THE LIBRARY OF THE ASSOCIATION OF THE ALUMNI i OF THE COLLEGE OF PHYSICIANS AND SURGEONS IN THE CITY OF NEW YORK SCHOOL OF MEDICINE OF COLUMBIA UNIVERSITY . 17. Phlebitis and Thrombosis 17 exhausting diseases, but this is much less common in the arteries than in the veins. Such a condition is illustrated by a specimen in the museum of St. George's Hospital (Series VI., 6id), taken from the body of a woman aged thirty-seven years, who died from gangrene of the lower limbs. The specimen shows part of the aorta and the iliac arteries filled with old coagula adherent to the internal coat of the artery, but the coats of the vessel are not thickened (Fig. 2). The general tendency to thrombosis is shown by the fact that similar coagula were found in the main arterial trunks and in the veins of both lower limbs, in the iliac veins and lower part of the vena cava, in the arteries and veins of the left kidney, and in the left ventricle and right auricle of the heart. A specimen from a similar case is shown in Fig. 3. Thrombosis of arteries has been observed in connection with various acute diseases, especially influenza, enteric fever, typhus fever, and pneumonia. Here again it is much less common than in the veins, and is found chiefly in the arteries of the lower extremities. Cases have also been recorded by Dr. Dickinson^ of death from rapid thrombosis of cerebral arteries in which there was no disease of the vessels and no acute illness. * It appears,' says Dr. Dickinson, * that in most of these cases two influences have been in operation. There has been disease of the heart, particularly contraction of the mitral opening. This occurred in four of the five cases. The general circulation has thus lost freedom, and a liability to venous and capillary congestion has been established. Besides this, there has been some especial cause by which the cerebral vessels have been overloaded or the circulation in them disturbed.' ^ SL George's Hospital Reports^ vol. i., 1886, p. 257. 2 iS Phlebitis and Thrombosis Mr. Jonathan Hutchinson^ has also recorded instances of the sudden occlusion of the femoral and other large arteries by thrombosis, in which he could discover no evidence of disease of the vessels. Professor Osier ^ has related a remarkable case of a labourer, aged twenty, who was attacked with diarrhoea, loss of appetite, and epistaxis, followed by abdominal pain, fever, and delirium. Beneath the skin of the anterior thoracic region and the abdomen were many localized blue spots, but no characteristic eruption. On the tenth day of the illness symptoms of gangrene of the lower limbs appeared ; the pulse was 120 to 140 ; tempera- ture, 101° to 103°; there was great restlessness, persistent delirium, and abdominal tenderness. No pulsation could be felt in the femoral or popliteal arteries. The blood was examined with negative result ; the urine was scanty and albuminous. The man died about two weeks from the beginning of his illness. The case was regarded as one of typhoid fever, but the autopsy negatived this : the ileum was normal. There was thrombosis of the lower two inches of the abdominal aorta, with plugging of iliacs and femorals, the clots firm, reddish-brown, and closely adherent. The mesenteric vessels were free, but two large branches of the splenic artery were plugged. There were infarcts in the right kidney and spleen, from the latter of which spread a general peritonitis. Heart, lungs, and brain were normal. No otitis, no bone lesions. No micro-organisms were found in the blood during life. After death numerous micrococci were found in the infarct of the spleen and the lymph covering it. In septic conditions it has been observed that the blood- platelets are abnormally numerous, and a primary arterial ^ Archives of Surgery, vol. vii., p. 29, and vol ix., p. 100. 2 Transactions of Association of America7i Physicians, 1887, p. 135. Phlebitis and Thrombosis 19 thrombosis may occur, to which the infection of the vascular wall is secondary. Arterial thromxbosis occurs most frequently in the lower limbs, but does not exhibit the preference shown by the veins for the left side. The symptoms are chiefly those due to obstruction of the vessel, and will depend very much upon whether this takes place rapidly or slowly, and also upon the position and importance of the artery concerned. When the artery is rapidly blocked the symptoms resemble those of embolism, from which it is often impossible to distinguish them. When the thrombus is of gradual formation there may be sufficient opportunity for the development of a collateral circulation to prevent any serious results, though this will, of course, depend upon the condition of the arteries generally, and their capacity to respond to the call upon their development. The gradual obliteration of an artery may only be recognisable by the increasing hardness and thickness of the vessel, its want of elasticity, and the feebleness of its pulsation. There is often, however, some pain and tenderness felt in the course of the artery. When more rapid arterial thrombosis occurs there is usually acute pain, and the artery is tender to pressure ; the nutrition of the limb is seriously imperilled, and, as in embolism, unless a collateral circulation is soon established, gangrene results. The danger of gangrene is less in the upper than in the lower extremities, but is greatly increased if the veins are also thrombosed, as in the case quoted on p. 17. Rapid obstruction of visceral and cerebral arteries is most often of embolic origin, although it may sometimes be due to thrombosis. ^ Dr. W. H. Brown has recorded a 1 See Dr. Dickinson's cases, S/. George^ s Hospital Eeports^ vol. i., p. 257. 2 — 2 20 Phlebitis and Thrombosis case of thrombosis of the abdominal aorta, iHac and femoral arteries, in which gangrene of the intestine occurred probably, I suppose, from thrombosis of the mesenteric artery.^ Obstruction of the coronary arteries is commonly due to a combination of arterial degeneration and thrombosis, the sudden development of symptoms (as, e.g., angina pectoris) depending upon the completion of obstruction by throm- bus of a vessel already narrowed by thickening of its coats. Thrombosis of the pulmonary arteries will be con- sidered in connection with venous thrombosis and pulmonary embolism. Senile gangrene is usually caused by thrombosis of the small terminal arteries, the first symptom of which is often acute pain. Doubtless arterio-sclerosis and feeble circulation play an important part in its production, and the mischief is often started by some slight injury or inflammation, but the thrombosis is the immediate cause. ^ It is important to recognise this because, if the condition is seen and appreciated at its commence- ment, the danger may be averted by appropriate treat- ment. The reason why thrombosis is not more common in connection with arterio-sclerosis is that the heart is usually hypertrophied, so that the arterial resistance is overcome by the increased heart power. Venous Thrombosis. The conditions under which coagulation of the blood occurs in the living veins are very similar to those which ^ Transactions of Clinical Society of Londofi, vol. xxvi., p. i. 2 Diabetic gangrene is probably caused by the same conditions. See remarks by^M. Barthdlemy at the Fifth International Dermato- logical Congress {^Transactions, vol. ii., part i. p. 252). Phlebitis and Thrombosis 21 lead to the formation of coagula in the arteries, but venous thrombosis is more common than arterial. It has already been pointed out that any impairment of the nutrition of the endothelium of the bloodvessels leads to the formation of thrombi upon the vessel wall, and such an impairment of nutrition occurs whenever the rapidity of the circulation is materially diminished for any length of time. ' This,' as pointed out by Dr. Lazarus- Barlow,^ ' depends upon the fact that the intima, in- cluding the endothelial cells, unlike the rest of the vessel wall, derives its nutriment from the blood in the lumen of the vessel, and not from that conveyed by the vasa vasorum. In most cases a diminution in velocity of blood-flow is the proximate cause of the thrombosis. Thus, in the heart the circulation is slowest in the appendices auriculae, behind the flaps of the auriculo-ventricular valves, and between the columnse carneas. Normally it is rapid enough even here to maintain the nutrition of the cardiac endothelium ; but when old age or wasting disease or any lesion of the valves has impaired the musculature of the heart, and it is no longer able to maintain the circulation at its normal velocity, the endothelium in these situations suffers first and to the greatest extent, and it is just in these situations that thrombi are found. For the same reason thrombosis more commonly occurs in veins than in arteries.' In wounds, injuries, and ligature of veins, coagulation of the blood occurs, partly as a consequence of the mechanical disturbance of the blood -flow, and partly from the interference with the integrity of the endo- thelium. It occurs more readily than in wounds of arteries, because of the slower and less forcible blood- ^ 'A Manual of General and Experimental Pathology,' by W. S Lazarus- Barlow, 1904, p. 117. 