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Spontaneous splenic rupture due to subcutaneous heparin therapy
The Journal of Emergency Medicine, Vol. 18, No. 4, pp. 421– 426, 2000 Copyright © 2000 Elsevier Science Inc. Printed in the USA. All rights reserved 0736-4679/00 $–see front matter
PII S0736-4679(00)00157-8
Clinical Communications
SPONTANEOUS SPLENIC RUPTURE DUE TO SUBCUTANEOUS HEPARIN THERAPY Steven J. Weiss,
MD,*
Timothy Smith,
DO,*
Erik Laurin,
MD,*
and David H. Wisner,
MD†
*Division of Emergency Medicine; †Department of Surgery, University of California, Davis, Medical Center, Sacramento, California Reprint Address: Steven Weiss, MD, Division of Emergency Medicine, UC Davis Medical Center, PSSB 2100, 2315 Stockton Blvd., Sacramento, CA 95817
e Abstract—We report a case of spontaneous splenic rupture in a 59-year-old woman who was receiving 15,000 units of heparin subcutaneously (s.c.) twice a day for deep venous thrombosis (DVT) prophylaxis. Her past medical history included multiple DVT, pulmonary emboli, and ovarian cancer stage III-C with known ascites. The diagnosis of splenic rupture was initially missed because of the ascites. This case illustrates both a previously undescribed complication of s.c. heparin therapy and a failure of ultrasound diagnosis. We emphasize the unique presentation, difficulty in diagnosis, and need for early surgical involvement to ensure the most favorable outcome. © 2000 Elsevier Science Inc.
spleen. Likewise, it has never been reported in patients receiving subcutaneous (s.c.) heparin therapy alone. We present a case representing spontaneous splenic rupture in a patient with ovarian cancer receiving s.c. heparin therapy. CASE REPORT A 59-year-old woman arrived in the Emergency Department (ED) with epigastric pain, nausea, and vomiting for approximately 16 h. She had been diagnosed with stage III-C ovarian cancer 18 months before presentation, and had completed 8 months of primary palliative chemotherapy with paclitaxil (Taxol), cisplatin, and carboplatin. She did well until 4 months before presentation, when she developed abdominal pain and ascites. A paracentesis indicated recurrence of the cancer. Therapy was begun using i.v. topetecan for 5 days. Three weeks before presentation, the patient received a first dose of i.v. doxorubicin, after which she reported symptoms similar to her present complaints. She was suspected of having a side effect to the doxorubicin and was treated with i.v. fluids for rehydration at the cancer center. She returned to baseline without problems. Three days before presentation, she received another dose of doxorubicin. The pain had begun the day before presentation. It was sudden in onset, dull, crampy, and nonradiating, without any exacerbating or relieving factors. The patient described it as similar to the pain she experienced with
e Keywords—spleen; anticoagulation; splenic rupture
INTRODUCTION Spontaneous splenic rupture (SSR) has been reported in patients receiving thrombolytic therapy, anticoagulation with warfarin, and anticoagulation with intravenous (i.v.) heparin (1– 6). It also has been reported in patients with hematologic malignancies, such as leukemia and lymphoma, and some solid tumors with metastatic invasion of the spleen (7–25). The cause of the splenic rupture has been reported as tumor cell lysis within the spleen parenchyma in hematologic malignancies and as a direct effect of splenic metastases in other malignancies. SSR has not, however, been described in patients with ovarian cancer or patients without metastatic disease to the
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the last dose of doxorubicin, but worse. At the time of presentation, she denied any history of trauma. She had taken extra doses of oral morphine without relief. She had tactile fever, chills, and several episodes of vomiting on the day of admission. She denied dysuria, hematuria, vaginal discharge, melena, or hematochezia. The last bowel movement, 1 day before admission, was normal in appearance. The woman was scheduled to visit the cancer center later on the day of admission for i.v. saline rehydration, as she had received after her last episode of illness following chemotherapy 3 weeks earlier. She presented to the ED because the pain was more intense than the previous time and was increasing. The past medical history was significant for the following: 1) ovarian cancer stage III-C with known ascites, status postchemotherapy twice with Taxol, cisplatin, and carboplatin; 2) colon adenocarcinoma stage C-2 diagnosed 12 years earlier, successfully resected without recurrence; 3) multiple deep vein thromboses (DVTs) and pulmonary emboli for which she had failed warfarin treatment and was placed on s.c. heparin; and 4) ascites with multiple ultrasound-guided paracenteses, the last one being 4 months before admission. The patient had been maintained on warfarin with an internal normalized ratio (INR) ranging from 1.8⫺8.7 (generally 2.5⫺3.0) until 3 months before admission when, after developing recurrent internal jugular vein thromboses, she was switched to heparin 15,000 units s.c. twice a day. Past surgical history was significant for total abdominal hysterectomy with bilateral salpingo-oophorectomy, laparotomy with hemicolectomy and reanastamosis, appendectomy, and cesarean section. Medications included heparin 15,000 U s.c. twice a day, meperidine and morphine elixir for pain, and prochlorperazine and ondansetron for nausea. Physical examination