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Effect of transurethral resection on coagulation in carcinoma of prostate
EFFECT OF TRANSURETHRAL COAGULATION V. BETKURER, P. GUINAN, A. VERMA, E. MORILLO,
RESECTION ON
IN CARCINOMA
M.D.
OF PROSTATE
R. J. ABLIN,
M.D.
PH.D.
A. SPARKUHL,
M.D.
A. COCHIN,
M.D. PH.D.
M.D.
From the Division of Urology, Cook County Hospital, the Department of Urology of Rush-PresbyterianSt. Luke’s Medical Center, and the Hektoen Institute for Medical Research, Chicago, Illinois
ABSTRACT - Eleuen patients with cancer of the prostate and 10 patients with benign prostatic hypertrophy (BPH) had thirteen parameters of coagulation evaluated before and after transurethral resection (TUR). Changes in fibrinogen and fibrin split products in both groups suggested potential incipient disseminated intravascular coagulation (DZC). It is concUed that prostatic cancer patients are no more susceptible to DZC than patients with BPH.
Unexpected and uncontrollable bleeding remains the principal fear of the surgeon performing transurethral resection. Since the original report in 1930 by Jurgens and Trautwein’ suggesting an increased incidence of excessive bleeding in prostate malignancy, urologists have assumed that a bleeding diathesis was associated with this disease. In an effort to verify the assumption that patients undergoing transurethral resection (TUR) for carcinoma of the prostate (CAP) had a more defective clotting mechanism than patients undergoing TUR for benign prostate hypertrophy (BPH), thirteen coagulation parameters were evaluated in 21 patients. Material
and Methods
Eleven consecutive patients with a histologic diagnosis of adenocarcinoma of the prostate were evaluated. Diagnosis had been made previously by transrectal needle biopsy. Ten patients with BPH, who served as controls, were also studied.
142
Blood was collected by venepuncture in Falcon plastic tubes containing 1 cc. of 3.8 per cent sodium citrate as an anticoagulant. The tube was inverted once after collection and centrifuged at 800 rpm with a rotor producing 150 g of force for fifteen minutes to harvest platelet rich plasma. Subsequent platelet poor plasma was obtained at 2,999 rpm for one-half hour. Blood for fibrin split products (FSP) was collected in a separate tube. Coagulation studies included hematocrit, prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, FSP, factors II, V, VII, VIII, IX, X, XI, and XII. The preoperative blood was collected in the twenty-four hours preceding the TUR and the postoperative blood within twenty-four hours after the TUR. The TUR was performed with a Stern-McCarthy resectoscope, and 1.5 per cent glycine was employed as an irrigant. No TUR exceeded 75 minutes, and no blood replacement was given. Approximately 1 L. of lactated Ringers solution was infused intravenously during each procedure.
UROLOGY
/ FEBRUARY
1979 / VOLUME
XIII.
NUMBER
2
TABLE I.
Coaeulation
Preoperative Mean S.D.
Normal Values
Study
BENIGNPROSTATICHYPERTROPHY 39-45% Hematocrit 11.8-12.1 sec. Prothrombin time 32.0-34.2 sec. Partial thromboplastin time Fibrinogen 200-350 mg./dl. Cl1 pg./ml. Fibrin split products 56-156% Factor II Factor V 50- 150% 50- 150% Factor VII 50-150% Factor VIII Factor IX 50- 150% 50 - 150% Factor X 50- 150% Factor XI Factor XII 50-150% CARCINOMA OF PROSTATE Hematocrit Prothrombin time Partial thromboplastin time Fibrinogen Fibrin split products Factor II Factor V Factor VII Factor VIII Factor IX Factor X Factor XI Factor XII
39-45% 11.8-12.1 sec. 32.0-34.2 sec. 200-350 mg./dl.
studies
37.5% 12.1 sec. 34.3 sec. 480 mg./dl. 12 pg./ml.
95.0% 82.2% 105.6% 169.4% 127.8% 107.8% 102.8% 123.3%
32.8% 12.6 sec. 35.3 sec. 395 mg./dl. 18 pg./ml.
