PULMONARY EMBOLISM IN CHILDRENBY

JOHN L. EMERYFrom the Children's Hospital, Sheffield

(RECEIVED FOR PUBLICATION JUNE 8, 1962)

Pulmonary embolism is generally believed to berare in childhood, and my own survey of the pub-lished material suggests that under 50 cases haveso far been recorded. Stevenson and Stevenson(1949), who surveyed published reports from allover the world and reported a case in 1949, couldfind only 30 reports of which only 16 had hadcomplete autopsies. Not all cases, however, arefatal. Cashman (1956) reported an embolus ina boy of 9 years who recovered completely.The first reported case appears to have been

almost exactly a century ago when Ldschner (1861)described a pulmonary embolus in a 9-year-old boy,which followed phlebitis associated with a fractureof the tibia. His case typifies many of the earliercase reports of the pre-antibiotic days where emboliappeared to follow injury to bones and muscles(Rosenbloom and Henderson, 1935). Rupp (1921)tabulated 11 cases of fatal pulmonary embolismthat had followed prolonged wasting disease inchildren under the age of 10 years. Several caseshave been reported following prolonged or acutesepsis (Wessen, 1922; Fleischmann, 1929; Stulik andRust, 1929; Jones, 1930; Hosoi, 1932).My own interest in pulmonary emboli in children

was stimulated by the symptoms and lethal com-plication of the ventricular-atrial Spitz Holter valvein children with hydrocephalus (Emery and Hilton,1961). Many of these children succumb frompulmonary embolism from clots that arise aroundthe tube in the right atrium. All cases of emboliassociated with the Spitz Holter valve or withprimary disease of the heart have, however, beenexcluded in the present survey.

This report concerns 25 cases of fatal pulmonaryembolism that we have seen in our own materialduring the past 10 years, and an attempt is made toassess its importance in the pathology of the lungin children.

Material and MethodsThe cases surveyed here came from a series of approxi-

mately 2,000 autopsies from liveborn children that havebeen carried out by the Department of Pathology at the

Sheffield Children's Hospital. These child deaths com-prise not only hospital admissions but also many deathsat home, referred into hospital by practitioners forautopsy, and children dying in such circumstances ashave been referred to the Coroner. The routine practiceat autopsy in this hospital has been designed to fix asmuch of the tissues of the body as possible before anymanipulation has taken place. The technique con-cerning heart and lungs has been to open the superiorand inferior vena cava while the heart and lungs arewithin the chest to ensure that the systemic venousreturn has been normal and there are no gross defor-mities in the vascular return to the heart. After removingthe tongue, heart and lungs, an incision is made throughinto the right ventricle. The ventricular septum iscarefully inspected and the pulmonary valve opened,including a short length of the main pulmonary trunk,but the blood throughout the pulmonary arterial systemis not removed and the heart and lungs from this pointonwards are placed in formalin for a period of approxi-mately 10 days before further dissection.

After fixation, blocks are taken from each lobe of thelung, the blocks being transverse to the general line of themain bronchi and vessels. Sections are routinelystained with Masson's trichrome.

In all but three cases (Fig. 1), the diagnosis of pul-monary embolism has rested upon the histologicaldiagnosis of ante-mortem thrombi in arteries, thethrombi being of such form and structure that theycould not have arisen as local thrombi (Fig. 2).The histological diagnosis of ante-mortem thrombosis

in situ is not easy, particularly if the thrombosis is ofrecent origin. I have excluded some equivocal cases.For the diagnosis of an ante-mortem thrombosis theremust be streaming and lamination of fibrin; the state ofblood in other vessels is used in comparison. Thediagnosis of emboli in the pulmonary arteries is easierand more certain.

ResultsSome details of the 25 cases are set out in

the Table.In these children the history falls into two definite

phases: first, the prodromal symptoms and disease,i.e. the disease associated with the onset and causeof the primary thrombosis; and secondly, thesymptoms apparently associated with the incident

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ARCHIVES OF DISEASE IN CHILDHOOD

FIG. 1.-The pulmonary artery with pulmonary valves showingan embolus obstructing the main right pulmonary artery.

(x 3.)

of the embolism and those intervening between thattime and death. Since the present series onlyconcerns morbid anatomy, possible cases of embol-ism with recovery have not been discussed orincluded, although such cases have been reportedand are probably much more common than isusually appreciated.The cases fall into two age-groups. There is a

neonatal group of five children. Two of thesedeaths followed cerebral venous thrombosis andtwo were secondary to thrombi in the venouschannels of the left liver. The following case reportis an example of this.

