Disseminated intravascular coagulation following extracorporeal circulation Arthur D. Boyd, M.D. (by invitation), Richard M. Engelman, M.D. (by invitation), Regent L. Beaudet, M.D. (by invitation), and Henriette Lackner, M.D. (by invitation), New York, N. Y. Sponsored by Frank C. Spencer, M.D., New York, N. Y.
_L/isseminated intravascular coagulation (DIC) has been identified with increasing frequency in many clinical conditions 1 ' 2 but has seldom been recognized following extracorporeal circulation.1' 3-4 This is surprising because many of the etiologic factors contributing to the production of DIC, such as shock, acidosis, sepsis, and hepatic failure, are often found in patients following cardiac surgery. Our first recognition of DIC as a complication of extracorporeal circulation was a tragic experience with a 42-year-old woman who, following mitral replacement (March 16, 1971), developed a severe depression in cardiac output to such an extent that survival seemed unlikely. The extremities became cold, cyanotic, and pulseless, and the patient subsequently developed abnormal bleeding. Because of the persistent bleeding, coagulation studies were obtained, and these demonstrated the presence of DIC. The details are given later in this paper (Case 1). Although the patient eventually recovered, gangrene of all four extremities necessitated quadruple amputations. In all From the Departments of Surgery and Medicine, New York University School of Medicine, New York, N . Y. 10016. Read at the Fifty-second Annual Meeting of The American Association for Thoracic Surgery, Los Angeles, Calif., May 1, 2, and 3, 1972. Address for reprints: New York University School of Medicine, 550 First Avenue, New York, N . Y. 10016.
likelihood, earlier recognition and treatment of the DIC syndrome would have prevented the extensive amputations, for there were no signs of peripheral vascular disease before the operation. Alerted to DIC as a possible complicating factor in the recovery of severely ill patients after cardiac procedures, we have in the past year (March, 1971, to March, 1972) identified nine additional instances of DIC among 572 patients undergoing open-heart operations at New York University Medical Center. Experiences with these 10 patients form the basis of this report. Methods Ten patients (Table I ) , 8 women and 2 men, ranging in age from 36 to 69 years, developed abnormal bleeding following valve replacement. Coagulation studies established the diagnosis of the DIC syndrome. Among the 10 patients, 6 had mitral and tricuspid valve replacements, 3 had isolated mitral replacement, and 1 had an aortic valve replacement. For comparison, coagulation profiles were routinely obtained before operation and on the first and fifth postoperative days in 27 patients who recovered uneventfully following cardiac surgery. The findings in this group provided a base line against which changes in the DIC syndrome could be 685
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Table I. Summary of data from 10 patients developing DIC following extracorporeal circulation
Patient (initials, age, sex)
Date of operation
Valve replacement (Starr-Edwards Series 6320)
Onset of DIC (days)
1 (V. E. 42, F.)
March 16, 1971
Mitral
2 (B. S., 66, F.)
July 16, 1971
Mitral, tricuspid
10
3 (N. J., 37, F.)
Sept. 14, 1971
Mitral, tricuspid
4 (F. P., 46, F.)
July 20, 1971
5 (R. C., 56, F.)
Clinical
manifestations
Underlying
conditions
Bleeding, peripheral cyanosis
Low output
Bleeding, peripheral cyanosis, mental symptoms
Low output, gram-negative sepsis
4
Bleeding
Low output, gram-negative sepsis
Mitral, tricuspid
7
Bleeding, peripheral cyanosis
Low output, gram-negative sepsis, liver impairment
Jan. 16, 1972
Mitral, tricuspid
4
Bleeding, peripheral cyanosis, mental symptoms
Low output
6 (R. A. 36, M.)
Aug. 6, 1971
Aortic (fascia lata)
5
Bleeding, peripheral cyanosis
Low output, liver impairment
7 (A. G , 67, F.)
May 10, 1971
Mitral
2
Bleeding, peripheral cyanosis
Low output
8 (R. C., 69, F.)
May 25, 1971
Mitral, tricuspid
3
Bleeding
Low output, gram-negative sepsis
9 (F. A. 41, M.)