Results Although the hematocrit dropped following TUR in the BPH group, this drop was not significant (Table I). Nor were any of the other postoperative parameters significantly different from the pre-TUR studies in this group. There were no statistically significant differences between the pre- and postoperative coagulation studies in the prostatic cancer group. No patient in either group bled excessively. However, there was a decrease in fibrinogen and an elevation in FSP in both groups after TUR. The fibrinogen dropped from 480 mg./dl. to 438 mg./dl. and from 395 mg./dl. to 283 mg./dl., and the FSP increased from 12 pg./ml. to 38 pg./ml. and from 18 pg./ml. to 25 pg./ml., in the BPH and CAP group, respectively. Comment Since Jurgens and Trautwein’s’ original article, several other investigators have reported
UROLOGY / FEBRUARY1979 / VOLUMEXIII, NUMBER2
79.1% 79.1% 88.9% 111.8% 119.1% 89.8% 109.6% 124.6%
Postoperative S. D. Mean
1.4 9.1 154 2 15.8 31.1 11.3 81.1 56.9 35.9 52.8 63.3
34.5% 12.0 sec. 32.2 sec. 438 mg./dl. 38 pg./ml. 87.6% 82.2% 97.0% 128.0% 119.0% 96.0% 113.0% 144.0%
10.9 1.2 6.3 197 4 17.0 29.8 15.7 70.8 53.2 11.7 54.2 61.1
4.9 1.3 10.2 99 15 22.6 22.1 20.3 56.2 59.7 34.6 62.2 80.1
32.2% 12.8 sec. 35.4 sec. 283 mg./dl. 25 pg./ml. 72.0% 77.6% 82.6% 101.0% 107.5% 84.0% 99.5% 122.0%
5.9 0.9 10.9 203 21 23.9 20.0 20.4 67.9 71.7 25.0 67.8 76.9
4.9
Significance NS NS
NS NS NS NS NS NS NS NS NS
NS NS
NS NS NS NS NS NS NS NS NS
NS NS NS NS
bleeding post TUR,2’3 as well as after open surgical procedures, 4 and even after prostatic biopsy5 in patients with CAP. Significant postoperative bleeding also occurred in patients with BPH following TUR6 and open procedures. ‘,* In 1969 Mertens et al., 3 employing the ethanol gelation test and serum fibrinolytic split products assay in 20 patients with CAP and 22 patients with BPH, concluded that patients with CAP had a more abnormal coagulation mechanism. In the 1930s and 1940s the hypofibrinogenemia was attributed to a diminished production by the bone marrow.’ In 1953, Tegnon et ~1.~ ascribed abnormal bleeding in a patient with prostatic cancer to the release of fibrinolysin. A decade later the concept of primary fibrinolysis was being disputed. Rapaport and ChapmanlO noted coexistent hypercoagulability and acute hypofibrinogenemia and suggested that this might not be on the basis of systemic fibrinolysis. More recently, the concensus appears to be that disseminated intravascular
143
coagulation (DIC) is the principal cause of excessive bleeding in CAP patients following TUR. 11-13 Most of these previous studies were biased in favor of finding coagulopathies in CAP patients, inasmuch as they were retrospective analyses of patients who had hemorrhaged. The present investigation was prospective and failed to detect either clinically excessive bleeding or a statistically significant coagulation defect in this small group of patients undergoing TUR. While no statistically significant changes in coagulation parameters either before or after TUR were manifested in these patients, a note of caution should be made. Changes in fibrinogen and FSP were noted after TUR that, while not statistically significant, could well be biologically significant. The trend in these two parameters suggests a potential incipient DIC. While there were no overt hemorrhages in these patients, any complications in the technical aspects of, or unexpected prolongation in the length of, the TUR could have resulted in serious bleeding. The suggestion of a potential DIC was not limited to the CAP group but was also seen in the BPH group. In this small group of patients those with cancer would not appear to be more susceptible to a bleeding diathesis than patients with BPH.
