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Conference on Therapy

Treatment of Thrombophlebitis

T HESE
are stenographic
of Pharmacology
reports of conferences by the members of the Department
and of Medicine of Cornell University Medical College and New
York Hospital, with collaboration of other departments and institutions. The qwstions
and discussions involve participation by members of the staff of the college and hospital,
students, and visitors. A selected group of these conferences is published in an annual
volumr, Cornell Conferences on Therapy, by the Macmillan Company.

DR. WM. DEWITT ANDRUS: The subject There has been an unfortunate tendency in
of the conference today is the treatment of recent years to confine the scope of dis-
thrombophlebitis. This disease has been a cussions on this subject to thrombophlcbitis
source of a great deal of worry and annoy- in postoperative patients and further. to
ance to clinicians and is the cause of a great thrombophlebitis of the lower extremities.
many tragedies. It is encountered in both There are many important types of the
medical and surgical cases. It is, therefore, disease. There is the one due to chemical
of interest to all of us. The discussion will be irritants, such as arsphenamine and con-
opened by Dr. Irving Wright. centrated vitamin C solutions. Another type
DR. IRVING WRIGHT: I may preface my is due to chronic trauma. for example, per-
remarks by saying that the treatment of sistently tying shoe laces too tightly over the
thrombophlebitis constitutes one of the most arch of the foot. There is suppurative
controversial subjects in the field of medicine thrombophlebitis in which the infection ex-
today, .just as it has been for the last fifteen tends from a nearby abscess or severe infec-
years. We have tried to steer a course be- tion There is thrombophlebitis associated
tween the two extremes, on the one hand, of with various blood dyscrasias, such as
prejudice and resistance to new advances in polycythemia and leukemia. There is the
therapy and on the other, of overenthusiastic type associated with thrombo-angiitis ob-
acceptance of therapeutic measures which literans. Frequently, it is the presenting
have not seemed especially sound. Such a problem in thrombo-angiitis obliterans, the
course has been quite difficult. Numerous underlying disease escaping recognition by
forms of treatment have been suggested, the physician. There is also thrombophlebi-
many of which have enjoyed only temporary tis migrans which is relentless and frequently
popularity. There was, for example, the spreads to all parts of the venous system,
plan of immediate ambulation without any ending fatally in a high percentage of pa-
supplementary measures such as venous tients. It is evident that the treatment of
ligation or anticoagulant therapy. The use thrombophlebitis cannot be reduced to a
of leeches was widely advocated abroad for simple routine. The treatment of each pa-
many years, and to a lesser degree in this tient must be decided on the basis of the
country. Lumbosacral block was advocated etiologic factors and the presenting patho-
as a curt, and although it has proven to be logic changes.
of value in some patients, it is no longer re- In any large hospital, the largest numbers
garded as a cure. of cases of thrombophlebitis are secondary
Thrombophlebitis is not a single disease. to surgical or obstetrical procedures, but in
232 Conference on Therapy
office practice and the practice of internal with a thin layer of petrolatum or similar
medicine one frequently sees cases due to the substance to prevent maceration of the skin
other causes. and a moist, hot pack is applied. This may
The difference between thrombophlebitis be in the form of turkish towels dipped in
and phlebothrombosis has received con- hot water, wrung out and laid loosely around
siderable emphasis, perhaps more than it the extremity which is then covered with a
deserves. It is true that thrombi in phlebo- rubber blanket and surrounded by hot
thrombosis are not fixed firmly to the walls water bags. The hot pack is kept on fqr
of the veins during the early days when there twenty out of twenty-four hours, allow-
is little inflammatory reaction. In most in- ing four hours for aeration and drying
stances as time elapses they become firmly of the skin. In severe cases with
fixed and cannot be distinguished patho- marked edema, both lumbosacral sympa-
logically from thromboses due to thrombo- thetic block and hot packs may be used
phlebitis. The important matter is that simultaneously. The application of hot
venous thromboses, except those due to packs to an extremity immediately after
thrombo-angiitis obliterans, are capable of lumbosacral block seems to prolong the
producing emboli. The silent thromboses vasodilating effect of the blodk, reducing
frequently produce emboli as devastating as vascular spasm and permitting more free
the ones that are easy to recognize. It is im- drainage.
