HEMOSTASIS & SURGICAL

BLEEDING
Dr. Rufon
July 3, 2013
Group 7
Case: A 26 y.o. male came in the ER with a
2cm stab wound on the right forearm.
How are we to manage this patient?
STOP BLEEDING!!
-foremost in our management
A. History of Present Ilness
NOI- Nature of Incidence
TOI- Time of Incidence
DOI- Date of Incidence
POI- Place of Incidence
What happened?
This is a case of stub wound Assult or
Contact?
Asault- there was an external force which
caused the wound
Contact the pressure will not as much as in
the assault
B. Past Medical History
ask for:
History of spontaneous bleeding
Family history if bleeding
Bleeding after a minor operation
Untoward bleeding during major
surgical procedure
Prior history of transfusion
C. Screening tests for Hemostasis
(Preoperative Evaluation of
Hemostasis)
Level I
History- negative
Nature of procedure/operationrelatively minor
No screening test is recommended

blood smear or CBC

PTT

Level III
History- suggestive of defective
hemostasis
Procedure/Operation- hemostasis may
be impaired
* operations using pump oxygenation
or cell savers
Post-operative bleeding could be
detrimental even if bleeding is minimal
(ex: Neurosurgical procedures)
Request:
Platelet count -assess platelet
Bleeding time function
Ptt
-evaluate coagulation
Aptt
Fibrin clot screen abnormal
fibrinolysis
Patient with a hemostatic problem
-most likely visit doctor
What IM specialty can a patient go to aside
from a Hematologist?
for Malignancy- Oncology
for Hepatic problem Gastroenterologist
for Kidney problem nephrologist
Level IV
History highly suggestive of
hemostatic defect
Hepatologic consult is necessary
Hematologic clearance is needed
Request:
Platelet count -assess platelet
Bleeding time function
Ptt
-evaluate coagulation
Aptt
Fibrin clot screen abnormal
fibrinolysis
aPTT & Platelet aggregation- check
in case of emergency; to detect
dysfibrinogenemia or a circulating
anticoagulant.

Level II
History is negative
(back to the case) We are now zeroing
Nature of procedure/operation- planned
in with Classical Hemophilia
*significant bleeding is not expected
- caused by Factor VIII deficiency
but
may present with
Request:
platelet count

Hemearthrosis- Orthopedic consult

Epistaxis- EENT consult
Hematuria- Urology
Intracranial bleeding neurosurgery
Gastrointestinal bleeding general surgery

Observation for more bleeding

PHYSIOLOGIC PROCESSES OF
HEMOSTASIS
1.
2.
3.
4.

There is still active bleeding

D. Additional Management

Vasoconstriction
Platelet function
Coagulation
Platelet function

Mechanical intervention
a.
Digital/Direct pressure
-applied over the bleeding area
-least traumatic intervention
b. Tourniquet
- applying pressure distally from the
wound
c. Gravitational suits
-in special centers
Thermal intervention
a. Cautery
- Denaturation of proteins
b. Cooling
-vasoconstriction

a.
b.
c.

Chemical factors
Vasoconstrictor
Pro-coagulant
Hygroscopic property

Does suturing affect hemostasis?

(aside from cosmesis)
*Hemostasis may also be achieved with
suturing.
E. Medication
Tetanus immunization TT 0.5; Ig
250IU, IV on diff sites
Antibiotics
Analgesics
F.

Other plans
Pressure dressing
-using a Fluffy dressing
-crumpled (make a ball out of it) then
apply
-distributes pressure more evenly
Elevation

1.

Vascular Constriction
initial response to vessel injury
more pronounced in vessels with
medial smooth muscles and is
dependent on local contraction of
smooth muscle
begins prior to platelet adherence as a
reflex response to various stimuli

Vasoconstrictors:
Thromboxane A2 (TXA2)
- produced at the site of injury via
the release of arachidonic acid
from platelet membranes
- potent constrictor of smooth
muscle.
Endothelin
- synthesized by injured
endothelium
- Serotonin (5-hydroxytryptamine)
- released during platelet
aggregation are potent
vasoconstrictors
Bradykinin and Fibrinopeptides
- involved in the coagulation
scheme but are capable of
contracting vascular smooth
muscle

*extent of vasoconstriction varies with

the degree of vessel injury
2.