144
Cook County Hospital Chicago, Illinois 60612 (DR. GUINAN) References 1. Jurgens R, and Trautwein H: Ueber Fibrinopenie (Fibrinogenopenie) beim Erwachsenen, nebst bermerkungen uber die Herkunft des Fibrinoenes. Dtsch. Arch. Klin. Med. 169: 28 (1936). 2. Phillips LL, W&s R, and Wolf C: Coagulation and fidrinolytic studies following use of proteinase inhibitors in prostatic surgery, Ann. N.Y. Acad. Sci. 146: 737 (1968). 3. Mertens BF, et al: Rapid sensitive method for measuring fibrinogen split-products in human serum, Mayo Clin. Proc. 44: 114 (1969). 4. Pergament ML, Swaim WR, and Blackard CE: Disseminated intravascular coagulation in the urologic patient, J. Urol. 116: 1 (1976). 5. Ross GJ, Thompson IM, and Samaha RJ: Subacute intravascular coagulation with prostatic carcinoma, MO. Med. 71: 177 (1974). 6. Friedman NJ, et al: Hemorrhagic syndrome following transurethral prostatic resection of benign adenoma, Arch. Intern. Med. 1.24: 341 (1972). 7. Kaufman JM: Prostatectomy in factor XI deficiency, J. Urol. 117: 75 (1977). 8. Jasper WS: Anticoagulants in open prostatectomies, ibid. 117: 72 (1977). 9. Tagnon HJ, Whitmore WF, Jr, Shulman P, and Kravitz SC: The significance of fibrinolysis occurring in patients with metastatic cancer of the prostate, Cancer 6: 63 (1953). 10. Rapaport SI, and Chapman CG: Coexistent hypercoagulability and acute hypofibrinogenemia in a patient with prostatic carcinoma, Am. J. Med. 27: 144 (1959). 11. Kursh ED, Ratnoff OD, and Persky L: Current clotting concepts in urology, J. Urol. 116: 214 (1976). 12. Rader ES: Hematologic problems in urology: basic mechanisms and clinical approach, Urology 5: 589 (1974). 13. Sun CJ: Blood coagulation studies in patients with cancer, Mayo Clin. Proc. 49: 636 (1974).
UROLOGY
/
FEBRUARY
1979
!
VOLUME
XIII,
NUMBER
2
RESECTION ON
IN CARCINOMA
M.D.
OF PROSTATE
R. J. ABLIN,
M.D.
PH.D.
A. SPARKUHL,
M.D.
A. COCHIN,
M.D. PH.D.
M.D.
From the Division of Urology, Cook County Hospital, the Department of Urology of Rush-PresbyterianSt. Luke’s Medical Center, and the Hektoen Institute for Medical Research, Chicago, Illinois
ABSTRACT - Eleuen patients with cancer of the prostate and 10 patients with benign prostatic hypertrophy (BPH) had thirteen parameters of coagulation evaluated before and after transurethral resection (TUR). Changes in fibrinogen and fibrin split products in both groups suggested potential incipient disseminated intravascular coagulation (DZC). It is concUed that prostatic cancer patients are no more susceptible to DZC than patients with BPH.
Unexpected and uncontrollable bleeding remains the principal fear of the surgeon performing transurethral resection. Since the original report in 1930 by Jurgens and Trautwein’ suggesting an increased incidence of excessive bleeding in prostate malignancy, urologists have assumed that a bleeding diathesis was associated with this disease. In an effort to verify the assumption that patients undergoing transurethral resection (TUR) for carcinoma of the prostate (CAP) had a more defective clotting mechanism than patients undergoing TUR for benign prostate hypertrophy (BPH), thirteen coagulation parameters were evaluated in 21 patients. Material
and Methods
Eleven consecutive patients with a histologic diagnosis of adenocarcinoma of the prostate were evaluated. Diagnosis had been made previously by transrectal needle biopsy. Ten patients with BPH, who served as controls, were also studied.
