Dabigatran approaching the realm of heparin-induced thrombocytopenia

Ho, Patricia J; Siordia, Juan A.

doi:10.5045/br.2016.51.2.77

Cited by 7 publications

(4 citation statements)

References 71 publications

(89 reference statements)

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“…This prothrombotic adverse reaction, named heparin-induced thrombocytopenia (HIT), is mediated by immunity and is also caused by an interaction between heparin and protein. Heparin products form multimolecular complexes with antigenic platelet factor 4 (PF4), resulting in the formation of IgG platelet-activating antibodies which are against the heparin/PF4 complex, which triggers an immune response and induces platelet activation and aggregation ( Ho and Siordia, 2016 ). This process leads to platelet reduction and thrombin generation, ultimately resulting in thrombocytopenia.…”

Section: Human Diseases Related To Gag-protein Interactionsmentioning

confidence: 99%

Glycosaminoglycan-Protein Interactions and Their Roles in Human Disease

Shi

Sheng

Chi

2021

Front. Mol. Biosci.

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Glycosaminoglycans (GAGs) are a family of linear and negatively charged polysaccharides that exist ubiquitously on the human cell surface as well as in the extracellular matrix. GAGs interact with a wide range of proteins, including proteases, growth factors, cytokines, chemokines and adhesion molecules, enabling them to mediate many physiological processes, such as protein function, cellular adhesion and signaling. GAG-protein interactions participate in and intervene in a variety of human diseases, including cardiovascular disease, infectious disease, neurodegenerative diseases and tumors. The breakthrough in analytical tools and approaches during the last two decades has facilitated a greater understanding of the importance of GAG-protein interactions and their roles in human diseases. This review focuses on aspects of the molecular basis and mechanisms of GAG-protein interactions involved in human disease. The most recent advances in analytical tools, especially mass spectrometry-based GAG sequencing and binding motif characterization methods, are introduced. An update of selected families of GAG binding proteins is presented. Perspectives on development of novel therapeutics targeting specific GAG-protein interactions are also covered in this review.

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Section: Human Diseases Related To Gag-protein Interactionsmentioning

confidence: 99%

Glycosaminoglycan-Protein Interactions and Their Roles in Human Disease

Shi

Sheng

Chi

2021

Front. Mol. Biosci.

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“…Argatroban has been used as the first‐line therapy for HIT. Moreover, dabigatran was reportedly effective against HIT 4 . The dose of dabigatran was reduced based on the patient's age, but this possibly reduced its efficacy.…”

Section: Discussionmentioning

confidence: 99%

A case of idiopathic intracardiac and pulmonary arterial thrombosis successfully treated with surgical thrombectomy

Maruyama

Shibata

Nagashima

et al. 2022

Neurology & Clinical Neurosc

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An 81-year-old Japanese man, who complained of right orbital pain and reduced right visual acuity to the level of light perception, was admitted to our hospital. He had a history of sustained atrial fibrillation and took dabigatran (220 mg/day).The blood laboratory data showed a mild inflammatory reaction, and the cerebrospinal fluid examination was essentially normal.The whole-body computed tomography (CT) showed no findings suggestive of a malignancy. Cerebral magnetic resonance imaging (MRI) with intravenous gadolinium administration showed marked enhancement of the bilateral cavernous sinuses and right orbital apex area (Figure 1A). A transorbital biopsy of the lesion was scheduled to confirm the pathological diagnosis. Four days before the biopsy, dabigatran was changed to unfractionated heparin. Dabigatran administration was immediately resumed after the biopsy. The biopsy specimen revealed nonspecific inflammatory cell infiltration.A definitive diagnosis was not achieved, but an idiopathic autoimmune reaction was suspected. After initiating steroid treatment, the patient's right orbital pain and abnormal imaging findings were resolved, but he remained blind in the right eye.On the 13th hospital day, a follow-up cerebral MRI revealed an asymptomatic cerebellar infarction (Figure 1B). On the 41st hospital day, a repeat cerebral MRI showed another small asymptomatic cerebral infarction in the right occipital lobe (Figure 1C). Chest CT and transesophageal echocardiography revealed an asymptomatic hillshaped pulmonary artery thrombus (Figure 1D) and a free-floating ball-shaped left atrial thrombus (Figure 1E). Dabigatran was changed to rivaroxaban (30 mg/day), but the intracardiac thrombus persisted.Therefore, the patient underwent a left atrial appendectomy for thrombus removal on the 61st hospital day (Figure 1F). Heparin-induced thrombocytopenia (HIT) was suspected because of the significant decline in platelet counts after heparin administration and the presence of multiple thromboses (Figure 1G).

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“…Recently, novel anticoagulants were proposed as alternative agents in the treatment of HIT. [ 14 ] Positive results have been reported for the use of NOACs in the treatment of HIT. [ 15 ] We had ten patients with suspected HIT, which dabigatran was prescribed for them.…”

Section: Discussionmentioning

confidence: 99%

New indications for dabigatran: A suggestion from a drug use evaluation study

2017

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Objective:Dabigatran etexilate is a novel oral anticoagulant with several advantages over warfarin such as no need for routine monitoring and fewer drug interactions. This drug was added to our hospital's formulary in 2012. The objective of this study was to assess the rational drug use of dabigatran at a large teaching hospital.Methods:A prospective cross-sectional study was performed from November to June 2015 at Alzahra teaching hospital, Isfahan, Iran. All patients who received at least one dose of dabigatran were eligible for inclusion. Data were collected on patient demographics, indication, dosing regimen, adverse events, concurrent anticoagulant therapy, and laboratory data (including renal function).Findings:A total of sixty patients were included in our study. The majority of patients (n = 40, 66.7%) was prescribed dabigatran for deep vein thrombosis prophylaxis. Only one patient received dabigatran with appropriate indication, dose, and duration. Thirty-six (60%) of our patients had thrombocytopenia at the time of dabigatran initiation. We also detected that ten patients (16.7%) received this drug for heparin-induced thrombocytopenia (HIT). In 32 patients, platelet levels increased after dabigatran initiation. Only seven patients received the appropriate dose of dabigatran (regarding both indication and renal function).Conclusion:Unlabeled use and incorrect dosing of dabigatran in this study emphasize the need to develop a hospital protocol for dabigatran use within our facility. We suggest proper education of clinicians about novel drugs, pharmacist interventions, and further studies about the safety and efficacy of dabigatran for the new indication (such as HIT).

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Dabigatran approaching the realm of heparin-induced thrombocytopenia

Cited by 7 publications

References 71 publications

Glycosaminoglycan-Protein Interactions and Their Roles in Human Disease

Glycosaminoglycan-Protein Interactions and Their Roles in Human Disease

A case of idiopathic intracardiac and pulmonary arterial thrombosis successfully treated with surgical thrombectomy

New indications for dabigatran: A suggestion from a drug use evaluation study

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