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Is thrombolytic therapy safe during active menstruation?
The Journal of Emergency Medicine, Vol 13, No 3, pp 345-348, 1995 Copyright 0 1995Elsevier ScienceLtd Printed in the USA. All rights reserved
Pergamon
0136-4619/95
$9.50 + .OO
0736-4679(95)00010-O
Selected Topics:
Cardiology
Commentary
Yao-Fob Sekyema,
MD
and Romulo F. Baltazar,
MD
Department of Medicine, Division of Cardiology, Sinai Hospital of Baltimore, Baltimore, Maryland Reprint Address: Romulo F. Baltazar, MD, Division of Cardiology, Sinai Hospital of Baltimore, Baltimore, MD 21215
0 Abstract-A 3byear-old female presented to the Emergency Department daring the fourth day of menstruation and within 2 hours of the onset of chest pain associated with dyspnea, diaphoresis, and emesis. An electrocardiogram showed acute inferior myocardial infarction and serial CPK enzyme levels peaked at 958 IU/L with 9% MB fraction. Along with aspirin and intravenous nitroglycerin, the patient was given thrombolytic therapy consisting of tPA with an initial bolus of 35 units, followed by 65 units infused within 60 minutes together with heparin 5000 units intravenous boks, and 1000 units/hour maintenance infusion for 5 days. The menses were prolonged 1 day longer than her usual 5 days; however, there was no increase in the amount of bleeding during any day. The hemoglobin dropped from 12.5 G/dl to 11.3 G/d1 in the first 6 hours, but remained stable thereafter. This initial drop in hemoglobin was considered a dilutional effect of 1.5 L of normal saline the patient received intravenously during that period. Although no available guidelines exist regarding the safety of thrombolytic agents during active menstruation, this case report and a few others reported in the literature suggest that normal menstruation is not a contraindication to thrombolytic therapy during acute myocardial infarction.
more uncommon is the occurrence of AM1 during a menstrual period. Although thrombolytic agents are now used routinely in the management of AMI, there are no available guidelines regarding the use of thrombolytic therapy during menstruation. The use of thrombolytic therapy for AM1 during active menstruation is likely to be uncommon and only a few such caseshave been reported (l-3). The following case report describes a young female who developed AM1 during her active menstrual period and received thrombolytic therapy without any unusual bleeding complications. CASE REPORT The patient is a 39-year-old female who was brought to the Emergency Department complaining of severe nonradiating retrosternal pressure of 2 hours duration associated with dyspnea, diaphoresis, and two episodes of emesis. She gave a history of diabetes mellitus and hypertension of several years duration and smoking approximately 1 pack of cigarettes per day for lo-15 years. She had no previous history of chest pain, dyspnea, dizzy or fainting spells, or palpitations. She had no known allergies and her only medication was glyburide 5 mg/day. She had regular menstrual periods, usually of 5 days duration. She was on her fourth day of a normal menstrual period at the time of admission.
