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The hemostasis (composed of ancient Greek αἷμα Haima , German , blood ' , and stasis of στάσις stasis , German , stowage' , hemostasis ', stagnation', 'stop') is a vital process of the injuries of the blood vessels resulting bleeding brings to a standstill. This prevents excessive leakage of blood from the bloodstream and is the prerequisite for wound healingcreated. In the event of an injury, hemostasis must start quickly enough to avoid major blood loss. It must be limited to the area of ​​injury and must not be erroneously triggered by other events such as inflammation or infection .

Hemostasis can be divided into two sub-processes, which, however, interact with one another. In primary (also: cellular) hemostasis, the (physiological ) hemostasis, the blood platelets ( thrombocytes ), the wall cells of the affected blood vessel ( endothelium and smooth muscle cells ), and tissue outside the vessel are involved. To put it simply, the vessel first narrows, then blood platelets adhere to the leak, stick to one another and thus create the first wound closure. In secondary (also: plasmatic) hemostasis, blood clotting , this still loose closure is reinforced by the formation of fibrin threads. The activation of around a dozen coagulation factors contained in the blood plasma plays an important role here. A genetic defect in coagulation factors can lead to diseases such as haemophilia ( blood disease). The onset of wound healing is initiated by growth factors that are released by platelets and endothelial cells. At the end of the wound healing process, the fibrin is dissolved by the fibrinolytic system of the blood plasma.

Hemostasis, with its two components, primary and secondary hemostasis, is often referred to as hemostasis.

Under hypercoagulable means the increased clotting activity. The Hemostasis is the study of hemostasis. A coagulopathy or a blood clotting disorder is understood to be a pathologically altered hemostasis.

This article describes hemostasis in humans. The statements mainly apply to other mammals , but only to a limited extent to other animal classes .

Physiological processes after a vascular injury

Running blood on a fresh cut
A gene of its own is responsible for the formation of each of the enzymes (coagulation factors). Only the expression of all of these genes enables the effects of all these enzymes, which gradually lead to blood clotting. The end product fibrin creates a natural wound closure. (See also gene-effect chain and polygeny ).

After injury to smaller vessels, bleeding usually stops quickly. The hemostasis responsible for this can be viewed as a sequence of the following processes. This subdivision is primarily used for easier understanding. There are close functional and temporal relationships between the processes; a clear demarcation is not possible.

Spontaneous arterial hemostasis
Arteries ( arteries ) the muscular type have the property of "einzukrempeln" after a cross-cutting by itself. This property is due to the wall structure of the arteries: the elastic inner skin of the artery (internal elastic membrane) contracts more than the other wall layers after it has been severed. As a result, the free edge of the severed artery is drawn into the interior of the vessel and thus ensures a very quick, temporary closure.
Cellular hemostasis
It consists of the attachment (adhesion) and bonding (aggregation) of platelets, the activation of further platelets and the formation of an occluding, white platelet thrombus. In addition, the release of substances triggers vasoconstriction, i.e. narrowing of the vessels. This will reduce blood flow and so minimize blood loss.
Plasma hemostasis
Components of the blood plasma create a meshwork of mechanically stable fibrin threads, in which the circulating red blood cells (erythrocytes) get caught and finally a red thrombus forms, which finally solidifies and contracts.

Cellular hemostasis

A person's blood normally contains between 150,000 and 400,000 platelets per microliter . The cell membrane of platelets contains numerous glycoproteins and receptors that play an important role in cellular hemostasis.

The inner cell layer of blood vessels is called the endothelium . This is covered on the inside with a glycocalyx , a kind of mucus layer for which platelets have no receptors. For this reason, among other things, platelets remain inactive in uninjured vessels and cannot attach themselves to the vessel wall. Various factors also counteract activation, for example prostacyclin and nitric oxide as well as heparin , which is formed, among other things, by mast cells and whose inhibitory effect on hemostasis can be used therapeutically .

From left to right: erythrocyte , activated platelet , leukocyte .

Platelet Adhesion and Activation

When a vessel is injured, the blood comes into contact with the surrounding connective tissue, including collagen fibers. Collagen is a structural protein that is present almost everywhere in the extracellular space . The platelets first adhere to these fibers ( platelet adhesion ), which leads to the formation of a thin covering of the wound. The adhesion (adhesiveness) is prepared by the Von Willebrand Factor mediated (vWF), a soluble blood protein of endothelial cells and megakaryocytes is formed. Together with fibronectin and laminin, it creates a connection between collagen fibers and a receptor on the platelets (GP Ib / V / IX). A defect in the Von Willebrand factor leads to Willebrand-Juergens syndrome .