revealed a thin woman who was obviously uncomfortable, holding her abdomen, pale and diaphoretic. The vital signs were: temperature 36.3°C, heart rate 84 beats per min, blood pressure 77/33 mm Hg, and respiratory rate 16 breaths per min. The lips and tongue were dry, and conjunctivae were slightly pale. There was no jugular venous distension. Cardiac and pulmonary examinations were normal. The abdomen had multiple small ecchymotic areas at the heparin injection sites. The abdomen was flat with decreased bowel sounds. There was tenderness in the epigastrium with firm voluntary guarding but minimal involuntary guarding and tenderness in other quadrants. The pelvic examination was status posthysterectomy. Rectal examination was nontender with brown, heme-negative stool. Extremities were cool and pale with weak distal pulses and a trace pedal edema bilaterally. Laboratory analysis revealed a WBC ⫽ 10,600/mm3, Hb ⫽ 13 g/dL, Hct ⫽ 39%, Plt ⫽ 280,000/mm3. The
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chemistries were as follows: Na ⫽ 137 mEq/L, K ⫽ 4.1 mEq/L, Cl ⫽ 103 mEq/L, HCO3 ⫽ 21 mEq/L, BUN ⫽ 25 mg/dL, Cr ⫽ 1.5 mg/dL, and Gluc ⫽ 209 mg/dL. Liver function tests were normal, amylase 33 U/L, lipase 75 U/L, INR ⫽ 1.12, PTT ⫽ 41 s. The urinalysis was within normal limits. The chest x-ray and abdominal studies were also normal. The electrocardiogram showed sinus tachycardia at 103 beats per min. An immediate abdominal ultrasound showed a moderate amount of peritoneal fluid that appeared to be loculated, and free fluid in both upper quadrants; the aorta, kidneys, and gall bladder were normal (Figure 1). No comment was made on the spleen or liver parenchyma.
HOSPITAL COURSE Because of the similarity with the previous chemotherapy-associated illness, the location of the pain, the elevated lipase, and the presence of ascites, our working diagnoses were a drug-related side effect (like the patient’s previous episode), pancreatitis, or spontaneous bacterial peritonitis. Because of the loculations in the peritoneal fluid, an ultrasound-guided paracentesis was requested. However, Radiology was unwilling to do the procedure until the patient’s mild coagulopathy was corrected. It was thought that by the morning, 8 h later, the coagulopathy would be improved and paracentesis could be performed. In the meantime, broad-spectrum antibiotics were administered for possible bacterial peritonitis. Surgery was consulted early during the ED course because of the patient’s marked abdominal tenderness, and agreed with the tentative diagnosis and recommended antibiotics, bowel rest, and fluid resuscitation. In the ED, the patient received 4 liters of crystalloid with only slight improvement. The systolic blood pressure remained between 70 and 90 mm Hg, diastolic pressure remained 50⫺60 mm Hg, and the pulse was 80⫺90 beats/min during the entire ED stay. There were never signs of deterioration during the patient’s 6-h stay in the ED. She was admitted to the medical intensive care unit (MICU). A repeat ultrasound revealed increased free fluid in both upper quadrants and poor visualization of the spleen. The patient’s morning hematocrit had dropped to 18%. An immediate abdominal computed tomography (CT) scan revealed heterogeneous hypodense splenic parenchyma surrounded by large amounts of hyperdense hemorrhagic material as well as massive hypodense ascitic fluid from the patient’s known ovarian cancer (Figure 2). Other images showed large amounts of hemorrhage in the lesser sac consistent with disrupted splenic capsule and thickening of the anterior perirenal and lateral conal fascia. For comparison, a CT scan of the
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Figure 1. Ultrasound image of the spleen obtained during patient presentation to the Emergency Department. The figure illustrates the fluid initially considered to be the ascites and a small islet of tissue thought to represent loculation of the peritoneal fluid.
Figure 2. CT scan of the spleen obtained during the first hospital day after the patient’s hematocrit dropped in the intensive care unit. The figure illustrates heterogeneous hypodense splenic parenchyma (a) surrounded by large amounts of hyperdense hemorrhagic material (b) as well as massive hypodense ascitic fluid (c) from the patient’s known ovarian cancer.
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patient 5 months earlier showed massive ascites and a normal spleen. Because of her profound drop in hematocrit, an exploratory celiotomy was done. At surgery, the perisplenic hemorrhage and hematoma were largely confined to the lesser sac. On opening the abdomen, the stomach was found to be stretched and displaced anteriorly by the large hematoma behind it. The hematoma contained approximately 1,500 milliliters of blood. There was a large hilar laceration in the spleen. There was no evidence of tumor invasion within the splenic remnants. Because of the patient’s underlying condition and uncertainty about the etiology of the splenic rupture, a splenectomy was performed. The patient had an uneventful postoperative course. Pathology reported “splenic rupture with acute hemorrhage,” also with no evidence of tumor invasion. The spleen weighed 220 gms (normal estimated at about 150 gms in a 60-year-old female) and measured 10 ⫻ 7 ⫻ 4 cm (normal for the patient’s age). Upon repeat questioning of the woman, no causative factors could be identified other than s.c. heparin use in a patient with ovarian cancer receiving chemotherapy.
