Use of hemostatic agents to stop bleeding

The main task of all methods of hemostasis with external bleeding at the prehospital stage is to stop it in order to create conditions for immediate evacuation of the wounded to the stage of providing qualified or specialized care.

During the first stage of medical care, bleeding is temporarily stopped and the correct and justified previously applied ligature is checked, the bleeding is stopped by bandage, the vessel in the wound is strung, the wound is clotted with a clot… But time does not stand still and technology is evolving.

Nowadays, the idea of using local hemostatic is becoming increasingly popular. This was largely due to the impossibility of using a blood-stopping device and the ineffectiveness of other measures for certain localization injuries. During the armed conflicts in Somalia and Afghanistan, hives and pelvis injuries were highly lethal due to the inability to stop bleeding by traditional methods (Mabry R., 2000). To combat the bleeding of such localization, each American soldier was provided with two hemostatic agents – a derivative of zeolite «QuickClot» (Z-Medica, Wallington Connecticut, USA) and a dressing based on the chitosan «HemCon» (HemCon Medical Technologies, USA) (Hasan V., 2005).

The efficacy of these drugs was demonstrated in animal experiments, they were relatively easy to use, compact, and did not require special storage conditions. Currently, along with experimental studies, data on their use in combat operations in Iraq and Afghanistan, as well as in peaceful conditions by both medical and para-medical personnel are published (Alam H., 2005; Todd O., 2008).

Over the past 5-7 years, many new hemostatic dressings have been developed, mainly for first aid. Despite the fact that these products contain various active substances in their basis, most of them implement a mechanism of action through intensive moisture absorption.

Upon contact with blood, the drugs due to special chemical-physical properties absorb its liquid part in a short period of time. This leads to local thickening of the cellular and protein components of the blood, including clotting factors, which stimulates the process of clot formation at the site of injury.

Thus, one of the promising directions in medical care for massive bleeding at the prehospital stage is the introduction of hemostatic preparations based on high sorption capacity.

Method description

The essence of the proposed method is to use a local hemostatic agent to stop intense bleeding in the case of damage to both venous and arterial blood vessels of various sizes and localization. It is proposed to be used as an alternative method of hemostasis or in addition to conventional methods of bleeding control in hospitals.

METHOD CHARACTERISTIC

This hemostatic agent is a synthetic derivative of zeolite, a natural mineral contained in the mineralized minerals of volcanic rocks. In the Greek translation, ceolith means «boiling stone». This name is due to the unique ability of the mineral to absorb water, which is related to the phenomenon of adsorption – the secretion of substance from the liquid phase on the surface of a solid body in the volume formed by its pore structure.

Ceolites are three-dimensional crystalline structures consisting of a system of pores and channels, the diameter of the inlet openings of which is equal to the size of water molecules (0.26 nm), but smaller than most organic molecules. The surface area of the mineral is hundreds of square meters per 1 g. It is believed that one teaspoon of zeolite in an area is equivalent to a football stadium (Kubasov A.A., 1998). This gives the mineral the ability to absorb a significant amount of water relative to its mass and volume. The moisture absorption process is exothermic and is accompanied by intense heat emission, up to steam formation.

The absorption capacity of natural zeolites is small compared to industrial samples. In addition, they absorb only small molecules – mainly water and oxygen. Synthetic zeolites have adsorptive properties far superior to natural analogues. By changing the synthesis conditions, we obtain samples differing in type of secondary structures with given types of spatial grids and certain pore sizes. Such zeolites are able to absorb molecules of a certain size (the effect of «molecular sieve»). To give the necessary properties, zeolite modification is carried out, the essence of which consists in the purposeful replacement of some ions in the composition of the mineral by others.

In the creation of local hemostatic agent «Hemofreeze» to increase the efficiency of hemostasis (effect on calcium dependent coagulation factors – X, IX, VII, II) sodium cations were substituted for calcium cations.

At the final stage of production, after synthesis and modification, zeolite was subjected to «activation», which is carried out by the programmatic heating of the carrier followed by cooling in an excipient and packaging in a hermetically sealed container.

The hemostatic effect of the drug is related to involvement in both vascular-thrombocytic and plasma-coagulation mechanisms of blood clotting. The zeolites of CaA and CaH, synthesized in kaolin granules, show the most pronounced hydrophilic properties. The unique combination of these zeolites with sorption, ion-exchange, molecular sieve properties provides a high rate of selective sorption of water from blood plasma.

Upon contact with blood, water molecules are captured by zeolite and retained by its surface potential and molecular structure due to the formation of hydrogen bonds («molecular sieve» effect), which helps to accelerate the aggregation of platelets and the formation of a fibrin clot. In a short period of time, a large amount of water is absorbed relative to the mass and volume of the drug, which leads to local concentration of cellular and large protein components of the blood, clotting factors, inducing the formation of a blood clot.

It is also known that the surface charge and isoelectric index of inorganic oxides such as zeolite triggers a fast coagulation reaction and formation of a durable clot. Similarly, the charge of zeolite is able to activate XII coagulability factor (Hageman factor), acting on the external pathway of the coagulation cascade.

During the development of a transfective hemostatic agent «Hemofrisis TM» to increase the efficiency of hemostasis (exposure to calcium dependent blood clotting factors – X, IX, VII, II) sodium cations were substituted for calcium cations. Modified synthetic zeolites have acquired the ability to extract different ions from solutions more efficiently and selectively, thus ensuring their concentration. Active calcium ions, which can accelerate the hemostasis multiple times, are in clusters of the crystal lattice of synthesized zeolites of two types of CaA and CaH. In addition, local hyperthermia above 60°C is an additional factor determining the effectiveness of hemostasis.

Thus, the process of hemostasis when using the transfecting agent of hemostatic «Hemofreeze TM» is carried out by implementing own systems of the body and based on physical properties of zeolite, the main one being the ability to selectively absorb water.