Hemostasis: meanings, phases, hemostasis disorders and diagnosis of the disease

What is hemostasis?

“Hemostasis is the study of all the physiological phenomena which allow the formation of a blood clot and its dissolution”, defines Hela Ketatni, biologist, specialized in hematology and hemostasis. It results in the search for the balance to be found between bleeding (hemorrhagic risk) and coagulation (thrombotic risk). It is a physiological process that is divided into several stages.

Stages, phases of hemostasis:

There are 3 phases of hemostasis, going from bleeding to healing:

• Phase 1 : Primary hemostasis, the actors of which are the vessels, platelets, fibrinogen and Von Willebrand factor – the formation of a platelet nail to close a breach;
• Phase 2 : Plasma coagulation, the main players of which are the coagulation factors synthesized mainly by the liver;
• Phase 3 : Fibrinolysis, the objective of which is the destruction of the fibrin clot.

The clotting process

Primary hemostasis

When we bleed, we have a breach vascular at the level of a blood vessel. “This primary phase will involve the vessels, platelets, fibrinogen and an important factor called Von Willebrand factor“, explains the biologist. All these factors will contribute to primary hemostasis via a whole cascade of reactions. “Platelet adhesion occurs through Von Willebrand factor and aggregation through fibrinogen… in fact, the ultimate goal is tostop the bleeding via the formation of the platelet nail” specifies our expert. The body tries to plug the vascular breach and thusavoid hemorrhages. A process which will require the intervention of several players in primary hemostasis.

Plasma clotting

This second phase really aims to stop the bleeding. “Secondary hemostasis is important, because in the event of a problem and when the latter is not done correctly, there is a risk of hemorrhage“, underlines Hela Ketatni. The players in plasma coagulation are the clotting factors. There are several, numbered in Roman numerals. The important role of amplification of this phase is attributed to X factor et factor V. “These factors will activate in cascade with each other to form a series of reactions and lead to what is called the complexe prothrombinase“, indicates the specialist. This complex will generate the activation of an essential factor, the prothrombinbe the factor II in thrombin (activated factor II). And, this activated factor II allows the transformation of fibrinogen into fibrin, first unstable and soluble and then stable and insoluble following the action of factor XIII. Fibrin is a filamentous protein produced by fibrinogen under the action of thrombin during blood clotting. In fact, fibrin does not pre-exist in the blood, it only appears at the time of coagulation. This is what you see when a small scar forms on a wound. “The bleeding stops thanks to the formation of the clot which becomes a crust because of the proliferation of fibrin filaments. This is the beginning of the development of the scar,” observes the biologist. Physiological inhibitors of coagulation exist to prevent the latter from getting out of control.observes the biologist.

Fibrinolysis

Then comes the last phase which we call fibrinolysis. “This is the stage of dissolution of the blood clot, once it has fulfilled its role”, says Hela Ketatni. This dissolution of the blood clot occurs through the degradation of fibrin. It participates with primary hemostasis and coagulation in a certain physiological balance.

And for good reason, “the phenomenon of stopping bleeding is regulated. In the event of excessive coagulation, patients run the risk of thrombosis”, recalls the biologist. In a healthy person who has everything necessary for hemostasis, a balance helps avoid thrombosis (formation of a clot in a blood vessel). In short, the patient will not bleed for nothing, nor thrombose for nothing. “But when there is a clotting factor deficiency – we can see hemorrhagic situations – in these deficient patients, the cascade does not take place correctly, there are not enough thrombin generations, therefore coagulation does not occur optimally.note l’expert.

Blood hemostasis disorders and their causes

In the event of deficits, “we risk falling into situations with a risk of hemorrhage, bleeding if the deficiency concerns coagulation factors and/or into situations with a risk of thrombosis if the deficiency concerns physiological inhibitors of coagulation”, reports the biologist. For example: the Factor VIII deficiency causes hemophilia A. The Factor IX deficiency is hemophilia B. For hemophilia, “the causes are generally constitutional, genetics. However, there are situations where it is from the domain of acquired knowledge“, she informs. In other words, the person will have antibodies that will act against factor VIII by neutralizing it instead of letting it do its job.

Additionally, as MSD Manual reports, “vitamin K is necessary for the synthesis certain coagulation factors (factors II, VII, IX and X) proteins that help control bleeding (coagulation factors) and therefore normal coagulation”. In fact, a deficiency in vitamin K, particularly in infants, can cause hemorrhagic disease and a tendency to bleed.

In the case of disorders giving rise to thromboses, it is quite the opposite, she reports. “So that the generation of thrombin is controlled and not excessive, physiological inhibitors (anticoagulant action) are responsible for regulating this process.“. The main inhibitors are Antithrombin (AT) which inhibits thrombin and the couple (protein C and Protein S) which inhibits coagulation factors VIII and V. In case of deficiency in these coagulation inhibitors, the body will continue to generate clots giving rise to embolisms or thromboses. Hence the importance of a physiological balance between the two, to avoid falling towards one or the other pathologies.

Tests to diagnose hemostasis abnormalities:

There is a bilan sanguin standard (Tp, Tca, fibrinogen) to be performed on the patient in the analysis laboratory. During these tests, we therefore study in particular the rate prothrombin (PT). The prothrombin level is normally between 80% to 100%. We also look for the fibrinogen level (its normal level is between 2 and 4 g/l). Depending on the results of the assessment, additional blood tests will be carried out. “In the case of a suspicion of a factor deficiency, it will be a question of dosing the factors to measure whether their coagulant activity is sufficient or not”specifies the biologist. “If it is a coagulation problem in the sense of hypercoagulability or thrombosis, it is rather the clotting inhibitors that we are going to dose. Genetic testing is also available.”she continues.

Hemostasis disorders: what treatments?

It all depends on the cause of this disorder. This may include taking medications such as anticoagulants in case of thrombosis. Indeed, anticoagulants are medications used to prevent or treat the formation of blood clots. Several families of anticoagulant treatments exist, notably: heparins, AVK (vitamin K antagonists) and DOACs (direct oral anticoagulants).

In case of vitamin K dependent factor deficiency, treatment based on vitamin K orally or intravenously can also be administered.

If it is a problem concerning primary hemostasis (platelet or Von Willebrand factor abnormalities), specific treatments for the diagnosed abnormality will be prescribed. For example, we can prescribe corticosteroids in immune thrombocytopenia (low blood platelet level). We can prescribe Willebrand factor concentrate in the event of a deficit of the latter.

In the event of hemophilia, replacement treatment will be prescribed to the patient for life. To conclude, If you suspect a hemostasis imbalance, consult your doctor who, after having analyze blood results of the patient looking for a possible hemostasis anomaly, will propose, if necessary, the medical treatment most suited to the disorder.