Coagulation Studies

Question 1

Define hemostasis

Answer 1

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 *

Question 2

Systems of Hemostasis

(4)

Answer 2

1. —Vascular
2. —Platelets–Primary Hemostasis
3. —Coagulation–Secondary Hemostasis
4. —Fibrinolysis

All four are active all of the time

Question 3

Vascular system actions

(2, regulating compounds)

Answer 3

1. —Vasoconstriction
   
   • —Narrowing of the vessel to minimize blood flow
   • —Serotonin and thromboxane A2
2. —Vasodilation
   
   • —Widening of the vessel to increase blood flow
   • —Prostacyclin PG I2

Question 4

Hemostatis Plug Formation

(7 steps)

Answer 4

1. Vascular injury
2. Tissue exposure
3. Adhesion - platelets adhere to exposed sub-endothelium
4. Aggregation - Platelets adhere to each other to form a plug and release dense bodies and alpha granules
5. Plug formation
6. Fibrin formation - solidifies platelet plug
7. Clot retraction (platelet mediated)

Question 5

Bleeding Time

(use, methods of eval)

Answer 5

—Used to diagnose primary hemostatic disorders
—Not a good predictor of surgical bleeding risk
—

Methods of eval:

1. Traditional method - fairly antiquated
   
   • use BP cuff as tournoquet
   • make identical incisions (~5cm each)
   • time how long the bleeding lasts
2. 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
  *

Question 6

PFA 10 Interpretation

(2)

Answer 6

​

1. Collagen/epinephrine - detects platelet disorders due to intrinsic platelet defects, vWD, or platelet inhibiting agents
2. 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 *

Question 7

Coagulation Cascade

(3 aspects)

Answer 7

Question 8

Fibrinogen to Fibrin Conversion

(3 steps)

Answer 8

Fibrinogen is a long protein, cleaves off fibronofactors A and B. Fibrin monomers go together like bricks

Question 9

Steps for Collecting Blood for Coagulation Studies

(5 requirements)

Answer 9

1. —Sodium citrate (blue top tube)
   
   • ​binds 1:1 c calcium to make calcium unavailible, keeping fibrinogen from activating and thus preventing clotting
2. —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
3. —Should not be the first tube drawn - might have tissue factor in it
   
   • ​antigoac monitoring tests (like for warfarin) can be the first tube
4. —Whole blood must be spun to obtain PPP
5. —Samples refrigerated until testing

Question 10

Prothrombin Time (PT)

(what it evals, three steps, normal range)

Answer 10

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

Question 11

Ativated Partial Thromboplastin Time (aPTT)

(what it tests, three steps)

Answer 11

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

Question 12

Thrombin Time/Fibrinogen

(mechanism, purpose of tests, mechanism)

Answer 12

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

Question 13

Factors that may Prolong PT

(3 categories, 5/1/4 specifics)

Answer 13

1. —Congenital factor deficiency
   
   • —I, II, V, VII, X
2. —Acquired factor deficiency
   
   • —May be single or multiple
     
     • —Production
     • —Consumption
3. —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

Question 14

Factors that may Prolong aPPT

(3 categories, 8/2/6 specifics)

Answer 14

1. —Congenital factor deficiency
   
   • —I, II, V, VIII, IX, X, XI, XII
2. —Acquired factor deficiency in intrinsic or common pathways
   
   • —May be single or multiple
     
     • —Production
     • —Consumption
3. —Inhibitors
   
   • —Heparin (some heparins)
   • —Specific factor inhibitor
   • —Lupus-like anticoagulant, phospholipid antibody
   • —Paraproteins (rare)
   • —Elevated FSP (rare)
   • Intrinsic liver disease

Question 15

Mixing Studies

(purpose, procedure, results)

Answer 15

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

Question 16

Fibrinolysis Diagram

(explain it)

Answer 16

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

Question 17

D-Dimer Test

Answer 17

Function - help c dx of increased thrombosis. Rules out PE.

Works by D-dimer assay thru beads coated c D-dimer

Question 18

Thrombin Inhibition

(3 meds)

Answer 18

1. —Unfractionated Heparin
2. —Low Molecular Weight Heparins
3. —Direct Antithrombins

Question 19

Anticoagulant Thearpy

(2 types)

Answer 19

1. —Heparin
2. —Warfarin compounds (Coumadin)

Question 20

Heparin

(2)

Answer 20

1. —Unfractionated- inhibits both IIa and Xa
   
   • —TT is extremely sensitive, too sensitive
   • —PTT is test of choice for monitor
2. —Low molecular weight heparin (LMW)-inhibits Xa
   
   • —PT, PTT, and TT are not sensitive
   • —Anti-Xa used for monitoring

Question 21

Unfractionated Heparin

Answer 21

1. —Heterogeneous mixture of many different size molecules (unfractionated)
2. —Acts by enhancing the effect of antithrombin
3. —Immediate action when it enters the bloodstream

Question 22

Heparin Risks

(3)

Answer 22

1. —Hemorrhage
2. —Heparin-induced thrombocytopenia
3. —Osteoporosis associated with long term therapy

Question 23

Heparin Induced Thrombocytopenia

Answer 23

• —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

Question 24

Heterogeneity of Anticoagulant Activity

Answer 24

• —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

Question 25

aPPT Considerations

(7)

Answer 25

• —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

Question 26

Low Molecular Weight Heparin

Answer 26

• —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

Question 27

Drugs - Low Molecular Weight Heparins

(list 6)

Answer 27

1. —Nadroparin calcium - Fraxiparin
2. —Enoxaparin sodium - Lovenox
3. —Dalteparin - Fragmin
4. —Ardeparin - Normiflo
5. —Tinzaparin - Innohep
6. —Revipatin - Clivarine

Question 28

Coumadin

(MOA, method of monitoring, pertinant admin information)

Answer 28

• —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

Question 29

International Normalized Ratio (INR)

(definition, method of calculation)

Answer 29

**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 = PT^ISI/Normal prothrombin time

*ISI - International Sensitivity Index *

Question 30

INR Therapeutic Ranges

(6)

Answer 30

—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