From the Guidelines
To manage elevated PT in patients on anticoagulant therapy, particularly those on direct oral anticoagulants (DOACs) such as dabigatran, rivaroxaban, apixaban, and edoxaban, it is crucial to interpret the results of common coagulation assays (CCA) like PT and aPTT with caution, as their sensitivity and specificity can vary significantly depending on the specific DOAC and the reagents used 1.
When dealing with elevated PT in the context of trauma or bleeding in patients on DOACs, the approach should prioritize rapid assessment and decision-making. Viscoelastic coagulation tests, such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM), are valuable tools for detecting coagulopathy associated with DOACs and guiding reversal therapy 1. These tests can provide immediate information on clot development, stabilization, and dissolution, which is critical in the trauma setting.
For patients on dabigatran, a direct thrombin inhibitor, thrombin time (TT) can be a useful tool for detecting the presence of dabigatran, with a normal TT assay excluding relevant dabigatran levels 1. However, for quantification of dabigatran levels above therapeutic ranges, dilute thrombin time (dTT) may be more appropriate due to its linear correlation with plasma drug levels 1.
In contrast, for patients on rivaroxaban, apixaban, and edoxaban, which are direct FXa inhibitors, PT can be a helpful tool in determining the presence of these DOACs, although its quantitative effect can vary based on different thromboplastins 1. It's essential to note that INR should not be interpreted in the same manner as for patients on vitamin K antagonists (VKAs), given the different mechanisms of action of DOACs.
Given the complexities and limitations of coagulation assays in the context of DOACs, a comprehensive approach that considers the patient's clinical presentation, the specific DOAC involved, and the results of available coagulation tests is necessary for optimal management 1. This may involve consultation with specialists and the use of specific reversal agents, such as idarucizumab for dabigatran or andexanet alfa for FXa inhibitors, in cases of severe bleeding or the need for urgent surgery.
Key considerations in managing elevated PT in patients on DOACs include:
- The specific DOAC involved and its pharmacokinetics
- The clinical context, including the presence of bleeding or the need for urgent surgery
- The interpretation of coagulation assays, including their limitations and variability
- The potential need for reversal therapy and the selection of appropriate reversal agents
- The importance of a multidisciplinary approach to patient management, involving trauma specialists, hematologists, and other relevant experts.
From the Research
Elevated Blood Pressure in Diabetes
Elevated blood pressure, or hypertension, is a common complication in patients with diabetes. Several studies have investigated the relationship between hypertension and diabetes, as well as the effects of various treatments on blood pressure in diabetic patients.
Mechanisms and Risk Factors
- Hypertension in diabetes is associated with insulin resistance, vascular stiffness, and cardiovascular disease 2.
- Molecular mechanisms promoting hypertension in diabetes include activation of the renin-angiotensin-aldosterone system, sympathetic nervous system, mitochondria dysfunction, oxidative stress, and systemic inflammation 2.
- Other factors that contribute to hypertension in diabetes include enhanced activation of epithelial sodium channels, alterations in extracellular vesicles and their microRNAs, abnormal gut microbiota, and increased renal sodium-glucose cotransporter activity 2.
Treatment and Management
- Lisinopril, an ACE inhibitor, has been shown to lower blood pressure and produce a renoprotective effect in patients with diabetes, without adversely affecting glycaemic control or lipid profiles 3.
- Intensive insulin therapy can reduce the long-term risk of developing hypertension in type 1 diabetes, and hyperglycemia is a risk factor for incident hypertension in type 1 diabetes 4.
- Combination treatment with lisinopril and empagliflozin has been shown to exert synergistic effects on renal histological outcomes in a mouse model of hypertension-accelerated diabetic kidney disease 5.
- Metformin has been found to improve glucose and lipid metabolism, and reduce blood pressure in hypertensive, obese women 6.