Sept. 10, 1971
Mitral, tricuspid
4
Bleeding, peripheral cyanosis, mental symptoms
Low output, gram-negative sepsis, liver impairment
Dec. 3, 1971
Mitral
5
Bleeding, mental symptoms
Low output
10 (G. C , 64, F.)
6
Legend: DIC, Disseminated intravascular coagulation. TRCHII, Tanned red cell hemagglutination inhibition immunoassay test.
evaluated. These findings are listed in Table II. In the 27 patients comprising the control group, complete coagulation profiles were obtained. These included platelet count, prothrombin time, fibrinogen, and fibrin split products (tanned red cell hemagglutination inhibition immunoassay in micrograms per milliliter). These coagulation studies were performed by standard techniques, with only minor modifications.5 Fibrinogen level was determined as thrombin-clottable protein either by the turbidimetric method of Ellis and Stransky6 or by harvesting the fibrin from a dilute plasma clot7 and quantitating the protein by the biuret method. Fibrin split products in the serum were mea-
sured by the tanned red cell hemagglutination inhibition immunoassay (TRCHII) of Merskey and colleagues.8 The diagnosis of DIC was made from a combination of coagulation abnormalities, including elevation of fibrin split products, depression of fibrinogen levels and platelet count, and elevation of prothrombin time. Therapy included the treatment of the underlying condition, usually low cardiac output often associated with sepsis and renal failure, as well as the administration of sufficient heparin to maintain a partial thromboplastin time of not more than 1.5 times normal. The amount of heparin, administered intravenously, ranged from 350 to 1,000 units per hour.
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Hematologic
parameters
at time of
diagnosis
Fibrinogen (mg. %)
Fibrin split products (TRCHU, Hg/ml.)
Prothrombin time (seconds)
Thrombin time (seconds)
39
40
89.6
18.5
22.0
Cardiovascular support; therapy for severe vasoconstriction; heparin; amputation
Survived
90
279
11.2
14.8
23.0
Cardiovascular support; heparin; dialysis
Died (July 28, 1971)
63
151
11.2
17.2
15.6
Cardiovascular support; heparin
Recovered
80
324
22.4
33.0
14.6
Cardiovascular support; dialysis; heparin therapy for gram-negative sepsis
Died (Aug. 12, 1971)
32
127
11.2
22.4
29.0
Cardiovascular support; heparin; dialysis
Recovered
62.5
386
22.4
30.0
16.0
Cardiovascular support; heparin; dialysis
Died (Aug. 21,1971)
120
268
14.4
14.2
11.0
Cardiovascular support; heparin
Recovered
20
181
22.4
15.4
23.7
Cardiovascular support; antibiotics for gram-negative sepsis; heparin; dialysis
Recovered
87
238
11.2
19.7
17.5
Cardiovascular support; antibiotics; heparin Died (Oct. 5, 1971)
25
188
22.4
17.0
21.0
Cardiovascular support; heparin; dialysis
Platelet counts (thousands Ic.mm.)
Results The findings in the control group are given in Table II. Fibrin split products rose from a preoperative level of 1.56 p,g per milliliter to an average of 2.48 (xg per milliliter on the first day after operation and subsequently to 3.45 ^g per milliliter on the fifth postoperative day, an increase of approximately 100 per cent over the preoperative level. Platelet counts decreased from an average range of 300,000 per cubic millimeter before operation to about 100,000 on the first day after operation, but they had risen again to almost 200,000 per cubic millimeter by the fifth postoperative day. The prothrombin time averaged near 13.8 seconds before operation and was elevated
Treatment
Result
Died (Dec. 14, 1971)
to the modest extent of 14.3 seconds by the fifth postoperative day. Fibrinogen levels on the first postoperative day were not significantly different from the average range of 330 mg. per cent the day before operation but had risen significantly to over 500 mg. per cent by the fifth postoperative day. In the patients with DIC, the most striking finding was elevation in fibrin split products to levels far above the maximum level of 5.6 p.g per milliliter found in the control group. These abnormal findings are shown in Table I but range from a low of 11.2 to as high as 89.6 fxg per milliliter, with a mean value of 23.8 jug per milliliter. Corresponding with this striking elevation in fibrin split products was a depression in
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Table II. Hematologic parameters—27
control patients and 10 patients with DIC Control series
Parameter
Preoperative
Fibrin split products (TRCHII, jug/ml.) Platelet count (thousands/c.mm.)
