Understanding Hemorrhage and Hemostasis
Hemorrhage, or severe bleeding, is a critical medical condition that can lead to shock and death if not controlled promptly. It is the second-leading cause of death in trauma patients, following central nervous system injuries [1.12.3]. The body's natural response to bleeding is hemostasis, the process of forming a blood clot to seal an injured vessel. However, in cases of major trauma, surgery, or certain medical conditions, this natural process is insufficient. In these situations, doctors intervene with hemostatic agents, which are substances that promote blood clotting and control hemorrhage [1.3.2]. These agents can be administered systemically (throughout the body) or applied topically (directly to the wound) [1.3.2].
Systemic Hemostatic Agents: Working from the Inside Out
Systemic agents are crucial for managing widespread bleeding or bleeding from inaccessible sites. They work by interacting with the body's coagulation cascade, a complex series of protein activations that lead to the formation of a stable fibrin clot [1.2.1].
Antifibrinolytics
These drugs prevent the breakdown of blood clots, a process called fibrinolysis [1.2.1]. By inhibiting this process, they help stabilize existing clots and prevent re-bleeding.
- Tranexamic Acid (TXA): A synthetic drug that reversibly binds to plasminogen, preventing its activation into plasmin—the enzyme responsible for dissolving clots [1.2.1]. TXA is widely used in trauma, surgery, and to treat heavy menstrual bleeding [1.2.1, 1.2.2]. Administering TXA within three hours of a traumatic injury has been shown to significantly reduce mortality from bleeding [1.14.2].
- Aminocaproic Acid (EACA): Similar to TXA, EACA also works by slowing the breakdown of blood clots [1.6.2]. It is about 7 to 10 times less potent than TXA and is used for similar indications, such as controlling bleeding after surgery [1.2.1, 1.6.2].
Other Systemic Agents
- Desmopressin (DDAVP): A synthetic hormone that increases plasma levels of von Willebrand factor (vWF) and Factor VIII, two key components in the clotting cascade [1.2.1, 1.7.2]. It is primarily used to treat patients with bleeding disorders like von Willebrand disease and mild hemophilia A [1.7.2].
- Prothrombin Complex Concentrate (PCC): A product derived from human plasma containing concentrated clotting factors (II, IX, X, and sometimes VII) [1.2.1, 1.8.1]. Its primary FDA-approved use is for the urgent reversal of warfarin, an anticoagulant [1.8.1]. It acts much faster and with less volume than fresh frozen plasma [1.8.1].
- Recombinant Factor VIIa (rFVIIa): A bio-engineered protein that enhances thrombin generation, leading to rapid clot formation at the site of injury [1.9.3]. It is licensed for use in hemophilia patients but is also used off-label in cases of catastrophic hemorrhage that don't respond to other treatments [1.2.1, 1.9.1].
- Vitamin K: An essential vitamin for blood clotting, as the body needs it to produce clotting factors in the liver [1.10.1]. Doctors administer Vitamin K to reverse the effects of anticoagulants like warfarin and to treat deficiencies that can cause bleeding [1.10.1]. All newborns in the U.S. receive a vitamin K shot to prevent Vitamin K Deficiency Bleeding (VKDB) [1.10.2].
Topical Hemostatic Agents: Direct Action at the Bleeding Site
Topical agents are applied directly to a wound during surgery or after trauma to control localized bleeding. They are particularly useful for diffuse oozing from surgical surfaces [1.4.3]. They are broadly classified into physical agents (passive) and biologically active agents.
Physical Agents (Mechanical Hemostats)
These agents provide a physical matrix that promotes clot formation.
- Gelatin Sponges (e.g., Gelfoam, Surgifoam): Made from porcine collagen, these sponges absorb blood, swell, and create pressure (tamponade) on the bleeding vessel [1.15.1, 1.15.3]. Their neutral pH allows them to be combined with active agents like thrombin [1.3.3]. They are absorbed by the body in 4-6 weeks [1.15.3].
- Oxidized Regenerated Cellulose (ORC) (e.g., Surgicel): A plant-derived material that acts as a scaffold for clotting [1.3.3]. It also has bactericidal properties due to its low pH, but this acidity prevents it from being used with thrombin [1.4.1, 1.16.2].
- Microporous Polysaccharide Hemospheres (e.g., Arista AH): Plant-derived particles that rapidly absorb fluid from blood, concentrating platelets and clotting factors to accelerate clotting [1.4.2].
Biologically Active and Combination Agents
These agents actively participate in or enhance the coagulation cascade.
- Topical Thrombin: Thrombin is an enzyme that directly converts fibrinogen into fibrin, forming the mesh of a blood clot [1.4.2]. It can be derived from human plasma, bovine sources, or made via recombinant DNA technology [1.3.3]. It is often used in combination with gelatin sponges [1.15.2].
- Fibrin Sealants (e.g., Tisseel, Evicel): These are two-component products containing fibrinogen and thrombin [1.3.3]. When mixed and applied to a wound, they mimic the final step of the clotting cascade to form an immediate fibrin clot [1.4.1]. They are useful for controlling diffuse bleeding from broad surfaces [1.15.2].
- Flowable Hemostats (e.g., Floseal, Surgiflo): These are combination products, typically a gelatin matrix mixed with thrombin [1.4.1]. They have a thick consistency that allows them to be applied to irregular surfaces and in wet fields, where they conform to the wound and promote clotting [1.4.1, 1.15.2].
Comparison of Common Topical Agents
| Agent Type | Mechanism | Key Features | Common Brands |
|---|---|---|---|
| Gelatin Sponge | Passive matrix, tamponade [1.15.1] | Absorbs 40x weight, neutral pH, combines with thrombin [1.15.1, 1.15.3] | Gelfoam, Surgifoam [1.3.3] |
| Oxidized Cellulose | Passive matrix [1.4.2] | Low pH (bactericidal), cannot be used with thrombin [1.4.1, 1.16.2] | Surgicel [1.3.3] |
| Topical Thrombin | Active enzyme [1.4.2] | Converts fibrinogen to fibrin directly [1.4.2] | Recothrom, Evithrom [1.3.3] |
| Fibrin Sealant | Active combination [1.3.3] | Fibrinogen + Thrombin, forms instant clot [1.3.3, 1.15.2] | Tisseel, Evicel [1.3.3] |
| Flowable Hemostat | Active combination [1.4.1] | Gelatin matrix + Thrombin, thick consistency for irregular wounds [1.4.1, 1.15.2] | Floseal, Surgiflo [1.4.1] |
Conclusion
The choice of what doctors give to stop bleeding depends on many factors, including the cause, severity, and location of the hemorrhage, as well as the patient's underlying medical conditions [1.4.1]. The arsenal of hemostatic agents, from systemic drugs like tranexamic acid that stabilize clots throughout the body to advanced topical sealants that provide instant control in surgery, is a cornerstone of modern medical and surgical practice. These medications are critical for reducing blood loss, decreasing the need for transfusions, and ultimately saving lives in both emergency and elective settings.
For more in-depth information, an authoritative resource is the National Institutes of Health (NIH): Drugs to reduce bleeding and transfusion in major open vascular surgery
