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Postperfusion nonthrombocytopenic purpura
Postperfusion
Nonthrombocytopenic
An Uncommon
Purpura
Sequel of Open Heart Surgery*
DOUGLAS M. BEHRENDT, M.D., STEPHEN E. EPSTEIN, M.D. and ANDREW G. MORROW, M.D., F.A.C.C. Bethesda,
Maryland
A recently patients who
contained many white cells, but no organisms were evident on microscopic examination. The spleen was palpable, which it had not been previously. Hematologic studies revealed a white blood cell count of 6,200 per cu. mm., with 42 per cent neutrophiles, 46 per cent lymphocytes and 2 per cent monocytes; the hematocrit was 33 per cent and the platelet count 163,000 per cu. mm. The urine contained innumerable red cells and a trace of albumin. Results of tests of liver function, the blood urea nitrogen and serum electrolytes were normal. Bacterial endocarditis was considered likely and, after blood cultures had been obtained, antibiotics were given intravenously. Subsequently, the blood cultures were reported sterile. Smears revealed that 54 per cent of the peripheral white cells were lymphocytes, and 20 per cent of these had an atypical appearance. Administration of antibiotics, warfarin and aspirin was discontinued, but successive crops of fresh petechiae appeared, and fever continued. During hospitalization, the following examinations revealed no abnormality: cystoscopy with retrograde pyelography, renal arteriography, skin and muscle biopsies, bone marrow biopsy and culture, lupus erythematosus preparation, antistreptolysin-0 titer, serum protein electrophoresis, heterophile antibody tests, purified protein derivative and multiple urine cultures. Autoantibodies against the patient’s own leukocytes could not be demonstrated. A mild anemia persisted. Because of a low reticulocyte count, lack of occult blood in the stool, negative findings on direct and indirect Coombs test, and normal results on bone marrow examination, the anemia was believed to represent depressed erythropoiesis secondary to the basic disease process. The patient became progressively lethargic and had recurrent fever. Hematuria persisted and red cell casts were discovered in the urine. The blood urea nitrogen gradually rose to a maximal 69 mg. per cent. At this time administration of prednisone, 60 mg. daily, was begun. Fever abated within 24 hours, the blood urea nitrogen fell progressively to normal in three weeks, and the lymphocyte count declined to normal limits in two weeks, with disappearance of the
PREVIOUSLY unrecognized syndrome has been encountered among 7 had had corrective intracardiac purpuric In all 7 generalized operations. eruptions of variable severity developed, and in each many atypical lymphocytes appeared in the peripheral blood. No patient had thrombocytopenia. The clinical significant manifestations of the illness were not uniform, however, and the condition frequently led to a diagnostic and therapeutic enigma. Pertinent findings in these 7 patients are summarized in the present report, and the etiology of the syndrome is considered. CLINICAL SUMMARIES The clinical courses of the 7 patients under consideration are detailed in the following case reports, and certain laboratory and clinical data are presented in Table I. CASE 1. A 37 year old electrician underwent mitral valve replacement for calcific mitral stenosis with associated severe pulmonary hypertension. Preoperatively, the he.matocrit, total white blood cell count and different.ial and results of urinalysis were normal. On the fourth postoperative day microscopic hematuria, proteinuria and coarsely granular casts developed. The blood urea nitrogen remained normal, and urine cultures were sterile. The urine contained no malignant cells, and two intravenous pyelograms showec! normal findings. The white blood cell count was 8,400 per cu. mm., with a normal differential, and physical examination was unrevealing. Anticoagulation with warfarin had been initiated on the first postoperative day. Five weeks after operation the patient’s temperature rose to 40’ C., and examination revealed multiple slightly indurated petechiae, 1 to 3 mm. in diameter, over the entire body. They were most prominent on the legs and penis, where they were confluent. Some of the lesions had minute necrotic centers that
* From the Clinic of Surgery and Cardiology Branch, National Heart Institute, Bethesda, Md. 20014. Address for reprints: Andrew G. Morrow, M.D., Clinic of Surgery, National Heart Institute, National Health, Bethesda, Md. 20014. VOLUME
22, NOVEMBER
1968
631
Institutes
of
Behrendt,
632
Epstein
and Morrow
TABLE I Pertinent Clinical and Laboratory Manifested Nonthrombocytopenic
&SC No. & Age (yr.)
OP. PrOC.
O”SU of Rash (postop. wk.)
DUIXtiO” Range of of WBC Ill”eSS During Rash (days) (per CU.mm.)