1.56
Postoperative day 1 2.48*
303.0
107.0*
13.8
14.1*
Prothrombin time (seconds) Fibrinogen (mg. %)
333.0
359.0
Postoperative day 5 3.45* 184.0* 14.28* 532.0*
DIC series 23.81 61.9t 20.2t 221.8t
Legend: The figures in the control series are mean values from 27 patients who underwent open-heart surgery without complication. The figures in the DIC series are mean values measured at diagnosis in 10 patients. DIC, Disseminated intravascular coagulation. TRCHII, Tanned red cell hemagglutination inhibition immunoassay. ♦Statistically significant difference from pre-operative values (p<0.02). tStatistically significant difference from control postoperative day 5 values (p<0.01).
fibrinogen in most patients from the mean control value of 532 mg. per cent (fifth postoperative day). Levels as low as 40 mg. per cent were found in 1 patient, while in others they ranged between 150 and 380 mg. per cent (Table I ) . Similarly, there was a marked depression in platelet count from the mean of 180,000 on the fifth postoperative day to levels as low as 20,000 to 40,000 per cubic millimeter. The prothrombin time rose from the mean value of 14.28 seconds on the fifth postoperative day to levels between 15 and 20, even reaching above 30 seconds in 1 patient (Patient 4, Table I). Clinical picture The finding which raised the question of the diagnosis in all 10 patients was abnormal bleeding. This often was moderate in nature but persistent. It came from the incision in 5 patients, the tracheobronchial tree in 6, the chest tube tracts in 3, the gastrointestinal tract in 2, and the genitourinary tract in 2. Five patients developed extensive ecchymoses. Preceding the abnormal bleeding was a profound depression of cardiac output in all patients with mixed venous saturations of blood from the pulmonary artery in the range of 35 to 55 per cent. With the marked depression in cardiac output there was an elevated left atrial pressure and hypotension requiring infusion of catecholamines such as epinephrine, isoproterenol, and occasionally norepinephrine. Oliguria progressed to
renal failure in 6 patients and necessitated peritoneal dialysis. Varying degrees of hepatic insufficiency, secondary to the low cardiac output, were also evident in 3 patients. Sepsis eventually complicated the clinical picture in 5 patients and was a leading cause of death. (Four of 5 with sepsis died.) A striking feature of DIC was an abnormal degree of peripheral vasoconstriction with cold, pulseless extremities and peripheral cyanosis (7 patients). Cerebral symptoms also appeared, with periods of confusion ranging to coma in 4 patients. The latter symptoms strikingly improved within 12 to 24 hours after administration of heparin. Both the degree of peripheral vasoconstriction and the cerebral symptoms were far out of proportion to the usual intensity of symptoms seen in patients with a low cardiac output. The severe nature of the illness is illustrated by the fact that 5 of the 10 patients ultimately died, a mortality rate of 50 per cent. Two illustrative case reports, showing the clinical picture and the disastrous sequelae of this syndrome CASE 1. V. E. (Table, I, Patient 1), a 42year-old woman, was admitted for chronic congestive failure. Cardiac catheterization disclosed severe mitral insufficiency and mitral stenosis with a cardiac index of 2.0 L. per minute per square meter. In March, 1971, the mitral valve was replaced with a No. 3 Starr-Edwards ball-valve prosthesis (Model 6320). There was no undue
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difficulty with operation, but an unexplained severe depression of cardiac output developed in the first few hours after operation, with hypotension, mixed venous oxygen saturation of 40 per cent, and severe oliguria. The gravity of the problem is indicated by the fact that on the first postoperative day there were three episodes of ventricular fibrillation, which responded to electrical defibrillation. A tracheostomy was done to provide ventilatory support, but survival was in serious doubt. With this clinical picture, the patient developed severe cyanosis, coldness, and absence of pulses in all four extremities. All pulses were normal before operation, with no signs of underlying vascular disease. On the second postoperative day she developed melena, and blood began to ooze from the tracheostomy stoma. Cyanosis and coldness of the extremities persisted. Recognizing the extreme degree of ischemia in the extremities, a wide variety of agents was employed to improve peripheral circulation. These included low-molecular-weight dextran, chlorpromazine, sympathetic blocks, and dibenzylene. It is noteworthy that all of these were ineffective. Unfortunately, heparin was not utilized at this time, because we feared the exacerbation of gastrointestinal bleeding. The melena was erroneously interpreted as being from a previously diagnosed