Translational research : the journal of laboratory and clinical medicine
-
Pregnancy associated venous thromboembolism (PA-VTE) is a leading cause of maternal morbidity and mortality worldwide. Despite the availability of international guidance on the prevention, diagnosis and treatment, practice differs between countries and clinical institutions. ⋯ This review includes best evidence in PA-VTE management, highlighting specific literature which supports current diagnosis, prevention, and treatment strategies. Additionally, we hope to demonstrate emerging trends in the field through discussion of ongoing trials designed to progress towards evidence-based practice in the context of PA-VTE.
-
A significant amount of clinical and research interest in thrombosis is focused on large vessels (eg, stroke, myocardial infarction, deep venous thrombosis, etc.); however, thrombosis is often present in the microcirculation in a variety of significant human diseases, such as disseminated intravascular coagulation, thrombotic microangiopathy, sickle cell disease, and others. Further, microvascular thrombosis has recently been demonstrated in patients with COVID-19, and has been proposed to mediate the pathogenesis of organ injury in this disease. ⋯ In this review, we discuss endogenous regulatory mechanisms that prevent thrombosis in the microcirculation, experimental approaches to induce microvascular thrombi, and clinical conditions associated with microvascular thrombosis. A greater understanding of the links between inflammation and thrombosis in the microcirculation is anticipated to provide optimal therapeutic targets for patients with diseases accompanied by microvascular thrombosis.
-
Endogenous and exogenous hormones have significant effects on coagulation and may tip the hemostatic balance toward thrombosis. The endogenous hormonal changes in pregnancy and polycystic ovary syndrome, and exogenous hormonal contraception, menopause replacement, and transgender cross-hormone replacement may increase thromboembolism risk. Using the lowest effective dose is critical for prevention, but once thrombosis occurs, anticoagulation may be required, in some, long term. We review the relative risk of thrombosis in these conditions, risk factors, and anticoagulation treatment and prevention. Implementation of lowest effective hormonal therapies, thrombosis reduction strategies, and current anticoagulation management are critical for optimal patient outcomes.
-
There are currently no effective substitutes for high intensity therapy with unfractionated heparin (UFH) for cardiovascular procedures based on its rapid onset of action, ease of monitoring and reversibility. The continued use of UFH in these and other settings requires vigilance for its most serious nonhemorrhagic complication, heparin induced thrombocytopenia (HIT). HIT is an immune prothrombotic disorder caused by antibodies that recognize complexes between platelet factor 4 (PF4) and polyanions such as heparin (H). ⋯ However, both clinical algorithms and test modalities have limited predictive values making diagnosis and management challenging. Given the unacceptable rates of recurrent thromboembolism and bleeding associated with current therapies, there is an unmet need for novel rational nonanticoagulant therapeutics based on the pathogenesis of HIT. We will review recent developments in our understanding of the pathogenesis of HIT and its implications for future approaches to diagnosis and management.
-
Post-thrombotic syndrome (PTS) is an end stage manifestation of deep vein thrombosis. This is an inherently inflammatory process, with consequent fibrosis. Multiple cellular types are involved, and are likely driven by leukocytes. Herein, we review the current gaps in therapy, and insights from rodent models of venous thrombosis that suggest possible targets to treat and prevent PTS.