Hemostasis and Thrombosis/Coagulation Flashcards
Describe the differences among primary, secondary and tertiary hemostasis
primary - platelet aggregation and forming a “plug”
secondary - stabilizing the plug and adding fibrin/coag cascade
tertiary - breaking the plug down during repair (via plasmin)
Under normal circumstances, endothelial cells secrete ___ which inhibits platelet function, and ___ which is a vasodilator to maintain blood flow and prevent clotting. ___ is also produced and converts plasminogen to plasmin which __
Under normal circumstances, endothelial cells secrete prostaglandin I2 (prostacyclin) which inhibits platelet function, and nitric oxide which is a vasodilator to maintain blood flow and prevent clotting. Tissue plasminogen activator (TPA) is also produced and converts plasminogen to plasmin which breaks down clots
TFPI works by directly inhibiting factor __ and through TF, inhibits factor __ in the coag cascade
TFPI works by directly inhibiting factor 10a and through TF, inhibits factor 7 in the coag cascade
On the surface of the endothelial cells are ___, which inhibits thrombin and factor 10a, and ___, which does what?
On the surface of the endothelial cells are heparan sulfate, which inhibits thrombin and factor 10a, and thrombomodulin, which binds to thrombin, ultimately leading to the breakdown of factors 5a and 8a
Describe how thrombomodulin works. What are the roles of Protein C and S?
(see image below)
Inside the dense granules of platelets are calcium, ___, and ___.
alpha granules contain von-Willibrand’s factor, ___, ___, fibrinogen and fibronectin, ___ and PF4
Inside the dense granules of platelets are calcium, ATP/ADP, and serotonin.
alpha granules contain von-Willibrand’s factor, platelet derived growth factor (PDGF), P selectin, fibrinogen and fibronectin, TGF-B, PF4, Protein S, PAT 1 and procoagulant factors
What are the functions of the following factors released by platelets?
(vWF, fibrinogen, fibronectin, thrombospondin, P-selectin, GPIIb/IIIa)
(Factor V, XI and XIII)
(Protein S)
(Plasminogen activator inhibitor-1)
(Platelet Factor-4)
(Platelet derived growth factor)
(TGF β)
The first step in forming a blood clot is ___, mediated by ___ which is released by endothelial cells
The first step in forming a blood clot is reflex vasoconstriction, mediated by endothelin which is released by endothelial cells
The 2nd step in forming a blood clot is ___, which is mediated by ___ and ___ that are in the subendothelial matrix. Both of these help to tether the platelet to the damaged vessel
The 2nd step in forming a blood clot is platelet adhesion, which is mediated by vWF (bound by GPIb/9) and collagen (GP6) that are in the subendothelial matrix. Both of these help to tether the platelet to the damaged vessel
Platelet activation and degranulation are mediated by ___ whose conformational change exposes the binding sites for vWF and fibrinogen. ___ and ___(platelet agonist) are also released
Platelet activation and degranulation are mediated by GPIIb/IIIa whose conformational change exposes the binding sites for vWF and fibrinogen. ADP and thromboxane (platelet agonist) are also released
Step 4 in forming a blood clot is ___, which involves platelet binding to fibrinogen and can be inhibited by aspirin
Step 4 in forming a blood clot is platelet aggregation, which involves platelet binding to fibrinogen and can be inhibited by aspirin
Describe a platelet aggregation study
What are 3 other ways you could measure platelet activity in a pts sample (measuring platelet quantity)?
- CBC: # of platelets
- Peripheral smear
- Bone marrow biopsy
Platelet aggregation study: Platelets in plasma >> measure baseline light transmission >> + platelet agonist >> wait for clot to form then measure second light transmission >> difference between initial and final transmission = amt of platelet clumping = degree of platelet function
Describe the platelet function assay. How do you interpret the results of the study?
Put sample of blood thru small opening surrounded by biologically active membrane; membrane is coated w/ collagen + adp/epinephrine (factors that help w/ clot formation) and a clot forms
You do the collagen/epi test first.
Normal closing time for collagen/epinephrine test= no defect; If closing time is prolonged, then you do the collagen/ADP test
If closing time for col/adp test normal, problem is aspirin induced platelet dysfunction (probably tell this from patient’s history); If closing time = prolonged, DDx = thrombocytopenia (check platelet count) or some other defect not due to aspirin
Match the coagulation factors to their names:
I
Fibrinogen
Prothrombin
III
Thromboplastin
II
IV
Calcium
I Fibrinogen
II Prothrombin
III Thromboplastin
IV Calcium
Number the following coagulation factors:
Proaccelerin
Same as V
Proconvertin
Antihemophilic
Proaccelerin: V
Same as V: VI
Proconvertin: VII
Antihemophilic: VIII
Name the following coagulation factors:
IX
X
XI
XII
XIII
IX Christmas
X Stuart-Prower
XI Plasma thrombo-plastin antecedent
XII Hageman
XIII Fibrin stabilizing
Outline the intrinsic pathway of the coag cascade
Outline the extrinsic pathway of the coag cascade
Describe the role of Calcium (aka Factor IV) in the coag cascade. What is the function of thrombin in the coag casade?