duodenal ulcer. On the fourth postoperative day, the cardiac output improved to a normal range, but the intense ischemia in the extremities persisted. Finally, on the sixth day after operation, because of continued oozing of blood from the tracheostomy stoma, a coagulation profile was obtained. At this time the platelet count was 39,000 per cubic millimeter, the fibrinogen level 40 mg. per cent, prothrombin time 18.5 seconds, and fibrin split products (TRCHII) 89.6 Mg per milliliter. These findings dramatically established the presence of a severe DIC syndrome. No signs of excessive fibrinolysis were present. Heparin therapy, initiated at a dosage of 500 units per hour, elevated the partial thromboplastin time to approximately 1.5 times normal. Following the institution of this therapy, bleeding rapidly stopped and peripheral circulation dramatically improved. Over the next 2 weeks the distal portions of both hands and feet became gangrenous. In spite of continued heparin therapy, laboratory findings of DIC continued for the next 10 days. Between the second and third months after operation, bilateral amputations were performed below the knee and at the mid-forearm. The Department of Rehabilitation Medicine managed her rehabilitation with prostheses for all four extremities. Despite her grave disability, she has functioned well with no further signs of cardiac failure.
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Comment. This catastrophic experience in a 42-year-old patient with no known peripheral vascular disease well emphasizes the hazards of the DIC syndrome and the inability to reverse the effects once they are firmly established. One can only speculate that an earlier diagnosis and administration of heparin, despite the presence of gastrointestinal bleeding, might have avoided the loss of all four extremities. CASE 2. R. A. (Table I, Patient 6), a 36year-old man, was hospitalized for severe aortic stenosis and insufficiency with dyspnea and chest pain. The diagnosis was confirmed by cardiac catheterization. In August, 1971, the aortic valve was replaced with a fascia lata valve. There were no unusual complications during operation, but subsequently he had a profound depression of cardiac output, with oliguria, and required vasopressors. On the first postoperative day a large hematoma was drained from the thigh incision. A tracheostomy was performed on the fourth day. Abnormal bleeding was evidenced with the passage of several tarry stools and continued oozing from the tracheostomy stoma. The extremities became cold and cyanotic. Coagulation studies at that time showed gross abnormalities in comparison to preoperative findings: The platelet count had decreased from 307,000 to 62,500 per cubic millimeter the fibrinogen level from 407 to 386 mg. per cent; the prothrombin time was elevated from 12 seconds to 30 seconds; and the fibrin split products increased to 22.4 ng per milliliter as compared to a preoperative value of 1.4 fig per milliliter. With a firm diagnosis of DIC, heparin therapy was instituted. Unfortunately the clinical response was not dramatic, and a progressive downhill course ensued, with complicating respiratory infection and renal failure. The patient died on the fifteenth postoperative day. Comment. This case illustrates several aspects of DIC. Again, the etiology is unclear but developed as a complication of a low cardiac output. It similarly illustrates that the low cardiac output, respiratory sepsis, and renal failure resulted in the death of the patient in spite of the reversal of the DIC with heparin. Discussion Etiology. DIC is not a distinct pathologic entity but rather a pathophysiologic condition seen in association with a variety of
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disease states.9 With DIC, thromboplastic materials, such as products of tissue breakdown, particulate matter, endotoxins, and other substances entering the circulatory system, may stimulate the deposition of fibrin and platelets in the microcirculation. If sufficient amounts of clotting factors and platelets are consumed in this process, there is widespread microvascular occlusion and abnormal bleeding. The corresponding changes in the coagulation factors permit the laboratory diagnosis of DIC. A low cardiac output with inadequate tissue perfusion, which Hardaway 10 has emphasized as an important etiologic factor in DIC, was a common denominator in all 10 of the patients described in this report. All patients required infusion of catecholamines to maintain systemic pressure There was corresponding oliguria, progressing to renal failure, which necessitated peritoneal dialysis in 6 of the 10 patients. Six patients developed striking cyanosis, coldness, and absence of pulses in the extremities. This intense vasoconstriction was undoubtedly due to the combination of excessive levels of catecholamines, both endogenous and