Hemostasis & Blood Coagulation Flashcards
Thrombocytes develop from ______ progenitor cells
megakaryocytes
Platelets synthesize what? Store what?
enzymes, ATP, ADP, prostaglandins, histamine, serotonin, thromboxane A2, clotting factors
Also store calcium ions
Functions of platelets
- initiate the coagulation cascade to stabilize the platelet plug
- Fibrin-stabilizing factor binds fibrin molecules into meshwork
vWF
what is it?
what does it carry?
Glycoprotein that acts as bridging molecule at sites of vascular injury for normal platelet adhesion
vWF binds collagen when it’s exposed beneath endothelial cells d/t damage to the blood vessel (rem. both endothelium and platelets release vWF)
Carries factor VIII (antihemophilic factor A) to circulation
Normal platelet count is
150K to 400K
If platelet count is below ______ then what is this called?
100K thrombocytopenia
<50,000 = r/f hemorrhage from minor trauma <20,000 = r/f spontaneous bleeding
Cell membranes of platelets have glycoproteins on surface that do what?
Also contain phospholipids that do what?
REPULSE ADHERENCE TO ‘NORMAL’ ENDOTHELIUM AND PROMOTE ADHERENCE TO INJURED ENDOTHELIUM
-phospholipids that activate several stages in the blood clotting cascade
How long do platelets live? Eliminated how?
8-10 days and are eliminated through spleen macrophage system and liver kupffer cells
Sequence of hemostasis? What activates the coagulation cascade? 5 steps
1- vascular injury leads to vasoconstriction
2-formation of a platelet plug (primary hemostasis)
3-tissue factor activates coagulation cascade - fibrin strands sew plug and make it stronger
4-formation of a blood clot (secondary hemostasis) - permanent plug
5-clot retraction and clot dissolution (fibrinolysis) - wound repair and formation of fibrous tissue
FUNCTIONS OF PLATELETS (4 of them)
- Help regulate blood flow into a damaged site by inducing VASOCONSTRICTION
- Initiate platelet-to-platelet interactions, resulting in the formation of a PLATELET PLUG
- ACTIVATE THE COAGULATION CASCADE to stabilize the platelet plug
- INITIATE REPAIR processes including clot retraction and clot dissolution (fibrinolysis)
Important biochemicals released from platelet granules?
Thromboxane A2
ADP
vWF
Platelet biochemical thromboxane A2 function?
- is a prothrombotic
- it is PRODUCED BY activated platelets
- STIMULATES ACTIVATION OF NEW PLATELETS
- INCREASES PLATELET AGGREGATION
- CAUSES VASOCONSTRICTION
Platelet biochemical ADP function?
- is a prothrombotic
- PLATELET ACTIVATION
- stimulate shape change
Platelet biochemical vWF function?
- acts as an anchor
- endothelial cells attached to collagen
- ACTS AS BRIDGING MOLECULE AT SITES OF VASCULAR INJURY FOR NORMAL PLATELET ADHESION
- under high sheer conditions - promotes platelet aggregation
- carries factor VIII in circulation
After injury: intravascular ______ ______ ______ reducing blood flow. Platelets are responsible for much of the ________ by means of ________.
smooth muscle contracts
vasoconstriction by means of thromboxane A2
Platelet plug formation 3 steps
ADHESION, ACTIVATION, AGGREGATION
ADHESION of platelet plug is mediated by?
the binding of the platelet surface receptor glycoprotein-Ib (GPIb) to vWF
ACTIVATION of platelet plug occurs how?
smooth spheres change to spiny projections and degranulation occurs (called platelet-release reaction). This results in the release of various potent biochemicals.
AGGREGATION is facilitated by?