Findings in Seven Patients Who Purpura after Cardiac Operations
Maximal Lymphocytosis.1 Atypical FOt-“IS (%)
Fever
Spleno- Hepatomegaly megaly
Ileterophile Agg. Test
l(37)
MVR
5
28
4100-9200
54/20
YeA
Yes
Neg.
2(23)
AVR
4
28
4500-11,000
79/20
YCS
Yes
Neg.
3(23J
AVR
6
5
4800-7200
49/60
Yes
?
Neg.
4 (57)
AVR & MVR
7
3800-9900
42/37
YeS
NO
Nes.,,
5(6)
Mustard pl-OC. AVR & MVR AVR & MVR
7
2-3
6700-9800
72/20
NO
Yes
Neg.
3
7
7600-9000
36/23
No
NO
6
2-3
7300-11,600
28/O
NO
NO
6f57) 7(38)
Clinical Setting and Course Associated with renal vasculitis; severely ill, requiring prednisonc Severely ill; treated initially for endocarditis, spontaneously XSOlVed
Agg. = agglutination; AVR = aortic valve replacement; MVR = mitral valve replacement; procedure; postop. = postoperative; WBC = white blood cell count.
atypical forms. Although several additional crops of petechiae occurred in association with localized arthralgias, the patient’s condition steadily improved; the dosage of prednisone was reduced and the drug was discontinued after three months of treatment. CASE 2. This 23 year old girl underwent aortic valve replacement. Her course was uncomplicated until four weeks after operation while she was at home ; then fever, splinter hemorrhages, “subcuta: neous nodules” on the fingers, and a petechial rash developed. Upon readmission to the Clinical Center five days later, her temperature was 38.3’ C., splinter hemorrhages were present, and fading petechiae were evident on the chest and thighs; no subcutaneous nodules were present. Initially, the spleen was not palpable, but in the fifth postoperative week its tip could be feit. The white blood cell count remained in the low-normal range, initially with a normal differential, but subsequently with as many as 79 per cent lymphocytes, 20 per cent of these being atypical, and 8 to 16 per cent eosinophiles. Platelet counts, serum electrophoresis, lupus erythematosus preparations, heterophile antibody tests, and antistreptolysin-0 titers were repeatedly performed and found to be within normal limits. After blood cultures were drawn, the patient was given antibiotics drugs intravenously because of the possibility of bacterial endocarditis. Despite therapy a spiking fever persisted, and the blood cultures remained sterile. Antibiotics were disconFive days later, during the eighth postoperatinued. tive week, the fever abated. In the subsequent two years the patient has remained well.
neg. = negative;
Part of stormy postoperative course; spontaneously resolved Associated with severe hepatitis; spontaneously resolved Associated with sevne congestive failure Associated with mild congestive failure Chance findine- on readmission for calf tenderness; (7) vasculitis op. = operative;
proc. =
CASE 3. A 23 year old Greek man underwent aortic valve replacement for rheumatic aortic regurgitation. His postoperative course was complicated by a myocardial infarction on the seventh day. An extension of the infarct occurred on the twenty-first postoperative day, and throughout this period his temperature was intermittently elevated. Two weeks later, an apical abscess developed in a left premolar tooth and necessitated dental extraction. The patient appeared to be recovering and had had fever for 10 days, when his temperature suddenly rose to 40° C. on the forty-fourth postoperative day. Examination revealed petechiae on the hard palate. The white blood cell count remained normal (4,800 to 7,200 per cu. mm.), but atypical lymphocytes became prominent, reaching a level of 60 per cent by the fiftysecond postoperative day. The platelet count was 254,000 per cu. mm. and the blood urea nitrogen was normal. The spleen was slightly enlarged. Results of the heterophile test and blood cultures were negative. There was progressive hematuria without casts, but a urologic examination, including intravenous and retrograde pyelograms, nephrotomograms and a renal scan, suggested that a renal infarct may have been responsible. Eventually, recovery was complete without specific therapy, and the patient was discharged. CASE 4. A 57 year old journalist had both the aortic and mitral valves replaced with Starr-Edwards prostheses. Four weeks after operation the white blood cell count was 4,800 per cu. mm., including 75 per cent neutrophiles, 16 per cent lymphocytes, 3 per cent monocytes and 5 per cent eosinophils. At this
THE AMERICAN JOURNAL
OF CARDIOLOGY
