COAGULATION & HEMOSTASIS Flashcards
What coagulation factors does Warfarin/Coumadin inhibit, and what are they dependent on?
It inhibits factors II, VII, IX, and X, these factors are dependent on vitamin K
What Causes increases in PT/INR?
- Factor deficiency I, II, V, VII and X
- Warfarin/Coumadin
- Liver Disease
- DIC
- Vitamin K deficiency
- GI disease
- Antibiotics
What does Antithrombin III inhibit?
Factors IIa, Xa (most important), IX, XI, XII, also has an inhibitory effect on plasmin and kalikrein
What factors does Protein C inhibit?
Va and VIIIa
What protein does Thrombin activate?
Protein C
What factors are part of the intrinsic pathway?
XII, XI, IX, VIII
What factors are measured by the extrinsic pathway?
VII, X, V, II, I
What factors are part of the common pathway?
X, V, II, I
How will the presence of hemolysis affect coagulation testing?
It will cause falsely shortened results
How will the presence of lipemia affect coagulation testing?
May falsely prolong results due to interference with light transmittance
How will partially clotted specimens affect coagulation testing?
May cause falsely shortened results due to the activation of factors VIIa and thrombin
How will fully clotted specimens affect coagulation testing?
Will give falsely elevated results due to consumption and depletion of coagulation factors. (contain no fibrinogen)
What is the proper centrifugation for coagulation testing?
3000rpm at 15min
What is the appropriate anticoagulant for coagulation?
3.2% sodium citrate tube
How does high hematocrit affect coagulation testing and why?
Falsely elevated results because high Na Citrate interferes with recalcification stage of testing
What temperature should PT/INR samples stored at and when do they have to be tested?
Stored at 18-24 C, tested within 24hrs
What should APTT samples be stored at and when do they have to be tested?
Stored at 18-24 C, tested within 4hrs provided they do not contain unfractionated heparin, samples containing unfractionated heparin must be centrifuged within a 1hr and tested within 4hrs.
Why do unfractionated heparin samples have to be centrifuged within an hour?
To reduce the effect of heparin neutralization by platelet factor 4
What is the storage of samples that have platelet-poor plasma (PPP)?
May be frozen at -20 C for up to 2 weeks and at -70 C for 6 months
What is the proper way to thaw a coagulation sample?
Rapidly thawed at 37 C to prevent deterioration of factors V and VII, mixed well and tested within an hour.
What is a thrombus?
A thrombus is an abnormal function of a platelet or fibrin clot obstruction of a blood vessel, leads to thrombosis
What does a positive or high D-Dimer indicate?
In vivo lysis of cross-linked fibrin
Which genetic risk factor is the most prevalent in patients with Thrombophilia?
Activated Protein C Resistance (Factor V Leiden)
What is the primary function of Protein S?
Functions as a cofactor for Protein C
What best describes Heparin-induced thrombocytopenia (HIT)?
Antibodies bind to Heparin/Platelet factor 4 complex
What is the most frequent cause of abnormal Primary Hemostasis?
Thrombocytopenia / platelet disorders
What is the purpose of the synthetic activator used in the activated partial thromboplastin time test (APTT)?
Activate factor XII
What is thrombin’s role in Hemostasis?
- Enhances the activity of Factors V and VIII
- Induce platelet aggregation
- Converts fibrinogen to fibrin
What is the source of phospholipids for the intrinsic pathway?
Platelet factor 3
What is the ISI an acronym for?
International sensitivity index
What is the preferred test for monitoring LMWH therapy?
Anti-X a
Patients with Protein S deficiency demonstrate what risk factor?
Increase risk for venous thromboembolic disease
What causes a prolonged APTT to correct in a mixing study?
Factor XI deficiency
What substances make up the PT reagent?
Thromboplastin and calcium chloride
What is the best definition of Thrombophilia?
Tendency to thrombosis
What is the function of von Willebrand factor?
Participates in platelet adhesion and transport of FVIII
What is Anti-thrombin?
The most important coagulation inhibitor, inhibits thrombin formation.
What increases Anti-thrombin activity?
Heparin sulfate (in vivo) or commercial heparin
What would you give someone who overdosed on Heparin?
Protamine sulfate
What can a deficiency in anti-thrombin lead to?
Can lead to severe, even fatal thrombotic events such as DIC, liver disease, nephrotic syndrome
What is the Prothrombin Mutation Test?
Gene defect which results to increased amounts of Prothrombin and increased risk of thrombosis.
What are lupus inhibitors/antibodies?
Anticoagulant, antibodies alter the phospholipid surface and are non-specific inhibitors.
What are the important mechanisms of thrombosis in Lupus inhibitors?
- Inhibition of fibrinolytic system (factors XII and prekalikrein)
- Inhibition of prostacyclin
- Inhibition of protein C and S systems
What is Heparin Co-Factor II?
An inhibitor inhibits thrombin more slowly than AT
What is TFPI?
Tissue Factor Pathway Inhibitor binds and inactivates factors Xa and the tissue factor complex (TF:VIIa)
What does Aspirin inhibit?
Inhibits platelet aggregation
What does Heparin (unfractionated) inhibit?
Inhibits factors II, IX, X, XI, XII
What is the therapeutic range for unfractionated Heparin?
0.2-0.4 units/mL
How is the therapeutic range for Heparin determined?
By the Heparin response curve
How is Low Molecular Weight Heparin produced?
From unfractionated heparin by depolymerization = reduced size.