0 Keywords-acute myocardial infarction; thrombolytic therapy; menstruation INTRODUCTION
Acute myocardial infarction (AMI) occurring in women below the age of 40 years is uncommon. Even =
Cardiology Commentary is coordinatedby StevenR. Lowenstein, MD, MPH, of the University of Colorado Health
v
SciencesCenter, Denver,Colorado 24 June 1994; FINAL SUBMISSION 4 November 1994
RECEIVED: ACCEPTED:
RECEIVED:
7 October 1994; 345
346
Physical examination showed a young female complaining of chest discomfort. She had a blood pressure of 120/80 mm Hg, a regular heart rate of 98 beats per minute (BPM), and a respiratory rate of 20 breaths/min. The head and neck findings were unremarkable. The neck veins were not distended. The lungs were clear to auscultation. The point of maximal cardiac impulse was not displaced and no gallops or murmurs were audible. The abdomen did not show any palpable visceromegaly. The extremities did not show any pedal edema and pulses were symmetrical. The electrocardiogram showed normal sinus rhythm with a rate of 98 BPM. There was 2 mm of ST segment elevation in leads II, III, and aVF with ST depression in aVL (Figure 1). The chest X-ray study did not show any cardiomegaly and no infiltrates were noted. After a diagnosis of acute inferior MI was made, the patient was given 325 mg of aspirin orally and was started on intravenous (IV) nitroglycerin. Heparin IV, 5000 units, was also given as a bolus followed by an infusion of 1000 units per hour. Front loaded tissue Plasminogen Activator (tPA) was given IV with an initial IV bolus of 35 units over 2 minutes, followed by 65 units infused within 60 minutes. Forty minutes later, the patient developed accelerated idioventricular rhythm associated with a drop in blood
Y.-F. Sekyema and R. F. Baltazar
pressure to 90/60 mm Hg. She was given 1.5 liters of normal saline IV within 6 hours. She later converted spontaneously to normal sinus rhythm. Over the next 2 days, there were further evolutionary changes in the electrocardiogram with inferior T wave inversion associated with new Q waves (Figure 2). Three serial creatine phosphokinase (CPK) determinations obtained on admission at 8 hour intervals showed a pattern consistent with AMI, with the initial level showing a total CPK of 125 IU/L and 18% MB fraction and a peak level of 958 IU/L with 9% MB fraction. Her menstrual period continued up to day 6, one day longer than usual, but there was no increase in the amount of bleeding during any day. Follow-up laboratory values 6 hours after admission showed a drop of hemoglobin level of 1.5 G/d1 from 12.5 to 11.0 G/dl. The hemoglobin remained unchanged when repeated 3 days later. The patient continued to improve without complications and was discharged on the sixth hospital day. DISCUSSION This patient underwent thrombolytic therapy during active menstruation without any alarming increase in uterine bleeding. The initial drop in the patient’s hemoglobin was largely a dilutional effect of IV fluid
Figure 1. Twelve lead electrocardiogram taken at admission show@ ST segment elevation In 2, 3, aVF, and V, with ST depression In aVL and V2 consistent with acute inferior myocardlal infarction.
Thrombolytic
Therapy
Figure 2. Follow-up electrocardiogram
347
taken 3 days later showing further evolutionary changes of the inferior infarction.
therapy. Three previous casesof the use of thrombolytic therapy involving women who presented with AM1 during menstruation have been reported. One 43year-old patient with acute anterolateral MI received intracoronary streptokinase without any consequent excessivemenstrual bleeding ( 1). Another 29-year-old patient with acute anteroseptal infarction received 100 mg of tPA intravenously using the standard 3 hour infusion. She experienced an increase in menstrual blood flow associated with a decreasein hemoglobin level although her entire period was shortened by one day (2). The third patient reported was a 40-year-old female with acute anterior infarction. She received intracoronary urokinase with no increased menstrual bleeding (3). Two additional casesare also reported in the literature; these patients did not have AM1 but received IV streptokinase for deep venous thrombosis. One 28-year-old patient, 2fi months post partum, developed withdrawal bleeding approximating her usual menstrual flow after discontinuing her oral contraceptives (4). Another 25year-old patient, also on oral contraceptives, was initially given IV heparin and subsequently streptokinase (5). In both patients, menstrual bleeding was not significantly altered. Investigators from the recently concluded Global Utilization of Streptokinase and tPA for Occluded coronary arteries (GUSTO), in which 41,000 AM1 patients were randomized to receive either streptokinase or tPA, were
able to identify 12 menstruating women among those enrolled in North America (6). These patients’ ages ranged from 24 to 51 years (median age 45 years). Three of the 12 women developed moderate bleeding complications, defined as requiring transfusion, presumed to be related to thrombolytic therapy. Two of the 3 bleeding complications were due to increased menstrual bleeding. The bleeding complications were not considered hemodynamically significant and the investigators conclude that despite the apparent increased risk of nonsevere vaginal bleeding, thrombolytic therapy is safe and effective in menstruating women. Normal menstrual bleeding occurs due to desquamation and sloughing of superficial endometrial tissues. These changes occur following withdrawal of oral estrogen or progesterone therapy or during normal menstrual cycle due to the natural cyclic decline in circulating steroidal hormones. The intense vasoconstriction of spiral arteries supplying the endometrium results in ischemia and necrosis of the superficial endometrial tissues. During initial bleeding, hemostasis is achieved by the formation of platelet plugs that are later stabilized by fibrin; however, when most of the superficial endometrium has been shed, usually within 20 hours after the start of bleeding, platelet and fibrin plugs are no longer important and hemostasis is achieved by the intense contraction
348
Y.-F. Sekyema and R. F. Baltazar
of spiral arteries (7). Heparin, which inhibits the formation of fibrin, and thrombolytic agents, which degrade fibrin clots, would not interfere with the hemostasis of normal menstrual bleeding since the hemostatic mechanisms are not dependent on fibrin clots (5,7). This is unlike pathologic bleeding involving mucous structures such as the gastrointestinal or genito-urinary tracts where abnormal rupture of
blood vesselsnecessitatesthe formation of thrombus for adequate hemostasis. The current case report provides another observation that thrombolytic therapy as well as the use of heparin therapy appear to be possible during menstruation, presumably because the mechanism of normal menstrual bleeding is unique and not affected by thrombus modifying agents.