Postperfusion Nonthrombocytopenic time his temperature rose to 40.5’C., and over the ensuing week intense jaundice became evident. Tests of liver function revealed total bilirubin, 20.9 mg. per cent, with 13.5 mg. per cent direct reacting; oxaloacetic transaminase, 2216; serum glutamic: serum glutamic pyruvic transaminase, 1,399 units; and alkaline phosphatase, 29 King-Armstrong units. Results of the heterophile antibody test were negative. Several days after the onset of illness atypical lymphocytes were noted in blood smears; these increased in number until, during the sixth postoperative week, the white blood cell count was 10,800 per cu. mm. with 60 per cent neutrophiles, 1 per cent monocytes and 32 per cent lymphocytes, 25 per cent of which were atypical. A diffuse petechial eruption then occurred, and The the lesions were confluent on the legs and thighs. platelet count was 119,000 per cu. mm. at this time. The rash cleared spontaneously over a period of one week, the patient slowly recovered from his hepatitis, and he was discharged three months postoperatively. CASE 5. A 6 year old girl had complete transposition of the great arteries which was functionally corrected by a Mustard operation. Her postoperative course was complicated by supraventricular arrhythmias, and when she was discharged five weeks after operation she was on maintenance doses of digoxin and procainamide. At this time she had no skin rash and the white blood cell count and differential were normal. Two weeks later she was readmitted with the signs and symptoms of cardiac decompensation. Although she was afebrile, a diffuse fine petechial rash was evident. The spleen was palpable, but had been so throughout the postoperative period. The white blood cell count was 9,800 per cu. mm. with 39 per cent neutrophiles and 59 per cent lymphocytes; 25 per cent of the lymphocytes had an atypical appearance. The platelet count was 70,000 per cu. mm. An intensive program of diuretics, digitalis and salt restriction considerably improved cardiac function, and the rash faded in a few days. However, atypical lymphocytes were still evident three weeks later when the patient was discharged. CASE 6. A 57 yea.r old housewife underwent aortic and mitral valve replacement. Although her early postoperative course was complicated by persistent hypotension, requiring administration of isoproterenol, and later by peripheral edema, necessitating diuretic therapy, by the third postoperative week she At this time, however, a purpuric was ambulatory. eruption occurred, primarily on pressure areas. Thirty-six per cent lymphocytes with 23 per cent atypical forms were seen on a peripheral blood smear. The rash spread ove:r both legs and became pruritic She was before spontaneously fading a week later. discharged to a convalescent home during the fourth postoperative week. CASE 7. A 38 year old man returned to the Clinical Center because of shoulder and calf pain six weeks VOLUME 22, NOVEMBER 1968
Purpura
633
after mitral and aortic valve replacement. On admission he was afebrile; petechiae were present on the legs, the spleen was not palpable and there was an area of definite tenderness deep in the left calf. Laboratory examination revealed a normal white The calf tenderness blood cell count and differential. was not thought to represent phlebitis, and a venoWithin a few days the gram of that leg was normal. petechiae faded, the calf tenderness discharged.
abated
and he was
DISCUSSION
Although transient nonpurpuric rashes have been described after open cardiac operations,ls2 the delayed appearance of a purpuric eruption in such circumstances has received only scant notice.3 It would thus seem that the clinical syndrome characterized by nonthrombocytopenic purpura and atypical lymphocytosis represents a relatively uncommon late complication of open heart surgery. However, it is quite evident that the clinical expression of this syndrome may range from small numbers of petechial lesions, which might easily escape detection without careful examination, to a severe generalized vasculitis resulting in a clinically alarming and potentially fatal illness. The incidence of this complication may, therefore, be higher than suspected, since it is possible that after discharge from the hospital a significant number of patients may have the illness, but in such a mild form as to remain undiagnosed. The purpuric eruption was observed to occur three to six weeks after operation. It was usually associated with the appearance of atypical lymphocytes in the peripheral blood and, less consistently, with fever and splenomegaly. Except for the presence of the atypical lymphocytes, indistinguishable from those seen in infectious mononucleosis or the postperfusion syndrome, laboratory tests were nonspecific. The platelet counts were normal or slightly reduced, never in the range usually believed to cause bleeding.4 Results of the heterophile test were within normal limits in each of the patients in whom the test was performed and, except for the patient with hepatitis, liver function tests revealed no consistent abnormalities. Henoch-Schdein Purpura: Each of the patients described posed a diagnostic problem, and the most frequent initial suspicion was bacterial endocarditis. However, all patients recovered spontaneously and completely, except for the patient in whom severe glomerulitis developed.