22 Phlebitis and Thrombosis stream, and perhaps also because of the greater coagula- bility of the venous blood. ^ Degeneration of the venous walls, dilatations, varices, and anything producing obstruction or retardation of the blood-current, are causes of thrombosis by disturbing the normal relations between the blood and the venous endothelium. Inflammation of veins is a common cause of thrombosis, and, owing to the thinness of the venous coats, any sur- rounding inflammation invading the outer tunic of the vein is easily conveyed to the endothelium. This is one reason for the greater frequency of venous as compared with arterial thrombosis. The presence of micro- organisms either in the blood or the venous wall will give rise to thrombosis, as is frequently seen in septic inflammations. Venous thrombosis also occurs in con- sequence of changes in the blood ; in connection with various acute and chronic diseases ; and in conditions of great debility. When coagulation occurs in a living vein, it is often difficult to say whether the thrombus is the cause or the result of phlebitis. If a vein is obstructed by a thrombus the nutrition of the endothelium at once suffers, and if the clot contains micro-organisms they will soon invade the intima, the resistance of which will be already lowered, and an endophlebitis will ensue. But, on the other hand, there are numerous cases in which it is certain that the changes in the vein precede the thrombosis ; for instance, in the chronic inflamma- tion which occurs in connection with varix, in syphilitic endophlebitis, in tubercular invasion of the vein, and in 1 Wooldridge has shown that the plasma of peptonized blood, which does not coagulate on the addition of fibrin ferment, coagulates freely if in addition a stream of carbonic acid is passed through it. (' The Chemistry of the Blood,' p. 294.) FIG. 4. — FEMORAL VEIN FROM A CASE OF INFECTIVE PHLEBITIS : SHOWING GREAT THICKENING OF COATS OF VEIN AND DISINTEGRATING CLOT. [ To face p. 23. Phlebitis and Thrombosis 23 other degenerative changes. So also in septic inflam- mation spreading to the outer coat of a vein from a neighbouring focus, invasion takes place from v^ithout inv^ards, and thrombosis does not occur till the intima is reached. The most serious of these conditions are those of septic origin. Here the presence of micro-organisms gives rise to coagulation, and the clot has an infective character which it communicates to any part to which it is carried. The process may begin in inflammation of the outer coat of a vein originating in a septic or suppurating wound, or in an infective focus, as in middle-ear disease or acute necrosis of bone ; this, spreading to the inner coats, leads to endophlebitis and consequent thrombosis ; or the organisms may invade the intima from the circulating blood or from an infected thrombus brought from a distant part. In these septic cases, whichever the mode of origin, the coats of the vein are always found much thickened (Fig. 4). Phlegmasia dolens is an example of septic phlebitis ex- tending from the uterine veins, through the iliacs, to the femoral and other veins. Thrombosis beginning in the uterine veins may extend from the uterus to the iliac and femoral veins, and even to the vena cava. Sometimes, however, the phlebitis would appear to. be the result of the transmission of infecting organisms by the blood, and not of direct extension from the uterus. There is an admirable paper on phlegmasia dolens, by Dr. David D. Davis, in the Transactions of the Royal Medical and Chirurgical Society for 1823,^ in which the author describes several cases of the affection, and proves by dissection that its proximate cause is an inflammation 1 Transactions of the Royal Medical and Chirurgical Society, vol. xii., p. 419, 1823. 24 Phlebitis and Thrombosis and obstruction of ' one or more of the principal veins within and in the immediate neighbourhood of the pelvis.' But he did not trace the disease of the veins to its source in the uterus, though he recognised its connection with parturition and with disease of the pelvic organs.^ The paper is illustrated by beautiful coloured drawings show- ing the condition of the iliac veins and the contained clot. Dr. Robert Lee^ in the year 1829 contributed two papers, with excellent coloured illustrations, to the same Society, in which he reported thirteen cases of phlegmasia dolens, in six of which the actual condition of the iliac and femoral veins was ascertained by dissection. ' From this I was led to infer,' says Dr. Lee, ' that inflammation of the iliac and femoral veins gives rise to all the pheno- mena of that disease in puerperal women, and that in phlegmasia dolens the inflammation commences in the uterine branches of the hypogastric veins, and subse- quently extends from them into the iliac and femoral trunks of the affected side.'^ In the second paper Dr. Lee^ reported three cases of cancerous ulceration of the uterus in which there was inflammation of the internal, common, and external iliac and femoral veins, with all the characteristic symptoms of puerperal phlegmasia dolens. In a third paper, published in 1853,^ Dr. Lee reported forty-three additional cases in confirmation of his ex- planation of the pathology of the disease, and he adds that it has been demonstrated by morbid anatomy that phlegmasia dolens is a disease which may take place in women who have never been pregnant, and in the male ^ Transactions of the Royal Medical and Chirurgical Society, vol. xii., p. 445. 2 Ibid., vol. XV., p. 132, and p. 369. ^ Ibid., vol. xxxvi., p. 281. ^ Ibid., vol. XV., p. 369. ^ Ibid., vol. xxxvi., p. 281. Phlebitis and Thrombosis 25 sex, and that under all circumstances the proximate cause is the same — namely, inflammation of the iliac and femoral veins. In the same volume of transactions is an elaborate paper by Dr. F. W. Mackenzie,^ containing ' Researches on the Pathology of Obstructive Phlebitis, and the Nature and Proximate Cause of Phlegmasia Dolens,' and record- ing a number of experiments on animals made with the view of studying the effects of inflammation of the iliac veins. From these experiments Dr. Mackenzie concluded that in a healthy animal the results of obstruction of the common iliac vein, produced by the application of a ligature or other irritants, were confined to the immediate seat of injury, and showed no tendency to spread beyond it. There was no attendant fever or constitutional disturb- ance, and only a slight and transient oedema of the limb. But, on the other hand. Dr. Mackenzie ascertained by another series of experiments, that if the blood was vitiated from local or constitutional causes, large portions of the venous system may become obstructed and inflamed independently of any injury of the veins ; and he assumed that these phenomena depended upon ' a disturbance of the relations which normally exist between the blood and the lining membrane of the veins.' Finally, applying the results of his experiments upon animals to an analysis of TOO cases of phlegmasia dolens in the human subject, he concluded that the obstruction and inflammation of the iliac and crural veins, which is an essential feature of the disease, depends upon the presence of abnormal material in the blood.^ Here, it will be observed, was a very close approach to ^ Transactions of the Royal Medical and Chirurgical Society, vol. xxxvi., p. 169. ^ Ibid., vol. xxxvi., p. 240. 26 Phlebitis and Thrombosis the recognition of a microbic origin for the disease ; and it may be noticed that the important and accurate advance in the knowledge of the causation of phlegmasia dolens, made by the three authors to whose work I have drawn attention, was the result of laborious pathological investi- gation, of experiments upon animals, and of careful clinical observation — a striking contrast to the wild and unfounded theories which had previously prevailed. Pylephlebitis is an example of suppurative inflammation and thrombosis of the portal vein, originating in an in- fective focus in some part of the area belonging to the branches of the vein. The most common origin is sup- puration in connection with the vermiform appendix, a point to be borne in mind in relation both to the diagnosis and treatment. The symptoms are often obscure, but are chiefly suggestive of pyaemia. Rigors, fever of the remittent type, sweating, jaundice, and enlargement and tenderness of the liver, would make the diagnosis probable, especially if there were evidence of intestinal disease, for which a careful search should be made. In the light of recent investigations it seems probable that many of the so-called idiopathic or spontaneous thromboses are of microbic origin ; but there are some in which no micro-organisms can be found in the thrombi : while, on the other hand, bacterial invasion of the wall of a vein may occur without the formation of a thrombus. Septic phlebitis is a condition attended by serious symptoms and grave danger. The severity of the symptoms will depend upon the virulence of the infection, the susceptibility of the individual, and the position of the mischief. In the acute form of suppurative phlebitis the wall of the vein is invaded by pyogenic organisms ; coagulation occurs in the inflamed vein, and the thrombus is itself Phlebitis and Thrombosis 27 infected, and by its softening carries infection into the blood-stream, giving rise to septicaemia and pyaemia. An admirable paper on this subject was communicated by Mr. Arnott to the Royal Medical and Chirurgical Society in 1828, in which he showed the relation between the primary and secondary affections in phlebitis.