Haemorrhagic Disease Pathophysiology

Introduction

Haemorrhagic diseases can be categorised by two different causal mechanisms:

• Increased vessel fragility which leads to a non-thrombocytopenic purpura.
• Inadequate haemostatic response. This may be caused by platelet dysfunction or deficiency, which leads to a primary or secondary thrombocytopenic purpura, or deficiencies/derangements of clotting factors.

Generally, syndromes caused by vascular fragility and platelet dysfunction tend to be purpuric and acquired. Syndromes caused by clotting factor defects tend to cause more severe bleeding and are usually congenital.

Vascular Fragility

There are several ways that vascular fragility may arise. Capillaries can be damaged by toxins - this occurs in severe bacterial infections in all species. Streptococcus, Pasteurella and anthrax infections would be good examples of organisms that feature capillary damage as a symtom of infection.

Drug-induced and heavy metal damage to the vascular system does occur, although the mechanisms are not clearly understood. Examples include lead, bismuth, mercury, iodides, fluorides, chlorinated hydrocarbon pesticides and salicylates.

Vascular fragility can occur as a consequence of an underlying disease state, which is seen in allergy or anaphylactic reactions, connective tissue diseases such as Ehlers-Danlos syndrome in dogs, diabetes mellitus and antibody-antigen complex reactions.

Platelet dysfunction

Bleeding disorders may occur if platelets are deficient (thrombocytopaenia) or if the platelets are unable to function adequately (thrombocytopathia). Immune-mediated thrombocytopaenia (ITP) is one common cause of thrombocytopaenia and this may be a primary or secondary disease. Thrombocytosis refers to an increase in the blood platelet concentration above the normal level, and has no clinical importance except as an indicator of another disease process. Thrombocytopaenia and thrombocytopathia both result in reductions in the effectiveness of primary haemostasis, giving rise to a bleeding disorder. Since heamorrhage is usually sealed by a fibrin clot, disorders of primary haemostasis tend to be less severe than those caused by deficiencies in the coagulation factors.

Clotting Factor Abnormalities

Deficiencies in clotting factors are often the result of congenital deficiency in one or more of the coagulation factors and can lead to ineffective blood clotting and development of a disease syndrome characterized by excessive bleeding - deficiencies are often detected following trauma or surgery. Occasionally bleeding may be spontaneous (e.g. into alimentary or urinary tracts). Deficiencies are often seen as familial inherited problems; Haemophilia (factor VIII deficiency) is probably the best understood condition.

Other coagulation defects can be induced by disease processes such as angiostrongylosis, vitamin K deficiency (rodenticide poisoning) or disseminated intravascular coagulation (DIC)