The past few decades have brought tremendous insight into the molecular and pathophysiological mechanisms responsible for thrombus generation. For a clinician, it is usually sufficient to explain the incident of deep vein thrombosis (DVT) with provoking factors such as trauma with vascular injury, immobilization, hormonal factors, or inherited or acquired coagulation defects. About half of DVTs are, however, lacking such triggers and are called unprovoked. Venous stasis and hypoxia at the valve sinus level may start a chain of reactions. The concept of immunothrombosis has added a new dimension to the old etiological triad of venous stasis, vessel wall injury, and changes in blood components. This is particularly important in COVID-19, where hyperinflammation, cytokines, and neutrophil extracellular traps are associated with the formation of microthrombi in the lungs. To better understand the mechanisms behind DVT and reach beyond the above-mentioned simplifications, animal models and clinical epidemiological studies have brought insight into the complex interplay between leukocytes, platelets, endothelium, cytokines, complements, and coagulation factors and inhibitors. These pathways and the interplay will be reviewed here, as well as the roles of cancer, anticancer drugs, and congenital thrombophilic defects on the molecular level in hypercoagulability and venous thromboembolism.

Unlike classic APS, CAPS causes multiple microthrombosis due to an increased inflammatory response, known as a “thrombotic storm”. CAPS typically develops after infection, trauma, or surgery and begins with the following symptoms: fever, thrombocytopenia, muscle weakness, visual and cognitive disturbances, abdominal pain, renal failure, and disseminated intravascular coagulation. Although the presence of antiphospholipid antibodies in the blood is one of the diagnostic criteria, the level of these antibodies can fluctuate significantly, which complicates the diagnostic process and can lead to erroneous interpretation of rapidly developing symptoms. Triple therapy is often used to treat CAPS, which includes the use of anticoagulants, plasmapheresis, and high doses of glucocorticosteroids and, in some cases, additional intravenous immunoglobulins. The use of LMWH is recommended as the drug of choice due to its anti-inflammatory and anticoagulant properties. CAPS is a multifactorial disease that requires not only an interdisciplinary approach but also highly qualified medical care, adequate and timely diagnosis, and appropriate prevention in the context of relapse or occurrence of the disease. Improved new clinical protocols and education of medical personnel regarding CAPS can significantly improve the therapeutic approach and reduce mortality rates.