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1.
Preoperative scenarios:
Patient is on chronic aspirin therapy:
When should the aspirin be stopped?
When is a bleeding time indicated?
How does aspirin affect the PT, aPTT, ACT?
When is regional anesthesia contraindicated?
Any difference in the risk of epidural versus single-shot spinal?
How much variation exists between hemostatic responses to aspirin therapy?
If the patient is on an NSAID other than aspirin, when should it be stopped?
What drugs reverse the effects of aspirin?
2.
3.
4.
5.
6.
1.
A hypotensive trauma patient is brought in with a blunt injury to the abdomen. The
peritoneal tap in the E.R. is positive for blood. Patient is rushed to the O.R., where a
ruptured spleen is removed, and the patient is found to also be bleeding from a pelvic
fracture. You have administered 10 units of blood, and the blood pressure has stabilized.
What is your a priori expectation that this patient now has a coagulation defect?
What clinical observations are relevant to the patients coagulation status?
What will an ACT tell you?
How does the ACT differ from the aPTT?
What additional information will you get from a PT, fibrinogen, fibrin splits,
clotting time, etc.?
2.
The same patient receives another 10 units of blood over 4 hours. The surgeons are
having difficulty obtaining hemostasis.
What is your a priori expectation that this patient now has a coagulation defect?
What blood products are you going to administer?
Who is responsible for the decision of what blood products to give?
3.
The patient receives another 15 units of blood over the next 4 hours. The field is very
wet. Your catheter sites are oozing. You are now administering every coagulation product
known to man.
What are all of the coagulation products known to man?
What benefits do you expect to get from each of them?
How likely is it that the factors in each blood product will address the
coagulopathy?
What interventions, other than blood products, per se, might help resolve the
coagulopathy?
October 9, 1995
Coagulopathy
Page 3
Data Base:
Coagulation Factors:
Final Common Pathway: Think of paper money: X -> V -> II -> I
Extrinsic Pathway: Factor X is activated (to Xa) by factor VII.
Intrinsic Pathway: Factor X is activated by factors XII, XI, IX, and VIII (e.g. everything
else)
Factor Name
I
II
III
IV
V
VI
VII
VIII
IX
X
XI
XII
XIII
Normal
(mg%)
Required
(mg%)
Half-life
at 4 degrees
fibrinogen
150-350
70 (50%)
4 days
prothrombin
70-130
20 (30%)
2-5 days
thromboplastin
calcium
proaccelerin
70-130
5 (10%)
12 hours
activated 5
proconvertin
70-150
20 (30%)
300 min
antihemophilic 50-200
30 (60%)
17 hours
7 days
Christmas
70-130
20 (30%)
40 hours
Stuart
70-130
10 (15%)
40 hours
PTA
70-130
20 (30%)
60 hours
Hageman
40-150
0 (0%)
fibrin stabilizing
50-200
1 (2%)
12 days
Stability
stable
stable
7 days
stable
stable
stable
7 days
stable
stable
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Coagulopathy
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Platelet concentrates contain some RBC's, which is why ABO typing is needed.
Platelet factor III, a phospholipid, activates factor X, using IX and VIII.
Pre-existing disorders:
Idiopathic Thrombocytopenic Purpura
Possibly from antiplatlet antibodies
Can occur acutely, especially in kids following viral illness
Symptoms:
Easy bruising
Epistaxis
Petechiae
G.I. Bleeding
Laboratory:
Platelet count: 5,000 - 20,000
Bleeding time: prolonged
PT: normal
PTT: normal
Clotting time: normal
Treatment:
Steroids
Splenectomy
Usually don't require platelets for splenectomy. If you plan to give
platelets, wait until the spleen is out before transfusing them.
Secondary Thrombocytopenic Purpura
Causes include malignancy (bone marrow invasion), sepsis, collagen disorders,
allergic reactions, DIC, and poisoning from insecticides and organic dyes.
