Download Coagulation

Coagulopathy
October 22, 1997
Steven L. Shafer, M.D.
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.
Patient is on heparin for DVT, 6 weeks following a small PE:
How risky is it to stop the heparin?
When should the heparin be stopped prior to surgery?
Is regional anesthesia contraindicated?
Would an axillary block be contraindicated?
How would assess residual heparin effect in the O.R.?
Is safe to reverse heparin with protamine prior to a regional anesthetic?
3.
Patient takes warfarin for chronic atrial fibrillation:
When should the warfarin be stopped?
How does warfarin affect the bleeding time, PT, aPTT, ACT?
Should vitamin K be administered?
If major surgery (e.g. AAA repair) is planned, should FFP be administered
prophylactically? If so, how much?
How about the patient taking warfarin for a mechanical aortic valve?
4.
Patient has a history of hemophilia:
What is the clinical spectrum of this disease?
How does factor VIII level relate to clinical disease?
What factor VIII levels are necessary for surgery?
What contains factor VIII?
What does not contain factor VIII?
How does hemophilia affect the bleeding time, PT, aPTT, ACT?
5.
Patient has a history of Christmas disease:
What is the clinical spectrum of this disease?
How common is it?
What factor IX level is necessary for surgery?
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What contains factor IX? What else is this used for?
How does this disease affect the bleeding time, PT, aPTT, ACT?
6.
Patient has a history of Von Willebrand's disease.
What is the clinical spectrum of this disease?
How common is it?
Why is it important to know the subtypes?
How does this disease affect the bleeding time, PT, aPTT, ACT?
What therapy might be helpful preoperatively?
What therapy might be helpful should bleeding develop intraoperatively?
What drugs should they avoid?
Intraoperative Scenarios:
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?
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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
Normal
(mg%)
Required
(mg%)
Half-life
at 4 degrees
Stability
I
II
III
IV
V
VI
VII
VIII
IX
X
XI
XII
XIII
150-350
70-130
70 (50%)
20 (30%)
4 days
2-5 days
stable
stable
70-130
5 (10%)
12 hours
7 days
70-150
50-200
70-130
70-130
70-130
40-150
50-200
20 (30%)
30 (60%)
20 (30%)
10 (15%)
20 (30%)
0 (0%)
1 (2%)
300 min
17 hours
40 hours
40 hours
60 hours
stable
7 days
stable
stable
7 days
stable
stable
fibrinogen
prothrombin
thromboplastin
calcium
proaccelerin
activated 5
proconvertin
antihemophilic
Christmas
Stuart
PTA
Hageman
fibrin stabilizing
12 days
Vitamin K dependent factors:
II, VII, IX, X
(Not to be confused with the cranial nerves that carry parasympathetic fibers:
III, VII, IX, X)
Platelets:
Thrombocytopenia is the most commonly identified coagulation defect.
Maintain platelet count above 50K. Transfuse platelets if platelet count is between 50
and 100K and abnormal bleeding is observed
It is difficult to decrease the platelet count to less than 50k with a normal bone marrow.
Preoperative platelet count correlates with the amount of blood which can be lost prior to
developing thrombocytopenia.
Platelets will probably be needed after 1.5 blood volumes. If medical bleeding develops,
platelets are the first choice in the absence of laboratory identification of the cause of
bleeding.
3-6 units of platelets have about 1 unit of plasma, which contains 50% of usual V, VIII
October 9, 1995
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and 80% of other factors.
Platelets lasts 5-7 days at room temperature.
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
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Hemophilia
Factor VIII deficiency
Prevalence: 1/10,000 to 1/25,000
Sex-linked inheritance
Factor VIII
Level
<1%
3-5%
10-15%
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
Factor VIII activity
activity units/ml
infusate
1
8
Volume
mls per unit
transfused
200
13
Volume required
units transfused
per kg body weight
.12
.24
The transfused units/kg can be calculated as follows:
FFP: 50% (target) /2% (bump in activity units/kg) x 1 unit transfused/200
activity units  0.12 transfused units/kg
Cryo: 50%/2% (bump/kg) x 1 unit transfused/13 mls x 1 ml/8 units factor VIII
activity  0.24 transfused units
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Thus, to reach 50% activity levels, a 70 kg adult requires 9 units of FFP (volume
= 1800 mls, or 17 units of cryoprecipitate (volume = 221 mls). DDAVP raises
factor VIII levels by 2-3 times normal, may be all that is necessary in some mild
cases. Danazol (an anabolic steroid) also raises factor VIII levels and has been
used, in combination with Amicar, in mild hemophiliacs to avoid transfusions
prior to surgery.