The adhesion triggers platelet activation: They release calcium ions, ADP , serotonin , thromboxane A 2 and other substances from so-called “electron-dense granules” . This attracts more platelets ( chemotaxis ). Thromboxane A 2 also contributes significantly to the narrowing of the blood vessels, which counteracts a high blood flow. The contents of the so-called "α-granules" of the platelets are also released: coagulation factors (factor V, factor VIII), adhesives (vWF, fibronectin, thrombospondin) and growth factors . By activating various metabolic pathways , substances such as thromboxane A 2 and the PAF (Platelet Activating Factor) are increasingly formed. Some of these substances induce plasmatic coagulation.

Platelet aggregation

Platelet-rich blood plasma (left) is a cloudy liquid. Adding ADP activates the platelets and binds them to one another, creating white flakes (right).

The aggregation of the activated platelets is promoted by a reorganization of the cytoskeleton , which causes the cell surface to be enlarged many times over. While the platelets are inactive, lens- shaped, when they are active they take on a spherical shape and carry long pseudopodia ( pseudopodia ) with which they can hook one another - the platelets become "prickly" and "sticky". The aggregated platelets eventually form a platelet plug known as a white thrombus. This ends the cellular hemostasis. Usually the process takes one to four minutes, this length of time is called the bleeding time .

The white thrombus is not very stable and can be washed away. The plasmatic hemostasis forms a tighter seal .

Plasma hemostasis

The coagulation cascade

The plasmatic hemostasis creates a meshwork of mechanically stable fibrin, in which not only thrombocytes but also red blood cells ( erythrocytes ) are captured, which is therefore referred to as “red thrombus”.

Activated platelets have a receptor complex (glycoprotein IIb / IIIa) on the cell membrane, to which fibrinogen from the plasma and the adhesives released from the activated platelets (fibronectin, thrombospondin) bind. Feedback mechanisms of the released substances ultimately lead to an irreversible aggregation in which the cell membranes of the platelets fuse with one another.

This secondary hemostasis, blood clotting, is also known as the coagulation cascade. It is divided into three phases: activation, coagulation and retraction phase.

Activation phase

When platelets come into contact with negatively charged surfaces such as glass, factors XII and XI are activated, which set in motion a coagulation cascade ( intrinsic system , see figure). If factor XII is not produced in an individual, this does not result in a significant disturbance of coagulation, in contrast to the deficiency of factors VIII, IX and XI, which leads to hemophilia A, B and C.

The normal physiological process ( extrinsic system or exogenous mechanism) is initiated by the contact of blood with tissue thromboplastin from injured subendothelial tissue. Tissue factor (also Tissue Factor (TF), tissue thromboplastin or factor III) is a membrane protein which, for example, in the adventitia occurs blood vessels - by endothelial cells it is released only after activation. It forms a complex with factor VII, which is converted into its active form. This creates some thrombin , but the process is inhibited relatively quickly by the TFPI (Tissue Factor Pathway Inhibitor). When enough thrombin has been formed, a so-called activator complex of factors IX and VIII is activated (see IXa and VIIIa in Figure). This complex in turn activates factor X.

The absence of factors VIII or IX leads to haemophilia, the hemophilia: the cascade is interrupted and the coagulation is not intensified. Patients can bleed to death from the smallest internal injuries.

With both mechanisms - intrinsic and extrinsic pathway - factor X is finally activated to factor Xa. This in turn splits prothrombin (factor II), thrombin (factor IIa) is formed. This reaction on the platelet membrane takes place only in the presence of calcium and is greatly accelerated by positive feedback with the complex of factors VIII and IX. The activation phase ends with the formation of enzymatically active thrombin.

Phases of coagulation and retraction

The enzymatically active thrombin is responsible for the polymerization of fibrin and thus the formation of the red thrombus: In the coagulation phase, it splits off low molecular weight units ( monomers ) from the inactive precursor fibrinogen (factor I) , which are non-covalently combined to form polymeric fibrin. Through the action of factor XIII, covalent bonds are finally made between the monomers and the thrombus is stabilized. The fibrin links the thrombocytes that are already attached to one another and thus strengthens the wound closure. Red blood cells are trapped in the network, a so-called red thrombus forms. The thrombin also causes a contraction of the actin-myosin skeleton within the platelets: the contracting platelets pull together on the fibrin network and thus the wound edges and close the wound mechanically. The contraction - supported by the PDGF ( platelet-derived growth factor ) - also promotes the penetration of connective tissue cells: wound healing begins.