^ If a superficial vein is affected it is observed to be swollen and tender, and the skin over it shows a red line. These conditions tend to spread rapidly along the vein in the direction of the blood-stream. If a deep vein is attacked pain is felt in the part, soon followed by swelling, tender- ness and suppuration. The constitutional symptoms are severe ; the temperature and pulse rise rapidly ; rigors supervene, followed by profuse sweating ; the tongue is dry, appetite is lost, and there may be delirium. To these symptoms are soon added those of general pyaemia : rapid oscillations of temperature, rigors, sweating, and disseminated suppurations. Such cases usually end fatally, partly by the general poisoning of the blood and the consequent fever and exhaustion, and partly by the occurrence in important organs, especially the lungs, of centres of inflammation and suppuration. Chaucer described the condition very accurately in the ' Knighte's Tale.' ' The clothred blood, for eny leche-craft, Corrumpith, and is in his bouk i-laft, That nother veyne blood, ne ventusyng, Ne drink of herbes may ben his helpyng. The vertu expulsif, or animal, Fro thilke vertu cleped natural, Ne may the venym voyde, ne expelle. The pypes of his lounges gan to swelle, And every lacerte in his brest adoun Is shent with venym and corrupcion. ^ Transactions of the Royal Medical and Chirurgical Society, vol. XV., p. I. 28 Phlebitis and Thrombosis Him gayneth nother, for to get his lyf, Vomyt up-ward, ne doun-ward laxatif ; Al is to-broken thilke regioun ; Nature hath now no dominacioun. And certeynly wher natur will not wirche, Farwel phisik ; go here the man to chirche.' When the infection is less virulent the symptoms are correspondingly less severe; and many gradations are met with down to cases in which, though there is a well- marked phlebitis, the symptoms of infection are but slight. I have no doubt that some of the cases of so- called idiopathic phlebitis are of this nature. The infection may be of a low degree of virulence, and the subject may have a high resisting power or immunity. Moreover, the infected thrombus may be isolated from the general circulation, and so produce only local effects. In other cases the phlebitis may become manifest, while the source of the infection may be obscure. For instance, I have seen a case in which a slowly-forming ischio-rectal abscess, accompanied by so little pain that the patient disregarded it, gave rise to a septic phlebitis, manifested by rigors, fever and sweating, as well as by severe local symptoms. In some of the cases of chronic pyaemia in which large superficial collections of pus occur I have found indubit- able evidence of thrombosis, and on opening the abscesses the pus was seen to be mixed with broken-down blood- clot. In all cases of phlebitis it is therefore well to seek for a source of infection, for in many instances in which the disease begins with but slight constitutional disturbance symptoms of severe infection subsequently develop. These symptoms probably arise coincidently with the disintegration of the infected thrombus and the entrance into the blood-stream of septic organisms. The successful Phlebitis and Thrombosis 29 treatment of such cases will, of course, depend very largely upon the removal of the focus of infection. Notable examples of this are the cases of chronic sup- puration of the middle ear giving rise to endophlebitis and purulent thrombosis of the lateral sinus, in which life may be saved by ligature of the internal jugular vein, and the thorough removal from the sinus of the infected clot. In other cases of phlebitis the focus of infection may be found in a deeply-seated abscess, a suppurating wound, or an osteomyelitis, and the first essential in the treat- ment is the removal or disinfection of such focus. Abscesses must be freely opened and thoroughly cleansed and drained ; suppurating or foul wounds must be disin- fected; bones the subject of osteomyelitis must be removed by resection or amputation ; an accessible vein suspected to contain a septic clot should be ligatured above and below the thrombus, and the portion between the ligatures excised. Beyond these local measures the treatment must be adapted to the general condition of the patient. In the severe and advanced cases it will be that of pyaemia. Quinine should be given in frequently repeated doses, and the strength supported by appropriate food and stimulants. The exclusion of all insanitary conditions should be carefully looked to, and the patient should be kept in a well-ventilated and light room, and removed as soon as possible into fresh and healthy surroundings. He should not remain ' in populous city pent, Where houses thick and sewers annoy the air';^ but should seek ' airs, vernal airs Breathing the smell of field and grove.''^ ^ Milton, 'Paradise Lost,' ix. 445. ^ Ibid.^ iv. 264. 30 Phlebitis and Thrombosis He should go where he can ' look into the fair And open face of heaven. '^ For pure air and sunshine are valuable aids to recovery, and the high moorlands are often more beneficial than the sea-coast. ^ Keats, ' Sonnets,' x. LECTURE II Varieties of phlebitis and thrombosis. — Thrombosis in connection with {a) varix ; {b) gout ; {c) syphilis ; {d) enteric fever ; {e) typhus fever ; (/) chlorosis ; {g) influenza ; {h) pneumonia ; {i) appendicitis ; {j) gastric ulcer and other abdominal diseases. — ' Idiopathic ' throm bosis. — Preference of venous thrombosis for left lower limb. Thrombosis of upper limb. Pulmonary embolism and thrombosis. Symptoms of non-infective phlebitis and thrombosis. — Explanation of occurrence or absence of oedema. — Results of venous obstruction and obliteration. — Obliteration of vente cava;. Leaving now the cases of undoubted septic origin, we come to the consideration of a class in which the phlebitis is of quite different character, and of which the dangers are of a quite different kind. Many of these undoubtedly depend upon changes in the blood which favour the occurrence of thrombosis, to which the phlebitis is secondary. It seems possible that in some of the diseases with which venous thrombosis is associated, toxic or other chemical changes in the blood may affect the nutrition of the leucocytes and red corpuscles, or favour the pro- duction and increase of the blood-plates, and thus, aided by an enfeebled circulation, lead to the formation of a thrombus. Professor Osier ^ has observed that in acute fevers the ■^ Osier, ' Cartwright Lectures,' op. at., p. 365. 31 32 Phlebitis and Thrombosis blood-plates do not become more numerous in the early- stage of the disease, but increase in number as the patient becomes weaker and more debilitated. In typhoid fever, for instance, there is no increase during the first week, but a notable increase in the third and fourth weeks. It will be observed that the increase in the number of the blood-plates occurs just in that stage of disease which is especially liable to thrombosis. Dr. J. H. Pratt/ of Boston, has reported a series of observations on the relative number of the platelets in various diseases. There was a marked increase in chlorosis ; the greatest diminution was observed in a case of purpura hemorrhagica. In other cases in which the slowness or feebleness of the circulation would seem to be the chief factor, it is difficult to say how far the diminished nutrition of the vessel wall is the immediate cause of coagulation, and how much is due to the invasion of micro-organisms. Mr. W. C. C. Pakes^ has recorded the case of an anaemic and phthisical girl of thirteen years who was admitted to Guy's Hospital with thrombosis of the left iliac vein and swelling of the left lower limb. A week before death the right leg became swollen, owing to thrombosis of the right iliac vein. Post-mortem there were thrombi in both iliac and femoral veins ; and in the thrombus of the left femoral vein, which was carefully excised and examined, was found the Bacillus proteus vulgaris. Mr. Pakes remarks that ' in health the bactericidal power of the blood is probably sufficiently great to destroy this organism if it should gain access to it ; but when from any cause this action is diminished, the ■'■ Johjts Hopkms Hospital Bulletin., May, 1905, p. 201. 2 Transactions of Pathological Society of London^ vol. li., p. 47. Phlebitis and Thrombosis 33 organism becomes relatively pathogenic. The bacteri- cidal power may be reduced in many ways, of which a wasting disease and a dose of ptomaines are two.' Dr. F. C. Turner^ has published a case of thrombosis of the iliac vein in a man, aged thirty-six, who died of Hodgkin's disease, a condition in which there are im- portant changes in the leucocytes, possibly due to micro- organisms. Thrombosis is a common occurrence in varicose veins, and is usually the result of injury ; but in gouty persons the subject of varix it is often seen in association with eczema, when no injury can be traced. Coagulation is especially apt to occur in the cyst-like dilatations and tortuous veins so frequently met with in the lower part of the thigh and the neighbourhood of the knee. Such varices are very liable to become inflamed because of their prominence on a part of the limb often exposed to injury, and because in this situation they are particularly subject to irritation from pressure and fric- tion, as in riding and other exercises. In varicocele also thrombosis is not infrequently caused by injury, and in some cases the resulting obliteration of the veins produces a complete cure of the varicocele. In gouty persons it is more often the smaller nasvus-like patches of varicose veins in the lower part of the leg, or the muscular branches of the calf, which are affected. Considering the frequency with which thrombosis occurs in varicose veins, it is remarkable that it is comparatively seldom attended with serious symptoms. There is usually but little constitutional disturbance, and the local discomfort is often but slight ; the chief danger is of displacement of the clot and consequent embolism. This serious event is fortunately not of very common ^ Transactions of Pathological Society of Lo?idon^ vol. xxix,, p. 344. 