BSI 2 Lecture 2-3: Hematology Flashcards
What is hemostasis?
The prevention of blood loss when a vessel is severed or ruptured
What are several mechanisms to limit blood loss in hemostasis?
- Vascular constriction
- Formation of a platelet plug
- Formation of a blood clot
- Clot retraction
- Removal of the clot (dissolved after repair)
What is the first line defense for a severed vessel?
Platelet plug and vasoconstriction
Local factors released from damaged tissues causes platelets to release ___________ which contributes to ____________.
- Thromboxane A2 (TXA2), [synthesized from arachidonic acid formed by PLA2]
- Vasoconstriction, (nervous reflexes initiated principally by pain receptors also contributes)
What releases prostaglandin I2 (aka PGI2 or prostacyclin)?
Adjacent undamaged endothelium and platelets
What is the purpose of prostacyclin (aka PGI2 or prostaglandin)?
Inhibits platelet aggregation from spreading inappropriately and vasodilator.
What are thrombocytes?
platelets
What happens when a platelet becomes activated?
It becomes sticky in order to form a platelet plug
What are platelets formed from?
Megakaryocytes in the bone marrow or blood especially as they squeeze through the smaller capillaries
Can platelets replicate?
No, they don’t have a nucleus because they are cell fragments
What contractile proteins do platelets contain, and what do they do?
Actin, myosin, and thrombosthenin which allow platelets to rapidly release intracellular granules as necessary
What do platelets contain that stimulates endothelial cells, vascular smooth muscle cells and fibroblasts to multiply and grow?
Prostaglandins, fibrin-stabilizing factor, and a growth factor. (Necessary for repair)
________ is on the external face of the platelet cell membrane which prevents them from adhering to the normal undamaged endothelial surface.
Glycoproteins
Platelets contain high concentration of __________ that are involved in blood clotting.
Phospholipids
Why do platelets contain remnants of the golgi apparatus and endoplasmic reticulum?
In order to produce enzymes and store calcium
Why do platelets contain remnants of mitochondria and enzymes?
To produce ATP
T or F? Platelets has a short half-life of 8-12 days and are removed by macrophages in the liver.
False, they are removed by the spleen
T or F? Platelets begin to swell and assume irregular shapes and radiating pseudopodia as they come in contact with damaged endothelium or exposed collagen.
True
During the formation of the platelet plug, the platelets become “sticky” and adhere to _____ and a protein called __________ from the blood.
damaged endothelium and/or collagen; von Willebrand factor
During the formation of the platelet plug, platelets secrete large amounts of _______ and ______ which activate nearby platelets which themselves adhere to the original ones in a positive feedback loop.
ADP; TXA2
How quickly can a blood clot form?
15-20 seconds if trauma is significant
1-2 minutes if minor.
After 3-6 minutes most reasonable holes are plugged by the clot.
(After 20-60 mins the clot retracts due to platelets and close the hole even more/more tightly)
What are the 2 options after a clot has formed?
- It can be invaded by fibroblasts (which form fibrous connective tissue throughout the clot)
- It can be dissolved
T or F? There are more than 50 substances found to affect or cause clotting.
True. (Anticoagulants dominate but when there is damage procoagulants dominate at the site)
What are the 3 simplified essential steps to clotting/coagulation?
- Trauma stimulating either of 2 enzyme cascades resulting in the formation of a complex called Prothrombin activator.
- Conversion of Prothrombin into the active enzyme Thrombin.
- Conversion of soluble plasma protein Fibrinogen into insoluble Fibrin.
What enmeshes platelets, red blood cells, and plasma to form the clot?
Fibrin fibers
What is Factor I?
Fibrinogen
What is Factor II?
Prothrombin
What is Factor III?
Tissue factor
What is Factor IV?
Calcium
What is Factor V?
Proaccelerin
What is Factor VII?
Serum prothrombin conversion accelerator (SPCA)
What is Factor VIII?
Antihemophilic factor (AHF)
What is Factor IX?
Plasma thromboplastin component
What is Factor X?
Stuart Factor
What is Factor XI?
Plasma thromboplastin antecedent
What is Factor XII?
Hageman factor
What is Factor XIII?
Fibrin-stabilizing factor
What is another name for Prekallikrein?
Fletcher Factor
What is another name for High-molecular-weight kininogen?
Fitzgerald factor
What are the two pathways that can form Prothrombin activator?
