia. Original trial data gave the recommendation of monitoring argatroban by Activated Partial Thromboplastin Time (APTT) stating a therapeutic target range of 1.5-3.0 times baseline APTT and not exceeding 100 s. APTT has limitations due to prolongation arising in factor deficiencies, lupus anticoagulants, liver disease, and high FVIII levels leading to potential overestimation of argatroban. Argatroban has demonstrated a plateau effect on APTT at higher concentrations; additionally, APTT reagents have different sensitivity to argatroban, potentially underestimating or overestimating the argatroban. Anti-IIa methods have been recommended as a suitable alternative to accurately quantify argatroban levels. However, there is a lack of consensus on what the target therapeutic range should be. This review will demonstrate how argatroban monitoring by APTT may not be the most suitable method to successfully dose argatroban based on the current state of knowledge and recent published guidelines and highlight the benefits of the anti-IIa methods.

This case describes an unusually severe presentation of immune-mediated heparin-induced thrombocytopenia type 2 (HIT2), marked by an abrupt and profound decline in platelet count to levels below 2000/µL. Although HIT typically presents with moderate thrombocytopenia and thrombotic complications, such an extreme nadir in the absence of disseminated intravascular coagulation (DIC) or other hematologic disorders is highly atypical. The patient's course reinforces the need to consider HIT even when thrombocytopenia appears disproportionately severe and highlights that appropriate anticoagulation can be initiated safely despite concurrent bleeding, provided the diagnosis is promptly recognized. A 76-year-old man with chronic kidney disease, diabetes, and cardiovascular disease was admitted with acute respiratory failure, community-acquired pneumonia, and a non-ST-elevation myocardial infarction complicated by complete heart block. He received multiple heparin products, including IV continuous heparin, prophylactic dosing, and heparin flushes for catheter maintenance, as well as piperacillin-tazobactam during his hospitalization. Within 12 hours, he developed mucosal bleeding, widespread purpura, and a sudden drop in platelet count from 93000/µL to below 2000/µL. Laboratory testing confirmed the diagnosis of HIT2, and alternative diagnoses such as DIC and thrombotic thrombocytopenic purpura were clinically excluded. Treatment included immediate cessation of heparin, initiation of argatroban, high-dose intravenous immunoglobulin, and corticosteroids. The patient's platelet count improved after the withdrawal of both heparin and piperacillin-tazobactam; however, re-exposure to the antibiotic later provoked another platelet decline, suggesting a secondary drug-induced immune mechanism. This case illustrates the diagnostic and therapeutic challenges posed by severe thrombocytopenia in HIT, especially when overlapping medication effects and bleeding risks complicate management decisions. It emphasizes the importance of timely recognition and the careful balancing of anticoagulation in patients at risk for both thrombosis and hemorrhage.

We conducted a post hoc analysis of the ARAIS (Argatroban Plus Recombinant Tissue-Type Plasminogen Activator for AIS) trial to investigate whether diabetes mellitus (DM) affects the efficacy of argatroban plus alteplase in patients with acute ischaemic stroke (AIS). Patients were categorized into DM and non-DM subgroups. In each subgroup, outcomes were compared between the argatroban plus alteplase group and the alteplase alone group. Additionally, the interaction between DM and treatment efficacy was assessed. The primary outcome was excellent functional outcome at 90 days, which was defined as a modified Rankin Scale score of 0-1. A total of 696 patients were included in this study. Regarding the primary outcome, the treatment effect was comparable between the argatroban plus alteplase group and the alteplase alone group both in the DM subgroup (58.4% versus 63.0%; adjusted risk difference, 1.1%; 95% CI, -13.8% to 16.1%; P = 0.88) and the non-DM subgroup (65.8% versus 65.3%; adjusted risk difference, 0.9%; 95% CI, -6.9% to 8.7%, P = 0.81). No significant interaction was observed between DM and treatment effect on the primary outcome (P = 0.93). Compared with alteplase alone, the efficacy of argatroban plus alteplase in achieving excellent functional outcomes at 90 days did not differ by DM status in patients with AIS.

Anticoagulation is used in intensive care medicine to prevent and treat thromboembolism. The increased risk of bleeding in this patient population requires a personalized approach to management including individualized anticoagulant selection and dose adjustment. While low-molecular-weight heparins are equivalent or superior to unfractionated heparin for thromboprophylaxis, unfractionated heparin is the preferred therapy for the treatment of thromboembolism. Its advantages include a relatively short half-life, the ability to monitor therapy using the activated partial thromboplastin time and the possibility of rapid and effective reversal. The direct thrombin inhibitor argatroban is a reserve anticoagulant used to treat patients with heparin-induced thrombocytopenia. The advantages of argatroban are its short half-life, hepatic clearance, and the ability to monitor therapeutic levels using the activated partial thromboplastin time.