634
Behrendt,
Epstein and Morrow
In this patient the diffuse renal vascular involvement led to progressive uremia and necessitated the use of steroids in high doses. Although it is obviously impossible to know what the natural course of the glomerulitis would have been, renal function did slowly return to normal concomitant with the initiation of steroid therapy. Clinically, the illness in this patient falls into the category of Henoch-Schonlein purpura and represents the first reported instance of this syndrome occurring after an open heart operation. It is interesting to note that in several series of patients with Henoch-SchGnlein purpura, nephritis was a feature of the illness in 22 to 48 per cent of cases,K-r and several such patients have died in uremia.8yg Relation to Postperfusion Syndrome and PostIt is not known whether transfusion Hepatitis: the syndrome described in this report is an integral part of the postperfusion syndrome or a separate entity. The similar latency period as well as such common features as atypical lymphocytes, fever and splenomegalY~~,iO--1~
SUMMARY Seven
operative sequel to open described. penic purpuric eruption blood, cases illustrate
surgery developed, and
postare
usually
splenomegaly.
during
an
illness
other respects renal vessels and resulting severe insufficiency. Although those tients with the mildest symptoms would have escaped detection other illness, those diagnostic fever and splenomegaly
drome
cause heart
of postperfusion nonthrombocytopenic should help to clarify the origin fevers of unknown procedures.
SMITH, D. R.
A syndrome resembling infectious after open surgery. 1964. 2. REYMAN, T. A. Postperfusion syndrome : A review report of 21 cases. Am. Heart
Philadelphia, 1961. Lea & Febiger. 5. PHILPOTT, M. G. The SchBnlein-Henoch
involvement. Pediatrics, 16: 196, 1955. 7. STERKY, G. and THILEN, A. A study on the onset and prognosis of acute vascular purpura (the Schonlein-Henoch
Postperfusion Nonthrombocytopenic ritis as a complication of the SchBnlein-Henoch syndrome. New England J. Med., 248: 530, 1953. 10. SEAMAN,A. J. and STARR, A. Febrile postcardiotomy lymphocytic splenomegaly : A new entity. Ann. Surg., 156: 956, 1962. 11. WHEELER, E. O., TURNER, J. D. and SCANNELL, J. G. Fever, splenomegaly and atypical lymphocytes: A syndrome observed after cardiac surgery utilizing a pump oxygenator. New England J. Med., 226: 454, 1962. 12. HOLSWADE, G. I~., ENGLE, M. A., REDO, S. F., GOLDSMITH, E. 1. and BARONDESS,J. A. Development of .viral diseases and a viral disease-
DRUGS
Purpura
635
like syndrome after extracorporeal circulation. Circulation, 27: 812, 1963. 13. KAHN, D. R., ERTEL, P. Y., MURPHY, W. H., KIRSH, M. M., VATHAYNON, S., STERN, A. M. and SLOAN, H. Pathogenesis of the post-cardiotomy syndrome. J. Thoracic G’ Cardiovas. Surg., in press. 14. REPLOGLE, R. L. and KEVY, S. V. Hematologic limitations of prolonged cardiopulmonary bypass. J. Thoracic &3 Cardiovas. Surg., in press. 15. ROSENBLUM,R. and HEIDENBERG,W. J. An evaluation of post-transfusion hepatitis and post-pump syndrome after the use of extracorporeal circulation. Clin. Res., 14:260, 1966.
IN USE U 3359/2Q Aadlmide RCl
Diagnosis [ypertenaion, essential mod. (out-patient) Bf systol‘ic Diaeto1ia Duration:
Cross-omr
Results
Placebo Rmiloride Hydrochlorothiazide
Laboratory Data Elevated SGOT, transient 1
6 weeks
stndy
Double-Blind St* s,ttati&l&al
t t
stuar
Uriq Sodim (@q/day Creatinine (gm/day)
E
Comeredtith: Placebo . Hydrochlorothiazide (U 0329/93) See also: Aadloride HCl (U 3359/u) Hydrochlorotbiazide (U 03Z9/94)
Tables given. 435 %
Author’e
Cenmtent
is therefore of I W&Cemiloridel _ . special intereat a~ a diuretic
since it may cause the wIthdrawal of sodium from compartments not usually
G$#$
@&p&%Y&%&
tipffmyer, n. & Conway, J.
CU. Hosp., U. Michigan Med. Ctr., h Arbor, f+ich.) ohs antihppert.emive aad diuretic effects of doride and of its combination with hydrocblorotbiazide. CI.IU. ~harmaool. Thor. 9: 3550-354 (~YJW) 1968 Prepared by Paul de Haen, Inc. for the drug index card system, “de Haen Drugs in Use.”
