664

H/EMATOLOGY IN GENERAL PRACTICE. �9

B y D ~ v m Mrrcm~L.

Diagnosis--Points of Practical Importance.

M ANY patients with quite low h~emoglobin have their anemic s ta te concealed unde r a sunbu rn t skin. While the conjunctivae, nails and mucous membranes afford a

f a i r ly reliable clinical guide, to be cer ta in of the p r e s e n c e or absence of anaemia the h~emoglobin should be est imated. This is the mos t impor tan t single invest igat ion in blood examina t ion and can be easily and quickly carr ied out by the prac t i s ing phy- sician. The Tal lquis t me thod is too mis leading to allow its sim- pl ici ty to recommend it. The Sahli method is probably the best, and the " Neoplan " i n s t rumen t of the Hel l ige Company al lows an accura te read ing to be t aken f rom a f inger p r i ck in five minutes. I f the r ead ing is less than 85 per cent., f u r t h e r inves- t iga t ion should be under t aken . F requen t h~emoglobin estima- t ions have several advantages . The pa t ien t is saved the expense o f ful l blood examina t ion in the case of the pale person wi th a no rma l blood; on the o ther hand, su rp r i s ing ly m a n y cases of anaemia are recognised in thei r earl ier s tages ; fu r the rmore , to fol low the effect of t r ea tment , h~emoglobin es t imat ions alone are sufficient when the type of anaemia has a l ready been established b y a ful l examinat ion. I f the hEemoglobin is found to be below 85 per cent., the f u r t h e r inves t iga t ion necessary is in most cases outside the scope of the physic ian in general pract ice. I n order tha t he and his pa t ient m a y get the best value f rom the h~emato- legist or clinical pathologist, two things are essential: (a) tha t the blood be collected in the most suitable manner , and (b) tha t the tests most suitable to the case be asked for.

Collection of Blood: Quite the most satisfactory method is to with- draw 5 c.cs. of venous blood from the eubital vein with the least possible stasis. This is immediately transferred to a small tube or bottle which contains finely divided oxalate with which the blood is well mixed by rolling. The common error is to use too much oxalate or in too large crystals. This results in some clotting before the oxalate dissolves in the plasma, and often later, some h~emolysis when all the oxalate has dissolved. This can be simply avoided as follows : - - I n 100 c.es. of water dissolve 1.2 gm. of atom. oxalate and 0.8 gln. of pot. oxalate. In the tube or bottle, place one drop of this solution for each c.c. of blood to be collected. Evaporation in an oven leaves the oxalate in very fine crystals. By using the above mixture of oxalates, the size of the red cells is preserved. Such tubes ready for use are generally supplied by the h~ematologist.

F r o m this oxa la ted blood the fol lowing examinat ions can read i ly be made : - -

1. Red cell count, 2. H~emoglobin percentage,

~Delivered at Stoevena' Hospit~d, June 23rd, 1939.

H 2 E M A T O L O G Y I N G E N E R A L P R A C T I C E 665

3. M e a n c o r p u s c u l a r vo lume,

4. W h i t e cell count ,

5. P l a t e l e t count ,

6. P e r c e n t a g e of r e t i cu locy tes ,

7. F r a g i l i t y of r ed cells i n h y p o t o n i e sal ine,

8. S e d i m e n t a t i o n ra te ,

9. I c te rus index or v a n den Bergh test.

Blood Films: I t is not possible to make proper smears from oxalated blood. They should therefore be made from the needle before the blood is transferred into the oxalate tube. Differential counts of the white cells are most important and can only be correct if thin even smears are examined. The one essential for good films is absolute cleanliness of slides or cover slips. The simplest way of ensuring this is to place a stock of slides or cover-slips in concentrated nitr ic acid overnight; then transfer them to running water for some hours and finally store them in alcohol. When needed, they are merely dried in the air or with a clean handkerchief or cr~pe paper. I t must be emphasised that the type of ansemia can rarely be established with certainty from the examination of blood films alone. If the red cells are normal in size and shape, any but the slightest degree of anaemia is unlikely; severe pernicious or severe microcytic anaemia can usually be recognised by an experienced h~ematologist, but in all other cases, blood counts must be done. The general custom in this country is to make blood films on slides. If this is done, it is essential that the slide used for spreading the films should be narrower than the other. Such a slide is easily prepared by knocking one or both corners off one of standard width. Films made on cover- slips have the great advantage of much more even distribution of the leucocytes, which in smears made on slides tend to collect along the edges. Provided the cover-slips have been cleaned as described and that a small enough drop of blood is used, good smears are easily made by this method.

