Coagulation Flashcards
What are the three layers of a blood vessel?
Intima, Media, Adventitia
What type of cells make up the intima?
primarily endothelial, some elastic and connective tissue
Which type of blood vessels (arteries, veins, capillaries) only have intima?
capillaries
Which layer of blood vessels are made up of smooth muscle, collagen and elastic tissues?
media (middle)
Disruption of which tissue type activates the clotting cascade?
collagen
What does collagen do to platelets during the coagulation cascade?
anchor platelets to the vasculature wall
Which layers of blood vessels are under the influence of vascular mediators?
media and adventitia
What is the outer layer of blood vessels, made up of connective and elastic tissue?
adventitia
What are the two functions of endothelial cells?
separates fluid from highly thrombotic material that lies beneath
synthesize and secrete procoagulants, anticoagulants, fibrinolytics
What are the procoagulants, anticoagulants, fibrinolytics secreted by endothelial cells?
Von Willebrand Factor, Tissue Factor
Tissue Factor Pathway Inhibitor
TPA, Urokinase
What does Von Willebrand factor do when secreted from endothelial cells?
adheres platelets to the subendothelial layer
What does tissue factor do when secreted from endothelial cells?
activates the clotting cascade
What does tissue factor pathway inhibitor do when secreted from endothelial cells?
aids in suppression of coagulation
What are TPA and Urokinase, and what do they do when secreted from endothelial cells?
Fibrinolytics.
activate plasminogen and initiates the process of fibrinolysis
When there is disruption to the endothelial lining, what happens to the vessel wall?
Contracts
What are the 4 mediators of vessel tone?
Thromboxane A2 and ADP
Nitric oxide and Prostacyclin
What does Thromboxane A2 and ADP do to the vessel wall?
Vasoconstricts, released from platelets
What does Nitric oxide and Prostacyclin do to the vessel wall?
Vasodilation. Released from surrounding endothelial cells to divert blood flow to other areas.
Where are platelets formed?
megakaryocytes in bone marrow
Hemostasis is not possible without an adequate number of what?
platelets
How do platelets arrive at the site of injury so quickly?
They flow towards the edges of blood vessels due to their size.
Why aren’t platelets constantly clotting blood vessels?
they are largely inactive until stimulated by trauma or plaque disruption
How are platelets different from whole cells?
Both contain mitochondria, actin, myosin. Platelets do not contain a nuclei and cant reproduce
What do platelets produce that activates other platelets to facilitate clumping?
thrombin
What do the alpha and dense granules in platelets do?
store proteins and non proteins, synthesize prostaglandins promoting vascular and tissue reactions
What are the three steps to clot formation/platelet plug?
Adhesion, Activation, Aggregation
What occurs during Adhesion stage?
vWF attaches to Gp1b receptors on the platelet surface.
What does vWF do to strengthen the forming clot?
attracts more platelets to the site of injury and increases their adhesion ability (stickiness)
What occurs during the Activation stage?
Platelets undergo conformation change to activated form
What is the conformational changes platelets undergo during activation?
Disk to oval
Develop spiky protrusion to aid in stickiness
During Activation: what are the 2 mechanism that activate phospholipase C?
Platelet binding to vWF initates “outside in” signaling to activate phospholipase C
Tissue factor, thrombin, ADP, TxA2 stimulate GPCR that signal more activation of phospholipase C
During Activation, what are the two things actually responsible for changing the shape of platelets?
Phospholipase C and calcium
What occurs during the Aggregation step to form an initial platelet plug?
GpIIb and GpIIIa receptors (for fibrinogen/fibrin) on platelet surface change shape and link platelets together with fibrinogen/fibrin
What does activated phospholipase C do during Aggregation?
initiates the “inside out” signaling that stimulates the change in GpIIb/IIIa receptors to allow binding with fibrinogen and fibrin
What does ADP and thromboxane A2 do during the Aggregation step?
act on nearby platelets to stimulate adherence to one another
What Factors are Vitamin K dependent?
2, 7, 9, 10
What blood clotting factors do not come from the liver?
3 and 4
What blood clotting factors are in the intrinsic pathway?
12, 11, 9, 8
What blood clotting factors are in the extrinsic pathway?
