Blood products and clotting factors
When coagulopathies associated with a deficiency of specific clotting factors develop, replacement therapy is the most effective method. Such deficiencies may be congenital (e.g., in hemophilia) or occur secondarily against the background of leukemias and pernicious anemia.
The following main agents are used in clinical practice:
- Direct plasma transfusion.
- Platelet concentrate.
- Prothrombin complex concentrate.
- Antihemophilic globulin.
- Cryoprecipitate.
A special place is occupied by fibrinogen, which is isolated from donor plasma. It is prescribed for hypofibrinogenemia, afibrinogenemia, and profuse bleeding of various etiologies exclusively as replacement therapy.
Management of fibrinolysis and the vascular wall
Specific fibrinolysis inhibitors are used to reduce excessive fibrinolytic activity in the blood. Their use is indicated in major surgical interventions on the lungs, heart, and prostate gland. They are also effective in septic conditions, liver cirrhosis, and after transfusions of large volumes of blood.
Fibrinolysis inhibitors are divided into two main groups:
- Biological: aprotinin.
- Synthetic: aminocaproic acid, aminomethylbenzoic acid.
In addition to inhibitors, angioprotectors and microcirculation correctors are used to correct hemostasis. Etamgesilat accelerates thromboplastin formation while improving microcirculation and normalizing vascular wall permeability. Rutoside and ascorbic acid have a similar effect on vascular permeability.
Role of vitamin K and calcium preparations
Menadione (menadione sodium bisulfite) is a synthetic, water-soluble analog of vitamin K. Its key mechanism of action consists in stimulating prothrombin synthesis. The drug is widely prescribed for acute hepatitis, obstructive jaundice, gastrointestinal bleeding, peptic ulcer disease, as well as for hemorrhoidal, prolonged nasal, parenchymal, and capillary bleeding (including after trauma and surgery).
The clinical role of calcium preparations is of interest. From a physiological standpoint, $Ca^{2+}$ ions are required to convert prothrombin into thrombin. However, the minimum required amount is virtually always present in human blood. Therefore, routine administration of calcium preparations as a hemostatic agent is unjustified. The only exception is the transfusion of massive doses of citrate blood, where calcium is administered specifically to neutralize the anticoagulant effect of citrate.
Antidotes and management of specific conditions
In bleeding caused by drug overdose, native or fresh frozen plasma administration is the baseline measure. Specific antidotes are used for targeted reversal:
- Overdose of indirect anticoagulants $\rightarrow$ menadione sodium bisulfite (vitamin K).
- Heparin sodium overdose $\rightarrow$ protamine sulfate.
- Inactivation of fibrinolytics $\rightarrow$ aminocaproic acid, aprotinin.
Management of DIC syndrome Management of disseminated intravascular coagulation syndrome requires a strictly staged approach:
- Elimination of the etiological factor.
- Restoration of circulating blood volume (CBV).
- Management of renal failure.
- Normalization of hemostasis (administration of heparin sodium, rapid infusion of native or fresh frozen plasma, administration of platelet concentrate).
- If necessary, transfer of the patient to mechanical ventilation.
Treatment of hemophilia Drugs of choice for patients with hemophilia include: cryoprecipitate, antihemophilic plasma, native (donor) plasma, as well as fresh citrated blood and direct blood transfusions.
Briefly: answers to topical questions
Which clotting factors are included in the «Prothrombin Complex Concentrate» preparation?
The «Prothrombin Complex Concentrate» preparation contains blood coagulation factors II, VII, IX, and X. Depending on the type of preparation, the following combinations are distinguished:
- 4-factor prothrombin complex — contains blood coagulation factors II, VII, IX, and X in combination.
- 3-factor prothrombin complex — contains blood coagulation factors II, IX, and X in combination.
Sources also mention a high content of factors II, VII, K, and X.
What is the mechanism of action of heparin sodium?
The mechanism of action of heparin sodium is that it acts as a cofactor for antithrombin III and does not directly affect clotting factors. The process involves the following stages:
- Binding — the drug binds to antithrombin III via a specific pentasaccharide sequence.
- Conformational change — induces a change in the spatial structure of the active center of antithrombin III.
- Rate acceleration — the rate of inactivation of clotting factors (thrombin, IXa, Xa, XIa, XIIa) by antithrombin increases approximately 1,000-fold.
Which agents are classified as local hemostatic agents?
Local hemostatic agents include a variety of biological materials, sponges, films, and topical preparations. This group includes:
- Oxidized cellulose — used to achieve local hemostasis.
- Absorbable gelatin sponge — used as a topical hemostatic agent.
- Hemostatic gauze — e.g., «Oxycelodex» or gauze impregnated with a solution of thrombin, hemophobin, epsilon-aminocaproic acid, «Caprofer», or tranexamic acid.
- Biological tampon — used for socket packing.
- Tranexamic acid — used as a mouthwash.
Which angioprotectors are used for the pharmacological correction of hemostasis?
Angioprotectors that normalize vascular wall permeability and improve microcirculation are used for the pharmacological correction of hemostasis. These include:
- Etamsylate — accelerates thromboplastin formation, normalizes vascular wall permeability, and improves microcirculation.
- Calcium dobesilate — has a more pronounced effect on normalizing vascular wall permeability compared to etamgesilat.
- Rutoside (Venoruton) — a derivative of rutin (vitamin P), strengthens vein and capillary walls, reduces vascular permeability, and inhibits platelet and erythrocyte aggregation.
- Ascorbic acid — used to normalize vascular wall permeability.
- Daflon — contains diosmin and hesperidin, reduces capillary permeability, and normalizes microcirculation.
To remember specific antidotes: Anticoagulants (indirect) are reversed by Vitamin K, Heparin by Protamine sulfate, and Fibrinolytics by Aminocaproic acid (A-V, H-P, F-A).
Class and exam questions
Is it advisable to use calcium preparations to stop routine bleeding?
No, it is unjustified. Coagulation requires a minimal amount of calcium ions, which is always present in the blood. Additional calcium is required only to neutralize citrate during transfusions of massive doses of citrate blood.
Which medications are the drugs of choice for hemophilia?
The basis of therapy is replacement correction of deficient factors. Cryoprecipitate, antihemophilic plasma, native donor plasma, and fresh citrated blood are used.
What is included in the algorithm for normalizing hemostasis in DIC syndrome?
In addition to eliminating the cause and restoring circulating blood volume (CBV), sodium heparin, platelet concentrate, and rapid IV infusion of native or fresh frozen plasma are used to normalize hemostasis.
What else to study on this topic
- Mechanism of action and pharmacokinetics of sodium heparin.
- Pathogenesis and stages of disseminated intravascular coagulation (DIC) syndrome.
- The role of vitamin K in hepatic synthesis of blood coagulation factors.
- Differences between native and fresh frozen plasma, and rules for their transfusion.
- Physiology and biochemistry of the fibrinolysis cascade.
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