34 Phlebitis and Thrombosis occurrence, but it is a danger which ought always to be borne in mind in the treatment of such cases, particularly those in which the blocked vein is near a joint or in direct communication with the main trunk, as, for instance, in the neighbourhood of the knee or of the saphenous opening. Gouty Phlebitis. — Since the publication in i865 of Sir James Paget's well-known lecture, gouty phlebitis has been a well-recognised disease. There can be no doubt that persons of gouty habit or ancestry are more than commonly liable to phlebitis, and that in them the affec- tion has usually certain distinguishing characters. To quote Sir James Paget's description : ' Gouty phlebitis is far more frequent in the lower limbs than in any other part ; but it is not limited to the limb that is, or has been, the seat of ordinary gout. It affects the superficial rather than the deep veins, and often occurs in patches, affecting, for example, on one day a short piece of a saphenous vein, and on the next day another separate piece of the same, or a corresponding piece of the opposite vein, or of a femoral vein. It shows herein an evident disposition towards being metastatic and symmetrical — characters which, I may remark by the way, are strongly in favour of the belief that the essential and primary disease is not a coagulation of the blood, but an inflammation of portions of the venous walls.'^ Sometimes gouty phlebitis begins in the deep veins of the calf, of which the first symptom may be a sudden and acute cramp-like pain, which is soon followed by deeply- seated tenderness to pressure. There is a tendency to ^ 'Clinical Lectures and Essays,' p. 293, 1875. See also Sir Prescott Hewett in Presidential Address to the Clinical Society ■{Transactions, vol. vi., p. xxxvii), who relates cases of gouty phlebitis, and points out that it often begins in the back of the leg, midway between the heel and the ham. Phlebitis and Thrombosis 35 frequent recurrences of the attacks, which are especially apt to occur when the patient is fatigued or below the usual standard of health. It is sometimes the only mani- festation of gouty inheritance, but is frequently combined with other obviously gouty symptoms. It is not usually attended with much constitutional disturbance. An example of troublesome and frequently recurring phlebitis occurred in a patient from whom I had on two occasions removed uric acid calculi by lithotrity. He lived most abstemiously and on a most carefully regulated diet, but nevertheless had frequent attacks of phlebitis, alternating with eczema, cystitis, and other symptoms of the uric acid diathesis. It seems to me, however, that it is the fashion at the present time to attribute many cases of phlebitis, as of other diseases, to gout or the uric acid diathesis, when there is no evidence whatever of either the presence or the inheritance of gout. Phlebitis is sometimes seen in association with, or during the convalescence from, acute rheumatism, but I do not think that this is sufficiently common to justify the inference that there is any special connection between the two diseases. Syphilitic phlebitis occurs in two forms. In one variety the superficial venous trunks are attacked, chiefly those of the lower, but sometimes those of the upper, extremities. The walls of the veins undergo inflammatory thickening, and thrombosis ensues. This is seen in the early erup- tive period. Later in the course of the disease a nodular phlebitis occurs, attacking chiefly the subcutaneous veins of the lower limbs, especially those which are varicose or sclerosed. The condition is characterized by nodular thickenings of the venous coats, with limited thrombosis. It is said to occur also in the corpus cavernosum and in 3—2 36 Phlebitis and Thrombosis the spermatic cord. In neither form is there usually any considerable constitutional disturbance, but the affected veins are painful and tender. The disease yields to the usual antisyphilitic treatment.^ Thrombosis is frequently met with during convalescence from enteric fever, and is not uncommon in other condi- tions of exhaustion such as result from prolonged or serious illness, and in the late stages of phthisis. It occurs occasionally, but not often, in the acute stage of enteric fever. Professor A. E. Wright and Dr. H. H. G. Knapp^ have proved that the coagulability of the blood is diminished in the acute stage, but increased in the convalescent stage of typhoid fever ; the coagulation time being four and a half minutes in the convalescent stage, as compared with twenty minutes during the pyrexia. They show, more- over, that the blood of these convalescents is not only much more coagulable than the normal, but that it also contains twice the normal amount of lime salts ; whereas, if the lime salts are brought within the normal limits, the coagulability is reduced to even less than that of normal blood. The authors suggest that the increased coagulability of the blood of typhoid convalescents is dependent upon an excess of lime salts, and that this excess is derived from the milk upon which typhoid patients are chiefly fed. Cow's milk, it is noted, contains i part in 600 of lime, as compared with i part in 800 contained in lime-water. The remedy indicated is the administration of citric ^ See Papers byJulHen, Barthelemy, E. Hoffmann, etc., in Transac- tions of the Fifth hiternatiojial Dermatological Co7tgress, 1904, vol. ii., part i., pp. 225-265. 2 ' On the Causation and Treatment of Thrombosis occurring in Connection with Typhoid Fever,' Transactions of the Royal Medical and Chiriirgical Society^ vol. Ixxxvi., p. i, 1903. Phlebitis and Thrombosis zi acid as a decalcifying agent ; and in seven patients, in all of whom the blood was found to be abnormally coagulable, it was observed that the administration of citric acid (36 grains three times a day) was followed by a decalcifi- cation of the blood and a corresponding diminution of its coagulability. It is suggested that, with a view to restrict- ing the intake of lime salts, the milk given might be partially decalcified, and thus rendered more easily digestible and less constipating. This can be effected by adding to each pint of milk from 20 to 40 grains of citrate of soda. These valuable suggestions appear to me to be applicable to many other conditions besides typhoid fever. Dr. W. W. Keen, of Philadelphia,^ in his work on * The Surgical Complications and Sequels of Typhoid Fever,' collected 128 cases of venous thrombosis following fever. Of these, ' only four involved the upper extremity alone, two involved both the arm and leg, and all the other 122 cases were limited to the lower extremities.' He observes that, whereas arterial thrombosis occurs with almost equal frequency on the two sides of the body, two-thirds of the cases of venous thrombosis were on the left side ; and that both forms of thrombi, arterial and venous, 'form most frequently during or just after the period of greatest cardiac weakness — a weakness felt most at such distant points as the legs.' Of 148 cases, 58 occurred in the second and third weeks. The influence of the enfeebled circulation is also shown in the location of the thrombus. ' The coagulation takes place at points mechanically favourable to slowing of the current — e.g., the bifurcation of arteries and the valves of the veins.^ Dr. Keen also gives reasons for thinking that ^ 'The Surgical Complications and Sequels of Typhoid Fever,' by W. W. Keen, M.D., LL.D., London, 1898, p. 74. 2 Op. cit., p. 363. 38 Phlebitis and Thrombosis some at least of the cases of necrosis of bone following typhoid may be due to thrombosis of the arteries or veins.^ Dr. Murchison^ recorded a remarkable case in which, during the course of a severe attack of typhus fever, gan- grene of both legs occurred in consequence of thrombosis of the iliac and femoral arteries, and of the femoral and popliteal veins of the left limb. The patient, a woman forty- five years of age, died on the forty-first day of illness. Dr. Murchison points out that, although there was gangrene of both legs, there was swelling only of the left leg, in which the vein, as well as the artery, was obstructed. He also remarks that in the venous thrombosis occurring in con- nection with fever it is almost invariably the left lower limb which is affected. Chlorosis, — This is a disease in which it is well known that there is an especial liability to thrombosis. This depends, no doubt, upon the condition of the blood, in which there is a great diminution both of the number of red corpuscles and also of their contained haemoglobin. The relatively greater number of white corpuscles in chlorosis and their slow movement along the walls of the bloodvessels are conditions favourable to the occurrence of thrombosis, as also is the increase in the number of platelets which has been observed. It would seem, also, that the chemical composition of the blood is altered, the potassium being diminished and the sodium and chlorine increased.