DISCUSSION The diagnosis of atraumatic splenic rupture was very challenging in this patient. The classic signs of abdominal pain, left shoulder pain, and shock were confounded by the other medical problems of malignancy, ascites, multiple abdominal operations, and chemotherapy. Additionally, her previous similar symptoms had been relieved with i.v. fluids, suggesting a more benign diagnosis. The case was discussed with the patient and family in retrospect to look for any possible cause for the splenic rupture. The only possibility found was that it was secondary to a small Shih Tzu dog (weight 10⫺15 lbs.) that routinely jumped up on her lap. Since there was no indication that this had occurred any more vigorously at the time of the splenic rupture, it was deemed by both the woman’s primary physician and the authors in speaking with her family as very unlikely to be related to the rupture. While the diagnosis of splenic rupture may be relatively straightforward in the trauma patient, concurrent disease in an atraumatic patient makes it a challenging diagnostic dilemma. To complicate matters, splenic rupture has been described with findings mimicking widely different problems such as cardiovascular disease and scrotal hematomas (26, 27). In retrospect, we may have diagnosed this patient with an earlier CT scan. However, since the primary diagnosis was bacterial peritonitis and all signs and symptoms
pointed to this diagnosis, we chose to observe the patient overnight in the MICU. This decision was made in conjunction with the MICU and Surgical attending staff. The CT scan was prompted by the dropping hematocrit the following day. Examination of the abdomen for splenic rupture can be done either with ultrasound or CT scan. Although more sensitive, a CT scan requires that the patient be moved, which may be undesirable if she or he is hemodynamically unstable. The ultrasound signs of splenic rupture are enlargement, displacement, double contour, irregularity of the spleen, and intraperitoneal (i.p.) fluid (28). The signs on CT scan include foci of hypodensity or hyperdensity that are not enhanced with contrast, and intracapsular, perirenal, and i.p. fluid (28). Pre-existing ascites can make the diagnosis of i.p. hemorrhage difficult. Many causes and concurrent illnesses have been related to SSR in the medical literature. In reviewing all cases reported since 1861, one author noted that pathologic rupture of the spleen had occurred almost exclusively in adults and that the ruptured spleens were generally moderately to severely enlarged (16). The primary risk factors for SSR were splenic infiltration by a hematologic disease, splenic infarcts, and coagulation disorders, male sex, adulthood, and severe splenomegaly (16). Cytoreductive chemotherapy has been associated with splenic rupture when leukemic cells in the spleen lyse, leaving a preponderance of proteolytic enzymes that injure the splenic capsule (29). Cancers associated with SSR primarily have been hematologic malignancies. These include acute lymphocytic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia (CML), and Hodgkin’s lymphoma (7–15,18). In addition, SSR has been attributed to such solid tumors as renal cell cancer, teratomas, esophageal cancer, and prostate cancer (21–24). Of 136 cases of pathologic splenic rupture identified by Giagounidis et al. since 1861, 34% were acute leukemias, 34% were non-Hodgkin’s lymphomas, and 18% were CML (16). They also found a male-to-female ratio of 3:1. No cases in the literature were associated with ovarian cancer. SSR has been attributed to viruses such as EpsteinBarr, hepatitis, and HIV (30 –33). Bacterial causes range from common diseases such as pneumonia, meningococcemia, endocarditis, and tuberculosis to rare disorders such as dengue fever, Legionnaire’s disease, and Q fever (34 – 43). In addition, SSR has been associated with the fungal infection aspergillosis (43,44). Worldwide, the most common infectious agent associated with SSR is malaria (45,46). Numerous other diseases have been related to SSR. Pancreatitis has been commonly associated with it (43,44,47– 49). Rheumatologic diseases that have been
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associated with SSR include systemic lupus erythematosus, immune thrombocytopenic purpura, rheumatoid arthritis, polyarteritis nodosum, and Wegener’s granulomatosis (50 –56). SSR also has been reported during both pregnancy and the postpartum period (57– 61). At least five procedures have been associated with SSR: electroconvulsive therapy, implantation of automatic defibrillators, shock wave lithotripsy, colonoscopy, and transesophageal echocardiography (62– 67). There are a number of cases of SSR related to streptokinase and tissue plasminogen activation administration (1– 4). Heparin alone in i.v. doses also has been associated with SSR (5). Additionally, Ticlodopine was associated with SSR in two cases (68). There are no previously reported cases of SSR related to s.c. heparin therapy. There is debate in the literature over whether SSR without a precipitating cause actually exists (69). Multiple cases have been reported in which there appeared to be no underlying cause for the SSR (26,70 –72). While some authors have postulated a mechanism involving repeated torsions of the spleen from increased motility or spasm of the splenic vein leading to venous congestion, other authors believe that the entity simply does not exist (71). Splenic rupture should be considered in any patient with abdominal pain and shock, regardless of a history of trauma or previously known risk factors for spontaneous rupture. Free fluid on abdominal ultrasound in a hypo-
tensive patient should be considered to be blood until proven otherwise, even in a patient with known ascites. Loculations seen on abdominal ultrasound within peritoneal fluid can represent not only septae from longstanding ascites or spontaneous bacterial peritonitis but also areas of blood clots floating within ascites fluid or blood. In this case, the fluid was localized to the lesser sac and therefore may have appeared to be loculated on ultrasound. Serial blood counts may be a useful adjunct to serial examinations in a select group of patients admitted with abdominal pain of unclear etiology who are awaiting the appropriate confirmatory diagnostic studies. In summary, we report a case of spontaneous splenic rupture in a patient with ascites secondary to ovarian cancer (with no tumor invasion of the spleen) who was treated with s.c. heparin for DVT prophylaxis. This case is unusual since there was no history or diagnostic information suggestive of splenic rupture and the patient had multiple complicating factors (chemotherapy, elevated lipase, and ascites) that prevented an earlier diagnosis. In fact, the presentation clearly suggested that another diagnosis (bacterial peritonitis) was more likely. The paracentesis that may have returned blood and revealed the diagnosis was initially unobtainable. Not until the hematocrit dropped was the diagnosis of spontaneous splenic rupture entertained. This case points out various unique characteristics of spontaneous splenic rupture that should be kept in mind when evaluating patients with abdominal pain.
