Thrombophlebitis and Pulmonary EmbolismBy JOHN A. SPITTELL, JR., M.D.

ACUTE venous thrombosis and its conmpli-lAw eations continue to be a challengingproblem to the physician. Ineomplete under-standing of the pathogenetic mechanisms, lackof objective measures for diagnosis, and dif-ferences of opinion coneerning therapy areparts of this problem. These difficulties, how-ever, should not discourage the physician inhis attempts to diagnose and treat venousthrombo-einbolism.Although thrombophlebitis may occur with-

out pulmonary embolism, and vice versa, thevare frequently associated. It bas been sug-gested that venous thrombosis can be dividedinto two types, thrombophlebitis and phlebo-thrombosis. Since the distinction has no prac-tical value in management or prognosis, thegeneric terni "thrombophlebitis" seems pref-erable when the clinical findings permit thediagnosis of acute venous thrombosis.

Three factors, known as Virchow 's triad,stasis of blood flow, damage of endothelium,and hypercoagulability of the blood, have beenconsidered important in the genesis of venousthrombosis, but the relative importance andinterdependenee of these factors are notunderstood. Nonetheless, they serve as a valu-able starting point in the management ofthrombophlebitis.The pathologic picture of venous thrombosis

includes both thrombosis and variable inflam-matory changes in the wall of the vein. Inthroinbophlebitis of more than a few days'duration, organization of the clot is also seen.The end result of thrombophlebitis usually isthickening of the vXenous wall with partialrestoration of the lumen and variable destruc-tion of the valves. The clinical manifestationsof both the inflammatory and obstructive com-ponents of aeute venous thrombosis are im-portant.Although there is no adequate explanation,

From the Section of Medicine, Mayo Clinic andMayo Foundationi, Rochester, Mfinnesota.

thrombophlebitis occurs more frequently inthe lower than in the upper extremities.

Superficial ThrombophlebitisClinical Aspects

Thrombophlebitis involving superficial veinsmay be caused by trauma (for example, afterinjection of various dyes or solutions), or bysystemic diseases (for example, blood dysera-sias, certain malignant lesions, and thrombo-angiitis obliterans), or it may occur repeatedlyfor no apparent reason. The veins most fre-quently involved are the small saphenous,median cephalic, and median basilic, and othersuperficial veins of the upper and lower ex-tremities. Thle superficial veins of the chestor abdominal wall rarely are involved.The characteristic appearance in thrombo-

phlebitis is a red, painful, tender nodular orlinear area in the skin (fig. 1). The involvedvein can be felt as a tender cord and the sur-rounding tissue nmay be indurated. Typically,the inflammatory reactionl subsides in 1 to 2weeks leaving a bluish or brownish area thatmay remain for several more weeks. Multiplesuperficial veins or segments of the same veinmay be involved simultaneously or in succes-sion. Systemie manifestations, edema, andpulmonary embolism rarely occur as a resultof superficial thrombophlebitis.Although the diagnosis of superficial throm-

bophlebitis is not difficult, one must differen-tiate it from cellulitis, which is more diffuse,from acute lymphangitis in which no throm-bosed vein is palpable but chills and fever areprominent symptoms, and from nodular le-sions such as erythema nodosum. The possi-bility of an underlying systemic process shouldbe considered unless there is an obvious eausesuch as trauma, varicose veins, or a postopera-tive or postpartum state.

Management

Superficial thrombophlebitis rarely is coni-plicated by pulmonary embolism, but the

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thrombotic process may extend to deep veins.Treatment should be dictated by the extenisive-ness of the process. For varicose vein andchenmical thrombophlebitis, warm moist packsand rest are usually all that is necessary.Phenylbutazone (Butazolidin) in a dose of200 mg. four times a day for 3 or 4 days ishelpful to reduce the inflammation.When superficial thrombophlebitis is more

extensive or extends despite this therapy, theuse of anticoagulant therapy with coumarin-tvpe or related drugs until the acute processsubsides is advisable.For recurrent bouts of superficial thrombo-

phlebitis for no apparent reason (idiopathicrecurrent thrombophlebitis), long-term anti-coagulant therapy is effective. In general, theuse of long-term anticoagulant therapy is in-dicated when attacks of superficial thrombo-phlebitis are frequent enough to warrant theexpense, the ineonvenience, and the risk ofsuch therapy.