Coagulation and Bleeding Times: These examinations are usually necessary in cases of obscure mucesal bleeding and can be quickly carried out by any physician.

Coagulatio~ Time: Important only in h~emophilia, a rare disease. Into a dry test tube place one or more cubic centimetres of the pat ient 's blood and into another, an equal amount from a control. Move the tubes ~ently every half minute. Clotting, when it occurs, is easily recognised. The normal time is four or five minutes, depending on the conditions. In h~emophilia, clotting is so delayed as to leave no doubt.

Bleeding Time: This is of course associated with low platelet counts and is most important in purpura h~emorrhagica. Prick the lobe of the ear with a large needle. Touch the drop of blood with blotting-paper every half minute and, when bleeding stops, count the stains, e.g., five stains means a bleeding time of two and a half minutes. The normal time is about three minutes. A common source of error is to use too fine a needle; almost no bleeding may occur from the narrow deep wound produced and, in addition, a larger needle is less painful.

Nature of Examinations to be Undertaken.--It is r a r e ly necessary to p e r f o r m al l the n i n e poss ib le e x a m i n a t i o n s l i s t ed above. The best co-operation between the p rac t i t i one r a n d the cl inical patho- log is t is o b t a i n e d i f a concise a ccoun t of the c l in ica l c o n d i t i o n a n d the n a m e or names of the blood diseases suspected are sub- mi t t ed wi th the blood. The l abora to ry m a n is t hen enabled to g ive the c l i n i c i an a s a t i s f a c t o r y a n s w e r w i t h the l eas t expendi - t u r e of t ime a n d energy. This is p a r t i c u l a r l y i m p o r t a n t as nowa- days mos t cases of anaemia have a l r eady h a d some t r e a t m e n t

666 IRISH JOURNAL OF MEDICAL SCIENCE

with liver or iron or even both and are sent for h~ematological investigation only if the response to treatment is poor. This partial treatment always obscures the diagnosis to some extent, and if such treatment has been given, the fact should be men- tioned when sending specimens.

Signifivanw of Various Findings.

1. R.B.C. and Hb.--These figures indicate primarily the balance between the rate of blood destruction and the rate at which cells are leaving the marrow. The average amount of h~emoglobin per red cell (colour index) is normally 1, and is related to the cell size as fol lows:--

Mean Conoent ra - H~emato log iea l Colour Vol. t ion of

Type. Index . of Hb. in Clinical Type. Cells. Cells.

N o r m o c y t i o . . . . . . . . . 1. N o r m a l N o r m a l Ap las t i c Anmmia

Maorooyt ic . . . . . . . . . 1.3 I n c r e a s e d N o r m a l Pe rn i c ious Aneemia

S i m p l e Microcyt ic ... 0.1 Dec reased N o r m a l " S e c o n d a r y " Ansvmia due to toxins, ere.

H y p o c h r o m i c Microcyt io 0.5 Dec reased D i m i n i s h e d I ron<lef lc iency Ans~mia

2. Mean Corgusvu~ar Volume.--This is easily determined. The red cells are packed to .constant volume by centrifuging in a l~ematocrit tube of the Wintrobe type and the volume of packed red cells divided by the total number of red cells in the same volume of whole blood. The mean ~orpnscular volume is a more useful criterion of the type of anaemia than the colour index, which, as has been seen, has two variable components, the cell size and the concentration of h~emoglobin in the cells.