VOLUME 22, NOVEMBER1968
.
,)
Nonthrombocytopenic
An Uncommon
Purpura
Sequel of Open Heart Surgery*
DOUGLAS M. BEHRENDT, M.D., STEPHEN E. EPSTEIN, M.D. and ANDREW G. MORROW, M.D., F.A.C.C. Bethesda,
Maryland
A recently patients who
contained many white cells, but no organisms were evident on microscopic examination. The spleen was palpable, which it had not been previously. Hematologic studies revealed a white blood cell count of 6,200 per cu. mm., with 42 per cent neutrophiles, 46 per cent lymphocytes and 2 per cent monocytes; the hematocrit was 33 per cent and the platelet count 163,000 per cu. mm. The urine contained innumerable red cells and a trace of albumin. Results of tests of liver function, the blood urea nitrogen and serum electrolytes were normal. Bacterial endocarditis was considered likely and, after blood cultures had been obtained, antibiotics were given intravenously. Subsequently, the blood cultures were reported sterile. Smears revealed that 54 per cent of the peripheral white cells were lymphocytes, and 20 per cent of these had an atypical appearance. Administration of antibiotics, warfarin and aspirin was discontinued, but successive crops of fresh petechiae appeared, and fever continued. During hospitalization, the following examinations revealed no abnormality: cystoscopy with retrograde pyelography, renal arteriography, skin and muscle biopsies, bone marrow biopsy and culture, lupus erythematosus preparation, antistreptolysin-0 titer, serum protein electrophoresis, heterophile antibody tests, purified protein derivative and multiple urine cultures. Autoantibodies against the patient’s own leukocytes could not be demonstrated. A mild anemia persisted. Because of a low reticulocyte count, lack of occult blood in the stool, negative findings on direct and indirect Coombs test, and normal results on bone marrow examination, the anemia was believed to represent depressed erythropoiesis secondary to the basic disease process. The patient became progressively lethargic and had recurrent fever. Hematuria persisted and red cell casts were discovered in the urine. The blood urea nitrogen gradually rose to a maximal 69 mg. per cent. At this time administration of prednisone, 60 mg. daily, was begun. Fever abated within 24 hours, the blood urea nitrogen fell progressively to normal in three weeks, and the lymphocyte count declined to normal limits in two weeks, with disappearance of the
PREVIOUSLY unrecognized syndrome has been encountered among 7 had had corrective intracardiac purpuric In all 7 generalized operations. eruptions of variable severity developed, and in each many atypical lymphocytes appeared in the peripheral blood. No patient had thrombocytopenia. The clinical significant manifestations of the illness were not uniform, however, and the condition frequently led to a diagnostic and therapeutic enigma. Pertinent findings in these 7 patients are summarized in the present report, and the etiology of the syndrome is considered. CLINICAL SUMMARIES The clinical courses of the 7 patients under consideration are detailed in the following case reports, and certain laboratory and clinical data are presented in Table I. CASE 1. A 37 year old electrician underwent mitral valve replacement for calcific mitral stenosis with associated severe pulmonary hypertension. Preoperatively, the he.matocrit, total white blood cell count and different.ial and results of urinalysis were normal. On the fourth postoperative day microscopic hematuria, proteinuria and coarsely granular casts developed. The blood urea nitrogen remained normal, and urine cultures were sterile. The urine contained no malignant cells, and two intravenous pyelograms showec! normal findings. The white blood cell count was 8,400 per cu. mm., with a normal differential, and physical examination was unrevealing. Anticoagulation with warfarin had been initiated on the first postoperative day. Five weeks after operation the patient’s temperature rose to 40’ C., and examination revealed multiple slightly indurated petechiae, 1 to 3 mm. in diameter, over the entire body. They were most prominent on the legs and penis, where they were confluent. Some of the lesions had minute necrotic centers that
* From the Clinic of Surgery and Cardiology Branch, National Heart Institute, Bethesda, Md. 20014. Address for reprints: Andrew G. Morrow, M.D., Clinic of Surgery, National Heart Institute, National Health, Bethesda, Md. 20014. VOLUME
22, NOVEMBER
1968
631
Institutes
of
Behrendt,
632
Epstein
and Morrow
TABLE I Pertinent Clinical and Laboratory Manifested Nonthrombocytopenic
&SC No. & Age (yr.)
OP. PrOC.
O”SU of Rash (postop. wk.)
DUIXtiO” Range of of WBC Ill”eSS During Rash (days) (per CU.mm.)
