Do you know about toxicity of blood - HEMATOTOXICITY

 

BLOOD TOXICITY (HEMATOTOXICTY)

The adverse outcomes of exogenous chemical on blood and blood forming tissues are called as blood toxicity which is also referred as Hematotoxicity.  Study of hematotoxicity is labelled as Hematotoxicology.

Types of Hematotoxicity:

On the basis of its affecting nature it can categorized into two types,

Ø  Primary hematotoxicity:

Direct involvement of one of or more blood component is termed as primary hematotoxicty. Xenobiotic drugs have tendency to precipitate out primary hematotoxicity.

Ø  Secondary hematotoxicity:

When toxic effects are the resultant of systemic disturbance and tissue injury that ultimately affect the blood and blood forming tissue, are called as secondary hematotoxicity.

Examples of Blood toxicity:

      HEMOLYTIC ANEMIA:

Hemolytic anemia is disorder in which destruction of red blood cells exceeds the production rate of red blood cells. Antibiotics used to treat leprosy and malaria (dapsone and primaquine) contain amine group that have greater tendency to cause methemoglobinemia and hemolytic anemia.

Effects:

Aromatic nitro compound enter in redox cycle and formed reactive specie in RBCs i.e. hydrogen peroxide. Redox cycle initiate from N-hydroxyl metabolite through hemoglobin oxidation. This reactive specie oxidize the cytoskeleton of red blood cell and destroy the RBCs membrane which can be visualized as Heinz bodies under microscope.

Abnormally shaped RBCs formed from aromatic amines that are asymmetrical, round, egg shape, sickle shape and round with spiny projections that are termed as anisocytes, spherocytes, elliptocytes, drepanocytes and acanthocytes respectively.

Free amines are absorbed dermally and causes serious effects when directly contact with skin. More hazardous effects cause by aromatic amine are hemorrhagic cystitis (bleeding from bladder damage) and bladder cancer.

Individuals with G6PD deficiency expose with aromatic compound results in life threating condition because they don’t have tendency to formed reduced glutathione in red blood cells. Reduced glutathione are scavenger of hydrogen peroxide (reactive oxygen species) produced in redox cycle. These individual do not combat with oxidation of reduced glutathione to glutathione Disulphide and GS-S protein.

Treatment:

 Treatment options for chemically induced hemolytic anemia are limited

1.      Methylene blue should be use, it potentiate the ability of methemoglobin reductase which reverse the methemoglobin formation back to ferrous haemoglobin.

2.      For replacement of red blood cell count, blood transfusion should be required.

3.      Supportive treatment should be given in mild anemic condition. Also, low levels of methemoglobin 30% or less do not remove red blood cell extensively and cause anemia.

 

      AUTOIMMUNE HEMOLYTIC ANEMIA:

It have different mechanism from hemolytic anemia. Here the immunoglobins IgG and IgM bind with RBCs and attract the complement towards itself. Afterwards complement bind to the RBCs surface and start destruction of RBCs membrane, RBCs burst and hemoglobin comes out of the cell. Intravascular hemolysis provoke the serious outcome of autoimmune hemolytic anemia, condition known as disseminated intravascular coagulation (DIC)

Treatment:

1.      Its treatment variate along with cause. Autoimmune hemolytic anemia caused by prescription drugs but most of time it is consider idiosyncratic. Standard treatment is high dose corticosteroid, if not managed then managed with azathioprine and cyclophosphamide.

2.      Blood transfusion is required in severe cases.

3.      If patient failed to respond above mentioned anti-inflammatory therapy then monoclonal antibody anti CD-20 rituximab is given.

 

      BONE MARROW SUPPRESSION:

Occupational chemicals like benzene and drugs for example Chloramphenicol (an important antibiotic used to treat resistant bacterial infections) Phenylbutazone (ant inflammatory used to treat arthritic conditions) Procainamide (an antiarrhythmic used to control cardiac arrhythmias) Allopurinol (a drug used to treat gout) Tolbutamide (used to treat maturity onset or type II diabetes) Methyldopa (an antihypertensive used to treat high blood pressure) Sulindac (anti-inflammatory agent) have tendency to cause blood dyscrasias i.e. neutropenia, thrombocytopenia and pancytopenia.

If patient deficient in myeloid series it will face severe internal hemorrhaging. For proper management and treatment first rule out the cause and manage specifically after the cessation of bone marrow suppressing agent.

      OTHER TYPES OF HEMATOTOXICITY: some other hematotoxicity that indirectly affect the RBCs are cyanide and hydrogen sulphide poisoning. Their toxic effects are specific to high oxygen demanding tissues of cardiovascular and nervous system. At toxic dose (100 mg of cyanide) it bind to the heme portion of haemoglobin and stop the energy production by mitochondrial heme oxidase. Amyl nitrate or sodium nitrate (IV) are the antidote of these two respiratory poison.