I divide up the haemolytic anemias like this:
A] Hemolytic anemias due to intrinsic properties of the red cell.
A red cell consists of three things: hemoglobin, membrane and a few enzymes. Things can go wrong with any of these to cause hemolysis. Mostly they are congenital conditions.
1 Hemoglobin problems. The most important is sickle cell disease, but there are many other polymorphisms that shorten red cell survival.
2 Membrane problems. Hereditary spherocytosis; hereditary elliptocytosis and the one acquired problem, paraoxysmal nocturnal hemoglobinuria.
3 Enzyme pathway problems. Red cells gain their energy by breaking down glucose (glycolysis). They lack the citric acid cycle and have to make do with the Embden-Meyerhof pathway that turns glucose into pyruvate. There are many enzymes on this pathway but only two important ones as far as hemolytic anemia is concerned, and both relate to little by-passes. About 10% of the traffic travels on the first by-pass, which has the purpose of generating hydrogen ions. It is known alternatively as the Hexose Monophosphate Shunt or the Pentose Phosphate Pathway.
The chief enzyme along it is Glucose 6-phosphate dehydrogenase (G-6PD). Around 250 million people in the world have a defect in their G-6PD. Hydrogen ions are needed by the cell to turn NADP to NADPH and thus to reduce glutathione. The normal activity of the cell leaves it susceptible to oxidation and the reduced glutathione prevents this. It is seldom that there is no G-6PD, but commonly there is no enough. Certain environmental agents increase the oxidative stress on a cell. Chief among these are anti-malarials and suphonamides. Dapsone can cause a hemolytic anemia in mormal people, such is the oxidative stress that it produces. In Mediterranean types of G-6PD deficiency Fava beans can cause the oxidative stress (I'm not sure about a good Chianti, though).
The second by-pass is called the Rappaport-Lubering Shuttle, which has the purpose of producing a chemical called 2,3,DPG. This is necessary for hemoglobin to be able to release oxygen to the tissues. The more 2,3,DPG, the easier it is to do this. The important enzyme here is pyruvate kinase. If it is absent then there is more 2,3,DPG and it is easier to get oxygen to muscles. There are only about 200 people in the world with this deficiency.
All the other enzyme deficiencies are so rare that you have to be a super-specialist even to have heard of them. The next commonest has 6 people affected in the world.
B] Hemolytic anemias due to extrinsic factors.
The most important of these are antibodies which come in warm and cold types. I shall discuss these at length at a later time.
Otherwise I tend to think of them under the headings of animal, vegetable and mineral.
There are few animals that cause hemolytic anemia and they are mostly very small, namely the malarial parasite and the bacteria Bartonella spp and Clostridium Welchii. Otherwise there are a few poisonous animals including snakes and spiders.
Vegetables include fava beans that we have mentioned and the poison ricin from the Castor Oil plant.
The mineral causes are mainly drugs, which again I will deal with separately. A special mention goes to water. I remember seeing a man with very severe hemolysis who had been swept through the drainage system of a local lake. He never recovered from his fresh-water drowning. Salt water would not have done the same thing. Finally we have hot and cold to remind us of burns and teh cold antibody symdromes.
Another way of classifying hemolytic anemia is to think about intravascular and extravascular hemolysis. Extravascular hemolysis releases free hemoglobin into the circualtion and causes renal failure accompanied by severe symptoms. The cause are incopatible blood transfusion, paroxysmal cold hemoglobinuria and paroxysmal nocturnal hemoglobinuria, microangiopathic hemolytic anemias, fresh water drowning, some toxins, severe G-6PD deficiency especially after some drugs or beans, severe AIHA, some forms of unstable hemoglobinopathies, and march hemoglobinuria. This last is caused by the squashing of red blood cells in the small vessels of the feet as they slap against the tarmac. It is a problem in long distance runners and schizophrenics who repeatedly slap their heads with the palms of their hands! All the rest are intravascular hemolytic anemias.
Yet another way of classifying hemolytic anemias is by what you see down the microscope. Spherocytes are formed when bits of membrane are chewed off. it happens mostly in the spleen to red cells coated with antibody, or with a membrane lacking the protein spectrin or to cells whose membrane has been damaged by the enzyme lecithinase, produced by the bacterium Clostridium Welchii. The cell assumes the shape with the largest volume and the smallest surface area, namely a sphere. The exit doors from the spleen are only two microns wide, but a sphere cannot squeeze itself through so small a gap, the way that a biconcave disc can, so spherocytes are doomed to a splenic death.
Fragmented cells are seen in anemias where the red cells are mechanically damaged. this can be from fibrin strands in the circulation, such as occur in disseminated intravacular coagulation and microangiopathic hemolytic anemias (thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, malignant hypertension, toxemia of pregnancy, meningococcal septicemia) or by mechanical heart valves or arterial grafts. The anemia can be acute (and usually intravascular) or chronic (also intravascular but without the symptoms) and likely to result in iron deficiency with stainable iron in the urine.