ROM the standpoint of hema

FR

tology the hemorrhagic conditions present many most interesting problems, in the study of which the names of Hayem and Frank stand out preeminently. These workers set aside the conception that bleeding and deficient coagulability of the blood went hand in hand. At the same time their investigations raised many difficult questions which unfortunately up to the present have not been answered. Since their work it has been recognized that the normal clotting power of the blood is but one of several factors to be considered. To the number and size of the platelets increasing importance is being attached. Further, according to Schultz and the observations of many others, there is added support to the view that the vessel wall plays an important part in hemorrhage. It may be said that in the purpuric state under all circumstances there is an "angiopathy" which may include altered nervous tone, contractibility, changes in the endothelium, and other very imperfectly understood but vital phenomena. These are so obscure that classification of the various purpuras on purely etiological or pathogenetic grounds is

1 Read before the Association of American Physicians, Atlantic City, May, 1924.

quite beyond our present knowledge. We therefore must have recourse to blood examination. From this viewpoint hemorrhagic conditions naturally divide themselves into three groups. Assuming that an alteration of the blood vessel walls is a prerequisite in all cases we base our distinctions upon alterations in the coagulability and platelet content of the blood.

In the first group may be included all cases in which the coagulation of the blood is not delayed and there is no thrombopenia. Is it a constitutional defect of the vessel wall, or a toxic injury to this structure? To this group belong Schoenlein's disease and Henoch's disease, scurvy and Barlow's disease, and the symptomatic purpuras of sepsis and toxemia, etc.

In the second group are found all those conditions in which the coagulability of the blood is delayed. There is no thrombopenia. Here one finds hemophilia, those cases associated with liver disease and icterus, and certain other conditions characterized by physio-chemical alterations in the blood. The blood platelets may show qualitative change.

In the third group in which marked diminution of the number of platelets is found, may be included the purpuras associated with leukemia and severe anemia, those arising in cases

of carcinoma and bone marrow metastases and those due to certain poisons such as benzol acting on the myeloid tissue. These are symptomatic, sharply contrasted with the essential thrombopenia or purpura hemorrhagica, or morbus maculosus Werlhofii, in which coagulability of the blood is not markedly altered; blood vessel changes we assume are present, but thrombopenia or a marked diminution in the number of platelets is the outstanding feature.

From the point of view thus described we have carried on repeated and more or less extensive morphological blood examinations on the 3 cases which are briefly outlined.

Case 1. G. L. No. 38794. The patient, a girl aged fifteen, was admitted September 1, 1923, complaining of loss of strength and color, of bleeding gums and diarrhea.

During the winter of 1923 she noticed that black and blue marks came out on the skin, and after two or three weeks disappeared giving her the impression that they were due to bruises although she had no recollection of having been even slightly injured at any time. The gums bled occasionally, yet her teeth were in good condition. Throughout the early summer her strength was not up to her usual standard, although she was apparently in health until August 1 when looseness of the bowels set in, the movements becoming frequent both by day and night. After two weeks she lost appetite, became quite weak and took to her bed. At that time blood was noticed in the stool, the gums bled more readily, and occasionally there was vomiting.

The family and personal history are alike negative. The conditions under which patient lived were satisfactory.

On examination in the hospital she was seen to be a fairly well-nourished young female. The surface of the body was pale and partook somewhat of a waxy hue. Her skin was warm and dry. Here and there upon the surface were seen a few petechiae.

Her conjunctivae were pearly white. The mucous membranes were pale, and at but one point within the mouth a little bleeding was discovered. Pulse 120; temperature 100; respirations 22.

The thyroid gland was slightly enlarged. No other glandular enlargement was discovered. The examination of the respiratory system including that by the X-ray was negative. The cardio-vascular system, save for a faint systolic murmur over the pulmonary area and the accelerated pulse rate was negative. The abdomen and pelvis on physical examination were also negative. There was amenorrhea which had been present for some months. The nervous system was negative. Both eyes showed retinal hemorrhages, without any swelling of the disc. The urine showed but a faint trace of albumin with no casts or other abnormal elements.