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426 20. Gupta PB, Harvey L. Spontaneous rupture of the spleen secondary to metastatic carcinoma. Br J Surg 1993;80:613. 21. Cook AM, Graham JD. Spontaneous rupture of the spleen secondary to metastatic teratoma. J R Soc Med 1996;89:710. 22. Baniel J, Bihrle R, Wahle GR, et al. Splenic rupture during occlusion of the porta hepatis in resection of tumors with vena caval extension (see comments), J Urol 1994;151:992– 4. 23. Van Poppel H, Aswarie H, Vandenhove J, et al. Spontaneous rupture of splenomegaly due to disseminated bone metastases from prostatic carcinoma. Br J Urol 1991;67:653– 4. 24. Murthy SK, Prabhakaran PS, Rao SR, et al. Unusual splenic metastasis from oesophageal cancer. Indian J Cancer 1991;28: 81–3. 25. Berrebi A, Bustan A, Mashiah A, et al. Splenic rupture as a presenting sign of lymphoma of the spleen. Isr J Med Sci 1984; 20:66 –7. 26. Buciuto R, Kald A, Borch K. Spontaneous rupture of the spleen. Eur J Surg 1992;158:129 –30. 27. Sujka SK, Evans EJ, Nigam A. Delayed rupture of the spleen presenting as a scrotal hematoma. J Trauma 1986;26:85– 6. 28. Paivansalo M, Myllyla V, Siniluoto T, et al. Imaging of splenic rupture. Acta Chir Scand 1986;152:733–7. 29. Borgeat A, Tran-Thang C, Bachmann F. Acute monoblastic leukemia complicated by fatal splenic rupture following initiation of chemotherapy. Schweiz Med Wochenschr 1989;119:227–9. 30. Lippstone MB, Sekula-Perlman A, Tobin J, et al. Spontaneous splenic rupture and infectious mononucleosis in a forensic setting. Del Med J 1998;70:433–7. 31. Asgari MM, Begos DG. Spontaneous splenic rupture in infectious mononucleosis: a review. Yale J Biol Med 1997;70:175– 82. 32. Guleria S, Dorairajan LN, Sinha S, et al. Spontaneous rupture of spleen in viral hepatitis A. Indian J Gastroenterol 1996;15:30. 33. Chien RN, Liaw YF. Pathological rupture of spleen in hepatitis B virus-related cirrhosis. Am J Gastroenterol 1993;88:1793–5. 34. Rao RC, Ghose R, Sawhney S, et al. Hemangioma of spleen with spontaneous, extra-peritoneal rupture, with associated splenic tuberculosis—an unusual presentation. Aust Radiol 1993;37:100 –1. 35. Domingo P, Rodriguez P, Lopez-Contreras J, et al. Spontaneous rupture of the spleen associated with pneumonia. Eur J Clin Microbiol Infect Dis 1996;15:733– 6. 36. Buist MD, Power RG, Keeley SR, et al. Severe meningococcal septicaemia associated with splenic rupture. Med J Aust 1991;155: 713– 4. 37. Sugimoto T, Minowa T, Uchino H, et al. Spontaneous splenic rupture after mitral valve replacement for infective endocarditis. Nippon Kyobu Geka Gakkai Zasshi 1998;46:482–5. 38. Ting W, Silverman NA, Arzouman DA, et al. Splenic septic emboli in endocarditis. Circulation 1990;82:IV105–9. 39. Redondo MC, Rios A, Cohen R, et al. Hemorrhagic dengue with spontaneous splenic rupture: case report and review. Clin Infect Dis 1997;25:1262–3. 40. Imbert P, Sordet D, Hovette P, et al. Spleen rupture in a patient with dengue fever. Trop Med Parasitol 1993;44:327– 8. 41. Saura P, Valles J, Jubert P, et al. Spontaneous rupture of the spleen in a patient with legionellosis (letter). Clin Infect Dis 1993;17:298. 42. Holmes AH, Ng VW, Fogarty P. Spontaneous rupture of the spleen in Legionnaire’s disease. Postgrad Med 1990;66:876 –7. 43. Baumbach A, Brehm B, Sauer W, et al. Spontaneous splenic rupture complicating acute Q fever. Am J Gastroenterol 1992;87: 1651–3. 44. Vernant JP, Durieux P, Cordonnier C, et al. Splenic rupture due to aspergillosis. Nouv Rev Fr Hematol 1983;25:385– 6. 45. al-Shehab S, Pugh RN. Spontaneous splenic rupture in malaria. Ann Trop Med Parasitol 1998;92:817–9. 46. Blaivas M, Quinn J. Diagnosis of spontaneous splenic rupture with emergency ultrasonography. Ann Emerg Med 1998;32:627–30.
