Case reports

Increased

serum acid phesphaiase a&w arterial emb&sm

Myron R. Sch.oenfeld, M.D.*

Yonkers, N. Y.

I n previous papers, we reported the oc- currence of acid hyperphenylphospha-

tasia during the acute stages of myocardial infarction, pulmonary embolism, and pe- ripheral thrombophlebitis.1-3 The present communication reports a similar phenom- enon in a case of recurrent systemic arterial embolism.

urea nitrogen, urinalysis, and serial serum glutamic- oxalacetic transaminase activities were within nor- mal limits. With bed rest, digitalis, diuretics, and a low-salt diet, her clinical state improved.

Case report The patient was a 58-year-old Negro woman who

was admitted to the hospital with a S-year history of exertional angina and dyspnea, and a 3-day his- tory of progressive worsening of these symptoms. There was no history of hypertension or diabetes. On admission, the blood pressure was 140/90 mm. Hg, the pulse was 90 per minute and regular, and the respirations were 16 per minute and quiet. The neck veins were distended, and there were a few moist rbles in both lung bases. Examination of the heart revealed an accentuated pulmonic second sound and a Grade 2/4 mid-systolic blowing mur- mur which was loudest at Erb’s area. The liver and spleen were not palpable, and there was no periph- eral edema. The femoral pulses were strong and equal, the popliteal pulses were weak bilaterally, and the dorsal pedal and posterior tibia1 pulses were absent bilaterally. The electrocardiogram showed normal sinus rhythm, left bundle branch block, left ventricular hypertrophy, and small Q waves in Leads I, aVL, and VI 2, suggestive of an- teroseptal myocardial infarction of indeterminate age. Subsequent electrocardiograms were unchanged. The chest x-ray film showed enlargement of the cardiac apex downward and outward, compatible with left ventricular hypertrophy, and mild bilateral hilar prominence suggestive of mild left ventricular failure. The blood count, fasting blood sugar, blood

On the fourth hospital day, severe pain and exquisite hypersensitivity developed in the entire right lower extremity. The right femoral pulse was no longer palpable, and pallor of the sole of the right foot was observed. A critical level of tempera- ture appeared at the junction of the middle and upper thirds of the right thigh. A diagnosis was made of embolism to the right common or external iliac artery. Shortly thereafter, the right femoral pulse again became forceful, and the critical level of temperature shifted to the mid-thigh. It was thought that the embolus had dislodged and moved distally. The patient was then transferred to the operating room for embolectomy. At operation, a 3-by-0.4-cm. embolus was removed from the distal portion of the common femoral artery at the point of its bifurcation into the superficial and deep fem- oral arteries. The right popliteal artery was explored and found to be patent. Postoperatively, the critical level of temperature moved to the region of the knee, and pain and hypersensitivity in the foot con- tinued despite anticoagulation. Presumably, small residual emboli were still lodged distally. Over the next 12 days, her symptoms gradually abated, the plantar pallor and coldness of the right foot pro- gressively waned, and the patient began to ambulate. Necrosis of tissue did not occur.

On the thirteenth hospital day, while anticoagu- lated, the patient became aphasic and lapsed into stupor. At the same time, the right foot became cold, edematous, and pale. The femoral pulses remained full and equal. A spinal tap revealed blood- tinged xanthochromic fluid under normal pressure with a protein content of 37.5 mg. per cent. Motor power and the reflexes were unimpaired. A dignosis was made of recurrent embolism to the brain and

With the technical assistance of Fanya Woll. From the Medical Service, Lincoln Hospital, New York, N.Y. Received for publication Jan. 16, 1963. *Address: 11 Bronx River Road, Yonkers, N.Y.

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Volume b? Numbcv 1 Increased serum acid phosphatase after arterial embolism 93

to the right lower extremity below the knee, prob- ably due either to a mural thrombus in the left ventricle at the site of previous myocardial infarc- tion or to nonbacterial thrombotic endocarditis. The aphasia and mental clouding slowly cleared over the next several weeks. The right foot, how- ever, underwent progressive dry gangrene, and she was again transferred to the operating room for amputation.

Serum acid phenylphosfihatase activities. The serum acid phenylphosphatase activities (SAPP) were determined almost daily over a period of 4 weeks on freshly drawn morning specimens of blood, using the Gutman modification of the King- Armstrong technique,dand observing the precautions described previously.2 Aliquots of the same sample of serum differed by no more than 0.1 units from each other. Grossly hemolyzed samples of serum (pink tint) were discarded. The substrate solution of sodium phenylphosphate was prepared fresh at intervals of 2 to 5 days. In our laboratory, the

Fig. 1. Fifty-eight-year-old Negro woman with arteriosclerotic heart disease. Right femoral arterial embolism occurred on day 4. Femoral embolectomy was performed on the same day. Symptoms and signs of ischemia in the right lower extremity pro- gressively decreased after embolectomy, but acid hyperphenylphosphatasia occurred, due to residual small emboli lodged below the knee. On day 8, thrombosis occurred in the antecubital portion of the right basilic vein, which had been used for repeated venipuncture. Acid hyperphenylphosphatasia again ensued. Organization of the thrombus into a thin, fibrotic cord proceeded over the following week. On day 13, arterial embolism occurred to the brain and to the right lower limb below the knee. Acid hyperphenylphosphatasia once more appeared. Cerebral dysfunction slowly waned, but gangrene of the right foot steadily progressed, necessitating eventual amputation.

normal SAPP range for women is 0.3 to 1.6 Gutman- King-Armstrong units.

