The Vascular System Flashcards
State 5 reasons why a thrombus does not normally form in intact vessels
- Smooth surface
- Prostacyclin
- Heparan sulfate
- Tissue factor pathway inhibitor (TFPI)
- Thrombomodulin
Platelet activation inhibitor
Prostacyclin
Activates antithrombin
Heparan sulfate
Inactivates VIIa…controls TF/extrinsic pathway
Tissue factor pathway inhibitor (TFPI)
Activates protein C pathway
Thrombomodulin
State 4 procoagulant properties of the vascular intima that lend to thrombus formation during vascular damage
- Vasoconstriction
- Basement membrane exposes collagen
- von Willebrand factor secreted
- Tissue factor exposed
Necessary for platelets to adhere to subendothelial collagen in arterioles; (and eventual) platelet aggregation
von Willebrand factor secreted
Activates plasma coagulation system (Factor VII)
Tissue factor exposed
Thrombopoiesis
- List 4 stages of maturation
- Megakaryoblast
- Promegakaryocyte
- Megakaryocyte
- Platelets (thrombocytes)
Thrombopoiesis
- Morphology of megakaryoblast
- Round nucleus; 2-6 nucleoli
- Homogeneous chromatin, loosely organized
- Basophilic cytoplasm
Thrombopoiesis
- Morphology of promegakaryocyte
- Indented nucleus; variable nucleoli
- Condensed chromatin
- Basophilic cytoplasm
Thrombopoiesis
- Morphology of megakaryocyte
- Nucleus, 2-32 lobes (8 most common)
- Blue to pink cytoplasm, abundant
- Reddish-blue granules
Thrombopoiesis
- Morphology of platelets (thrombocytes)
- No nucleus
- Light blue to colorless cytoplasm
- Red to violet, abundant granules
Thrombopoiesis
- Site of platelet production
- BM = medullary
- Lungs = extramedullary
Thrombopoiesis
- Regulatory mechanism
Growth factor, specifically thrombopoietin (hormone)
Morphology of normal platelet when stained w/ Wright’s stain
- Chromomere aka granulomere
- Hyalomere
- Outside of platelets is light color and round
Two pools into which platelets are distributed
- Circulatory (2/3)
- Splenic (1/3)
Average life span of the platelet
8-12 days
Four platelet functions
- Source of PF3
- Source of PF4
- Maintain vessel integrity
- Formation of platelet plug
Phospholipid found w/in platelet membrane is essential reaction site in the cascade
Source of PF3
Protein found in platelet’s alpha granules and is capable of neutralizing heparin
Source of PF4
What is the job of maintaining vessel integrity in platelets?
Platelets adhere to the subendothelial collagen, and fill in the gaps until new endothelial cells grow
List 4 causes of platelet activation caused by traumatic venipuncture and/or shaking of the sodium citrate tube
- Subsequent release of PF4
- PF4 will neutralize heparin in blood sample
- Falsely shorten APPT
- Potential for subsequent over anticoagulation of the patient
Formation of platelet plug
- Primary or secondary hemostasis?
Primary
Formation of platelet plug
- Short or long-term effect?
Short-term effect
Formation of platelet plug
- Two hemostatic systems involved w/ primary hemostasis
- Vascular intimia
- Platelets
Formation of platelet plug
- List type of bleeding w/ disorder involved w/ primary hemostasis
- Temporarily arrests bleeding
- Excessive bruising and mucocutaneous bleeding
Formation of platelet plug
- Type of diagnostic tests involved w/ primary hemostasis
Platelet tests
List 3 steps involved in primary hemostasis
- Platelet adhesion
- Platelet activation
- Platelet aggregation
Discuss platelet adhesion
- Platelets first adhere to collagen
- GPIb binds platelet to vWF (bridge)
- GPIb/IX necessary to attach vWF bridge to subendothelium for platelet adhesion
Discuss platelet activation
Platelets release procoagulant factors and synthesize prostaglandins to activate platelets
Discuss platelet aggregation
Fibrinogen bridge and glycoprotein IIb/IIIa complex needed for platelets to attach to one another
List 3 zones of platelet ultrastructure
- Peripheral zone
- Sol-gel zone
- Organelle zone
Functions as receptor and transmitter region as well as it’s essential for adhesion and aggregation
Peripheral zone
Functions as cytoskeletal/contractile region
Sol-gel zone
Functions as metabolic/organelle region and has two types of granules
Organelle zone
Two types of granules in organelle zone
Alpha and dense bodies
Differentiate quantitative vs. qualitative platelet testing
Quantitative tests → NUMBERS - Platelet count or slide estimate Qualitative tests → FUNCTION - Bleeding time - Platelet function analyzer (PFA-100) - Platelet aggregation - Clot retraction
Why is EDTA the anticoagulant of choice when performing electronic platelet counts?