New cell-based model of coagulation

The classic model of coagulation differentiates between intrinsic and extrinsic activation and thus describes a multi-stage sequence of activation of proteins in cell-free plasma. The classic coagulation tests aPTT and PT correspond to this idea. This model is not suitable for describing blood coagulation in damaged blood vessels in the body, so that in 2001 a cell-based model of coagulation was established, which describes three overlapping phases:


As a result of tissue damage, cells that are otherwise outside the blood vessel come into contact with the blood stream below the vascular endothelium. The cells now lying open in the bloodstream carry the tissue factor (III) on their surface (tissue-factor- (III) -bearing cell). The complex of tissue factor (III) and proconvertin (VII) now catalyzes the activation of thrombokinase (X), which initially can only activate small amounts of thrombin (II). However, this small amount of thrombin (II) is sufficient to activate platelets and the coagulation factors proaccelerin (V) and proconvertin (VII) and thus trigger the amplification of thrombin formation. This first phase takes place in a small space on the subendothelial injury.


Proaccelerin (V) activated in the initiation phase forms the prothrombinase complex (X, V) with thrombokinase (X), which can activate thrombin (II) to a greater extent. The amplification phase, during which platelets adhere to subendothelial structures (adhesion), overlaps in time. This happens via GPVI receptors, which bind to collagen, and via the GPIb / IX receptor, which binds to Von Willebrand factor. The Von Willebrand complex releases the bound factor VIII, which binds in an active form to the surface of the platelets. Furthermore, the platelet pours out its internal stores, which also contain proaccelerin (V). The tissue factor (III) and proconvertin (VII) not only activate thrombokinase (X), but also serine protease (IX). The first small amounts of thrombin (II) not only activate fibrin (I) but also factor (VIII). The tenase complex formed from VIII and IX in turn activates thrombokinase (X), so that a self-reinforcing loop is formed. This important step is also known as the Josso loop. Now there are numerous coagulation factors in high concentration on the surface of the subendothelial injury and on the surface of the thrombocyte adhering to it and are protected from the anticoagulant proteins in free blood.

The tissue factor (TF, III) and proconvertin (VII) not only activate thrombokinase (X), but also serine protease (IX). The first small amounts of thrombin (II) not only activate fibrin (I) but also factor (VIII). The tenase complex formed from VIII and IX in turn activates thrombokinase (X), so that a self-reinforcing loop is formed. This important step is also known as the Josso loop.


The factors accumulated on the platelet surface form tenase complexes (VIII, IX), which support the formation of the prothrombinase complex (X, V). The thrombokinase (X) now activates large amounts of thrombin (II) (thrombin burst). Thrombin (II) finally forms the fibrin networks in which platelets bind with their GPIIb / IIIa receptors. Factor XIII stabilizes these networks through additional fibrin cross-connections.

Control of unwanted spread of the clot

To prevent a clot from forming outside the endothelial injury (thrombosis), the endothelium and the free-flowing blood have different mechanisms: Dissolving thrombin (II) is quickly deactivated in the bloodstream by the anticoagulant protein antithrombin. Dissolving thrombokinase (X) and proconvertin (VII) are bound by TFPI. Thrombomodulin (TM) is located on the surface of the endothelium, which binds trombin (II) so that it can no longer form fibrin (I). At the same time, the formation of protein C (APC) by the bound thrombin (II) is a thousandfold, so that thrombin now has an anticoagulant effect. Protein C (APC) then forms a complex with protein S, which deactivates coagulation factors V and VIII. Furthermore, the endothelium has membrane-bound ADPases that break down ADP and thus down-regulate platelet function.

Transition to wound healing

After the plasmatic hemostasis, the wound heals when cells that form connective tissue ( fibroblasts ) grow into the thrombus and transform it into connective tissue. Damaged cells die and are broken down. A protein called plasmin is primarily responsible for breaking down the thrombi , which is also formed from an inactive precursor (plasminogen) through complexly regulated mechanisms. Plasmin dissolves the covalent bonds between the fibrin strands and thus the network that holds the thrombus in place.