Laboratory:
Platelet count: <60,000
Bleeding time: prolonged
Assuming normal platelets, below 100K, Bleeding time (min) = 30.5 - Platelet
count/3850
Hemophilia
Factor VIII deficiency
Prevalence: 1/10,000 to 1/25,000
Sex-linked inheritance
October 9, 1995
Coagulopathy
Factor VIII
Level
<1%
3-5%
10-15%
Page 5
Symptoms
Spontaneous bleeding
Rare spontaneous bleeding
Probably asymptomatic until
surgery or dental procedures
Lab:
Bleeding time: normal
PT: normal
PTT: increased
Clotting time: increased
Therapy
By definition, each ml of FFP contains 1 factor VIII activity
unit. Each activity unit transfused raises the activity in the blood by roughly
2%/kg of body weight. So, in a 70 kg patient, each ml of FFP (1 factor
VIII activity unit) would raise the activity level by 2%/70 kg = .03%. For
surgery we want to have 50% factor VIII activity. We can compute the
number of mls as 50% divided by 0.03% bump in factor VIII activity per
ml, which equals 1750 mls of FFP (about 9 units).
Alternatively, we can use a simple formula to reach 50%
factory VIII activity levels as follows:
Preparation
FFP
Cryoprecipitate
Volume
mls per unit
transfused
200
13
Volume required
units transfused
per kg body weight
.12
.24
October 9, 1995
Coagulopathy
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An even easier rule of thumb is that there are about 15 units of FFP in an
adult. To get 50% activity requires about 7.5 units of FFP.
Recombinant Factor VIII:
Recombinant human antihemophilic factor is now commercially available.
Evidently (according to the WWW site of Genetics Institute, Inc) recombinant
Factor VIII is the largest protein ever produced using genetic engineering
technology. Recombinant Factor VIII is very expensive, but the price will likely
drop as more pharmaceutical companies introduce recombinant factor VIII into the
market place. Presently there are two products, Kogenate and Recombinate. There
is probably no reason to use Factor VIII from donors, now that recombinant
Factor VIII is available.
Christmas Disease
Also known as Hemophilia B
Factor IX deficiency
Clinically indistinguishable from hemophilia
Prevalence: 1/10,000
Sex-linked inheritance
Lab:
Bleeding time: normal
PT: normal
PTT: increased
Clotting time: increased
Therapy:
Proplex, Konnyne
Risk of hepatitis has been greatly reduced over past 10 years
through heat sterilization, treatment with detergents, filtering, and
treatment with specific antibodies to remove residual viral particles.
BeneFIX
Recombinant Factor IX
Approved April, 1997
See www.genetics.com for details
von Willebrand's Disease
Clinically: mild form bleeding disorder, associated
with nosebleeds, bruising, increased surgical bleeding, and excessive
menstruation. Clotting factors are OK but platelet function is not.
Three types:
Type 1: Low levels of von Willebrands
factor, but the protein is normal. Autosomal dominant, clinically
mild
Type 2: von Willebrands protein is present
but structurally altered. Autosomal dominant.
2A: Large multimers are absent from
plasma and platelets
2B: Large multimers have
INCREASED affinity for the platelet receptor, resulting in
October 9, 1995
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Uremia
Causes platelet dysfunction
Bleeding time may increase 3 to 4 fold
May be reversible with DDAVP or cryoprecipitate.
Liver failure
In complete failure, patients may require 2 units of FFP every 2 hours to maintain
adequate hemostasis.
Preoperative Drug Therapy:
Warfarin
Factor 7 is the first factor depleted, which is why the PT is affected before the
aPTT.
Warfarin has a half-life of 40 hours.
Warfarin-like effect from broad-spectrum antibiotics, probably from interference
with bacterial flora.
Vitamin K usually corrects a Vitamin K dependent coagulopathy in 6 - 12 hours.
If PT is less than twice normal, it may be safer to operate than to risk the
thrombosis that the patient has been placed on coumarin to prevent.
For emergency surgery, or when vitamin K is contraindicated (e.g. artificial
valvular prosthesis), use 2 units of FFP, then check PT.
Aspirin
Aspirin is in many combination medications, e.g. cold remedies. Patient's may not
realize they have been taking aspirin.
As high as 50% of patients undergoing unexpected surgery have a history of recent
aspirin ingestion.
If patient is otherwise normal, aspirin usually prolongs the bleeding time by 1.5 - 2
minutes. If patient has an undiagnosed, otherwise asymptomatic, disorder (e.g.
heterozygous von Willebrand disease), a single aspirin can increase the bleeding
time to > 30 minutes.
Stop aspirin 3-4 days prior to surgery.