Findings in Seven Patients Who Purpura after Cardiac Operations
Maximal Lymphocytosis.1 Atypical FOt-“IS (%)
Fever
Spleno- Hepatomegaly megaly
Ileterophile Agg. Test
l(37)
MVR
5
28
4100-9200
54/20
YeA
Yes
Neg.
2(23)
AVR
4
28
4500-11,000
79/20
YCS
Yes
Neg.
3(23J
AVR
6
5
4800-7200
49/60
Yes
?
Neg.
4 (57)
AVR & MVR
7
3800-9900
42/37
YeS
NO
Nes.,,
5(6)
Mustard pl-OC. AVR & MVR AVR & MVR
7
2-3
6700-9800
72/20
NO
Yes
Neg.
3
7
7600-9000
36/23
No
NO
6
2-3
7300-11,600
28/O
NO
NO
6f57) 7(38)
Clinical Setting and Course Associated with renal vasculitis; severely ill, requiring prednisonc Severely ill; treated initially for endocarditis, spontaneously XSOlVed
Agg. = agglutination; AVR = aortic valve replacement; MVR = mitral valve replacement; procedure; postop. = postoperative; WBC = white blood cell count.
atypical forms. Although several additional crops of petechiae occurred in association with localized arthralgias, the patient’s condition steadily improved; the dosage of prednisone was reduced and the drug was discontinued after three months of treatment. CASE 2. This 23 year old girl underwent aortic valve replacement. Her course was uncomplicated until four weeks after operation while she was at home ; then fever, splinter hemorrhages, “subcuta: neous nodules” on the fingers, and a petechial rash developed. Upon readmission to the Clinical Center five days later, her temperature was 38.3’ C., splinter hemorrhages were present, and fading petechiae were evident on the chest and thighs; no subcutaneous nodules were present. Initially, the spleen was not palpable, but in the fifth postoperative week its tip could be feit. The white blood cell count remained in the low-normal range, initially with a normal differential, but subsequently with as many as 79 per cent lymphocytes, 20 per cent of these being atypical, and 8 to 16 per cent eosinophiles. Platelet counts, serum electrophoresis, lupus erythematosus preparations, heterophile antibody tests, and antistreptolysin-0 titers were repeatedly performed and found to be within normal limits. After blood cultures were drawn, the patient was given antibiotics drugs intravenously because of the possibility of bacterial endocarditis. Despite therapy a spiking fever persisted, and the blood cultures remained sterile. Antibiotics were disconFive days later, during the eighth postoperatinued. tive week, the fever abated. In the subsequent two years the patient has remained well.
neg. = negative;
Part of stormy postoperative course; spontaneously resolved Associated with severe hepatitis; spontaneously resolved Associated with sevne congestive failure Associated with mild congestive failure Chance findine- on readmission for calf tenderness; (7) vasculitis op. = operative;
proc. =
CASE 3. A 23 year old Greek man underwent aortic valve replacement for rheumatic aortic regurgitation. His postoperative course was complicated by a myocardial infarction on the seventh day. An extension of the infarct occurred on the twenty-first postoperative day, and throughout this period his temperature was intermittently elevated. Two weeks later, an apical abscess developed in a left premolar tooth and necessitated dental extraction. The patient appeared to be recovering and had had fever for 10 days, when his temperature suddenly rose to 40° C. on the forty-fourth postoperative day. Examination revealed petechiae on the hard palate. The white blood cell count remained normal (4,800 to 7,200 per cu. mm.), but atypical lymphocytes became prominent, reaching a level of 60 per cent by the fiftysecond postoperative day. The platelet count was 254,000 per cu. mm. and the blood urea nitrogen was normal. The spleen was slightly enlarged. Results of the heterophile test and blood cultures were negative. There was progressive hematuria without casts, but a urologic examination, including intravenous and retrograde pyelograms, nephrotomograms and a renal scan, suggested that a renal infarct may have been responsible. Eventually, recovery was complete without specific therapy, and the patient was discharged. CASE 4. A 57 year old journalist had both the aortic and mitral valves replaced with Starr-Edwards prostheses. Four weeks after operation the white blood cell count was 4,800 per cu. mm., including 75 per cent neutrophiles, 16 per cent lymphocytes, 3 per cent monocytes and 5 per cent eosinophils. At this
THE AMERICAN JOURNAL
OF CARDIOLOGY
