Hémolyse

The hémolyse is the destruction of the red Globules (G.R.) releasing the Hémoglobine (Hb) in the Blood plasma. In the long term a regenerative Anémie appears.

Definition

the haemolytic anemias are those caused by an accelerated destruction of the red globules (G.R.) .

This definition is imperfect, for 2 reasons:

On the one hand , the phenomenon of a shortening of average globular survival is observed in the majority of the feeble states, whatever their cause. Often this anomaly is so discrete that its description requires techniques refined like the method of marking with radioactive chromium: it is the case in the ferriprive Anémie and the majority of the medullary insufficiencies. Other times the haemolytic note are sufficiently marked to result in light a Hyperbilirubinémie and a Subictère: as for example in the Anemia of Biermer or weakens pernicious and Saturnisme weakens. However, these affections are not described among haemolytic anemias because the globular destruction is not the main cause of the feeble state .
In addition , any shortening of globular survival does not involve anemia fatally. This one occurs only when osseous marrow is unable sufficiently to increase its production of G.R. to entirely compensate for the losses due to the hémolyse. Apart from any diminution of the medullary potential, marrow can increase up to 4 or 5 times its production of G.R. It result from it that anemia should normally occur only when the average survival of the G.R. becomes lower than a score of days (normally the lifespan of a G.R. is 120 more or less 10 days). If marrow is in a defective state, the least shortening of average globular survival will cause an anemia: it is in particular the case during the weakens pernicious of Biermer. According to the cases, the hémolyse can thus be compensated or décompensée.

Clinical symptoms of the haemolytic states

It is advisable to separately describe the acute haemolytic episode and the chronic state of hyperhémolyse.

1) Symptoms of the acute haemolytic crisis: one will be able to take as example the acute hémolyse caused by an incompatible transfusion.

a) acute pains , generally compared with Ache S, occur particularly on the level:

of the Lombe S = symmetrical areas located behind abdomen, on each side of the spinal column (drawing the attention to the kidneys),
of the Abdomen (sometimes giving place to one diminishes abdominal which is likely to cause a Laparotomie),
of the Membre S (that the patient describes as being coiled blows),
and in the form of Céphalée S .

b) shivers and a abrupt rise of the temperature are the consequence of the release of substances Pyrogène S coming from the destroyed G.R.

the temperature can go up until 40°C in the serious cases (p. e.g. in the crisis of Malaria).
It is interesting to note that any transfusion of blood, even perfectly tolerated, usually causes a thermal rise of some tenth of degrees.

c) The weakness, the Prostration, of the Hypotension, the Tachycardia, of nauseas (and sometimes of the vomiting), of the diarrhea are symptoms of a state of shock. This shock can be serious and especially, it can become, together with the Hémoglobinurie which will follow, a cause of Néphropathie acute Tubulaire, even of necroses Corticale kidneys.

d) As urinary symptoms one will note:

on the one hand, a Anurie or temporary Oliguria, caused by the state of shock and the concomitant Vasoconstriction of the renal arteries; in the event of persistence of oliguria one will fear the development of tubular nephropathy
in addition, the hémoglobinurie, whose causal relationship with tubular nephropathy is certain though indirect. The intensity of the hémoglobinurie, and even its absence or presence, do not make it possible to judge importance of the hémolyse. In certain cases, the hémoglobinurie is the most manifest symptom of the haemolytic crisis: the diseases where it draws the attention particularly were indicated under the name of hémoglobinuries Paroxystique S.

e) The haemolytic Ictère is a late symptom which develops as soon as possible only the shortly after the crisis and which will be accentuated during a few days before disappearing. He is opposed to the mechanical ictères and hépatocellulaires by a whole series of clinical natures: the absence of Bradycardia and Prurit (being given of absence of biliary salt retention), the dark coloring of the saddles (due to the excretion by the bile of increased quantities of Bilirubine). Moreover the urines are sunk in consequence of their content of Urobiline, but do not contain a bilirubine and do not foam (absence of biliary salts).
f) Symptoms common to all anemias (weakness, Dyspnea, etc…) exist with a degree which depends primarily on the mass of blood lost by hémolyse.

