Coagulation Lecture 3 Flashcards

1
Q

What is Disseminated intravascular coagulation (DIC)

A
  • 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)
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2
Q

DIC overview

A

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

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3
Q

Why is the fibrinolytic system initiated in DIC

A

As a result of excess clotting

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4
Q

During the final stages of the coagulation sequence what is converted into plasma?

A

Plasminogen

** plasmin splits apart the fibrin clot by fibrinolysis

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5
Q

Describe FDPs/ FSPs

A

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

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6
Q

DIC triggers – extrinsic pathway

A

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
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7
Q

DIC triggers – intrinsic pathway

A
Activation of the intrinsic pathway with factor 12a formation
• burns 
•acidosis 
•immune complex disease 
•heat stroke
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8
Q

DIC triggers -common pathway

A

With direct activation of factors 10 or 2
•snake venom
•acute pancreatitis
•liver disease

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9
Q

Laboratory diagnostic tests for DIC

A
  • 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
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10
Q

D-Dimer

A
  • 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
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11
Q

D-Dimer contd

A

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

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12
Q

Qualitative D Dimer

A
  • 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
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13
Q

Semi-quantitative d dimer

A
  • 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
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14
Q

Fibrinogen

A
  • plasma protein found in the liver

- required for the formation of fibrin clot

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15
Q

Afibrinogenemia

A

-rare inherited recessive trait characterized by lack of fibrinogen
-profuse bleeding after slight trauma
-delay in wound healing
Treatment: cry,ffp and whole blood

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16
Q

Hypofiibrinogemia

A
  • 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

17
Q

Dysfibrinogenemia

A
  • 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

18
Q

Fibrinogen Test Methods

A
  • 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
19
Q

Fibrinogen Test Methods contd

A
  • 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

20
Q

Bleeding Time Overview

A
  • 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:

  1. Capillary integrity
  2. # of platelets
  3. Platelet function
21
Q

Clinical significance of bleeding time

A

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

22
Q

T/F Abnormality or deficiency of coag factors does not usually affect bleeding time

A

True

23
Q

Method of choice for bleeding time

A

-Simplate method
-blood pressure on vessel is constant (40 mm Hg)
-5mm long,1mm deep
Normal values:
2.3-9.5 minutes

24
Q

Sources of error for Bleeding time simplate method

A
  • 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
25
Q

IVY bleeding time

A
  • 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

26
Q

Coagulation disorders- Inherited disorders

A
  • usually present at birth
  • mild disorders may only appear in adulthood
  • Hemophilia A
  • Von Willebrands disease
27
Q

Hemophilia A

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
28
Q

Von Willebrands Disease

A
  • 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

29
Q

Coagulation Disorders Acquired

A
  • Generalized bleeding
  • no family history
  • usually onset in adult life
  • plasma platelet factors may be affected
30
Q

Coagulation Disorders Acquired - associated diseases

A
  • Liver disease fibrinogenolysis acquired with liver disease
  • hyperfunction of spleen
  • mass transfusion
  • VIT K def.
  • anticoag therapy
  • scurvy
31
Q

Vascular Disorders results in

A

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

32
Q

Fibrin Endpoint Methods

A

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

33
Q

Automated PT/APTT Assays

Semi automated Fibrometer

A

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

34
Q

Automated PT/APTT Assays

Fully auntomated

A

-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)

35
Q

Chromogenic Assays

A
  • Anti-Thrombin III
  • Heparin
  • 2- antiplasma
  • Plasminogen

Fibrinogen

36
Q

Point of Care testing for Coag

A

-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