Case 3. This was a full-term child born in bluecyanosis. She improved in colour during the nextfew hours, but later on the day of birth she becameshocked and remained apparently in this shocked statefor approximately 24 hours. She was admitted tohospital in extreme cyanosis and died almost immedi-ately, three days after birth. Autopsy showed deep redlungs but not heavy as in hyaline membrane disease.Histology revealed emboli in many of the pulmonaryarteries. The left lobe of the liver was deep red and ina state of partial collapse with many thrombosed hepaticveins, the thrombi being very similar to the emboliseen in the lungs. In this case the primary cause of theembolism was apparently the shocked state of the child,which made it unable to maintain an adequate circulationthrough the left liver.

FIG. 2.-Section of a pulmonary artery containing a coiled embolus. ( x 12.)

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TABLE: DETAILS OF 25 CHILDREN DYING WITH PULMONARY EMBOLISM

Naked-eye HistologyCase Age Prodromal Disease Terminal Symptoms Primary EmboliNo. at and Site of in Emboli in Thrombi in

Death Symptoms Duration Duration Thrombosis Pulmonary Pulmonary PulmonaryTrunk Arteries Veins

._- 1--~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~_2 Exomphalos; bowel

resection

3 'Mucousy'; tracheo-oesophageal fistula

3 Shocked

6 Cerebral irritation

7 Jaundice; cerebralirritation

Months2 Skin rash and snuffles

2 Sticky eye, 'unwell'

3 Nasal dischargeFell onto head from

cot

3 Off foodAcute abdominal pain

4 Off foodColic and diarrhoea

4 Off food

5 Skin sepsis'Purpura necrotica'

6 Nasal discharge

7 CoughVomitingConvulsions

9 Sore throat

9 Cough

Refusing food

Abdominal pain - in-testinal obstruction

Laparotomy followedby sepsis

Cold

Acrodynia; ulcerationofgums

Vomiting

Poliomyelitis injectionin buttocks

Tonsillitis

Adrenogenital syn-drome

Vomiting and tonsillitis

Vomiting and nasaldischarge

Nasopharyngeal tum-our

Nasal sepsis

24 hrs

2 days

2 days

4 days

3 days

1 wk

1 day

3 days1 day

7 days6 hrs

3 days1 day

2 days

2 days1 day

Severaldays

3 wks3 days2 days

4 days

2 wks

3 days

2 days

2 wks

6 days

3 mths

4 wks

4 wks

1 wk

Birth

4 days

2 days

9 mths

3 wks

Distressed breathing,blood in stomach,flaccid; 1 hour

One day after operation;sudden death

Sudden severe cyanosis;4 hours

Convulsions for 12 hours

Found dead in cot inhospital 2 days afteradmission

Bleeding from nose, sud-den death i hr later

Found dead

Sudden death

Sudden, unexpected deathwithin an hour oflaparotomy

Sudden death in mother'sarms after period ofextreme restlessness

Found dead at home incot

Sudden extreme dys-pnoea for 1 hour

Sudden severe dyspnoealasting 4 hours

Sudden death in hospital1 day after admission

Acute respiratory distressfor 8 hours

Acute collapse and cyan-osis; sudden death 2days after admission

Convulsions for 6 hours

Sudden death in hospital6 weeks following op-eration

Severe respiratory dis-tress, asthma for 4hours

Found dead in bed havingbeen in hospital severalweeks

Acute respiratory dis-tress for 12 hours

Pain in thigh; suddendeath in parent's arms

Sudden collapse anddeath 2 days after ad-mission to hospital

Sudden death in parent'sarms

Sudden death havingbeen in hospital manyweeks

Renal veinand I.V.C.and mesen-tery

Left liver

Left liver

Cerebral sinus

Cerebral

Inferior venacava andrenal

Naso-pharyngeal

Cerebralsinuses

Pelvis (sepsis)

Cerebral

Not found

Cerebral andrenal

Not found

Cerebral

Naso-pharyngeal

Cerebral ?

