but without much benefit. Quinine, iron, and cod-liver oil are useful
as tonics, but have no influence on the size of the tumors. Arsenic is
the only medicine which has seemed to me of positive value, and under
its use I have seen the gland-tumors decrease greatly in size. It
should be given in increasing doses until some of the unpleasant
effects of the drug are manifested, when a return should be made to a
small dose, and again gradually increase. When well borne, large doses,
20 or 25 minims, of the liquor arsenicalis should be taken three times
a day for many weeks. In two cases with moderate enlargement of the
cervical and axillary glands the progress of the disease seemed
arrested, and the glands certainly became smaller and softer. In the
history of these cases the patients will often speak of changes in the
volume of the gland quite uninfluenced by any treatment; and these
fluctuations must be taken into account in estimating the value of a
drug; but, making due allowance for this, the beneficial effects of the
arsenic are unquestionable when given early in large doses and the
administration kept up for months. Many recent writers have borne
testimony to this, among them Karewski,[156] who reports three
recoveries.
[Footnote 156: _Berl. klin. Wochenschrift_, 1884, 17 and 18.]
Phosphorus has been of service in the hands of Gowers and Broadbent,
and when arsenic is not well borne it should be tried.
Change of air and scene has benefited some cases. The patient's
strength must be supported by every possible means; fortunately,
gastro-intestinal disturbance is not so marked as in leukæmia, and even
with most extensive and progressive enlargement of many groups of
glands the appetite may be good and the digestion excellent.
When the glands of the neck compress the trachea, or when the lymphoid
elements of the tonsils and pharynx obstruct the orifice of the
glottis, tracheotomy may be necessary.
HÆMOPHILIA.
DEFINITION.--An hereditary or congenital fault of constitution,
characterized by a tendency to bleeding, spontaneous or traumatic, and
often associated with swelling of the joints.
{932} SYNONYMS.--Hæmatophilia; Hereditary hæmorrhage; Hæmorrhagic
diathesis; Idiosyncrasia hæmorrhagica. _Ger._ Bluterkrankheit,
Blutsucht; _Fr._ Hémophilie. The term bleeder is applied to a patient.
CLASSIFICATION.--In this article the congenital or hereditary disease
will alone be considered, to the exclusion of cases of transient
hemorrhagic diathesis, the hemorrhages of scurvy, fevers, anæmia,
purpura simplex, and purpura hæmorrhagica.
HISTORY.--So far as is known, the classical writers make no mention of
the disease, though in the _Pharsalia_ of Lucan there is a passage,
quoted by Legg,[157] which well describes the hemorrhagic diathesis.
The first positive reference is in the writings of Alzaharvi, a
physician of Cordova who died in 1107 A.D. A doubtful case is mentioned
by Benedictus in 1539, who relates the history of a barber who bled to
death from slight wounds of the nose caused by clipping the hairs.
Hochstetter described a case in 1674 to which Virchow has called
attention.[158] Legg[159] found a well-recorded case by Banyer in the
_Philosophical Transactions_ (1743). Fordyce in 1784 described a
Northamptonshire family the members of which suffered from
hemorrhages.[160] With brief references to the disease by two German
writers in 1793 and 1798, these scanty materials comprise the facts
known at the beginning of this century.
[Footnote 157: _Hæmophilia_, London, 1872.]
[Footnote 158: _Virchow's Archiv_, Bd. xxviii.]
[Footnote 159: _Loc. cit._]
[Footnote 160: _Fragmenta Chirurgica et Medica_, London, 1784.]
To American physicians belongs the credit of the full recognition and
description of the disease and the discovery of its remarkable
hereditary nature.
Otto[161] gave an account of a New England family members of which had
been bleeders for several generations. He also referred to a Maryland
family observed by Rush. Otto appears to have been the first to note
the immunity of females in bleeder families, and their tendency to
transmit the disposition. In the _Philadelphia Medical Museum_, vol.
i., 1805, a letter of E. H. Smith is published, written in 1794, in
which he gives an account of a boy affected with the disease. Hay[162]
reported the Appleton-Swain families of Reading--one of the most
remarkable histories ever published of the disease. In 1817 the Buel
Brothers described the Collins family,[163] and Coates[164] a family in
Delaware county, Pa. Hughes[165] and Gould[166] also described notable
examples. Holton, Harris, and Dunn have studied other American bleeder
families, and a brief record of the local literature of the subject
will be found at the end of this article.
[Footnote 161: _Medical Repository_, New York, 1803, vol. vi.]