exogenous, complicated by the presence of microthrombi in the peripheral circulation. Gram-negative sepsis and hepatic failure contributed to the development of DIC, but the basic etiology was low cardiac output. Diagnostic considerations. Numerous studies of changes in coagulation factors before and after open-heart surgery have been done. 3 '" Platelet levels decrease during and after cardiopulmonary bypass, reaching levels well below 100,000 per cubic millimeter, but gradually increase toward normal over the next few days. There is a slight elevation in prothrombin time (Table II) and a similar slight decrease in fibrinogen level, although the latter rises above preoperative levels by the fifth postoperative day (Table I I ) . To our knowledge, fibrin split products have not been measured in patients immediately following extracorporeal circulation. Therefore, the findings in Table II, which show an elevation to a mean of 3.45 /xg per milliliter on postopera-
tive day 5, may represent a normal expected change as compared to the preoperative level of 1.5 /xg per milliliter. In all likelihood, the modest elevation in fibrin split products following open-heart surgery is due to a minimal amount of clotting in the operative area, microcirculation, or pump during bypass. Adequate heparinization undoubtedly is the greatest protection against more extensive changes. It is significant that in none of the patients was there any evidence of excessive fibrinolysis. The diagnosis of DIC has been greatly facilitated by the introduction of methods for measuring the level of split fibrin products in blood. The TRCHII test has been the most useful agent. From our present data, levels above 11.2 /xg per milliliter following extracorporeal circulation are thought to be indicative of the presence of DIC. Corresponding with this abnormal elevation, there should be a qualitative or quantitative change in fibrinogen. Other abnormal findings include a prolonged prothrombin time and decreased platelet concentration. Two supplemental tests which have been reported to detect abnormalities of fibrinogen are the 3P test,11 which detects circulating fibrin monomer, and the staphylococcal clumping test,12 again a simple hematologic test which can detect the presence of circulating fibrin split products. Unfortunately, these are not routinely available in most clinical laboratories. With the increasing availability of these specific studies, the diagnosis of DIC can now be readily established with considerable certainty. Therapeutic considerations. The basic treatment for DIC is reversal of the underlying disease process. Low cardiac output was present in all 10 patients, and supportive therapy was essential. When sepsis, renal failure, and respiratory failure complicated the problem, appropriate therapy was carried out. Heparin, administered in sufficient amount to elevate the partial thromboplastin time to about 1.5 times normal, was the effective therapy for the intravascular coagulation. The patients were started on 500 units
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of intravenous heparin per hour with the dosage regulated by serial partial thromboplastin time. A dramatic observation with the administration of heparin was the cessation of abnormal bleeding within a few hours, the remission of peripheral cyanosis, and improved peripheral circulation. Similarly, cerebral symptoms such as coma and confusion dramatically cleared at the same time. The rapidity of disappearance of fibrin split products from the blood depended both upon the efficacy of heparin therapy and the ability to correct the underlying condition. In the patients in this report, fibrin split products returned to normal levels within periods varying from 2 to 10 days. To a similar degree, the platelet count and the fibrinogen concentration gradually returned to normal levels. Summary In this report the detection of diffuse intravascular coagulation is described in 10 patients who underwent valve replacement during a period of 1 year at New York University Medical Center, during which time 572 open-heart procedures were performed. A common denominator was a severe depression in cardiac output. Subsequently, abnormal bleeding developed. Renal failure, hepatic failure, and sepsis were also complicating factors. Five of the 10 patients ultimately died. The laboratory diagnosis of DIC was established by an elevated level of fibrin split products (above 11.2 [xg per milliliter), a prolonged prothrombin time, a decreased level of fibrinogen, and a decreased platelet count. Treatment consisted of the intravenous administration of heparin and appropriate therapy of any underlying etiologic factors. The crucial point with DIC is the availability of tests for fibrin split products (TRCHII) which makes the diagnosis possible at a much earlier time than was previously possible. Prompt early diagnosis is especially important because early administration of heparin may reverse intravascular coagulation before it causes irreversible