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.
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Clotting factors are OK but platelet function is not.
Three types:
Type 1: Low levels of von Willebrand’s factor, but the protein is
normal. Autosomal dominant, clinically mild
Type 2: von Willebrand’s 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 rapid clearance from the
plasma
Pseudo von Willebrand’s: looks like 2B, but the
problem is not with von Willebrand’s factor, but
with the platelet receptor that has INCREASED
affinity for the von Willebrand’s factor. End result
is the same: rapid clearance of von Willebrand’s
factor from plasma.
Type 3: von Willebrand’s protein is absent. Autosomal recessive.
Types 2 and 3 are most severe.
Lab:
Bleeding time: prolonged
PT: normal
PTT: normal
Clotting time: normal or prolonged
Lab results may be normal and repeated testing required to
establish diagnosis. Tests such as the ristocetin cofactor, antibody
assay to the von Willebrand’s factor, ristocetin-induced platelet for
aggregation (RIPA), FVIII assay, and bleeding time are used to
separate types I, 2, and 3.
Treatment:
Cryoprecipitate
FFP transfusion has a sustained beneficial effect.
DDAVP 0.3 to 0.4 mcg/kg normalizes bleeding time for Type 1
and 2A von Willebrand’s
Contraindicated in type 2B and pseudo von Willebrand’s
disease because it will cause platelet aggregation and
thrombocytopenia.
Amicar and Cyclokapron are useful for 5-7 days after bleeding
episodes.
Miscellaneous Factor Disorders
Factor I deficiency (fibrinogen)
sex-linked inheritance
PT: increased
PTT: increased
Factor VII deficiency
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autosomal recessive
Bleeding time: normal
PT: prolonged
PTT: normal
Factor X deficiency (Stuart factor)
Bleeding time: increased
PT: increased
PTT: increased
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
October 9, 1995
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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:
Only 1 case in which an epidural hematoma followed an epidural anesthetic when
coagulation status was normal.
100 cases of spontaneous epidural hematomas in anticoagulated patients with no
history of instrumentation of the epidural space.
Two studies, with 4164 patients receiving heparin during and after (but not
before) surgery found no incidence of epidural hematomas (Oberg & Thoren, Acta
Physiol Scand 85:164, 1972; Rao & El-Etr, Anesthesiology 55:616, 1981). The
catheter was placed the night prior to surgery.
Avoid epidurals if platelet count is less than 100,000, or if the bleeding time is
greater than 8 minutes.
If a patient brought to the O.R. is on heparin, "epidural block is not used in any
form."
Key is to look for evidence of neurologic sequelae, and than rapidly
evaluate it and decompress the spinal cord should sequelae develop.
Spinal:
Gross abnormality in blood clotting mechanisms is considered to be an absolute
contraindication to spinal anesthesia. Minor abnormalities (e.g. mini-dose heparin
prior to surgery) is a relative contraindication to spinal anesthesia.
Tests of hemostasis:
WATCH FIELD FOR BLEEDING!
Whole blood clotting time
a red top tube in your pocket
should clot in less than 15 minutes
clot dissolution (especially within 20 minutes) suggests DIC
can be done in O.R.
PT
Monitors extrinsic pathway (factor VII)
Used for warfarin monitoring because first factor depleted is factor VII.
aPTT
Measures intrinsic pathway.
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Responds to heparin effect first because of heparin's inhibition of factor IX.
Usually just called the PTT, but it is actually a different test.
PTT is not done routinely any more.
Factor XII activation is variable and can skew results dramatically.
Includes contribution of platelets (in the form of platelet factor 3)
Phospholipid micelles mimic the platelet function in the PTT.
"activated" to shorten the time of the test and eliminate the variable activation of
factor XII. Citrated plasma is mixed with diatomaceous earth, which converts XII
into active XIIa. After mixing everything together (plasma, phospholipid
micelles, diatomaceous earth), the clot is timed from the addition of CaCl2 to the
formation of clot.
ACT (activated clotting time)
Measures same pathway (intrinsic) as the aPTT.
May be a better measurement of in vivo activity because the whole, uncitrated,
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:
Negative history, minor operation. No tests necessary.
Negative history, major operation. aPTT and platelet count.
Suspicious history, or operation which requires unusually good
hemostatic function (e.g. open prostatectomy, bypass): platelet
count, aPTT, PT, Bleeding time.