Deep ThrombophlebitisClinical Aspects

WRhile distal edema is uneomnmon in super-ficial thrombophlebitis, it is a characteristicfeature of thrombosis of the large deep veins,such as the iliofemoral or the axillary. Thedeep veins serve as the "final common path-way " for the return of blood from the ex-tremities and, when they are acutely throm-bosed, the collateral venous return throughthe superficial venous system is usually inade-quate. Edema varies with the deep vein in-volved, being slight or absent in sural throm-bophlebitis and usually of greater degree iniliofemoral thrombophlebitis.

Generally, the systemic reaction accompany-ing deep venous thrombosis is minimal evenwhen thrombosis is extensive. A slight fever(100 to 102 F.) and a proportional increasein pulse rate are the only constitutional symp-toms. Malaise, chills, and high fever are notclinieal manifestations of deep venous throm-bosis. Local findings in the extreimity involved,lhowever, are characteristic and include dullaching pain, tenderness and, if a large vein isinvolved, signs of venous obstruction.

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Figure 1Superficial thrombophlebitis of the left leg andthigh in a patient with cancer of the lung.

The signs and symptoms of thrombophle-bitis occur acutely and subside in 1 to 3 weeks.Residual edema, when it occurs, is the resultof fibrosis and valvular incompetency and isnot due to "chronic thrombophlebitis, " whichis a misnomer. The findings in the extremityhave no prognostic value as to the risk of pul-monary embolus, since a pulmonary embolusmay be the initial manifestation of venousthromboembolism with local symptoms in theextremity either being absent or appearingwithin several days.

Sural thrombophlebitis rather frequentlycomplicates trauma, bed-confining illness, andpostoperative and postpartum states. Theclinical features of thrombophlebitis of thesural veins typically include pain in the calfand tenderness; firmness and slight enlarge-ment of the affected calf are found frequentlybut edema is seldom present. Although painin the calf on dorsiflexion of the foot (Ho-mans ' sign) is usually present, it is not aspecific indication of thrombophlebitis. Othercauses of calf pain, which may mimic suralthrombophlebitis, are myositis, sciatica, herni-ation of a Baker's cyst beneath the gastrocne-mius muscles, popliteal aneurysm, and musclestrain or tear.

Thrombophlebitis of the popliteal and fem-oral veins frequently appears as an extensionof sural thronmbophlebitis and is similar to itwith the additional findings of edema of vary-ing degree, of the leg and ankle, increasedsuperficial venous pattern, and tenderness on

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palpation of the popliteal space and lowerpart of Hunter's canal.

Iliofemoral thrombophlebitis produces ach-

ing and tenderness of the groin and thigh,increased venous pattern of the leg and thigh,and frequently a suffused or slightly cyanoticcolor of the affected limb (fig. 2). Generally,systemic manifestations are mild fever andslight tachyeardia. The simultaneous occur-

rence of similar findings in both lowerextremities indicates inferior vena cavalthrombophlebitis. A severe and extensive formof ileofemoral thrombophlebitis, phlegmasiacerulea dolens, is a rare complication in some

Figure 2Left iliomfentoral thoabophlebitis.

cases of advanced malignancy. In addition tothe findings mentioned, there mnav be massiveedema, shock, arterial spasm, and gangrene.

Conditions in the differential diagnosis offemoral or iliofemoral thrombophlebitis in-clude (1) lymphedema which is typically apainless, firm edema, (2) acute lymphangitiswhich produces erythema, chills, and highfever (to 105 F.), and (3) acute arterial oc-elusion which produces a pale, cool, an-d pulse-less extremity.

