Blood and blood cells can be negatively impacted by toxins, known as haemotoxicology. Toxins may cause anemia through decreased red blood cell production or increased destruction. They can also lead to issues with white blood cells like neutropenia or increased infection risk, and problems with platelets such as thrombocytopenia or altered clotting function. Understanding these toxic responses is important for hematology and evaluating chemical safety.

1. TOXIC RESPONSES
OF BLOOD
RVS Chaitanya Koppala
Assistant professor
Vignan Institute of Pharmaceutical Technology

2. TOXIC RESPONSES OF BLOOD AND BLOOD CELLS
Blood is circulating blood fluid that provides body with nutrition, oxygen and waste removal.it
maintains homeostasis and fights infections.to perform all these functions blood cells are
produced at fast rate of 1-3 million cells per second. These characteristic makes hematopoietic
tissue vulnerable to certain kinds of drugs, particularly those interfere with cellular respiration
and division, and to secondary effects of toxic agents. When blood components are directly
affected, the toxicity is regarded as primary and where damage occur as a consequence of other
tissue injury or systemic disturbance.it is called secondary toxicity. the study of adverse effects
of exogenous chemicals on blood and blood forming tissue is called haemotoxicology. To
understand haemotoxicology it is essential to understand the blood components, their purpose
and the site of production.
1. TOXICOLOGY OF ERYTHROCYTES
Erythrocytes (RBC) constitute of 40-45% of circulating blood volume and serves to transport
O2 and CO2 to and from tissue. Since RBCs also act as barrier for all chemicals entering the
body, they are very sensitive to the presence of such chemicals in the body. The chemical cause
change in structure, production, function and even survival of erythrocytes. This in turn leads
to change in erythrocytes volume in blood which can very dangerous. A decrease in
erythrocytes volume due to toxins is more common and is known anemia. Anaemia is due to
either decreased production or increased destruction of erythrocytes. Increase in erythrocytes
volume is known as erythrocytosis. This is essentially thickening of the blood and is less
commonly caused by toxins.
a) Alternation in erythrocytes productions: production of erythrocytes is a continuous
process involving frequent cell division and high rate to hemoglobin synthesis. Xenobiotics
that interfere with these processes cause a change in cell production.
Different types of anemia are due to abnormalities in erythrocytes synthesis. Hemoglobin
is tetramer consisting of 2 alpha and 2 beta globulin chains with heme groups present at top
of each chain. A heame group consist of an iron atom and porphyrin ring.

3. Type Cause Xenobiotic involved
Congenital thalassemia Defect in globin chain synthesis
Sideroblastic anemia Defect in synthesis of porphyrin
ring of heme
Chloramphenicol, ethanol,
zinc or lead intoxication
etc.
Iron deficiency anaemia Dietary deficiency or increased
blood flow
Antacids, aspirin, lead
intoxication, alcohol
abuse
Megaloblastic anemia Deficiency of folate or vit B12. It is
characterized by hypocellular bone
marrow that produce megaloblast.
Antimetabolites,
neomycin, colchine,
zidovudine.
Aplastic anemia Injury to bone marrow and
hemopoietic tissue. It is
characterized by the presence of
hypocellular bone marrow and
pancytopenia
Allopurinol,
chloramphenicol,
phenylbutazone,
diclofenac, penicillin.
b) Alternation in the respiratory function of erythrocytes: the respiratory function of
erythrocytes is impaired by binding of other ligands to the binding sites as seen in carbon
monoxide poisoning. Some chemicals like sodium nitrate, aniline, mercaptans etc.,
change hemoglobin so that it cannot bind to oxygen. This condition is called
methemoglobinemia.
c) Alternation in erythrocytes survival: normal life span of erythrocytes is 120 days.
However, in any case of any insult that increase oxidative injury. Reduces metabolism
or alter the membrane integrity, erythrocytes concentration decreases and a
corresponding anaemia is produced. Examples includes mechanical injury, inhalations
of gaseous chemicals like arsenic, infectious diseases etc.
2. TOXICOLOGY OF LEUCOCYTES:
 Leucocytes includes granulocytes (basophils, neutrophils and eosinophils), the
monocytes and the lymphocytes. They are primary responsible for engulfing and
destroying foreign bodies.
 Toxic effects on granulocytes are wide and varied. Similar to erythrocytes, high
proliferation rate of neutrophils makes them particularly sensitive to the presence of
toxins in their blood. They are susceptible to chemical having antimitotic action. For

4. instance, anticancer agents often suppress the immune system. Agents that effect both
neutrophils and monocytes pose a greater risk of infection to patients. Drugs and
chemicals are also known to alter the function of erythrocytes.
 Examples:
a) alcohol, glucorticoids and iohexol and ioxaglate components of radiographic contrast
media impair phagocytosis.
b) acne treatment with zinc salts impairs chemotaxis
usage of parenteral heroin reduces superoxide production.
 Agranulocytosis is of particular concern.it is idiosyncratic and characterized by a
neutrophil count of less than 500uL. xenobiotic induced agranulocytosis is sudden.
Concomitant with drug exposure and persists as long as the causative agent is in the
system. Neutropenia is caused by xenobiotics. Example includes ampicillin, lidocaine,
allopurinol, rifampicin etc.
 Exposure to drugs and chemical is reported to cause leukemia. Alkylating agents used
for cancer treatment can cause acute myelogenous leukemia (AML) and
myelodysplastic syndrome (MDS). Exposure to high dose X or gamma radiation is also
known as cause leukemia other agents includes 1,3-butadiene, formaldehyde, cigarette
smoking etc.
3. TOXICOLOGY OF PLATELETS:
 The hemostasis system consists of circulating platelets, different plasma proteins and
vascular endothelial cells, it functions to prevent blood loss from sites of vascular injury
and to maintain circulating blood in a fluid state.
a) Toxic effects on platelets:
 Platelets are important for the formation of stable hemostatic plug. Xenobiotics alter the
platelet response by reducing platelet count to less than 10,000/uL (thrombocytopenia)
or affecting platelet functions.
 Thrombocytopenia is caused by decreased production or increased destruction of
platelets. It is a common manifestation of heparin. Beta lactam antibiotics and intensive
chemotherapy.
 Thrombotic thrombolytic purpura is a sudden onset of thrombocytopenia, a
microangiopathic hemolytic anemia and multisystem organ failure. This syndrome
occurs due to infectious disease or certain drug like clopidogrel, mitomycin, ticlopidine
etc. Some drug used to reduce the risk of thrombosis produce platelet dysfunction. Drugs

5. that alter platelet function include beta blockers, NSAIDS, beta lactam antibiotics,
antihistamines and psychotropic drugs.
b) Toxic effects of fibrin clot formation:
 Protein involved in fibrin clot formation are synthesized in the liver.so any agent
that impairs hepatic function causes decrease in production of coagulation factors.
 Vitamin K is essential for the complete synthesis of factors II, VII, IX and X. agent
that interfere with vitamin K absorption lead to deficiency of these factors and
subsequent bleeding.
 Xenobiotics cause certain antibodies to develop which complex with coagulation
proteins and are rapidly cleared from the circulation leading to deficiency of clotting
factors.