^ Dr. Lee Dickinson^ has pointed out * that the intra- vascular coagulation brought about by the injection of foreign substances (snake venom and nucleo-proteid) into ^ O^. ciL, p. III. 2 Transactions of the Pathological Society of London, vol. xvi., p. 93. 3 Biernacki, Wiener Medicinische Wochenschrift, 1893^ pp. 1721 and 1765. '* Transactions of Clinical Society of London, vol. xxix., p. 63. Phlebitis and Thrombosis 39 the circulation of animals, takes place by preference in the venous system, and is greatly favoured by excess of carbonic acid in the blood. Chlorotic blood, by reason of its poverty in haemoglobin, is certainly deficient in oxygen, and probably equally overloaded with carbonic acid. The comparative infrequency of thrombosis in the cerebral sinuses, where the mechanical conditions seem so favour- able, is perhaps explained by the observation of Dr. Leonard Hill ' that the blood obtained from the torcular Herophili contained far less carbonic acid than that from the femoral vein.' Dr. A. E. Wright^ has shown that an increase of the carbonic acid in the blood much increases its coagulability, and he relates a case of haemophilia in which haemorrhage was arrested by the inhalation of carbonic acid gas. Chlorotic thrombosis is apt to be extensive and recurrent. When its seat is the cerebral sinuses, it is a condition of extreme gravity ; when affecting the ex- tremities, its chief danger is pulmonary embolism. 1 Proceedings of Royal Society., vol. Iv., p. 279 ; and ' On Methods of Increasing and Diminishing the Coagulability of the Blood,' Brit. Med. Jou7'n.., July, 14, 1894, p. 57. 2 Professor W. H. Welch, in an admirable article in Allbutt's ' System of Medicine ' (vol. vi., p. 200), analyzes a collection of 78 cases of venous chlorotic thrombosis, from which he deduces some instructive facts. These may be tabulated thus : Of 78 cases of venous chlorotic thrombosis — There was thrombosis of the cerebral sinuses in 32 (39 per cent.). Six of these had also thrombosis of the veins of the lower extremities (19 per cent.) ; in 4 the thrombus extended into the internal jugular vein. In 50 there was thrombosis of the veins of the lower extremities. (Bilateral in 46 per cent. ; unilateral in 54 per cent. — 34 left, 20 right. 64 per cent, began in left limb ; 29 percent, in right limb ; 7 per cent, in both limbs simultaneously. 25 percent, had pulmonary embolism — all but 2 fatal.) In 2 there was thrombosis of the veins of upper and lower extremities. In I there was thrombosis of the veins of upper extremities only. 40 Phlebitis and Thrombosis Thrombosis may occur in the condition of debility sequential to influenza, as to other febrile diseases ; but it is also not uncommon during the acute stage of the attack, when it is possibly due to the influenzal bacillus. Dr. T. J. Horder^ has recorded two cases of influenzal endocarditis in which the Bacillus influenzce from the blood was cultivated during life. In both cases there was marked leucocytosis. Thrombosis is also sometimes associated with pneumonia. It has been observed that inflammatory exudations that are associated with the presence of the pneumococcus show a marked tendency to coagulate.^ Peripheral thrombosis is a well-recognised complication of appendicitis. Notes of 1,000 cases of operation for appendicitis at the London Hospital were furnished by Mr. Hugh Lett at the discussion at the Royal Medical and Chirurgical Society in February, 1905. Among these 1,000 cases there were twelve of thrombosis of the veins of the lower extremities, and one case of pulmonary embolism. Of 442 cases of operation for appendicitis at St. George's Hospital, of which notes were furnished by Mr. Laurence Jones for the same discussion, nine had thrombosis of the lower limbs and three had pulmonary embolism. Of 863 cases reported by Dr. H. P. Hawkins, of Professor Welch says : ' After making due allowance for the undoubteoly disproportionate representation of embolism of the large pulmonary arteries in published records, this catastrophe remains sufficiently frequent to impart a certain gravity to the prognosis even of simple femoral thrombosis in chlorosis.' ^ Transactions of Royal Medical and Chirurgical Society^ vol. Ixxxix., p. I. '^ Lazarus-Barlow, ' Manual of Pathology,' second edition, 1904, p. 197. Phlebitis and Thrombosis 4^ St. Thomas's Hospital, there were two cases of throm- bosis of the veins of leg and two cases of pulmonary embolism. Mr. Aslett Baldwin reported 234 cases from the Middlesex Hospital, with one case of pulmonary embolism and thrombosis of iliac veins. Mr. Lockwood, of St. Bartholomew's Hospital, con- tributed 200 cases, with two cases of thrombosis of mesen- teric veins and one case of thrombosis of the iliac vein. Mr. G. E. Gask reported 795 cases at St. Bartholomew's Hospital, with five cases of venous thrombosis. Of 125 cases reported by Mr. H. S. Clogg and Mr. H. A. T. Fairbank, of Charing Cross Hospital, there was one case of thrombosis, both femoral veins being affected. Three hundred and fifteen cases were collected by Mr. Ralph Thompson, of Guy's Hospital, among which were six cases of femoral thrombosis and one of pulmonary embolism. Mr. G. R. Turner, of St. George's Hospital, reported 140 cases, with one case of thrombosis of the femoral vein and one case of pulmonary embolism. TABLE I. Operations for i\ppENDiciTis, showing Number of Cases of Thrombosis and of Pulmonary Embolism. London Hospital ... St. George's Hospital St. Thomas's Hospital Middlesex Hospital St. Bartholomew's Hospital Charing Cross Hospital ... Guy's Hospital No. of Cases. 1,000 442 863 234 795 125 315 Throm- bosis. 12 9 2 I 5 I 4 Pulmonary Embolism. I 3 2 I 3.77^ 42 Phlebitis and Thrombosis Thrombosis is also met with in connection with opera- tions for gastric ulcer and other abdominal diseases. Of fifty cases of operation at St. George's Hospital for per- forated gastric and duodenal ulcer recorded by Mr. T. Crisp English, there were three cases of thrombosis, all of the veins of the left lower extremity.^ Dr. A. H. Corder, of Kansas, has collected 232 cases of phlebitis following abdominal and pelvic operations. In 213 cases the left saphenous or femoral vein was affected. Dr. Corder asserts that phlebitis occurs in about 2 per cent, of all abdominal operations, and is especially frequent after operations on patients anaemic from hsemorrhage, as, e.g., abdominal hysterectomies for bleed- ing fibroids.^ There still remain a certain number of cases of throm- bosis and phlebitis in which no association with any precedent disease or injury can be traced, but which occur in apparently healthy individuals. This is the class usually spoken of as ' idiopathic' In the light of recent researches and increasing facilities for the detection of micro-organisms, it seems probable that some of these are really of infective origin, although the source of infection has not always been discovered. But there are others in which neither clinical nor pathological evidence of infec- tion can be obtained, and of which it must be admitted that the origin is obscure. Sir James Paget related two such cases.2 In both of these the upper extremity was affected, and the patients were healthy men. In the first case 4 inches of the axillary vein could be ^ Transactions of the Royal Medical and Chiriirgical Society., vol. Ixxxvii., p. 27. '■^ Journal of tJie American Medical Associatiojt, December 9, 1905, p. 1792. ■^ ' Clinical Lectures and Essays,' p. 305. Phlebitis and Thrombosis 43 felt blocked. The arm was swollen, and there were enlarged superficial veins over the upper part of the chest. Sir James Paget says : ' No cause whatever could be traced for this condition — no injury or pressure, no known inheritance of disease, no disturbance of the general health, past or present.' With the help of the hot douche, warmth, and friction, recovery took place in the course of a year. In the second case the arm was in a similar condition, and no cause for it could be discovered. ' It was uncer- tain how long this state of the arm had existed ; it had been observed only a week ; its rate of increase was unknown.' The patient remained in the same condition for a month, and was then treated by leeching and mercury, after a fortnight of which he had an attack of scarlatina, and while this was running its course all signs of the affection of the arm disappeared.-^ I will add another case. A healthy man, fifty-four years of age, living a temperate and healthy but busy life, was suddenly seized with acute cramp-like pain in the left calf. This was on the evening of a somewhat fatiguing day, but no unusual exercise or exertion had been undertaken. The pain subsided after a few hours' rest, but next day recurred, when walking and standing were somewhat painful. A careful examination revealed some deep-seated tenderness in the calf, but no swelling. The patient showed no sign of illness ; the temperature and pulse were natural, the urine clear and of normal acidity. He was not anaemic ; he had never had any signs of gout, nor was he of gouty ancestry ; he was not aware of having received any injury. Complete rest was prescribed ; the patient was confined to bed, and the limb covered with a layer of wool and lightly bandaged ^ ' Clinical Lectures and Essays,' p. 307. 