Blood count. Red blood cells 1,800,000; leucocytes 4800; blood platelets were greatly reduced and fell rapidly; hemoglobin 25 per cent; differential count, polymorphonuclear neutrophiles 52 per cent; lymphocytes 43 per cent; eosinophiles 1 per cent; myelocytes 1 per cent; mast cells 1 per cent. One nucleated red cell was found on the first examination. The Widal test done on two occasions was negative. The stools showed blood, while the test for tubercle bacilli was negative.

A diagnosis of purpura hemorrhagica was made, and the case was considered to belong to the type recently described under the term of thrombopenia or thrombocytopenia.

The course of her case in the hospital was fairly satisfactory. The temperature was febrile until October 21, when it ranged about 99 until November 11. The pulse was always rapid, from 100 to 120, and even when discharged on November 11, it was between 90 and 100. From this time there was favorable progress, bleeding ceased. Another transfusion was given of 450 cc. of fresh blood in December. Early in January she seemed to suffer a relapse with practically all her former complaints except that of diarrhea. In spite of transfusion, small doses of arsenic, and feeding, the blood values sank very low; the red blood cells in March were 1,620,000; white blood cells 5,700; hemoglobin 25 per cent.

In April, however, she again is much improved after another transfusion, though still quite unable to go about.

Case 2. The patient, M. G., a girl aged sixteen years, was admitted January 28, 1923, for weakness and loss of color, spots on the skin, excessive menstruation and nose bleeding. In December, 1922, the patient began to have bleeding from the nose practically every morning. About the same time small hemorrhages appeared all over her body and on the legs and thighs. Her menstrual flow which began two years before rarely lasted three days. In November and December, 1922, it lasted ten days in each period. By this loss of blood she thought she could explain her weakness and fainting attacks as well as the pallor upon which her friends remarked.

The personal history previous to November, 1922, is negative. In the family history there is one sister who often has nose bleeding; otherwise negative.

When admitted to the ward the patient had already been treated for nasal hemorrhage, and from the packing in the left nostril there was considerable oozing. She was fairly well nourished, and very pale; petechiae were seen over the face and head and widely over the body, more particularly on the thighs. There was no edema and no jaundice. The glandular system including the thyroid was negative. The respiratory system was also negative. The cardio-vascular system apart from the increased pulse rate and hemorrhages was negative. Gastrointestinal system: The teeth were in good condition. There was some bleeding from the mucous membrane of the mouth chiefly about the teeth. The odor with the breath was very foul. The spleen was not enlarged. Vomiting was frequent throughout her illness. The abdomen and pelvis were negative. Both eyes showed intense hemorrhagic retinitis: the hemorrhage of the left eye was large, extending from the lower part of the optic nerve to the temporal side below and including the macula.

Blood count. On admission, red cells 2,830,000; white cells 19,820; hemoglobin 50 per cent, platelets 14,000. The differential count showed polymorphonuclear neu

trophiles 68 per cent; lymphocytes 27 per cent; large mononuclears 2 per cent; eosinophiles 2 per cent, and mast cells 1 per cent. Coagulation time was normal.

In February the first transfusion was given with citrated blood. This was followed by six subsequent transfusions from that time until March 5, sometimes by the indirect and sometimes by the direct method. The results of these transfusions were not uniformly satisfactory in stopping the hemorrhage. Indeed on one or two occasions immediately after the operation the flow of blood increased. On March 3 and 5 the red cells were considerably below 1,000,000 and the white cells 20,000. Thereafter, however, the blood steadily gained in value although no further transfusions were given.

From the time of admission the pulse rate was greatly increased reaching 140 and more, and even when the patient was discharged it was very readily increased. The temperature was irregular for about six weeks, then gradually became more settled and finally normal.

