Erythrocyte clotting Flashcards Preview

Biochemistry - Sarah > Erythrocyte clotting > Flashcards

Flashcards in Erythrocyte clotting Deck (58):
1

Life span of RBC

~120 days

2

Anemias caused by:

Iron deficiency, B12 deficiency, folate deficiency, thalassemia, RBC loss

3

Erythrocyte metabolism is dependent on ___.
They also require ___.

glucose (glycolysis) (because RBCs do not have mitochondria)

NADPH reducing equivalents for glutathione

4

Erythrocytes use ___ to reduce ferric iron to ferrous iron.

NADH (from glycolysis)

5

Erythrocytes use __ to modulate oxygen binding to hemoglobin, which stabilizes deoxy-hemoglobin.

2,3-bisphosphoglycerate

6

Glucose-6-phosphate dehydrogenase deficiency results in ___.

hemolytic anemia
(NADPH keeps glutathione reduced, helps prevent buildup of ROS, low NADPH results in hemolysis, deficiency decreases NADPH)

7

What are some sources of oxidative stress for red blood cells?

primaquine for malaria, aspirin, sulfonamide antibiotics (folic acid inhibitors), and fava beans

8

What causes microcytotic anemia?

iron deficiency, lead poisoning, or thalessemia
(They cause impaired hemoglobin synthesis)

Microcytic anemia is also known as hypochromic anemia

9

What causes macrocytic anemia?

B12 or folate (B9) deficiency

This causes impaired DNA synthesis

Macrocytic anemia is also known as normochromic anemia

10

What causes normocytic anemia?

Severe bleeding, sickle cell anemia, pyruvate kinase deficiency, or glucose-6-phosphate dehydrogenase deficiency

This causes red blood cell loss

Normocytic anemia is normochromic anemia

11

Hemostasis

The process of clot formation and susequent dissolution

12

Four major events associated with hemostasis

Vascular constriction, Platelets activated by thrombin and aggregate at injury site, fibrin clot formation: intrinsic and extrinsic pathways, dissolution of clot: action of plasmin

13

Platelets are derived from ___.

megakaryocytes

14

Hormone that controls platelet formation

thrombopoeitin

15

True or false: Platelets contain mitochondria.

True

16

Life span of platelet

7-10 days

17

Platelet activation

Adhesion, aggregation, and activation

adhesion: At damaged site, glycoprotein IA (GPIa) binds collagen and GPIb binds VonWillebrand factor (vWF) that is attached to collagen

Aggregation: glycoprotein IIb/IIIa molecules on platelets bind other platelets through fibrin

Activation: Release of hemostasis chemicals from intracellular granules

18

Phospholipase A

Stimulation of platelet membrane receptors triggers activation of platelet membrane phospholipase A2 (PLA2)
Hydrolyzes membrane phospholipids, platelets release arachidonic acid

19

PGI2

prostacyclin, major arachidonic acid metabolite formed by vascular cells (potent vasodilator, inhibitor of platelet aggregation)

20

Platelet-related bleeding disorders

Congenital bleeding disorders:
Bernard-Soulier syndrome: GPIb-IX deficiency causes bleeding disorder

Acquired platelet disorders:
Thrombocytopenia (low platelet count): defective formation of platelets by megakaryocytes, bone marrow neoplasia; excessive destruction of platelets - anti-platelet antibodies

21

Platelet inhibition drugs

Plavix (inhibits ADP-induced platelet aggregation acting by direct inhibition of adenosine diphosphate (ADP) binding to its receptor and of the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex

22

Antiplatelet drugs (examples)

dipyridamole, ticlopidine, clopidogrel (plavix)
(Less gastric bleeding than aspirin)

23

Dipyridamole

inhibits uptake of adenosine, leading to increased platelet A2 receptor stimulation and suppression of ADP receptor action

24

Blood Clotting cascade (intrinsic)

Prekallikrein -->Kallikrein
Factor XII --> Factor XIIa
Factor XI --> Factor XIa
Factor IX --> Factor IXa
Factor X ---> Factor Xa (uses VIIIa)
Factor II / Prothrombin --> IIa /Thrombin
Factor I / Fibrinogen --> Factor Ia / Fibrin and XIII ---> XIIIa
Crosslinked fibrin clot/XIIIa

25

Blood Clotting cascade (extrinsic)

Factor VII --> Factor VIIa
Factor X ---> Factor Xa (uses VIIIa)
Factor II / Prothrombin --> IIa /Thrombin
Factor I / Fibrinogen --> Factor Ia / Fibrin and XIII ---> XIIIa
Crosslinked fibrin clot/XIIIa

26

Fibrin is synthesize as ___ and cleaved by ___.

fibrinogen,
thrombin (A serine protease)

27

What does Transglutaminase do?