142
Blood was collected by venepuncture in Falcon plastic tubes containing 1 cc. of 3.8 per cent sodium citrate as an anticoagulant. The tube was inverted once after collection and centrifuged at 800 rpm with a rotor producing 150 g of force for fifteen minutes to harvest platelet rich plasma. Subsequent platelet poor plasma was obtained at 2,999 rpm for one-half hour. Blood for fibrin split products (FSP) was collected in a separate tube. Coagulation studies included hematocrit, prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, FSP, factors II, V, VII, VIII, IX, X, XI, and XII. The preoperative blood was collected in the twenty-four hours preceding the TUR and the postoperative blood within twenty-four hours after the TUR. The TUR was performed with a Stern-McCarthy resectoscope, and 1.5 per cent glycine was employed as an irrigant. No TUR exceeded 75 minutes, and no blood replacement was given. Approximately 1 L. of lactated Ringers solution was infused intravenously during each procedure.
UROLOGY
/ FEBRUARY
1979 / VOLUME
XIII.
NUMBER
2
TABLE I.
Coaeulation
Preoperative Mean S.D.
Normal Values
Study
BENIGNPROSTATICHYPERTROPHY 39-45% Hematocrit 11.8-12.1 sec. Prothrombin time 32.0-34.2 sec. Partial thromboplastin time Fibrinogen 200-350 mg./dl. Cl1 pg./ml. Fibrin split products 56-156% Factor II Factor V 50- 150% 50- 150% Factor VII 50-150% Factor VIII Factor IX 50- 150% 50 - 150% Factor X 50- 150% Factor XI Factor XII 50-150% CARCINOMA OF PROSTATE Hematocrit Prothrombin time Partial thromboplastin time Fibrinogen Fibrin split products Factor II Factor V Factor VII Factor VIII Factor IX Factor X Factor XI Factor XII
39-45% 11.8-12.1 sec. 32.0-34.2 sec. 200-350 mg./dl.
studies
37.5% 12.1 sec. 34.3 sec. 480 mg./dl. 12 pg./ml.
95.0% 82.2% 105.6% 169.4% 127.8% 107.8% 102.8% 123.3%
32.8% 12.6 sec. 35.3 sec. 395 mg./dl. 18 pg./ml.
Results Although the hematocrit dropped following TUR in the BPH group, this drop was not significant (Table I). Nor were any of the other postoperative parameters significantly different from the pre-TUR studies in this group. There were no statistically significant differences between the pre- and postoperative coagulation studies in the prostatic cancer group. No patient in either group bled excessively. However, there was a decrease in fibrinogen and an elevation in FSP in both groups after TUR. The fibrinogen dropped from 480 mg./dl. to 438 mg./dl. and from 395 mg./dl. to 283 mg./dl., and the FSP increased from 12 pg./ml. to 38 pg./ml. and from 18 pg./ml. to 25 pg./ml., in the BPH and CAP group, respectively. Comment Since Jurgens and Trautwein’s’ original article, several other investigators have reported
UROLOGY / FEBRUARY1979 / VOLUMEXIII, NUMBER2
79.1% 79.1% 88.9% 111.8% 119.1% 89.8% 109.6% 124.6%
Postoperative S. D. Mean
1.4 9.1 154 2 15.8 31.1 11.3 81.1 56.9 35.9 52.8 63.3
34.5% 12.0 sec. 32.2 sec. 438 mg./dl. 38 pg./ml. 87.6% 82.2% 97.0% 128.0% 119.0% 96.0% 113.0% 144.0%
10.9 1.2 6.3 197 4 17.0 29.8 15.7 70.8 53.2 11.7 54.2 61.1
4.9 1.3 10.2 99 15 22.6 22.1 20.3 56.2 59.7 34.6 62.2 80.1
32.2% 12.8 sec. 35.4 sec. 283 mg./dl. 25 pg./ml. 72.0% 77.6% 82.6% 101.0% 107.5% 84.0% 99.5% 122.0%
5.9 0.9 10.9 203 21 23.9 20.0 20.4 67.9 71.7 25.0 67.8 76.9
4.9
Significance NS NS
NS NS NS NS NS NS NS NS NS
NS NS
NS NS NS NS NS NS NS NS NS
NS NS NS NS
