Emergency situations

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Emergency situations

Haemostasis

The term haemostasis signifies the stopping of blood flow from a wound. In the body it does not consist solely of the process of blood clotting with assistance from the blood platelets, but is made up of a complex series of interactions of tissues, cells and enzyme reactions. Blood clotting itself has already been described (pp. 48–51).

The process of haemostasis varies according to the size of the vessels which have been damaged. In small capillaries the loss of blood may be very small because the endothelial cells of the wall come into contact with each other and stick together. In larger capillaries the platelets adhere to the damaged area, forming a temporary plug, over which the endothelial cells slide to renew the wall.

A more complex sequence of events proceeds fairly rapidly in small vessels such as arterioles or venules up to about 150 μm in diameter. Its time course as observed in the thin tissue of a rabbit’s ear is outlined below. The process in human tissues under physiological conditions is slower, probably by a factor of 5–10 times.

The first few seconds

Injury to the wall of a blood vessel produces an almost instantaneous reaction of vasoconstriction. This is probably due to an axon reflex, although in other circumstances axon reflexes are always vasodilator. However, if sympathetic nerves are damaged (as they may be in the vessel wall) they may become active. Another possibility is that the smooth muscle cells contract in response to stimulation by the injury just as they contract in response to stretching(P.94).

Damage to the vessel wall has other effects. The local endothelium ceases to produce prostacyclin (PGI2) which inhibits platelet aggregation. The pattern of blood flow is changed by the injury itself and by the vasoconstriction.

The permeability of the red cell membranes is changed either by the changed stresses due to the alteration in the flow pattern of the blood, or by contact of the cells with the vessel wall as the axial stream of cells breaks up at a slower flow rate: ATP and ADP leak out of the cells. Adenosine diphosphate causes the platelets to become sufficiently adhesive to stick to any exposed tissue surfaces. This happens within a few milliseconds (as assessed from the rate of flow of platelets past the site of damage) but occurs only if red cells are present. Another possible activation mechanism for platelet adhesion is the formation of thromboxane A2 as a result of distortion of platelet membranes in the slight turbulence at the injury site. The inhibitory influence of the prostacyclin from the normal endothelium is lost after damage to the endothelium. The von Willebrand factor (part of the factor VIII complex – see Table 3.3) is essential for platelet adhesion to take place.

The damage to the vessel wall allows the blood plasma to come into contact with the collagen fibres and the smooth muscle of the vessel wall instead of the endothelial cell lining. Contact with extravascular tissues and the contents of damaged cells may also occur. These processes activate the intrinsic clotting mechanism through factor XII, but also activate factor VII of the extrinsic system. The combination of factors XII and XI (the Contact Product) also helps to activate factor VII in these circumstances. Endothelial cells contain a thromboplastin which is released as they are damaged. They also release a plasminogen activator; and activated factor XII activates a plasminogen pro-activator.

Between 3 and 15 seconds

In the next few seconds a number of processes occur simultaneously. There may be some red cell haemolysis, releasing more ATP and ADP, and also a factor which acts as a partial thromboplastin. Central release of adrenaline causes some general peripheral vasoconstriction. The intrinsic clotting system proceeds slowly through the cascade of reactions towards thromboplastin formation (Fig. 3.4). In the extrinsic system the interaction between the lipoprotein tissue factor, factor VII, and calcium ions, activates factor X. Activated factor X forms a complex with phospholipid, factor V and prothrombin; this releases thrombin. The thrombin increases the conversion of ATP to ADP; this raises the concentration of ADP sufficiently to maintain the local vasoconstriction and accelerate the process of platelet adhesion so that a primary platelet aggregation rapidly closes the defect in the vessel wall. The primary platelet aggregation is not stable unless supported by later fibrin formation. Platelets begin to lose their granules, but not yet to any significant extent.

After 30 seconds

During the second half minute a fibrin network develops over the surface of the primary platelet plug. The platelets, under the influence of thrombin, begin to lose their granules and disintegrate, releasing ATP and ADP, platelet fibrin stabilising factor, antiheparin, fibrinogen, and serotonin. This takes over the role of maintaining vasoconstriction. Formation and release of thromboxane A2 acting together with serotonin and ADP, further increases platelet adhesion and aggregation. Contact of the platelets with collagen and thrombin stimulates thromboxane and prostaglandin endoperoxide (PGG2 and PGH2) formation. These, like thrombin itself, cause shape changes, aggregation and degranulation of the platelets. Platelet factor III, a phospholipoprotein, appears on the surface of the aggregation, and accelerates the extrinsic and, more particularly, the intrinsic pathways of thrombokinase production. The thrombin formed locally on the aggregation is soon present in sufficient concentration to overcome the counter-coagulation agents in the blood and so fibrin formation now proceeds prapidly. Platelets and red cells become trapped in the fibrin network, and this secondary aggregation produces a firm seal to the defect. Over 24 h the platelet-rich plug is covered and stabilised by a mass of fibrin. There is some evidence that the intrinsic clotting mechanism is more important than the extrinsic in this process.