REFERENCES 1. de Gregorio B, Goldstein J, Haft JI. Administration of intracoronary streptokinase during menstruation. Am Heart J. 1985; 109908-910. 2. Chop Jr WM, Evans PJ, Felty K. Thrombolytic therapy during active menstruation: a case report. J Family Practice. 1991;33: 19-81. 3. Conti CR. Is menstruation a contraindication to thrombolytic therapy? Clin Cardiol. 1992;15:625-626. 4. Powers JC. Is Menstruation a contraindication to thrombolytic therapy? (Letter to the editor). Clin Cardiol. 1992;15:875.
5. Simel DL, Moorman JR, Pryor SL, Piscitelli JT, Sharma GVRK. Is streptokinase safe during menses?Ann Intern Med. 1984;144:841-842. 6. Karnash S, &anger C, Kline-Rogers E, Smith DD, Top01 EJ, Califf RM. Menstruating women may be safely and effectively treated with thrombolytic therapy: experience from the GUSTO trial. J Am Co11Cardiol. February 1994;315A. 7. Christiaens GCML, Sixma JJ, Haspels AA. Hemostasis in menstrual endometrium: a review. Obstet Gynecol Surv. 1982;37: 281-303.
Pergamon
0136-4619/95
$9.50 + .OO
0736-4679(95)00010-O
Selected Topics:
Cardiology
Commentary
Yao-Fob Sekyema,
MD
and Romulo F. Baltazar,
MD
Department of Medicine, Division of Cardiology, Sinai Hospital of Baltimore, Baltimore, Maryland Reprint Address: Romulo F. Baltazar, MD, Division of Cardiology, Sinai Hospital of Baltimore, Baltimore, MD 21215
0 Abstract-A 3byear-old female presented to the Emergency Department daring the fourth day of menstruation and within 2 hours of the onset of chest pain associated with dyspnea, diaphoresis, and emesis. An electrocardiogram showed acute inferior myocardial infarction and serial CPK enzyme levels peaked at 958 IU/L with 9% MB fraction. Along with aspirin and intravenous nitroglycerin, the patient was given thrombolytic therapy consisting of tPA with an initial bolus of 35 units, followed by 65 units infused within 60 minutes together with heparin 5000 units intravenous boks, and 1000 units/hour maintenance infusion for 5 days. The menses were prolonged 1 day longer than her usual 5 days; however, there was no increase in the amount of bleeding during any day. The hemoglobin dropped from 12.5 G/dl to 11.3 G/d1 in the first 6 hours, but remained stable thereafter. This initial drop in hemoglobin was considered a dilutional effect of 1.5 L of normal saline the patient received intravenously during that period. Although no available guidelines exist regarding the safety of thrombolytic agents during active menstruation, this case report and a few others reported in the literature suggest that normal menstruation is not a contraindication to thrombolytic therapy during acute myocardial infarction.
