Artificial blood and

blood substitute
Dr. Bishowdeep Timilsina
Ass. Prof. General Surgery
ARTIFICIAL BLOOD

 also called Blood Substitute or Blood

Surrogate) is a substance used to mimic
and fulfil some functions of biological
blood
 aims to provide an alternative to blood
transfusion
Physiology of Oxygen transport

 1g Hb binds to 1.39ml of Oxygen

 Oxygen dissociation curve is characteristic
sigmoid shape
Characteristics of an ideal Blood
Substitute
 Deliver oxygen
 Require no compatibility testing
 Have few side effects
 Have prolonged storage capabilities
 Persist in the circulation
 Be cost-effective
History
History

 hemoglobin-basedfluids dates back to the 1920s

when the stroma of the cells was lysed to obtain
hemoglobin.
3 decades (the 1930s, 1940s, and 1950s),efforts
concentrated on stabilizing the hemoglobin
molecule to increase its persistence in the
circulation and to prevent toxic effects.
Blood substitute can be

 Plasma Expanders: either entirely synthetic or

processed from natural proteins that serve as
infusion solutions which expand intravascular
volume ie dextran and hydroxyethyl starch
 RBC Substituents :- these are oxygen carriers
i.e perfluorochemical emulsions and stroma-free
hemoglobin.
Platelet Substitute
InfusiblePlatelet Membranes(IPM)
Thrombospheres
Lysophilized Human Platelets
Dextran

 Introduced in 1944
 polysaccharides produced by the conversion of sucrose
into long glucose polymers by the bacterial enzyme
dextransucrase.
 Clinically used dextran is produced by Leuconostoc
mesenteroides.
 Dextran-40 and Dextran-70 are clinically used.
 Can stored for many years at room temperature either in
powdered form or in solution.
Other physiological effect of dextran

 dextran solutions have antithrombotic effects which

contribute to augmentation of microcirculatory blood flow
 This effect is mediated by two mechanisms:
(1) the viscosity of blood is decreased by hemodilution, as
with any effective volume expander;
(2) low-molecular-weight dextrans specifically inhibit
erythrocytic aggregation and, thus, reverse and prevent
erythrocytic sludging.
 anaphylactic reactions occurring in 0.03% to 0.07%
 larger doses of dextran have been associated with
significant bleeding complications. Precipitation of acute
renal failure has been thought to follow infusion of
dextran, common with Low-molecular-weight dextran
 often reported when renal perfusion is reduced or when
preexisting renal damage is present.
 subsequent difficulty in cross matching blood for
transfusion d/t mediated by the adherence of the
dextrans to antigens on the red cell membrane.
 effective modalities in treating patients with
myocardial ischemia, cerebral ischemia and
peripheral vascular disease and in maintaining
vascular graft patency.
Hydroxyethyl Starch(HES)

 successfully
produced by substituting
hydroxyethyl groups with starch average
molecular weight of 69,000
 eliminated from plasma within two days (half-life
is 17 hours)
 extremely well-tolerated plasma expander, with
adverse effects infrequent and relatively mild;
unlike dextran, HES is not antigenic
 only adverse effect is dose related anti-coagulant
 low doses have no effect on coagulation, whereas
moderate doses (20 ml per kg) can cause platelet counts
decrease transiently
 no evidence of clinical bleeding problems with HES
infusions of as much as 20 ml per kg.2
 occasional elevation of the serum amylase level.
 does not interfere with the typing or cross
matching of blood, and there appears to be no
adverse effect on renal function
 (6% solution in saline) increases plasma volume
from 71 % to 230% of the volume infused
 colloidosmotic pressure remains elevated two to
five days following HES infusion,
RBC substitute

 Main function is to carry oxygen, as natural

hemoglobin
 Two basic approaches to constructing an oxygen
therapeutics
Perflurocarbons(PFC) and its compounds
Stroma free haemoglobin derived from human.
Perfluorocarbons

 8 to 10 carbon fluorinated hydrocarbons.