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changes, such as gangrene, and should improve the patient's chances for survival. We wish to thank Mrs. Joyce Javid for her valuable technical assistance. REFERENCES 1 Damus, P. S., and Salzman, E. W.: Disseminated Intravascular Coagulation, Arch. Surg. 104: 262, 1972. 2 Kwaan, H. C : Disseminated Intravascular Coagulation, Med. Clin. North Am. 56: 177, 1972. 3 Signori, E. E., Denner, J. A., and Kahn, D.: Coagulation Defects and Bleeding in Open Heart Surgery, Ann. Thorac. Surg. 8: 521, 1969. 4 Thurnherr, N.: Blood Coagulation Studies and Extracorporeal Circulation in Man, Thromb. Diath. Haemorrh. 18: 634, 1967. 5 Lackner, H., Hunt, V., Zucker, M. B., and Pearson, J.: Abnormal Fibrin Ultra-structure, Polymerization and Clot Retraction in Multiple Myeloma, Br. J. Haematol. 18: 625, 1970. 6 Ellis, B. C , and Stransky, A.: A Quick Accurate Method for the Determination of Fibrinogen in Plasma, J. Lab. Clin. Med. 58: 477, 1961. 7 Fearnley, G. R.: An Accurate Method of Fibrin Recovery for the Determination of Plasma-Fibrinogen (Letter), Lancet 2: 501, 1951. 8 Merskey, C , Lalezari, P., and Johnson, A. J.: A Rapid, Simple, Sensitive Method for Measuring Fibrinolytic Split Products in Human Serum, Proc. Soc. Exp. Biol. Med. 131: 871, 1969. 9 Colman, R. W., and Rodriguez-Erdmann, F.: Terminology of Intravascular Coagulation, N. Engl. J. Med. 282: 99, 1970. 10 Hardaway, R. M.: Disseminated Intravascular Coagulation in Shock, Thromb. Diath. Haemorrh. Suppl. 36: 159, 1969. 11 Niewiarowski, S., and Gurewich, V.: Laboratory Identification of Intravascular Coagulation: The Serial Dilution Protamine Sulfate Test for the Detection of Fibrin Monomer and Fibrin Degradation Products, J. Lab. Clin. Med. 77: 655, 1971. 12 Hawiger, J., Niewiarowski, S., Gurewich, V., and Thomas, D. R.: Measurement of Fibrinogen and Fibrin Degradation Products in Serum by Staphylococcal Clumping Test, J. Lab. Clin. Med. 75: 93, 1970.
Discussion DR. H E N R I E T T E L A C K N E R New
York, N.
Y.
I would like to comment on the diagnosis of diffuse intravascular coagulation in patients after cardiac surgery and extracorporeal circulation. The first prerequisite is clinical suspicion of this
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complication. In our patients, decreased cardiac output, hypotension, peripheral cyanosis, cold extremities, and oozing have suggested the possible presence of diffuse intravascular coagulation, leading to a request for a coagulation study. Second, the diagnosis depends on adequate laboratory facilities. Besides the usual tests, such as platelet count, prothrombin time, thrombin time, partial thromboplastin time, fibrinogen level, and some coagulation factor assays, the determination of fibrin split products in the serum has proved to be one of the most helpful diagnostic tests for this condition. Third, the diagnosis clearly depends on interpretation of the hemostatic abnormalities. As Dr. Boyd has stressed, certain changes normally occur following extracorporeal circulation, among them, a drop in platelet count, a slight rise in prothrombin time, and a much more gradual rise in fibrinogen level. Although in this series there were marked differences in the mean value of these parameters between the control and patient groups, the changes were often slight in individual patients. We have found a rise exceeding 11.2 /ig per milliliter in fibrin split products in the serum to be the most helpful diagnostic test. Continuous, low-dose heparin infusion appears to be a safe and effective form of therapy in these patients who are at risk from renewed hemorrhage at the operative site. If hemorrhage occurs, despite precautions, the heparin infusion can be immediately stopped. The residual amount in the body is excreted or metabolized in 1 to 2 hours, obviating heparin neutralization. Patients with diffuse intravascular coagulation frequently have circulating fibrin monomer which can be precipitated from plasma in vitro by protamine sulfate. Since a similar precipitation of fibrin monomer could possibly occur in vivo, we feel that protamine sulfate should be avoided in these patients. The usual starting dose of 500 units of heparin per hour can be raised or lowered depending on results of further coagulation studies. The partial thromboplastin time has provided one of the parameters for monitoring heparin dosage; our aim is a partial thromboplastin time of 1.5 times the normal value. These patients have responded well to low-dose, continuous heparin therapy. The usual intermittent high-dose heparin treatment—indicated in thrombophlebitis or pulmonary embolism—would be unsuitable and even dangerous for this group. D R . N O E L L. M I L L S New Orleans,
La.
