Anticoagulation Monotherapy vs. Combined Antiplatelet Treatment

Redacción Farmacosalud.com

Under the organization of the Spanish Society of Hematology and Hemotherapy (SEHH)the National Conclusions Meeting about the last Congress of the American Association of Hematology (ASH). From the SEHH meeting it is clear that anticoagulation in monotherapy is preferable to combined treatment with antiplatelets, since double therapy is associated with a higher risk of complications. This conclusion is based on data from clinical trials in patients with a history of chronic ischemic heart disease (chronic being understood as meaning that at least 6 months had passed since the last coronary revascularization procedure), “for which they were receiving antiplatelet treatment, and in whom there was a circumstance with an indication for therapeutic anticoagulation (for example, atrial fibrillation or an episode of venous thrombosis),” details Dr. Ramón Lecumberri Villamediana, hematologist at the University of Navarra Clinic (Pamplona).

“It has been shown that, in this scenario, treatment with anticoagulants alone is superior to combined therapy with antiplatelet + anticoagulation, not only in terms of lower risk of hemorrhagic complications, but also due to a lower rate of thrombotic complications, death from cardiovascular causes and even lower mortality from any cause,” adds Lecumberri, who was a speaker at the post-ASH meeting at the Roundtable on Hemostasis and Thrombosis.

“It is not prudent to generalize these results to other scenarios, such as patients with a history of ischemic stroke or peripheral arterial disease, but these are data that represent an important wake-up call in order to properly evaluate the risks/benefits of combined therapy. However, real-life data from large registries have also been presented, in which, in patients with antiphospholipid syndrome with arterial thrombosis, anticoagulation with vitamin K antagonists (VKA) is better than the combination of AVK + anti-aggregation”, establishes the expert.

Possible “attractive” therapeutic targets in pancreatic adenocarcinoma or glioblastoma
Regarding the developments in research on thrombosis associated with cancer, it should be said that, within the pathophysiological aspects, the importance of the fibrinolytic system* in the processes of tumor progression/dissemination stands out. “Molecules such as urokinase-type plasminogen activator (U-PA) and its receptor (U-PAR) could constitute attractive therapeutic targets in tumors such as pancreatic adenocarcinoma or glioblastoma,” says Dr. Lecumberri.

*Editor’s note: fibrinolytic system It is the enzymatic mechanism responsible for eliminating the fibrin clot. The fibrin is a protein that provides a semisolid character to the blood clot

At the SEHH meeting, Glanzmann’s thrombasthenia was also discussed, a rare disease that has a frequency of approximately one case per million inhabitants. It is an inherited disorder that is caused by mutations in the ITGA2B and ITGB3 genes, responsible for the production of the αIIbβ3 integrin. This integrin is essential so that platelets can aggregate and form the platelet plug, a fundamental step in clot formation.

“When this protein is not expressed adequately or functions poorly, platelets cannot aggregate and, as a consequence, patients have a tendency to bleed,” explains Dr. José Mª Bastida Bermejo, hematologist at the Salamanca University Care Complex and the Biomedical Research Institute of that city. “Bleeding in our patients mainly affects the skin and mucous membranes. Among the most frequent symptoms are nosebleeds, gastrointestinal hemorrhages and metrorragias. Although, usually, bleeding episodes are mild or moderate, sometimes they can be serious, appear spontaneously or even be life-threatening, especially in situations such as surgery or childbirth,” says Bastida.

Dr. José Ma Bastida Bermejo
Fuente: SEEHH

These recurrent and spontaneous bleeding can lead to chronic anemia that requires the continued use of iron treatments, or even receiving periodic blood transfusions. To control acute bleeding episodes, transfusions of platelets or activated recombinant factor VIIa are used, which remains the only drug approved to date to treat bleeding in this disease.

Bi-specific antibodies and hemostasis rebalancers
“However, today we do not have any approved treatment that prevents bleeding, that is, our patients lack prophylactic therapies that prevent the appearance of new bleeding episodes. This lack of preventive options continues to be one of the main unmet needs and that is why new therapies are being investigated in the form of bi-specific antibodies, such as sutacimig, or hemostasis rebalancing agents, such as anti-TFPI,” comments Dr. Bastida, in turn member of the Board of Directors of the Spanish Society of Thrombosis and Haemostasis (SETH) and speaker at the post-ASH meeting at the Table on Haemostasis and Thrombosis.

