Lisa's got normal and abnormal blood
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- Thrombocytopenia
- Decreased platelet count resulting in bleeding
- Thrombocytosis
- Increased platelet count
- One cause of hereditary thrombocytopenia?
- May Hegglin anomaly (autosomal dominant)
- Two causes of abnormal hematopoiesis (acquired)?
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1. B12/folate deficiency
2. pre-leukemic state - What are five causes of drug induced thrombocytopenia?
- Heparin, gold, quinine, sulfonamides, GP IIb/IIIa inhibitors
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VIP
Explain what happens in heparin induced thrombocytopenia? - Heparin binds to PF-4 to form a complex that induces pathologic antibody formation. This causes thrombocytopenia (decrease in the # of circulating platelets) by activating platelets. However, at the same time it is using those platelets randomly to form clot (high risk of thrombosis)
- What is can GPIIb/IIIa inhibitors cause?
- drug induced thrombocytopenia
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VIP VIP VIP
ITP and TTP cause systemic thrombocytopenia: How? - ITP: Immune thrombocytopenic purpura, mediated
- Where is the Platelet factor 4 that is made?
- Platelet: light granules
- What is HUS?
- Hemolytic uremic syndrome: just like TTP but with out CNS problems
- What is thrombocytosis?
- increase number of circulating platelets
- What are three conditions that can lead to thrombocytosis?
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1. spleenectomy - thrombocytosis eventhough platelets are normal
2. Reactive thrombocytosis - caused by cancer, infection, drugs, iron def
3. Autonomous thrombocytosis clonal disorder - platelet number is very high naturally can cause thrombosis. - What can a diet high in omega-3-fatty acids cause?
- reduced platelet function
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VIP VIP VIP
What is Glanzmann's Thrombasthenia? - An autosomal recessive disorder in which there is defective GP IIb/IIIa (no fibrinogen bridge can occur)resulting in aggregation defects and increased bleeding time.
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VIP VIP VIP
What is Bernard-Soulier disease? - Autosomal recessive disorder with a defect in GP Ib causing platelets to be unable to anchor to vWF leading to no formation of primary platelet plug thus increasing bleeding time.
- What happens in the storage pool disease?
- There is a decrease in dense granular content of platelets inhibiting aggregation.
- What is non-thrombocytopenic purpura?
- A disorder that does not result in severe bleeding diathesis since coagulation is normal, patients just bruise easily.
- What is Ehler-Danlos syndrome?
- Hypermobile jts from a defect in collagen synthesis
- What is telangiectasia?
- spider veins
- What does a PT test?
- Extrinisic pathway:7, 10, 5, 2 and fibrinogen
- What does an aPPT test?
- Intrinsic pathway: 12, 11, 9, 8, 10, 5, 2 (all factors except 7, 13, protein C and S
- Under what three diagnostic conditions do you run an aPPT?
- When you suspect hemophilia A or B or the patient is on Heparin.
- In a patient with Hemophilia what kind of value would you except on an aPPT?
- High
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VIP
Describe Hemophilia A (classical): - F 8 deficiency that stops the bodies ability to clot and increases bleeding tendency. Symp: bleeding in jts and m.
- Describe Hemophilia B (x-mas disease)
- F 9 deficiency, same symp as Hemo A
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VIP
What is vonWilledebrand disease? - Adhesion defect due to vWF defects. Can't form primary plug thus an increase in BLEEDING TIME (BT) and a slightly elevated APTT.
- What happens in a patient with Activated Protein C resistance?
- Since protein C normally cleaves 8a and 5a to inhibit clotting this resistance causes a longer generation of thrombin and leads to a hypercoaguable state.
- What goes wrong in Dead Fetus Syndrome?
- Massive amount of fibrinogen are degraded and so clots can not be formed.
- What happens in some snake bites? Similar to what syndrome?
- Fibrinogen is degraded just as in Dead Fetus Syndrome
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VIP VIP VIP
Explain secondary fibrinolysis (disseminated intravascular coagulation) - Both fibrin and fibrinogen are digested by plasmin resulting in a simultaneious digestion of clotting factors and consumption of platelets.
- What is the main cause of DIC?
- Sepsis (overwhelming infection of blood stream produced by toxin-producing bacteria)
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VIP
What does sepsis cause the release of? What does this cause? - Tissue factor!!! Causing widespread thrombosis
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VIP
What is caused from a deficiency of alpha-2 antiplasmin? - Since antiplasmin inhibits plasmin thus inhibiting clot breakdown. A deficiency of this inhibitor causes an increase in clot breakdown = increase in bleeding.
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nL
What three things are immediately released when a blood vessel is damaged? -
1. endothelin - vasoconstriction
2. NO
3. prostacylin - both are released to cause vasodilation and prevent clots -
nL
After a blood vessel is damaged primary hemostasis occurs. Describe this process: -
Platelet adhesion occurs from the exposed collagen of the endothelium.