[Footnote 162: _New England Medical Journal_, 1813, vol. ii.]
[Footnote 163: _Transactions of the Medical and Physical Society of New
York_, 1817.]
[Footnote 164: _North American Medical and Surgical Journal_, Philada.,
vol. vi., 1828.]
[Footnote 165: _Transylvania Journal_, 1831, vol. iv., and _American
Journal Med. Sciences_, 1833, vol. xxi.]
[Footnote 166: _Boston Medical and Surgical Journal_, 1857.]
In Germany, Nasse (1820), Rieken (1829), Schönlein, Canstatt,
Wachsmuth, Lange, Virchow, and others added greatly to our knowledge of
the disease. Grandidier published a monograph in 1855, a new edition of
which in 1877[167] contains a most exhaustive account of the disease
and a statistical résumé of all cases to date. In England the disease
has not attracted much attention. Legg published an important monograph
in 1872, and many papers of value are scattered through the
_Transactions_ and journals.
[Footnote 167: _Die Hämophilie_, Leipzig, Zweite Auflage, 1877.]
In France the articles in the encyclopedias and a few theses--of which
Gavoy's (1861) and Simon's (1874) are the most important--comprise the
chief literature.
ETIOLOGY.--The disposition is, in the majority of cases, hereditary,
but there may be a spontaneous origin, the disease appearing in the
child of a family in which no previous cases had occurred. Nothing is
known of the {933} conditions under which the disease may thus arise in
a healthy stock. Many of such cases die early, but others live and may
become the starting-points of new bleeder families. In the history of
sixty families Grandidier[168] found statements of this mode of origin
of the affection.
[Footnote 168: _Op. cit._, p. 136.]
The two most interesting features in the etiology relate to sex and
heredity. The disease is much more common in males than females, the
proportion being variously estimated at 11 to 1, or even 13 to 1. In 64
bleeder families, in 5 were sons and daughters alike affected; in 27
all the sons were bleeders; and in 6 of these there were no daughters.
There is no disease with so marked a tendency to transmission, and it
may appear in four or five generations in succession. In the
Appleton-Swain family of Reading, Mass., there have been cases since
the early part of the last century, and F. F. Brown of that town writes
me that cases still occur in the descendants.[169] Legg gives a chart
of the Clitherow family, in which it has existed for the past two
hundred years.[170]
[Footnote 169: The last case Brown has been able to ascertain was in a
lad, Warren Coburn, aged seventeen, who died about twelve years ago.
His mother's brother was a bleeder, and died of hemorrhage from a
slight scalp wound after having been brought to death's door on three
or four other occasions by trivial wounds. Mrs. Coburn was a daughter
of Daniel Hart, whose wife was a Norton. Her mother was a Bacheller and
a granddaughter of Oliver Appleton's daughter. This lad is an instance
of the transmission of the disposition to the seventh generation within
a period of two hundred years. Brown further states that there do not
appear to be in the vicinity of Reading any Appleton or Swain families
in which bleeders exist. As the tendency is chiefly transmitted through
the female members of a family, who lose the patronymic by marriage, it
is often difficult to trace the relationship. I think if we had fuller
genealogical details we should find that several of the bleeder
families now thought to be distinct belonged to the same stock.]
[Footnote 170: _St. Barth. Hospital Reports_, 1881.]
YEATON.
|
+----------+-------------+---------+---------+----------+
| | | | | |
Son, bleeder. Daughter. Daughter. Daughter. Daughter. Daughter.
| | | | |
| | | | |
+----------+-----+ | | | |
| | | | | |
Son, bleeder. Three daughters. | | | |
| | | | |
Son, bleeder. | | | |
| | | |
+------------+-----------+ | | |
| | | | | |
Son, bleeder. Daughter; Daughter. | | |
children not bleeders. | | |
| | |
+-----------+-----------------+----+ | |
| | | | |
Son, bleeder. Daughter. Daughter. | |
| | | |
Son, bleeder. +-----+-----+ | |
| | | |
One son Four daughters. | |
bled to death. | |
| |
+-----------+----------+----------+----------+ |
| | | | |
Son, bleeder. Daughter. Daughter. Daughter. |
| | | |
Twin boys, Son, not Son, not |
bleeders. a bleeder. a bleeder. |
|
+--------------+-----------+----+
| | |
Son, bleeder. Son, bleeder. Daughter.
