Coagulation Studies Flashcards
Define hemostasis
The property of circulation whereby blood is maintained as a fluid within the vessels
- Maintained as a fluid - it doesn’t clot
- *Within the vessels - they don’t leak or leave the vessels and we have mechanisms to keep htem in if bleeding occurs *
Systems of Hemostasis
(4)
- Vascular
- Platelets–Primary Hemostasis
- Coagulation–Secondary Hemostasis
- Fibrinolysis
All four are active all of the time
Vascular system actions
(2, regulating compounds)
- Vasoconstriction
- Narrowing of the vessel to minimize blood flow
- Serotonin and thromboxane A2
- Vasodilation
- Widening of the vessel to increase blood flow
- Prostacyclin PG I2
Hemostatis Plug Formation
(7 steps)
- Vascular injury
- Tissue exposure
- Adhesion - platelets adhere to exposed sub-endothelium
- Aggregation - Platelets adhere to each other to form a plug and release dense bodies and alpha granules
- Plug formation
- Fibrin formation - solidifies platelet plug
- Clot retraction (platelet mediated)
Bleeding Time
(use, methods of eval)
Used to diagnose primary hemostatic disorders
Not a good predictor of surgical bleeding risk
Methods of eval:
- Traditional method - fairly antiquated
- use BP cuff as tournoquet
- make identical incisions (~5cm each)
- time how long the bleeding lasts
- PFA 100 Principle
- Citrated whole blood aspirated thru a capillary towards a membrane coated c agonists
- Collagen/Epi
- Collagen/ADP
- Agonists in combination c high shear stresses create an environment where adhesion, activation, and aggregation can be evaluated
*
PFA 10 Interpretation
(2)
- Collagen/epinephrine - detects platelet disorders due to intrinsic platelet defects, vWD, or platelet inhibiting agents
- Collagen/ADP - abnormal result would indicate intrinsic platelet defect or vWF
*Usually you don’t do this first. You start c platelet count. If pt still has s/sx c normal number of platelets then you progress to this. Also do this before surgery *
Coagulation Cascade
(3 aspects)
Fibrinogen to Fibrin Conversion
(3 steps)
Fibrinogen is a long protein, cleaves off fibronofactors A and B. Fibrin monomers go together like bricks
Steps for Collecting Blood for Coagulation Studies
(5 requirements)
- Sodium citrate (blue top tube)
- binds 1:1 c calcium to make calcium unavailible, keeping fibrinogen from activating and thus preventing clotting
- Ratio of blood to anticoagulant 9:1 - allow clot prevention s changing the test results due to excesss anticoag. High hematocrit may present too much material to be deactivated by antigoag. so a little clotting will occur
- Tube must be full
- High hematocrit
- Invert the tube a couple times to mix it
- Should not be the first tube drawn - might have tissue factor in it
- antigoac monitoring tests (like for warfarin) can be the first tube
- Whole blood must be spun to obtain PPP
- Samples refrigerated until testing
Prothrombin Time (PT)
(what it evals, three steps, normal range)
Eval - Functionality of CF 1, 2, 5, 7 and 10 (extrinsic pathway). Measures time to form a soluble fibrin clot
Normal Range - Between 10 and 14 seconds
Procedures - See attachment
Ativated Partial Thromboplastin Time (aPTT)
(what it tests, three steps)
Eval - Intrinsic Pathway, factors 1, 2, 8, 9, 11, and 12.
Procedure - See attachment. Activated by “contact activator” to activate 11 and 12. Reintroduce calcium and time how long it takes to form a clot
Thrombin Time/Fibrinogen
(mechanism, purpose of tests, mechanism)
Two tests c one mechanism
Purpose - evaluate the time for plasma c thrombin to form a soluble clot. Each test has a different purpose
- Thrombin Time- low concentration of thrombin will be sensitive to things like heparin
- Fibrinogen- high thrombin to compare pt to standard times to estimate amount of fibrinogen present in pt’s sample
Factors that may Prolong PT
(3 categories, 5/1/4 specifics)
- Congenital factor deficiency
- I, II, V, VII, X
- Acquired factor deficiency
- May be single or multiple
- Production
- Consumption
- May be single or multiple
- Inhibitors
- Heparin (some heparins in some test systems)
- Lupus-like anticoagulant (high dose)
- Paraproteins (rare)
- Elevated FSP – fibrinogen split proteins (rare)
- Competitive inhibition for thrombin
Factors that may Prolong aPPT
(3 categories, 8/2/6 specifics)
- Congenital factor deficiency
- I, II, V, VIII, IX, X, XI, XII
- Acquired factor deficiency in intrinsic or common pathways
- May be single or multiple
- Production
- Consumption
- May be single or multiple
- Inhibitors
- Heparin (some heparins)
- Specific factor inhibitor
- Lupus-like anticoagulant, phospholipid antibody
- Paraproteins (rare)
- Elevated FSP (rare)
- Intrinsic liver disease
Mixing Studies
(purpose, procedure, results)
Procedure
- Typically performed on the APTT
- Patient plasma is mixed with an equal amount of normal plasma and the APTT repeated
- Correction = APTT decreases to within 5 seconds of the normal plasma run alone
**Function - **Determines deficiency vs inhibitor
Results -
- If pt is deficient in factors, other plasma will remove the deficiency and reduce the PTT (correction). Heparin is in this category.
