Serum lactic dehydrogenase in abruptio placentae

Serum lactic dehydrogenase in abruptio placentae JOHN G. BOUTSELIS, M.D. JEROME A. WENSINGER, M.D.

ROBERT J. SOLLARS, M.D. Columbus, Ohio

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T H E determination of lactic dehydrogenase (LDH) activity has received attention in several medical centers, both as an investigative tool and as a clinical laboratory procedure, because of the promise that it has shown in the diagnosis and prognosis of certain diseases. Elevation of this enzyme in the sera of patients with neoplastic diseases, 2 • 8 • 9 • 14• 17 • 24 nephritis, 21 • 24 hepatitis, 21 • 24 myocardial infarction/4• 17 • 18 • 21 ' 22 • 24 and other disease conditions 2 • 7 • 14 • 17 • 21 • 24 have been reported. In equivocal cases of myocardial infarction, LDH has proved superior to the transaminase determinations, since LDH elevations persist for a significantly longer period of time after the initial necrosis. 10 • 11 Normal values in the uncomplicated pregnancy have been reported by West/ 9 Smith/ 6 Little/ 3 and Heimback and Prezyna. 5 A variety of obstetric complications have been reported by Little. 13 Significant elevations of LDH were noted in 6 cases of abruptio placentae. Lactic dehydrogenase, an enzyme of the glycolytic cycle, reversibly catalyzes the conversion of pyruvate to lactate, utilizing diphosphopyridine nucleotide (DPNH or DPN) as an oxidizable-reducible coenzyme for the reaction.

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The large number of conditions which have been reported to alter .LDII activity in the serum indicate the need for a broader survey of the specific conditions which affect this determination. The p1,.1rpose of this study is to report our experience with LDH de:. terminations in a number of complications of pregnancy, particularly abruptio placentae.

Methotls and material Venous blood was ob.tained fron1 the antecubital vein of 75 pregnant patients during various periods of gestation. After centrifugation at 2,500 r.p.m. for 20 minutes the clear serum was stored in the freezer at -20° C. for no longer than 2 weeks (no loss of activity in 2 weeks). Care was exercised in handling of ali specimens to prevent erroneous elevations due to hemolysis and all grossly hemolyzed speci..mens were discarded since erythrocytes exhibit greater enzyme activity than sera and would there-, fore give spurious high results. Enzyme activity is generally expressed in terms of arbitrary "units." The exact definition of a unit of LDH varies frequently from one laboratory to another, so that data from different laboratories often cannot be directly compared. The mcpression of LDH in optical

From the Department of Obstetrics and Gynecology, Mount Carmel Hospital.

762

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Abruptio placentae 763

density units, when the normal range is

mole was associated with a slight LDH

known, is useful clinically since little or no mathematical manipulation is involved. Serum LDH in the present study was determined by the method described by Berger and Broida1 and normal levels ranged between 100 to 350 units.

elevation of 380 units. Although the length of gestation was 5 months by history, examination disclosed the uterus to be the size of a 4 months' pregnancy. One of the highest serum LDH elevations, 3,380 units, was obtained on a patient with macrocytic anemia 10 hours post partum. Sheehan's syndrome was one of the most interesting findings encountered in the present study. At 35 weeks' gestation, with a confirmed intrauterine fetal death of 2 weeks' duration, spontaneous labor occurred and a macerated fetus was delivered. Defibrination, puerperal hemorrhage, and prolonged shock ensued and during the subsequent 3 months the patient developed a classical picture of Sheehan's syndrome. During the early puerperal period serial serum LDH levels were all elevated, the average value being 1,780 units. Of particular interest in this study were the patients with abruptio placentae and placenta previa. Their values are noted on Table I and illustrated graphically in Figs. 1 and 2. Normal LDH values were obtained in 12 cases of placenta previa, the length of gestation varying bctvvccn 27 and 37 weeks. Conversely, 26 of 33 cases of abruptio placentae revealed elevations varying between 360 and 910 LDH units. Abruptio placentae associated with normal LDH values was further analyzed and classed as mild abruptio placentae with minimal or no retroplacental blood clots. Six out of these 7 cases revealed values between 300 and 350