The first specimen of blood was drawn on the fourth hospital day, approximately 3 hours after the onset of pain and before embolectomy was per- formed; the SAPP on this specimen was 0.4 units. On hospital days 5, 6, and 7, the SAPP progressively climbed to 2.3 units, and, then, on the eighth day it fell back to 1.0 units.

On the eighth hospital day, thrombosis occurred in the antecubital portion of the right basilic vein at the site of repeated venipuncture. The thrombosed segment of vein measured 0.3 by 2.0 cm. Resolution and organization of this thrombus proceeded over the following week or so. On hospital days 9 through 12, immediately subsequent to this episode of venous thrombosis and during which time the symptoms and signs of ischemia in the right lower limb had progressively decreased almost to the vanishing point, the SAPP, as determined in samples of blood obtained from the right basilic vein central to the site of thrombosis, steadily climbed to 3.3 units.

On the thirteenth hospital day, recurrent arterial embolism occurred to the right lower extremity and to the brain. A specimen of blood drawn a few hours after onset of symptoms had a SAPP of 2.7 units, a fall from the level of 3.3 units on the previous day. Subsequently, on hospital days 14 through 18, the SAP P rose to a height of 3.9 units.

Thereafter, on hospital days 19 through 30, the SAPP fell and leveled off to 1.8 to 2.9 units. This period correlated with the occurrence of progressive gangrene of the right foot and with the resolution of cerebral dysfunction incident to the cerebral embolism.

These changes in serum acid phenylphosphatase, activity are diagramed in Fig. 1.

Discussion

In each of the episodes of thrombo- embolism observed in this patient, the onset of acid hyperphenylphosphatasia fol- lowed the onset of symptoms by several hours, reached a peak 48 to 72 hours later, and lasted 3 to 6 days. This pattern is similar to that noted after some cases of myocardial infarction,l and suggests a common pathogenesis.

As described previously,* we have en- tertained several possible explanations for the acid hyperphenylphosphatas.ia of thromboembolism: (a) degeneration of enzyme-rich parenchymal tissue subserved

by the occluded vessel; (b) autolysis of enzyme-rich cells (particularly erythrocytes and platelets) enmeshed within the blood clot; (c) generalized hypoxic injury to (with consequent release of enzymes from) all body organs-but particularly the prostate, liver, spleen, kidney, and mar- row-caused by an associated hypotension

94 Schoenfeld

and shock; (d) thrombocytosis caused by stress-induced splenic contraction and by increased thrombocytogenesis due to tissue necrosis. Arguments have already been presented against the first three of these possibilities,l and the present case provides further evidence against the first. Thus, 011 hospital days 9 through 12, the serum acid phenylphosphatase activity progres- sively increased to high levels, whereas objective and subjective evidence of is- chemia in the right lower extremity had been steadily decreasing since day 4, and had, by day 12, almost disappeared. Again, during hospital days I9 through 30, overt gangrene of the foot was progressively increasing in extent, yet the serum acid phenylphosphatase activities were much lower than on days 14 through 18 immed- iately after the embolism. Finally, acid hyperphenylphosphatasia occurred after thrombosis of a small segment of the right basilic vein, but in this instance there was no edema, ischemia, inflammation, or necrosis of extravascular tissue.

All this is not to deny that degenerating parenchyma subserved by an occluded artery or vein may make some contribution to the acid hyperphenylphosphatasia. In- deed, the high phosphatase activities noted on days 19 through 30 coincided with pro- gressive gangrene of the right foot, and presumably were caused by a combination of necrosis of bone and soft tissue in the foot and/or progressive thrombosis of vessels distal to the site of embolic occlu- sion.

Summary

A case is described of a .58-year-old Negro woman with arteriosclerotic heart disease who successively developed arterial embolism to the right lower extremity, with transient ischemia of the limb, thrombosis in the right basilic vein caused by repeated

venipunctures, and simultaneous recurrent arterial embolism to the right lower ex- tremity, with gangrene of the foot, and to the brain, with symptoms and signs of cerebral infarction. The emboli presumably originated in the heart.

Serial serum acid phenylphosphatase ac- tivities were determined almost daily throughout this 4-week period. Starting from a basal level of 0.4 Gutman-King- Armstrong units, acid hyperphenylphos- phatasia which lasted from 3 to 6 days and reached a maximum of 2.3, 3.3, and 3.9 units, respectively, was noted after each of the three episodes of thromboembolism.

A similar phenomenon has been noted after acute myocardial infarction, pul- monary embolism, and thrombophlebitis, and presumably a common mechanism is involved in all thromboembolic diseases. The nature of this mechanism is not at all clear, although thrombocytosis is con- jectured to play an important role. The available evidence indicates that autolysis of erythrocytes and platelets within the blood cIots themselves may also contribute to the serum acid phenylphosphatase ac- tivity. Release of the enzyme from pa- renchymal tissue injured by ischemia or inflammation may also occur but is not essential.

REFERENCES

Schoenfeld, M. R.: Acid phosphatase in serum: increase in acute myocardial infarction, Science 139:51, 1963. Schoenfeld, M. R., Lepow, H., Woll, F., and Edis, G.: Acid hyperhenylphosphatasia in thrombophlebitis and pulmdnary embolism, Ann. Int. Med. 57:468. 1962. Schoenfeld, M. R.: I&h serum acid phos- phatase activity in various thrombo-embolic diseases, Clin. Res. lO:lSO, 1962. Gutman, E. B., and Gutman, A. B.: Estimation of “acid” phosphatase activity of blood serum, J. Biol. Chem. 136:201, 1940.