Coagulation Lecture 3 Flashcards
What is Disseminated intravascular coagulation (DIC)
- A pathological condition that causes consumption of coagulation factors and platelets
- coagulation response is accentuated and Out of control
- normal cloudy inhibitory mechanisms are overwhelmed (anti-thrombin 3, protein C, and protein S)
DIC overview
Under certain circumstances, the coagulation system consumes platelets and coagulation factors and forms a thrombus not only at the injury site, but throughout the microcirculation within the vital organs
Why is the fibrinolytic system initiated in DIC
As a result of excess clotting
During the final stages of the coagulation sequence what is converted into plasma?
Plasminogen
** plasmin splits apart the fibrin clot by fibrinolysis
Describe FDPs/ FSPs
FTPs have anticoagulant properties contributing to the bleeding problem the body is trying to correct
FTPs interfere with platelet function in the formation of fibrin
DIC triggers – extrinsic pathway
Activation of the extrinsic coagulation pathway by the release of thromboplastin
- placental abruption trauma
- retained dead fetus syndrome
- amniotic fluid leakage into blood or lymphatic tissues
DIC triggers – intrinsic pathway
Activation of the intrinsic pathway with factor 12a formation • burns •acidosis •immune complex disease •heat stroke
DIC triggers -common pathway
With direct activation of factors 10 or 2
•snake venom
•acute pancreatitis
•liver disease
Laboratory diagnostic tests for DIC
- PT
- PTT
- D Dimer
- Platelet count
- RBC morph (schistocytes and helmet cells)
- thrombin time
- Lab results will reflect both direct and indirect effects of excess thrombin and plasmin generation
D-Dimer
- specific for D Dimer
- D Dimer is a FSP/FDP that is formed when fibrin degrades
- FSP/FDPs are capable of being immunogenic
- an Anti-D Dimer monoclonal antibody is used to bind and D Dimer present in pt plasma
D-Dimer contd
Quantity of D Dimer present is proportional to the quality of fibrin being degraded
**Qualitative test usually done and POS tests are followed by a semi-quantitative method where serial dilutions are performed
Qualitative D Dimer
- Pt sample mixed with anti-d dimer coated latex particles
- Mixture placed onto glass slide and rotated
- slide observed for agglutination (POS result)
- Agglutination = >0.20 g/ml
- NO agglutination = <0.20g/ml
Semi-quantitative d dimer
- Pt samples and controls are diluted in a 2 fold manner
- Each dilution is separately mixed with a constant amount of anti-d dimer coated latex particles
- comparing the highest dilution of the pt sample showing agglutination to that of the control, the pts semi-quan. d dimer concentration can be determined
Fibrinogen
- plasma protein found in the liver
- required for the formation of fibrin clot
Afibrinogenemia
-rare inherited recessive trait characterized by lack of fibrinogen
-profuse bleeding after slight trauma
-delay in wound healing
Treatment: cry,ffp and whole blood
Hypofiibrinogemia
- inherited condition where fibrinogen levels are decreased
- hemorrhage after trauma is uncommon
- Umbilical stump bleeding and other hemmorhagic symptoms are common
Treatment: Cryo or ffp
Dysfibrinogenemia
- inherited defect or can be acquired with liver disease
- normal interaction of fibrinogen with its enzyme is disrupted causing defective fibrin formation and thrombosis
-Treatment: anti coag therapy for thrombosis
Fibrinogen Test Methods
- Best is comparison b/w pt plasma clotting time to that of known fibrinogen standard
- Pt plasma mixed with thrombin reagent and the time required for clot formation is INVERSELY proportional to the concentration of fibrinogen in the pts plasma
- Pts clotting time is then compared to the time it takes for a known fibrinogen standard to clot under the same conditions
Fibrinogen Test Methods contd
- Pts fibrinogen concentration is read directly off a previously prepared graph called a calibration curve
- prepared using dilutions of fibrinogen standard