Results

Tab:le I illustrates serum LDH determinations which were made on 73 adult patients with normal or complicated pregnancies. In many instances more than one determination was made and the average levels are recorded. Nonnal pregnancy. Several authors 12 ' 13 , 16 have recorded normal serum LDH levels during various trimesters of pregnancy; therefore, it seems unnecessary for us to repeat such well-documented studies. Uncomplicated labor and puerperium. Similarly normal values of LDH have been reported during labor15 and our results based on 10 cases confinn these findings. Contrary to the results of Little 13 and Smith and associates, 16 our findings based on 6 normal l-}()stpa:rtum patients reveal no elevation of serum LDH. Obsttetric complications. Five patients with missed abortions between 12 and 14 weeks' gestation revealed normal serum LDH values. Similarly normal values were obtained in 5 patients with incomplete abortion, the length of gestation varying between 10 and 12 weeks. One of the 2 cases of hydatidiform

Table I. Serum LDH values in pregnancy and puerperium Diagnosis Normal labor Normal post partum Missed abortion Hydatidiform mole Macrocytic anemia Sheehan's syndrome ( hypofibrinogenem ia) Incomplete abortion Placenta previa Abruptio placentae Total cases

Range

10

6 5 2 1

1 5 12 33 75

39 40 13 16 40 35 11 33 37

37-40 12-14 12-20 (Post partum) (Post partum)

10-12 27-36 28-40

Average LDH/units

No. LDH elevations

287 225 260 270 3,380

None None None

1,780 230 228 450

(380) (3380) (1780) None None

26 (360-910)

.July 15, 196:!

764 Boutselis, Wensinger, and Sollars

Am.]. Obst. & Gynec.

units, values considered near borderline elevations. Fig. 3 illustrates a patient with abruptio placentae and a patient with placenta previa, each at 28 weeks' gestation, delivered by cesarean section for maternal indications. In the case of abruptio placentae, admission

•

100

LDH was 420 units, which sharply rose to 910 units 4 hours post partum and thereafter decreased to normal values as indicated graphically. Conversely, in placenta previa. admission LDH was 330 units, which remained at normal levels throughout the 48 hour postpartum period .

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Fig. l. LDH in abruptio placentae (33 cases).

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Fig, 2. LDH in placenta previa ( 12 cases).

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Abruptio placentae

Volume 81i Number 6

765

Consideration of etiology of

in gradations of Couvelaire uterus, and acute

LDH elevations

placental infarction when present. Little 1 a also noted that LDH alterations usually occurred within 6 to 10 hours after the onset of symptoms; this concurred with the observations in myocardial infarction.""· "'' When abruptio placentae is associated with any degree of defibrination, intravascular clotting and erthrocyte destruction may be considered a factor in LDH elevation. This was well demonstrated in the case of Sheehan's syndrome associated with afibrinogenemia.

In myocardial infarction and some other diseases, several authors 4 • 10 • 22 • 23 have suggested that an increase in serum LDH was correlated with tissue necrosis and release of intracellular LDH. Drefus and his associates3 demonstrated that serum LDH was elevated in animals given large doses of corticoids and suggested that the high levels might be in part a general reaction to stress. Hess6 regards the degradation of erythrocytes as the major source of normal serum LDH. Among other factors White 20 · 21 postulated an increase LDH to be due to muscle degeneration. Little, 13 in his excellent study of LDH as related to placental abruption prior to delivery, showed an increase LDH correlated with the amount of retroplacental clot present. From these observations it is not unreasonable to conclude that in abruptio placentae an elevated serum LDH level is attributed to a general stress reaction, destruction of erythrocyte con= stituents of retroplacental blood clots, tissue necroses in the vicinity of placental separation (decidual bed and placental), variable degrees of myometrial destruction as noted

Comment

It appears that serum lactic dehydrogenase has a practical clinical application in bleeding complications of pregnancy. Consistently normal values were obtained in placenta previa and incomplete abortion, while consistently elevated values were noted in abruptio placentae. Several factors may be responsible for LDH elevation in abruptio placentae. One of the richest sources of LDH in the body is the red blood cell; therefore, retroplacental blood clots associated with this bleeding disorder would yield elevated LDH values. Placenta and decidual dis-

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Fig. 3. LDH in abruptio placentae and placenta previa.