possible to predict whether or not a patient The matter of activity versus rest has
who has a thrombophlebitis in the legs is long been debated and it is still unsettled.
going to have a fatal pulmonary embolus; There were some who believed that one
therefore, all thrombophlebitis must be re- should wrap a bandage tightly around an
garded as serious and potentially fatal if affected leg and instruct the patient to walk
steps are not taken to prevent the formation forty or sixty blocks a day, if there were no
of emboli. symptoms. I have seen some very poor re-
Let us consider briefly the several thera- sults from this form of therapy. There are
peutic measures which have long been those who believe in keeping the patient at
studied, although in the case of some of them complete rest in bed until signs of the disease
considerable doubt still prevails regarding have completely subsided, as determined by
the best procedure. I believe there is a the return to normal of the sedimentation
fairly universal agreement today that, in the rate, blood count, heart rate and tempera-
case of a patient with thrombophlebitis of ture. A middle course between these two
the lower extremity with edema, elevation extremes seems to be the present tendency.
of the extremity is helpful in reducing the Those who have been using anticoagulant
edema to a minimum. To keep the affected therapy have been allowing their patients
extremity in a dependent position or at the up earlier, keeping them in bed between six
level of the body is of no therapeutic value and ten days rather than twenty-eight or
and may actually be harmful. thirty days.
Whether heat or cold should be applied The control of epidermophytosis is a
to such patients has long been debated. The point of very great importance in those pa-
consensus at present seems to favor heat, if tients with the idiopathic type of thrombo-
properly applied. I am not sure that we phlebitis. Some believe’that there is a very
know how to apply it properly. The technic close causal relationship between fungus
described by Barker is now most acceptable. infection and thrombophlebitis of the lower
The affected extremity is carefully covered extremities, either allergic or by direct
AMERICAN JOURNAL OF MEDICINE
Conference on Therapy 233
invasion of the vein by the infectious agent. tory. It appears as though its exponents
;Zlso, the fungus produces cracks in the skin have been chasing the rainbow’s end from
which facilitate entry of secondary invaders. the lower saphenous vein all the way up to
In many patients who have had thrombo- the superior vena cava. One of the short-
phlebitis repeatedly, recurrences are appar- comings of treatment by ligation is that
ently prevented by the simple expedient of emboli may result from thrombi forming at
keeping the dermatophytosis under control. the site of any ligation. Thrombophlebitis
‘l-here is one point, the importance of and varicosities also sometimes recur after
\vhich I cannot emphasize too strongly, ligation of the affected vein. I have a patient
namely, that of refraining from making in the hospital now who never did have an
physical examinations of the chest in which embolus from the original thrombophlebitis,
patients are instructed to take deep breaths but promptly after a bilateral femoral liga-
for the purpose of determining whether or tion she began to have emboli and con-
not an infarction of the lungs has taken tinued to have them until treated with
place or the location of the infarct. Deep anticoagulants. Edema may also sometimes
breathing increases the negative pressure in occur following ligation. It is maintained
the chest, thereby increasing the speed of by the exponents of ligation of the inferior
blood flow from the extremities and which vena cava that following this procedure
may break off the loose tails of the thrombi. there is less edema than is seen after femoral
If a person was operated upon ten days ligation, but on reading the reports of a few
previously or if he has an acute phlebitis years ago one sees that some enthusiasts
and suddenly develops a stabbing pain in the then maintained that there was no edema
chest and coughs up some blood, it is quite following femoral ligations. I believe there
probable that he has developed a pulmonary are specific indications for ligation but this
embolus. It is of minor importance to learn procedure should not be used indiscrimi-
exactly where the infarct is. It is purely an nately. It is indicated if there is a lesion in a
academic question. There have been several lower extremity which gives rise to recurring
deaths following shortly upon such examina- emboli. Ligation is a much safer procedure
tions. So far this dangerous procedure has now that anticoagulant therapy is available
received only brief mention in the literature. and anticoagulant therapy should always bc
Sliding an x-ray cassette under the patient’s used following venous ligation. Varicose
chest is a much safer way of locating an veins, of course, constitute the major field
infarct. for ligation and no one can dispute the im-
11 patient should also be advised against portance of the operative procedure in these
violent coughing and straining at stool, and cases.