In the celebrated bleeder families of Tenna, Switzerland, five
generations have been affected. The modes of transmission are as
follows: (1) Father {934} to son, grandson, etc. This is rare, but
instances are on record. (2) Father not a bleeder, but of bleeder
stock, transmits the tendency to son--very uncommon. (3) Father to
daughter, granddaughter, etc.--not common. The daughters of a bleeder
are usually free, though their brothers may be affected. (4) Mother a
bleeder, transmits to sons and daughters. (5) Mother not a bleeder, but
daughter of one, transmits to her sons, the daughters remaining free,
but their sons affected. This is the most common mode of inheritance.
Atavism by transmission through the female line is almost the rule, and
the daughters of a bleeder, though healthy and free from any tendency,
are almost certain to transmit the disposition to their male offspring.
The 657 cases analyzed by Grandidier occurred in two hundred families.
The chief facts of heredity are well illustrated by the preceding chart
of the Yeaton family, given by Gould in the _Boston Medical and
Surgical Journal_, 1857.
The Anglo-Germanic nations appear especially prone to the disease. Of
194 families in Grandidier's table, 154 were of the Teutonic stock.
Records of the disease among the Latin races are rare. Jews are
probably not more liable than other people, but the rite of
circumcision gives an unusual opportunity for its manifestation at an
early age.
The age at which the bleeding tendency first appears was determined by
Grandidier in 113 cases as follows: in 63 during the first year; in 17
during the second, and up to the end of the second year in 93. It is
rare for the first manifestation to occur after the twelfth year, and
there was only one case in which the first bleeding appeared after the
fifteenth year.
The constitution and temperament of bleeders, about which the older
writers had much to say, probably present no peculiar characteristics.
Some persons claim to be able to recognize bleeders even before they
have manifested any tendency to hemorrhage. They are usually fresh,
healthy-looking persons, with fine, soft skins, through which the
superficial veins may show with more than usual distinctness. A
division of cases into erethetic and atonic forms has been made by
Wachsmuth and Grandidier. The mental activity of bleeders has been
noted to be above the average, due, doubtless, to the fact that the
liability to bleed from slight blows and cuts has made sedentary and
studious habits preferred to out-of-door employments and amusements.
Families in all conditions of life are affected. Much interest was
excited in the disease in England from the fact that the late Prince
Leopold was a sufferer.
Climate appears to have an influence in determining attacks. Cold,
damp, changeable weather is favorable, while a residence in a warm,
equable climate diminishes the tendency in a very marked manner. Some
patients have an extraordinary susceptibility to changes in the
weather.
All observers have noted the great fertility of bleeder families. Those
first born seem less liable to bleed than subsequent ones.
SYMPTOMS.--The existence of the defect of constitution may not be
suspected until an uncontrollable hemorrhage follows some trivial
injury or operation, or a spontaneous bleeding may occur and present
great or insuperable difficulties in its arrest. The symptoms usually
occur in the first years of life, and in the great majority of cases,
as mentioned above, the first bleeding occurs before the fifth year.
The symptoms may be grouped under three divisions (Legg, Grandidier):
external bleedings, spontaneous and traumatic; interstitial bleedings,
petechiæ, and ecchymoses; and the joint affections. Legg recognizes
three grades of the disease. The first and most severe is characterized
by bleedings of every kind, external and internal, and by troublesome
joint affections: this form is most often seen in men. The second grade
is less severe; there are spontaneous hemorrhages from the mucous
surfaces, but no traumatic bleeding or ecchymoses and no joint {935}
troubles: this form is most often seen in women. The third and lowest
degree is when there is a tendency simply to ecchymoses; no dangerous
bleedings occur: this form is often seen in members of bleeder
families, and if in women the menstruation may be early and profuse.
External Bleedings.--The spontaneous bleedings may occur from the skin,
the mucous, and in rare instances the serous, membranes. There are
frequently preliminary symptoms--prodromata--such as flushing, fulness
of the head, and throbbing of the arteries--signs of so-called
plethora; often there is irritability of temper, but sometimes, in
children, extra cheerfulness has been observed. The localities affected
and the frequency are shown by the following analysis of 334 cases by
Grandidier: Epistaxis, 169 times; from the mouth, 43; stomach, 15;
bowels, 36; urethra, 16; lungs, 17; cerebral hemorrhage, 2; skin of
head, 4; tongue and finger-tips, 4 each; tear-papilla, 3; eyelids, 2;
external ear, 5; female generative organs, 10; ulcer of skin, 2; navel
(long healed), 2. An odd situation for spontaneous bleeding is
mentioned by Townsend,[171] in which a child bled to death from the
scrotum. In many cases these spontaneous hemorrhages prove fatal--most
frequently the epistaxis. The traumatic bleeding may result from blows,
cuts, scratches, etc., and the blood may be effused into the tissues or
discharged externally. Fatal hemorrhages have occurred from the
following wounds: blow on head, 11 times; slight scratches on skin or
abrasion of dermis; laceration of the frænum of the lip, slight cut
(two lines deep) in a duel wound; bite of the tongue (7 cases); fall on
the mouth; blow on the nose; blow of a stone on the finger; cut in
paring the nail; fall on the head with meningeal hemorrhage (2 cases,
brothers); and rupture of the hymen on the wedding-night.