S. J. Weiss et al. 47. Malka D, Hammel P, Levy P, et al. Splenic complications in chronic pancreatitis: prevalence and risk factors in a medicalsurgical series of 500 patients. Br J Surg 1998;85:1645–9. 48. Ammori BJ, Madan M, Alexander DJ. Haemorrhagic complications of pancreatitis: presentation, diagnosis and management. Ann R Coll Surg Engl 1998;80:316 –25. 49. Toussi HR, Cross KS, Sheehan SJ, et al. Spontaneous splenic rupture: a rare complication of acute pancreatitis. Br J Surg 1996; 83:632. 50. Tolaymat A, al-Mousily F, Haafiz AB, et al. Spontaneous rupture of the spleen in a patient with systemic lupus erythematosus. J Rheumatol 1995;22:2344 –5. 51. Javier Penalver F, Somolinos N, Villanueva C, et al. Splenic peliosis with spontaneous splenic rupture in a patient with immune thrombocytopenia treated with danazol (letter). Haematologica 1998;83:666 –7. 52. Levy J. Spontaneous rupture of the spleen in association with idiopathic thrombocytopaenic purpura (letter: comment). Postgrad Med J 1994;70:239. 53. Winslet MC, Webberley MJ, Melikian V, et al. Spontaneous rupture of the spleen in association with idiopathic thrombocytopaenic purpura (see comments). Postgrad Med J 1993;69:744 – 6. 54. Marcus RW. Rupture of the spleen in rheumatoid arthritis. Ann Rheum Dis 1985;44:142. 55. Ford GA, Bradley JR, Appleton DS, et al. Spontaneous splenic rupture in polyarteritis nodosa. Postgrad Med J 1986;62:965– 6. 56. Franssen CF, Ter Maaten JC, Hoorntje SJ. Spontaneous splenic rupture in Wegener’s vasculitis (letter). Ann Rheum Dis 1993;52: 314. 57. McCormick GM II, Young DB. Spontaneous rupture of the spleen. A fatal complication of pregnancy. Am J Forensic Med Pathol 1995;16:132– 4. 58. Simpson CJ. Splenic rupture in pregnancy (letter). Postgrad Med 1984;60:504. 59. Holt S. Spontaneous rupture of a normal spleen diagnosed as ruptured ectopic pregnancy. Two case reports. Br J Obstet Gynaecol 1982;89:1062–3. 60. Bhagrath R, Bearn P, Sanusi FA, et al. Postpartum rupture of the spleen. Br J Obstet Gynaecol 1993;100:954 –5. 61. Kaluarachchi A, Krishnamurthy S. Post-cesarean section splenic rupture. Am J Obstet Gynecol 1995;173:230 –2. 62. Gitlin MC, O’Neill PT, Barber MJ, et al. Splenic rupture after electroconvulsive therapy. Anesth Analg 1993;76:1363– 4. 63. Dumas MD, Bach DB, Guiraudon GM. Ruptured spleen as a complication of insertion of an automatic implantable cardioverterdefibrillator. Can Assoc Radiol J 1995;46:226 – 8. 64. Rashid P, Steele D, Hunt J. Splenic rupture after extracorporeal shock wave lithotripsy. J Urol 1996;156:1756 –7. 65. Bergamaschi R, Arnaud JP. Splenic rupture from colonoscopy (letter). Surg Endosc 1997;11:1133. 66. Olshaker JS, Deckleman C. Delayed presentation of splenic rupture after colonoscopy. J Emerg Med 1998;17:455–7. 67. Chow MS, Taylor MA, Hanson CW III. Splenic laceration associated with transesophageal echocardiography. J Cardiothorac Vasc Anesth 1998;12:314 – 6. 68. Loizon P, Nahon P, Founti H, et al. Spontaneous rupture of the spleen under ticlopidine. Apropos of two cases. J Chir 1994;131: 371– 4. 69. Gallerani M, Vanini A, Salmi R, et al. Spontaneous rupture of the spleen (letter). Am J Emerg Med 1996;14:333– 4. 70. Wergowske GL, Carmody TJ. Splenic rupture from coughing (letter). Arch Surg 1983;118:1227. 71. Kumar S, Gupta A, Shrivastava UK, et al. Spontaneous rupture of normal spleen: an enigma recalled. Br J Clin Pract 1992;46:67– 8. 72. Lieberman ME, Levitt MA. Spontaneous rupture of the spleen: a case report and literature review. Am J Emerg Med 1989;7:28 –31.
