HAEMOSTASIS

1. HAEMOSTASIS

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. 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. Overview of Haemostasis Vascular damage collagen exposure vessel- constriction release of tissue thromboplastin extrinsic pathway vWF (von Willebrand Factor) intrinsic pathway PLT aggregation common pathway THROMBIN fibrinogen FIBRIN PRIMARY HAEMOSTASIS: primary platelet plug SECONDARY HAEMOSTASIS: final haemostatic plug

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

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

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. 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. Laboratory Findings THROMBOCYTOPENIA THROMBOCYTOSIS PLT count: markedly and persistently  (> 1,000 x 109/L) BMBT:  or N N PTin 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. Thrombocytopathy: Laboratory findings • Platelet number: in reference range • BMBT:  • PT, aPTT in reference ranges • Alteration of PLT function assays • (e.g. clot retraction)

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 • Classifiedas inherited or acquired

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/orinternal bleeding)

15. Laboratory Findings

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

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

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)