Ovarian hemorrhage complicating warfarin sodium anticoagulant therapy STEPHEN MATSEOANE, M.D .. F.A.C.O.G. JAMES A. BATTS, ]R., M.D., F.A.C.O.G. EDGAR 0. MANDEVILLE, M.D.
NPw York, New York
Three cases of women in the reproductive age group who received warfarin sodium therapy for pulmonary embolism are presented. The therapy was complicated lry rupture of ovarian cysts with intraperitoneal hemorrhage necessitating exploratory laparotomy. The possibility of intraperitoneal hemorrhage must be considered in patients who present with abdominal pain and a history of anticoagulant therapy. Lack of awareness of the complication may result in delay in making a corrpct diagnosis and instituting appropriate therapy.
anticoagulant therapy for the treatment and prevention of thromboembolic phenomena is widely accepted. Hemorrhagic complications of anticoagulant therapy occur despite precautions. 1 Although the most common site of bleeding secondary to anticoagulants is the urinary tract, 2 bleeding into the ovary with the formation of a hemorrhagic cyst can occur. These cysts may subsequently rupture with intraperitoneal hemorrhage. Three cases of patients with pulmonary embolization were given long-term warfarin sodium anticoagulant therapy. They developed ruptured hemorrhagic cysts of the ovary with intraperitoneal hemorrhage requiring exploratory laparotomy.
medical clinics where she was given warfarin sodium because of recurrent thrombophlebitis. The patient was readmitted to the gynecologic ward because of lower abdominal pain. Pelvic examination revealed a right adnexal mass and a full pouch of Douglas. Culdocentesis yielded 15 mi. of unclotted blood. A clinical diagnosis of hemoperitoneum was made. An exploratory laparotomy revealed that the right ovary was replaced by a 4 by 5 by 6 em. hemorrhagic cyst, and 300 mi. of free blood was present in the peritoneal cavity. Because the patient previously had a left oophorectomy, a subtotal hysterectomy and right salpingo-oophorectomy were performed. The patient's condition had improved when she was discharged, with follow-up to be performed at the gynecology clinic. The pathologic diagnosis of the submitted surgical specimen was hemorrhagic cyst of the ovary. Case 2. A 38-year-old, black patient, para 1-0-1-1, was admitted to the gynecologic ward on july 22, 1974, with lower abdominal pain. She had pulmonary embolization in June, 1973, and was given warfarin sodium and followed by the medical service. She had a left salpingectomy for an ectopic pregnancy ten years previously. On pelvic examination, a 6 by 7 em. right cystic ovarian mass was found. Exploratory laparotomy was performed on july 23, 1974, and there was 100 ml. of free blood in the peritoneal cavity. The right ovary contained a 4 by 5 by 7 em. cyst, filled with blood. A right ovarian cystectomy was performed. The pathologic diagnosis of the specimen submitted was hemorrhagic corpus Iuteum cyst of the ovary. On the sixth postoperative day, the patient complained of left parasternal chest pain. A lung scan and blood gas analyses suggested recurrent pulmonary embolism. Inferior vena cava ligation was suggested; however, the
THE vALUE OF
Case reports Case 1. A 28-year-old, black woman, para 1-0-0-J, was admitted to the gynecologic ward because of lower abdominal pain. Two years previously, she had an inferior vena cava ligation for repeated pulmonary thromboembolism and was subsequently given warfarin sodium because of chest pains suspected to be due to recurrent pulmonary thromboembolisn. On admission, a left cystic 5 by 6 em. ovarian mass was palpated. The patient had an exploratory laparotomy. The left ovary was occupied by a 5 by 7 by 7 em. cystic mass. A left oophorectomy was performed. She was well when discharged and was followed in the gynecology and From the Department of Obstetria and Gynecology, Harlem Hospital Center, Columbia University. Reprint requests: Dr. Stephen Matseoane, Department of Obstetrics and Gynecology, Harlem Hospital Center, Columbia University, New York, New York IOO.J7.
