Abnormalities of Haemostasis

Hi, in this post we'll take a look at what happens when the haemostatic mechanism doesn't work properly. We'll take a look at haemorrhage, thrombosis, and emboli.

Haemorrhage

Haemorrhage is the loss of blood from a damaged blood vessel. It can occur externally, into a body cavity or into tissue spaces. Haemorrhage can be caused by several factors including:

• Mechanical trauma: eg a bruise (which is also known as a contusion)
• Congenital or acquired vessel wall weakness: eg arteriosclerosis
• Toxic damage to the endothelium: eg arsenic poisoning
• Disorders of the clotting mechanism: this can be seen in hemophilia. 

Small, pinpoint haemorrhages in mucous membranes and the skin are called petechiae. Grossly, these look like little red dots on the skin or mucous membrane. Larger haemorrhages that cause lesions similar to petechia are ecchymoses. Petechiae are less than a centermeter in diameter while ecchymoses are 2-3cm in diameter.

Diapedesis

Diapedesis refers to the microscopic leakage of a small amount of blood cells through intact vessels into the surrounding extravascular tissue. It is not true haemorrhage.   

Nomenclature

Haemorrhage may occur in several parts of the body and the nomenclature reflects this. For example: a haemorrhage in the thorax is known as haemothorax and a haemorrhage in the pericardium is referred to as haemopericardium. Similarly, haematemesis refers to the vomiting of blood and haematuria is blood in the urine.   

The Resolution of a Significant but Non-Fatal Haemorrhage

Once a significant but non-fatal haemorrhage has occurred the body employs several mechanisms to increase the blood volume and to return blood pressure to its normal level. This occurs in three phases:

Phase 1
In this phase the body tries to maintain blood flow to the vital organs.

1.  The blood remaining in the body is redistributed.
2. This lowers the venous return.
3. This results in a decrease in cardiac output
4. Arterial blood pressure falls 
5. The carotid and aortic bodies detect this and stimulate the vasomotor centres which send out a strong sympathetic signal.
6. The superficial blood vessels as well as those leading to and from the spleen (splenic vessels) narrow. This causes blood to be directed towards the vital organs (the brain and respiratory muscles). 
7. Tachycardia occurs.
8. Adrenalin and Noradrenalin are released
9. Noradrenalin is a general vasoconstrictor but causes coronary arteries to dilate.
10. The fall in blood pressure also causes the kidneys to release renin which cause the production of angiotensin which is a strong peripheral vasocontrictor. Aldosterone is also released, this causes more sodium to be reabsorbed at the kidneys which means that more water is retained in the blood.

Phase 2
In this phase the body tries to restore the blood volume.

1. Despite the mechanisms utilised by the body in phase 1, the blood volume is bound to fall. 
2. Due to the loss of blood, some plasma proteins have been lost. However, most plasma proteins remain in the blood vessels. This creates an osmotic force which pulls the fluid from the extravascular spaces into the circulation.  

Phase 3

1. Erythropoiesis occurs and the red blood cell and haemoglobin content of the blood is restored to normal. The liver also increases its production of plasma proteins. 
2. Reticulocytes and metarubricytes (immature red blood cells) circulate the blood after about 4 days.  

 The Resolution of Haemorrhage at Tissue Level

1. Haemorrhage releases many red blood cells (RBCs) into the area as well as plasma and some other cell types. 
2. RBCs breakdown, releasing haemoglobin. Most RBCs stay at the site of the haemorrhage but some will enter the circulation. 
3. In the tissues, macrophages are attracted to the site of the haemorrhage where they phagocytose RBCs through erythrophagocytosis.
4. The haemoglobin that is within RBCs phagocytosed by the macrophages is broken down to iron and bilivedin (which makes the green colour of a bruise). Biliverdin is then metabolised to bilirubin (orange-brown) and then released into the circulation to be transported to the liver by albumin where it is excreted in bile. 
5. Haemoglobin is also released into the circulation and is transported to the liver bound to plasma proteins and recycled into bilirubin and then excreted in bile.
6.  Macrophages store iron from the RBCs in haemosiderin molecules. Iron is slowly recycled from these molecules. 
7. Globin is broken down within the macrophages into amino acids which are recycled.
8. Haemorrhage release plasma proteins, including fibrinogen into the tissues. When fibrinogen leaves the vascular system it is converted to fibrin which encourages fibroblasts to enter and produce fibrous connective tissue (fibrosis).

Thrombosis

As mentioned in the previous post, thrombosis occurs when the haemostasis mechanism isn't activated properly or there is "too much" haemostasis. Sluggish blood flow, irregularities in the vascular wall, and hypercoagulability of the blood predispose a region to thrombosis.

The Consequences of Thrombosis

Once a thrombus has been formed there are three potential four potential outcomes which may occur:

1. Cause immediate death: particularly if the vessel supplies a critical organ (eg. brain, heart).
2. Be lysed by the fibrinolytic system: plasmin causes fibrin to break down.
3. Undergo Organisation: If the thrombus does not completely block the lumen of the vessel, endothelium may migrate over the thrombus to restore vascular integrity. Fibrocytes then cause collagen to be produced over the fibrin, causing it to contract and the size of the thrombus decreases. If the thrombus does occlude the vessel, cells may migrate through the thrombus to create small vascular channels for blood to flow through.
4. Produce emboli.

An emboli is a plug of some material that travels throughout the circulation system. When the embolus reaches a part of the system where it is too narrow for it to pass through, it causes a blockage called an embolism. Often the embolus comes from a thrombus but it may arise from air, fat, parasites, bone marrow etc.

How much damage a thrombus or embolus causes depends on the vascular anatomy of the area which it blocks. If the tissue has an end arterial blood supply, infarction (death) of the tissue will occur. This can occur in the brain, heart, spleen, kidney and intestine. If the contents of the embolus have a high tendency to cause the formation of more thrombi, disseminated intravascular coagulation may occur. If a collateral circulation of the region affected by the embolus is present, it is likely that there will be no effect.

Thrombus vs Post-Mortem Clot

Once an animal dies, its blood is likely to form clots and it is important to be able to distinguish between post mortem clots and thrombi.

Clots tend to be moist, granular and rough while thrombi are dry, smooth and shiny. Thrombi are white or buff in colour while clots are red or yellow. In addition thrombi form attached to the vascular wall and are stratified as layers of fused platelets are added to the damaged endothelium during blood flow in a living animal. Clots are not attached to the vessel walls and are uniform in consistency as they develop from fibrin in a stagnant column of blood in the dead or dying and contain all blood elements trapped in the fibrin. The vascular endothelium remains intact.  Finally, thrombi may be partially organised and vary in shape while clots are never organised and mould the blood vessels like jelly. 


That's it for this post, see you next time :)