Physiology and Biology of

Hemostasis and Transfusion

Wendi Rachman

Biology of Hemostasis
Process to prevents or terminates blood loss
4 major events:
Vascular constriction
Platelet plug formation
Fibrin formation
Fibrinolysis

Vascular Constriction

Initial vascular response, before any

platelet adherence
Occurs even at capillary level
Linked to platelet plug formation
- TXA2
- endothelin
- Serotonin, 5-HT - bradykinin &
fibrinopeptides
Also affected by the surrounding
tissue pressure

Platelet Function
2 pathways:
1. Forming hemostatic plug
2. Contributing to thrombin formation

Platelet Function
Normally do not adhere
Forming a plug when vascular disruption
occurs
Adhere to subendothelial collagen in 15
seconds
Requires vWF that binds to GP I/IX/V on the
platelet membrane
Also mediated by interaction between
collagen and GP IaIIa on the platelet surface

Platelet Function
Expand and develop pseudopodal and also
recruits other platelets to aggregates
This process is reversible and also known as
primary hemostasis
ADP and serotonin are the principal
mediators in this process
PGI2, ASPIRIN, and NSAIDs act to inhibit this
process.

Platelet Function
Properties of the endothelium related to
hemostasis and thrombosis
ANTITHROMBOTIC

PROTHROMBOTIC

Antiplatelet activities

Platelet-activating properties
Endothelin production
von Willebrand factor production
Procoagulant properties
Tissue factor production
Binding of clotting factors
Fibrinolysis inhibition
Plasminogen activator inhibitor-1
production
Endothelial-mediated vasoconstriction
Endothelin production
Endothelial barrier function

Prostacyclin production
Nitric oxide production
Ecto-ADPases

Anticoagulan activities

Thrombomodulin protein C
Heparan sulfate antithrombin

Fibrinolytic activation

Plasminogen activator production

tPA
uPA

Platelet Function
In the second wave, platelet discharge
ADP, Ca+ and granule
Fibrinogen required as a bridge for the
GP IIbIIIa receptor on the activated
platelets
The process made platelets compact to
form amorphous plug, and no longer
reversible

Platelet Function
Thrombospondin stabilizes fibrinogen binding
to the activated platelet surface
thrombo globulin and PF4 inhibit
plasminogen activation
The second wave inhibit by NSAIDs, cAMP
and nitric oxide
This process also allowed calcium and
clotting factor to bind to the platelet surface

Coagulation
2 pathways:
Intrinsic (factor, XII, XI, IX, VIII)
- requires no surface to initiate
- prolongation aPTT is associated with
abnormal function of this pathway
Extrinsic (factor VII, X, II, I)
- requires exposure of tissue factor on the
surface of the injured vessel to initiate
- prolongation PT is associated with
abnormality of this pathway

Coagulation

Coagulation
Vit K and warfarin use affect factor II,
VII, IX, X
Platelet number or function can be
insufficient to adequately support
coagulation

Fibrinolysis
Fibrin degraded by plasmin, a serine protease
derived from the proenzyme plasminogen
Plasminogen converted by plasminogen
activators (e.g tPA, uPA)
Plasmin cleaves fibrin and degrade fibrinogen
Several characteristics of enzymatic reactions
ensure that the process occurs at controlled
rate and at the site of the clot

Fibrinolysis
Plasmin inhibit by 2 antiplasmin, a protein
which is crosslinked with factor XII
TAFI also inhibit fibrinolytic system by
removes lysine residues, that are essential
for binding plasminogen
Clot lysis yields fibrin degradation products
including E-nodules and D-dimers

Hemostatic Defects
CONGENITAL
Coagulation factor deficiencies
- Hemophilia
deficiencies factor VIII (A), factor IX (B), factor
XI
sex linked recessive disorders
- von Willebrands disease
deficiency factor VIII
autosomal dominant disorders

Hemostatic Defects
ACQUIRED
Platelet abnormalities
ITP, TTP
Acquired hypofibrinogenemia
Defibrinogen syndrome
Primary fibrinolysis
Myeloproliperative disorders
Coagulopathy of liver disease
Acquired coagulation inhibitors
Other disease
Paraprotein disorders
Hypersplenism

DIC
Syndrome: Enhanced fibrin forming
Impaired fibrin degradation
Lab : Prolonged PT, aPTT, Low platelet
count, fibrin degradation result
Th/ : Plasma and platelet concentrate
Heparin and low molecular weight
heparin

Anticoagulation and Bleeding

Spontaneous bleeding may be a complication of
anticoagulant therapy
It may present only with ecchymoses or even GI tract
bleeding.
Surgical treatment can be undertaken without
discontinuing the anticoagulant program
Laboratory finding
- aPTT les than 1,3 control in a heparinized patient
- INR less than 1,5 in a patient on warfarin
Patient who have been heparinized as treatment of
DVT, can still be operated within several hours delay
or for more rapid reversal, 1 mg of protamine sulfate
for every 100 units heparin most recently
administered

Anticoagulation and Bleeding

Cardiopulmonary bypass
overheparinization, heparin rebound, inadequate
protamine neutralization, protamine excess and
thrombocytopenia all have been indicate as causes of
excessive bleeding in patient undegoing
cardiopulmonary bypass