PII S0736-4679(00)00157-8
Clinical Communications
SPONTANEOUS SPLENIC RUPTURE DUE TO SUBCUTANEOUS HEPARIN THERAPY Steven J. Weiss,
MD,*
Timothy Smith,
DO,*
Erik Laurin,
MD,*
and David H. Wisner,
MD†
*Division of Emergency Medicine; †Department of Surgery, University of California, Davis, Medical Center, Sacramento, California Reprint Address: Steven Weiss, MD, Division of Emergency Medicine, UC Davis Medical Center, PSSB 2100, 2315 Stockton Blvd., Sacramento, CA 95817
e Abstract—We report a case of spontaneous splenic rupture in a 59-year-old woman who was receiving 15,000 units of heparin subcutaneously (s.c.) twice a day for deep venous thrombosis (DVT) prophylaxis. Her past medical history included multiple DVT, pulmonary emboli, and ovarian cancer stage III-C with known ascites. The diagnosis of splenic rupture was initially missed because of the ascites. This case illustrates both a previously undescribed complication of s.c. heparin therapy and a failure of ultrasound diagnosis. We emphasize the unique presentation, difficulty in diagnosis, and need for early surgical involvement to ensure the most favorable outcome. © 2000 Elsevier Science Inc.
spleen. Likewise, it has never been reported in patients receiving subcutaneous (s.c.) heparin therapy alone. We present a case representing spontaneous splenic rupture in a patient with ovarian cancer receiving s.c. heparin therapy. CASE REPORT A 59-year-old woman arrived in the Emergency Department (ED) with epigastric pain, nausea, and vomiting for approximately 16 h. She had been diagnosed with stage III-C ovarian cancer 18 months before presentation, and had completed 8 months of primary palliative chemotherapy with paclitaxil (Taxol), cisplatin, and carboplatin. She did well until 4 months before presentation, when she developed abdominal pain and ascites. A paracentesis indicated recurrence of the cancer. Therapy was begun using i.v. topetecan for 5 days. Three weeks before presentation, the patient received a first dose of i.v. doxorubicin, after which she reported symptoms similar to her present complaints. She was suspected of having a side effect to the doxorubicin and was treated with i.v. fluids for rehydration at the cancer center. She returned to baseline without problems. Three days before presentation, she received another dose of doxorubicin. The pain had begun the day before presentation. It was sudden in onset, dull, crampy, and nonradiating, without any exacerbating or relieving factors. The patient described it as similar to the pain she experienced with
e Keywords—spleen; anticoagulation; splenic rupture
INTRODUCTION Spontaneous splenic rupture (SSR) has been reported in patients receiving thrombolytic therapy, anticoagulation with warfarin, and anticoagulation with intravenous (i.v.) heparin (1– 6). It also has been reported in patients with hematologic malignancies, such as leukemia and lymphoma, and some solid tumors with metastatic invasion of the spleen (7–25). The cause of the splenic rupture has been reported as tumor cell lysis within the spleen parenchyma in hematologic malignancies and as a direct effect of splenic metastases in other malignancies. SSR has not, however, been described in patients with ovarian cancer or patients without metastatic disease to the
RECEIVED: June 11, 1999; FINAL ACCEPTED: December 6, 1999
SUBMISSION RECEIVED:
November 15, 1999; 421
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the last dose of doxorubicin, but worse. At the time of presentation, she denied any history of trauma. She had taken extra doses of oral morphine without relief. She had tactile fever, chills, and several episodes of vomiting on the day of admission. She denied dysuria, hematuria, vaginal discharge, melena, or hematochezia. The last bowel movement, 1 day before admission, was normal in appearance. The woman was scheduled to visit the cancer center later on the day of admission for i.v. saline rehydration, as she had received after her last episode of illness following chemotherapy 3 weeks earlier. She presented to the ED because the pain was more intense than the previous time and was increasing. The past medical history was significant for the following: 1) ovarian cancer stage III-C with known ascites, status postchemotherapy twice with Taxol, cisplatin, and carboplatin; 2) colon adenocarcinoma stage C-2 diagnosed 12 years earlier, successfully resected without recurrence; 3) multiple deep vein thromboses (DVTs) and pulmonary emboli for which she had failed warfarin treatment and was placed on s.c. heparin; and 4) ascites with multiple ultrasound-guided paracenteses, the last one being 4 months before admission. The patient had been maintained on warfarin with an internal normalized ratio (INR) ranging from 1.8⫺8.7 (generally 2.5⫺3.0) until 3 months before admission when, after developing recurrent internal jugular vein thromboses, she was switched to heparin 15,000 units s.c. twice a day. Past surgical history was significant for total abdominal hysterectomy with bilateral salpingo-oophorectomy, laparotomy with hemicolectomy and reanastamosis, appendectomy, and cesarean section. Medications included heparin 15,000 U s.c. twice a day, meperidine and morphine elixir for pain, and prochlorperazine and ondansetron for nausea. Physical examination revealed a thin woman who was obviously uncomfortable, holding her abdomen, pale and diaphoretic. The vital signs were: temperature 36.3°C, heart rate 84 beats per min, blood pressure 77/33 mm Hg, and respiratory rate 16 breaths per min. The lips and tongue were dry, and conjunctivae were slightly pale. There was no jugular venous distension. Cardiac and pulmonary examinations were normal. The abdomen had multiple small ecchymotic areas at the heparin injection sites. The abdomen was flat with decreased bowel sounds. There was tenderness in the epigastrium with firm voluntary guarding but minimal involuntary guarding and tenderness in other quadrants. The pelvic examination was status posthysterectomy. Rectal examination was nontender with brown, heme-negative stool. Extremities were cool and pale with weak distal pulses and a trace pedal edema bilaterally. Laboratory analysis revealed a WBC ⫽ 10,600/mm3, Hb ⫽ 13 g/dL, Hct ⫽ 39%, Plt ⫽ 280,000/mm3. The
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chemistries were as follows: Na ⫽ 137 mEq/L, K ⫽ 4.1 mEq/L, Cl ⫽ 103 mEq/L, HCO3 ⫽ 21 mEq/L, BUN ⫽ 25 mg/dL, Cr ⫽ 1.5 mg/dL, and Gluc ⫽ 209 mg/dL. Liver function tests were normal, amylase 33 U/L, lipase 75 U/L, INR ⫽ 1.12, PTT ⫽ 41 s. The urinalysis was within normal limits. The chest x-ray and abdominal studies were also normal. The electrocardiogram showed sinus tachycardia at 103 beats per min. An immediate abdominal ultrasound showed a moderate amount of peritoneal fluid that appeared to be loculated, and free fluid in both upper quadrants; the aorta, kidneys, and gall bladder were normal (Figure 1). No comment was made on the spleen or liver parenchyma.