Factor XIIIa (transglutaminase) links lysine side chains to glutamine side chains

28

What activates Transglutaminase?

Factor XIIIa is activated by Factor IIa (thrombin)

29

True or false: Factor XIIIa is a serine protease.

FALSE

30

What is prothrombinase?

Factor Xa and V form it and it catalyzes the proteolysis of prothrombin to thrombin.

31

What does thrombin do?

This thrombin catalyzes the activation of factors V, VII, VIII, and XIII (triggering VIII is key for starting the intrinsic path)

It also catalyzes the formation of fibrin from fibrinogen

32

___ inhibits thrombin.

Hirudin from leeches

33

Vitamin K is important for ___.

The synthesis of prothrombin and other clotting factors

(Cofactor for the enzyme that carboxylates Glutamine)

34

Gamma-carboxyglutamate binds ___.

Calcium

35

Antagonist of Vitamin K

warfarin

36

Vitamin K dependent clotting factors

X, II, VII, IX
also regulatory factor protein C

37

Activated partial thromboplastin time

Phospholipid and silica added (test of the intrinsic pathway)

Prolonged aPTT indicates a deficiency in VIII, IX, XI, XII (all except XIII and VII) (used to monitor IV heparin)

38

Prothrombin time

Used to test the extrinsic pathway

Factor III added to plasma. Specific for reduced factor VII but also X and II (used to monitor warfarin)

39

Common pathway for clotting (simplified)

10/5 = 2. Factor X goes to Factor V goes to Factor 2

40

Pnemonic for remembering extrinsic pathway

You do PT outside at 7 AM
(Prothrombin time = extrinsic, uses Factor VII, then common pathway)

41

Prothrombin time can reveal ___.

Acquired bleeding disorders:
Vitamin K deficiency
Oral anticoagulants (Warfarin)
and Liver disease (Reduced hepatic synthesis of Factor II, VII, IX, X)

42

Activated prothrombin time can reveal ___.

Hemophilia A (Factor VIII)

43

Hemophilia A is associated with ___.

Factor VIII

44

Antithrombin II

Serine protease inhibitor: inhibits activity of thrombin, Factos IXa, Xa, and XIa

45

What does heparin do?

It binds to antithrombin III and increases its affinity for thrombin (thereby reducing clotting)

46

Where is antithrombin synthesized?

In the liver

47

Deficiency of antithrombin can lead to __.

increased risk of venous thromboembolism

48

Factor V Leiden

Factor V variant that is resistant to protein C (increases clotting)

49

Thrombin binds ___ on the surface of endothelial cells and activates ___.

thrombomodulin,
protein C

50

Protein C forms a complex with ___ and provides selective proteolytic degradation of ___.

protein S,
Factor Va and VIIIa

51

____ (a serine protease), degrades fibrin clot.

Plasmin

52

Converts plasminogen to activated plasmin

tPA (tissue-type activator)

53

T-PA inactivators

Plasminogen activator-inhibitor types 1 and 2 (PAI-1, PAI-2)

54

t-PA

converts plasminogen to activated plasmin, made by endothelial cells, Has Kringle domains (binds fibrin), low basal concentrations in plasma

55

Hemophilia A

Classic hemophilia
Deficiency in factor VIII (cofactor activating Xa)
X-linked
prolonged bleeding from wounds, easy bruising
treat with human plasma or recombinant factor VIII

56

Von Willebrand Disease

Defective platelet adhesion (prolonged bleeding time)
different forms with different severity
more common than Hemophilia A

57

Antithrombin deficiency

Causes deep vein thrombosis and pulmonary embolism

58

Pyruvate Kinase deficiency

Separate isoforms in humans (one for erythrocyte; active tetramer)
Reduced ATP production results in failure to maintain cation gradient, loss of potassium and water, cell dehydration, hemolytic anemia
Hemolytic anemia has symptoms less severe than expected due to increased 2,3-bisphospholgycerate (2,3-BPG), results in greater release of oxygen to tissues
Partial block of PK increases 1,3-BPG and therefore 2,3-BPG
Wide range of severity, from infant death to asymptomatic adults
Treatment: transfusions and possible splenectomy (to prevent hemolytic anemia)