Cerebral

Pelvic veinsand venacava

Not known

Inferior venacava andrenal

Cerebral andrenal

Deep glutealpelvis

Naso-pharyngeal

Cavernoussinus andnaso-pharyngeal

Nasopharynx

+

I

+

+

+

+

+

+

+

+

+

+

+

+

+

9

±

+

+

9

Days

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17 10

18 11

19 16

20 23

Years21 2

22 21

23 3a

24 3i

25 7

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ARCHIVES OF DISEASE IN CHILDHOODChildren of older age varied from 13 weeks to

7 years.The primary sites of venous thrombosis appear

to be the cerebral venous sinuses in nine cases,nasopharyngeal in five, lower abdominal and pelvicin four, and inferior vena cava and renal in two.In three instances the site of primary thrombosiswas not discovered.Only three of the cases were post-operative, one

in a 3-day-old child who collapsed and died suddenlysome six hours after operation for repair of atracheo-oesophageal fistula; the site of thrombosiswas the left liver. Two other cases occurred afterabdominal sepsis and were associated with pelvicand retroperitoneal abscesses, one was secondaryto an intestinal perforation and the other associatedwith a urachal cyst and abscess. The small numbersof post-operative deaths in this series are probablysignificant in view of the fact that more than halfof the beds in the hospital were for acute surgery,and there was a very rapid turnover.Of the older children, less than one-half presented

as sudden and unexpected deaths. The otherschiefly presented as very acute infections of thelung, and the following is a report of one such child.

Case 19. This was a 16-month-old child who wasadmitted as an emergency for what was thought to bean attack of acute asthma. There was no response toadrenaline, and the child died within two hours ofadmission. Although ante-mortem emboli were foundin the pulmonary arteries in this child, the primary siteof thrombosis was not identified.

A particular group was related to infection of thenasopharynx. Such was a boy of a little over3 years (Case 23).

Case 23. He was admitted because of vomiting.He had shown adrenogenital syndrome as a newbornand had been well maintained on corticosteroids. Hehad grossly enlarged tonsils and severe inflammationof the pharynx. Two days after admission, he collapsedand died suddenly. Autopsy showed the lungs to becongested, and the only other abnormality was an acuteinflammation of the tonsils and nasopharyngeal tissue.Histology showed venous thrombosis in veins in theperitonsillar tissues, emboli in the pulmonary arteriesand some thrombi in pulmonary veins. There was littledoubt that the immediate cause of death in this childwas pulmonary embolism from clots formed in thevessels of the nasopharynx.

Case 24. This boy, who had achondroplasia and was3A years of age, one day vomited several times. He wasseen by his doctor and found to have pyrexia with puscoming from his nose. The practitioner said that theboy had a severe pharyngitis and tonsillitis and gave him

oral penicillin. In the early afternoon of the followingday he had a deep sleep and when he awoke he againvomited several times. Later that evening his fatherpicked the boy up in his arms to take him to bed, and hesuddenly kicked, fought for breath and died in hisfather's arms. At autopsy the only abnormal featureswere congestion of the lungs and extreme oedema of theperinasal tissues with possible early quinsy, but therewas no obstruction of the airways. Later P-haemolyticstreptococci were grown from the nasal cavities. Anante-mortem thrombosis of the cavernous sinus wasconfirmed histologically and a large twisted emboluswas found packed in the main pulmonary artery (Fig. 2).Thrombosed vessels were also found in the peritonsillartissue and also associated with some of the deep cervicallymph nodes.

A further group of cases was associated withcerebral symptoms, some of these related to trauma.

Case 8. A 3-month-old child who had apparently beenquite fit had fallen from his cot onto the floor on the daybefore death. The following morning he took three-quarters only of his feed and after bringing up wind, sud-denly became cyanosed, limp and died in his mother'sarms. Autopsy revealed the presence of a recent superficialbut extensive subdural haematoma up to 5 mm. inthickness. The haemorrhage had come from a tornvein running into the longitudinal sinus. There weresmall blood clots within the venous cerebral system.No clot was found within the longitudinal sinus itself,but only in the vessels running into it. The lungsshowed the presence of emboli in the pulmonary arteriesand a few ante-mortem clots within the pulmonaryveins. This child had apparently died from pulmonaryembolism and thrombosis secondary to clots probablycoming from the longitudinal sinus.

