I. Coagulation Testing of Secondary Hemostasis (L6, L7 & L9 & Lab 3) Flashcards
What are the 4 main tests of secondary hemostasis/coagulation cascade?
• PT, PTT, TT and Fibrinogen concentration
What prolongs secondary hemostasis?
- Coagulation factor dysfunction
- Coagulation deficiency (rare)
- Drugs like heparin leading to inhibition
- Antibody inhibition
Why is citrate added to blood samples? What is the downside to this?
- Citrate removes the Ca from the sample –> prevents clotting before the tests can be performed
- Ca must be added back before coagulation tests are performed
The PTT measures which portions of the coagulation cascade?
- Intrinsic and common
* Think more letters in PTT than PT, PTT measures side with more numbers (more coag factors)
The PT measures which portions of the coagulation cascade?
- Extrinsic and common
* Think more letters in PTT than PT, PTT measures side with more numbers (more coag factors)
What does aPTT stand for?
• Activated partial thromboplastic time
What does TT stand for?
Thrombin time
What is added to a sample for PTT?
- Ca
- Negatively charged silica
- Partial Thromboplastin which is really just phospholipid
What is added to a sample for PT?
- Ca
* Thromboplastin (Phospholipid and Tissue activator)
How does Warfarin/Coumadin act as an anticoagulant?
• Prevents Vit K recycling –> Vit K deficiency –> inhibits Vit K dependent coagulation factors –> inhibit 7, 10 & 2
Which coagulation factors are vitamin k deficient?
2, 7,9 & 10
A prolonged PT means what? (asking about relationship to cascade, not clinical presentation)
• Deficiency, dysfunction or inhibition of VII, X, 5, 2 and/or 1
What clinical presentations cause prolonged PT?
- Liver disease
- Vit K antagonist (Warfarin or Coumadin)
- Fibrin/fibrinogen fragments
- DIC –> factor consumption and fibrin/fibrinogen fragments created which inhibit normal organized interactions
Why does liver disease potentially prolong PT and PTT?
- Vit K is a fat soluble vitamin, therefore liver disease –> decreased bile –> decreased fat absorption –> vit k deficiency
- Liver if site of production for coagulation factors –> liver disease can cause factor deficiency
Where in the body are coagulation factors created?
Liver
A prolonged PT means what? (asking about relationship to cascade, not clinical presentation)
• Deficiency, dysfunction or inhibition of 12, 11, 9, 10, 5, 2 and/or 1
What clinical presentations cause prolonged PTT?
- Heparin (inhibits 10 and 2)
- DIC –> factor consumption and fibrin/fibrinogen fragments created which inhibit normal organized interactions
- Lupus anticoagulant
How does Heparin work?
• Inhibits 10 and 2 –> anticoagulant
What clinical disorder results in a deficiency of factor XI? How is it inherited?
- Hemophilia C
* Autosomal dominant
What clinical disorder results in a deficiency of factor IX? How is it inherited?
- Hemophilia B
* X linked recessive
What clinical disorder results in a deficiency of factor VIII? How is it inherited?
- Hemophilia A
* X linked recessive
Which test (PT and/or PTT) is affected by heparin? Which one is more sensitive?
- Both are prolonged
* PTT is affected more
Which test (PT and/or PTT) is affected by lupus anticoagulant? Which one is more sensitive?
- Both are prolonged
* PTT is affected more
Which test (PT and/or PTT) is affected by Warfarin/Coumidin? Which one is more sensitive?
- Both are prolonged
* PT is affected more
Which (PTT or PT) is better for measuring effectiveness of heparin and cumodin?
- Hep = 3 letters, PTT = 3 letters
* Cumodin = PT
What is a Thrombin Time (TT)? What does it measure?
- Add exogenous thrombin and Ca –> measure fibrin formation
- Ability to convert fibrinogen to fibrin
What are the 2 types to measure the Thrombin Time and what are the testing for?
- Functional assay = concentration and function
* Mass assay/immune assay = concentration only
How is the Functional Assay for TT different than the mass assay?