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patient refused the operation. She was then given heparin and subsequently warfarin sodium. The patient was discharged on August 12, 1974, after her condition improved. Warfarin sodium was continued, and she was to be followed in the gynecology and medical clinics. She was readmitted to the gynecologic ward on September 14, 1974, because of the sudden onset of lower abdominal pain. Pelvic examination showed lower abdominal distention and a pelvic mass, 7 by 8 em., in the right adnexal area. The uterus was difficult to delineate but appeared to be of normal size and separate from the mass. After the prothrombin time returned to normal with vitamin K administration and blood transfusion, and exploratory laparotomy was performed. In the peritoneal cavity was 800 mi. of free blood. The left ovary contained a 4 by 3 by 6 em. ruptured hemorrhagic cyst, and left ovarian cystectomy was performed. The patient had an uneventful postoperative course and was discharged and followed in the gynecology clinic. The pathology diagnosis of the submitted surgical specimen was hemorrhagic cyst of the ovary. Case 3. A 27 -year-old, black patient, para 1-0-0-1, admitted with lower abdominal pain, dizziness, and shoulder pain. Six months previously, the patient had a cesarean section for cephalopelvic disproportion. On the fifth postoperative day, she experienced chest pain. A lung scan revealed areas of decreased perfusion in the apex of the right lung. Anticoagulation therapy with heparin and warfarin sodium was started. The patient's condition improved, and she was discharged on the twelfth postoperative day, to be followed in the medical and postpartum clinics. Warfarin sodium was continued, and the patient was followed with prothrombin time, determinations in the medical clinic. Eight weeks after discharge, the patient was readmitted to the gynecologic ward because of intense lower abdominal pain. Pelvic examination revealed the cervix to be displaced behind the pubic symphysis. The uterus and adnexa were not well delineated because of moderate abdominal distention. The pouch of Douglas was bulging. Culdocentesis retrieved 20 mi. of unclot· ted blood, and diagnosis of hemoperitoneum was REFERENCES I. Pollard,]. W., Hamilton, M. ]., and Christenson, W. A.:
Problems associated with long term anticoagulant therapy, Circulation 25: 311, 1970. 2. Zweiffier, A.]., Coon, V. W., and Willis, P. W.: Bleeding during oral anticoagulant therapy, Am. Heart J. 711: 118, 1966. 3. Askey,]. M.: Hemorrhage during long term anticoagulant
Ovarian hemorrhage with warfarin therapy
767
made. An exploratory laparotomy was performed and revealed 500 mi. of free blood in the abdominal cavity. The left ovary, tube, and uterus were normal. The right ovary was occupied by a 6 by 7 by 8 em. ruptured hemorrhagic cyst, and right ovarian cystectomy was performed. The pathologic diagnosis of the submitted specimen was hemorrhagic corpus luteum cyst.
Comment The incidence of hemorrhagic complications following anticoagulant therapy is approximately 10 per cent if minor and major complications are included. 3 Nevertheless, these agents are indispensable in the management and prevention of thromboembolic phenomena. In a study of 1,626 patients, Askey3 showed that intracranial and gastrointestinal hemorrhage are the most serious complications as measured by deaths and account for over 90 per cent of serious bleeding episodes following anticoagulant therapy. Corpus luteum cyst hemorrhage may occur with anticoagulant therapy; however, massive hemoperitoneum is rare. 4• Life-threatening intraperitoneal hemorrhage secondary to ruptured ovarian hemorrhagic cyst due to anticoagulation, which occurred in the cases presented, is not uncommon. Premenopausal patients on long-term anticoagulant therapy are at a risk of developing ovarian hemorrhagic cysts. The treating physicians must be aware of the possibility of hemoperitoneum in these patients. Pelvic examination should be performed frequently to determine the presence of ovarian enlargement. In the obese patient, pulsed ultrasound may be of assistance in determining the presence of ovarian cysts. Early termination of anticoagulant therapy should be considered in patients with enlarging ovarian masses. Diagnostic culdocentesis should be performed in patients with abdominal pain, and laparotomy is indicated when free blood is foui1d in the pouch of Douglas. Protamine sulfate and vitamin K and/or fresh blood will reverse the effect of warfarin sodium.
drug therapy. Part !-Intracranial hemorrhage, Calif. Med. 104: 6, 1966. 4. Sopper, I. M.: Fatal corpus luteum hemorrhage during anticoagulant therapy, Obstet. Gynecol. 37: 695, 1971. 5. Wesley, A. 1., Neustadter, M., and Levine, W.: Massive intraperitoneal hemorrhage of ovarian follicular origin during anticoagulant therapy, AM. j. 0BSTET. GYNECOL. 73: 693, 1957.