it is up to the doctor to see that the patient Now we come to another sub.ject of con-
dots not indulge in either. There have been siderable controversy, namely, anticoagu-
a number of patients with thrombophlebitis lant therapy. Heparin was the first of the
who have died during defecation. I knew chemically effective anticoagulant agents.
one patient who died under these circum- We have followed its use with great interest
stances a month after she was discharged since it became available in this country for
from the hospital, at a time when the the treatment of thrombophlcbitis. It pro-
thrombophlebitis appeared to have subsided longs the coagulation time. Statistics clearly
completely. show that it markedly reduces the number
Venous ligation as an aid in treating of pulmonary emboli and the number of
thrombophlebitis has had a troubled his- deaths. It is administered, as most of you
AMERlCAN JOURNAL OF MEDlCINE
Conference on Therapy
know, either by continuous intravenous in- even remotely represent coagulation time as
fusion so as to keep the coagulation time it occurs in the blood vessels. I should like to
preferably between twenty and forty-five quote some hitherto unpublished figures
minutes, or by repeated intravenous injec- from Dr. Kadish of the Mayo Clinic. Using
tions of 75 mg. every three or four hours. the Lee-White method he found the coagu-
This method produces marked fluctuations lation time from six to seven minutes with
in the coagulation time, as high as one the glass tube, from thirteen to fourteen and
hundred minutes shortly after the injection, even up to nineteen minutes with the lucite
with a return to normal before the next tube and considerably higher values with
injection. Dr. Loewe has been developing the collodion or paraffin tube. With the lu-
a menstruum which releases heparin slowly. cite tube the normal value of thirteen to
The present menstruum for an intramuscu- nineteen minutes is found shortened to six
lar injection cannot be considered entirely to eight minutes in those patients with
satisfactory; its injection is extremely pain- thrombophlebitis and prolonged to thirty
ful to the patient, it is difficult to control and to forty minutes or more in a patient taking
it produces nausea in some patients, but I dicumarol. Even with the glass tube, if the
think it is a move in the right direction and test is carefully performed, it can be shown
the subject should be pursued further. There that dicumarol prolongs the coagulation
are many disadvantages in the use of time but the use of the lucite tube provides
heparin. It is an expensive procedure. So far, a much more sensitive method for demon-
it can be administered only by injection and strating this change. In our laboratory,
the danger of hemorrhage from improper however, the results with the lucite and
use is well known. It requires close super- other tubes have been too unpredictable to
vision by the house staff both day and night be used as a guide to dicumarol dosage.
for the duration of its administration in Dicumarol therapy also has several dis-
order to check the blood coagulation time, advantages. It requires daily prothrombin
although with the intermittent method the tests and the laboratory must be prepared
number of checks of coagulation time is to do them. It is difficult to get laboratories
reduced markedly. to do the test accurately. As with heparin
Dicumarol has now become more popu- there is the risk of hemorrhage if the patient
lar. It is inexpensive. It can be given by oral is not watched carefully. There are several
administration. Dicumarol interferes with gaps in our knowledge of the action of
the production of prothrombin and it affects dicumarol. Work on intravascular clotting
the coagulation time. There has been some in animals is not sufficient, so our knowledge
question about the effect of dicumarol on the of the action of dicumarol has to advance
coagulation time and unless the test is largely by cautious experiments on man.
properly made one may fail to detect a There are some very striking figures on
prolongation of the coagulation time. In the value of dicumarol therapy. One might
this connection a word should be said about mention those of Barker and his group at the
the Lee-White glass tube method. Some im- Mayo Clinic in which they compared the
portant work has recently been undertaken results in 897 patients with thrombophlebitis
in a number of institutions to study the types treated without anticoagulant agents before
of tubes other than glass, because it has long emboli developed, with the results in 138
been recognized by those of us working in similar patients treated with dicumarol. An
the field of peripheral vascula,r diseases that incidence of 10.6 per cent of subsequent
the glass tube Lee-White method does not thrombophlebitis or pulmonary embolism
Conference on Therapy 235
was rcduccd to 2.9 per cent in the group of postoperative thrombophlcl)i t is. l’cr-
with dicumarol; also, an incidence of 5.7 mitting the blood pressure to fall to a low
per tent of fatal pulmonary embolism was level and the associated shock ccrtainlp
reduced to 0 per cent in those treated with predispose to coagulation of blood. espe-
dicumarol. They also made another type of cially in the vessels of the lower cstremity.