- You add excess thrombin in the functional
* So if there is just a deficiency of fibrinogen this will be overcome by the excess thrombin
What causes a prolonged TT?
- Fibrinogen deficiency, dysfunction or inhibition
- Thrombin inhibition (heparin or thrombin Ab)
- Increased fibrin polymerization/fibrin split products
When clotting time is prolonged, how can it be determined if there is a deficiency/dysfuntion or inhibition?
Mixed Study
What is a mixed study? What do the results tell you?
- Mix patients plasma with plasma from a healthy individual
- If clotting time corrects –> deficiency or dysfunction
- If clotting time doesn’t correct –> inhibition (whatever is inhibiting the patients’ blood effects the healthy blood)
What conditions can increase fibrinogen concentration?
- Estrogen
- Pregnancy
- Acute phase response
How are blood samples stored in a way to protect damage of coagulation factors?
• Stored in refrigerator because coagulation factors are heat sensitive
The last step in the common pathway of the coagulation cascade is tested with what?
TT
What is the purpose of an INR?
- Way to standardize TT across labs (which can report different numbers)
- Used to test patients response to warfarin/Coumadin
What does INR stand for?
• International Normalized Ration
How is INR calculated?
- = (Patients PT/MNPT)^ISI
- MNPT (Mean Normal Prothrombin Time) = mean PT for population measured at that lab
- ISI (International Sensitivity Index) = characteristic of agent used to cause clotting (provided by manufacturer)
INR should only be used to test for what? Why should it not be utilized for other therapies/conditions?
- Coumidin/warfarin response
- The ISI which is used to calculate INR is determined by testing healthy patients and patients on Coumadin (not patients with other conditions)
What are the results of a mixing study on patients taking Warfarin/Coumidin and Heparin?
- Haprin does not correct (acts as inhibitor)
* Warfarin does correct (causes factor deficiency)
Does Warfarin/Coumidin cause inhibition, deficiency or dysfunction of clotting factors?
• Deficiency by removing K which is needed for synthesis
Does Heparin cause inhibition, deficiency or dysfunction of clotting factors?
Inhibition
If want to test for a potential deficiency in a single coagulation factor you can perform what test?
Biological assay
What is most likely if PT is normal, PTT is prolonged, PTT is corrected with mixing study and Thrombin times are normal?
Hemophilia A or B
What is suspected if there is a factor VIII deficiency, normal PT and normall PTT (occasionally this disorder presents with prolonged PTT that is corrected with mixing study)?
VWF disease
What causes bleeding in Von Willebrand Disease?
- Decreased platelet adhesion causes bleeding
* Decrease in VIII half like usually does not cause enough of a deficiency to cause bleeding
If the PT is prolonged and the PTT is normal, which pathway(s) are affected?
• Extrinsic (if PTT is normal than common is fine)
If the PT is prolonged but you do not know the status of the PTT, which pathway(s) could be affected?
• Extrinsic or common
If the PTT is prolonged but you do not know the status of the PT, which pathway(s) could be affected?
• Intrinsic or common
If the PTT is prolonged and the PT is normal, which pathway(s) are affected?
• Intrinsic (if PT is normal than common is fine)
If the PT and the PTT is prolonged, which pathway is affected?
- Common only
* Very unlikely to have 2 unrelated problems in the extrinsic and intrinsic present at the same time
Should coagulation tests be performed on somebody without bleeding history?
• No, abnormal labs on their own are not sufficient for a disorder unless there are symptoms
If a patient with abnormal bleeding history has normal labs, what should be done?
• Avoid unnecessary surgeries, but a full work up is not needed
What ethnic group gets Hemophilia more often?
Hemophilia has the same risk across all ethnic groups
Does hemophilia have to be inherited?
No spontaneous cases are present about 30% of the time
Which is the most common hemophilia?
A
How do levels of VIII correlate with severity of the disease in Hemophilia A?
5-25% = Mild
1-5% = Moderate
<1% = Severe
What causes acquired FVIII Inhibitor?
Ab against VIII
Present in elderly, pregnant, people with autoimmune disorders
When narrow down disorder to common pathway, what is the next test?
TT