Platelets are then activated, changing shape, and releasing their granules. -
nL
Where is vWF produced? - Constituitively in the endothelium
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nL
After a blood vessel is damaged secondary hemostasis occurs. Describe: - Tissue factor is released immediately at site of injury from endothelial cells. This produces a coag cascade that results in the formation of thrombin and thus fibrin. Therefore secondary hemostasis is responsible for forming a STABLE clot via COAGULATION.
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nL
Three things thrombin does: -
1. stimulates recruitment of additional platelets
2. stimulates activation of additional platelets
3. converts fibrinogen to fibrin -
nL
After clot is fully formed what two things are released? -
1. t-PA (tissue plasminogen activator) - for fibrinolysis; forms plasmin
2. thrombomodulin - binds with thrombin to activated protein C. Protein C lysis 8a and 5a -
nL
How to antithrombins (anticoagulant medications) mediate their effect? - Antithrombins bind with heparin-like molecules and inactivate thrombin (2a) and 9a, 10a.
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nL
How does the left over thrombin floating around get inactivated and end up helping to stop coagulation cascade? - Thrombin can bind to a thrombomodulin receptor forming a complext that activated protein C which lysis 8a and 5a
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nL
What do normal endothelial cells secrete to prevent platelet aggregation? - NO, prostacyclin, PGI2, ADP
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nL
What produces "heparin-like" molecules? - Endothelial cells
- Where are thrombomodulin receptors (VIP) located?
- On the endothelial cells
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nL
What is the function of the PGI2, NO, and ADP that the endothelial cells release? - To inhibit platelet aggregation
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nL
How does the presence of fat on the walls of the arteries change the vessels responses? - fat inhibits antithombotic mechanisms
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nL
What do infections do to the characteristics of the blood? - Slow blood down, produce plasma lipids, and ischemia (change endothelial cell function)
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nL
What three diseases exhibit prothrombotic states? -
1. diabetes
2. CHF
3. hypervisocosity syndrome -
nL - VIP
What do light granules contain? Dark? -
Light: fibrinogen, fibronectin, coag factors 5 and 8, platelet factor 4, growth factors, PDGF, TGF-beta
Dark: ADP, ATP, Ca, histamine, serotonin (VIP), epinephrine -
nL
What does platelet factor 4 do when released? - Neutralizes heparin
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nL
What does serotonin do when released by platelets? - Vasoconstricts
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nL
How are platelets activated? What happens once they are activated? -
To activate: Platelets molecules must bind to their GPIIa/IIIb receptors forming a fibrinogen bridge.
Once activated they release their granules and activate other phospholipids on platelets to expose their GPIIb/IIIa -
nL
VIP!!
What happens at the GP IIb/IIIa site? - Here coagulation factors combine with ionized Ca (from dense granules) to activate the intrinsic pathway to form thrombin
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nL
What forms the primary hemostatic plug? Secondary? -
Primary: release of ADP and thromboxane A2 from platelets - recruits other platelets to form plug
Secondary: Fibrin from coag cascade surrounds platelets forming this irreversible plug. -
nL
What is released during an MI that increases thrombosis formation? What is given to these patients to combat this? -
Released: massive amounts of thromboxane A2 - accelerates platelet aggregation.
Give: t-PA - lyse clots -
nL
What pathway does Heparin inhibit? - Intrinsic
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nL
How is the effect of Warfarin measured? - using PT (measure inhibition of factor 7)
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nL
Which factor is: Prothrombin? - 2
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nL
Which factor is: Proconvertin? - 7
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nL
Which factor is: Stuart factor? - 10
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nL
Which factor is: Hageman factor? - 12
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nL
Which factor is: Fibrin stabilizing factor - 13
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nL
Fibrinogen group of factors: - 1, 5, 8, 13
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nL
Prothrombin group of factors: - 2, 7, 9, 10
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nL
Describe how inhibitors of the coagulation system work? - These inhibitors are plasma proteins which are capable of inhibiting the formed serine protease enzymes involved in the regulation of the clotting process
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nL
What are two inhibitors of the coagulation system? -
1. antithrombin III - inactivates enzymes of coagulation system
2. tissue factor pathway inhibitor -
nL
What three things are responsible for the anticoagulation effects of heparin? -
1. antithrombin
2. heparin
3. tissue factor pathway inhibitor -
nL
Function of the fibinolytic system? - Dissolve clots using proenzymes like plasminogen activator.
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nL
What is Plasminogen activator inhibitor do and in what condition is it upregulated? - Decreases bodies ability to lyse clots. Diabetes has an upregulation of this PAI.
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nL
VIP
What does alpha-antiplasmin do? - It inhibits formed plasmin - threre for inhibiting clot breakdown
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nL
VIP VIP VIP
What is Virchow's Triad? -
Three major factors that contribute to thrombosis:
1. injury to endothelium
2. alterations in blood composition and flow
3. stasis