Postperfusion Nonthrombocytopenic time his temperature rose to 40.5’C., and over the ensuing week intense jaundice became evident. Tests of liver function revealed total bilirubin, 20.9 mg. per cent, with 13.5 mg. per cent direct reacting; oxaloacetic transaminase, 2216; serum glutamic: serum glutamic pyruvic transaminase, 1,399 units; and alkaline phosphatase, 29 King-Armstrong units. Results of the heterophile antibody test were negative. Several days after the onset of illness atypical lymphocytes were noted in blood smears; these increased in number until, during the sixth postoperative week, the white blood cell count was 10,800 per cu. mm. with 60 per cent neutrophiles, 1 per cent monocytes and 32 per cent lymphocytes, 25 per cent of which were atypical. A diffuse petechial eruption then occurred, and The the lesions were confluent on the legs and thighs. platelet count was 119,000 per cu. mm. at this time. The rash cleared spontaneously over a period of one week, the patient slowly recovered from his hepatitis, and he was discharged three months postoperatively. CASE 5. A 6 year old girl had complete transposition of the great arteries which was functionally corrected by a Mustard operation. Her postoperative course was complicated by supraventricular arrhythmias, and when she was discharged five weeks after operation she was on maintenance doses of digoxin and procainamide. At this time she had no skin rash and the white blood cell count and differential were normal. Two weeks later she was readmitted with the signs and symptoms of cardiac decompensation. Although she was afebrile, a diffuse fine petechial rash was evident. The spleen was palpable, but had been so throughout the postoperative period. The white blood cell count was 9,800 per cu. mm. with 39 per cent neutrophiles and 59 per cent lymphocytes; 25 per cent of the lymphocytes had an atypical appearance. The platelet count was 70,000 per cu. mm. An intensive program of diuretics, digitalis and salt restriction considerably improved cardiac function, and the rash faded in a few days. However, atypical lymphocytes were still evident three weeks later when the patient was discharged. CASE 6. A 57 yea.r old housewife underwent aortic and mitral valve replacement. Although her early postoperative course was complicated by persistent hypotension, requiring administration of isoproterenol, and later by peripheral edema, necessitating diuretic therapy, by the third postoperative week she At this time, however, a purpuric was ambulatory. eruption occurred, primarily on pressure areas. Thirty-six per cent lymphocytes with 23 per cent atypical forms were seen on a peripheral blood smear. The rash spread ove:r both legs and became pruritic She was before spontaneously fading a week later. discharged to a convalescent home during the fourth postoperative week. CASE 7. A 38 year old man returned to the Clinical Center because of shoulder and calf pain six weeks VOLUME 22, NOVEMBER 1968
Purpura
633
after mitral and aortic valve replacement. On admission he was afebrile; petechiae were present on the legs, the spleen was not palpable and there was an area of definite tenderness deep in the left calf. Laboratory examination revealed a normal white The calf tenderness blood cell count and differential. was not thought to represent phlebitis, and a venoWithin a few days the gram of that leg was normal. petechiae faded, the calf tenderness discharged.
abated
and he was
DISCUSSION
Although transient nonpurpuric rashes have been described after open cardiac operations,ls2 the delayed appearance of a purpuric eruption in such circumstances has received only scant notice.3 It would thus seem that the clinical syndrome characterized by nonthrombocytopenic purpura and atypical lymphocytosis represents a relatively uncommon late complication of open heart surgery. However, it is quite evident that the clinical expression of this syndrome may range from small numbers of petechial lesions, which might easily escape detection without careful examination, to a severe generalized vasculitis resulting in a clinically alarming and potentially fatal illness. The incidence of this complication may, therefore, be higher than suspected, since it is possible that after discharge from the hospital a significant number of patients may have the illness, but in such a mild form as to remain undiagnosed. The purpuric eruption was observed to occur three to six weeks after operation. It was usually associated with the appearance of atypical lymphocytes in the peripheral blood and, less consistently, with fever and splenomegaly. Except for the presence of the atypical lymphocytes, indistinguishable from those seen in infectious mononucleosis or the postperfusion syndrome, laboratory tests were nonspecific. The platelet counts were normal or slightly reduced, never in the range usually believed to cause bleeding.4 Results of the heterophile test were within normal limits in each of the patients in whom the test was performed and, except for the patient with hepatitis, liver function tests revealed no consistent abnormalities. Henoch-Schdein Purpura: Each of the patients described posed a diagnostic problem, and the most frequent initial suspicion was bacterial endocarditis. However, all patients recovered spontaneously and completely, except for the patient in whom severe glomerulitis developed.