2) Symptoms of a chronic haemolytic state:

a) the symptoms of anémie' are of variable expression, supported often well being given the chronicity of the feeble state.

b) the ictère and the feeble paleness mix in variable proportions with the level of the skin and the mucous membranes. The ictère is described above. The evolution of the majority of the chronic haemolytic states is from time to time intersected by episodes with abrupt aggravation with anemia; one of those can even involve the fatal outcome. These " crises of déglobulisation" are of 2 types:

sometimes it acts of a haemolytic push, marked by an aggravation of the ictère,

sometimes of a medullary exhaustion, marked on the contrary by a retrocession of the ictère to the profit of the paleness.

c) the Rate is always increased by volume and sometimes rather large. It is painless with palpating and its behavior with the test with the Adrénaline is variable according to the degree of sclerosis of which it is the object.
d) the Foie is sometimes moderately increased volume.

e) Often the patient presents biliary crises intermittently painful generally caused by the passage of pigmentary calculations . These biliary complications result from the sometimes considerable increase in the biliary excretion of the bilirubine.

f) There exist sometimes turbid Trophique S on the level of the skin of the legs (Ulcère S chronicles, disorders of the pigmentation).

g) In dertains case, the skeleton shows radiological deteriorations in connection with the hyperplasy of osseous marrow (thickening of certain bones, thinning of their Corticale, rehandlings of the spongy bone).

Acquired etiologies

Poisons

This etiology must be required in front of all Hémolyse brutal of especially intravascular mechanism and imposes the search for a toxic exposure:

Drug (Have-methyl-doped or the L-dopa);
Venom of Snake, bite of Spider, puncture of Wasp;
intoxication with the Copper, the Lead within the framework of a Lead poisoning, with the Nitrobenzine, the Naphthalene, the Paradichlorobenzene, the arseniuretted Hydrogen or the Aniline;
some Mushroom S.

Immunological

hémolyse auto-immune = hyperhémolyse (shortening of the lifespan of the red Globules < at 120 days) by fixing of a Antibody on the Red blood corpuscle S involving their destruction exceeding the capacities of Medullary regeneration
hémolyse Immuno-allergic
blood Incompatibility

Mechanics

cardiac valvular Prosthesis
Hémangiome of cerebellum
the haemolytic and uremic Syndrome of the infant
Syndrome of Moschcowitz in the adult

Infectious

Babésiose S
parasite the such Plasmodium S persons in charge of the Paludism
Septicaemia with Clostridium perfringens

HELLP syndrome

night paroxystic Hémoglobinurie

Particular case of an acquired corpuscular haemolytic anemia.

Hereditary etiologies

And of many causes:

the corpuscular Sphérocytose and other anomalies
the Enzymopathie S
the Thalassaemia S
the Drépanocytose
the Deficit of glucose-6-phosphate déshydrogénase (Favism)

Blood hematologic examinations

a) current Measurements

The number of red globules (G.R.) (Red blood corpuscle S), the rate of Hemoglobin (Hb) and the Hématocrite (Hct) are not necessarily lowered in the haemolytic states: they become it only when marrow is décompensée. In the haemolytic anemias caused by a cause extramédullaire (antibody, haemolysing poisons), the G.R. are in theory normochromes and normocytaires. In haemolytic anemias of globular cause, the intrinsic anomaly of the G.R. can sometimes communicate to them a globular volume and a load in Hb very different from the normal and characteristics for each type of affection.

b) Examination of the blood smear

b1) A fact is of constant observation:

the réticulocytose is high (the Réticulocyte S can represent until 40% of the red globules. N.B. The normal level is from 0,2 to 2,0%). The réticulocytose watch the index of the effort of regeneration undertaken by marrow; this réticulocytose is erased really only at the time of the moments of exhaustion of marrow and is then the prelude of a fast aggravation of anemia.

b2) Other anomalies are frequently present and their observation often allows the diagnosis of the affection in question:

of the signs of globular immaturity , of which formed part already the réticulocytose, and who include/understand the presence of some érythroblaste S and G.R. Polychromatophile S (c.à.d. of color grisâtre because noncharged with Hb);
of the anomalies of form of the G.R. : one can observe Sphérocyte S (year. hémol. with autoantibody, hereditary Microsphérocytose), Elliptocyte S, Drépanocyte S (= Red blood corpuscle S in sickle: in the Drépanocytose), red blood corpuscles out of target (Target concealments: in the Thalassaemia S and much of Hémoglobinose S), Acanthocyte S (crenelated G.R.: at the flarings and in the congenital Lipoprotéinémie); the Poïkilocytose (inequality of form) is rather exceptional except in thalassaemias where it is striking;
of the anomalies of globular volume and diameter : p. e.g. the Microcytosis (hereditary thalassaemia, microsphérocytose) and the Leptocytose (abnormal thinness of the G.R.: in thalassaemias); the Anisocytose is rather frequent;
of the anomalies of load in Hb : p. e.g. the Hypochromie in thalassaemias or the hyperchromy connects (dense coloring) Sphérocyte S
of the globular inclusions : Body of Heinz (intoxications, certain affections Idiopathique S), Body of Pappenheimer (ferruginous granules of the Sidérocyte S), basophilic punctuations (Saturnine weakens).

c) The osmotic Résistance is often normal. It on the other hand is very clearly decreased at the sphérocytes (particularly in the hereditary Microsphérocytose) and is increased at the Leptocyte S (in thalassaemia). Frequently, one observes a car-hémolyse with the incubation of blood under various conditions.

d) The white globules and the plate S behave in a variable way according to the affections in question.

Examination of osseous marrow

Marrow is almost always very rich and strongly erythroblastic (decreased report/ratio granulo-erythropoietic) in consequence of the intense effort of regeneration whose it is the object. The érythroblaste S rarefy only at the time of the episodes of medullary exhaustion. In certain cases, of car-immunizing nature especially, one can observe images of érythro Phagocytose.

Metabolic data in haemolytic anemias

1) IRON

The serum rate of Fer is generally higher than 150 microgr. /100 ml, owing to the fact that there do not exist in theory abnormal iron losses, while the iron profits are increased (by transfusion, the erroneous iron administration and the increase in the intestinal absorption of food iron caused by the state of Anoxie. The rate of saturation of the Transferrine is consequently high. The secondary Hémochromatose is one of the complications of the chronic haemolytic state.

2) HEMOGLOBINEMIE

The " term; hémoglobinémie" is reserved for the cases where plasma is frankly red in consequence of a massive release of globular Hb: it is a traditional symptom of the acute haemolytic crisis, where it is observed during several hours.

3) PLASMATIC HAPTOGLOBINE

The plasmatic Haptoglobine has the property to combine with the Hb to form a complex haptoglobine-hemoglobin (HP-Hb) which is very quickly collected by the cells of S.R.E (reticulo-endothelial System). The excessive release of Hb in plasma, following a haemolytic crisis, causes to quickly consume the haptoglobine which is there, the Clearance by the S.R.E of the complex HP-Hb thus formed creates in a few hours a state of anhaptoglobinemy (disappearance of the haptoglobine) which persists in general several days. In the even light chronic hémolyses (p. e.g. in pernicious anemia), the plasmatic absence of haptoglobine is the rule.

4) HEMOGLOBINURIE

The Hémoglobinurie, considered separately, does not constitute a measure of the gravity of a haemolytic crisis.

5) HEMOSIDERINURIE

The minor amount of hemoglobin reabsorbed by the cells of the circumvented tubes of the kidney, at the time of a Hémoglobinurie, is degraded locally and its iron put in reserve in these cells in the shape of grains of Hémosidérine. By the degradation of the epithelium, these grains intra- or extracellular, can find themselves in the base of centrifugation of the urine, and be there identified thanks to the reaction to the Prussian blue . The description of a Hémosidérinurie constitutes the proof, a posteriori, that the patient presented, before, one or more hémoglobinuries.

6) METHEMOGLOBINEMIE AND METHEMALBUMINEMIE

Free hemoglobin remaining in circulation, after saturation of the capacity of fixing of the haptoglobine, is unstable and oxidizes quickly in Méthémoglobine. The méthémoglobine is in its unstable turn and quickly yields its groupings Tétrapyrrolique S (hematin) to two plasmatic proteins: the Hémopexine and, especially, the Albumin. The complex hematin-albumin is indicated by the name of Méthémalbumine. A massive methemalbuminemy is observed in 2 circumstances:

in the days which follow an acute haemolytic crisis (p. e.g. the overshrill crisis of Malaria),
in some Pancréatite S acute hemorrhagic (where a great quantity of blood is destroyed by the Enzyme S of gland necrosed).

A discrete methemalbuminemy exists in all the states of hémolyse intravascular.

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