HOSPITAL COURSE Because of the similarity with the previous chemotherapy-associated illness, the location of the pain, the elevated lipase, and the presence of ascites, our working diagnoses were a drug-related side effect (like the patient’s previous episode), pancreatitis, or spontaneous bacterial peritonitis. Because of the loculations in the peritoneal fluid, an ultrasound-guided paracentesis was requested. However, Radiology was unwilling to do the procedure until the patient’s mild coagulopathy was corrected. It was thought that by the morning, 8 h later, the coagulopathy would be improved and paracentesis could be performed. In the meantime, broad-spectrum antibiotics were administered for possible bacterial peritonitis. Surgery was consulted early during the ED course because of the patient’s marked abdominal tenderness, and agreed with the tentative diagnosis and recommended antibiotics, bowel rest, and fluid resuscitation. In the ED, the patient received 4 liters of crystalloid with only slight improvement. The systolic blood pressure remained between 70 and 90 mm Hg, diastolic pressure remained 50⫺60 mm Hg, and the pulse was 80⫺90 beats/min during the entire ED stay. There were never signs of deterioration during the patient’s 6-h stay in the ED. She was admitted to the medical intensive care unit (MICU). A repeat ultrasound revealed increased free fluid in both upper quadrants and poor visualization of the spleen. The patient’s morning hematocrit had dropped to 18%. An immediate abdominal computed tomography (CT) scan revealed heterogeneous hypodense splenic parenchyma surrounded by large amounts of hyperdense hemorrhagic material as well as massive hypodense ascitic fluid from the patient’s known ovarian cancer (Figure 2). Other images showed large amounts of hemorrhage in the lesser sac consistent with disrupted splenic capsule and thickening of the anterior perirenal and lateral conal fascia. For comparison, a CT scan of the
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Figure 1. Ultrasound image of the spleen obtained during patient presentation to the Emergency Department. The figure illustrates the fluid initially considered to be the ascites and a small islet of tissue thought to represent loculation of the peritoneal fluid.
Figure 2. CT scan of the spleen obtained during the first hospital day after the patient’s hematocrit dropped in the intensive care unit. The figure illustrates heterogeneous hypodense splenic parenchyma (a) surrounded by large amounts of hyperdense hemorrhagic material (b) as well as massive hypodense ascitic fluid (c) from the patient’s known ovarian cancer.
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patient 5 months earlier showed massive ascites and a normal spleen. Because of her profound drop in hematocrit, an exploratory celiotomy was done. At surgery, the perisplenic hemorrhage and hematoma were largely confined to the lesser sac. On opening the abdomen, the stomach was found to be stretched and displaced anteriorly by the large hematoma behind it. The hematoma contained approximately 1,500 milliliters of blood. There was a large hilar laceration in the spleen. There was no evidence of tumor invasion within the splenic remnants. Because of the patient’s underlying condition and uncertainty about the etiology of the splenic rupture, a splenectomy was performed. The patient had an uneventful postoperative course. Pathology reported “splenic rupture with acute hemorrhage,” also with no evidence of tumor invasion. The spleen weighed 220 gms (normal estimated at about 150 gms in a 60-year-old female) and measured 10 ⫻ 7 ⫻ 4 cm (normal for the patient’s age). Upon repeat questioning of the woman, no causative factors could be identified other than s.c. heparin use in a patient with ovarian cancer receiving chemotherapy.