There are balanced equilibria between the blood coagulation systems and the fibrinolysis system , which dissolves the red thrombus in the vascular system. Minor disturbances of this equilibrium can lead to serious bleeding or the formation of thrombi in places where there is no injury (see also Thrombosis ).

Overview of coagulation factors and inhibitors

Except for calcium ions (factor IV), the coagulation factors are proteins. A Roman number is assigned to each factor. A lowercase a after the number means that it is in the active form. For historical reasons (see under research history ) the number VI is not assigned (anymore), the corresponding factor is identical to Va.

number Name (s) Functions Deficiency Syndromes
I. Fibrinogen Precursor molecule for the formation of the fibrin network. Afibrinogenemia (congenital or consumption coagulopathy )
II Prothrombin The active form thrombin (IIa) activates factors I, V, VIII, XI and XIII. Hypoprothrombinemia (congenital, vitamin K deficiency or consumption coagulopathy )
III Tissue factor , tissue thromboplastin, tissue factor (TF) As the only one not in the blood, but in the subendothelial tissue.

TF and VIIa form the extrinsic tenase with Ca 2+ , which activates X.

IV Calcium Many factors require the calcium cation Ca 2+ in order to bind to the negatively charged phospholipids in the plasma membrane.
V Proaccelerin Va and Xa form the prothrombinase complex with Ca 2+ and phospholipids , which activates II. Parahemophilia (congenital)
VI corresponds to factor Va
VII Proconvertin VIIa and TF form the extrinsic tenase that activates X with Ca 2+ . Hypoproconvertinemia (congenital, vitamin K deficiency)
VIII Antihemophilic Globulin A. VIIIa and IXa form the intrinsic tenase with Ca 2+ and phospholipids , which activates X. Hemophilia A (congenital, X-linked recessive inheritance)
IX Christmas factor , antihemophilic globulin B VIIIa and IXa form the intrinsic tenase with Ca 2+ and phospholipids , which activates X. Hemophilia B (congenital, X-linked recessive inheritance)
X Stuart Prower Factor Va and Xa form the prothrombinase complex with Ca 2+ and phospholipids , which activates II. Factor X deficiency (congenital)
XI Rosenthal Factor , Plasma Thromboplasmin Antecedent (PTA) XIa activated IX. Hemophilia C (congenital) or PTA deficiency in consumption coagulopathy
XII Hageman factor XIIa activated XI. Hageman syndrome is more likely to lead to disorders of fibrinolysis (congenital or consumption coagulopathy )
XIII Fibrin stabilizing factor XIIIa converts fibrin monomers to crosslinked fibrin. Factor XIII Deficiency

To avoid clotting in the absence of injuries, the blood plasma contains various inhibiting substances ( inhibitors ). Protease inhibitors inhibit the formation of fibrin. Antithrombin inhibits several coagulation proteases in the activation phase and coagulation phase. The inhibitory effect is significantly increased by its cofactor, heparin . Heparin is produced by endothelial cells and mast cells . Thrombomodulin , which also comes from the endothelium, binds to thrombin and activates protein C , which after binding to protein S inactivates the cofactors Va and VIIIa.

Research history

Until 1772 the idea of Aristotle was held that the coagulation of blood can be compared to the freezing of liquids.

The first theories of hemostasis interpreted coagulated blood against the background of humoral pathology as " black bile ". From the 17th century the study of physiological mechanisms began. In 1772, William Hewson showed that there is a lymph in the blood that is responsible for coagulation. In the 18th century, the opinion prevailed again that when blood clots, the movement of the blood comes to a standstill and that when the suspended particles settle out, the impression of blood clotting occurs. In 1821, Jean Louis Prévost and Jean Baptiste André Dumas made a breakthrough in research: Coagulation is the coming together of blood cells and fibrin. Johannes Müller stated that the fibrin must be dissolved in the blood; Rudolf Virchow was able to provide further explanation in 1856 when he came across the precursor of fibrin, which he called fibrinogen. 1830 to 1859 Prosper Sylvain Denis de Commercy (1799-1863) carried out several studies in which he found, among other things, the instability of the clot. He also managed to precipitate serofibrin from the plasma, which he called plasmin.

Alexander Schmidt (1831–1894) proposed a coagulation theory in 1876 based on interacting proteins. He also described the role of calcium. It has long been discussed which substances are really necessary for coagulation and whether the cellular or the plasmatic phase is the more important.