What happens during clot retraction?
fibrinogen bridges b/w receptors on the platelets
-clot retraction: fibrin strands shorten and become denser and stronger to approximate the edges (edges of blood vessel wall come together)
See slide 46 steps?
starts with injured vascular surface –>platelets swell –> change shape –> contractile proteins contract (release granules) –> become sticky –> adhere to collagen & vWF –> secrete ADP and thromoxane A2 –> activates nearby platelets –> cycle continues
vWF factor is
1-essential for platelet activation
2-necessary for platelet adhesion
3-needed to stimulate platelet aggregation
4-required for Hageman factor to degrade platelets
2-necessary for platelet adhesion
*remember that vWF is found in the sub-endothelial matrix, and can be released by endothelial cells and platelets
Clotting factors
FACTOR I = FIBRINOGEN FACTOR II = PROTHROMBIN FACTOR III = TISSUE THROMBOPLASTIN FACTOR IV = CALCIUM Factor V = proaccelerin Factor VII = proconvertin
FACTOR I = ______. Where is it synthesized and what is it converted to? Function?
First factor in ______? Activates what?
fibrinogen is synthesized in the liver and converted to fibrin by thrombin enzyme
The function of fibrin = threadlike protein fibers that trap RBCs, platelets & fluid during clotting. Fibrin is the 1st factor in intrinsic coagulation, and activates factor XII.
FACTOR II = prothrombin. Where is it synthesized in the presence of ______. Converted to?
Synthesized in the liver in the presence of vitamin K, and converted to thrombin during coagulation.
FACTOR III = tissue thromboplastin. Required for? Released by?
released from damaged tissue, required to initiate second phase = the extrinsic pathway
Also catalyzes the conversion of prothrombin to thrombin
FACTOR IV =
CALCIUM - REQUIRED THROUGHOUT THE ENTIRE CLOTTING SEQUENCE
FACTOR VIII =
antihemophilic factor A = vWF IS THE CARRIER FOR FACTOR VIII
Calcium and vitamin K deficiency can cause a problem with _____
clotting
Fibrin is…
threadlike protein fibers that trap RBCs, platelets, and fluid during clotting
CALCIUM IS REQUIRED FOR…
MULTIPLE STEPS IN THE PROCESS TO ACTIVATE CLOTTING FACTORS
VITAMIN K ESSENTIAL IN THE…
SYNTHESIS OF CERTAIN CLOTTING FACTORS IN THE LIVER
SEQUENCE OF EVENTS IN BLOOD CLOT FORMATION
*Injury to the blood vessel induces formation of what? Steps from here with this first thing…
What does prothrombin attach to?
What assists in clot retraction?
1- injury to the blood vessel wall or to blood induces formation of PROTHROMBIN ACTIVATOR - release of Tissue thromboplastin
2- prothrombin activator changes PROTHROMBIN TO THROMBIN
- this is DEPENDENT ON ADEQUATE CALCIUM
- prothrombin attaches to platelets adherent to injured area
3- Thrombin changes FIBRINOGEN TO FIBRIN
-fibrin meshes with blood cells, platelets and plasma to form the clot
4- Clot retraction, assisted by platelets, expresses serum. Remember serum is plasma without clotting factors, such as fibrinogen. Plasma can clot, serum cannot.
INTRINSIC PATHWAY
- includes which factors?
- activated when?
Factors XII, XI, IX, and VIII
-is activated when the Hageman factor (Factor XII) contacts sub-endothelial substances exposed by vascular injury
EXTRINSIC PATHWAY
- which factors
- is activated when?
FACTOR VII, FACTOR III
- IS THE MOST DOMINANT - is a faster pathway b/c it’s shorter
- IS ACTIVATED WHEN THE TISSUE FACTOR (TISSUE THROMBOPLASTIN) IS RELEASED BY DAMAGED ENDOTHELIAL CELLS
Both the intrinsic and extrinsic pathways lead to…what factors are included? What happens in this pathway?
A COMMON PATHWAY (factors X, V, II)
- prothrombin to thrombin
- fibrinogen to fibrin
Three essential steps in synthesis of blood clot? Reiterate what is on clotting paper.
1- injury to the blood vessel wall or to blood induces formation of PROTHROMBIN ACTIVATOR
2- prothrombin activator changes PROTHROMBIN TO THROMBIN
- this is DEPENDENT ON ADEQUATE CALCIUM
- prothrombin attaches to platelets adherent to injured area
3- Thrombin changes FIBRINOGEN TO FIBRIN
-fibrin meshes with blood cells, platelets and plasma to form the clot
ENDOTHELIUM PREVENTS THE FORMATION OF SPONTANEOUS CLOTS IN NORMAL VESSELS BY SEVERAL ANTICOAGULANT MECHANISMS?