analysis. They compared the results in 678 The care of the patient after operation is
patients who had suffered one or more non- equally important. Having the patient do
fatal embolus and did not receive anticoagu- exercises while in bed and employing early
lant therapy, with the results in 180 similar ambulation help to reduce the incidence of
patirnts treated with dicumarol. An inci- thrombophlehitis and cmboli, cspccially
dence of 43.8 per cent of subsequent throm- those fatal emboli which arise from the lower
bosis or cmbolus was reduced to 1.1 per extremity. Statistics from various labora-
cent in thosr treated with dicumarol; also, tories of pathology show that the rnajority
an incidence of 18.3 per cent of fatal pul- of these fatal cmholi from the lower ex-
monary embolus was reduced to 0.6 per tremity arise from the deep femoral circula-
cent in those treated with dicumarol. It is tion. When conservative measures fail to
noteworthy that substantially similar results prevent the appearance of cmboli or
in very large groups of patients have been thrombophlebitis the surgeon naturally
reported by Jorpes and his collaborators tends to take more active steps.
from the Karolinska Institut in Stockholm, There has been a great deal said about
where they used heparin in some patients ligation. In our clinic here we do not follow
and dicumarol in others. in the footsteps of some of those farther up
DR. ANDRUS: As Dr. Wright has pointed the coast who even do prophylactic ligation.
out the therapy of thrombophlebitis is com- Nevertheless, when one is confronted with
plicatcd and none of the various methods of what appears to be a thrombophlebitis
treatment which have been used in the past with embolism, interruption of the deep
have been entirely satisfactory, but cer- circulation is certainly indicated. It should
tainly a great advance has been made with be undertaken immediately. Where one
the use of anticoagulant therapy. I think may limit treatment to the use of anticoagu-
that perhaps the internists and surgeons, lant therapy alone, especially in the surgical
while they see the problem from a common cases, is a question that has certainly not
point of view in many ways, look upon cer- been settled.
tain aspects of it somewhat differently. I In tracing the history of ligation one finds
will ask Dr. Glenn to discuss this problem that the first approach involved ligation of
from the surgical point of view. the superficial circulation. Division of the
DR. FRANK GLENN: To the surgeon, pul- deep femoral circulation was not attempted
monary embolism is always a matter of until later. For the majority of patients the
grave concern and the surgeon’s attack on it division of the deep femoral vessels is
must be,gin with the preoperative prepara- probably the procedure of choice. I cer-
tion of the patient and the care of the patient tainly believe that following ligation of’
during the operation. these vessels the incidence of emholi has
It stems to me that the care which has been reduced. Along with the interruptions
been excrcisccl in the operating room in the of the deep femoral circulation, anticoag-u-
i
past Sew years to maintain an individual’s lant therapy as already outlined. is certainly
blood pressure at a proper level has been of indicated. Some object to operative pt-o-
great importance in reducing the incidence cedures because of the edema and disabilit!
236 Conference on Therapy
which may result. Generally speaking, we Dr. Wright, will you make a few remarks
have found that division of the deep femoral on the diagnosis of thrombophlebitis? How
circulation is not followed by as much edema do you demonstrate its presence?
as one is led to believe. Usually, the higher DR. WRIGHT: I wish to say first, that I
the interruption of the venous return the agree with Dr. Andrus in that if we keep
better is the collateral circulation which is these individuals active, get them out of bed
thereafter established. If a patient has been very early, move their legs, have them
ill for a long time or has had some surgical exercise in bed and take deep breathing
procedure involving one extremity and exercises the number of thrombi that will
thrombophlebitis has developed, then the be available for pulmonary emboli will
choice rests between a bilateral ligation of probably be markedly reduced. The diag-
the femoral and the common iliac vessels. nosis of most cases of thrombophlebitis is
In patients with pelvic involvement ligation usually relatively easy. One of the first
of the inferior vena cava is indicated. This symptoms is pain, which is frequently along
is an heroic procedure and is occasionally the course of a vein. One can usually see
fatal but I believe it can be utilized to good some redness along the course of the vein
advantage if combined with anticoagulant and detect tenseness on palpation. Some-
therapy. times the vein is still patent but often the
DR. ANDRUS: The topic today is the treat- lumen is obliterated quickly by thrombus.