Known coagulation defect: specific factor assays.
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.
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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
Acute massive bleeding
Splenectomy, may give 20 units preoperatively
For ECMO or CPB within 24 hours of procedure.
Fresh Frozen Plasma
Major justification is to give factor VIII.
Factor VIII rapidly synthesized in response to injury.
Maintain PT between 12 and 15.
Consider FFP after 1.5 - 2 blood volumes.
Not indicated for:
Volume expansion
To reconstitute pRBCs.
Routine administration of FFP is increasingly controversial.
Your body contains about 12 units of FFP. Thus, 12 units of FFP should fully
restore normal coagulation.
Indications per Stanford QA Program:
Congenital coagulation disorders, liver disease, Coumadin overdose
DIC, nephrotic syndrome, newborn hemorrhagic diathesis, septic shock,
protein losing enteropathy, plasmapheresis, newborn exchange
transfusion, thrombotic thrombocytopenic purpura, hemolytic uremic
syndrome
"Suspected coagulopathy due to deficiency of soluble coagulation factors
in a patient who is bleeding where coagulation studies are pending at the
time of infusion."
During surgery or active bleeding if PT > 18, PTT > 45
"Active bleeding with blood loss > 20%"
During CPB or ECMO with TT > 17
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"Other indications."
Cryoprecipitate
Major justification is to give factor VIII.
Also useful in von Willebrand’s
Factor VIII: 80 units
Fibrinogen: 230 mg
Other factors: none is significant quantities.
Fibrinogen is stable in banked blood. If fibrinogen is low, it is very unlikely to be
from dilutional coagulopathy, since pRBC, FFP, and platelets all contain
fibrinogen. Therefore, low fibrinogen is probably from DIC.
shelf life: 6 months
Usual indication is severe hypofibrinogenemia from DIC
Indications per Stanford QA Program:
Documented Factor VIII deficiency
History of prolonged APTT
Von Willebrand's disease
Hypofibrinogenemia and active bleeding
Active bleeding in a uremic patient
During CPB or ECMO with TT > 17, reptilase clotting time > 14
DIC or Septic Shock
"Other indications."
Recombinant Factor VIII:
Kogenate and Recombinate
Factor IX Concentrates
Contain factor II, VII, IX, X (the vitamin-K dependent factors).
May also contain activated factors, and can cause thrombotic complications with
intense use.
Use only for documented factor IX deficiency, or for bleeding
unresponsive to other measures, as infusion itself can lead to DIC!
Might be useful as a specific antidote to warfarin, except that the risk of hepatitis
approaches 100%, and FFP works well for restoring vitamin-K dependent factors.
Trade names: Proplex, Konyne
Recently approved recombinant factor IX: BeneFIX
Indications per Stanford QA Program:
Documented factor II, VII, IX, X deficiency in bleeding or surgical patient
Documented high Factor VIII inhibitor in bleeding or surgical patient
PT > 1.5 times normal
DDAVP (vasopressin)
Yes, I know it is not a blood product, but I didn't know where else to put it.
Increases factor VIII and von Willebrand's factor by releasing them from
endothelial cells.
Factor VIII levels may peak 2-3 times higher than baseline.
Second dose within 48 hours of first dose will have reduced response because
October 9, 1995
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intercellular stores must be replenished.
May normalize Taspirin induced coagulopathy.
May correct uremic coagulopathy.
Reduces postoperative blood loss following cardiac surgery
Buy stock today.
Fibrinolytics
Aprotinin
Nonspecific serine protease inhibitor extracted from bovine lung.
Discovered in 1930
Contact activation during CPB
mediated by kallikrein system
activation of intrinsic pathway on contact with pump material
causes thrombin formation
impairs platelet adhesive function
High dose blocks contact activation
protects platelet adhesive receptors
preserves platelet aggregation
in synergy with heparin, prevents thrombin formation
Low dose: just blocks fibrinolysis, cheaper drugs may do just as well
Raises ACT as an artifact.
Maintain ACT >750?
Perhaps us a different test of heparin activity.
Reserved for complex cases with long anticipated CPB time. At Stanford
often used for “redo” surgery.
Synthetic antifibrinolytic amino acids:
Epsilon-Aminocaproic acid (EACA)
para aminomethylbenzoic acid (PAMBA)
tranexamic acid
Useful to treat excessive bleeding following cardiac surgery
Only action is antifibrinolysis, no protective effect as found with
aprotenin
Amicar is often used in routine cardiac surgery to reduce transfusion
requirements.