Olof Hammarsten (1841–1932) and Léon Fredericq (1851–1939) showed in 1875 that fibrin ferment and fibrinogen are the only substances that lead to hemostasis and that it is not a fibrinoplastic substance. Schmidt continued researching this ferment and named it thrombin. He also created the thesis that there must be prothrombin in the plasma.

In 1904 Paul Morawitz described the system almost as it is known today. He coined the term plasmatic coagulation and described the following two phases

The molecular mechanisms of blood coagulation were largely discovered during the 20th century. A first indication of the complexity of the mechanisms of blood coagulation was the discovery of proaccelerin by Paul Owren (1905–1990) in 1947, which was designated as factor V. The complete amino acid sequence was published in 1987 by Jenny et al. released. Owren already suspected that this factor produced accelerin, which he called factor VI. It later turns out that factor V is the inactive precursor of factor VI. Therefore factor VI is now referred to as factor Va.

Factor IX was discovered in 1952 due to the illness of a young patient with haemophilia B named Stephen Christmas, in whom the absence of this factor caused the illness. That's why it's called the Christmas factor. Many of the other factors were also discovered in the 1950s and are often named after the patients in whom they were found. Details of these discoveries are described in the articles for the respective factors.

It was only recently discovered that the intrinsic pathway probably does not play a physiological role, i.e. that it can be observed in vitro , but not in vivo .

Clinical significance

Medicinal anticoagulant

Before, during and after operations, as well as when bedridden for other reasons, temporary anticoagulant drugs (often incorrectly referred to as blood thinners) are often used to prevent thromboses and pulmonary embolisms . This approach is called thrombosis prophylaxis .

The most common reason for long-term therapeutic anticoagulation nowadays is atrial fibrillation or flutter. With this cardiac arrhythmia there is an increased risk of embolism, which in many patients has to be reduced by thinning the blood. The second most common reason is thrombosis, mostly of the leg veins. In this case, the anticoagulant in the acute phase is intended to prevent further expansion of the thrombosis and later recurrence (relapse).


For drug inhibition of coagulation in vivo may heparin and heparinoids, may be used. It is an extremely strongly negatively charged chain of sugars that attaches to the protein antithrombin already mentioned . This complex now more effectively binds the factors thrombin and Xa, which are thereby deactivated: the coagulation cascade comes to a standstill. The effect starts immediately after intravenous administration. Heparin for medicinal use is usually obtained from animal tissues.


Another possibility are so-called vitamin K antagonists such as the coumarin derivatives phenprocoumon and warfarin . Vitamin K is required as a coenzyme for the synthesis of most coagulation factors . Coumarin works in the liver and prevents the reduction of vitamin K ( phylloquinone ). This participates in the γ- carboxylation of the coagulation factors (II, VII, IX, X) and is itself oxidized (release of electrons ). Without a subsequent reduction (uptake of electrons), vitamin K remains functionless. The effect only sets in after a certain time, but it can be administered orally.

Antiplatelet drugs

Acetylsalicylic acid can intervene in platelet aggregation, i.e. in cellular hemostasis. A cyclooxygenase (COX), which is required for the synthesis of the platelet factor thromboxane A 2 , is irreversibly inhibited by the attachment of an acetic acid residue. Clopidogrel also acts on the aggregation of blood platelets by inhibiting ADP-dependent platelet activation through irreversible receptor blockage. Abciximab is a recombinant monoclonal antibody that blocks the glycoprotein IIb / IIIa of the platelets and thereby also prevents platelet aggregation. Tirofiban has the same attack site .


Fibrinolytics activate plasminogen and thus promote the dissolution of thrombi ( thrombolysis ). This is used for the therapy of heart attacks , pulmonary embolisms , leg vein thromboses , peripheral occlusive diseases and, within a four-hour time window, also for acute cerebral infarctions . While active substances such as streptokinase and urokinase have a non-specific effect on both fibrinogen and fibrin, newer substances such as alteplase ( recombinant tissue type plasminogen activator , rt-PA) have a selectivity for cross-linked fibrin in thrombi, which is intended to reduce systemic side effects, especially bleeding . The use of fibrinolytics is subject to strict indications.