NPw York, New York
Three cases of women in the reproductive age group who received warfarin sodium therapy for pulmonary embolism are presented. The therapy was complicated lry rupture of ovarian cysts with intraperitoneal hemorrhage necessitating exploratory laparotomy. The possibility of intraperitoneal hemorrhage must be considered in patients who present with abdominal pain and a history of anticoagulant therapy. Lack of awareness of the complication may result in delay in making a corrpct diagnosis and instituting appropriate therapy.
anticoagulant therapy for the treatment and prevention of thromboembolic phenomena is widely accepted. Hemorrhagic complications of anticoagulant therapy occur despite precautions. 1 Although the most common site of bleeding secondary to anticoagulants is the urinary tract, 2 bleeding into the ovary with the formation of a hemorrhagic cyst can occur. These cysts may subsequently rupture with intraperitoneal hemorrhage. Three cases of patients with pulmonary embolization were given long-term warfarin sodium anticoagulant therapy. They developed ruptured hemorrhagic cysts of the ovary with intraperitoneal hemorrhage requiring exploratory laparotomy.
medical clinics where she was given warfarin sodium because of recurrent thrombophlebitis. The patient was readmitted to the gynecologic ward because of lower abdominal pain. Pelvic examination revealed a right adnexal mass and a full pouch of Douglas. Culdocentesis yielded 15 mi. of unclotted blood. A clinical diagnosis of hemoperitoneum was made. An exploratory laparotomy revealed that the right ovary was replaced by a 4 by 5 by 6 em. hemorrhagic cyst, and 300 mi. of free blood was present in the peritoneal cavity. Because the patient previously had a left oophorectomy, a subtotal hysterectomy and right salpingo-oophorectomy were performed. The patient's condition had improved when she was discharged, with follow-up to be performed at the gynecology clinic. The pathologic diagnosis of the submitted surgical specimen was hemorrhagic cyst of the ovary. Case 2. A 38-year-old, black patient, para 1-0-1-1, was admitted to the gynecologic ward on july 22, 1974, with lower abdominal pain. She had pulmonary embolization in June, 1973, and was given warfarin sodium and followed by the medical service. She had a left salpingectomy for an ectopic pregnancy ten years previously. On pelvic examination, a 6 by 7 em. right cystic ovarian mass was found. Exploratory laparotomy was performed on july 23, 1974, and there was 100 ml. of free blood in the peritoneal cavity. The right ovary contained a 4 by 5 by 7 em. cyst, filled with blood. A right ovarian cystectomy was performed. The pathologic diagnosis of the specimen submitted was hemorrhagic corpus Iuteum cyst of the ovary. On the sixth postoperative day, the patient complained of left parasternal chest pain. A lung scan and blood gas analyses suggested recurrent pulmonary embolism. Inferior vena cava ligation was suggested; however, the
THE vALUE OF
Case reports Case 1. A 28-year-old, black woman, para 1-0-0-J, was admitted to the gynecologic ward because of lower abdominal pain. Two years previously, she had an inferior vena cava ligation for repeated pulmonary thromboembolism and was subsequently given warfarin sodium because of chest pains suspected to be due to recurrent pulmonary thromboembolisn. On admission, a left cystic 5 by 6 em. ovarian mass was palpated. The patient had an exploratory laparotomy. The left ovary was occupied by a 5 by 7 by 7 em. cystic mass. A left oophorectomy was performed. She was well when discharged and was followed in the gynecology and From the Department of Obstetria and Gynecology, Harlem Hospital Center, Columbia University. Reprint requests: Dr. Stephen Matseoane, Department of Obstetrics and Gynecology, Harlem Hospital Center, Columbia University, New York, New York IOO.J7.