44 Phlebitis and Thrombosis to a splint. Nevertheless, the phlebitis spread upwards to the femoral vein, with severe pain and moderate constitu- tional disturbance. Subsequently the right femoral vein was attacked, and in the second week symptoms of pulmonary embolism occurred. The patient, after a tedious illness, gradually recovered. 1 have seen other analogous cases, and I must admit that I cannot explain them. A paper was published in 1905 on this class of cases by Dr. John Bradford Briggs, of Washington.^ He describes a variety of phlebitis affecting the veins of the extremities, and occurring in the absence of all conditions that are commonly recognised as predisposing to inflammation of the veins. The condition occurs suddenly in persons apparently in perfectly good health, and, without fever or other disturbance, leads to obliteration of the affected vein. It is apt to recur, and to spread from the point at which the vein has previously become obstructed. Dr. Briggs quotes cases in which the saphena, the femoral, and the axillary veins were respectively the seat of the disease. He admits that the cases are * obscure alike in their pathology and in their remote and imme- diate etiology,' but thinks that the affection is due to sclerosis of the veins, and is concerned with the wall rather than with the contents of the vessel. Dr. Briggs refers to a French thesis by Dr. Daguillon,^ in which is described what the author calls a primitive form of phlebitis — i.e., a phlebitis without any immediate determining cause. It has a special clinical picture — that of limited, localized, superficial phlebitis, affecting the lower limbs, causing slight local and no general reaction. ^ ' On Recurring Phlebitis of Obscure Origin,' by J. B. Briggs, M.D.,/okns Hopkins Hospital Bulletin, June, 1905, p. 228. 2 Paris, 1894. 5. — THE RELATIONS OF THE ILIAC ARTERIES AND VEINS. THE LEFT COMMON ILIAC VEIN (w) IS SEEN CROSSED AT A RIGHT ANGLE BY (a) THE RIGHT COMMON ILIAC ARTERY AND {/>) THE LEFT INTERNAL ILIAC ARTERY. [ To face p. 45. Phlebitis and Thrombosis 45 It is of slow evolution, and shows a progressively ascend- ing march by successive attacks and relapses. The prognosis is serious, owing to the facility with which embolism occurs. This differs somewhat from the cases described by Dr. Briggs, and Dr. Daguillon believes that the process is mainly one of parietal thrombosis, and * is an indication of a general diathetic influence, shown in an arthritic constitution, with or without actual gout ' — a statement which does not appear to me to throw much light upon its causation or pathology. It will be observed that thrombosis occurring in connec- tion with fever, chlorosis, phthisis, and other debilitating diseases, after operations, and, indeed, whatever its cause, shows a curious preference for the left lower limb. The only reason for this preference which, so far as I know, has been suggested is the position of the left common iliac vein, the current in which may possibly be somewhat obstructed by the pressure of the right common iliac artery, under which the vein passes. On looking carefully at the anatomy of the vessel, I noticed that not only was the vein crossed by the right common iliac artery, but also by the left internal iliac artery as it passes downwards to the sacro-sciatic foramen, both of the arteries crossing the vein almost at a right angle, and in marked contrast to the relations on the other side (Fig. 5). This may not seem a very strong reason for the great predominance of thrombosis in the left vein, yet if the blood is in a condition in which a slight retardation of the current would be sufficient to turn the balance towards coagulation, this anatomical difference may be enough to determine the thrombus to the left side. It is possible also that the pressure of a loaded rectum may to some extent interfere with the venous circulation of the left side of the pelvis. 46 Phelbitis and Thrombosis Thrombosis may, however, occur in the upper Hmb. I have alluded to two cases of Sir James Paget's. Sir Prescott Hewett^ recorded a case in which, after small-pox, both axillary veins, as well as both external ihac veins, became permanently blocked. The patient, ' an officer in a heavy cavalry regiment, was nevertheless able to remain in the service and efficiently to discharge his duties, for a vast collateral circulation had been developed, and there was a mass of large tortuous veins spreading over the belly and chest.' Dr. Ormerod^ has published a case in which ' there was complete obstruction of both innominate veins, internal jugulars, subclavians, and anterior and external jugulars. They were filled with adherent clot. The clot was rather firmer on the right side than on the left. A projecting end of clot hung into the superior cava, but was not adherent there. The clot ceased at the opening of the azygos. The azygos, and the superior intercostal opening into it, were pervious and dilated. There was no clotting in the cerebral sinuses. The patient was under Dr. Gee's care, and was admitted for mitral stenosis. There was much dilatation of the left auricle and right chambers. The symptoms of thrombosis, which developed in the hospital, pointed to its commencement in the right subclavian vein. No local cause could be found for it post-mortem.' I have seen thrombosis of the veins of the upper arm occurring in, and associated with, simple debility. Dr. F. C. Turner ^ has recorded a case of thrombosis of the innominate, internal jugular, and subclavian veins, occurring in an anaemic man, aged forty-four years, who had suffered from severe haemorrhage from a malignant 1 Trans xctions of CI itiical Society of London^ vol. vi., p. xxxvii. 2 Transactiotts of Pathological Society of Lo?ido7i, vol. xL, p. 75. ^ Jbid., vol. xliii., p. 64. Phlebitis and Thrombosis 47 ulcer of the stomach. There was much swelHng of the arm, shoulder, and neck, and enlargement of the surface veins over the chest and upper arm. Dr. Wilberforce Smith has described^ an instance of thrombus, organized and adherent in the innominate and subclavian veins, in a case of pulmonary phthisis. There was a cavity in the apex of the lung, over which the pleura was thickened, and the adjacent part of the subclavian vein was thickened and narrowed. Four weeks before death cedema and lividity of the arm appeared. Besides these examples of thrombosis occurring in con- ditions which are of themselves of grave import, it is easily provoked in persons who are debilitated by over- fatigue, anxiety, starvation, or other depressing influences. Herein, although the debility is the predisposing cause, the immediate cause is most often some severe muscular effort, and the thrombus starts in the strained or over-used muscle. Such is the origin of most of the cases of non- infective thrombosis of the upper limbs, a condition not very often met with. Pulmonary Embolism. Pulmonary embolism may occur in any case of phlebitis or thrombosis, in the course of slight as well as severe attacks. The second and third weeks are the periods most liable to this danger, which is not often met with after the sixth week. Nevertheless, fatal embolism may be produced by violence, such as a blow or severe pressure applied to a blocked vein, at much later periods. Dr. Play fair, in a paper in the Transactions of the Patho- logical Society,^ collected twenty-five cases of thrombosis and embolism of the pulmonary artery occurring in women ^ Transactions of Pathological Society of London^ vol. xxxii., p. 70. ^ Ibid., vol., xviii., p. 68, and the Lancet, 1867, vol. ii., pp. 66, 93, 153- 4^ Phlebitis and Thrombosis after delivery, and pointed out that thrombosis occurs before the fourteenth day, often on the second or third day (fifteen cases) ; but that embolism does not occur until after the nineteenth day (seven cases). The detachment of a large venous thrombus, and its lodgment in the main trunk or in one of the chief divisions of the pulmonary artery, may cause almost immediate death. This detachment of clot usually ensues upon some movement of the limb or of the body, some sudden change of posture, or some pressure upon a blocked vein. Thus, sitting up in bed, which involves flexion at the groin, stooping, kneeling, or the movements concerned in leaving or returning to bed, have often been the immediate cause of this disaster. Sudden and intense dyspnoea occurs, with great pain in the chest, cyanosis, and feeble, irregular pulse, followed directly, or in a few minutes, by death. When smaller branches of the pulmonary artery are blocked the symptoms are less severe, and may either gradually increase and lead to a fatal end, or diminish and be followed by recovery. In other cases a localized pneumonia, with hsemorrhagic expectoration, may ensue. I have known this sequence of symptoms to recur several times, with eventual recovery ; but the condition is, of course, one of grave danger, demanding the most absolute quiet on the part of the patient. Pulmonary Thrombosis. Obstruction of the pulmonary artery may also occur from thrombosis. It is probable that in some of the cases recorded as instances of pulmonary embolism the obstruct- ing plug may have been formed in situ, and have been really due to thrombosis. Dr. Newton Pitt^ has collected ■^ Trajisactions of Pathological Society of London, vol. xliv., p. 48. Phlebitis and Thrombosis 49 orty cases of thrombosis of the pulmonary artery out of 3,218 autopsies at Guy's Hospital, and gives reasons for thinking that the condition is of much more frequent occurrence than is usually supposed. In many cases the clot forms gradually, and is situated in the smaller branches, so that there are no sufficiently characteristic symptoms to enable a diagnosis to be made during life.