Local Hemostasis
Mechanical procedures
the oldest method is digital pressure, than develop to hemostat
generally ligature or a hemoclip replaces hemostat as permanent
method on effecting hemostasis of a single disrupt vessel
1st century Aulus Cornelius Celsus devise the use of ligature
1552 Pare rediscovered the principle of ligature
1800 Philip Sying Phsick employ absorbable suture
1858 Simpson introduce fine wire suture, 1881 Lister used catgut
1900 Halsted indicated the advantages of non absorbable silk
1911 Cushing use silver clips to effect hemostasis in areas that
are hard to reach
Recently introduced Harmonic scalpel, an instrument that cuts
and coagulates tissue via vibration at 55 kHz

Local Hemostasis
Thermal Agents
Heat achieves hemostasis by denaturation of protein that result in
coagulation of large are of tissue
The electrocautery can be AC or DC
Local cooling has been applied to control bleeding from the eroded
mucosa of the eophagus and stomach, direct cooling with iced saline
is effective but may provoke hypothermia
Cryogenic procedure, at tempertures of -20 C, tissue, capillaries and
arterioles undergo necrosis

Chemical Agents
Epinephrine
1911 Cushing use skeletal muscle, shortly thereafter hemostatic
fibrin was introduced
Gelatin, oxydized cellulose, oxydized regenerated cellulose and
micronized collagen are the most widely used

Transfusion
Backgound
1667 Jean-Baptiste Denis and Emmerez
transfused sheep blood into 15 y.o boys
1668 transfusion in humans were forbidden
unless approved by a Faculty of Medicine in
Paris
1900 Landsteiner introduce the ABO concept
1939 Levine and Stetson found Rh group

Replacement Therapy
Typing and Crossmatching
Blood typing established by he antigen
on the surface of the RBC, wherethere
A, B, A and B, or none.
Crossmatching between the donors red
blood cells and the recipients sera is
perform to establish the serologic
compatibility

Replacement Therapy
Replacement Blood type
Fresh whole blood
blood that administered within 24hr
Banked whole blood
rarely indicated, because after 24hr of
storage there are some changes in
blood components, pH, ions

Replacement Therapy
Packed red cells
product of choice for most clinical situations,
removing most of supernatant plasma and reduce
potassium, sodium, lactic acid and citrate
Washed red cells
is the standard red cells product in most western
nations
Leukocyte reduction reduce non hemolytic
transfusion reactions
Platelet concentrates
should be used within 120hr of donation

Replacement Therapy
Frozen plasma
prepared from freshly donated blood
source of Vit K, factor II,IX,XI
Dextran
combination of serum albumin and lactated Rigers
solution
max 1L/d
Concentrates and DNA recombinant technology
anti hemophilic concentrates (factor VIII, factor IX) and
albumin
PolyHeme
human polymerized hemoglobin

Indications of Replacement Therapy

GENERAL INDICATIONS
Improvement in Oxygen-Carrying Capacity
1988 National Institutes of Health Consensus Report
Hb less than 10 g/dl or Ht less than 30%
Volume replacement
in patient with normal preoperative value:
Blood loss up to 20% replaced with crystalloid
Blood loss up to 50% replaced with crystalloid and
PRC
Blood loss above 50% receive same components
plus FFP

Methods of Administration
Routine administration
usually 5ml/min for 1st min then 1020ml/min
Other methods
intramedullary or intraperitoneally

Complications
HEMOLYTIC REACTIONS
incompatibility of ABO and Rh groups
the most common symptoms are heat and
pain along the entrance vein, flushing face,
pain in the lumbar region, and constricting
chest pain
Stop immediately, insert Foley catheter, urine
alkalinizing, diuretics
If oliguria or anuria occur, treat like renal
failure

Complications
ALLERGIC AND FEBRILE
May occur after administration of any blood product
Antihistamines, epinephrine, or steroids
BACTERIAL SEPSIS
Contaminated blood or blood bag
Stop immediately, blood culture, O2and antibiotics
EMBOLISM
SUPERFISCIAL THROMBOPHLEBITIS
OVERTRANSFUSION AND PULMONARY EDEMA
Avoidable by measuring CVP
Symptom are arise in venous pressure, dyspnea, couhg, rale at
the lung bases
Stop immediately, diuretics, placing the patient in sitting position,
intensive pulmonary support, sometimes intubation
TRANSMISSION OF DISEASE

Evaluation of the Surgical Patient as a

Hemostatic Risk
PREOPERATIVE

Patients history
1. Prolonged bleeding or swelling after biting the li or
tongue
2. Bruises without apparent injury
3. Prolonged bleeding after dental extraction
4. Excessive menstrual bleeding
5. Bleeding problems associated with major or minor
operatives
6. Medical problems receiving a physicians attention
within the past 5 year
7. Medications including aspirin or remedies for
headache taken within past 10 days
8. A relative wit a bleeding problem

Laboratory findings (PT, aPTT, INR, Platelet count)

Evaluation of the Surgical Patient as a

Hemostatic Risk
EVALUATION OF EXCESSIVE
INTRAOPERATIVE OR POST OPERATIVE
BLEEDING
Maybe the result of the following factors:
1. Ineffective local hemostasis
2. Complications of blood transfusion
3. A previously undetected hemostatic defect
4. Consumptive coagulopathy
5. Fibrinolysis