Platelet Plug Formation

Platelets
- anucleate fragments of
megakaryocytes.
- normal count:150,000- 400,000/ L
- average life span of 7 to 10 days
- removed by spleen
- llife span of 7-10 days
- forms a hemostatic plug and
contributes to thrombin formation
2 processes:
I. Reversible: Primary Hemostasis
1. Injury to the intimal layer in the
vascular wall exposes subendothelial
collagen to which platelets adhere
2. Platelet adhesion by the action of von
Willebrand's factor (vWF)
a. vWF- a protein in the
subendothelium which binds to
glycoprotein I/IX/V on the
platelet membrane
2. Platelets initiate a release reaction that
recruits other platelets from the
circulating blood to seal the disrupted
vessel.
*This process is reversible, not associated
with secretion, and not affected by heparin.
*Principal mediators:
Adenosine diphosphate (ADP)
Serotonin
II. Irreversible
- second wave of platelet aggregation
results to compaction of the platelets
into a plug (irreversible)
Fibrinogen
-required as a cofactor
-acting as a bridge for the glycoprotein
IIb/IIIa receptor on the activated platelets
the release reaction produces:
ADP
Ca2+
Serotonin
TXA2

-granule proteins
Thrombospondin
- secreted by the -granule stabilizes
fibrinogen binding to the activated
platelet surface and strengthens the
platelet-platelet interactions
Platelet factor 4 (PF4)- potent heparin
antagonist
-thromboglobulin

*This part is inhibited by aspirin and NSAIDs,

by cyclic adenosine monophosphate (cAMP),
and by nitric oxide.
After the release reaction,
- alterations occur in the phospholipids
of the platelet membrane allowing
calcium and clotting factors to bind to
the platelet surface, forming
enzymatically active complexes.
*altered lipoprotein surface
a.k.a. platelet factor 3
3.

Coagulation/ Fibrin Clot Formation

Coagulation refers to a cascade of zymogen

activation that ultimately results in the
cleavage of fibrinogen to insoluble fibrin that
stabilizes the platelet plug.
I. Intrinsic pathway
- begins with factor XII and through a
cascade
of enzymatic reactions activates factors
XI, IX, and VII in sequence.
- all of the components leading
ultimately to fibrin clot formation are
intrinsic to the circulating plasma and
no surface is required to initiate the
process
II. Extrinsic pathway
- requires exposure of tissue factor on
the surface of the injured vessel wall to
initiate the arm of the cascade
beginning with factor VII.
- The two arms of the coagulation
cascade merge to a common pathway
at factor X, and activation proceeds in
sequence of factors II (prothrombin)
and I (fibrinogen).
- Clot formation occurs after proteolytic
conversion of fibrinogen to fibrin.

Factor VIIIa combines with factor IXa

= intrinsic factor complex
-which is responsible for the bulk of
the conversion of factor X to Xa
Factor Xa combines with factor Va
=prothrombinase complex
-which is responsible for converting
prothrombin to thrombin.
*(ss with) VIIIa-IXa complex
prothrombinase is significantly more
effective at catalyzing its substrate
than is factor Xa alone

Thrombin is formed
- leaves the membrane surface and
converts fibrinogen by two cleavage
steps into fibrin and two small peptides
termed fibrinopeptides A and B.

Removal of fibrinopeptide A permits

end-to-end polymerization of the fibrin
molecules

Cleavage of fibrinopeptide B allows

side-to-side polymerization of the fibrin
clot
- facilitated by thrombin-activatable
fibrinolysis inhibitor (TAFI) which acts
to stabilize the resultant clot.

Regulation of Coagulation
1. feedback inhibition on the coagulation
cascade, which deactivates the enzyme
complexes leading to thrombin
formation
2. mechanisms of fibrinolysis allow for
breakdown of the fibrin clot and
subsequent repair of the injured vessel
with deposition of connective tissue.
*aPTT
activated partial thromboplastin time
-evaluates Intrinsic pathway
*PT
-prothrombin time
- evaluates Extrinsic pathway
4.

Fibrinolysis
Fibrin clot undergoes clot lysis, which
permits restoration of blood flow
Plasmin- degrades the fibrin mesh at
various places, which leads to the

production of circulating fragments that

are cleared by other proteases or by
the kidney and liver.
Initiated at the same time as the
clotting mechanism under the influence
of circulating kinases, tissue activators,
and kallikrein.
Fibrin is degraded by plasmin produces
plasminogen.
- may be converted by one of
several plasminogen activators:
o tPA
synthesized by endothelial
cells and released by the
cells on thrombin
stimulation as single-chain
tPA. This is then cleaved
by plasmin toform twochain tPA.
o uPA
Bradykinin, a potent endotheliumdependent vasodilator cleaved from
high molecular weight kininogen by
kallikrein
causing:
- contraction of nonvascular
smooth muscle
- increases vascular permeability
- enhances release of tPA
Both tPA and plasminogen bind to fibrin
as it forms, and this trimolecular
complex cleaves fibrin very efficiently.
After plasmin is generated it cleaves
fibrin, somewhat less efficiently, and it
also will degrade fibrinogen.
Plasminogen activation may be
initiated by activation of factor XII,
which leads to the generation of
kallikrein from prekallikrein and
cleavage of high molecular weight
kininogen by kallikrein.