[Footnote 171: _Boston Med. and Surg. Journal_, lv.]
After operations, trivial and severe, many fatal cases have occurred,
and the statistics of the same author give the following: cutting of
the frænum linguæ, 1; leeching, 5; venesection, 4; blister, 2;
extraction of tooth, 12; circumcision, 8; cutting umbilical cord, 4;
vaccination, 2; fistula, stone, ligation of carotid, of radial, of
ulnar, of femoral arteries, amputation of arm and of thigh, 1 each;
phimosis, 2. Leeching, extraction of teeth, and circumcision are most
dangerous operations in bleeders.
The bleeding is always a capillary oozing, and the vessels are not
seen. It may last for hours, or even many days and weeks, and the
amount of blood lost may be enormous. Epistaxis may be fatal in
twenty-four hours. In Coates' case a medical student lost half a gallon
of blood in twenty-four hours, and in the ten days which the bleeding
continued it was estimated that he lost about three gallons.
The healing of a wound in a bleeder may take place rapidly, either with
or without suppuration. When the hemorrhage is large or prolonged,
severe anæmia follows, from which, as a rule, the patients recover with
remarkable rapidity.
The interstitial hemorrhages--petechiæ, ecchymoses, hæmatoma--may be
spontaneous or the result of injuries. The petechiæ occur most
frequently in the skin, particularly of parts distant from the
heart--the legs and arms, less often the face. On the mucous and serous
surfaces they are less common. They resemble ordinary purpuric spots,
and crops may come out with symptoms of swelling and pain in the
joints. Large extravasations--hæmatoma--are most frequently of
traumatic origin and may follow the slightest blow, as in a case of Sir
Wm. Jenner's, in which from the fall of a rubber ball on the thigh an
enormous extravasation took place between the knee and trochanter.[172]
They are blue, black, or reddish-black at first, and in their
absorption go through the various changes in color which we notice in a
bruise. These blood-tumors may occasionally arise spontaneously.
[Footnote 172: Legg, etc., p. 68.]
The arthritic affections in hæmophilia are very remarkable, and so
{936} common as to form prominent features in the disease. There may be
simple pain in and about the joints, or swelling with redness and signs
of intense inflammation. The attacks may come on suddenly with fever,
resembling closely acute rheumatism. The large joints are usually
affected, the knees most often, then the elbows, ankles, and shoulders.
There may be repeated attacks, and at last great crippling and
deformity. The small joints are rarely affected. In cold, damp weather
the attacks are most common; occasionally they follow traumatism. In
addition to the joint troubles, bleeders suffer much with irregular
pains in the limbs, particularly during change of weather, or these
pains with arthritis may usher in an attack of hemorrhage.
Many other irregular symptoms are described in the monographs, some of
which have no intimate relation with the disease. The anæmia has, of
course, all the features of the traumatic form. Digestive troubles,
after the bleeding, are common, and are due to the anæmia. The Buel
Brothers[173] mention that in two of their cases the patients showed a
marked inclination to eat sand and earth. Children with the hemorrhagic
tendency pass through the ordinary diseases of infancy like others.
Whooping cough is very liable to cause epistaxis. Rheumatism and
scrofula are said to be common in bleeder families.
[Footnote 173: _Op. cit._]
The blood in bleeder cases is, as a rule, normal, so far as our present
means of investigation enable us to decide. When a hemorrhage has
continued for some time, it is thin and watery, but at the beginning of
the bleeding the blood is usually rich in corpuscles and fibrin and
coagulates firmly. The salts have been found increased in quantity. No
change has been noted in the corpuscles, the number of which is stated
by several observers to be increased. Prior to a hemorrhage there may
be, according to some writers, a state of plethora or increase in the
total quantity of blood, and the tolerance of the loss, so much greater
in bleeders than in ordinary persons, is adduced in support of this
view.
