Enoxaparin-induced spontaneous massive retroperitoneal hematoma with fatal outcome Nikolaos S. Salemis, Ioannis Oikonomakis, Emanuel Lagoudianakis, Georgios Boubousis, Christos Tsakalakis, Sotirios Sourlas, Stavros Gourgiotis PII: DOI: Reference:
S0735-6757(14)00349-0 doi: 10.1016/j.ajem.2014.05.026 YAJEM 54309
To appear in:
American Journal of Emergency Medicine
Received date: Accepted date:
28 April 2014 14 May 2014
Please cite this article as: Salemis Nikolaos S., Oikonomakis Ioannis, Lagoudianakis Emanuel, Boubousis Georgios, Tsakalakis Christos, Sourlas Sotirios, Gourgiotis Stavros, Enoxaparin-induced spontaneous massive retroperitoneal hematoma with fatal outcome, American Journal of Emergency Medicine (2014), doi: 10.1016/j.ajem.2014.05.026
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT ENOXAPARIN-INDUCED SPONTANEOUS HEMATOMA WITH FATAL OUTCOME.
MASSIVE
RETROPERITONEAL
T
Nikolaos S. Salemis1, Ioannis Oikonomakis1, Emanuel Lagoudianakis1, Georgios Boubousis1, Christos Tsakalakis2, Sotirios Sourlas2, Stavros Gourgiotis3 1
Second Department of Surgery, 401 Army General Hospital, Athens, Greece ICU, 401 Army General Hospital, Athens, Greece 3 First Department of Surgery, 417 NIMTS Veterans' Fund Hospital, Athens, Greece
RI P
2
SC
Corresponding author: Nikolaos S. Salemis MD, PhD, FACS
MA NU
Consultant Surgical Oncologist
Head of 2nd Department of Surgery Army General Hospital, Athens, Greece 19 Taxiarhon Street, 19014 Kapandriti, Athens, Greece
ED
Email: [email protected].
CE
PT
Key words: Enoxaparin, retroperitoneal hematoma, spontaneous, fatal
AC
Sources of support: None
Conflicts of interest: None
Abbreviated title: Enoxaparin-induced fatal retroperitoneal hematoma
ACCEPTED MANUSCRIPT Abstract Spontaneous retroperitoneal hematoma (SRH) is a severe and potentially fatal
T
complication of anticoagulation therapy. We describe a case of fatal spontaneous
RI P
massive retroperitoneal hematoma in a female patient receiving bridging therapy with enoxaparin for atrial fibrillation. Physicians should be cautious when prescribing
SC
enoxaparin in elderly patients, in patients with impaired renal function and in patients receiving concomitant oral anticoagulants. Emergency physicians should always
MA NU
consider SRH in the differential diagnosis in patients under enoxaparin therapy presenting with abdominal pain. Computed tomography (CT) scan is the imaging modality of choice for evaluating SRH. Early diagnosis and aggressive treatment are
ED
of paramount importance as SRH is associated with high mortality and morbidity
PT
rates.
Spontaneous retroperitoneal hematoma (SRH) is defined as a retroperitoneal
CE
hemorrhage that is unrelated to trauma, surgery, invasive procedures or any
AC
underlying pathology [1]. It is a rare clinical entity associated with high mortality and morbidity rates [2]. Anticoagulation therapy has been associated with SRH. Sunga et al [1] reported that 66.3% of the patients diagnosed with SRH were anticoagulated. The incidence of SRH has been reported in 0.6-6.6% of the patients receiving anticoagulant therapy [3]. Although the exact etiology and pathogenesis of SRH has not been clearly defined, several hypotheses regarding potential predisposing factors have been proposed such as diffuse occult vasculopathy and arteriosclerosis of small retroperitoneal vessels, anticoagulation-induced immune microangiopathy, forceful muscular strain and unrecognized minor trauma [3,4]. We describe a case of
ACCEPTED MANUSCRIPT enoxaparin-induced massive spontaneous retroperitoneal hematoma with fatal
T
outcome and review the relevant literature.
RI P
A 75-year-old Caucasian female presented with a 12-hour history of gradually worsening left lower abdominal pain and tachycardia. Her medical history was
SC
significant for atrial fibrillation, arterial hypertension, chronic obstructive pulmonary disease and ischemic stroke. She had been on long-term therapy with warfarin which
MA NU
in the last seven days had been switched to bridging anticoagulation with enoxaparin (60mg/12h) due to a scheduled breast cancer surgery. She did not have any history of bleeding disorder or coagulopathy.
