V. DIMINUTION OF THE WHITE BLOOD CORPUSCLES (LEUKOPENIA).
W. Myers translation
Diminution of the white blood corpuscles plays—comparatively with their increase—a very unimportant rôle in clinical observations. It occurs in but few groups of diseases, and but seldom attains a marked degree. Koblanck has described a most marked fall in the number of the colourless cells, in the following remarkable blood condition. In a strong man, 25 years of age, whose internal organs were found to be healthy, short epileptiform attacks occurred, in one of which death took place. The autopsy gave no indication of the cause of death. Two examinations of the blood were made in the course of the three days he was under observation. In one of these, out of ten cover-glass preparations, not a single white blood corpuscle was found, and in the second only one example.
We have mentioned this case here, because it is remarkable as an extreme leukopenia never before observed. An explanation however is impossible owing to the obscurity of the general clinical condition.
For the rest the conditions, under which a considerable diminution of the leucocytes occurs, are very well-known. We distinguish two chief groups:
1. Leukopenia from destruction of a portion of the white blood corpuscles (Löwit);
2. Leukopenia from deficient inflow of white corpuscles:
α. in infectious diseases from negative chemiotaxis;
β. in anæmia etc. from defective action of the bone-marrow.
We have entered more fully into the leukopenia experimentally produced by Löwit, in the chapter on leucocytosis. We there explained, that according to present views, we have to deal, not with an actual destruction of the white elements, but merely with an altered distribution within the blood-stream.
Amongst the infectious diseases where an hypoleucocytosis occurs, typhoid fever must first be mentioned. The diminution is chiefly at the expense of the polynuclear cells. Uncomplicated measles too, generally runs its course with a marked leukopenia, specially distinct during the breaking out and at the height of the exanthem. These cases of infectious leukopenia are to be explained, not by a destruction of white corpuscles, but rather by a diminished inflow, brought about by the circulation of substances negatively chemiotactic for the polynuclear elements.
Leukopenia has still another meaning in certain cases of severe anæmia, where it indicates a highly unfavourable prognosis. Ehrlich has described (Charité Annalen 1888) a case of posthæmorrhagic anæmia ending fatally, where an extreme diminution of the leucocytes occurred. Exact figures shewed that the greater proportion (80%) of white blood corpuscles consisted of lymphocytes, whilst the polynuclears amounted to 14% (instead of 70-72% normally). Eosinophil cells and nucleated red blood corpuscles were entirely absent. Ehrlich explained these phenomena by a deficient activity of the bone-marrow, which found expression in the insufficient formation of red and white blood corpuscles. As the anatomical basis of this deficient activity, he conjectured that in this case the fatty marrow of the big long bones could not have been changed to blood forming red marrow, as is the rule in severe anæmias. In two cases the autopsy fully confirmed this diagnosis made during life.
The blood platelets.—The hæmoconiæ.
The blood-platelets were first described by Hayem, later by Bizzozero, as a third formed element of normal blood. They are roundish or oval discs free from hæmoglobin. They are extremely unstable under mechanical, thermal, and chemical influences. Their size amounts to some 3 µ. Specially characteristic is their tendency, the result of their extraordinary stickiness, to run together into largish clumps, "grape clusters." This circumstance greatly facilitates the distinction of the blood platelets from the other formed elements, but renders their enumeration most difficult. The apparatus usually used for counting the blood corpuscles is, for this reason, deceptive; for the platelets rapidly cling to its walls and remain there. All early authors (e.g. Bizzozero) endeavoured to obviate this error by some particular diluting fluid; but a number of these elements still remained fastened to the walls of the capillary tube of the mixing apparatus.
Recently Brodie and Russell have recommended a new mixture in which the platelets remain quite isolated, and are stained at the same time. They allow the drop of blood as it comes from the puncture to enter a drop of the fluid, and then estimate the relative proportion of red blood corpuscles to platelets[36]. The prescription for their solution is as follows:
Dahlia-glycerin, 2% solution of common salt ... equal parts.
Another method, used by the majority of more recent authors, is the relative enumeration of blood platelets in the stain dry specimen. Ehrlich found that the blood platelets were picked out by their deep red colour, corresponding to the amount of alkali they contain, in preparations treated by the iodine eosine method (see p. 46). Rabl's new method is much more complicated and in no way more serviceable, depending on a stain with iron hæmatoxylin recommended by E. Haidenhain for demonstration of the centrosomes. A process of Rosin's, not yet published, is more convenient. It consists in fixing the dry preparation for 20 minutes in osmic acid vapour, and staining in a concentrated watery solution of methylene blue.
With regard to the significance of the blood platelets, most authors, of whom we should before all mention Hayem, Bizzozero, Laker, assume justifiably that they are preformed in the living blood. The view opposed to this, advocated more particularly by Löwit, that these forms first arise in the blood after it has left the vessels, we may describe on the grounds of our own extensive observations as inaccurate.
The blood platelets, on the grounds of their small size and complete lack of nuclear substance, are generally regarded as not analogous to real cells. Whether they represent intravital precipitation of substances of the plasma, or whether they are budded off from the cells, cannot at the present be decided with certainty, though many facts seem to support the latter assumption. That they contain glycogen (see p. 45), marks them as descendants of the blood cells. Moreover, appearances are often met with in dry preparations that arouse the suspicion that the platelets arise from the red blood corpuscles (Kœppe). Arnold has further observed processes of budding in the red blood corpuscles not only extravascularly but also intravascularly in the mesentery of young guinea-pigs, and has seen the elements that were cut off change into forms free from hæmoglobin.
Our knowledge too of the physiological function of the blood platelets still needs much amplification. The original view of Hayem, who regards the blood platelets as early stages of the red blood discs, and for this reason calls them "hæmatoblasts," is, according to the judgment of most hæmatologists, untenable.
Nearly all more recent papers, on the other hand (cp. Löwit's compilation), recognise the close connection of the blood platelets with coagulation, first observed by Bizzozero. Whether the substance of the platelets directly yields the material for fibrin formation, as Bizzozero holds, or whether according to the observations on thrombus production of Eberth and Schimmelbusch they play but a subordinate part, is not yet decided. To enter here into the chemical side of this complicated problem, would lead us much too far, and we will only refer to a few clinical observations which illustrate the relations between the clotting power of the blood and the number of platelets it contains.
Marked increase of the blood platelets occurs in chlorosis (Muir) and in posthæmorrhagic anæmia (Hayem). In both conditions there is a decided increase in the clotting power of the blood. In contrast, is the important observation of Denys, who found in two cases of purpura, where as is well-known the clotting power of the blood is always much lowered or may even be entirely destroyed, only one morphological blood change, a very marked diminution of the blood platelets. Ehrlich likewise had occasion to examine a similar case, in which the blood platelets were entirely absent.
H. F. Müller has described a fourth formed constituent of the blood, and given it the name of "hæmoconiæ" or "blood atoms," "blood dust." It is found in the plasma of the blood as very small granule- or coccæ-like colourless corpuscles, highly refractile, with a very active molecular movement, which keep their shape under observation for a very long time without any special precautions. According to Müller these bodies are not blackened by osmic acid, and probably contain no fat; they seem to have no connection with fibrin formation, as they always lie outside the fibrin network. Müller found them in every normal blood, in varying numbers however; much increased in a case of Morbus Addisonii; diminished in hunger and cachexias.
More detailed observations are necessary to determine the chemical nature of these forms. Experiments in this direction by extraction with ether, or by the use of fat staining substances, alkanna, Soudan dye, and comparative investigations on lipæmic blood should be successful.