*2-antiplasmin
-inhibits plasmin
-a protein that is cross-linked to fibrin by
factor XIII
*E-nodules and D-dimers
-fibrin degradation products
-from clot lysis
*TAF
-final inhibitor

- a procarboxypeptidase that is activated by

the thrombin-thrombomodulin complex.
-enzyme removes lysine residues from fibrin
that are essential for binding plasminogen.
TRANSFUSION
Volume per Volume Replacement
-only true for GI losses not for blood loss
How much blood is lost to cause hypotension?
-40% blood loss

Replacement Therapy
*Cross-matching
-Serologic compatibility for A, B, O, and Rh
groups is established routinely
-matching of donors' red blood cells and
recipients' sera (the major cross-match) is
performed
Types of Blood
Banked Whole Blood
-once the gold standard, is rarely available
-shelf life -6 weeks
-at least 70% of the transfused erythrocytes
remain in the circulation for 24 hours after
transfusion and are viable
- stored at 4C
-storage life 35 days
-60 days- 50% RBCs survive
-Poor source of platelets
-Factors II,VII, IX, XI are stable
-Factor VIII rapidly deteriorates
Chemical changes:
1. Increase in lactate
2. Increase in potassium
3. Increase in ammonia
4. Decrease in pH
*for repeated transfusions- serum drawn less
than 48 hours before crossmatching should
be used
Fresh whole blood
-blood that is administered within 24 hours of
its donation
-provides greater coagulation activity than
equal units
of component therapy
Packed Reed Blood Cells
-prepared by removing most of the
supernatant plasma after centrifugation

-reduces, but does not eliminate, reaction

caused by plasma components
-reduces the amount of sodium, potassium,
lactic acid, and citrate
administered
70% of volume of whole blood
Frozen Red Blood Cells
-not available for use in emergencies
-used for patients who are known to have
been previously sensitized reduce risk of
infusing antigens to which patients have
previously been sensitized
*freezing RBCviability is theoretically
improved, and the ATP and 2,3diphosphoglycerate concentrations are
maintained
Leukocyte Reduced and Leukocyte
Reduced/Washed Red Blood Cells
-prepared by filtration that removes
approximately 99.9% of the white blood cells
and most of the platelets (leukocyte-reduced
red blood cells), and if necessary, by
additional saline washing (leukocytereduced/washed red blood cells)
-Leukocyte reduction prevents almost all
febrile, nonhemolytic transfusion reactions
(fever and/or rigors), alloimmunization to HLA
class I antigens, and platelet transfusion
refractoriness and cytomegalovirus
transmission
Platelet Concentrates
-for thrombocytopenia caused by massive
blood loss and replacement with platelet-poor
products, thrombocytopenia caused by
inadequate platelet production, and
qualitative platelet disorders
-shelf life of platelets is 120 hours from time
of donation
-1 unit of platelet concentrate is 50mL
*Platelet preparations are capable of
transmitting infectious diseases and can
provoke allergic reactions similar to those
caused by blood transfusion.
-Therapeutic levels of platelets reached after
therapy are in the range of 50,000 to
100,000/L.
-platelet transfusion thresholds can safely be
lowered in patients who have no signs of
hemostatic deficiency and who have no
history of poor tolerance to low platelet
counts

Fresh Frozen Plasma (FFP)

-prepared from freshly donated blood
-usual source of the vitamin Kdependent
factors
-only source of factor V
-carries infectious risks similar to those of
other component therapies
factors V and VIII require plasma to be
fresh or freshly frozen
Risk of hepatitis is the same as that of
whole blood or packed RBCs
Human Polymerized Hemoglobin
(Polyheme)
- universally compatible, immediately
available, disease-free, oxygen-carrying
resuscitative fluid
-been successfully used in massively bleeding
patients when red blood cells were not
transfused
-Advantages of an artificial oxygen carrier:
*absence of blood-type antigens (no
cross-match needed) and viral infections
*long-term stability, which allows
prolonged periods of storage
-Disadvantages:
*shorter half-life in the bloodstream
*potential to increase cardiovascular
complications
Indications for Replacement of Blood
and Its Elements
Improvement in Oxygen-Carrying
Capacity
Treatment of Anemia
Volume Replacement
* Volume expanders
-lactated Ringers solution can be
administered in amounts 2-3 times the
estimated blood loss
-Dextran or lactated Ringers solution with
albumin can be used for rapid plasma
expansion
Blood loss of 20% - can be replaced by
crystalloids
Blood loss of more than 20% - require the
addition of packed red blood cells and FFP

Group 7
References:
-Dr. Rufons slides
-Previous Notes
-Audio
-Chapter 4 in Schwartzs Principles of
Surgery 9th ed