ED
Physical examination revealed a large tender mass measuring approximately 15x15cm in the left lower abdomen. The patient was tachycardic with a heart rate of 115
PT
beats/min, blood pressure of 90/70mmHg and an oxygen saturation of 95% on room air. Laboratory investigations revealed a white blood count of 35.1K/mL, hemoglobin
CE
of 8.9g/dl, hematocrit of 25.9%, platelets of 113K/Ml, blood urea nitrogen of 125.1
AC
mg/dl (range 20.0-50.0), creatinine 1.10 mg/dl (range 0.20-1.50), activated-partial thromboplastin time (APTT): 28.2s (range 26.0-38.0) and international normalized ratio (INR): 1.14 (range 0.85-1.15). Urinalysis revealed hematuria. An emergent contrast enhanced CT scan revealed a large retroperitoneal hematoma measuring 17x16cm involving the lower abdomen and pelvis (Fig. 1). The patient was admitted to the intensive care unit for hemodynamic monitoring. Enoxaparin was discontinued and the patient was tranfused with three units of packed red blood cells (PRBC), two units of fresh frozen plasma (FFP) and volume resuscitation with crystalloids.
ACCEPTED MANUSCRIPT Despite aggressive resuscitation the patient was hemodynamically unstable and her clinical status continued to deteriorate. Emergency angiography was obtained but
T
failed to localize any bleeding vessel. Due to the presence of hemodynamic instability
RI P
the patient underwent emergency laparotomy. A huge retroperitoneal hematoma was found displacing the left colon medially. There was no intraperitoneal bleeding. The
SC
retroperitoneal space was not explored because this maneuver was considered of high risk for worsening the bleeding due to the release of the tamponade effect. The
MA NU
abdomen was primarily closed after a pelvic drain was placed. Intraoperatively the patient received four units of RPBC and two units of FFP. Intraoperatively and after surgery the patient’s hemodynamic status stabilized. Unfortunately, twelve hours after
ED
surgery she suffered a cardiac arrest and died despite vigorous resuscitation.
PT
Low-molecular-weight heparins (LMWHs) have proven to be at least as safe and effective as unfractionated heparin for the prophylaxis and treatment of acute
CE
coronary syndrome, non-Q wave myocardial infarction, venus thrombosis and
AC
pulmonary thomboembolism [2,5]. Apart from safety and efficacy LMWH have several advatages over unfractionated heparin because of the decreased laboratory monitoring and the ability for administration in an oupatient setting [2,6]. Enoxaparin is a low molecular weight heparin which was approved by the US Food and Drug administration (FDA) in 1993 for the treatment of deep venous thrombosis and pulmonary embolism [7]. It is one of the mostly commonly prescribed LMWH both in Europe and US [8]. The use however of enoxaparin is not without risks. Several major bleeding events have been reported in patients treated with enoxaparin, such as abdominal wall
ACCEPTED MANUSCRIPT hematoma,
intrahepatic
hemorrhage,
thigh
hematoma,
psoas
hematoma,
retroperitoneal hematoma and spinal or epidural hematoma [8].
T
Spontaneous retroperitoneal hematoma is a severe complication of enoxaparin therapy
RI P
accounting for 5% of enoxaparin-induced complications [7]. It has been reported to occur within five days of therapy [2]. Less than twenty cases have been reported in
SC
the literature according to a review conducted by Quartey et al [7]. From our literature review we found ten cases of SRH with fatal outcome [6,8-13]. Table 1.
MA NU
The main risk factors for developing SRH are advanced age, impaired renal function, doses of enoxaparin approaching 1mg/kg, and concomitant administration of drugs that alter haemostasis [2,7,10].
ED
Clinical manifestations of SRH are highly variable and may be vague especially in the early stages thus resulting in delayed diagnosis [3]. Sunga et al [1] reported that
PT
10.1% of patients with SRH were misdiagnosed at initial presentation. Clinical signs and symptoms vary from abdominal or back pain to catastrophic hypovolemic shock
CE
[3,4,10]. Most common symptoms and signs of SRH include anterior abdominal pain,
AC
leg pain, hip pain, back pain, neurologic deficiencies hematuria and vomiting [1,6]. Signs of hypovolemic shock may also be present depending on the extent and duration of bleeding. Computed tomography (CT) scan is the diagnostic imaging modality of choice [1,3,6]. It is a rapidly obtainable and highly sensitive examination that can provide detailed information about the site and extent of SRH [3,6]. In addition, if the CT shows active extravasation of the contrast material, an emergency angiography and embolization of the bleeding vessel is indicated [3]. Early diagnosis and aggressive treatment of SRH is of paramount importance [1]. The management is multifactorial and should better be implemented in an intensive care
ACCEPTED MANUSCRIPT setting [2,11]. Basic principles of conservative management include discontinuation of enoxaparin, administration of protamine, PRBC, FFP and volume resuscitation.