more uncommon is the occurrence of AM1 during a menstrual period. Although thrombolytic agents are now used routinely in the management of AMI, there are no available guidelines regarding the use of thrombolytic therapy during menstruation. The use of thrombolytic therapy for AM1 during active menstruation is likely to be uncommon and only a few such caseshave been reported (l-3). The following case report describes a young female who developed AM1 during her active menstrual period and received thrombolytic therapy without any unusual bleeding complications. CASE REPORT The patient is a 39-year-old female who was brought to the Emergency Department complaining of severe nonradiating retrosternal pressure of 2 hours duration associated with dyspnea, diaphoresis, and two episodes of emesis. She gave a history of diabetes mellitus and hypertension of several years duration and smoking approximately 1 pack of cigarettes per day for lo-15 years. She had no previous history of chest pain, dyspnea, dizzy or fainting spells, or palpitations. She had no known allergies and her only medication was glyburide 5 mg/day. She had regular menstrual periods, usually of 5 days duration. She was on her fourth day of a normal menstrual period at the time of admission.
0 Keywords-acute myocardial infarction; thrombolytic therapy; menstruation INTRODUCTION
Acute myocardial infarction (AMI) occurring in women below the age of 40 years is uncommon. Even =
Cardiology Commentary is coordinatedby StevenR. Lowenstein, MD, MPH, of the University of Colorado Health
v
SciencesCenter, Denver,Colorado 24 June 1994; FINAL SUBMISSION 4 November 1994
RECEIVED: ACCEPTED:
RECEIVED:
7 October 1994; 345
346
Physical examination showed a young female complaining of chest discomfort. She had a blood pressure of 120/80 mm Hg, a regular heart rate of 98 beats per minute (BPM), and a respiratory rate of 20 breaths/min. The head and neck findings were unremarkable. The neck veins were not distended. The lungs were clear to auscultation. The point of maximal cardiac impulse was not displaced and no gallops or murmurs were audible. The abdomen did not show any palpable visceromegaly. The extremities did not show any pedal edema and pulses were symmetrical. The electrocardiogram showed normal sinus rhythm with a rate of 98 BPM. There was 2 mm of ST segment elevation in leads II, III, and aVF with ST depression in aVL (Figure 1). The chest X-ray study did not show any cardiomegaly and no infiltrates were noted. After a diagnosis of acute inferior MI was made, the patient was given 325 mg of aspirin orally and was started on intravenous (IV) nitroglycerin. Heparin IV, 5000 units, was also given as a bolus followed by an infusion of 1000 units per hour. Front loaded tissue Plasminogen Activator (tPA) was given IV with an initial IV bolus of 35 units over 2 minutes, followed by 65 units infused within 60 minutes. Forty minutes later, the patient developed accelerated idioventricular rhythm associated with a drop in blood
Y.-F. Sekyema and R. F. Baltazar
pressure to 90/60 mm Hg. She was given 1.5 liters of normal saline IV within 6 hours. She later converted spontaneously to normal sinus rhythm. Over the next 2 days, there were further evolutionary changes in the electrocardiogram with inferior T wave inversion associated with new Q waves (Figure 2). Three serial creatine phosphokinase (CPK) determinations obtained on admission at 8 hour intervals showed a pattern consistent with AMI, with the initial level showing a total CPK of 125 IU/L and 18% MB fraction and a peak level of 958 IU/L with 9% MB fraction. Her menstrual period continued up to day 6, one day longer than usual, but there was no increase in the amount of bleeding during any day. Follow-up laboratory values 6 hours after admission showed a drop of hemoglobin level of 1.5 G/d1 from 12.5 to 11.0 G/dl. The hemoglobin remained unchanged when repeated 3 days later. The patient continued to improve without complications and was discharged on the sixth hospital day. DISCUSSION This patient underwent thrombolytic therapy during active menstruation without any alarming increase in uterine bleeding. The initial drop in the patient’s hemoglobin was largely a dilutional effect of IV fluid
Figure 1. Twelve lead electrocardiogram taken at admission show@ ST segment elevation In 2, 3, aVF, and V, with ST depression In aVL and V2 consistent with acute inferior myocardlal infarction.