ment of thrombophlebitis but I am sure that Sometimes there are cramps in the muscles
all of those interested in the subject agree and there is usually fever, tachycardia and
that the most important aim is the preven- increased sedimentation rate. Those are all
tion of thrombophlebitis. Unfortunately, cardinal signs; however, many patients
our understanding of the factors which complain of only vague pain in the calf and
produce it is very meager. However, I think Homans’ sign is equivocal. This sign is con-
that we do know of certain measures which sidered positive when pain is produced in
tend to diminish the incidence of thrombo- the gastrocnemius area as the result of
phlebitis, such as the avoidance of infection, dorsiflexing the foot by pressure on the distal
the prevention of stasis in the veins of the portion of the sole of the foot with the patient
legs resulting from the use of tight dressings, in the supine position. A positive sign is sug-
from distention of the abdomen or from the gestive of thrombophlebitis, although other
low blood pressure of shock. The use of conditions such as strains and injuries of the
deep breathing exercises prophylactically soleus muscle may simulate it. The amount
after operation has been widely employed, of pain may depend on how hard the ex-
as well as the use of routine postoperative aminer presses against the ball of the foot
exercises with the patient in bed until early because one can produce pain in a normal
ambulation is feasible. Deep breathing is soleus muscle by overtaxing it. I am sure
used to prevent venous stasis. It is certainly there are some false Homans’ signs elicited
to be carefully avoided if thrombophlebitis by too strenuous dorsiflexion of the foot but
is present or even suspected. No methods of at any rate one must watch for the minimal
prevention are universally successful. It is to signs. There are patients with marked
be hoped that continued investigation will thrombosing processes and fatal embolisms
give us greater understanding of this com- in whom there are no signs prior to the
plicated group of diseases and will reveal emboli.
more effective means of prevention and bet- DR. ANDRUS: As Dr. Wright said, whether
ter therapeutic agents. a patient with thrombophlebitis should be
AMERICAN JOURNAL OF MEDICINE
Conference on Therapy 237
kept quiet or should be active has been the per cent but there is no satisfactory proof
sub.ject of a good deal of difference of opin- that so much depression of prothrombin
ion. You may be interested in the story activity is necessary.
which was told about Dr. Bloodgood at DR. GOLD: Perhaps a word should
Johns Hopkins. He preached to his students be said here about the meaning- of the terms
most assiduously that all patients with “prothrombin time” and “prothrombin
thrombophlebitis should be kept perfectly activity.” There is a good deal of misunder-
quiet. He himself, in the course, I think, of a standing about them. The prothrombin
pneumonia for which he was treated at content of the blood is expressed as “pro-
home. developed a thrombophlebitis. Dur- thrombin activity.” This may bc greatly
ing sleep he fell out of bed and spent the reduced before there is any striking change
next ten days on the floor, refusing to be in blood clotting. Since the test for “pro-
moved. At least he was consistent and had thrombin time” depends on speed of clotting
the courage of his convictions. Dr. Wright this test becomes abnormal only after con-
mentioned that some compromise might be siderable reduction has taken place in the
reached between complete quiet and early prothrombin content of the blood. In actual
activity. Would you care to say a little more testing of the “prothrombin activity” using
about where the compromise should be blood dilutions (which are in effect the same
made? as reducing the concentrations of prothrom-
11~. WRIGHT: In the light of our present bin) it has been found. for example, that by
knowledge I should say that the patient the time the prothrombin content has been
should be kept quiet until he is under ade- reduced from 100 to as low as 30 per cent
quate anticoagulant therapy. Experience at of the normal, clotting has been only
the Mayo Clinic and in Sweden indicates moderately impaired as shown by the fact
that these patients may be allowed out of that the “prothrombin time” has only risen
bed with very little risk, within five days from about twelve to eighteen seconds, or a
after adequate anticoagulant therapy has rise of only about 50 per cent. Beyond a
been established. given point, however, further reduction in
A word about what we consider adequate the prothrombin content ( prothrombin
therapy. With heparin, I think, a prolonga- activity) begins to influence greatly blood
tion of the coagulation time to between clotting (prothrombin time) and small
twenty and forty-five minutes is adequate. further reductions in the content of pro-
