Antithrombotic therapy

Pharmacological targets and types of anticoagulants

Anticoagulants are divided into two main groups that fundamentally differ in their mechanism of action and route of administration:

• Direct anticoagulants (e.g., Heparinum). They inhibit already activated coagulation factors, primarily IXa, Xa, and IIa (thrombin). Administered parenterally.
• Indirect anticoagulants (e.g., Warfarinum). They disrupt the synthesis of vitamin K-dependent coagulation factors (VII, IX, X, and II — prothrombin). Designed for long-term oral administration (per os).

There are drugs with various dosage forms. For example, Sulodexidum is available for both parenteral (intravenous, intramuscular) and oral use. For thrombosis prevention in COVID-19, medications are usually administered subcutaneously.

Clinical tactics in acute vascular events

In acute coronary syndrome (ACS) and cardioembolic stroke, therapy is always initiated with direct anticoagulants. In ST-segment elevation myocardial infarction, Heparinum is often the drug of choice. Nadroparinum calcium, Rivaroxabanum, and Dabigatranum etexilatum are also actively used in the initial phase. Subsequently, the patient is switched to indirect anticoagulants (Acenocoumarolum, Warfarinum) for long-term maintenance therapy.

Special attention is required for ischemic stroke patients who have undergone systemic thrombolysis. In such cases, the initiation of anticoagulants is delayed. Their administration is permitted no earlier than 24 hours after the administration of the thrombolytic agent, which is critically important to minimize the risk of hemorrhagic transformation of the ischemic zone.

Thrombosis prevention in surgery and onco-orthopedics

The choice of prevention method for venous thromboembolism (VTE) is strictly individual. It depends on the scale of surgery, duration of immobilization, time to recovery of motor activity, and the nature of the pathology. Prevention must cover the entire period of risk.

• Benign bone tumors (low VTE risk): Only mechanical prophylaxis is indicated (elastic compression of the lower extremities, calf muscle electrical stimulation, intermittent pneumatic compression). Pharmacoprophylaxis is prescribed only in the presence of additional risk factors.
• Malignant neoplasms: Malignancy itself is a major risk factor. During hospitalization, medical prophylaxis is necessary for such patients.
• Patients on chronic antithrombotic therapy: If the risk of thrombosis outweighs the risk of bleeding, the use of low-molecular-weight heparins (LMWH) or direct oral anticoagulants is indicated. In elective orthopedic procedures with low or moderate bleeding risk (up to joint arthroplasty, where transfusions are possible), discontinuing Acidum acetylsalicylicum is not recommended.

Therapy monitoring, interactions, and antidotes

The efficacy and safety of treatment require careful monitoring and an understanding of drug-drug interactions:

• Monitoring of heparin therapy: The adequacy of anticoagulation when using unfractionated heparin is assessed by the activated clotting time (ACT). This is especially important during vascular reconstructions (e.g., administering 50–100 IU/kg of the drug before aortic cross-clamping). In case of diffuse bleeding after restoration of perfusion, the antidote Protamini sulfas is used.
• Warfarin monitoring: Performed strictly according to the international normalized ratio (INR). Patients must be educated on the importance of a stable diet: foods high in vitamin K (spinach, cabbage) replenish the artificially induced deficiency and reduce drug efficacy.
• Bleeding during indirect anticoagulant therapy: For emergency care, vitamin K₁ preparations are used as a pathogenetic antidote, along with prothrombin complex concentrate (containing factors II, VII, IX, X) for rapid deficit correction.
• Combination therapy: The simultaneous use of anticoagulants and antiplatelet agents (Clopidogrelum, Acidum acetylsalicylicum) significantly enhances the antithrombotic effect by acting on different parts of the pathogenesis, but proportionally increases the risk of hemorrhages. A careful risk-benefit assessment is required.

Choice in comorbid conditions: In cancer patients (e.g., with multiple myeloma) and patients with nephrotic syndrome, LMWHs (Dalteparinum, Nadroparinum) are preferred. In hemophilia, only short-acting drugs are permissible under strict monitoring.

Class and exam questions

What else to study on this topic

• Mechanisms of action of low-molecular-weight heparins (LMWH)
• Specifics of sulodexide use in various formulations
• Prevention of thrombotic complications in COVID-19
• Antithrombotic therapy in patients with nephrotic syndrome
• Specifics of prescribing anticoagulants in hemophilia

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.