I would like to congratulate Dr. Boyd on an excellent paper. Recently at the Ochsner Clinic a patient developed disseminated intravascular coagulation
after a triple aorto-coronary bypass. The patient did not have peripheral vascular disease, and the diagnosis was confirmed by the hematology laboratory. Heparin was given within 8 hours of the onset of symptoms. The clinical course in our patient was the same as that described by Dr. Boyd. [Slide] The patient went on to have severe tissue loss of the toes. [Slide] However, the patient lost only a minimal amount of tissue in the hands. DR. SAFUH ATTAR Baltimore,
Md.
I would like to congratulate Dr. Boyd on an excellent study. However, I would like to wonder with him, as well as my colleagues, why we have not recognized this entity, having been doing open-heart surgery since 1955 all over the world? I suspect that the entity has existed but not under the term of disseminated intravascular coagulation. I feel that this term is a misnomer. It is unfortunate that it has crept into the literature, initially into the literature of the pathologic entities that cause shock, trauma, and low-output syndrome following open-heart surgery. We investigated a large number of patients who had severe shock and trauma. We ran a whole battery of coagulation and fibrinolytic studies, and they all indicate that there are changes that could be attributed to disseminated intravascular coagulation. However, when you examine the tissues of these patients, by electronmicroscopy and immunofluorescence, you find that there is no evidence of disseminated thrombi. Where do they disappear? We feel that there is not an entity called disseminated intravascular coagulation in the frequency that has been propagated in the literature. These changes that we see can be attributed to changes that occur inherently with sepsis, shock, and trauma. The author did not indicate whether these patients did develop shock, and the changes we are seeing are probably secondary to the shock state and do not represent a real pathologic entity of disseminated intravascular coagulation. Over the last 1,000 open-heart operations we have done at the University of Maryland, I can recall only 1 patient with massive pulmonary embolism that developed into real disseminated intravascular coagulation with gangrene of all the four extremities, proved by autopsy. Therefore, this entity is very rare, and I believe the dissemination of this concept will probably lead to more complications associated with the use of heparin. If this entity is really disseminated intravascular coagulation, why should we use small amounts of heparin? If it is clotting, we should give the patient complete anticoagulation therapy. I do not think we should just do it
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halfway if we want to get an effective result. In addition, heparin by itself is not the best way to combat intravascular thrombosis. We must realize that thrombosis is made of two factors: platelet aggregation and fibrin formation. If we are going to combat thrombosis, we should combat platelet aggregation that initiates the whole process, as well as fibrin formation. DR. A R T H U R D. BOYD (Closing) I am not sure that I can answer all of Dr. Attar's questions. We had not recognized disseminated intravascular coagulation before a year ago. We became acutely aware of this possibility in the case which I briefly described, and, after examining our patients more carefully, we recognized the 9 additional cases. Only time will tell whether this was indeed a true reflection of the incidence of
Disseminated intravascular coagulation 6 9 3
this complication or whether this was some abnormal distribution of sampling in the last year. However, it is our impression that if DIC is recognized and as a possible complication, it will be seen more frequently. As far as amounts of heparin are concerned, in the doses which we used, which ranged from about 350 to 1,000 units per hour, there was a dramatic cessation of the bleeding, the peripheral cyanosis improved, and the patient's mental symptoms cleared markedly. It was our clinical impression that they were greatly improved by this dosage of heparin. Also, over 48 to 72 hours, fibrinogen levels, platelet levels, and other coagulation parameters returned to normal. Therefore, we believed that there was both clinical and laboratory evidence that this amount of heparin was reversing the situation toward normal.