3. White Cell Coun~.--This should always be considered in con- junction with the differential count. Since the polymorphonu- clear leucocytes are more affected by disease processes than the others, leueocytosis is usually produced by an increase in the number of these cells in response to an acute infection, while leucopenia, as seen in enteric fever or pernicious anaemia, is due to diminution in the absolute number of the granular cells with a resulting relative increase in the lymphocytes.

4. Pla~el~ Count.--This is probably the least satisfactory of the examinations of the blood. In spite of the fact that numerous methods have been devised, none is entirely satisfactory. Two points are of practical importance: one is that an experienced observer can exclude any severe decrease in the number of plate- lets by examining good blood smears; the second is the value of the " tourniquet test ". I f no petechi~ appear on the forearm after a sphygmomanometer cuff has been left on at the diastolic pressure for five minutes, no significant decrease in the number of platelets is likely.

5. Re~cu/ocyfes.--Normally somewhat less than 1 per cent. of the red cells have a reticulum. As this is only present during the

H/EMATOLOGY IN GENERAL PRACTICE 667

first three or four days of the lifo of the red cell, it follows that an increased number of retieulocytes means an increased rate of liberation of new cells from the marrow into the blood. Reticu. loeytosis thus occurs transiently during treatment when the de- ficiency is made good and the marrow pours out a large number of new normal cells; it also occurs permanently in acholuric jaundice where the marrow by overactivity compensates for the increased rate of h~emo]ysis.

6. Br of Serum.--Just as the degree of reticulocytosis is a measure of the rate at which new red cells arrive in the blood stream so the amount of bilirubin in the serum is a measure of the rate at which old ones are being removed. Thus the bili- rubin is increased in the hmmolytie anaemias proper and in per- nicious anmmia where, as well as abnormal production, increased destruction occurs.

7. Fragility.--Important only in acholuric jaundice. The abnor- mally spherical red cells in this condition are much less resistant to hypotonic saline solution than are normal cells.

1. H~Toc~romis Microc~tw A~m~da.~This is always due to lack of iron, whether from insui~eient intake or from loss o~ iron by repeated or continued bleeding. Treatment consists of dis- covering and checking any source of bleeding, and in giving adequate amounts of iron salts by mouth. The most satisfactory and simplest preparations to use are either ferrous sulphate (12 to 18 grains a day) or iron ammonium citrate scales (grs. xxT t.i.d.) Iron is absorbed in any amount only from the upper part of the small intestine and it is therefore useless to give iron by injection; hmmoglobin itself is ineffective; and organic or colloidal preparations of iron or the inorganic salts in the ferric state are relatively inactive.

2. Normoc~ic and gimplr Microo!gic A~z.--Tho toxins of chronic nephritis, tuberculosis and other chronic inflammations, the invasion of a secondary carcinoma or other turnout, the action of x-rays or radium, or poisoning by benzol or the heavy metals may all interfere with the blood-forming function of the marrow. Lastly, the marrow may become aplastie for no known reason. Both red cells and hmmoglobin are progressively reduced in amount. The cells may be smaller than normal but contain a normal concentration of hmmoglobin. Thus a normoeytic or simple microeytie anmmia with some lowering of the colour index results. The white cells are usually reduced in number except in toxic eases. The serum is pale as there is no increased blood destruction. Unless the cause can be identified and removed, treatment is unsatisfactory. Continued transfusions are of tem- porary benefit, but may be the decisive factor in recovery by tiding the patient over till the marrow regains sufficient function after the damaging element has been removed.

668 IRISH JOURNAL OF MEDICAL SCIENCE

3. Pernicious ~4n~m/a.--The treatment of pernicious amemia is now so well understood that satisfactory results are obtained in almost all cases. Theoretically the amemias of this group may be treated with either stomach or liver extracts, the latter being given orally or parenterally. In practice the parenteral liver extracts are so convenient and now uniformly potent that they are to be preferred. In cases where absorption from the intes- tine is poor, this is, of course, the only method. The more crude extracts of e.c. doses every second day quickly bring about a remission and the blood can then be kept normal !by injections of the highly concentrated extracts given at intervals of some weeks.