 immiscible in aqueous solutions, an emulsion suitable for
intravascular infusion
 quite small, with a mean diameter of 0.1 micron, which
contributes to elimination through the alveolar membrane.
 20 times the solubility for oxygen as plasma, significant
volumes of oxygen are still only dissolved at high Pao2
values
 nearly all oxygen dissolved in PFC at arterial oxygen
tensions will be released to peripheral tissues at tissue
oxygen tensions.
 improveperipheral blood flow
by improved microcirculatory
flow.
 Adverse effects includes
transient leukopenia, elevated
liver function test values,
increased pulmonary arterial
pressures, transient hypotension
and pulmonary failure
Fluosol-DA 20%" (Fluosol)

 this emulsion is 20% PFC and uses two PFC molecules,

perfluorodecalin and perfluorotripropylamine.
 Poloxamer 188 (Pluronic F-68) and egg yolk phospholipid
are emulsifying agents, and hydroxyethyl starch is added
to increase oncotic pressure
 stored frozen and infused within 24 hours after thawing.
 its use in cases of ischemic heart disease, cerebrovascular
disease, peripheral vascular disease, wound healing,
microsurgery and cancer therapy.
Advantages of PCF

 Do not react with oxygen

 Inexpensive
 Allow easy transportation of the oxygen to the
body
 They allow increased solubility of oxygen in
plasma
 minimize the effects of factors like pH and
temperature in blood circulation
Disadvantages

 Often causes flu-like symptoms

 Unable to remain mixed as aqueous solutions
 Thrombocytopenia
 theproblem with Fluosal-DA was that they
dissolve less oxygen than pure liquids
PERFLUOROCARBONS
Stroma Free Hemoglobin

 hemoglobin solutions as oxygen-

carrying blood substitutes.
 currently utilized solutions are
generally made from the hemolysis of
washed, outdated, banked, human
packed erythrocytes.
 This hemolysate is then sequentially
crystallized and washed until pure
crystalline hemoglobin is
produced.This protein may be stored
in dry form or it may be reconstituted
into a solution.
 the increased affinity for oxygen by stroma-free hemoglobin solutions
could lead to inadequate release of oxygen to the tissues, even in the
face of adequate circulating volumes of oxygen.
Advantages

 Available in much larger quantities

 Can be stored for long durations
 Can be administered rapidly without typing or
cross matching blood types.
 Can be sterilized via pasteurization. 
Disadvantages

 Short half-life
 Disrupts certain physiological structures,
especially the gastrointestinal tract and normal
red blood cell haemoglobin
 They release free radicals into the body
 Availability and cost
Applications
 Blood substitutes :
 Hemorrhagic shock; hemorrhage (war, surgery);
anaemia.
 Whole-body rinse out : acute drug intoxication; acute
hepatic failure.
 Local Ischemia : acute Myocardial infraction ; evolving
MI; cardiac failure; brain infarction; acute arterial
thrombosis and embolism.
 General Ischemia : CO intoxication. Aid for organ
recovery : acute renal failure; acute hepatic failure;
acute pancreatitis.
  Adjuvant therapy : radiotherapy; chemotherapy
 Perfusional protection of organs during surgery –
cardiopulmonary bypass
 Preservation of donor organ.
 Drug carrier - drug-conjugated haemoglobin and
perfluorochemicals.
  NON CLINICAL APPLICATIONS :- 
 Culture medium Chemical examination - oxygen sensor;
standard solution for oxygen calibrator
 Bioreactor

 PARADOXICAL UTILISAIONS (of high-oxygen affinity) 

Oxygen absorbent  Oxygen pulse therapy for malignant
tumour in combination with radiotherapy or chemotherapy
INFUSIBLE PLATELET MEMBRANE (IPM)

  Produced from outdated human platelets.

 The source platelets are fragmented, virally inactivated,
and lyophilized; they can then be stored up to 2 years.
 for use in patients who have become refractory to platelet
transfusions because of the formation of antibodies to HLA
antigen or platelet antigens. Overall, the product appears
to be safe.
 Cypress Bioscience Incorporated, manufactures an IPM
product that is currently in phase II trials.
THROMBOSPHERES

 Thrombospheres (Hemosphere, Irvine, Calif) are not

platelets.
 They are composed of cross-linked human albumin with
human fibrinogen bound to the surface.
 Experimentally, the thrombospheres appear to enhance
platelet aggregation but do not themselves activate
platelets.
 No evidence of thrombogenicity.
 A similar product, Synthocytes (Andaris Group Ltd,
Nottingham, UK), has just entered into clinical trials in
Europe.
 LYOPHILISED HUMAN PLATELETS

 This product has been under development since the late

1950s.
 PROCESS:-  briefly fixing human platelets in
paraformaldehyde (Kills microbes) prior to freeze-drying
in an albumin solution( increase shelf life)
 The adhesive properties of the platelets appear to be
maintained.
 This product is currently in animal trials.