Thrombolytic
Therapy
Figure 2. Follow-up electrocardiogram
347
taken 3 days later showing further evolutionary changes of the inferior infarction.
therapy. Three previous casesof the use of thrombolytic therapy involving women who presented with AM1 during menstruation have been reported. One 43year-old patient with acute anterolateral MI received intracoronary streptokinase without any consequent excessivemenstrual bleeding ( 1). Another 29-year-old patient with acute anteroseptal infarction received 100 mg of tPA intravenously using the standard 3 hour infusion. She experienced an increase in menstrual blood flow associated with a decreasein hemoglobin level although her entire period was shortened by one day (2). The third patient reported was a 40-year-old female with acute anterior infarction. She received intracoronary urokinase with no increased menstrual bleeding (3). Two additional casesare also reported in the literature; these patients did not have AM1 but received IV streptokinase for deep venous thrombosis. One 28-year-old patient, 2fi months post partum, developed withdrawal bleeding approximating her usual menstrual flow after discontinuing her oral contraceptives (4). Another 25year-old patient, also on oral contraceptives, was initially given IV heparin and subsequently streptokinase (5). In both patients, menstrual bleeding was not significantly altered. Investigators from the recently concluded Global Utilization of Streptokinase and tPA for Occluded coronary arteries (GUSTO), in which 41,000 AM1 patients were randomized to receive either streptokinase or tPA, were
able to identify 12 menstruating women among those enrolled in North America (6). These patients’ ages ranged from 24 to 51 years (median age 45 years). Three of the 12 women developed moderate bleeding complications, defined as requiring transfusion, presumed to be related to thrombolytic therapy. Two of the 3 bleeding complications were due to increased menstrual bleeding. The bleeding complications were not considered hemodynamically significant and the investigators conclude that despite the apparent increased risk of nonsevere vaginal bleeding, thrombolytic therapy is safe and effective in menstruating women. Normal menstrual bleeding occurs due to desquamation and sloughing of superficial endometrial tissues. These changes occur following withdrawal of oral estrogen or progesterone therapy or during normal menstrual cycle due to the natural cyclic decline in circulating steroidal hormones. The intense vasoconstriction of spiral arteries supplying the endometrium results in ischemia and necrosis of the superficial endometrial tissues. During initial bleeding, hemostasis is achieved by the formation of platelet plugs that are later stabilized by fibrin; however, when most of the superficial endometrium has been shed, usually within 20 hours after the start of bleeding, platelet and fibrin plugs are no longer important and hemostasis is achieved by the intense contraction
348
Y.-F. Sekyema and R. F. Baltazar
of spiral arteries (7). Heparin, which inhibits the formation of fibrin, and thrombolytic agents, which degrade fibrin clots, would not interfere with the hemostasis of normal menstrual bleeding since the hemostatic mechanisms are not dependent on fibrin clots (5,7). This is unlike pathologic bleeding involving mucous structures such as the gastrointestinal or genito-urinary tracts where abnormal rupture of
blood vesselsnecessitatesthe formation of thrombus for adequate hemostasis. The current case report provides another observation that thrombolytic therapy as well as the use of heparin therapy appear to be possible during menstruation, presumably because the mechanism of normal menstrual bleeding is unique and not affected by thrombus modifying agents.
REFERENCES 1. de Gregorio B, Goldstein J, Haft JI. Administration of intracoronary streptokinase during menstruation. Am Heart J. 1985; 109908-910. 2. Chop Jr WM, Evans PJ, Felty K. Thrombolytic therapy during active menstruation: a case report. J Family Practice. 1991;33: 19-81. 3. Conti CR. Is menstruation a contraindication to thrombolytic therapy? Clin Cardiol. 1992;15:625-626. 4. Powers JC. Is Menstruation a contraindication to thrombolytic therapy? (Letter to the editor). Clin Cardiol. 1992;15:875.
5. Simel DL, Moorman JR, Pryor SL, Piscitelli JT, Sharma GVRK. Is streptokinase safe during menses?Ann Intern Med. 1984;144:841-842. 6. Karnash S, &anger C, Kline-Rogers E, Smith DD, Top01 EJ, Califf RM. Menstruating women may be safely and effectively treated with thrombolytic therapy: experience from the GUSTO trial. J Am Co11Cardiol. February 1994;315A. 7. Christiaens GCML, Sixma JJ, Haspels AA. Hemostasis in menstrual endometrium: a review. Obstet Gynecol Surv. 1982;37: 281-303.