Rational Transfusion Therapy: Does it exist?
Mathematically, 30% of the original blood elements are still present after 1 blood volume
of hemorrhage and replacement. Clinically, the percentage is closer to 40%.
"Routine replacement of clotting factors and platelets based on the volume of blood
transfused is difficult to justify" - John Collins (Former Chairman, Stanford Department
of Surgery), World J. Surg. 11:75-81, 1987
"Clearly red cell transfusions should be freely supplemented with platelet and/or
concentrated coagulation components for the correction of underlying hemostatic
October 9, 1995
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deficiencies if such are considered contributory to hemorrhage." V. Lovric, Anaesth
Intens Care 12:246-251, 1984.
"It would be wasteful to administer platelets prophylactically to all patients for a
condition that, at most, may affect only one out of 16 (6.25%) of those with massive
transfusion, and for a condition that is so readily and effectively treated when it occurs."
R. Reed, Ann Surg 203:40-48, 1986
"There appears to be no clear advantage to the prophylactic infusion of platelets in
comparable patients ... who receive massive transfusions but do not have medical
bleeding." C Harrigan, et al, 98:836-843, 1985
"The mathematics of exchange transfusion would support the contention that specific
hematologic derangements attributable to massive transfusion per se should not become
critical until a patient has received a transfusion volume of approximately twice his
estimated blood volume." T Phillips, J Trauma 27:903-910
"Important principles include ... the administration of platelets to trauma patients ...
receiving 12 or more units of rapid transfusion, especially those who have been truly
massively transfused with volumes of 20 units or more; and the administration of FFP to
those receiving large volumes of factor free fluids." T Phillips, J Trauma 27:903-910
"Where the wound is large .... or where there is head injury, [we recommend]
administration of FFP ... on a one-to-one ratio with pRBC to avoid dilutional
coagulopathy." J Hewson, et al, Crit Care Med 13:387-391, 1985
"Pending controlled studies in man, the routine use of plasma supplementation in the
resuscitation regimen for hemorrhagic shock should be abandoned." D. Martin, et al, Ann
Surg 202:505-511, 1985
"Although the concentrations of factor V and particularly factor VIII are reduced in stored
whole blood, concentrations in massively transfused patients do not correlate with the
number of transfusions and remain sufficiently high to support the coagulation cascade.
Concentrations of other soluble coagulation factors are not affected by massive
transfusions of stored whole blood." in "Massive Transfusion" (chapter 56), from
Hemostasis and Thrombosis, 1987.
I was unable to find any studies which justify a cookbook approach to platelet and FFP
administration. As the above quotations indicate, there is controversy within the surgical
and anesthetic literature regarding routine administration of these products. However, the
clinical reality is that, in the massively transfused patient, relevant laboratory data may
not be available when the decision is made to treat what appears to be medical bleeding.
Rational therapy involves a trade off between an intellectually satisfying approach
(administer dangerous drugs only for clear indications) and the time constraints of
resuscitating a patient who is bleeding to death. Rational therapy is also an explicit
October 9, 1995
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admission that in situations in which there are no useful therapeutic options for the
patient, treating ourselves may still be in the patient's best interest. Also, the O.R. is not a
rational place to debate transfusion policy with the surgeons.
Rough Guidelines:
Monitor the surgical field for evidence of medical bleeding
If that is observed and is causing you or the surgeons concern, in the
absence of other data, administer platelets.
After 1 blood volume:
Check whole blood clotting time
Check ACT
Send off PT, aPTT, platelet count, and fibrinogen level.
Order platelets
After 1.5 blood volumes:
Repeat whole blood clotting time, ACT
Order FFP
Specific situations:
Massive transfusion
Dilutional thrombocytopenia is the most likely cause of medical bleeding.
Rarely, bleeding may be caused by a deficiency in factors V of VIII.
Very rarely, bleeding from dilution of other factors.
If fibrinogen is low, it is probably because of DIC and not from dilution.
Disseminated intravascular coagulation
Refractory coagulopathy is common after massive transfusions and probably
caused by prolonged hypotension, hypoperfusion, and vascular damage.
Fibrinogen is rapidly consumed by thrombin, producing fibrin.
Fibrin is rapidly degraded by plasmin, producing fibrin split products.
Fibrin split products interfere with clot formation.
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
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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.
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:
October 9, 1995
Coagulopathy
Take contents in plasma (table 1) and adjust for 200 cc!
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