bleeding post TUR,2’3 as well as after open surgical procedures, 4 and even after prostatic biopsy5 in patients with CAP. Significant postoperative bleeding also occurred in patients with BPH following TUR6 and open procedures. ‘,* In 1969 Mertens et al., 3 employing the ethanol gelation test and serum fibrinolytic split products assay in 20 patients with CAP and 22 patients with BPH, concluded that patients with CAP had a more abnormal coagulation mechanism. In the 1930s and 1940s the hypofibrinogenemia was attributed to a diminished production by the bone marrow.’ In 1953, Tegnon et ~1.~ ascribed abnormal bleeding in a patient with prostatic cancer to the release of fibrinolysin. A decade later the concept of primary fibrinolysis was being disputed. Rapaport and ChapmanlO noted coexistent hypercoagulability and acute hypofibrinogenemia and suggested that this might not be on the basis of systemic fibrinolysis. More recently, the concensus appears to be that disseminated intravascular
143
coagulation (DIC) is the principal cause of excessive bleeding in CAP patients following TUR. 11-13 Most of these previous studies were biased in favor of finding coagulopathies in CAP patients, inasmuch as they were retrospective analyses of patients who had hemorrhaged. The present investigation was prospective and failed to detect either clinically excessive bleeding or a statistically significant coagulation defect in this small group of patients undergoing TUR. While no statistically significant changes in coagulation parameters either before or after TUR were manifested in these patients, a note of caution should be made. Changes in fibrinogen and FSP were noted after TUR that, while not statistically significant, could well be biologically significant. The trend in these two parameters suggests a potential incipient DIC. While there were no overt hemorrhages in these patients, any complications in the technical aspects of, or unexpected prolongation in the length of, the TUR could have resulted in serious bleeding. The suggestion of a potential DIC was not limited to the CAP group but was also seen in the BPH group. In this small group of patients those with cancer would not appear to be more susceptible to a bleeding diathesis than patients with BPH.
144
Cook County Hospital Chicago, Illinois 60612 (DR. GUINAN) References 1. Jurgens R, and Trautwein H: Ueber Fibrinopenie (Fibrinogenopenie) beim Erwachsenen, nebst bermerkungen uber die Herkunft des Fibrinoenes. Dtsch. Arch. Klin. Med. 169: 28 (1936). 2. Phillips LL, W&s R, and Wolf C: Coagulation and fidrinolytic studies following use of proteinase inhibitors in prostatic surgery, Ann. N.Y. Acad. Sci. 146: 737 (1968). 3. Mertens BF, et al: Rapid sensitive method for measuring fibrinogen split-products in human serum, Mayo Clin. Proc. 44: 114 (1969). 4. Pergament ML, Swaim WR, and Blackard CE: Disseminated intravascular coagulation in the urologic patient, J. Urol. 116: 1 (1976). 5. Ross GJ, Thompson IM, and Samaha RJ: Subacute intravascular coagulation with prostatic carcinoma, MO. Med. 71: 177 (1974). 6. Friedman NJ, et al: Hemorrhagic syndrome following transurethral prostatic resection of benign adenoma, Arch. Intern. Med. 1.24: 341 (1972). 7. Kaufman JM: Prostatectomy in factor XI deficiency, J. Urol. 117: 75 (1977). 8. Jasper WS: Anticoagulants in open prostatectomies, ibid. 117: 72 (1977). 9. Tagnon HJ, Whitmore WF, Jr, Shulman P, and Kravitz SC: The significance of fibrinolysis occurring in patients with metastatic cancer of the prostate, Cancer 6: 63 (1953). 10. Rapaport SI, and Chapman CG: Coexistent hypercoagulability and acute hypofibrinogenemia in a patient with prostatic carcinoma, Am. J. Med. 27: 144 (1959). 11. Kursh ED, Ratnoff OD, and Persky L: Current clotting concepts in urology, J. Urol. 116: 214 (1976). 12. Rader ES: Hematologic problems in urology: basic mechanisms and clinical approach, Urology 5: 589 (1974). 13. Sun CJ: Blood coagulation studies in patients with cancer, Mayo Clin. Proc. 49: 636 (1974).
UROLOGY
/
FEBRUARY
1979
!
VOLUME
XIII,
NUMBER
2