Inhibition in vitro

In vitro , e.g. B. in blood tubes, EDTA and citrate are often used, chelators that form a complex with the calcium cations required for clotting. Anticoagulation with heparin is also possible in vitro. The selection of the anticoagulant is based on which examination is planned later with the blood that has been rendered incoagulable. For investigations of the coagulation itself, citrate is used almost exclusively as a coagulation inhibitor, by diluting the blood sample in a ratio of 9 + 1 with a 3.8% sodium citrate solution. As a rule, industrially prefabricated tubes are used for this, which already contain 0.3 ml of sodium citrate solution and are then filled with 2.7 ml of blood. For the reliability of the resulting analyzes, it is important that this mixing ratio is precisely adhered to and that the blood sample is carefully mixed with the sodium citrate solution immediately after collection.

Drug enhancement of hemostasis

It makes sense to want to influence the hemostasis in the opposite direction and, in the case of life-threatening bleeding, to administer drugs that lead to increased hemostasis. In the past, the development of such drugs, called hemostyptics in technical terms , was less successful than with drugs that inhibit hemostasis.

Preparations that remedy a congenital or acquired deficiency of coagulation factors, for example factor VIII concentrate for hemophilia  A, vitamin K and PPSB for bleeding under coumarin therapy, or frozen fresh plasma for disseminated intravascular coagulation have become important for medical treatment . If there is a pronounced shortage of blood platelets, they can be replaced in the form of platelet concentrates . The effects of heparin can be canceled out by protamine .

Furthermore, the hemostasis can be increased by inhibiting the natural antagonist of coagulation, fibrinolysis. Drugs with this mechanism of action are called antifibrinolytics . The active ingredients used are tranexamic acid , para- aminomethylbenzoic acid and ε-aminocaproic acid . The previously frequently used aprotinin was withdrawn from the market in November 2007 due to increased mortality during treatment.

Butyl alcohol in the preparation hemostyptic Revici proved to be unsuitable because its mode of action was within the range of speculation .

Coagulation studies

The measurement of blood clotting (coagulability, coagulation, coagulability) is called coagulometry , corresponding devices are called coagulometers. The result of the blood coagulation measurement is the coagulation status ( coagulogram ).

Abbr. designation unit Standard value material Activator Monitoring of
TPZ, PT Thromboplastin time, prothrombin time Seconds 11-16 Citrated plasma after centrifugation Tissue thrombokinase = tissue factor = thromboplastin = factor III Start of the extrinsic coagulation system, therapy with vitamin K antagonists
Quick corresponds to TPZ, PT compared to standard plasma percent 70-125% Citrated plasma after centrifugation s. O. s. O.
INR corresponds to standardized TPZ, PT compared to standard plasma 0.8 - 1.2 Citrated plasma after centrifugation s. O. s. O.
aPTT (activated) Partial Thromboplastin Time Seconds 20-38 Citrated plasma after centrifugation Phospholipids (also outdated: partial thromboplastin or platelet factor 3, a protein-free phospholipid extract), and a surface-active substance (e.g. kaolin) Time onset of the intrinsic coagulation system, heparin therapy
ACT Activated Coagulation Time, Kaolin Clotting Time Seconds 100-130 Whole blood surface-active substance (e.g. kaolin) Start of the intrinsic coagulation system, heparin therapy, measurement close to the patient from whole blood possible e.g. B. with HLM or ECMO
PTZ, TZ Plasma thrombin time, thrombin time Seconds 20-38 Citrated plasma after centrifugation Thrombin Start of time of the common end section of the coagulation system, heparin therapy
Multiplate® ASPI commercial platelet impedance aggregometry Area under the curve > 40 Hirudin whole blood Arachidonic acid (as a substrate for the COX for the production of Thromboxane A2) Platelet function, COX inhibitors: ASA (e.g. aspirin), NSAIDs
Multiplate® ADP commercial platelet impedance aggregometry Area under the curve > 40 Hirudin whole blood ADP Platelet function, ADP receptor antagonists: clopidogrel, prasugrel platelet function
Multiplate® TRAP commercial platelet impedance aggregometry Area under the curve > 40 Hirudin whole blood Thrombin Receptor Activating Peptide (TRAP-6) Platelet function, glycoprotein IIb / IIIa antagonists, mechanical platelet defect
ROTEM® EXTEM commercial thrombelastometry

CT = Clotting Time CFT = Clot Formation TIme MCF = Maximum Clot Firmness ML = Maximum Lysis

