Normal Hemostasis

Question 1

What is haemostasis?

Answer 1

Haemostasis is the mechanism that keeps blood in a fluid state.

Question 2

What are the three categories of normal haemostasis?

Answer 2

Primary hemostasis, secondary hemostasis, and tertiary hemostasis.

Question 3

What are the five major components involved in haemostasis?

Answer 3

Blood vessels, blood platelets, coagulation factors, coagulation inhibitors, and fibrinolysis.

Question 4

What are blood platelets?

Answer 4

Fragments of cytoplasm of megakaryocytes, non-nucleated.

Question 5

Where are blood platelets produced?

Answer 5

Mainly by the bone marrow.

Question 6

What is the normal platelet count range?

Answer 6

95-400 x 10^9/l.

Question 7

What is the lifespan of a platelet?

Answer 7

About 7-10 days.

Question 8

What percentage of platelets are typically trapped in the spleen?

Answer 8

About 1/3.

Question 9

What are the dimensions of a platelet?

Answer 9

Measures about 3x0.5 μm.

Question 10

What is the volume of a platelet?

Answer 10

About 7-11 fl.

Question 11

What are the three types of storage granules in platelets?

Answer 11

Dense granules, alpha/specific granules, and lysosomes.

Question 12

What substances are contained in the specific granules of platelets?

Answer 12

Fibrinogen, Factor V, vWF, platelet-derived growth factor, fibronectin, β-thromboglobulin, heparin antagonist (PF-4), thrombospodin, other coagulation factors.

Question 13

What substances are contained in the dense granules of platelets?

Answer 13

Nucleotides (ADP, ATP, 5-HT), calcium, serotonin.

Question 14

What do lysosomes in platelets contain?

Answer 14

Catalase.

Question 15

What is the main function of platelets?

Answer 15

Formation of haemostatic plugs in response to vascular injury.

Question 16

What happens in the absence of platelets?

Answer 16

Spontaneous leakage of blood through vessel walls.

Question 17

Define primary haemostasis.

Answer 17

Formation of the primary platelet plug involving platelets, the blood vessel wall, and von Willebrand factor.

Question 18

What are the consequences of abnormalities in primary haemostasis?

Answer 18

Hemorrhage from mucosal surfaces, petechial or ecchymotic hemorrhages, prolonged bleeding after venipuncture or wounds.

Question 19

How does the normal endothelium prevent hemostasis?

Answer 19

By providing a physical barrier and secreting products that inhibit platelets, including nitric oxide and prostaglandin I2 (prostacyclin).

Question 20

What are the key steps involved in the formation of the primary platelet plug?

Answer 20

Platelet adhesion, platelet activation, and aggregation to form a platelet plug.

Question 21

What is the first event in hemostasis?

Answer 21

Adhesion of platelets to exposed subendothelium.

Question 22

How is platelet adhesion mediated in areas of high shear rate?

Answer 22

Mediated by vWF, which binds to gp Ib in the platelet membrane.

Question 23

How is platelet adhesion mediated in areas of low shear rate?

Answer 23

Mediated by fibrinogen, binding to gp Ia/IIa.

Question 24

What occurs during platelet activation?

Answer 24

Platelets change shape, activate the collagen receptor, undergo the release reaction, synthesize and release TXA2 and PAF.

Question 25

What substances are synthesized and released by platelets during activation?

Answer 25

TXA2 and platelet activating factor (PAF).

Question 26

How is platelet aggregation mediated?

Answer 26

Primarily by fibrinogen, with vWF playing a secondary role.

Question 27

What stabilizes the primary platelet plug?

Answer 27

Formation of fibrin.

Question 28

What is platelet procoagulant activity?

Answer 28

Exposed membrane phospholipid (PF3) becomes available for tenase and prothrombinase reactions.

Question 29

What characterizes blood coagulation?

Answer 29

Sequential activation of a cascade of circulating precursors culminating in the generation of thrombin.

Question 30

What are the components involved in blood coagulation?

Answer 30

Circulating coagulation factors, cofactors (factors V and VIII), calcium, and platelets.

Question 31

What are the manifestations of defects in the coagulation cascade?

Answer 31

Bleeding into cavities (chest, joints) and subcutaneous hematomas.

Question 32

List the coagulation factors.

Answer 32

Fibrinogen (fibrin), prothrombin, tissue factor, labile factor, proconvertin, antihaemophylic factor, Christmas factor, Stuart power factor, plasma thromboplastin antecedent, Hageman factor, fibrin stabilizing factor.

Question 33

Describe the coagulation cascade.

Answer 33

Involves enzyme complexes: extrinsic tenase (VIIa, TF, PL, Ca2+→Xa), intrinsic tenase (IX, VIII, PL, Ca2+ →Xa), prothrombinase complex (Xa, Va, PL, Ca2+).

Question 34

What physiological mechanisms limit blood coagulation?

Answer 34

TFPI, antithrombin III, heparin cofactor II, C1 esterase inhibitor, protein C, protein S.

Question 35

What is TFPI and what does it inhibit?

Answer 35

TFPI inhibits Xa, VIIa, and TF.

Question 36

What is the role of antithrombin III?

Answer 36

Inhibits thrombin and is enhanced by heparin.

Question 37

What is the role of protein C?

Answer 37

Inhibits FVa and FVIIIa.

Question 38

How is protein C activated?

Answer 38

Thrombin binds to thrombomodulin, activating protein C.

Question 39

What is tertiary haemostasis?

Answer 39

Formation of plasmin for breakdown of the clot.

Question 40

Define fibrinolysis.

Answer 40

Dissolution of the fibrin clot.

Question 41

How does tissue plasminogen activator (tPA) function?

Answer 41

Binds to fibrin, ensuring fibrin generation is localized to the clot.

Question 42

What is the role of activated protein C (APC) in fibrinolysis?

Answer 42

Destroys plasma inhibitors of tPA.

Question 43

How does thrombin inhibit fibrinolysis?

Answer 43

By activating thrombin-activated fibrinolysis inhibitor (TAFI).

Question 44

What substances can plasmin digest?

Answer 44

Fibrinogen, fibrin, FV, FVIII.

Question 45

List some therapeutic fibrinolytic agents.

Answer 45

Recombinant tPA, urokinase, streptokinase.

Question 46

What inhibits plasmin?

Answer 46

Plasminogen activator inhibitor (PAI), alpha2 antiplasmin.

Question 47

What are the possible causes of defective haemostasis with abnormal bleeding?

Answer 47

Vascular disorder, thrombocytopenia, defective blood coagulation.

Question 48

What is the normal range for thrombin time?

Answer 48

14-16 seconds.

Question 49

What conditions can prolong thrombin time?

Answer 49

Dysfibrinogenaemias, FDPs, DIC, heparin therapy.

Question 50

What does APTT measure and what is its normal range?

Answer 50

Intrinsic pathway, 30-40 seconds.

Question 51

What conditions can prolong APTT?

Answer 51

Haemophilia.

Question 52

What does PT measure and what is its normal range?

Answer 52

Extrinsic pathway and common pathway, 10-14 seconds.

Question 53

What conditions can prolong PT?

Answer 53

Liver disease, warfarin therapy, DIC.

Question 54

What is the indication for a fibrinogen assay?

Answer 54

Fibrinogen deficiency, reduced in DIC.

Question 55

What is the normal range for bleeding time?

Answer 55

3-8 minutes.

Question 56

What does the platelet count test measure?

Answer 56

Number of platelets in the blood.