766
Volume 124 Number 7
patient refused the operation. She was then given heparin and subsequently warfarin sodium. The patient was discharged on August 12, 1974, after her condition improved. Warfarin sodium was continued, and she was to be followed in the gynecology and medical clinics. She was readmitted to the gynecologic ward on September 14, 1974, because of the sudden onset of lower abdominal pain. Pelvic examination showed lower abdominal distention and a pelvic mass, 7 by 8 em., in the right adnexal area. The uterus was difficult to delineate but appeared to be of normal size and separate from the mass. After the prothrombin time returned to normal with vitamin K administration and blood transfusion, and exploratory laparotomy was performed. In the peritoneal cavity was 800 mi. of free blood. The left ovary contained a 4 by 3 by 6 em. ruptured hemorrhagic cyst, and left ovarian cystectomy was performed. The patient had an uneventful postoperative course and was discharged and followed in the gynecology clinic. The pathology diagnosis of the submitted surgical specimen was hemorrhagic cyst of the ovary. Case 3. A 27 -year-old, black patient, para 1-0-0-1, admitted with lower abdominal pain, dizziness, and shoulder pain. Six months previously, the patient had a cesarean section for cephalopelvic disproportion. On the fifth postoperative day, she experienced chest pain. A lung scan revealed areas of decreased perfusion in the apex of the right lung. Anticoagulation therapy with heparin and warfarin sodium was started. The patient's condition improved, and she was discharged on the twelfth postoperative day, to be followed in the medical and postpartum clinics. Warfarin sodium was continued, and the patient was followed with prothrombin time, determinations in the medical clinic. Eight weeks after discharge, the patient was readmitted to the gynecologic ward because of intense lower abdominal pain. Pelvic examination revealed the cervix to be displaced behind the pubic symphysis. The uterus and adnexa were not well delineated because of moderate abdominal distention. The pouch of Douglas was bulging. Culdocentesis retrieved 20 mi. of unclot· ted blood, and diagnosis of hemoperitoneum was REFERENCES I. Pollard,]. W., Hamilton, M. ]., and Christenson, W. A.:
Problems associated with long term anticoagulant therapy, Circulation 25: 311, 1970. 2. Zweiffier, A.]., Coon, V. W., and Willis, P. W.: Bleeding during oral anticoagulant therapy, Am. Heart J. 711: 118, 1966. 3. Askey,]. M.: Hemorrhage during long term anticoagulant
Ovarian hemorrhage with warfarin therapy
767
made. An exploratory laparotomy was performed and revealed 500 mi. of free blood in the abdominal cavity. The left ovary, tube, and uterus were normal. The right ovary was occupied by a 6 by 7 by 8 em. ruptured hemorrhagic cyst, and right ovarian cystectomy was performed. The pathologic diagnosis of the submitted specimen was hemorrhagic corpus luteum cyst.
Comment The incidence of hemorrhagic complications following anticoagulant therapy is approximately 10 per cent if minor and major complications are included. 3 Nevertheless, these agents are indispensable in the management and prevention of thromboembolic phenomena. In a study of 1,626 patients, Askey3 showed that intracranial and gastrointestinal hemorrhage are the most serious complications as measured by deaths and account for over 90 per cent of serious bleeding episodes following anticoagulant therapy. Corpus luteum cyst hemorrhage may occur with anticoagulant therapy; however, massive hemoperitoneum is rare. 4• Life-threatening intraperitoneal hemorrhage secondary to ruptured ovarian hemorrhagic cyst due to anticoagulation, which occurred in the cases presented, is not uncommon. Premenopausal patients on long-term anticoagulant therapy are at a risk of developing ovarian hemorrhagic cysts. The treating physicians must be aware of the possibility of hemoperitoneum in these patients. Pelvic examination should be performed frequently to determine the presence of ovarian enlargement. In the obese patient, pulsed ultrasound may be of assistance in determining the presence of ovarian cysts. Early termination of anticoagulant therapy should be considered in patients with enlarging ovarian masses. Diagnostic culdocentesis should be performed in patients with abdominal pain, and laparotomy is indicated when free blood is foui1d in the pouch of Douglas. Protamine sulfate and vitamin K and/or fresh blood will reverse the effect of warfarin sodium.
drug therapy. Part !-Intracranial hemorrhage, Calif. Med. 104: 6, 1966. 4. Sopper, I. M.: Fatal corpus luteum hemorrhage during anticoagulant therapy, Obstet. Gynecol. 37: 695, 1971. 5. Wesley, A. 1., Neustadter, M., and Levine, W.: Massive intraperitoneal hemorrhage of ovarian follicular origin during anticoagulant therapy, AM. j. 0BSTET. GYNECOL. 73: 693, 1957.