Citrated whole blood Tissue thrombokinase = tissue factor = thromboplastin = factor III Time onset of the extrinsic coagulation system, clot strength, clot persistence, therapy with vitamin K antagonists


s. O. Citrated whole blood Partial thromboplastin phospholipid from rabbit brain Time onset of the intrinsic coagulation system, clot strength, clot persistence time, heparin therapy
ROTEM® HEPTEM s. O. Citrated whole blood Partial thromboplastin phospholipid from rabbit brain

+ Heparinase to end the heparin effect

Time onset of the intrinsic coagulation system, clot strength, clot duration,

after removal of the heparin effect

ROTEM® FIBTEM s. O. Citrated whole blood Tissue thrombokinase = tissue factor = thromboplastin = factor III

+ Cytochalasin D to inhibit platelets

Start of time of the extrinsic coagulation system, clot strength, clot persistence time WITHOUT platelet effect d. H. the isolated fibrinogen effect is evident


s. O. Citrated whole blood Tissue thrombokinase = tissue factor = thromboplastin = factor III

+ Aprotinin to inhibit hyperfibrinolysis

especially clot persistence, which is shortened by hyperfibrinolysis
Blood plasma after adding thromboplastin (quick test). The resulting gel is strong enough to hold a steel ball.

Medical laboratory diagnostics are used to measure the coagulability of the blood

  • the Quick value for the selective determination of the function of the exogenous system by adding tissue factor and Ca 2+ to the blood sample and then determining the clotting time compared to normal blood, for example in coumarin therapy, as well as the INR (International Normalized Ratio) derived from it, which corresponds to the Quick test is increasingly being replaced. The INR offers better comparability between different laboratories than the Quick value. However, both values ​​are normal in hemophilia.
  • the PTT (Partial Thromboplastine Time) for the selective determination of the function of the endogenous system and the common path of blood clotting. In the case of hemophilia, this value is above the standard value of approx. 30 seconds.
Blood samples; right: whole blood before centrifugation; left: after centrifugation, the lower phase contains cellular components, the upper phase the soluble, blood plasma.

These tests are known as the global tests of coagulation. They can only recognize a reduced coagulation (risk of bleeding) and serve to monitor treatment with anticoagulant drugs such as Marcumar, but not too much ( thrombophilia ). Other, less frequently used tests for measuring the coagulability of the blood are thrombin time and the functional fibrinogen determination according to Clauss.

The activation state of the coagulation system in the entire body can be determined by measuring the D-dimers (fibrin breakdown products). In this way, certain disease states that are present at the time of blood collection and are associated with activation of the plasmatic coagulation can be recognized ( thrombosis , pulmonary embolism , disseminated intravascular coagulation and heparin-induced thrombocytopenia type II). A distinction between various possible causes of coagulation activation and a reliable assessment of a future risk (thrombophilia) is not possible by determining the D-dimers. A suitable search test for thrombophilia does not currently exist; rather, if there is a corresponding suspicion, all possible causes must be excluded individually.

An assessment of the Quick value and the PTT in connection with a bleeding tendency should always include a detailed bleeding history, the number and possibly also the function of the blood platelets ( thrombocytes ). The cellular hemostasis is much more difficult to assess than the plasmatic. Only the number of blood platelets can be determined easily and reliably, but not their function. The tests provided for this purpose are either unreliable (bleeding time) or complex and therefore not available everywhere ( thrombelastogram , platelet function analyzer).

Before operations, even in patients who are not taking any blood-thinning medication, a rough assessment of the coagulation situation based on these three parameters (Quick, PTT and platelet count) is often carried out in order to identify non-drug-related hemostasis disorders. This practice is now controversial in expert circles, as only around 13% of hemostasis disorders are recognized here and a feeling of false security is created for doctors. The coagulation disorders that are most common epidemiologically and affect platelet function or the Von Willebrand factor are not recorded by the three standard tests, so that it is only recommended if there is a positive bleeding history. Other authors consider this to be negligent and recommend the routine preoperative determination of platelet count, activated partial thromboplastin time (aPTT), Quick value and fibrinogen, even with a negative bleeding history, so that further studies appear necessary.

Arterial blood coagulates faster than venous blood, which is due to the differences in gas content. The coagulation of arterial blood can be slowed down by adding carbonic acid , but that of venous blood can be accelerated by increasing its oxygen content . The differences in the temperature of the two types of blood are much less regular, because while in organs with a very lively metabolism (e.g. glands and muscles) the outflowing blood is warmer than the incoming blood, organs with only insignificant heat production capacity (e.g. the outer skin) show the opposite Behavior.