T
Serial coagulation and hemoglobin measurements are essential [2,4,10,11].
RI P
Although most patients with SRH can be treated conservatively [3], surgical intervention has its role if conservative treatment fails. Surgery, however, is limited
SC
by the inability to locate the bleeding vessel and the risk of worsening the bleeding due to release of the tamponade effect [3,4]. Abdominal gauze packing may be the
MA NU
only surgical option if no specific arterial but general oozing is present [3,7]. If a diagnosis of abdominal compartment syndrome is made, a decompression laparostomy may be required [7]. Despite aggressive treatment, the mortality rate of
ED
SRH remains high [10].
In conclusion, SRH is a severe and potentially fatal complication of enoxaparin
PT
therapy. The case described here is the eleventh reported in the literature with fatal outcome. Phycisians should be cautious when prescribing enoxaparin in elderly
CE
patients, in patients with impaired renal function and in patients concomitantly
AC
receiving oral anticoagulants or antiplatelet agents. SRH should always be included in the differential diagnosis in patients under enoxaparin treatment presenting with abdominal pain. CT scan is the diagnostic imaging modality of choice. Early diagnosis and aggressive treatment are of paramount importance as SRH is associated with high mortality and morbidity rates.
References 1 Sunga KL, Bellolio MF, Gilmore RM, Cabrera D. Spontaneous retroperitoneal hematoma: etiology, characteristics, management, and outcome. J Emerg Med 2012;43:e157-61
ACCEPTED MANUSCRIPT 2 Ernits M, Mohan PS, Fares LG 2nd, Hardy H 3rd. A retroperitoneal bleed induced by enoxaparin therapy. Am Surg 2005;71:430-3
T
3 Chan YC, Morales JP, Reidy JF, Taylor PR. Management of spontaneous and
RI P
iatrogenic retroperitoneal haemorrhage: conservative management, endovascular
SC
intervention or open surgery? Int J Clin Pract 2008;62:1604-13
4 Won DY, Kim SD, Park SC, Moon IS, Kim JI. Abdominal compartment syndrome to
spontaneous
retroperitoneal
hemorrhage
MA NU
due
in
a
patient
undergoing
anticoagulation.Yonsei Med J 2011;52:358-61
5 Besir FH, Gul M, Ornek T, Ozer T, Ucan B, Kart L. Enoxaparin-associated giant
ED
retroperitoneal hematoma in pulmonary embolism treatment. N Am J Med Sci
PT
2011;3:524-6
CE
6 Lissoway J, Booth A. Fatal retroperitoneal hematoma after enoxaparin administration in a patient with paroxysmal atrial flutter. Am J Health Syst Pharm
AC
2010;67:806-9
7 Quartey B, Nelson J. Massive spontaneous retroperitoneal hemorrhage induced by enoxaparin and subsequent abdominal compartment syndrome requiring surgical decompression. A case report and literature review. IJCRI 2011;2: 14-18
8 Vayá A, Mira Y, Aznar J, Todolí J, Arguedas J, Solá E. Enoxaparin-related fatal spontaneous retroperitoneal hematoma in the elderly. Thromb Res 2003;110:69-71
ACCEPTED MANUSCRIPT 9 Montoya JP, Pokala N, Melde SL. Retroperitoneal hematoma and enoxaparin. Ann
T
Intern Med 1999;131:796-7
RI P
10 Fernández-Ruiz M, Guerra-Vales JM. Enoxaparin-induced retroperitoneal
SC
haematoma in patients with renal insufficiency. Swiss Med Wkly 2010;140:122-3
11 Chan-Tack KM. Fatal spontaneous retroperitoneal hematoma secondary to
MA NU
enoxaparin. South Med J 2003;96:58-60
12 Haq MM, Taimur SDM, Khan SR, Rahman MA. Retroperitoneal hematoma
ED
following enoxaparin treatment in an elderly woman. Cardiovasc J 2010;3:94-7
PT
13 Lee SH, Park JS, Kim W, Hong GR, Shin DG, Kim YJ, Shim BS. Enoxaparin induced fatal retroperitoneal hematoma in elderly patient with acute coronary
AC
CE
syndrome-Case report. Yeungham University J Med 2007;24:Suppl S642-646
Figure legends Figure 1. Contrast enhanced CT scan demostrating a huge retroperitoneal hematoma (stars) measuring 17x16cm involving the lower abdomen (A) and pelvis (B).
