Coagulation tests Flashcards
1
Q
Primary vs secondary hemostasis
A
- Hemostasis: the ability to clot
- Primary: initial platelet plug (front line defense)
- Areas of body under its control: skin, mucosa, endothelium
- Things involved: platelets, vonWillebrand’s (vW), fibrinogen
- Secondary: proteins to finalize the plus
- Areas under control: joints, deep tissue
- Involved: clotting factors
2
Q
Manifestations of hemostasis deficiencies
A
- Primary: can see from the skin (petechiae, ecchymoses, purpura), prolonged bleeding time (BT)
- Secondary: can only see in joints
3
Q
Tests of primary hemostasis
A
- History (menstrual, dental, family)
- Peripheral smear (look for abnormal platelets)
- Bleeding time (make thin slice in skin and measure time to clot, should be <9min)
- PFA100 (platelets function analyzer)
4
Q
Inherited conditions that prolong BT
A
- Glanzmann’s thrombasthenia (IIbIIIa receptor deficiency)
- Bernard Soulier (IbIX receptor deficiency)
- vW disease (vWD; defective or low vW)
- Platelet granule defects
5
Q
Acquired conditions that prolong BT
A
- Uremia
- Paraproteinemia
- Severe anemia
- Liver disease
- Drugs (NSAIDs, aspirin)
- BT does not correlate w/ exposure to NSAIDs
6
Q
PFA100
A
- Anticoagulated whole blood passed through pore coated w/ collagen + ADP
- Measure closure time (CT), time it takes to occlude aperture via clot
- Superior test to BT as a screen for platelet dysfunction (can detect moderate to severe vWD, aspirin’s effect)
- Cannot distinguish btwn type 1 vWD (not enough vW) and type 2 vWD (poor quality vWD)
7
Q
Specific tests of platelet function
A
- Platelet aggregometry: tests platelet response to agonists that induce aggregation (rare diseases)
- vWF Ag: quantitaive measure of vWF (vW made in endothelial cells, amount in blood surrogate to amount being made)
- Ristocetin cofactor assay (RCA): tests the ability of vWF to bind to its receptor (GPIbIX)
- RCA tests the functional aspect of vW (the high weight multimer form)
- If vWF Ag and RCA do not parallel, usually means problem in activity (quality) of vW
- Comparing the vWF Ag and RCA allows you to distinguish btwn type 1 and type 2 vWD (both low-> type1, vWF Ag normal and RCA low-> type2A or M)
8
Q
Secondary hemostasis (coagulation cascade) 1
A
- 3 parts: instrinsic, extrinsic, and common pathways
- Extrinsic: starts w/ tissue factor (TF) activating factor VII to its active form VIIa (requires Ca and phospholipid, PL)
- VIIa+TF+Ca/PL is able to activate factor X to Xa
9
Q
Secondary hemostasis (coagulation cascade) 2
A
- Common: starts w/ X being activated to Xa (requires Ca and PL), either by TF+VIIa or IXa+VIIIa complex (from extrinsic pathway)
- Once Xa is activated, it complexes w/ active Va (activated by trace thrombin) and Ca/PL (Xa/Va/Ca/PL is prothrombinase complex) to activate prothrombin (factor II) to thrombin (IIa)
- Once thrombin is active it cleaves fibrinogen (factor I) to fibrin (Ia), which is insoluble and precipitates out of solution to form the clot
10
Q
Secondary hemostasis (coagulation cascade) 3
A
- Intrinsic: Starts w/ factor XIIa (activated by negatively charged surfaces) which complexes w/ HMWK (high molecular weight kininogen), PK (prekallekrein), and factor XI to activate XI-> XIa (XI usually activated by thrombin)
- XIa activates factor IX (w/ Ca) to IXa (IX can also be activated by VIIa+TF)
- IXa must complex w/ active VIIIa (activated by trace thrombin) and Ca to form the intrinsic tenase complex
- This IXa/VIIIa/Ca/PL tense complex activates X to Xa and thus begins the common pathway
11
Q
-Tests for secondary hemostasis
A
- PT (prothrombin time): tests the extrinsic + common pathways
- aPTT (activate partial thromboplastin time): tests the intrinsic + common pathways
12
Q
aPTT
A
- Add citrated (anticoaged) plasma + PL + contact activator + Ca and measure time to clot
- Most sensitive to the intrinsic pathway (prolongs when 60-70% deficient)
- Only test that is sensitive to heparin (PT test the system is overloaded w/ TF and is not sensitive to heparin)
- More sensitive to VIII and XI than to IX
- Less sensitive to thrombin and fibrinogen
- Accuracy depends on reagents, mild but significant deficiencies can be missed, deficiencies in common pathway prolong both aPTT and PT
- Correlation btwn degree of prolongation and factor level better for VIII than others
- HMWK, prekallikrein, and XII affect the aPTT but deficiencies in these do not cause bleeding
- Normal aPTT in adult: 23-33
13
Q
Spurious prolongation of aPTT
A
- Elevated HCT (increases the citrate:plasma ratio, removing some Ca)
- Heparin in tube (inactivates thrombin and Xa)
- Clotted sample (pulls factors out of solution)
14
Q
Workup of a prolonged aPTT
A
- If an aPTT is prolonged it means there is either a deficiency in a factor or an inhibitor of a factor present, but doesn’t tell you which
- Must do a 50/50 mix (50% patient blood and 50% normal blood) to increase all factor levels to at least 50% (and therefore they are all at high enough level to clot)
- If the mix clots, that means there was a deficiency in the patients blood
- If the mix doesn’t clot, that means there was an inhibitor in the patients blood that is still inhibiting the factor(s) in the mix
15
Q
Workup based on result of 50/50 (after prolonged aPTT)
A
- If the 50/50 corrected the blood, assay for individual factors (XI, IX, VIII) to see where the deficiency lies (since XII is unimportant, but the rest are)
- If the 50/50 did not correct the blood, test for lupus anticoagulant Abs, anticardiolipin Abs
- If those Ab tests are negative then test for specific inhibitor Abs