Management

Treatment for acute deep venous thrombo-sis should include measures to relieve venouscongestion, prevent further thrombosis andpulmonary embolism and restore venous flowto as near normal as possible. Rest in bedwith elevation of the affected extremity, theuse of analgesies, and the application of moistwarm packs to the involved limb are acceptedgenerally as valuable measures.No unanimity of opinion exists, however,

concerning the more definitive measures oftreatment, which include anticoagulant ther-apy, thrombolytic therapy, or ligation of thevein with or without thrombectomy. Advo-cates can- be found for each of these forms oftreatment, and until there is valid statisticalproof of the superiority of one, treatmientmust be determined on the basis of availableknowledge of the pathogenesis and the clinicalcourse of venous thrombo-embolism.The ligation of the involved femoral vein

h-as the distinct advantage of preventing pul-monary embolism provided proximal or addi-tional throinbi in the opposite extremity donot occur. Ligation of the inferior vena eava,a niore formidable procedure, has the samelimitation as ligation of the femoral veini withthe added disadvantage of producing chronicvenous insufficiency in many instanees. Liga-tion of veins is best used in cases in whiehanticoagulant therapy is contraindicated orhas proved ineffective.The dissolution of thrombi by lytic enzvmes

holds promnise as effective therapy in venousthronmbosis. At present, however, limIted ex-perienee with this measure indicates that it

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is best suited for investigative rather than forgeneral use.

Short-term anticoagulant therapy has cer-tain definite advantages over the other formsand is preferred by many for venous throm-bosis. If one assumes that hypercoagulabilityis a factor in the formation of a thrombus,effective doses of the anticoagulant drugsshould preveiit further thrombosis. This hasbeen the experience of most physicians. Inaddition, evidence indicates that anticoagu-lant therapy hastens recanalization of throm-bi. While bleeding is a hazard during anti-coagulant therapy, sufficient experience withthese drugs has been accumulated to minimizethe risk provided dosages are regulated byadequate laboratory tests. The choice of hep-arin or an oral anticoagulant drug depends onthe experience of the physician and the avail-ability of laboratory facilities. When reliabledeterminations of prothrombin time are notavailable, oral anticoagulants should not beused. Details of the action, use, and controlof anticoagulant therapy are available in sev-eral recent reports.Although the duration of treatment for

acute deep venous thrombosis depends on theclinical response of the patient, in general, itvaries from 1 to 2 weeks. Rest in bed andelevation of the extremity affected should becontinued until the edema and tenderness havedisappeared. An adequate elastic supportshould be used (from the ankle to the knee)whenever the patient is out of bed and walk-ing. Anticoagulant therapy should be contin-ued for several days after the patient is am-bulant. The use of elastic support on the limbshould be continued for at least a month; itcan then be discontinued unless chronic ve-nous insufficiency is present.

It is well to remember that recurrent throm-bophlebitis of either superficial or deep veinsmay be the first clinical manifestation of anobscure visceral malignancy.

Pulmonary EmbolismClinical Aspects

Treatnment for deep venious thrombosis in-cludes the prevenition of pulmonlary embolisml.Circulation, Voltme XXVII, May 1963

Unfortunately, in many cases pulmonary em-bolism is the first sign of venous thrombo-em-bolic disease. The diagnosis of pulmonaryembolism is often difficult because the symp-toms, physical signs, and roentgenographiefindings are vague and inconclusive. Theclassic triad of symptoms, thoracic pain, dysp-nea, and hemoptysis, is not present in themajority of cases. The most frequent symp-tom is sudden pain in the thorax; dyspnea isless frequent except when large emboli arepresent, and hemoptysis occurs in less than20 per cent of the cases. Consequently, thediagnosis of pulmonary embolism often mustbe presumptive, based on the occurrence ofchest complaints in a situation likely to becomplicated by venous thrombo-embolism.

Physical examination may reveal little orno abnormality in patients with small pulmo-nary emboli. Elevation of the diaphragm, im-paired percussion, or a localized patch of ralesmay be detected, but a pleural frietion rubis heard in only about 10 per cent of cases.The roentgenographic manifestations may

vary from minimal areas of fibrosis and smallaccumulations of pleural fluid to the uncom-mon classic wedge-shaped density. Electro-cardiographic changes frequently are absent.When they occur, they are usually transient.These changes may consist of inversion of Twaves in the right precordial leads, evidenceof right bundle-branch block, or the changesof acute cor pulmonale. The last-mentioned isthe most characteristic. Electrocardiographicchanges oceur within the first 48 hours afterpulmonary embolism and disappear rapidly.