Prevents clumping of platelets in most patients
Anticoagulant used in automated platelet counts
EDTA
What manual method is used for platelet counts?
Unopette method
Anticoagulant used in Unopette method
- Ammonium oxalate is used as the diluting fluid → lyses RBCs and platelets are mostly left behind
Type of microscopy used in Unopette method
Phase microscopy retards wavelength and gives platelets a dark contrast → hard to see w/ a light microscope
What should you do when you notice that no platelets are seen when performing a differential directly from a fingerstick?
Check the edges and tail on low power of the smear for platelet clumps
Formula for estimated platelet count
Avg # of platelets x 20,000 (make sure you’re in OIF of 200 RBCs)
Normal range for platelet counts
150-450 x 10^3/cumm; 150-450 x 10^9/L (in SI units)
How will a hemolyzed sample affect an electronic platelet count?
↓ RBCs, hematocrit; H and H not in balance
What should you do if you have a hemolyzed specimen?
Redraw the specimen or a manual Unopette method if ONLY a platelet count is ordered
How do platelet clumps affect an electronic platelet count?
Causes falsely low results
How can a valid count be obtained if platelet clumps exist?
Redraw specimen w/ sodium citrate and multiply the count by 1.1 for a valid count (b/c blood: anticoagulant ratio different)
How do giant platelets affect an electronic platelet count?
Causes falsely low platelet counts
How can a valid platelet count be obtained if giant platelets exist?
Performed manual Unopette method for a valid count b/c they’re greater than the threshold for the instrument
How does platelet satellitism affect an electronic platelet count?
Causes falsely low platelet counts
This test is defined as the time it takes for a standardized wound to stop bleeding and is concerned w/ both the # of platelets and their ability to form a viable platelet plug
Bleeding time (BT or TBT-Template Bleeding Time)
Normal reference range for bleeding time
2-10 minutes
6 clinical conditions that lead to an ↑ BT result
- Thrombocytopenia
- Aspirin
- vWD
- Bernard-Soulier Syndrome
- Glanzmann’s thrombasthenia
- Afribrinogenemia
This is the most accurate test than the BT test where platelet adhesion and aggregation following vascular injury are stimulated in vitro
Platelet Function Analyzer (PFA-100)
How is the PFA-100 performed?
Test cartridges are coated with platelet agonists and WB is aspirated through a microscopic cut in the cartilage membrane. The time required to occlude the aperature (“closure time”) is noted.
What is considered the gold standard for platelet function testing?
Platelet aggregation
How is platelet aggregation performed?
Platelet agonists/activating agents added to platelet rich plasma causing platelets to clump together, undergo shape change, and release granular contents. Clumping causes a clearing and patterns of light transmittance are charted and analyzed
6 common agonists used in platelet aggregation studies
- ADP (most common)
- Arachidonic acid
- Collagen
- Epinephrine
- Ristocetin
- Thrombin
This wave of aggregation is reversible and is a direct cause of adding ADP to PRP and causes platelet clumping
Primary wave
This wave of aggregation is irreversible where alpha and dense bodies release factors
Secondary wave
What does the ADP aggregation curve look like with aspirin ingestion?
Do not get to release factor so only primary curve is present
What does the arachidonic acid curve look like with aspirin ingestion?
Absent platelet aggregation, no curve at all
What does the ristocetin curve look like in vWD?
Flat line b/c you need vWF to have aggregation
ONLY _____ aggregation has primary and secondary curves
ADP
This drug inhibits both the release reaction and secondary wave of aggregation
Aspirin
What enzyme is inactivated by aspirin?
Cyclo-oxygenase
What hormone/final product is blocked w/ aspirin?
Thromboxane A2 (TXA2)
How long does inactivation due to aspirin last?
For entire life of platelet → 8-12 days