^ Sometimes, however, a thrombus may form in a large branch, giving rise to symptoms similar to those of embolism — severe and distressing dyspnoea, faint- ness, cyanosis, and great circulatory disturbance. These symptoms may subside, and recur at varying intervals with each addition to the clot, until at last the complete occlusion of the vessel brings about a fatal result. More rarely, thrombosis of the main trunk or its primary divisions is a cause of sudden death. Pulmonary thrombosis occurs under similar conditions to thrombosis of other arteries and veins, especially in feeble and cachectic states with lowered vitality and weak circulation ; and, although degeneration of the coats of the vessel is much less common in the pulmonary than in the other large arteries, yet such disease may be the starting- point of a thrombus. I have collected from the post-mortem records of St. George's Hospital for the last ten years, which include 2,903 necropsies, the following cases of venous thrombosis. The list shows the relative frequency with which the veins were affected in fatal cases. ^ Cf. Paget, Transactions of Royal Medical a?id Chirurgical Society, vol. xxvii., p. 162, and vol. xxviii., p. 353, who shows 'that a large and quickly increasing part of the pulmonary circulation may be arrested without immediate danger to life, or any striking indication of what has happened.' 50 Phlebitis and Thrombosis TABLE II. Fatal Cases of Venous Thrombosis, showing Veins affected. Iliac veins Inferior vena cava Lateral sinus Femoral ... Internal jugular... Saphenous Hepatic ... Cerebral cortex ... Portal Superior mesenteric Innominate Subclavian Splenic ... Renal Ovarian ... Inferior mesenteric Pelvic Uterine ... the 31 cases 15 )) 15 i> 12 >> 7 5> 7 >) 5 >> 4 M 3 J> 3 >> 2 >J 2 )i 2 J> 2 )> 2 >> I case. I )> I )9 Dr. Newton Pitt gives the following list of venous thromboses found in 3,128 autopsies during seven years at Guy's Hospital (Trans- actions of Pathological Society, vol. xliv., p. 48). Iliac veins Femoral veins Prostatic veins Internal jugular vein Lateral sinus Uterine veins Inferior vena cava . . . Innominate veins ... Renal vein Pelvic veins Portal veins Broad ligament veins Hepatic veins Superior mesenteric veins Longitudinal sinus Popliteal vein Subclavian vein Cerebral veins Besides these there were forty cases of thrombosis of the pulmonary artery, and twenty-six cases entered as pulmonary embolism, of which Dr. Pitt thinks some were more probably instances of thrombosis. 34 cases 33 27 17 15 12 12 9 8 8 7 6 4 4 4 3 3 3 Phlebitis and Thrombosis 51 14 cases 12 6 >> 4 5) Table III. shows the diseases in connection with which the thrombosis occurred. TABLE III. Fatal Venous Thrombosis, giving the Diseases of Origin. Middle-ear disease... Cancer (various organs) ... Inflamed varix Appendicitis Gastric ulcer Ovariotomy... Abscess of liver Peritonitis ... Puerperal septicaemia Inflammation of uterus Ulceration of bowel Heart disease Pleurisy Cystitis Stricture and prostatic abscess^ ... Pyosalpinx ... Ansemia Phthisis Suppurating ovarian cyst ... Necrosis of femur ... Ulceration of leg ... Impacted tooth-plate in oesophagus Gonorrhoea... Lardaceous disease Gall-stones... Renal calculus Cirrhosis of liver ... Pneumonia ... Pancreatitis... Sclerosis of spinal cord Suppuration of hip-joint ... Fractured leg Actinomycosis Uterine hsemorrhage Operation for radical cure of hydrocele Empyema ... ^ This was the only case in which gangrene occurred, and there was thrombosis of the external iliac and femoral arteries, as well as the femoral and profunda veins. 4—2 I case. 52 Phlebitis and Thrombosis Thrombosis of the pulmonary artery occurred in eight cases in connection with the conditions shown in Table IV. TABLE IV. Diseases in connection with which Thrombosis OF Pulmonary Artery occurred. Sex. Age Cirrhosis of liver Female . • 41 Radical cure of hydrocele Male • 47 Pleurisy . 18 Carcinoma of stomach . 66 Gastric ulcer ... • 49 Appendicitis ... . 58 Tropical abscess of liver (exhaustion) • 32 Disease of heart • 4 Phlebitis and Thrombosis 53 Fatal pulmonary embolism occurred in fifteen cases in connection with the conditions shown in Table V., of which it will be observed that eleven had reference to abdominal disease. TABLE V. The Conditions in connection with which Fatal Pulmonary Embolism occurred in Fifteen Cases. Thrombosis of varicose saphenous vein ... >3 J) )) JJ ••• Ovariotomy : Thrombosis of both internal iliac veins and inferior vena cava Ovariotomy : Thrombosis of saphenous vein Removal of cyst of broad ligament : Throm- bosis of femoral and iliac veins ... Pyosalpinx : Thrombosis of ovarian and iliac veins ... Appendicitis: Operation ... Gastric ulcer : Thrombosis of internal iliac vein Empyema : Thrombosis of internal iliac vein Renal calculus : Thrombosis of femoral vein... Ulceration of rectum, pelvic abscess : Thrombosis of renal vein Abscess of liver : Thrombosis of hepatic veins Tubercular peritonitis : Thrombosis of iliac veins Thrombosis of uterine veins Fractured leg : Thrombosis of veins of leg Sex. Male Female Age. 36 40 J) 54 } J 41 >j 42 29 21 23 >} 27 Male 44 Female Male 43 34 3> Female Male 51 53 31 54 Phlebitis and Thrombosis TABLE VI. The Veins in which Thrombosis occurred in con- nection WITH Fatal Pulmonary Embolism. Iliac veins ... ... 6 cases Saphenous veins ... .-. 3 „ Femoral veins ... 2 „ Inferior vena cava ... ... I case Renal vein ... I „ Hepatic vein ... I „ Uterine vein ... I „ Ovarian vein ... I „ Veins of leg ... I „ The symptoms of simple non-infective phlebitis are chiefly those of a localized thrombosis ; the constitutional disturbance if the case is uncomplicated is not usually severe. There may be an initial rigor, followed by a rise of temperature and pulse, but more often the first noticeable symptom is pain, felt most commonly in the left calf. This pain may at first be intermittent, subsiding for a few hours and then recurring with increased severity; if the deep veins are affected, it is of cramp-like character. These symptoms are coincident with the formation of a thrombus and the commencement of phlebitis. If the phlebitis spreads the temperature rises, perhaps to ioi° or 102° F., and there is sometimes sweating ; pain increases, especially if the large veins are concerned, and there is local tenderness. The amount of oedema is variable, for the occurrence of oedema in cases of venous obstruction depends upon a variety of conditions, and is by no means the simple matter which it has been sometimes repre- sented. It results from * a disturbance of the normal equilibrium which exists between blood, bloodvessels. Phlebitis and Thrombosis 55 tissues, and lymphatics.'^ Much will depend upon the rapidity, extent, and position of the thrombosis, the con- dition of the venous coats, the possibility of collateral circulation, the force of the blood-stream, the precedent degree of venous and arterial pressure, and the composi- tion of the blood. Variations in these factors account for the remarkable differences observed as to the occur- rence of oedema in venous obstruction ; thrombosis of the femoral vein or inferior vena cava, for instance, may be attended by extreme oedema, by very little, or by none. Doubtless the production of cedema depends largely, as Cohnheim taught, upon increased intravascular pressure, increased permeability of the vessel wall, or both of these conditions. The obstruction to the return of venous blood caused by the thrombus will give rise to increased intravascular pressure behind the obstruction, and the interference with the nutrition of the capillary endothelium will lead to increased permeability of the capillary walls, and therefore to the easier transudation of serum. This will also be influenced by the hydrostatic pressure, as seen in the effect of position, and the greater frequency of oedema in connection with thrombosis of the lower than of the upper limbs. But this is not sufficient to account for all the phenomena of oedema ; for if the lymphatics can carry off the effused fluid there will be no oedema. And the facility of absorp- tion depends not only upon the quantity, but also upon the quality of the fluid to be absorbed. The larger the amount of proteid contained in the fluid, the slower and more difficult is absorption, and watery solutions of crystalloids are absorbed with a rapidity proportionate to their dilution. The presence or absence of inflammation is therefore of importance in the production of oedema, ^ Lazarus- Barlow, ' Manual of Pathology,' 1904. p. 218. 