Heparin-induced thrombocytopenia (HIT) is an immune prothrombotic disorder characterized by the binding of platelet-activating immunoglobulin G antibodies to platelet factor 4/heparin. In platelets, this leads to cross-linking of the immunoreceptor tyrosine-based activation motif (ITAM)-bearing receptor FcγRIIa, platelet activation, and thrombocytopenia, which in combination with extensive thrombin generation significantly increases the risk of thrombosis. Our laboratory has previously demonstrated that 12-lipoxygenase (12-LOX), an oxygenase primarily expressed in platelets, plays a critical role in platelet activation through FcγRIIa. In this study, we aimed to determine the effectiveness of VLX-1005, a potent and selective inhibitor of 12-LOX, alone or in combination with argatroban, in preventing HIT. Pretreatment with VLX-1005 attenuated aggregation of human washed platelets stimulated with a HIT immune complex in vitro. VLX-1005 prevented ITAM-induced human whole-blood impedance alone or in combination with argatroban. VLX-1005 treatment impaired platelet adhesion and accumulation on a collagen-coated surface under shear stress. Mice expressing transgenic human FcγRIIa and 12-LOX experienced severe thrombocytopenia and thrombosis after a HIT-like challenge, whereas mice expressing transgenic human FcγRIIa with 12-LOX knockout were completely refractory to HIT pathology. VLX-1005 treatment did not affect coagulation or increase the risk of bleeding. This study demonstrates that inhibition of 12-LOX might be an effective intervention for preventing ITAM-regulated platelet activation, such as in HIT, and is independent of argatroban effects in blood. Importantly, VLX-1005 prevents platelet activation and does not increase the bleeding risk associated with direct thrombin inhibitors, such as argatroban.

Thrombus in transit (TIT), defined as mobile right atrial or right ventricular thrombi often associated with acute pulmonary embolism (PE), carries a high risk of morbidity and mortality. Optimal management remains controversial, with options including anticoagulation, systemic thrombolysis, surgical embolectomy, and percutaneous thrombectomy. We describe two elderly women with a history of thromboembolic disease who presented with acute decompensation in the setting of TIT and recurrent PE. The first case involved an 81-year-old female with massive bilateral PE and right atrial thrombus who underwent suction thrombectomy but died perioperatively. The second case involved a 74-year-old female with prior right atrial thrombectomy for TIT who presented with acute hypoxemic respiratory failure, large left pleural effusion, recurrent PE, and septic shock; despite anticoagulation with Argatroban and intensive care support, she developed cardiac arrest and died. These cases underscore the diagnostic and therapeutic challenges of TIT, particularly in elderly patients with multiple comorbidities. Early recognition, multidisciplinary coordination, and individualized management remain essential, but outcomes can be poor despite aggressive interventions.

Heparin-induced thrombocytopenia (HIT) is a serious and potentially life-threatening reaction to heparin, affecting 0.1% to 5% of patients. Those with end-stage renal disease face an and even higher risk because of repeated exposure to heparin during dialysis. HIT Type II, an immune-mediated condition, results from antibodies against heparin/platelet factor 4 (PF4) complexes, leading to platelet activation and thromboembolism. We present a 78-year-old woman with end-stage kidney disease (ESRD) who developed HIT Type II after low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) exposure during hemodialysis. Despite a negative PF4/heparin ELISA, a 4T score of 7 confirmed the presence of clinical HIT. She experienced thrombocytopenia (30×109/L) and severe thrombotic events. Heparin was discontinued, and anticoagulation transitioned to argatroban and later nafamostat mesilate (NM) due to argatroban shortage. Platelet counts normalized (223×109/L), and NM was effective without clotting complications. This case highlights the challenges in HIT diagnosis, emphasizing the role of clinical evaluation over laboratory tests, and underscores the utility of NM as an alternative anticoagulant in resource-limited settings. Key questions remain regarding heparin rechallenge safety, causative agent identification in multi-heparin exposure, and rapid differentiation of HIT from anaphylactoid reactions. Further studies are needed to optimize HIT management in high-risk populations.

Coagulation is a physiological process necessary to achieve homeostasis. Many pathologies lead to spontaneous activation of the coagulation pathways and increase the risk of venous thrombosis (e.g., atrial fibrillation, orthopaedic surgery, cancer). Therefore, a lot of patients need anticoagulant drugs as preventive or curative treatment. In general, older molecules (unfractionated heparin, low-molecular-weight heparins, vitamin K antagonists) have good efficacy. Still, their adverse reactions, increased risk of bleeding, or difficult administration led to low adherence to treatment and had even limited their use. Recently, new molecules were authorised to improve patient adherence to treatment, mainly formulated for oral administration (e.g., dabigatran, rivaroxaban, apixaban, etc.). This therapeutic approach has a low risk of bleeding and does not require special monitoring by laboratory tests. Also, new anticoagulants for patients with heparin-induced thrombocytopenia (e.g., argatroban, lepirudin, bivalirudin, etc.) were obtained. Moreover, reversal agents for the new anticoagulant molecules used in overdoses or in situations where immediate cessation of the anticoagulant effect is required (e.g., emergency surgery) were studied, some of them being authorised on the pharmaceutical market. This narrative review aims to provide a pharmacological and therapeutic overview of anticoagulant drugs, underlining their implementation and limitations.