Intrinsic and Extrinsic
Which pathway is initiated by trauma to the endothelium and surrounding/supporting tissue?
The extrinsic pathway
Which pathway is initiated by damage to the blood vessel itself?
The intrinsic pathway
What are the plasma proteins called that both pathways use?
clotting factors
What two factors can block the intrinsic pathway?
No factor VIII or no platelets
The absence of what element will prevent blood clotting in either pathway?
Calcium
Which pathway is faster? Intrinsic or Extrinsic?
Extrinsic, it can form a clot in about 15 seconds
What protein is expressed on the endothelial surface which binds to Thrombin and inhibits its function as a procoagulant?
Thrombomodulin
What acts as an anticoagulant by inactivating factors Va and VIIIa?
Activated Protein C (activated by Thrombomodulin + Thrombin)
Name 2 important anticoagulants found in the blood itself.
Fibrin fibers (absorbs Thrombin) Antithrombin III (alpha-globulin) (combines and inactivates thrombin)
Heparin + Antithrombin III complex removes which activated factors?
IXa, Xa, XIa, and XIIa
Heparin is secreted by many cell types but especially by _____ cells in connective tissues and _____ in blood.
Mast; basophils
How are prothrombin levels estimated?
By measuring the clotting time in the presence of excess Ca2+ and tissue factor.
What are 3 conditions that are particularly significant in excessive bleeding?
- Vitamin K deficiency
- Hemophilia (deficiency of factor XIII)
- Thrombocytopenia (low platelet counts)
How long does it take for Heparin to work, and what breaks it down?
Heparin is effective immediately delaying clot time up to 30 minutes. It is inactivated by an enzyme in the blood called Heparinase
Vitamin K (synthesized by symbiotic gut bacteria) is important in the production of which clotting factors?
II, VII, IX, X. Also anticoagulant Protein C
How does Vitamin K interact with the clotting factors and calcium?
Vitamin K allows the clotting factors to be carboxylated. Once they are carboxylated, Calcium is able to bind to the clotting factors and continue the clotting mechanism.
T or F? Hemophilia is primarily inherited as “sex-linked” and is almost exclusively found in males.
True
A thrombus is loose in the blood vessel it is called a(n) ______
embolus
What are 2 main reasons for inappropriate clotting?
1) Arteriosclerotic plaque
2) Disseminated intravascular coagulation (caused by traumatized or necrotic tissue that can result in increased amounts of tissue factors into the blood where it can cause widespread clotting)
What “digests” fibrin fibers, fibrinogen, prothrombin, and factors V, VIII, and XII?
Plasmin (forms from plasminogen found in plasma)
Tissue plasminogen activator (t-PA) is released very slowly (so repairs can be done) from the ______ ______.
damaged tissue (plasminogen are trapped inside the clot)
T or F? Any situation that produces hypoxia in tissues inhibits Erythropoietin production?
False, it stimulates
Sickle cell anemia is due to what?
A single base-pair mutation in the beta-globin chain
What mechanism/s are employed initially (before activation of the clotting cascades) to limit blood loss from a severed vessel?
Vasoconstriction and platelet plug
Thromboxane A2 (TXA2) and prostaglandin I2 (PGI2) are synthesized from?
Arachidonic acid via PLA2
Activated platelets release?
Phospholipids (such as platelet Factor III), Ca2+, ADP (+Fb), PG’s and TXA2 (principle ones!).
T or F? Activated factor X (Xa) combines with phospholipids and factor V in the presence of Ca2+ to form the Prothrombin activator?
True
What activates factor V?
Thrombin (positive feedback loop)
Factor Va is part of what?
prothrombin activator +Fb loop
How is Va inactivated/how is its effect limited?
Activated protein C inactivates Va while thrombin is inactivated principally by absorption into fibrin fibers (separate mechanisms to stop +Fb loops)
Vitamin K is necessary for the synthesis of?
Factors II, VII, IX, X, and protein C
Warfarin acts how?
It competes with vitamin K for the reductase enzyme that activates vitamin K (vitamin K antagonist)
Heparin acts how?
Removes activated factors IIa, IXa, Xa, XIa, and XIIa
LMW heparin acts how?
Increases the actions Anti-thrombin III to increase its actions on removing Xa
How do you measure clotting times?
Prothrombin levels are estimated by measuring the clotting time in the presence of excess Ca2+ and tissue factor.