What is the function of Low Molecular weight heparin?
Causes a reduced activity to bind thrombin but increased ability to bind Xa
What is LMWH effective in?
Deep Vein Thrombosis (DVT)
What are the advantages of LMWH over standard heparin? (4)
1). Does not interact with platelets (less chance of bleeding)
2). No binding to plasma proteins, providing greater bioavailability and more predictable clearance from the circulation than standard heparin
3) Lower incidence of HIT
4) Lab monitoring is not necessary
What is Warfarin (Coumadin)?
It is an oral anticoagulant
What is the purpose of fibrinolysis?
To lyse unwanted clots and maintain hemostatic balance
What is the purpose of a Tissue Plasminogen Activator?
It converts plasma plasminogen to activate Plasmin which breaks down fibrin
What aids in the conversion of plasminogen to plasmin?
Factor XII, XIIa and Kalikirein
What does Plasmin release when clots are dismissed?
D-Dimer
What are the 3 pathways by which the fibrinolytic system is activated?
Extrinsic, Intrinsic and exogenous activation
What is the primary source of extrinsic activation?
Comes from vascular endothelium
What are the most commonly used exogenous activators? (3)
Urokinase, streptokinase and tissue plasminogen activator
What is Urokinase responsible for?
Dissolves clots formed in the renal tubes of the kidney
What is hemostatic balance?
A regulatory system of inhibitors exists to control both coagulation and fibrinolysis mechanisms.
What is Alpha 2 Antiplasmin?
Principle inhibitor of fibrinolysis, 1:1 binding with plasmin, resulting in neutralization
What is the function of the Thrombin-Activator Fibrinolysis Inhibitor (TAFI)?
Inhibits TPA and Urokinase
What can a deficiency of TAFI lead to?
A hemorrhagic disorder
What factors are in the contact group?
HMWK, Prekallikrein, XI and XII
What factors are in the prothrombin group?
Factors II, VII, IX and X
What factors are in the fibrinogen group?
Factors I, V, VIII and XIII
What is secondary hemostasis?
Composed of the coagulation response (extrinsic and intrinsic pathways) to injury
What is the purpose of the PT test in monitoring hemostasis?
- Detects factor deficiencies of the extrinsic pathway
- Detects Vitamin K deficiency
- Used to monitor therapeutic range for Coumadin therapy
What is the advantage of using LMWH over UFH?
LMWH has less risk of heparin associated thrombocytopenia
How would an APTT result be affected if the citrated plasma had platelets and was collected from a patient on unfractionated heparin?
Falsely decreased
If the Prothrombin Time is prolonged and the Activated Partial Thromboplastin Time is normal, what is the likely cause of the abnormality?
Factor VII deficiency
What factor deficiency might a patient have with a PT of 20.0s and an APTT of 35.0s?
VII
Which of the following deficiencies can NOT be identified using the prothrombin time and the partial thromboplastin time?
Thrombocytopenia
What will cause an acute hemorrhage in a patient?
Factor VIII deficiency
What clinical conditions present with a low fibrinogen?
Liver disease, DIC, fibrinolysis (risk for bleeding)
What causes a prolonged APTT and normal INR?
Factor VIII deficiency
What disorder/condition would have a normal PT/INR result?
Factor IX deficiency
What best describes a Clauss Fibrinogen?
Patient’s results are read against a fibrinogen concentration reference curve
What are the ingredients in APTT?
Silia ( activator), calcium (replaces calcium inactivated by anticoagulant)
What does INR stand for?
International normalizing ratio
Purpose of INR
Adjust for difference in thromboplastin sensitivity standardizing PT results worldwide
What is the purpose of a mixing study?
Will correct within normal units for factor deficiency, will only show partial correction for lupus anticoagulant or factor inhibitors
What clinical conditions present with a high fibrinogen?
Acute phase response, hyper coagulable state, dysfibrinogenemia (risk for thrombosis)
What causes an elevated D-Dimer?
DVT, DIC,pregnancy, inflammation, trauma, post-OP
State 2 different disease process/states that can cause elevated INR but normal APTT
- acquired Vitamin K deficiency (antibiotic Tx)
-Vitamin K deficiency
What does HIT cause?
Cause decreased platelet count and risk of thrombosis due to platelet activation
What reagent is used for the Fibrinogen assay?
Thrombin
How is DDIMER formed in a patient?
D-D fragment is composed of 2 D domains from separate fibrin molecules crosslinked by
the action of Xllla. DDIMER is the specific product of digestion of crosslinked fibrin only
What is the significance of a high DDIMER result?
Patient has a clot. Not specific as to what is causing the clot. A low DDIMER is sometimes
of more value than a high DDIMER result. A low DDIMER rules out a clot
The plasma of a patient with an APTT of 62.0s was mixed with 1:1 normal pooled plasma which resulted in an APTT of 58.0s. What does this suggest?
A lupus inhibitor
A citrated blood sample with a hematocrit of 0.600 L/L or more is run for coagulation studies. If the APTT results are 65.0s should the volume of the anticoagulant used:
Reduced in volume
If the Prothrombin Time is prolonged and the Activated Partial Thromboplastin Time is normal, what is the likely cause of the abnormality?
Factor VII deficiency
A prolonged plasma thrombin time indicates a deficiency in:
Fibrinogen
Hemophilia A and B may be suspected in patients with a:
Prolonged APTT, normal INR
What best describes a Clauss Fibrinogen?
Patient’s results are read against a fibrinogen concentration reference curve