- If a pt has defected inhibitors then PTT will not correct
Fibrinolysis Diagram
(explain it)
Picture Key
- Empty arrow are what cause fibrinolysis
- Full arrows are the fibinolysis
Note- Factor XII can be bypassed in clotting but not in fibrinolysis. Therefore, XIIa deficiency may have thrombolytic symptoms but not bleeding symptoms
D-Dimer Test
Function - help c dx of increased thrombosis. Rules out PE.
Works by D-dimer assay thru beads coated c D-dimer
Thrombin Inhibition
(3 meds)
- Unfractionated Heparin
- Low Molecular Weight Heparins
- Direct Antithrombins
Anticoagulant Thearpy
(2 types)
- Heparin
- Warfarin compounds (Coumadin)
Heparin
(2)
- Unfractionated- inhibits both IIa and Xa
- TT is extremely sensitive, too sensitive
- PTT is test of choice for monitor
- Low molecular weight heparin (LMW)-inhibits Xa
- PT, PTT, and TT are not sensitive
- Anti-Xa used for monitoring
Unfractionated Heparin
- Heterogeneous mixture of many different size molecules (unfractionated)
- Acts by enhancing the effect of antithrombin
- Immediate action when it enters the bloodstream
Heparin Risks
(3)
- Hemorrhage
- Heparin-induced thrombocytopenia
- Osteoporosis associated with long term therapy
Heparin Induced Thrombocytopenia
- 1-5% hospital patients exposed to heparin will develop HIT
- 30% of those will suffer a thrombosis
- Patient forms antibodies to the complex of heparin with PF4 found in the alpha granules of platelets
- Most common in unfractionated heparin
- Platelet drop in first few days after heparin initiation
- Monitor c platelet count = constant for a few days then huge dramatic quick drop
Heterogeneity of Anticoagulant Activity
- Anticoagulation and clearance are influenced by chain length
- Accumulation of LMW fraction
- Responsible for discrepancies between plasma heparin concentration and aPTT
- Binding to plasma proteins, macrophages, endothelial cells and platelets affects dose-response relationship
aPPT Considerations
(7)
- Tube type
- Plastic vs. glass
- Citrate concentration
- Lupus like anticoagulant –antibody against phospholipid in lab (wont do anything in the pt but will effect heparin monitoring)
- Concommitant factor deficiency
- Antithrombin level – won’t have appt changes. This is because heparin doesn’t act directly on clotting factors it just acts on antithombin. If your antithrombin is messed up then you wont see changes
- Acute phase reactants – stress, pregnancy, etc. will showrten PTT more than heparin will
- Coumadin
- Detection method – tell lab if things like triglycerides are high. Stuff like this will effect the testing mechanism
- If something is abnormal and you didn’t anticipate that, call the lab and ask them about the test type
Low Molecular Weight Heparin
- Longer biologic half-life
- Weight adjusted dosing without monitoring in most cases
- Exceptions: children, pregnancy, renal insufficiency, obesity
- Higher cost may be offset by lower administration costs and/or shorter hospital stays
- Derived from heparin by chemical or enzymatic depolymerization
- Reduced binding to proteins and cells is responsible for more predictable dose-response relationship
- Reduced binding to platelets and PF4 may explain lower incidence of HIT
Drugs - Low Molecular Weight Heparins
(list 6)
- Nadroparin calcium - Fraxiparin
- Enoxaparin sodium - Lovenox
- Dalteparin - Fragmin
- Ardeparin - Normiflo
- Tinzaparin - Innohep
- Revipatin - Clivarine
Coumadin
(MOA, method of monitoring, pertinant admin information)
- Inhibit vitamin K dependent factors (II, VII, IX, X, protein C, and protein S)
- Effect is seen clinically in 3-5 days (when the K dependent factors degrade and not replaced)
- Factor VII (shortest half-life)
- PT is test of choice for monitoring
- Stable effect usually reached within 2 weeks
International Normalized Ratio (INR)
(definition, method of calculation)
**Definition - **International effort to standardize reporting of prothrombin (PT) times. PT times may vary from lab to lab but calculation will normalize the value across facilities
**Formula - ** INR = PTISI/Normal prothrombin time
*ISI - International Sensitivity Index *
INR Therapeutic Ranges
(6)
Pulmonary Embolus 2.0-3.0
DVT 2.0-3.0
Prophylaxis 2.0-3.0
Atrial fibrillation 2.0-3.0
Prosthetic heart valve 3.0-4.5
Recurrent systemic embolism 3.0-4.5
Note - these may not be the most updated values
