Page 329 - Textbook of Pathology, 6th Edition

The etiology of cold antibody remains unknown. It is seen In each type of drug-induced immunohaemolytic 313
in the course of certain infections (e.g. Mycoplasma anaemia, discontinuation of the drug results in gradual
pneumonia, infectious mononucleosis) and in lymphomas. disappearance of haemolysis.
2. Paroxysmal cold haemoglobinuria (PCH). In PCH, cold
antibody is an IgG antibody (Donath-Landsteiner antibody) Isoimmune Haemolytic Anaemia
which is directed against P blood group antigen and brings Isoimmune haemolytic anaemias are caused by acquiring
about complement-mediated haemolysis. Attacks of PCH are isoantibodies or alloantibodies by blood transfusions,
precipitated by exposure to cold. pregnancies and in haemolytic disease of the newborn. These
PCH is uncommon and may be seen in association with antibodies produced by one individual are directed against
tertiary syphilis or as a complication of certain infections such red blood cells of the other. These conditions are considered
as Mycoplasma pneumonia, flu, measles and mumps. on page 340.

CLINICAL FEATURES. The clinical manifestations are due
to haemolysis and not due to agglutination. These include B. MICROANGIOPATHIC HAEMOLYTIC ANAEMIA
the following: Microangiopathic haemolytic anaemia is caused by
1. Chronic anaemia which is worsened by exposure to cold. abnormalities in the microvasculature. It is generally due to CHAPTER 12
2. Raynaud’s phenomenon. mechanical trauma to the red cells in circulation and is
3. Cyanosis affecting the cold exposed regions such as tips characterised by red cell fragmentation (schistocytosis). There
of nose, ears, fingers and toes. are 3 different ways by which microangiopathic haemolytic
4. Haemoglobinaemia and haemoglobinuria occur on anaemia results:
exposure to cold. 1. EXTERNAL IMPACT. Direct external trauma to red
Treatment consists of keeping the patient warm and blood cells when they pass through microcirculation, espe-
treating the underlying cause. cially over the bony prominences, may cause haemolysis
during various activities e.g. in prolonged marchers, joggers,
LABORATORY FINDINGS. The haematologic and karate players etc. These patients develop haemoglobi-
biochemical findings are somewhat similar to those found naemia, haemoglobinuria (march haemoglobinuria), and
in warm antibody AIHA except the thermal amplitude. sometimes myoglobinuria as a result of damage to muscles.
These findings are as follows:
1. Chronic anaemia. 2. CARDIAC HAEMOLYSIS. A small proportion of
patients who received prosthetic cardiac valves or artificial
2. Low reticulocyte count since young red cells are affected grafts develop haemolysis. This has been attributed to direct
more. mechanical trauma to the red cells or shear stress from
3. Spherocytosis is less marked. turbulent blood flow.
4. Positive direct Coombs’ test for detection of C3 on the
red cell surface but IgM responsible for C3 coating on red 3. FIBRIN DEPOSIT IN MICROVASCULATURE.
cells is not found. Deposition of fibrin in the microvasculature exposes the red
5. The cold antibody titre is very high at 4°C and very low cells to physical obstruction and eventual fragmentation of
red cells and trapping of the platelets. Fibrin deposits in the
at 37°C (Donath-Landsteiner test). IgM class cold antibody small vessels may occur in the following conditions:
has specificity for I antigen, while the rare IgG class i) Abnormalities of the vessel wall e.g. in hypertension, Introduction to Haematopoietic System and Disorders of Erythroid Series
antibody of PCH has P blood group antigen specificity.
eclampsia, disseminated cancers, transplant rejection,
haemangioma etc.
Drug-induced Immunohaemolytic Anaemia ii) Thrombotic thrombocytopenic purpura.
Drugs may cause immunohaemolytic anaemia by 3 different iii) Haemolytic-uraemic syndrome.
mechanisms: iv) Disseminated intravascular coagulation (DIC)
v) Vasculitis in collagen diseases.
1. αα α α α-METHYL DOPA TYPE ANTIBODIES. A small All these conditions are described in relevant sections
proportion of patients receiving α-methyl dopa develop separately.
immunohaemolytic anaemia which is identical in every
respect to warm antibody AIHA described above.
C. HAEMOLYTIC ANAEMIA FROM
2. PENICILLIN-INDUCED IMMUNOHAEMOLYSIS. DIRECT TOXIC EFFECTS
Patients receiving large doses of penicillin or penicillin-type Haemolysis may result from direct toxic effects of certain
antibiotics develop antibodies against the red blood cell-drug agents. These include the following examples:
complex which induces haemolysis.
1. Malaria by direct parasitisation of red cells (black-water
3. INNOCENT BYSTANDER IMMUNOHAEMOLYSIS. fever) (Fig. 12.22).
Drugs such as quinidine form a complex with plasma 2. Bartonellosis by direct infection of red cells by the
proteins to which an antibody forms. This drug-plasma microorganisms.
protein-antibody complex may induce lysis of bystanding 3. Septicaemia with Clostridium welchii by damaging the red
red blood cells or platelets. cells.