MORBID ANATOMY.--Not many changes other than those of profound anæmia
have been found in the bodies of bleeders. An unusual thinness of the
walls of the vessels, first noted by Bladgen in 1817,[174] has been met
with in a number of cases; in a few instances hypertrophy of the heart;
in others a rounded foetal shape of the organ. Within the past few
years careful microscopical examination has been made of the tissues
and blood-vessels of bleeders. Kidd[175] found degeneration of the
muscle-fibres of the middle coat of the arteries, and the endothelium
of the small arteries, veins, and capillaries was swollen,
proliferated, and some of the small veins were blocked with the
products. Legg[176] reports a case in which Klein made a most careful
examination with negative results, and he stated that of six such
examinations which had heretofore been made, in only one case (Kidd's)
were important changes found. At the same meeting of the London
Pathological Society, Theodore Ackland also reported a case with
negative results as regards histological changes.
[Footnote 174: _Medico-Chirur. Transactions_.]
[Footnote 175: _Medico-Chirurgical Society's Transactions_, vol. lxi.]
[Footnote 176: _Lancet_, Oct. 27, 1884.]
The joint changes have been studied in a number of cases. Hemorrhage
has been found in and about the capsule, and the acute swelling may be
due largely to it, as was shown in Hutchinson's case,[177] in which he
aspirated the joint. When it lasts any time, there is great staining of
the cartilages and discoloration. There may be inflammation of the
synovial fringes and erosion and destruction of the articular surfaces
(Legg).
[Footnote 177: _Trans. State Med. Soc. N.Y._, 1877.]
The PATHOLOGY of the disease is unknown. No doubt two circumstances
combine in hæmophilia--congenital fragibility of the vessels and a
defect in coagulability of the blood--but whereon these depend we are
as yet entirely ignorant. There is no evidence of the nature of the
anatomical changes in {937} the vessels which permits of their ready
laceration, and none on the nature of the alteration of the blood which
prevents the normal thrombus formation in a wound; and in the absence
of information on these points theories must necessarily be
unsatisfactory, and their discussion, in a work of this practical
nature, profitless.
The DIAGNOSIS presents no difficulty in members of a bleeder family, in
whom slight joint trouble and petechiæ are as much manifestations of
the disease as the more severe hemorrhages. In a large majority of
cases the tendency becomes manifest at an early date. The spontaneous
umbilical hemorrhages of infants are, as a rule, to be excluded, being
dependent upon, or associated with, jaundice or syphilis or a mycosis
(Weigert[178]). The hemorrhagic diathesis may develop in children or
members of a healthy family and prove fatal, and the question in such
cases always comes up, Are they instances of hæmophilia? There seems to
be a desire to limit this term to cases of an hereditary nature only;
but when a child shows a marked tendency to multiple hemorrhages,
spontaneous or traumatic, which tendency persists and is not merely
transitory, and particularly if there are joint troubles, I think that
under these circumstances we have a genuine case of hæmophilia; and
such a child, if he--it is more likely to be a male--survives and
marries, may be the founder of a bleeder family. These are the
congenital in contradistinction to the hereditary cases. In the
histories of the bleeder families we frequently come back to the origin
in a person born of a healthy stock in which there have been no
hemorrhagic tendencies. On the other hand, single severe uncontrollable
hemorrhages in children or adults are not to be ranked as hæmophilia
unless there have been other features pointing to the existence of the
diathesis. The literature abounds in cases of this kind, many of which
are described as hæmophilia. In doubtful cases it is very difficult to
decide, as in a case of Forscheimer brought before the Academy of
Medicine of Cincinnati.[179] In the review of American literature we
have excluded all cases in which the hereditary or congenital
characters were not well marked.
[Footnote 178: _Cohnheim's Pathologie_, i. 382.]
[Footnote 179: _Cincinnati Lancet and Clinic_, 1884.]
It may be useful to put down here for the guidance of the practitioner
the varieties of bleeding commonly met with, and which must not be
confounded with hæmophilia:
(1) The umbilical hemorrhages of infants, due to jaundice or to
syphilis hæmorrhagica neonatorum, etc.
(2) Purpura simplex, seen often in debilitated, rarely in healthy,
children, usually confined to the legs, and in some cases I have seen
it associated with rheumatic pains or swellings in the knees and
ankles.
(3) Peliosis rheumatica, an affection which in the large interstitial
hemorrhages and the joint swellings touches hæmophilia in a curious
way. It too may show itself in several members of the same family.