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BIOCHEMISTRY II > WEEK 7 (Hemostasis) > Flashcards

WEEK 7 (Hemostasis) Flashcards

1
Q

What is Hemostasis?

A

The physiological process by which bleeding stops

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2
Q

What happens in primary hemostasis?

A
  • VASUCLAR HEMOSTASIS (transient vasoconstriction and vWF activation following endothelial injury)
  • PLATELET HEMOSTASIS (adhesion, activation and aggregation of platelets -> platelet plug)
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3
Q

What happens in secondary hemostasis?

A

Activation of the coagulation cascade which results in the formation of a fibrin clot

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4
Q

What is the mechanism behind vasoconstriction?

A
  • Local myogenic spasm (systemic release of adrenaline)
  • Local release of Thromboxane A2
  • Stimulation of nerve impulses and vasocontraction
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5
Q

What are the properties of platelets?

A
  • Small cytoplasmic fragments derived from megakaryocytes
  • Life span of 8-10 days
  • Approximately 1/3 of platelet pool is stored in the spleen
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6
Q

What is the Von Willebrand factor (vWF)?

A

Plasma protein that is synthesised by and stored in endothelial cells and platelets

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7
Q

Describe what happens in platelet hemostasis

A

1) ENDOTHELIAL DAMAGE -> transient vasoconstriction via neural stimulation reflex and endothelin
2) Exposure of SUBENDOTHELIAL COLLAGEN causes circulating vWF to bind to the exposed collagen
3) After binding to vWF, platelets change their shape and release mediators (ADP, THROMBOXANE A2, CALCIUM) that lead to activation of more platelets
4) Mediated by GpIIb/IIIa-receptor and fibrinogen -> formation of a white thrombus composed of platelets and fibrinogen [white thrombus is transient, unstable and easily dislodged -> stabilises through secondary hemostasis]

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8
Q

What is a Clot?

A

A meshwork of fibrin fibers running in all directions entrapping blood cells, platelets and plasma

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9
Q

What is Blood clotting?

A

The transformation of blood from a liquid into a solid gel

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10
Q

What is the Extrinsic pathway of coagulation triggered by?

A

Endothelial injury

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11
Q

Where is Tissue Factor expressed?

A

On the surface of sub endothelial muscle cells and fibroblasts

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12
Q

Where is Calcium (Factor IV) found?

A

On the surface of fibrocytes and activated platelets

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13
Q

What triggers the Intrinsic pathway of coagulation?

A

Activation of XII-Hageman Factor

[Occurs when blood comes in contact with foreign surface such as glass, injured blood vessel and exposed collagen or endothelium]

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14
Q

What is the role of Vitamin K in coagulation?

A

Vitamin K acts as a CO-FACTOR for vitamin K-dependent clotting factors (II, VII, IX and X) which are involved in the activation of blood-clotting proteins

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15
Q

Describe what happens in Anticoagulation

A

1) Protein C and its cofactor protein S serve to suppress the activity of the coagulation cascade & after activation, protein C forms a complex with protein S
2) Protein S anchors the activated protein C complex (APC) to the cloth through Ca2+/y-carboxyglutamate binding to platelet phospholipids
3) APC destroys the active blood coagulation cofactors factor VIIIa and Va by PROTEOLYTIC CLEAVAGE, decreasing the production of thrombin
4) APC stimulates endothelial cells to increase secretion of prostaglandin I2 which reduces platelet aggregation

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16
Q

What is Antithrombin?

A

A small glycoprotein that inactivates several enzymes of the coagulation system

17
Q

What are the properties of Antithrombin?

A
  • Produced by the liver
  • Consists of 432 amino acids
  • Degrades thrombin and factors IX and Xa
  • Activates tissue plasminogen activator (tPA)
18
Q

How is further propagation of the blood clot prevented?

A

By switching off blood coagulation and by turning on fibrinolysis

19
Q

What is a D-dimer test?

A

A blood test that measured D-dimer which is a protein fragment that your body makes when a blood clot dissolves in your body

20
Q

What are the three coagulation tests?

A
  • Prothrombin time (PT)
  • Bleeding time
  • Partial thromboplastin time (PTT)
21
Q

Describe Prothrombin time (PT)

A
  • Extrinsic pathway
  • Add plasma to tissue factor
  • Measure time to form a clot (normal - 10s)
22
Q

Describe Bleeding time

A
  • A medical test that measures how fast small blood vessels in the skin stop bleeding
  • 2-9 mins
23
Q

Describe Partial Thromboplastin Time (PTT)

A
  • Intrinsic pathway
  • Add plasma to charge substance
  • Measure time to form clot (normal - 30s)
24
Q

What are Hemophilias?

A

X-linked recessive diseases which affect mostly males and female carriers are usually asymptomatic. Hemophilia A: deficiency of factor VIII. Hemophilia B: deficiency of factor IX.

SYMPTOMS:
- Spontaneous/easy bleeding
- Hemarthrosis
- PTT usually prolonged

TREATMENT:
- Mild haemophilia: DESMOPRESSIN (releases subendothelial stores of factor VIII but does not work for haemophilia B)
- Severe haemophilia: replacement of the specific factor

25
Q

Describe Vitamin K deficiency

A

Deficiency of vitamin k-dependent factors (II, VII, IX & X). it is caused by dietary deficiency (rare) ad GI bacteria.

SYMPTOMS:
- Bleeding
- Prolonged PT
- Prolonged PTT

TREATMENT:
- Antibiotics (deplete GI bacteria)
- Newborns - sterile GI tract
- Malabsorption - treat with vitamin K

26
Q

Describe Von Willebrand Disease

A

Deficient function of von Willebrand Factor which binds platelets to endothelium and other platelets. Most common inherited bleeding disorder.

DIAGNOSIS:
- Normal CBC and PT
- Increased PTT
- Increased Bleeding Time
- VWD screening tests

SYMPTOMS:
- Mild, non-life-threatening bleeding
- Easy bruising
- Skin bleeding
- Prolonged bleeding from mucosal surfaces
- Severe nosebleeds
- Heavy menstrual bleeding

TREATMENT:
- vWF concentrate
- Desmopressin
- Aminocaproic acid-antifibrinolytic agent

27
Q

What is the difference between anticoagulants and antiplatelets?

A

Anticoagulants prevent the formation of the fibrin-meshwork whereas Antiplatelets prevent activated platelets

28
Q

Which drugs are Anticoagulants?

A
  • Heparin
  • Warfarin
  • Thrombin Inhibitors
  • Factor Xa Inhibitors
29
Q

Which drugs are Antiplatelets?

A
  • Aspirin
  • ADP Blockers
  • Phosphodiesterase Inhibitors
  • IIB/IIIA Inhibitors
30
Q

Which drugs are Thrombolytics?

A
  • tPA
  • Alteplase
  • Reteplase

BIOCHEMISTRY II (12 decks)

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