Acquired Bleeding Disorders

Hurwitz, Alisheba; Massone, Richard; Lopez, Bernard L.

doi:10.1016/j.emc.2014.04.010

Cited by 10 publications

(3 citation statements)

References 109 publications

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“…The early and protracted permanence of UPR and subsequent onset of “terminal” UPR sustained by SRs modulators could very quickly lead to the death of the cells before they have the time to adopt a more malignant phenotype or allow the viral life cycle completion. Thienopyridine derivatives with antiplatelet activity, including ticlopidine, are widely prescribed for patients with cardiovascular diseases [ 31 , 32 ]. In addition to their antiplatelet activity being closely related to the inhibition of P2Y 12 receptor, the literature data highlighted their potential anticancer and antimetastatic properties [ 33 , 34 , 35 , 36 ].…”

Section: Resultsmentioning

confidence: 99%

Repurposing the Antiplatelet Agent Ticlopidine to Counteract the Acute Phase of ER Stress Condition: An Opportunity for Fighting Coronavirus Infections and Cancer

et al. 2022

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Different pathological conditions, including viral infections and cancer, can have a massive impact on the endoplasmic reticulum (ER), causing severe damage to the cell and exacerbating the disease. In particular, coronavirus infections, including SARS coronavirus-2 (SARS-CoV-2), responsible for COVID-19, cause ER stress as a consequence of the enormous amounts of viral glycoproteins synthesized, the perturbation of ER homeostasis and the modification of ER membranes. Therefore, ER has a central role in the viral life cycle, thus representing one of the Achilles’ heels on which to focus therapeutic intervention. On the other hand, prolonged ER stress has been demonstrated to promote many pro-tumoral attributes in cancer cells, having a key role in tumor growth, metastasis and response to therapies. In this report, adopting a repurposing approach of approved drugs, we identified the antiplatelet agent ticlopidine as an interferent of the unfolded protein response (UPR) via sigma receptors (SRs) modulation. The promising results obtained suggest the potential use of ticlopidine to counteract ER stress induced by viral infections, such as COVID-19, and cancer.

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Section: Resultsmentioning

confidence: 99%

Repurposing the Antiplatelet Agent Ticlopidine to Counteract the Acute Phase of ER Stress Condition: An Opportunity for Fighting Coronavirus Infections and Cancer

et al. 2022

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“…Acquired bleeding disorders are characterised by abnormal haemostasis and represent a major challenge for emergency room physicians. They can develop predominantly as a result of medical conditions, such as liver disease, traumatic injury, surgical procedures, medical interventions, or iatrogenic causes such as anticoagulation medications or massive transfusions [ 1 ]. Disrupted balance between coagulation and fibrinolysis leads to coagulopathy and is typically characterised by impaired clot formation leading to spontaneous, prolonged or excessive bleeding, as well as thrombotic tendency [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Management of Coagulopathy in Bleeding Patients

Hofer

Schlimp

Casu

et al. 2021

JCM

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Early recognition of coagulopathy is necessary for its prompt correction and successful management. Novel approaches, such as point-of-care testing (POC) and administration of coagulation factor concentrates (CFCs), aim to tailor the haemostatic therapy to each patient and thus reduce the risks of over- or under-transfusion. CFCs are an effective alternative to ratio-based transfusion therapies for the correction of different types of coagulopathies. In case of major bleeding or urgent surgery in patients treated with vitamin K antagonist anticoagulants, prothrombin complex concentrate (PCC) can effectively reverse the effects of the anticoagulant drug. Evidence for PCC effectiveness in the treatment of direct oral anticoagulants-associated bleeding is also increasing and PCC is recommended in guidelines as an alternative to specific reversal agents. In trauma-induced coagulopathy, fibrinogen concentrate is the preferred first-line treatment for hypofibrinogenaemia. Goal-directed coagulation management algorithms based on POC results provide guidance on how to adjust the treatment to the needs of the patient. When POC is not available, concentrate-based management can be guided by other parameters, such as blood gas analysis, thus providing an important alternative. Overall, tailored haemostatic therapies offer a more targeted approach to increase the concentration of coagulation factors in bleeding patients than traditional transfusion protocols.

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“…4,32 Bleeding disorders have been previously found to be a risk factor for higher complication rates in certain orthopaedic procedures. 1,9,14,25 One study investigating outcomes following total hip arthroplasty in patients with hemophilia found an increased rate of complications including infection and aseptic loosening. 25 A longitudinal study following patients for an average of 9 years found that patients with bleeding disorders still had high satisfaction following total knee or total hip arthroplasties.…”

Section: Introductionmentioning

confidence: 99%

Association of Bleeding Disorders and Risk of Complications Following Open Reduction and Internal Fixation of the Ankle

et al. 2021

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Background: Open reduction and internal fixation (ORIF) of the ankle is a common procedure performed to correct ankle fractures in many different patient populations. Diabetes, peripheral vascular disease, and osteoporosis have been identified as risk factors for postoperative complications following surgery for ankle fractures. To date, there have not been any studies evaluating postoperative outcomes in patients with bleeding disorders undergoing operative treatment for ankle fractures. The aim of this study was to determine the postoperative complication rate following ORIF of the ankle in patients with a bleeding disorder vs those without a bleeding disorder. Methods: From 2006 to 2018, patients undergoing operative treatment for ankle fracture were identified in the National Surgical Quality Improvement Program database. Two patient cohorts were defined: patients with a bleeding disorder and patients without a bleeding disorder. Patients who underwent either inpatient or outpatient ORIF of the ankle were included in this study. In this analysis, demographics, medical comorbidities, and postoperative complications variables were assessed between the 2 cohorts. Bivariate and multivariate analyses were performed. Results: Of 10 306 patients undergoing operative treatment for ankle fracture, 9909 patients (96.1%) had no bleeding disorder whereas 397 patients (3.9%) had a bleeding disorder. Following adjustment on multivariate analysis, compared to patients who did not have a bleeding disorder, those with a bleeding disorder had an increased risk of any postoperative complications (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.05-2.08, P = .024), requirement for postoperative blood transfusion (OR 2.86, 95% CI 1.53-5.36, P = .001), and extended length of hospital stay greater than 5 days (OR 1.46, 95% CI 1.10-1.93, P = .010). Conclusion: Patients with bleeding disorders are associated with increased risk of postoperative complications following ORIF for ankle fractures. Determining patient risk factors and creating optimal preoperative and perioperative management plans in patients with bleeding disorders undergoing ORIF can be beneficial in reducing postoperative complications, improving patient outcomes, and reducing overall morbidity. Level of Evidence: Level III, retrospective cohort study.

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Acquired Bleeding Disorders

Cited by 10 publications

References 109 publications

Repurposing the Antiplatelet Agent Ticlopidine to Counteract the Acute Phase of ER Stress Condition: An Opportunity for Fighting Coronavirus Infections and Cancer

Repurposing the Antiplatelet Agent Ticlopidine to Counteract the Acute Phase of ER Stress Condition: An Opportunity for Fighting Coronavirus Infections and Cancer

Management of Coagulopathy in Bleeding Patients

Association of Bleeding Disorders and Risk of Complications Following Open Reduction and Internal Fixation of the Ankle

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