4. ~Anvemia due to Blood Dvstruct~on.---Normal red cells may be broken up in the circulation by extrinsic agents, such as phenyl- hydrazine, sulphonamide or lead, malaria, or h~emolytic strep- tococci. Or abnormal cells may be too rapidly destroyed by the spleen, as in acholuric jaundice (and, as has been seen, in per- nicious amemia). In cases where the bone-marrow is normal, the anmmia is usually not severe. The h~emolytic nature of the pro- cess is readily reeognised by the yellow serum due to hyperbili- rubinmmia. In acholuric jaundice, the essential abnormality of the red cells is reeognised by the " fragility " in hypotonic saline solutions. In the cases of extrinsic origin, the causative agent must be removed. In acholuric jaundice splenectomy, while not remedying the abnormality of the red cells, often corrects the anmmia and jaundice by slowing the rate of destruction.

5. Polycyth~mia Vera.--Here for some unknown reason the mar- row is hyperplastic. The blood contains red and white cells in increased numbers; the total plasma volume likewise is increased. There are three methods of treatment. Diffuse long distance x-ray treatment (" spray therapy ") exposes the red marrow throughout the body to the rays with destructive effect on the mar- row ; the only drawback to this form of treatment is the difficulty of controlling the dose, as overdosage can easily produce aplastie anmmia. The other methods do not attack the abnormality of the marrow but merely reduce the amount of circulating blood. Phenylhydrazine (gr. 1�89 may be given for one or two weeks and then stopped; the h~emolysis produced ~ontinues for some time longer; later a maintenance dose of 1�89 grains once or twice a week will keep the cell count within normal limits. The third method consists of repeated venesection; this has the advantage of reducing not only the number of cells but the volume of plasma. The only objection to this method is that repeated removal of blood stimulates the marrow further.

6. Leuka3mia.--In the acute forms and in chronic lymphatic leukmmia, treatment of any kind has little effect. In chronic myelogenous leuk~emia, however, the patient 's life can be consi- derably prolonged by treatment. X-ray treatment of the spleen is probably the most satisfactory; where this is not available,

SOME OBSTETRICAL H~EMORRHAGES 669

gradually increasing amounts of Fowler 's solution produce con- siderable reduction in the number of leucocytes. In several American clinics it is now the custom to treat myelogenous leuk~emia with arsenic as long as it produces any effect, reserving the more potent radiotherapy for the later stages of the disease.

7. Agranulocytosis.--The important points about this rare condi- tion are the sudden onset, often with fever and ulceration of the throat, while the blood shows almost complete absence of polymorphonuclear cells, but relatively little anoemia. Treatment consists of identifying and stopping any drug, such as amido- pyrin, N.A.B., or gold, to which the patient may be sensitive and in giving large amounts of pentonucleotide.

8. Purpura.--When one is satisfied that the purpura is primary and not merely symptomatic on some condition such as acute leuk~emia, the question of splcnectomy must be considered. The operation produces the most marked results when the platelet count is very low and after blood transfusions have been liberally given.

9. Scurvy.--Mild scurvy is not as rare in this country as might be supposed. The response to Vitamin C is usually remarkably satisfactory. The possibility of scurvy should be kept in mind when dealing with obscure anaemia associated with bleeding.

10. Hc~mophil~a.mTrue h~emophilia is rare. The disease almost always shows itself in infancy. The clotting time of the blood is so much increased as to leave the diagnosis in no doubt.

SOME OBSTETRICAL H~EMORRHAGES.*

By R. M. CORB~-~.

T HE subjects discussed were placenta pr~evia, accidenta~ h~emorrhage and post partum h~emorrhage.

Placenta Prvzvia.

With modern transport facilities and the increase of hospitaI accommodation, the majority of these cases are now treated in institutions and the general trend of modern treatment is to diminish the number of eases treated by version and bringing down a leg. The indications for C~sarean section have been ex- tended for the more serious type of case and, at the other end of the scale, puncture of the membranes and compressing the placenta by means of WiUett 's forceps attached to the foetal head

*Abstract of Lecture delivered at the Coombe Hospital, June 24th, 1939.