5 6 Phlebitis and Thrombosis for if inflammation is present the fluid which escapes into the tissues contains more proteid and is of higher specific gravity than fthat which escapes as the result of mere venous congestion. The influence of the nervous system must also be taken into account, for, as shown by Cornil and Ranvier, if in an animal a vein is tied and the vaso-motor nerves divided, the arteries dilate, more blood is carried to the part, and the tension in the capillaries leads to exudation of fluid and to oedema. Ranvier had previously shown that if |the inferior vena cava is ligatured and the sciatic nerve is divided in one limb, oedema only occurs in the limb in which section of the nerve has been made. Dr. Lazarus- Barlow, who has done important work in this relation, has called attention to the part played by the tissues in the production of oedema. He says:^ 'It is astonishing how in all discussions concerning lymph and oedema formation the tissues have been left out of con- sideration, when we remember that every condition which affects the small bloodvessels, and especially the capil- laries, must at the same time affect the tissues also. In some cases even in which oedema occurs the tissues are affected first and to the greatest extent. It is a fault in the mechanical explanation both of lymph and of oedema formation that it places the tissues absolutely at the mercy of the vascular system. The amount of lymph which the tissues receive, according to that explanation, does not depend upon the needs of the tissues, but upon the con- dition of the bloodvessels. And yet the whole raison d'etre of the circulating system is the existence of the tissues. Normal lymph formation and oedema formation must be the ultimate result of at least two processes, one in which the tissue cells are paramount, the other in which the bloodvessels are paramount.' ^ ' Manual of Pathology,' p. 202 note. Phlebitis and Thrombosis 57 During hsemostasis the tissues are affected in two ways : they are deprived of nutriment, and the waste products of their own metabohsm are not removed. This leads to an active arterial congestion and an increased flow of lymph. Part of this lymph is carried away by the lymphatics, but if there is more than can be so disposed of oedema results. It is evident that in venous thrombosis both these con- ditions are present : there is diminished nutrition of the tissues and accumulation within them of the products of their metabolism. Upon this follows an increased flow of lymph, and upon the capacity of the lymphatics to carry this away depends the occurrence or not of oedema. It has already been pointed out that the degree in which absorption of effused fluid takes place depends upon the nature of the fluid, and this again will depend upon the composition of the blood, the condition of the vessels, and the presence or absence of inflammation. Enough has been said, I think, to show that the pro- duction of oedema in venous thrombosis is the result of a variety of complex conditions. Moreover, it will depend somewhat on the size and position of the affected veins. If a superficial vein is inflamed, the skin over it shows a dull red line wider than the vein, along which is an area of tenderness ; the vein may be felt solid with clot ; there is little or no oedema. If the intramuscular veins are implicated there will be more pain, and some deep swell- ing, the limb feeling tight and heavy, but showing little superficial oedema. If a main trunk is obstructed, as the femoral, there will be more general oedema, and the limb may become tensely swollen. There may still be but little constitutional disturbance, and the chief danger to be apprehended is the detachment of clot. If the patient is kept at rest these symptoms may gradually subside, the circulation through the veins involved may become 5 8 Phlebitis and Thrombosis re-established, and the limb after a time completely regain its normal condition. But in many cases some of the affected veins are permanently obliterated, and when large trunks are involved they are often left with the walls thickened and lumen diminished by the adhesion and shrinking of organized clot (Fig. 4). I have found some of the smaller veins of the calf blocked by firm adherent clot in cases where the limb appeared to have completely recovered from attacks of phlebitis. The veins of the lower extremity are much more often attacked than those of the upper limb, and those of the left more often than those of the right limb. The disease begins very commonly in the deep veins of the left calf. In this class of cases there is not so great a liability to recurrence as in those of gouty origin. I have had the opportunity of observing several patients for varying periods up to ten years, in whom there has been no recurrence after a severe first attack. A satisfactory subsidence and recovery is, however, not always the rule. The thrombus may extend in the direction of the blood-current, and so to the larger trunks, causing increasing embarrassment to the circulation. Thus from the femoral vein coagulation may spread through the iliacs to the inferior vena cava, or from the veins of the neck and upper extremity to the superior cava, and thus to the heart. Professor Humphry de- scribed such cases with characteristic accuracy in a thesis on coagulation of the blood in the veins, published in 1859.^ I have seen a case in which the thrombus ex- tended as high as the renal vein, and in which recovery took place, but with permanent obstruction of part of the 1 ' On Coagulation of the Blood in the Venous System during Life,' by George Murray Humphry, M.D., F.R.S. : Macmillan, Cambridge, 1859. FIG. 6. — PHOTOGRAPH SHOWING THE DEVELOPMENT OF THE SUPERFICIAL VEINS TWENTY-ONE YEARS AFTER OBLITERATION OF PART OF THE INFERIOR VENA CAVA. ( To precede Fig. 7. FIG. 7. — PHOTOGRAPH SHOWING THE DEVELOPMENT OF THE SUPERFICIAL VEINS TWENTY-ONE YEARS AFTER OBLITERATION OF PART OF THE INFERIOR VENA CAVA. To face p. 59. Phlebitis and Thrombosis 59 vena cava. When this occurs an enormous development of the superficial veins of the groin and abdominal wall usually takes place for carrying on the collateral circula- tion. A similar condition has been observed in connection with obstruction of the superior vena cava, though this event is rare except in consequence of the pressure of intrathoracic tumours. Figs. 6 and 7 are from photographs, showing the development of the superficial veins twenty-one years after obliteration of part of the inferior vena cava. In this patient it took about ten years for these veins to reach a troublesome degree of enlargement, and it is only lately that the circulation has become completely com- pensated, so that now there is no difference in the size of the limbs at night and in the morning, and the outline of the muscles is easily perceptible. Sir Thomas Watson/ in his ' Lectures on the Principles and Practice of Physic,' has described in his inimitable manner two cases illustrating the effects of obliteration of the venae cavse, and has given diagrams which show the collateral circulation. One of these was the case of a man who exhibited in a remarkable degree the results of obliteration of the superior vena cava by an aneurism of the innominate artery. The whole surface of the thorax in front, with that of the shoulders and of part of the abdomen, was thickly overspread with a network of prominent veins, * whereby the blood descending from the head found its way at length, through many circuitous channels, to the heart.' The second case related by Sir Thomas Watson was that of a woman in whom 3 inches of the inferior ^ ' Lectures on the Principles and Practice of Physic,' 1857, vol. ii., P- 350- 6o Phlebitis and Thrombosis vena cava was obliterated by the pressure of a tumour of the liver, a great development of the superficial veins of the thorax and abdomen contributing to the collateral circulation. Sir Thomas Watson draws attention to the tortuosity of the veins in which the direction of the current is retrograde. Mr. C. Mansell Moullin^ has recorded a case of throm- bosis of the inferior vena cava following a fall on the back and over-extension of the spine. The vein was obliterated from a point immediately below the entrance of the renal vein, and the left common and external iliacs and the femoral vein were blocked. The right leg was scarcely oedematous ; the left was 6 inches more-in circumference, hard, brawny, and severely ulcerated. The contrast be- tween the two limbs was striking and showed that even when the inferior cava has been obliterated, if the other veins are not interfered with, a collateral circulation may be established quite sufficient for all ordinary purposes. But complete and permanent obstruction of the inferior vena cava may occur without any marked development of the superficial veins, as in a case examined at St. George's Hospital, where the collateral circulation seemed to have been carried on almost entirely by the greatly-enlarged azygos veins. The patient, a woman of fifty years, died of pneumonia ; and post-mortem it was discovered that the inferior vena cava, from just above the entrance of the right renal vein to immediately below the entrance of the hepatic vein, had been converted into an impervious fibrous cord. The azygos veins were greatly dilated and tortuous, but the veins of the surface of the body were not dilated nor prominent. ^ Dissections of similar conditions in cases of oblitera- ^ Transactions of Clinical Society of Londoji, vol. xvii., p. 115. 2 * Post-mortem and Case Book,' 1896, No. 145. Phlebitis and Thrombosis 6i tion of the vena cava were described many years ago by Dr. Matthew Baillie^ and by Mr. Wilson.^ UncompHcated peripheral venous thrombosis does not cause gangrene. When this does occur it is in conse- quence of arterial as well as venous obstruction, or else of the addition of inflammatory disturbance. ^ Transactio7is of Society for the Irnproveinejit of Medical and Chirurgical Knowledge, vol. i., p. 127, plate v. ^ Ibid., vol. iii., p. 65. See also Dr. Peacock in Transactions of Royal Medical and Chirurgical Society, vol. xxviii., p. r, 'On Throm- bosis of the Vena Cava Superior ;' with References to other Published Cases.' LECTURE III Thrombosis of — (a) cerebral sinuses ; (d) mesenteric veins ; (c) gastric veins ; (