In the differential diagnosis of pulmonaryembolism one must consider atelectasis, pneu-monia, myocardial infaretion, and intra-ab-dominal processes such as subdiaphragmaticabscess. In postoperative patients atelectasisis likely to develop in the first 3 postoperativedays whereas pulmonary embolism is morelikely to occur in the second postoperativeweek. Fever, cough, and physical findings inthe chest are more prominent in pneumoniathan in pulmonary embolism. In acute miyo-eardial ilnfaretion tlle pain is not pleuritic,

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Table 1Conditions with Increased Risk of Venous Throm-bosis

1. Postoperative period following pelvic operation,splenectomy, or any abdominal operation for amalignant lesioni

2. Periods of immobilization of patientsa. With a past history of venous thronmbo-embolic

diseaseb. With leg traumiac. With cardiac disease or obesity

Table 2Valuable Measures in the Prophylaxis of VenousThrombo-embolism

1. Measures to minimize venous stasisa. Early ambulationb. Avoidanee of constrieting dressings on limlbs

2. Measures to retard hypercoagulabilitya. Avoidance of dehydration and shockb. Anticoagulant therapy

3. Other measuresa. Avoidance of injections into veins of legsb. Correction of anemia

and the thoracic roentgenogram usually re-veals no abnormalities; very often the electro-cardiographic changes of acute myocardialinfaretion are the best differential point. In-tra-abdominal processes such as subdiaphrag-matic abscess can be very difficult to distin-guish from pulmonary embolism, but, in theformer, abdominal pain and tenderness aremore promninent.Management

The therapy of pulmonary embolism shouldinclude those measures outlined for deep ve-nous thrombosis. In cases of large emboli withcardiorespiratory embarrassment, oxygen isindicated and atropine may be desirable torelieve associated bronchial spasm. Anticoag-ulant therapy should be initiated with heparinbecause of its immediate effect and should becontinued until the prothrombin time is

withini the therapeutic range. Anticoagulanttherapy should be continued for several daysafter the patient is ambulatory. Rest in bedis advisable until all signs anid symptoms havedisappeared, usually 8 to 10 days.The morbidity and mortalitv associated with

venous thrombo-embolic disease indicate theiieed for strong, concerted prophylactic ineas-ures when the risk of venous thrombosis ishigh (table 1).

Valuable measures in the prophylaxis of ve-

nous thrombo-einbolism are listed in table 2.

Relevant References1. ALEXANDER, B., AND WESSLER, S.: A guide to

anticoagulant therapy. Circulation 24: 123,1961.

2. ALLEN, E. V., BARKER, N. W., AND HINES,E. A., JR.: Peripheral Vascular Diseases. Ed.

3, Philadelphia, W. B. Saunders Company, 1962.

3. COON, WM. W., AND WILLIS, P. W.: Deep venous

thrombosis and pulmonary embolism. Am. J.Cardiol. 4: 611, 1959.

4. COOPER, T., AND BAXRKER, N. WV.: Recurrentvenous thrombosis: An early complication ofobscure viseeral carcinoma. Minnesota Med. 27:31, 1944.

5. PARKER, B. M., AND SMITH, J. R.: Pulmonaryembolismi and infaretion: A review of thephysiologic consequences of pulmonary arterialobstruction. Am. J. Med. 24: 402, 1958.

6. Ross, J. V., JR., BAGGENSTOSS, A. H., ANDJUERGENS, J. L.: Gangrene of lower extremitysecondary to extensive venous occlusion. Circu-lation 24: 549, 1961.

7. SAWYER, W. D., ALKJAERSIG, N., FLETCHER, A. P.,AND SHERRY, S.: Thrombolytic therapy: Basicand therapeutic considerations. Arch. Int. Med.107: 274, 1961.

8. STEIN, G. N., CHEN, J. T., GOLDSTEIN, F., IRAEL,H. L., AND FINKELSTEIN, A.: The importanceof chest roentgenography in the diagnosis ofpulmonary einbolism. Am. J. Roentgenol. 81:255, 1959.

9. WESSLER, S., AND DEYKIN, D.: Theory anid prac-

tice in acute venous thrombosis: A reappraisal.Circulation 18: 1190, 1958.

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Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 1963 American Heart Association, Inc. All rights reserved.

is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231Circulation doi: 10.1161/01.CIR.27.5.976

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