48

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766 Boutselis, Wensinger, and Sollars

ruption in the nature of infarction, ischemia, and necrosis would release intracellular LDH into the circulation, resulting in elevated serum LDH. Abruptio placentae is commonly associated with variable degrees of Couvelaire uteri in which extravasated blood into the uteri musculature not only results in localized red blood cell destruction but also in myometrial disruption. Drefus and associates 3 have demonstrated elevated values of serum LDH whenever a genera! stress reaction was produced in the experimental animal; therefore, this principle would be applicable to abruptio placentae if we accept the hypothesis that a stress reaction exists. That the fetus may be a source of LDH production was postulated by LittleY Of 10 instances of LDH elevation, 8 were associated with fetal distress. The purpose of this study was to see if LDH values were significantly different in placenta previa and abruptio placentae.

REFERENCES l. Berger, L., and Broida, D.: Sigma Technical Bulletin No. 500, Revised October, 1960. 2. Bierman, H. R., et al.: Cancer Res. 17: 660, 1957. 3. Drefus, J. C., Schapira, G., and Schapira, F.: Ann. New York Acad. Sc. 75: 235, 1958. 4. Hanson, A., and Biorck, G.: Acta med. scandinav. 157: 493, 1957. 5. Heimback, D. P., and Prezyna, A. P.: Obst. & Gynec. 79: 108, 1960. 6. Hess, B.: Ann. New York Acad. Sc. 75: 235, 1958. 7. Hess, B., and Gelm, P.: Klin. Wchnschr. 33: 91, 1955. 8. Hill, B. R.: Cancer Res. 16: 460, 1956. 9. Hill, B. R., and Levi, C.: Cancer Res. 14: 513, 1954. iO. LaDue, J. S.: Arn. J. Cardiol. 1: 308, 1-958. I I. LaDue, J. S., Wroblewski, F., and Karmen, A.: Science 120:497, 1954. 12. Linton, E. B., and ~..filler, & Gynec. 78: 11, 1959.

july 15, 196J Am . .J. Obst. & (;ynnc.

Further observations of additional cases will be necessary to see if a-ny correlation exists between the severity of abruptio placentae and the degree of LDH elevation and what degree of LDH elevation is associated with fetal distress. Summary

1. Serum LDH values were studied in 75 pregnant patients, including 33 with abruptio placentae. 2. Of 33 patients with abruptio placentae, 26 had significant LDH elevations. The remaining 7 patients showed high normal to borderline LDH elevations. All patients with placenta previa exhibited normal values. 3. Serum LDH may be of some value in differentiating between placenta previa and abruptio placentae. 4. The possible mecha1:1isms by which LDH elevations occurred in abruptio placentae have been discussed.

13. Little, W. A.: Obst. & Gynec. 13: 152, 1959. 14. MacDonald, R. P., Simpson, J. R., and Nossae, E.: J. A. M. A. 165: 35, 1957. 15. Richardson, D. E., and Coker, S. D., Jt.: Bull. Tulane Med. Fac. 17: 45, 1957. 16. Smith, J. ]., Schwartz, E. D., and Schwartz, M. K.: Obst. & Gynec. 13: 163, 1959. 17. Vallee, B. L., and Wacker, W. E. C.: J. Am. ""'n ro \.....inem. ~oc. 10: 111 1, l:::tJo. 18. Wacker, W. E. C., Ulmer, D. D., and Vallee, B. L.: New England J. Med. 255: 449, 1956. 19. West, M., and Zimmerman, H.: Am. J M. Sc. 235: 443, 1958. 20. White, L. P.: Clin. Res. Proc. 5: 84, 1957. 21. White, L. P.: New England J. Med. 2,')5: 984, 1956. 22. Wroblewski, F.: Am. Heart J. 54: 219, 1957. 23. 'A/roble\vski, F., and LaDue, J. S.: Proc. Soc. Exper. Bioi. & Med. 90: 210, 1955. 24. Zimmerman, H. ]., and Weinstein, H. G.: .1'"'1.1

J.

1 ..,'"71

1 rH~r

Lab. & C!in. Med. 48: 607, 1956.