634
Behrendt,
Epstein and Morrow
In this patient the diffuse renal vascular involvement led to progressive uremia and necessitated the use of steroids in high doses. Although it is obviously impossible to know what the natural course of the glomerulitis would have been, renal function did slowly return to normal concomitant with the initiation of steroid therapy. Clinically, the illness in this patient falls into the category of Henoch-Schonlein purpura and represents the first reported instance of this syndrome occurring after an open heart operation. It is interesting to note that in several series of patients with Henoch-SchGnlein purpura, nephritis was a feature of the illness in 22 to 48 per cent of cases,K-r and several such patients have died in uremia.8yg Relation to Postperfusion Syndrome and PostIt is not known whether transfusion Hepatitis: the syndrome described in this report is an integral part of the postperfusion syndrome or a separate entity. The similar latency period as well as such common features as atypical lymphocytes, fever and splenomegalY~~,iO--1~
SUMMARY Seven
operative sequel to open described. penic purpuric eruption blood, cases illustrate
surgery developed, and
postare
usually
splenomegaly.
during
an
illness
other respects renal vessels and resulting severe insufficiency. Although those tients with the mildest symptoms would have escaped detection other illness, those diagnostic fever and splenomegaly
drome
cause heart
of postperfusion nonthrombocytopenic should help to clarify the origin fevers of unknown procedures.
SMITH, D. R.
A syndrome resembling infectious after open surgery. 1964. 2. REYMAN, T. A. Postperfusion syndrome : A review report of 21 cases. Am. Heart
Philadelphia, 1961. Lea & Febiger. 5. PHILPOTT, M. G. The SchBnlein-Henoch
involvement. Pediatrics, 16: 196, 1955. 7. STERKY, G. and THILEN, A. A study on the onset and prognosis of acute vascular purpura (the Schonlein-Henoch
Postperfusion Nonthrombocytopenic ritis as a complication of the SchBnlein-Henoch syndrome. New England J. Med., 248: 530, 1953. 10. SEAMAN,A. J. and STARR, A. Febrile postcardiotomy lymphocytic splenomegaly : A new entity. Ann. Surg., 156: 956, 1962. 11. WHEELER, E. O., TURNER, J. D. and SCANNELL, J. G. Fever, splenomegaly and atypical lymphocytes: A syndrome observed after cardiac surgery utilizing a pump oxygenator. New England J. Med., 226: 454, 1962. 12. HOLSWADE, G. I~., ENGLE, M. A., REDO, S. F., GOLDSMITH, E. 1. and BARONDESS,J. A. Development of .viral diseases and a viral disease-
DRUGS
Purpura
635
like syndrome after extracorporeal circulation. Circulation, 27: 812, 1963. 13. KAHN, D. R., ERTEL, P. Y., MURPHY, W. H., KIRSH, M. M., VATHAYNON, S., STERN, A. M. and SLOAN, H. Pathogenesis of the post-cardiotomy syndrome. J. Thoracic G’ Cardiovas. Surg., in press. 14. REPLOGLE, R. L. and KEVY, S. V. Hematologic limitations of prolonged cardiopulmonary bypass. J. Thoracic &3 Cardiovas. Surg., in press. 15. ROSENBLUM,R. and HEIDENBERG,W. J. An evaluation of post-transfusion hepatitis and post-pump syndrome after the use of extracorporeal circulation. Clin. Res., 14:260, 1966.
IN USE U 3359/2Q Aadlmide RCl
Diagnosis [ypertenaion, essential mod. (out-patient) Bf systol‘ic Diaeto1ia Duration:
Cross-omr
Results
Placebo Rmiloride Hydrochlorothiazide
Laboratory Data Elevated SGOT, transient 1
6 weeks
stndy
Double-Blind St* s,ttati&l&al
t t
stuar
Uriq Sodim (@q/day Creatinine (gm/day)
E
Comeredtith: Placebo . Hydrochlorothiazide (U 0329/93) See also: Aadloride HCl (U 3359/u) Hydrochlorotbiazide (U 03Z9/94)
Tables given. 435 %
Author’e
Cenmtent
is therefore of I W&Cemiloridel _ . special intereat a~ a diuretic
since it may cause the wIthdrawal of sodium from compartments not usually
G$#$
@&p&%Y&%&
tipffmyer, n. & Conway, J.
CU. Hosp., U. Michigan Med. Ctr., h Arbor, f+ich.) ohs antihppert.emive aad diuretic effects of doride and of its combination with hydrocblorotbiazide. CI.IU. ~harmaool. Thor. 9: 3550-354 (~YJW) 1968 Prepared by Paul de Haen, Inc. for the drug index card system, “de Haen Drugs in Use.”
VOLUME 22, NOVEMBER1968
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