DiscussionVenous thrombosis is by no means an uncommon

finding at autopsy in children, and, in a series of1,000 autopsies that we recently surveyed, 81 werefound in whom thrombosis of veins in some partof the body was considered to be a factor contri-buting to death. Thrombosis in pulmonary vesselsis also not rare particularly associated with symptomsusually considered to be those of a very severerespiratory infection (Emery, 1953) and probably isas common in children as in adults (Spain andMoses, 1946). It is these thrombi that are probablythe major factor in the lethal outcome of a chestinfection. The role of embolism in such cases isdifficult to elucidate. Within our own material ofknown cases of embolism, we have found that ifsevere respiratory symptoms have existed for morethan a matter of two to three hours, a pulmonaryembolus is usually associated with pulmonaryvenous thrombosis. In general, the only cases inwhich we have not found pulmonary venous

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PULMONARY EMBOLISM IN CHILDREN 595thrombosis associated with pulmonary embolism,are those that have died apparently from the shockof the embolism.The symptoms following pulmonary embolism

are very like those of an acute infection of therespiratory tract (Emery and Hilton, 1961). Thiswas a feature of the child deaths following embolismfrom clots around the auricular end of the tube inthe Spitz Holter valve shunt and largely stimulatedthe present survey. In those children the diagnosisin the early cases was that of 'acute pneumonia',and we suspect that many of the deaths reportedfrom such children as being due to acute broncho-pneumonia were in fact embolism deaths.The reason why we have found so many cases

of pulmonary embolism is probably due to thetechnique used at autopsy. On simple grossdissection we have only found three cases; the other21 cases came from microscopy of the pulmonaryvessels, the vessels not having been separated fromthe heart and thus emptied of their blood beforehistological examination. It is possible that, ifmore detailed and thorough examination had beencarried out, even greater numbers of pulmonaryemboli would have been discovered.Pulmonary embolism is never a primary disease

but an accidental complication of other diseasesin children where there is venous thrombosis(Zuelzer, Kurnetz and Fallon, 1951). In our ownmaterial common precipitating lesions have beencerebral haemorrhage or cerebral thrombosis, sepsisin the lower abdomen, cachexia or acute severenasopharyngeal infection. Only approximately one-third of the cases that have come into our handshave died in a sudden dramatic way; the others havehad an abrupt onset of severe respiratory symptoms.It seems likely that a number of cases of pulmonaryembolism in children do survive, such as the case

reported by Cashman (1956), but many are undiag-nosed or are diagnosed as acute pneumonia. It isnot the function of this paper to discuss therapy,but to draw attention to the possibility of pulmonaryembolism in children. Whenever unexpected symp-toms of infection of the lung arise in a child, undertreatment for disease in some other part of thebody, pulmonary embolism and thrombosis shouldbe considered.

SummaryThe clinical symptoms of pulmonary embolism

in children are usually those of an acute infectionof the respiratory tract. Common sites of originof emboli in babies under 1 month of age arehepatic veins and, in older children, the cerebralsinuses and the veins of the nasopharynx.

REFERENCES

Cashman, M. (1956). Massive pulmonary embolism in a boy aged 9.Arch. Dis. Childh., 31, 474.

Emery, J. L. (1953). Pulmonary thrombosis and its associationwith unexpected death in childhood. ibid., 28, 187.and Hilton, H. B. (1961). Lung and heart complications of

the treatment of hydrocephalus by ventriculo-auriculostomy.Surgery, 50, 309.

Fleischmann, R. (1929). Embolie' der Arteria pulmonalis beiMasern. Z. Kreisl.-Forsch., 21, 377.

Hosoi, K. (1932). Pulmonary embolism and infarction. Ann. Surg.,95, 67.

Jones, J. A. (1930). Pulmonary embolism in an infant followingaural infection. Lancet, 2, 1070.

Loschner (1861). Cited by Stevenson and Stevenson (1949).Rosenbloom, H. and Henderson, R. J. (1935). Pulmonary infarct

in a child. Brit. med. J., 2, 64.Rupp, A. (1921). Postoperative Thrombose und Lungenembolie.

Arch. klin. chir., 115, 672.Spain, D. M. and Moses, J. B. (1946). Thrombosis and embolism

of pulmonary vessels with special reference to pulmonary veinthrombosis. Amer. J. med. Sci., 212, 707.

Stevenson, G. F. and Stevenson, F. L. (1949). Pulmonary embolismin childhood. J. Pediat., 34, 62.

Stulik, C. K. and Rust, B. K. (1929). Pulmonary embolism ininfancy. Amer. J. Dis. Child., 37, 1246.

Wessen, N. (1922). Totliche Lungenembolie bei einem 4-jahrigenKinde nach Rippenresektion bei Pleuraempyem. Acta chir.scand., 54, 123.

Zuelzer, W. W., Kurnetz, R. and Fallon, R. (1951). Thrombosis ofrenal veins. A.M.A. Amer. J. Dis. Child., 81, 27.

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