57. Hereditary hemolytic anaemias.

3 Groups:

1. Membranopathies – based on erythrocytic membranes defects:

1. determined by membrane proteins disorders:

   1. microspherocytic anaemia of Minkovsky-Shoffar;

   2. elliptocytic haemolytic anaemia (ellipticytosis, ovalocytosis);

   3. stomatocytosis;

2. connected with membrane lipids disorders:

   1. acanthocytosis (abetalipoproteinemia manifestation);

   2. anaemia determined by lecitine-cholesterol-acyltranspherase.

1. Enzymopathies – determined by erythrocytes enzymes hereditary disorders:

1. pentose cycle enzymes deficiency- glucose-6-phosphate-dehydrogenase deficiency;

2. glycolysis enzymes defects (11 from 13 existing) – pyruvatekinase is the mostly widely-spread; ATP deficiency leads to Na and water coming to Er and spherocytosis with following phagocytosis;

3. glutathione cycle enzymes deficiency such as glutathionesynthetase, glutathionereductase and glutathioneperoxidase – free-radical lipid oxidation is increased in Er;

4. ATP utilization enzymes deficiency – deficiency of protein components of Na-K-ATPase – Na and water come inside Er.

3. Haemoglobinopathies – due to Hb qualitative changings:

1. Thalassaemia (alpha- and beta-or Kuli’s disease).

2. Circle-celled anaemia (drepanocytosis) with HbS formation – its solubility is less in 100 times comparatively to normal Hb→sedimentation of Hb, Er deformation→Er can’t pass through capillaries, hypoxy, viscosity decreasing→very often – death during first years of life.

58. Acquired haemolytic anaemias.

Reasons:

1. Due to Er mechanic injury:

   1. mechanical haemolysis at vessels or heart valves prosthesis;

   2. “march” haemoglobinuria – Er traumatization in feet capillaries during prolonged march;

   3. microangiopathic haemolytic anaemia (Moshkovich’s disease) – Er injury at their pushing with fibrin fibers – it can be at disseminated intravascular coagulation syndrome.

2. Immune:

   1. alloimmune (isoimmune):

• antibodies coming outside against own ER (new-borned haemolytic disease);

• coming into organism Er against which there are antibodies in plasma (transfusion of blood incompatible by ABO or Rh);

1. autoimmune – due to antibodies formation in organism against own Er because of:

• primary Er changings (autoantigens appearance);

• changings in immune system (immunological tolerance liquidating);

1. heteroimmune (gaptenic) – at side antibodies (gaptenes) fixation on Er surface, particularly medicines (penicillin), viruses.

1. Toxic:

   1. exogenous chemicals: AsH₅, lead, copper salts, phenylhydrasine, resorcine et al.;

   2. endogenous chemicals: biliary acids, products forming at burning disease or uremia;

   3. toxins of biological origin: snake, beer, some spiders.

2. Infectious – haemolytic streptococci, malaria plasmodium, toxoplasma, leushmanias; haemolysis can be caused both by microbs reproducing in Er (plasmodium) and by toxins-haemolysins action (haemolytic streptococci).

3. Acquired membranopathies – haemolytic anaemias occurring as a result of Er membranes defects appearing during ontogenesis:

   1. Markiafava-Mikelli disease or paroxysmal night haemoglobinuria.