Calcium has a net + charge; PL scramblase creates negatively charged phosphotidyl serine rafts that bind to one of calcium’s +ve charges, and the coagulation factors (also –vely charged, can bind to the other +ve charge)
(basically calcium helps to bind the coagulation factors to the platelet membrane)
Thrombin acts as an activator >> promotes positive feedback
Factors 2, __, __ and 10 are Vitamin K dependent
While the rest of the coag factors are made in the liver, only factor __ is made by endothelial cells
Factors 2, 7, 9 and 10 are Vitamin K dependent (remember 7+2=9 and 10 is Kind)
While the rest of the coag factors are made in the liver, only factor 8 is made by endothelial cells
The prothrombin (PT) time test measures the activation of which pathway of thecoag cascade? Which factors are being measured in the test?
Briefly describe the test
Extrinsic (remember PT = 2 letters, extrinsic has 2 i’s in it)
Fcators 7, X, V, II and fibrinogen
(see below)
Which pathway of the coag cascade does the PTT test?
The test will be prolonged with ___ and any other factor deficiency except __ and __
Intrinsic and common
Heparin; VII and XIII
Thrombin time measures the conversion of ___ to ___ upon addition of ___ to a patient’s plasma sample
A prolonged thrombin time would suggest a deficiency in ___
Thrombin time measures the conversion of fibrinogen to fibrin upon addition of thrombin to a patient’s plasma sample
A prolonged thrombin time would suggest a deficiency in fibrinogen
Patients lacking __, __, or __ have a long aPTT but no bleeding
Patients lacking FXI have a ___ aPTT and __
Patients lacking ___ or ___ have an equally long aPTT and ___ bleeding
- Patients lacking FXII, HMK, or PK have a long aPTT but no bleeding
- Patients lacking FXI have a long aPTT and may or may not have bleeding
- Patients lacking FVIII or FIX have an equally long aPTT and serious bleeding
Describe the mixed study to determine the presence of a factor deficiency or the presence of a factor inhibitor. How would you interpret the results of the test?
(see image below)
Mix patient plasma (sans deficiency) w/ normal plasma >> if clotting time is prolonged, there’s a factor inhibitor (right, b/c you should see normal clotting time a longer time suggests that they’re inhibitors in the pt sample that are blocking the clotting process)
Mix patient plasma (+ clotting factor deficiency) w/ normal plasma >>if clotting time is normal or goes down to near normal, this suggests a clotting factor deficiency (which makes sense because if there is a deficiency, the only reason we’re able to form a clot is because of the normal plasma which has normal levels of clotting factors in it)
Is there any way to measure how all the parts of the coagulation system work together? Explain how this works.
Sure, the #TEG
Basically the pin is spun until the clot forms and restricts spinning of pin. The pressure against the pin = tracing
Match the following conditions and tracings
What kind of graphs would you expect to see in a platelet aggregation study to distinguish between Bernard-soulier syndrome and Glanzmann thrombastenia?
How does aspirin work to prevent platelet aggregation?
Aspirin inhibits COX which mediates the production of prostaglandins (PGH2) that later become thomboxane, which is necessary for platelet aggregation
How does warfarin work to block clot formation?
Clotting factors have glutamate residue, which becomes carboxylated (gives clotting factor negative charge necessary for binding calcium)
Warfarin blocks effects of epoxide reductase (which recycles Vit K back to functional form so we can get carboxyl group to bind calcium)
Inability to bind calcium >> can’t proceed with clotting cascade
Primary targets of heparin are factor ___ and ___, and secondary targets are factor ___ and ___
How does heparin work?
Primary targets of heparin are factor 12a and 11a, and secondary targets are factor 10a and thrombin
Heparin inactivates thrombin and activated factor X (Xa) through antithrombin (AT)-dependent mechanism
What patterns of PT and PTT results would you see in defects in the extrinsic, intrinsic or common pathway? which factors are affected?
Explain what happens with disseminated intravascular coagulation
What are the downstream effects of DIC and how do they occur?
Systematic activation of clotting system due to existing illness (in this case, clotting is activated by sepsis, which the body responds to by activating inflammatory mechanisms that then shut down anti-coagulation mechanisms so clotting is constantly on)
End organ damage due to clot travelling to smaller and smaller vessels, resulting in occlusion, and bleeding due to platelet depletion (coz we’re clotting so much)
Morphologically, what kinds of cellswould you see in a smear of a pt who has DIC?
Helmet cells and schistocytes