-PRODUCTION OF NITRIC OXIDE (NO) AND prostacyclin I2 (PGI2) or prostaglandin, thrombin inhibitors (ANTITHROMBIN III), tissue factor inhibitors (tissue factor pathway inhibitors), and degrading activated clotting factors (THROMBOMODULIN-PROTEIN C)
control of clotting - what can fibrin do?
FIBRIN in clot absorbs excess thrombin
ANTI-THROMBIN III in controlling clotting can do what?
inactivate excess thrombin
Heparin in controlling clotting does what? Enhances what? Released by?
heparin is produced by basophils and mast cells, and enhances the activity of antithrombin III
COUMADIN acts by…to control clotting
acts by competing with vitamin K and inhibits the production in the liver of prothrombin and other clotting factors
PLASMINOGEN (also called?) does what to control clotting. Released from?
(profibrinolysin) is activated and becomes plasmin (fibrinolysin)
- plasminogen activator is released by damaged tissues, which then activate plasmin
- plasminogen activators are used clinically to dissolve coronary artery clots in pts with acute MIs
-plasmin degrades fibrin clots
Bone marrow aspiration usually from?
sternum or pelvis
How is the intrinsic pathway activated
through exposed endothelial collagen
How is the extrinsic pathway activated
release of tissue factor from damaged endothelial cells after external damage
Blood tests of intrinsic pathway
- whole blood clotting time: time it takes for whole blood to clot in the test tube (9-15 minutes normally)
- PTT (partial thromboplastin time): clotting in test tube is initially prevented by removing calcium, and this measures the time for re-calcified citrated plasma to clot in the test tube
Blood tests of the extrinsic pathway (shorter pathway) - remember extrinsic pathway starts d/t presence of?
What is normal?
Presence of tissue thromboplastin
- PT (prothrombin time): is the time needed for recalcified citrated plasma to clot in the presence of tissue thromboplastin – “pro time” adds the critical tissue ingredient (tissue thromboplastin) that is necessary to start off the extrinsic pathway
- normal PT is 11-15 seconds
- INR (international normalized ratio) = PT test/PT normal *normal is 0.9-1.3; and people on anticoagulation like Warfarin or eliquis (apixaban) should have INR = 2-3 or 2.5-3.5
Platelet function test assesses what?
number of platelets
What is normal “bleeding time” which assess platelet function
Remember this tends to be normal when?
2-7 minutes
Tends to be normal in coagulation disorders of the extrinsic and intrinsic pathway? Idk how?
If it is prolonged, it usually suggests a defect in platelet function.
PTT and PT tests are useful to do what?
distinguish extrinsic and intrinsic coagulation disorders
In liver failure, Coumadin or heparin therapy what will happen to PT and PTT values?
both the PT and PTT will be abnormal
Blood cell counts go above or below adult levels at birth?
increase (d/t trauma of birth and cutting umbilical cord), and these levels decline during childhood
What is the major cause of increased RBC production in newborn/fetus? What does this result in?
HYPOXIC INTRAUTERINE ENVIRONMENT STIMULATES ERYTHROPOIETIN PRODUCTION
THIS RESULTS IN POLYCYTHEMIA OF THE NEWBORN
Large number of what in full-term neonates?
Large number of immature erythrocytes (reticulocytes) are in full-term neonates
In full-term and premature infants what is the lifespan of RBCs?
full-term 60-80 days; premature 20-30 days
Children have more ______ lymphocytes d/t frequent viral infections
atypical
Neutrophil count at birth is?
high and rises during the first days of life
after two weeks levels fall to below or around adult, and by four years old the same as adult
Which wbcs are high the first year of life?
eosinophils (also higher in children) and monocytes
Platelet count in full-term newborn vs adult?
about the same
Humoral immune system and lymphocyte function with age?
lymphocyte function declines, and humoral immune system is less responsive