Significance in diseases

Basically, the balance between hemostasis and fibrinolysis can derail in both directions: increased coagulation is known as thrombophilia (the resulting blood clots that cause disease are called thrombus or embolus ), and reduced coagulation is called hemorrhagic diathesis . A bleeding tendency can also arise as a result of a previous strong coagulation activation with consumption of coagulation factors.

Bleeding tendency

The above-described physiological processes of hemostasis after an injury (blood vessels, cellular and plasmatic hemostasis) can be disrupted in any phase, so that a number of different disorders can each lead to a tendency to bleed. Like hemostasis itself, its disorders can begin in the area of ​​the blood vessels. For example, a congenital malformation of the blood vessels, which leads to their expansion and is known as Osler's disease , can be the cause of an increased tendency to bleed.

Cellular hemostasis is impaired when there is a pronounced lack of blood platelets ( thrombocytopenia ) or when there are dysfunction of the blood platelets. The latter are the most common cause of increased bleeding tendencies. They can be caused by medication (see section platelet aggregation inhibitors above), the most common congenital disorder of cellular hemostasis (and at the same time the most common congenital bleeding disorder of all) is the Willebrand-Jürgens syndrome .

The lack of many plasmatic coagulation factors can also lead to sometimes life-threatening diseases, for example hereditary diseases such as haemophilia . This most commonly affects coagulation factor VIII (haemophilia A), less often also coagulation factor IX (haemophilia B).

In addition to congenital forms of bleeding tendency, which are usually caused by genetic defects in individual components of hemostasis, there are also acquired conditions that lead to an increased bleeding tendency. The plasmatic coagulation can, for. B. be impaired by a vitamin K deficiency . As a result, the coagulation factors II, VII, IX and X can no longer be sufficiently carboxylated in the liver , which can lead to a functional deficiency and consequently to severe cerebral haemorrhage, especially in premature infants. Since all coagulation factors are produced in the liver, severe liver diseases almost always lead to a lack of coagulation factors with the consequence of an increased risk of bleeding.

A disseminated intravascular coagulopathy is a life-threatening disease in which the body's own by an abnormally high level mediators such as histamine, serotonin and adrenaline an excessively draining blood clotting takes place. This leads to a high consumption of the plasmatic coagulation factors that cannot be replaced by the body quickly enough. One speaks therefore of a consumption coagulopathy.

In patients with a bleeding disorder, prophylactic plasma transfusions can be used prior to surgery. Regarding the effect of prophylactic plasma transfusions before invasive procedures in patients without congenital bleeding disorders, the evidence for all- cause mortality , for major bleeding, for the number of transfusions per patient, for the number of patients who require a transfusion, and for transfusion-related complications is very uncertain . Different transfusion triggers for fresh frozen plasma (FFP) may help reduce the number of people who need such a transfusion.

Thrombosis and embolism

Thrombosis is a vascular disease in which a blood clot (thrombus) forms in a vessel. Causes for this can be found in damage to the vessel wall and generally in reduced blood flow. However, coagulation disorders also play a major role here: For example, a hereditary or drug-induced increased tendency to coagulate can quickly lead to thrombosis. For this reason, countermeasures such as medical thrombosis prophylaxis stockings (MTPS) , intermittent pneumatic compression , or anti-coagulants such as heparin or phenprocoumon must be taken, for example, even if the legs are immobilized for a long time.

An embolism is a thrombus that has been washed away from its place of origin. This can lead to serious complications including a cerebral infarction .


There are a large number of congenital and acquired diseases in which there is an increased tendency to clot. What they all have in common is that there is increased vascular occlusion such as thrombosis and embolism . In some diseases, the high pressure system of the arteries is more affected, in others the low pressure system of the veins. The most common and important thrombophilias are:

A special form of thrombophilia can occur during treatment with the anticoagulant drug heparin . This drug, paradoxically, in some cases activates the platelets, causing them to clump together and start the clotting cascade. This can lead to severe thrombosis throughout the body. The decrease in the number of blood platelets can be measured, which is why the clinical picture is referred to as heparin-induced thrombocytopenia (type II).

See also

  • Hemostasis for other methods of medical hemostasis


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Web links

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This version was added to the list of articles worth reading on November 29, 2007 .