1. Constituents of the blood: Platelets and plasma
Dr D J Hampshire
University of Sheffield

2. Two phases of the blood Cellular component (45%) Fluid component (55%)
Red cells
White cells
Platelets
Plasma
Fluid component (55%)

3. Haemostasis Blood inside the vessels remains fluid
Blood outside the vessels should clot
Balance

4. Blood is usually fluid inside vessels
Haemostasis
Blood is usually fluid inside vessels
Platelets and proteins of the coagulation cascade circulate in an inactive state
Endothelial cells, anticoagulant pathway and fibrinolytic pathway actively keep it fluid

5. Haemostasis Thrombosis Bleeding Balance Blood clots inside the vessel
Blood fails to clot outside the vessel
Balance

6. Platelets
Anucleate cells Circulate in an inactive state Responsible for primary haemostasis
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7. Platelets and primary haemostasis
Platelets circulate in an inactive state

8. Platelets and primary haemostasis
Damage to the blood vessel
Bind (adhere)

9. Platelets and primary haemostasis
Damage to the blood vessel
Bind (adhere)
Change shape (activate)

10. Platelets and primary haemostasis
Damage to the blood vessel
Bind (adhere)
Change shape (activate)
Release contents (degranulate)

11. Platelets and primary haemostasis
Aggregate to form a platelet (haemostatic) plug
Lack of platelet function leads to bleeding

12. Thrombocytosis Arterial thrombosis Venous thrombosis
Platelet number
Normal = x 109 / L
Reduced
Increased
Thrombocytopenia ≥80 - <140 x 109 / L Increased bleeding ≥20 - <80 x 109 / L Spontaneous bleeding
Thrombocytosis Arterial thrombosis Venous thrombosis

13. Soluble and in plasma component
Proteins
Soluble and in plasma component
Albumin
Immunoglobulins
Carrier proteins
Coagulation proteins

14. Albumin
Produced in the liver Determines oncotic pressure Keeps intravascular fluid in that space Lack of albumin: Oedema, liver disease, nephrotic syndrome

15. Immunoglobulins
Produced by B lymphocytes Antibodies generated when stimulated by foreign antigens Several classes: IgA, IgE, IgG, IgM Basis of immunity and vaccination

16. Coagulation proteins IIa Xa Va IIa II V TF VII X IX XIIa TF VIIa XIa
IXa
VIIIa Xa Va II
IIa
VIII
VWF V
Fibrinogen
Fibrin Monomer
Fibrin Polymer
XIII
XIIIa
Stable Fibres
IIa

17. Coagulation proteins TF
VII X IX
XIIa TF
VIIa
XIa XI
IXa
Series of enzymes that circulate in an inactive state
Sequentially activated in a cascade sequence
Convert soluble fibrinogen into insoluble fibrin polymer
Generate a stable clot
VIIIa Xa Va II
IIa
VIII
VWF V
Fibrinogen
Fibrin Monomer
Fibrin Polymer
XIII
XIIIa
Stable Fibres
IIa

18. Why is the coagulation cascade so complicated?
Multiple steps allows for biological amplification of the response
Multiple steps allows for regulation, not an all or nothing response
Response can be graduated depending on the severity of the haemostatic challenge

19. Coagulation cascade and haemostasis
Thrombosis
Coagulation proteins are overactive
Bleeding
Failure of coagulation proteins
Balance

20. Haemophilia Haemophilia A Haemophilia B
Severe bleeding into muscles and joints Incidence 1 in 10,000 males Deficiency of factor VIII Treat with recombinant factor VIII
Severe bleeding into muscles and joints Incidence 1 in 50,000 males Deficiency of factor IX Treat with recombinant factor IX

21. von Willebrand disease (VWD)
Usually mild bleeding disorder often unrecognised and underdiagnosed Prevalence between 1% and 1 in 10,000 Defect or deficiency in von Willebrand factor (VWF) Binds platelets and factor VIII

22. VWD types Normal individual: normal VWF
Type 1: reduced quantity, essentially normal VWF 69% of cases
Type 2: functionally deficient VWF 27% of cases
Type 3: virtually no VWF 4% of cases

23. Muco-cutaneous bleeding
Epistaxis Menorrhagia Prolonged bleeding from cuts Easy bruising Bleeding after haemostatic challenge including; tooth extraction, trauma, surgery, childbirth

24. Acquired bleeding disorders
Recent onset; not lifelong and no family history Can manifest as generalised or localised bleeding Medicinal drugs can result in acquired bleeding

25. Liver disease
Often associated with bleeding and prolonged prothrombin time Coagulation factors and fibrinogen are synthesised in the liver

26. Vitamin K deficiency
Manifests as prolonged prothrombin time Vitamin K necessary for correct synthesis of coagulation factors II, VII, X and XI Can be treated with intravenous vitamin K

27. Disseminated intravascular coagulation (DIC)
Breakdown of haemostatic balance Simultaneous bleeding and microvascular thrombosis (life threatening) Cause can be sepsis, obstetric or malignancy Administering plasma and platelets can be considered (if required)

28. Drugs and bleeding
Aspirin and clopidogrel affect platelet function Heparin and warfarin affect the coagulation cascade Steroids make tissues thin causing bruising and bleeding