1. 1 HAEMOSTASIS

2. 2 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.

3. 3 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.

4. 4 THROMBIN fibrinogenFIBRIN 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)

5. 5 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)

6. 6 Secondary Haemostasis Factor XII Factor XI Factor IX Factor VIII Factor III Factor VII Factor X + Factor V Prothrombin Thrombin Fibrinogen Fibrin INTRINSIC PATHWAY EXTRINSIC PATHWAY COMMON PATHWAY

7. 7 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

8. 8 -Inherited thrombocytopenia a)  production (bone marrow disorders) b) Consumption (DIC) c)  destruction (immune-mediated) -Acquired thrombocytosis thrombocytopathy Platelet Disorders

9. 9 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

10. 10 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)

11. 11 Laboratory Findings THROMBOCYTOPENIA THROMBOCYTOSIS PLT count:  markedly and persistently  (> 1,000 x 10 9 /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

12. 12 - Platelet number: in reference range - BMBT:  - PT, aPTT in reference ranges - Alteration of PLT function assays (e.g. clot retraction) Thrombocytopathy: Laboratory findings

13. 13 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

14. 14 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)

15. 15 Laboratory Findings Tests ResultsFactors 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)

16. 16 Acquired Disorders of Coagulation Factors – Vitamin K antagonism and deficiency – Disseminated Intravascular Coagulation (DIC) – Liver disease

17. 17 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

18. 18 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).

19. 19 Laboratory Findings  Platelet (  PLT count,  bleeding time)  Plasma coagulation factors (  PT, aPTT or ACT)  Haematological abnormalities: Schistocytes Regenerative haemolytic anaemia Haemoglobinaemia (intravascular haemolysis)

20. 20 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)