While no signs of organic disease were found in the nervous system, the patient was often restless and at times excitable. Again she was heavy and took but little notice of those about her. At one time she became semi-comatose, looking very pale, with coldness of the body surface.

The urine usually showed a trace of albumin. On one occasion only it gave a positive benzidine reaction. There were no casts.

About the middle of April the red blood cells were 4,500,000; the white cells between 5000 and 8000 and the hemoglobin 65 per cent. The platelets never returned to their normal number, running between 10,000 and 28,000 when discharged on April 16, 1923.

A year has elapsed since this patient was discharged from the hospital, and her condition while not altogether satisfactory remains greatly improved. She shows a mild anemia, and the red cell count is about 4,000,000.

Case 3. The patient, M. A., a girl of twenty, was admitted on February 3, 1924, complaining of pain in the back and abdomen, bleeding from the nose, bleeding from

the vagina, loss of appetite and vomiting, headache and weakness.

The present illness set in rather suddenly with nausea and vomiting toward the end of one of her menstrual periods. At that time also she suffered a hemorrhage from the nose with which since the beginning of menstruation at sixteen years of age she had from time to time been troubled. The loss of blood with menstruation on this occasion was excessive, which with her nasal bleeding induced marked pallor and pronounced weakness. Dysmenorrhea was experienced for the first time. Late in 1923 reddish spots came out over her neck and arms. Her personal history is otherwise negative. There are no bleeders in the family.

When admitted to the ward she was seen to be a well-nourished young female with waxy pallor of the skin and the mucous membranes. There was tenderness over the lower quadrants of the abdomen: several areas of ecchymosis upon the arms and legs. Temperature 97.4; pulse 120; respirations

24.

The urine was normal beyond an occasional faint trace of albumin.

Blood. Red blood cells 2,500,000; white blood cells 11,200; hemoglobin 22 per cent. Blood platelets under 20,000. Coagulation time normal. Imperfect or no clot retraction. Bleeding time prolonged.

The eyes showed a small hemorrhage in the left fundus. Elsewhere the retinae were pale.

There were no signs of organic disease discovered on examination. The patient was treated with transfusions of fresh blood on three occasions during the first three weeks after coming into the hospital. At the end of the fourth week she showed signs of improvement, and favorable progress was made for the next six weeks. Then petechiae came out more widely than before over the trunk and limbs, the capillary resistance test became positive: again the mucous membranes about the teeth and nostrils oozed blood. The menstruation came on, and even with a red cell count of 3,000,000 she again became very weak and miserable.

These three clinical sketches concern young girls from fifteen to twenty years of age, who, while never specially robust, showed about puberty the tendency to bleed spontaneously into the skin and from mucous membrane, nose, mouth, uterus and digestive tract. The bleeding was greatly increased in 2 of our patients at the time of menstruation; slight pressure to the skin was followed by signs of bruising.

While a few spots had been seen upon the skin and an occasional slight nose bleed had been present in 2 of our cases, yet it seemed that there was in these patients a rapid change from comparative health to illness of a severe degree. Diarrhea with much blood in the stools in 1, excessive bleeding at the nose and moderate menorrhagia in another, while in the third case nasal and uterine bleeding seemed to account for this rapid change. Retinal hemorrhages are common to the group. Case 2 is now comparatively well; a chronic case or one in a long remission. Cases 1 and 3 may be considered as in a second relapse.

While the clinical signs are characteristic of purpura hemorrhagica, yet upon the morphology of the blood, studied in particular by one of us (T. R. W.), mainly depends the diagnosis that of essential thrombopenia or thrombocytopenia.

The broad outlines of the blood picture, details of which follow, are those enumerated by Brill and Rosenthal in their interesting article read before this Association last year, viz:

1. Diminution of the blood platelets. 2. Normal coagulation time of venous blood.