It is much safer than if it is allowed to go up thrombin begin to produce large increases
to seventy-five minutes. Beyond this a dan- in the prothrombin time; for example: a
gcrous level is reached very quickly. We reduction of the prothrombin activity from
have had very satisfactory results in some 30 to 10 per cent of the normal. delays
hundreds of patients, with the coagulation clotting so much that it raises the pro-
time no higher than forty-five minutes. thrombin time from 18 to 38 seconds, that
With dicumarol we seek to maintain the is, a rise of about 100 per cent. The point of
prothrombin time between thirty and fifty this is to emphasize the need for bearing in
seconds which with the technic we use is mind the difference between the terms
between 20 and 10 per cent of the normal “prothrombin activity” and ‘.prothrombin
prothrombin activity. That seems to be an time.” ‘The further point is that after a con-
adequate range. Some workers believe that spicuous rise in prothrombin time has taken
thr anticoagulant effect is satisfactory only place with dicumarol therapy, the patient
if the prothrombin activity is lower than 20 must be watched carefully, for small addi-
238 Conference on Therapy
tional doses of the drug by causing further look carefully enough in medical patients
small reductions in the prothrombin con- confined to bed.
tent, may produce abrupt rises in the DR. ANDRUS: I would certainly claim no
prothrombin time, blood clotting being so special ability for the surgical service, for I
markedly impaired as to give rise to spon- know there are many patients in whom we
taneous hemorrhages. recognize the thrombophlebitis only after
In the actual carrying out of the test for the embolus but there are certainly a great
the prothrombin time in the laboratory, many in which we recognize thrombophle-
there appear to be so many variables that it bitis beforehand.. I would guess that we
is necessary to have a control subject tested recognize the phlebitis in about half of the
at the same time, as a means of insuring the patients before they have an embolus.
accuracy of the test. It might be well for the DR. WRIGHT: Do you not think that that
physician to consult with the laboratory represents a very strong teaching point,
which performs the prothrombin test for namely, our house physicians should be
him, in order to be sure of the precise mean- trained to make daily observations post-
ing of the figures which are reported to him operatively on the legs of all patients? I am
since the results obtained by different sure that many more of these cases would
laboratories are somewhat different de- be recognized if that were a standard pro-
pending on the conditions of the test. cedure on all surgical services.
I should like to ask Dr. Wright what DR. PARDEE: How long do you believe
percentage of bed patients who develop a anticoagulant therapy should be continued
pulmonary embolus give evidence of throm- and what criteria would you use for stopping
bophlebitis prior to the”embolus. it?
DR. WRIGHT: I do not know of any ade- DR. WRIGHT: It depends on the type of
quate figures on that point. Perhaps some of case. We like to keep the individual who has
the surgical staff can answer the question had a simple thrombophlebitis of short
more specifically. duration on anticoagulant therapy for
DR. ANDRUS: After an embolism occurs three to four weeks. I have recently been
you can nearly always determine where it told that at the Mayo Clinic they continue
came from, but I know of no figures on the dicumarol therapy for only eight to ten days
number of patients in whom the diagnosis of and that their results have not changed with
thrombophlebitis is made or is possible be- this brief therapy. We have perhaps been
fore emboli have occurred. playing overly safe. However, we see a
DR. HAROLD E. B. PARDEE: In relation to considerable number of patients who have
Dr. Gold’s question I think it is only in a thrombophlebitis for from four months to
small percentage of patients in whom one three years almost without interruption. The
recognizes signs of thrombophlebitis prior phlebitis is sometimes migratory and some-
to the embolic phenomena. times largely localized to one set of veins. It
DR. GOLD: I agree with that. I have seen seems desirable to keep these patients on
many cases of pulmonary embolus in non- anticoagulant therapy for four weeks at
surgical patients but I can recall only two least. Such prolonged treatment has been
instances in which signs of phlebitis pre- strikingly successful in interrupting chronic
sented themselves prior to the embolus, to phlebitis.
suggest the possibility of embolus. It may STUDENT: How do you manage the post-
be that the signs of thrombophlebitis are operative patient who develops a hemor-
often not very conspicuous and we do not rhage while on the anticoagulant therapy?