Specifically, sutacimig is a bispecific antibody designed to simultaneously bind to two targets involved in hemostasis. On the one hand, it binds to activated factor VII (FVIIa), a key element of coagulation that makes it possible to generate thrombin and, thus, promote clot formation. On the other hand, it binds to a specific receptor or protein present on activated platelets, which allows it to selectively target the site of bleeding. “Thanks to this double mechanism, it is capable of increasing the half-life of endogenous FVIIa and enhancing clot formation using the platelets that are active in the area of the injury,” he specifies.

At the last American Congress of Hematology (ASH 2025) the initial results of a phase II clinical trial with sutacimig were presented. 34 people with Glanzmann’s thrombasthenia and severe, spontaneous and recurrent hemorrhagic symptoms participated in it. Patients were randomized to different doses of the drug, administered weekly or every two weeks, with the additional advantage that the treatment is subcutaneous, which facilitates its use. As is usual in a phase II clinical trial, the main objectives were to evaluate the safety, tolerability and pharmacodynamics of the drug. In this study, no serious adverse effects were observed, with the majority of side events being mild, mainly headache and a transient increase in blood pressure. dímero D.

Dr. Lucrecia Yáñez San Segundo
Fuente: SEEHH

“However, a patient with important cardiovascular and thrombotic risk factors developed venous thrombosis in the higher dose arm, which is why his treatment was suspended. Even so, the data suggest that the most stable and, at the same time, effective dose, although preliminary, is 0.3 mg/kg/week, since it managed to very significantly reduce all types of bleeding, including those that are difficult to manage. Taken together, these results, although still preliminary, are very encouraging, so We are waiting for the phase III trial, which will make it possible to solidly assess the real effectiveness of the drug,” states Dr. Bastida.

The unstoppable advance of personalized medicine
On the other hand, at the SEHH meeting it was confirmed that it is necessary to move towards more individualized treatment strategies. For many years, medicine has treated different patients with the same condition in a similar way, but “today we know that some therapies can cause side effects depending on the patient’s other conditions, while in other cases the therapy may be insufficient to stop the disease. The conclusions of the recent American congress tell us that, finally, we are entering the era of tailored treatment, in which therapeutic decisions are outlined following the biology of each individual and their pathology,” emphasizes Dr. Lucrecia Yáñez San Segundo, hematologist at the Marqués de Valdecilla University Hospital (Santander) and one of the coordinators of the post-ASH meeting.

“This change is born from genetic and molecular advances that are allowing us to have a deeper knowledge of blood diseases. Now, hematologists can begin to predict, through biomarkers, which molecule will be most useful for our patient. Consequently, the most used treatment for decades, chemotherapy, with which we eliminated tumor cells, but also healthy cells, is being gradually displaced by new drugs, directed more towards the tumor cell and its specific alterations,” he argues.

To all this, Dr. Yáñez San Segundo takes the opportunity to highlight “the magnificent atmosphere generated” at the event held in Santander. A success that has been based on “the great attendance of participants, the excellent presentations of speakers and the support of the SEHH in holding this type of training meetings, totally necessary to always be up to date in our specialty.”

Romiplostim and PTI

Finally, it should be said that a European study coordinated by the Virgen del Rocío University Hospital (Seville) has shown that adding an active ingredient, romiplostim, to the standard treatment of primary immune thrombocytopenia (ITP) doubles the proportion of patients who can increase the periods in which they do not need medication, thereby avoiding the chronicity of the disease. ITP is an autoimmune pathology that causes a significant decrease in platelets and increases the risk of bleeding.

The clinical trial, called RODEX (Romiplostim Plus Dexamethasone versus Dexamethasone as first line treatment), represents a milestone in hematological research as it is the first randomized and prospective study that compares this therapeutic combination as a first line of treatment in newly diagnosed patients.