DDAVP is effective in normalizing the prolonged bleeding time caused by aspirin.
If urgent surgery, transfuse platelets at least 90' after the last dose of aspirin to
allow it to clear from the circulation.
Heparin
Binds antithrombin III with thrombin, inactivating thrombin.
Blocks activation of factor X, XI, IX.
Small doses initially inhibit factor IX, which is why the aPTT is prolonged before
the PT is affected.
Can cause thrombocytopenia, which is sometimes profound.
Regional versus General Anesthesia in the anticoagulated patient: (from Cousins)
Epidural:
October 9, 1995
Coagulopathy
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blood is used, and the patient's platelets are used are used instead of micelles.
Not used outside of the O.R. because the test must be run immediately after
drawing the sample.
Useful to subsequently observe the clot for lysis.
INR: (International Normalized Ratio)
PTPatient
Calculated as
. Generally want to have below 1.2
PTNormal
Rapaport Scale:
Level 1:
Level 2:
Level 3:
Level 4:
Blood products:
Whole blood
If less than 5 days old, contains some clotting factors and active platelets
Factors V and VIII start to degrade after 24 hours
Packed red blood cells
Hct: 57-88% (mean: 73%)
Stored at 4 degrees centigrade.
One third of the amount of fibrinogen in whole blood.
Otherwise, contains no significant amounts of clotting factors or platelets.
Platelets
Stored at room temperature.
Platelet levels start to fall after 4 hours of cold storage.
Nearly normal factor levels.
Indications for platelet transfusion:
Platelet count less than 20,000 (except in ITP patients undergoing
splenectomy)
Platelet count less than 60,000-70,000 in patients scheduled for surgery
Patients with a bleeding time greater than 12-15 minutes, regardless of
platelet count.
Patients whose transfused blood volume exceeds about 1.5 blood volumes.
Pump runs greater than 2 hours.
Large tissue injuries may cause a functional defect in platelets, independent of
dilutional and consumptive thrombocytopenia.
Each unit contributes 5000 platelets/ul at 1 hour.
Indications per Stanford QA Program:
Platelet count less than 20,000/mm3
Platelet count less than 50,000/mm3 with active bleeding
Platelet count less than 100,000/mm3, + high risk bleeding (e.g. CNS, eye)
Platelet dysfunction (e.g. uremia) and active bleeding or surgery
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Diagnosis:
Bleeding diathesis
platelet count < 80K
low fibrinogen
elevated fibrin split products
Other lab results:
TT (thrombin time): increased
PT: increased
PTT: increased
Clot time: greater than 10 minutes, shouldn't subsequently lyse.
Marked decrease in factors V, and VIII also.
Treatment:
Treat the underlying disorder
Platelets
FFP
Cryoprecipitate
Concentrated factor I and VIII.
Factors most likely depleted.
Needed in the highest level for adequate hemostasis.
Lost most rapidly from banked whole blood, red cells, and
platelets.
Vitamin K
Nothing may be effective.
Amicar is contraindicated.
"From 4 to 6 h, by which time ongoing surgical bleeding has usually been brought
under control, our data clearly revealed a very close correlation between
coagulation and ... antecedent shock" J. Hewson, et al, Crit Care Med 13:387-391,
1985
Hypothermia
Inhibits platelet function.
Platelet counts decrease.
Decreases enzyme activity leading to clot formation.
Fibrinolytic activity increases.
Acid-base imbalance
Enzymes are sensitive to pH. Anybody have any references to specific acid-base
effects on hemostasis? I couldn't find any references.
Citrate toxicity
Calcium is an essential cofactor for coagulation. However, I could find no
documentation that the serum calcium ever drops so low as to contribute to a
coagulopathy. Any data or references would be appreciated.
Autotransfusion
No associated coagulopathy from recycled blood as long as it is washed.
October 9, 1995
Coagulopathy
Page 16
Extracorporeal circulation:
The pump eats platelets.
Small amounts of fibrin form in the perfusion circuit despite adequate
heparinization.
Neutralize heparin with protamine, 1.0 mg for every 100U of heparin.
Heparin rebound 2-3 hours after protamine, possible from different rates of
elimination of the drugs.
Factors V and VIII are depleted during bypass, but usually not enough to require
FFP.
FFP Contents:
Take contents in plasma (table 1) and adjust for 200 cc!