Some time later clot retraction occurs, possibly by contraction of a contractile protein from the platelets, thrombosthenin, or by a contraction of a complex formed from the actin and myosin that have been identified in the platelets. Microtubules appear to be important in the platelet shape changes in the early stages, but play no role in clot retraction.

Fibroblasts move into the clot when the healing process begins, endothelial cells slide across the gap to re-establish the lining of the vessel, and finally the vessel wall is renewed.

The role of thromboxane A2 and the prostaglandin endoperoxidases is not entirely clear since aspirin does not always inhibit haemostasis as might be expected if they were critically important.

In larger vessels the platelet plug may be insufficient to seal the gap and blood passes out into the wound, where platelets and fibrin together may form a seal over the vessel. In the tooth socket, where a number of vessels are damaged, the clot forms over the damaged vessels. Bleeding from a large vessel, however, cannot be stopped by haemostatic processes alone, but requires pressure on the vessel to slow the loss of blood and allow clotting to take place.

Haemostasis as observed in the patient

The process of haemostasis is complex, involving many interactions and mutually accelerating processes. Plasmin and other factors operate against clot formation. Whilst tests of blood clotting may be performed in the test tube and deficiencies of specific factors identified, the whole process of haemostasis can be examined only in the patient. The crude test of bleeding time, which depends mainly on the vascular reactions to a calibrated stab, usually in the earlobe, tries to allow for factors other than blood clotting alone. The bleeding time measured in this way is much shorter (2–7 min) than the clotting time of 5–11 min in a glass capillary. Formation of the primary platelet plug is probably a key factor in determining bleeding time, since patients who lack factor VIII, or only the von Willebrand factor, have extended bleeding times. Patients in whom bleeding continues for apparently abnormally long periods after dental extractions do not necessarily suffer from deficiencies of clotting factors. Continual disturbance of a forming clot in the stage of the primary platelet plug, by repeated rinsing, or simply an inquisitive tongue, may result in bleeding beyond the normal time interval. The effect of a suture across the socket, or a gelatine pad, may simply be that of a defence against interference with a forming clot. Temperature is another factor which affects haemostasis: cold increases vasoconstriction, favouring the vascular response, whilst warmth increases the rate of reactions within the clotting sequence. Rinsing with warm, saline after tooth extractions may help in stopping blood flow.

The fibrinolytic system

The process of haemostasis involves the formation of fibrin: other mechanisms exist to break it down. The degradation and removal of excess or inappropriately formed fibrin is termed fibrinolysis. The fibrinolytic enzyme is plasmin, which is formed from plasminogen (p. 51) by the actions of various plasminogen activators. The most important of these is synthesised and secreted by the endothelium of blood vessels. It is released in response to circulating adrenaline, venous occlusion, and possibly also the action of thrombin. The mechanism of activation appears to be by the binding of the activator and the plasminogen to adjacent sites on the fibrin molecules. This sets in motion the process of fibrinolysis at those sites. It is possible that factor XII, which itself has been shown to be a weak stimulator of activator production, may also activate plasminogen via the production of kallikrein. This could provide a means of controlling fibrin produced when the intrinsic blood clotting mechanism only is activated by minor trauma to vessel walls. The blood cells, with the possible exception of the macrophages, are not capable of activating plasminogen. Both plasma and platelets contain antiplasmins and antiplasmin activators. These restrict the action of plasmin to the sites where it is actually attached to the fibrin molecules.

Hormonal effects on the process of haemostasis

Adrenaline, released in stress, not only causes vasoconstriction, but also increases platelet numbers by stimulating their release from the spleen, and, in the presence of fibrinogen and ADP, causes platelet aggregation. It increases the concentrations in the blood of factor VIII. All these effects help to promote clot formation when damage to tissues or blood vessels occurs. In addition, adrenaline stimulates release of plasminogen activator to assist in the breakdown of fibrin if necessary.

In high concentrations the corticosteroids, also released in stress, promote the release of factor VIII and enhance the effect of adrenaline on the plasma concentration of this factor.

The third hormone released in stress which can affect haemostasis is antidiuretic hormone. This increases the amount of factor VII in the blood and, like adrenaline, increases the amount of plasminogen activator. The hormones of stress, then, help provide for enhanced activity of the extrinsic clotting system and also of the fibrinolytic system, both protective measures.

An increased incidence of thrombus formation (clotting in the absence of damage to vessels, p. 51) has been observed in subjects taking contraceptive formulations over long periods of time. The effect appears to be due to the oestrogen content of the tablets. Oestrogens increase the activity of factors VII and X in the extrinsic clotting system, and factors XII and X in the intrinsic. Antithrombin activity is reduced, although plasminogen and plasmin are increased in concentration.

In pregnancy the main effect on the haemostatic system is an inhibition of urokinase activity causing decreased activation of plasminogen.

Shock and the recovery from haemorrhage

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Dec 5, 2015 | Posted by in General Dentistry | Comments Off on Emergency situations
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