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HAEMOSTASIS

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Definition

Haemostasis is a complex sequence of

physical and biochemical changes

induced by damage to tissues and

blood vessels, which transform the

blood into a clot, and, later, bring

about the repair of damaged vascular

endothelium.

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Fundamental Steps in Haemostasis Primary Haemostasis is the interaction between

platelets and damaged vascular endothelium to form an unstable platelet plug at the site of injury.

Secondary Haemostasis is the process of blood coagulation, which is focused on the generation of Thrombin which in turn converts soluble fibrinogen to insoluble fibrin and forms a stable clot.

Fibrinolysis follows repair of vascular damage. Fibrinolyis involves breakdown of the fibrin clot to re-establish vascular patency and normal blood flow.

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THROMBINfibrinogen FIBRIN

SECONDARY HAEMOSTASIS:

final haemostatic plug

PRIMARY HAEMOSTASIS:primary platelet

plug

common pathway

extrinsic pathway

Vascular damage

collagen exposure release of tissue thromboplastin

intrinsic pathway

PLT aggregation

vessel-constriction

Overview of Haemostasis

vWF(von Willebrand Factor)

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Primary Haemostasis

VASCULAR PHASE- Vessel constriction - Pressure by external blood lost into surrounding tissues

PLATELET PHASE- Immediate accumulation of PLT at the site of blood vessel damage - PLT adhesion to the subendothelial collagen by means of exposure of vWF - PLT shape changes and release of its internal substances (ADP, serotonin…) which induce aggregation of further PLTs

Formation of primary platelet plug

- vWF (von Willebrand Factor)

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Secondary HaemostasisFactor XII

Factor XI

Factor IX

Factor VIII

Factor III

Factor VII

Factor X + Factor V

Prothrombin Thrombin

Fibrinogen Fibrin

INTRINSICPATHWAY

EXTRINSICPATHWAY

COMMONPATHWAY

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Classification of Haemostatic Disorders

Platelets• Alterations in platelet count• Alterations of platelet function

Coagulation factors• Inherited disorders • Acquired disorders• Disseminated Intravascular

Coagulation Fibrinolytic system

• Disseminated Intravascular Coagulation

• Thrombosis

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-Inherited

• thrombocytopenia

a) production (bone marrow disorders)b) Consumption (DIC)c) destruction (immune-mediated)

-Acquired

• thrombocytosis

• thrombocytopathy

Platelet Disorders

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Causes of Thrombocytosis

Increased PLT production Myeloproliferative disorders

(thrombocythaemia, polycythaemia vera, leukaemia), neoplasia (e.g. carcinoma)

Chronic inflammation (and possibly liver disease)

Infection, acute haemorrhage Increased release from tissue stores From spleen and lungs following exercise,

pregnancy, excitement Drugs

Eg vincristine, adrenalin

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Causes of Thrombocytopathy

Acquired Many causes such as: renal failure,

myeloproliferative disorders, dysproteinaemia, liver disease, hyperfibrinolysis, systemic lupus erythematosus, congenital cardiac disease, anaemia, leukaemia, hypothyroidism, hyperoestrogenism, virus infection, drugs (ie aspirin, ibuprofen, phenylbutazone)

Hereditary PLT adhesion defect (von Willebrand disease,

thromboasthaenia) Deficient function (Chediak-Higashi)

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Laboratory Findings

THROMBOCYTOPENIA THROMBOCYTOSIS

PLT count: markedly and persistently

(> 1,000 x 109/L)

BMBT: or N N

PT in ref. range in ref. range

aPTT “ “

- production (bone marrow disorders): reduction of megakaryocytes in bone marrow. Ehrlichia canis or FeLV serology should be recommended

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- Platelet number: in reference range

- BMBT:

- PT, aPTT in reference ranges

- Alteration of PLT function assays

(e.g. clot retraction)

Thrombocytopathy:Laboratory findings

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Disorders of Coagulation Factors

Disorders are induced by a deficiency of

(biological) clotting activity of one or more

clotting factors.

Clinically characterized by large

haemorrhages, haematomas and bleeding

into body cavities

Classified as inherited or acquired

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Inherited Disorders of Coagulation Factors

GENERAL CHARACTERISTICS

- Usually affect young animals

- Usually affect a single coagulation factor

- Will present as a defect in secondary

haemostasis (with external and/or internal

bleeding)

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Laboratory Findings

Tests Results Factors possibly affected

APTT - normal PT XII, XI, IX or VIII

PT - normal APTT III or VII

PT and APTT X or other factor in the common pathway (prothrombin, fibrinogen)

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Acquired Disorders of Coagulation Factors

– Vitamin K antagonism and deficiency

– Disseminated Intravascular

Coagulation (DIC)

– Liver disease

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Vitamin K Antagonism/Deficiency

Main Causes:

- Rodenticide ingestion, (most common), i.e. warfarin poisoning. - Gastrointestinal disorders, i.e. Coccidiosis can cause severe intestinal lesions and Vit. K malabsorption.- Grass-eating species can be affected by plants contain coumarol.

Laboratory findings:- Platelet number: in reference range- BMBT: in reference range PT and aPTT

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DIC

DIC is defined as a systemic thrombo-haemorrhagic disorder, associated with well-defined clinical situations in which there is an excessive activation of pro-coagulant and anticoagulant mechanisms. Additionally, there may be biochemical evidence of organ damage or failure (eg. involving liver or kidneys).

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Laboratory Findings

Platelet ( PLT count, bleeding time) Plasma coagulation factors ( PT, aPTT or ACT) Haematological abnormalities:

Schistocytes Regenerative haemolytic anaemia Haemoglobinaemia (intravascular haemolysis)

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Disorders of the Fibrinolytic System

Thrombosis Is defined as an ischaemic condition resulting

from intravascular deposition of a fibrin-platelet mass.

Involved the fragmentation of a thrombus produces emboli which may induce blockage or ischaemia at remote sites.

The main causes are: Vascular endothelial injuries (eg dirofilariasis,

bacterial endocarditis, deposition of immune complexes) Cardiomyopathies in cats Nephrotic syndrome (i.e. amyloidosis) Diabetes mellitus

Disseminated Intravascular Coagulation (DIC)