Haemolysis due to drugs and chemicals

Haemolysis due to drugs and chemicals

Haemolysis due to drugs and chemicals

This can be caused by :

1. Direct toxic action.
    -> Naphthalene.
    -> Nitrobenzene.
    -> Phenacetin.
    -> Lead.

Heinz bodies are seen in abundance.

2. Drug action on G-6-PD deficient RBC
3. Immunological mechanism which may be : 
    -> Drug induced  autoantibody haemolysis, Antibodies are directed against RBC.
    -> Hapten-cell mechanism where antibodies are directed against which is bound to cell surface e.g. Penicilin.

Related Questions HAEMATOLOGY


-As part of pancytopenia.
-Steroid administration.

Megaloblastic anaemia

Metabolism: B12(cyanocobalamin) is a coenzyme in DNA synthesis and for maintenance of nervous system. Daily requirement 2 micro grams. Absorption in terminal ileum in the presence gastric intrinsic factor. It is stored in liver mainly-

Folic acid (Pteroylglutamic acid) is needed for DNA synthesis.. Daily requirement 100 micro grams. Absorption in duodenum  and jejunum

Causes of deficiency .-

- Nutritional deficiency-
- Malabsorption syndrome.
- Pernicious anaemia (B12).
- Gastrectomy (B12).
- Fish tapeworm infestation (B12).
- Pregnancy and puerperium (Folic acid mainly).
- Myeloproliferative disorders (Folic acid).
- Malignancies (Folic acid).
- Drug induced (Folic-acid)


(i) Megaloblastic anaemia.
(ii) Glossitis.
(iii) Subacute combined degeneration (in B12deficiency).

Blood picture :

- Macrocytic normochromic anaemia.
- Anisocytosis and poikilocytosis with Howell-Jolly bodies and  basophilic stippling.
- Occasional megalo blasts may be-seen.
- Neutropenia with hypersegmented neutrophills and macropolycytes.
- Thrombocytopenia.
- Increased MVC and MCH with normal or decreased MCHC.

Bone marrow:

- Megaloblasts are seen. They are larger with a more open stippled chromatin. The nuclear maturation lags behind. the cytoplasmic maturation. Maturation arrest is seen (more of early forms).
- Immature cells of granulocyte series are also larger.
 -Giant stab forms (giant metamyelocytes).

Iron deficiency anaemia.

Absorption of iron is affected by :
- Iron stores.
- Rate of erythropoiesis
- Acid pH aids absorption.
- Phosphates and phytates in diet impair absorption.

Causes  of deficiency:

- Increased demand:
o    Growth (in children)
o    Menstruation, Pregnancy, lactation.
- Inadequate intake and absorption.
o    Dietary deficiency.
o    Achlorhydria or gastrectomy.
o    Malabsorption states.

- Chronic blood loss
o    Peptic ulcer, bleeding piles
o    Menorrhagia.
o    Hook worm infestation

- Anaemia.
- Koilonychia.
- Atrophic glossitis and angular stomatitis.
- Dysphagia-Plummer Vinson syndrome.

Blood findings:

- Microcytjc_hypochromic cells, ring cells and pessary cells.
- Anisocytosis and poikilocytosis.
- Low MCV. MCH and MCHC.
- Serum iron is low but iron binding capacity is increased

Bone marrow

Erythroid hyperplasia with imcronormoblasts. Iron stains reveal depleted stores

Differential  diagnosis .-

- Sideroblastic anaemia which is also microcytic hypochromic  but there is excess iron in the erythroid cells .Some are pyridoxine responsive.
- (ii) Thalassaemia


Normal homeostasis depends on

 -Capillary integrity and tissue support.

- Platelets; number and function

(a) For integrity of capillary endothelium and platelet plug by adhesion and aggregation

(b) Vasoactive substances for vasoconstriction

(c) Platelet factor for coagulation.

(d) clot retraction.

- Fibrinolytic system(mainly Plasmin) : which keeps the coagulatian system in check.