- Results plotted as time vs concentration of fibrinogen
-normal range 200-400mg/dl
Bleeding Time Overview
- Time it takes for cessation of bleeding after a standardized capillary puncture to a capillary bed
- Evaluates platelets and vascular disorders
Time required depends on:
- Capillary integrity
- # of platelets
- Platelet function
Clinical significance of bleeding time
TTP- thrombocytopenic purpura:
rare blood disorder that causes blood clots to form in the small blood vessels throughout the body-characterized by petechiae and hemorrhage
–usually mild and self limiting; can require platelet transfusion and plasma exchange
-prolonged in poor capillary intergity
T/F Abnormality or deficiency of coag factors does not usually affect bleeding time
True
Method of choice for bleeding time
-Simplate method
-blood pressure on vessel is constant (40 mm Hg)
-5mm long,1mm deep
Normal values:
2.3-9.5 minutes
Sources of error for Bleeding time simplate method
- nonstandardized puncture
- inadequate puncture-falsely decrease bleeding time
- too deep-falsely increased bleeding time
- ingestion of aspirin can affect platelet function for up to 8 days
- avoid veins, scars, bruises and hair in the puncture site
IVY bleeding time
- historical method on which the simplate bleeding time is based
- same procedure as simplate except a lancet with standardized dimensions is used
**Mielke modification of IVY bleeding time is the same except 2 bleeding times are used
Coagulation disorders- Inherited disorders
- usually present at birth
- mild disorders may only appear in adulthood
- Hemophilia A
- Von Willebrands disease
Hemophilia A
- Sex linked
- females carry trait, passed to sons
- intra-articular,intramuscular and cerebral bleeding
- 85% occurrence in pts with history of bleeding
- Decreased VIIIc
- Normal Bleeding Time
- Normal PT, APTT
- Decreased VIII antigen
- Normal ristocetin co-factor
- normal platelets
- treat with Cryo and VIII concentrates
Von Willebrands Disease
- Affects platelets
- Autosomal dominant
- Cutaneous and mucosal bleeds
- variable severity
- Prolonged bleeding time
- Decreased platelet adhesion, VIII, VIII antigen, ristocetin aggregation
- Treated with Cryo or FFP
**found in about 20% of all hemophilia pts
Coagulation Disorders Acquired
- Generalized bleeding
- no family history
- usually onset in adult life
- plasma platelet factors may be affected
Coagulation Disorders Acquired - associated diseases
- Liver disease fibrinogenolysis acquired with liver disease
- hyperfunction of spleen
- mass transfusion
- VIT K def.
- anticoag therapy
- scurvy
Vascular Disorders results in
Purpura- rash of purple spots on the skin caused by internal bleeding from small blood vessels
Petechiae- a small red or purple spot caused by bleeding into the skin
Nosebleeds
Fibrin Endpoint Methods
Electromechanical- detects fibrin strands
Optical density- measures the rate of change of light absorbance; a more reproducible method & MOST COMMON
Synthetic substrate enzyme- uses endpoint and rate kinetics
Automated PT/APTT Assays
Semi automated Fibrometer
Electromechanical instrument which detects a clot by means of moving electrode
-has individual sample and reagent wells where samples and reagents are incubated at 37 Celsius
-Sample reagents hand pipetted and timer is activated
Automated PT/APTT Assays
Fully auntomated
-Many use the optical density method to detect formation of the clot
- Automated instruments include
- incubator 37 C
- timer- records time to nearest 0.2s
- Automatic pipetting system
- barcode
some automated analyzers also perform individ factor assays Many also analyze other coag components (protein S,C and thrombin time)
Chromogenic Assays
- Anti-Thrombin III
- Heparin
- 2- antiplasma
- Plasminogen
Fibrinogen
Point of Care testing for Coag
-POC assays are always useful when on the spot testing is required
- also for home use so pts on long term therapy can better control their medication
- POC is much more expensive than traditional lab methods