AMERICAN JOURNAL OF MEDICINE
Conference on Therapy 239
DR. ANDRUS: The first thing is to discon- VISITOR: Is the treatment with dicumarol
tinue the anticoagulant. By giving massive stopped abruptly?
transfusions and massive doses of vitamin K, DR. WRIGHT: We usually find it desirable
the hypoprothrombinemia associated with to taper the dosage down gradually over
dicumarol can be corrected to a degree. several days. With an intelligent and co-
For hemorrhage occurring during the use operative patient it is sometimes possible to
of heparin, protamine has been suggested continue the dicumarol with the patient
for neutralizing the heparin but its use is ambulant outside the hospital, having him
still in the experimental stage. Transfusions go to a laboratory for tests of the prothrom-
are also useful. bin time.
DR. GOLD: Cromer and Barker gave a DR. JANET TRAVELI,: How often are these
single intravenous dose of menadione bi- patients checked and how much dicumarol
sulfite (a synthetic vitamin K), 64 mg. (4 do they receive?
mg. per cc.) to a group of patients in whom DR. WRIGHT: Most of our present ambu-
dicumarol had produced excessive pro- latory patients receive approximately 600
longation of the prothrombin time to such mg. a week in doses of 100 mg. daily; the
levels as eighty-five seconds or more, and dose is omitted on Sunday. That seems to be
fairly regularly obtained a prompt lowering adequate for most patients. Whenever possi-
of the prothrombin time. The result ap- ble we have the prothrombin time checked
peared in about two hours and reached a daily or every other day and, of course, the
maximum in about eighteen hours. These dose is omitted on any day when the pro-
doses of vitamin K are harmless. thrombin activity is below 15 per cent of
DR. WRICHT: The risk of hemorrhage in the normal.
these patients is very slight, if the prothrom- DR. ANDRUS: How predictable is the ef-
bin time is accurately tested and the daily fect of a given dose of dicumarol in a given
dose of dicumarol is withheld until the individual?
prothrombin level for that day is known. We DR. WRIGHT: In general, I believe that
have treated, or supervised the treatment after a patient receiving dicumarol has been
with anticoagulants of more than 800 pa- under observation for a period of two or
tients. We have had people die of carcinoma three weeks, one learns enough about that
or progressive thrombophlebitis migrans patient to predict fairly accurately what the
but we have not had, so far, a single patient effect of a dose will be. However, the sus-
die of hemorrhage from dicumarol. In the ceptibility of individuals varies greatly and
recently operated surgical case, of course, it is unsafe to predict the effect of a dose at
the risk is greater. It is customary at the the start of therapy. Every once in a while
Mayo Clinic to start dicumarol therapy on an article appears recommending 1,000 mg.
the second or third day postoperatively in of dicumarol as the first dose. Such dosage
order to lessen the danger of hemorrhage. is extremely dangerous. One may give 300
VISITOR: How long do you continue the mg. as the first dose relatively safely, and
dicumarol after the patient is ambulatory? 300 mg. on the second day, then tapering
DR. WRIGHT: We continue the patients off gradually to 200 mg., and 100 mg. daily.
on anticoagulant therapy after we get them If that dosage system is accompanied by a
up and about. We may keep them ambulant careful daily check of the prothrombin time,
in the hospital for an extra week or ten days. I do not think one will get into trouble very
It is like having a bear by the tail. We do frequently but one may anticipate some
not know exactly when to let go. minor hemorrhages.