Coagulation disorders

These may be factors :

Deficiency .of factors

  • Genetic.
  • Vitamin K deficiency.
  • Liver disease.
  • Secondary to disseminated intravascular coagulation.or defibrinatian

Overactive fibrinolytic system.

Inhibitors of  the factars (immune, acquired).

Anticoagulant therapy as in myocardial infarctian.

Haemophilia. Genetic disease transmitted as X linked recessive trait. Comman in Europe. Defect in fcatorVII  Haemophilia A .or in fact .or IX-Haemaphilia B (rarer).


  • May manifest in infancy or later.
  • Severity depends  on degree of deficiency.
  • Persistant woundbleeding.
  • Easy Bruising with Haemotoma formation

Nose bleed , arthrosis, abdominal pain with fever and leucocytosis

Prognosis is good with prevention of trauma and-transfusion of Fresh blood or fTesh plasma except for danger of developing immune inhibitors.

Von Willebrand's disease. Capillary fragility and decreased factor VIII (due to deficient stimulatory factor). It is transmitted in an autosomal dominant manner both. Sexes affected equally

Vitamin K  Deficiency. Vitamin K is needed for synthesis of factor II,VII,IX and X.

Deficiency maybe due to:

Obstructive jaundice.


Gut sterilisation by antibiotics.

Liver disease results in :

Deficient synthesis of factor I II, V, Vll, IX and X  Incseased fibrinolysis (as liver is the site of detoxification of activators ).

Defibrination syndrome. occurs when factors are depleted due to disseminated .intravascular coagulation (DIC). It is initiated by endothelial damage or tissue factor entering the circulation.


Obstetric accidents, especially amniotic fluid embolism. Septicaemia. .

Hypersensitivity reactions.

Disseminated malignancy.

Snake bite.

Vascular defects :

(Non thrombocytopenic purpura).

Acquired :

Simple purpura a seen in women. It is probably endocrinal

Senile parpura in old people due to reduced tissue support to vessels

Allergic or toxic damage to endothelium due to  Infections like Typhoid Septicemia

Col!agen diseases.


Uraemia damage to  endothelium (platelet defects).

Drugs like aspirin. tranquillisers, Streptomvcin pencillin etc.

Henoc schonlien purpura Widespeard vasculitis due to hypersensitivity to bacteria or foodstuff

It manifests as :

Pulrpurric rashes.


Abdominal pain.

Nephritis and haematuria.

Hereditary :

(a) Haemhoragic telangieclasia. Spider like tortous vessels which bleed easily. There are disseminated lesions in skin, mucosa and viscera.

(b) Hereditary capillary fragilily similar to the vascular component of von Willbrand’s disease

.(c) Ehler Danlos Syndrome which is a connective tissue defect with skin, vascular and joint manifestations.

Platelet defects

These may be :

(I) Qualitative thromboasthenia and thrombocytopathy.

(2) Thrombocytopenia :Reduction in number.

(a) Primary or idiopathic thrombocytopenic purpura.

(b) Secondary to :

(i) Drugs especially sedormid

(ii) Leukaemias

(iii) Aplastic-anaemia.

Idiopathic thrombocytopenic purpura (ITP). Commoner in young females.

Manifests as :

Acute self limiting type.

Chronic recurring type.


(i) Spontaneous bleeding and easy bruisability

(ii)Skin (petechiae), mucus membrane (epistaxis) lesions and sometimes visceral lesions involving any organ.

Thrombocytopenia with abnormal forms of platelets.

Marrow shows increased megakaryocytes with immature forms,

vacuolation, and lack of platelet budding.


hypersensitivity to infective agent in acute type.

Plasma thrombocytopenic factor ( Antibody in nature) in chronic type

Multiple myeloma.

Blood picture:

- Marked rouleaux formation.
- Normpcytic normochromic anaemia.
- There may be leucopenia or leucoery!hrohlastic reaction.
- Atypical plasma cells may be seen in some patients
- Raised ESR
- Monoclonal hypergammaglobulinaemia 
- If light chains are produced in excess, they are excreted in urine as bence jones protein

Bone marrow

- Hyper cellular
- Plasma cells from at least 15 – 30% atypical forms and myeloma cells are seen.