3, 7
What blood clotting factors are in the common pathway?
10, 5, 2, 1, 13
What activates the extrinsic pathway?
activated when traumatized vessels/tissues come in contact with blood
How is the intrinsic pathway activated?
activated by exposure of blood to collaged in traumatized vessels
Where do the intrinsic and extrinsic pathways merge?
Factor X (10)
State the steps in the Intrinsic pathway.
Initiated by platelet phospholipids and activation of Hageman factor (XII)
XII activates plasma thromboplastin antecedent (XI), which activates Christmas (IX), which activates antihemophiliac (VIII)
VIII, IX, calcium, and platelet phospholipids work together to activate X
What is considered rate limiting step in blood coagulation?
Factor 10 and 5 forming prothrombin activator
What causes a clot to retract?
action of contractile proteins and calcium within the platelet
State the steps in the Extrinsic Pathway.
Tissue factor (III) is released which forms a complex with proconvertin (VII) in the presence of calcium; activates X Tissue factor pathway inhibitor immediately begins to inhibit tissue factor (III)
State the steps in the Common Pathway
Factor 10, Along with factor V forms prothrombin. Prothrombin is converted to thrombin.
Thrombin converts Fibrinogen into Fibrin
Fibrin with factor 13 form a stable fibrin clot
What acts as a positive feedback mechanism within the clotting cascade?
Thrombin
What factor activates factor 13?
thrombin (2a)
What factors does thrombin activate?
5, 7, 8, 11, 13
What are some important things thrombin does?
Recruits platelets to the site of injury
accelerates clot retraction
prevents excess clot formation
What happens when thrombin activates protein C?
inactivates factors 5 and 8
What does protein S do to protein C?
increases the ability of Protein C
Which factors activate fibrinolysis?
tissue plasminogen activator (tPA), Urokinase, Factor 11a, 12a, kallikrein
What factors inhibit fibrinolysis?
Plasminogoen activator inhibitor 1 and 2 (inhibits tPA and urokinase), alpha2 antiplasmin, alpha2 macroglobulin, thrombin-activatable fibrinolysis inhibitor
How does plasminogen get converted to plasmin?
tPA, urokinase, factor 11a, factor 12a, kallikrein
What helps to breakdown fibrin into fibrin degradation products?
Plasmin
What stops the breakdown of fibrin into fibrin degradation products?
thrombin-activatable fibrinolysis inhibitor
What is the normal platelet count?
150-300
what is the normal bleeding time?
3-7 minutes
What does bleeding time measure?
capability of contraction in the microvasculature, function of platelets
What is the normal prothrombin time?
10-12 seconds
What is the normal and therapeutic INR?
normal 0.9-1.2
Therapeutic 1.5-3
What is the normal aPTT?
25-38 seconds
What is the normal ACT?
90-150 seconds
What is the normal thrombin time?
9-35
What is the normal fibrinogen assay? what increases it?
200-400 mb/mL. Pregnancy
What is the normal fibrin degradation products and D dimer?
0-11 and < 500 ng/mL
What is the most essential regulator of erythropoietin and RBC production?
tissue oxygenation
What are some important components for RBC production?
vitamin B12, folic acid, iron, and kidney function
What do RBCs contain that converts H2O and CO2 to H2CO3?
carbonic anhydrase
How do you calculate oxygen bound to hemoglobin?
Hgb x 1.34 x O2 sat
14 x 1.34 x .95 = 17.82
How do you calculate oxygen dissolved in blood?
PaO2 x 0.003
PaO2 88 x 0.003 = 0.26
How do you calculate total oxygen content?
O2 bound to Hgb + oxygen dissolved in blood
How do you calculate the amount of CO2 dissolved in blood?
PaCO2 x 0.067
40 x 0.067 = 2.68
If given EtCO2 add 5-10 to get PaCO2
How do you calculate MABL?
MABL = EBV x (Hct-mHct)/Hct
how much blood does a 4x4 hold?
10mL of blood
How much does a Ray-tech hold?
10-20mL blood
How much do Lap sponges hold?
75-150mL blood
What are the average blood volumes for neonate for adults?
premature 95mL/kg full term neonate 85 mL/kg infant 80mL/kg male 75mL/kg female 65mL/kg use ideal for obese