240 Conference on Therapy
Before we close this discussion I think I of cool water, which frequently gives relief.
should say a word about the care of the pa- If it lasts more than three hours, they should
tient after he recovers from the acute call their physician. Most of them will say,
thrombophlebitis. Such care is one of the “Well, now that I know I don’t have to
most important, but also one of the most worry about pain that lasts less than an hour,
neglected, phases of the management of this I go ahead and do what I want to do and
disease. We must remember that thrombo- have stopped worrying about it.” There is
phlebitis can be arrested but it should never the fact that some pains may recur for
be regarded as cured. Most of these patients several years after an acute attack, and the
have pains when they stand a long time and patient’s failure to understand this may re-
when the barometer changes. They worry sult in much needless physical and psycho-
about these pains and many of them become neurotic invalidism.
psychoneurotic because they never know
whether the pain presages another attack of SUMMARY

phlebitis. The neglect of proper prophylactic DR. LAWRENCE W. HANLON: Some of the
care increases the tendency of edema, ulcers problems of treatment of thrombophlebitis
and varicose veins. We can prevent these were explored this afternoon. There are
unfortunate sequelae by several means. It many varieties of thrombophlebitis differing
was found that a group of patients wearing in their causes, clinical aspects and patho-
knee length, well made, individually fitted logic changes. The regimen of treatment
elastic stockings for the first year after their should be adjusted to the special requirements
thrombophlebitis had at the end of five of the particular patient. The differentiation
years far less edema, far fewer pains and far between phlebothrombosis and thrombo-
fewer ulcers of the legs than those patients phlebitis has limited value, since after a time,
who went without stockings. I think that the the thrombi in the two become pathologic-
use of such stockings is very important. It is ally indistinguishable. While thrombophle-
essential to instruct the patient on how to bitis often makes its appearance with
prevent dermatophytosis. It is also most characteristic signs and symptoms, such as
necessary to explain to the patient that pains pain, tenderness, swelling, fever and ele-
in the legs do not always mean a recurrence vated sedimentation time in many of these
of the thrombophlebitis. Fear of a recurrence patients the onset is silent and the first indi-
may be one of the most serious disabilities. cation of the disease is a pulmonary embolus.
We have seen patients who, five years after Emphasis was placed on the desirability of
the attack, are fearful of moving about or making routine systematic examinations of
unnecessarily restrict their activities because the legs in surgical and non-surgical patients
they fear that when they have a pain in confined to bed, as a means of uncovering
their leg they are on their way to a recur- cases of thrombophlebitis sufficiently early
rence. This reaction. is understandable in to make it possible to prevent pulmonary
people who have passed through two or complications.
three attacks. We have formulated some The discussion covered measures that are
arbitrary rules which have proved helpful useful in the prevention of thrombophle-
to these patients. If the pain lasts less than bitis, such as care against traumatization of
an hour they should ignore it, for most of vessels, prevention of infection, control of
these pains last less than fifteen minutes. If epidermophytosis, free movement in bed,
it lasts one to three hours, they should lie early ambulation, deep respiratory exercises
down and elevate the feet or get into a tub and the avoidance of the latter in thrombo-
AMERICAN JOURNAL OF MEDICINF
Conference on Therapy 241

phlebitis to prevent pulmonary embolism. tremity in order to prevent embolism,


Attention was called to the highly contro- although others prefer a more conservative
versial nature of the measures used in the course, ligating only after there is proof that
treatment of thrombophlebitis; the applica- the vein is a source of recurrent emboliza-
tion of heat and cold, the use of leeches, tion. The choice of site for ligation depends
prolonged rest, free exercise, early ambula- on the location of the phlebitis.
tion, dependent and elevated position of the The use of the anticoagulant agents,
extremity, lumbosacral sympathetic block, heparin and dicumarol, appears to be an
prophylactic venous ligation and the use of advance of the first importance in the treat-
anticoagulant agents. It was indicated that ment of thrombophlebitis. Figures were
the consensus favors hot, moist packs to the cited showing most extraordinary results
affected extremity, the elevated position following their use; for example, second
of the limb to control swelling, a middle thrombosis or embolus was reduced from an
course in relation to rest and activity, the incidence of nearly 50 per cent to about
patient being allowed up and about after a 1 per cent, cases of fatal pulmonary
short period of rest even though the disease embolus with an incidence of nearly 6 per
is not fully checked provided anticoagulant cent completely vanished. The discussion
therapy is employed. There are those who embraced the details of application dosage,
recommend prophylactic ligation of the mode of action, dangers and methods of
veins in thrombophlebitis of the lower ex- control of anticoagulant therapy.

AMERICAN JOURNAL OF MEDICINE