DISCUSSION The diagnosis of atraumatic splenic rupture was very challenging in this patient. The classic signs of abdominal pain, left shoulder pain, and shock were confounded by the other medical problems of malignancy, ascites, multiple abdominal operations, and chemotherapy. Additionally, her previous similar symptoms had been relieved with i.v. fluids, suggesting a more benign diagnosis. The case was discussed with the patient and family in retrospect to look for any possible cause for the splenic rupture. The only possibility found was that it was secondary to a small Shih Tzu dog (weight 10⫺15 lbs.) that routinely jumped up on her lap. Since there was no indication that this had occurred any more vigorously at the time of the splenic rupture, it was deemed by both the woman’s primary physician and the authors in speaking with her family as very unlikely to be related to the rupture. While the diagnosis of splenic rupture may be relatively straightforward in the trauma patient, concurrent disease in an atraumatic patient makes it a challenging diagnostic dilemma. To complicate matters, splenic rupture has been described with findings mimicking widely different problems such as cardiovascular disease and scrotal hematomas (26, 27). In retrospect, we may have diagnosed this patient with an earlier CT scan. However, since the primary diagnosis was bacterial peritonitis and all signs and symptoms
pointed to this diagnosis, we chose to observe the patient overnight in the MICU. This decision was made in conjunction with the MICU and Surgical attending staff. The CT scan was prompted by the dropping hematocrit the following day. Examination of the abdomen for splenic rupture can be done either with ultrasound or CT scan. Although more sensitive, a CT scan requires that the patient be moved, which may be undesirable if she or he is hemodynamically unstable. The ultrasound signs of splenic rupture are enlargement, displacement, double contour, irregularity of the spleen, and intraperitoneal (i.p.) fluid (28). The signs on CT scan include foci of hypodensity or hyperdensity that are not enhanced with contrast, and intracapsular, perirenal, and i.p. fluid (28). Pre-existing ascites can make the diagnosis of i.p. hemorrhage difficult. Many causes and concurrent illnesses have been related to SSR in the medical literature. In reviewing all cases reported since 1861, one author noted that pathologic rupture of the spleen had occurred almost exclusively in adults and that the ruptured spleens were generally moderately to severely enlarged (16). The primary risk factors for SSR were splenic infiltration by a hematologic disease, splenic infarcts, and coagulation disorders, male sex, adulthood, and severe splenomegaly (16). Cytoreductive chemotherapy has been associated with splenic rupture when leukemic cells in the spleen lyse, leaving a preponderance of proteolytic enzymes that injure the splenic capsule (29). Cancers associated with SSR primarily have been hematologic malignancies. These include acute lymphocytic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia (CML), and Hodgkin’s lymphoma (7–15,18). In addition, SSR has been attributed to such solid tumors as renal cell cancer, teratomas, esophageal cancer, and prostate cancer (21–24). Of 136 cases of pathologic splenic rupture identified by Giagounidis et al. since 1861, 34% were acute leukemias, 34% were non-Hodgkin’s lymphomas, and 18% were CML (16). They also found a male-to-female ratio of 3:1. No cases in the literature were associated with ovarian cancer. SSR has been attributed to viruses such as EpsteinBarr, hepatitis, and HIV (30 –33). Bacterial causes range from common diseases such as pneumonia, meningococcemia, endocarditis, and tuberculosis to rare disorders such as dengue fever, Legionnaire’s disease, and Q fever (34 – 43). In addition, SSR has been associated with the fungal infection aspergillosis (43,44). Worldwide, the most common infectious agent associated with SSR is malaria (45,46). Numerous other diseases have been related to SSR. Pancreatitis has been commonly associated with it (43,44,47– 49). Rheumatologic diseases that have been
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associated with SSR include systemic lupus erythematosus, immune thrombocytopenic purpura, rheumatoid arthritis, polyarteritis nodosum, and Wegener’s granulomatosis (50 –56). SSR also has been reported during both pregnancy and the postpartum period (57– 61). At least five procedures have been associated with SSR: electroconvulsive therapy, implantation of automatic defibrillators, shock wave lithotripsy, colonoscopy, and transesophageal echocardiography (62– 67). There are a number of cases of SSR related to streptokinase and tissue plasminogen activation administration (1– 4). Heparin alone in i.v. doses also has been associated with SSR (5). Additionally, Ticlodopine was associated with SSR in two cases (68). There are no previously reported cases of SSR related to s.c. heparin therapy. There is debate in the literature over whether SSR without a precipitating cause actually exists (69). Multiple cases have been reported in which there appeared to be no underlying cause for the SSR (26,70 –72). While some authors have postulated a mechanism involving repeated torsions of the spleen from increased motility or spasm of the splenic vein leading to venous congestion, other authors believe that the entity simply does not exist (71). Splenic rupture should be considered in any patient with abdominal pain and shock, regardless of a history of trauma or previously known risk factors for spontaneous rupture. Free fluid on abdominal ultrasound in a hypo-
tensive patient should be considered to be blood until proven otherwise, even in a patient with known ascites. Loculations seen on abdominal ultrasound within peritoneal fluid can represent not only septae from longstanding ascites or spontaneous bacterial peritonitis but also areas of blood clots floating within ascites fluid or blood. In this case, the fluid was localized to the lesser sac and therefore may have appeared to be loculated on ultrasound. Serial blood counts may be a useful adjunct to serial examinations in a select group of patients admitted with abdominal pain of unclear etiology who are awaiting the appropriate confirmatory diagnostic studies. In summary, we report a case of spontaneous splenic rupture in a patient with ascites secondary to ovarian cancer (with no tumor invasion of the spleen) who was treated with s.c. heparin for DVT prophylaxis. This case is unusual since there was no history or diagnostic information suggestive of splenic rupture and the patient had multiple complicating factors (chemotherapy, elevated lipase, and ascites) that prevented an earlier diagnosis. In fact, the presentation clearly suggested that another diagnosis (bacterial peritonitis) was more likely. The paracentesis that may have returned blood and revealed the diagnosis was initially unobtainable. Not until the hematocrit dropped was the diagnosis of spontaneous splenic rupture entertained. This case points out various unique characteristics of spontaneous splenic rupture that should be kept in mind when evaluating patients with abdominal pain.
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