SC
RI P
T
ACCEPTED MANUSCRIPT
AC
CE
PT
ED
MA NU
Figure 1
ACCEPTED MANUSCRIPT Table 1. Enoxaparin-induced spontaneous retroperitoneal hematomas with
fatal
outcome. Sex/Age
Enoxaparin indication
Enoxaparin dose
Concomitant medication
1999
M/69
DVT
80mg/12h
Aspirin
Supportive
2003
F/77
DVT
100mg/12h
Acenocoumarol
Supportive
2003
F/B3
MI
1mg/kg/12h
Aspirin
Supportive
Lee
2007
M/83
UA
50mg/12h
Aspirin, Clopidogrel
Surgery
Fernandez10 Ruiz
2010
M/69 M/77 M/71
AF AF AF
80mg/12h 60mg/12h 80mg/12h
--------Aspirin
Supportive Supportive Supportive+ Embolization
AF
60mg/12h
-----
Chan-Tack
11
13
Haq12
PT
M/73
RI P
8
SC
Vaya
9
MA NU
Montoya
T
Year
ED
Author
Management
Supportive
F/66
MI
1mg/kg/12h
Aspirin, Clopidogrel
Supportive
Lissoway
2010
F/63
AF
80mg/12h
Aspirin
Supportive
Salemis
2014
F/75
AF
60mg/12h
--------
Surgery
AC
6
CE
2010
(present case)
Abbreviations: M: male, F: female, AF: atrial fibrillation, DVT: deep vein thrombosis MI: myocardial infarction, UA: unstable angina
S0735-6757(14)00349-0 doi: 10.1016/j.ajem.2014.05.026 YAJEM 54309
To appear in:
American Journal of Emergency Medicine
Received date: Accepted date:
28 April 2014 14 May 2014
Please cite this article as: Salemis Nikolaos S., Oikonomakis Ioannis, Lagoudianakis Emanuel, Boubousis Georgios, Tsakalakis Christos, Sourlas Sotirios, Gourgiotis Stavros, Enoxaparin-induced spontaneous massive retroperitoneal hematoma with fatal outcome, American Journal of Emergency Medicine (2014), doi: 10.1016/j.ajem.2014.05.026
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT ENOXAPARIN-INDUCED SPONTANEOUS HEMATOMA WITH FATAL OUTCOME.
MASSIVE
RETROPERITONEAL
T
Nikolaos S. Salemis1, Ioannis Oikonomakis1, Emanuel Lagoudianakis1, Georgios Boubousis1, Christos Tsakalakis2, Sotirios Sourlas2, Stavros Gourgiotis3 1
Second Department of Surgery, 401 Army General Hospital, Athens, Greece ICU, 401 Army General Hospital, Athens, Greece 3 First Department of Surgery, 417 NIMTS Veterans' Fund Hospital, Athens, Greece
RI P
2
SC
Corresponding author: Nikolaos S. Salemis MD, PhD, FACS
MA NU
Consultant Surgical Oncologist
Head of 2nd Department of Surgery Army General Hospital, Athens, Greece 19 Taxiarhon Street, 19014 Kapandriti, Athens, Greece
ED
Email: [email protected].
CE
PT
Key words: Enoxaparin, retroperitoneal hematoma, spontaneous, fatal
AC
Sources of support: None
Conflicts of interest: None
Abbreviated title: Enoxaparin-induced fatal retroperitoneal hematoma
ACCEPTED MANUSCRIPT Abstract Spontaneous retroperitoneal hematoma (SRH) is a severe and potentially fatal
T
complication of anticoagulation therapy. We describe a case of fatal spontaneous
RI P
massive retroperitoneal hematoma in a female patient receiving bridging therapy with enoxaparin for atrial fibrillation. Physicians should be cautious when prescribing
SC
enoxaparin in elderly patients, in patients with impaired renal function and in patients receiving concomitant oral anticoagulants. Emergency physicians should always
MA NU
consider SRH in the differential diagnosis in patients under enoxaparin therapy presenting with abdominal pain. Computed tomography (CT) scan is the imaging modality of choice for evaluating SRH. Early diagnosis and aggressive treatment are
ED
of paramount importance as SRH is associated with high mortality and morbidity
PT
rates.
Spontaneous retroperitoneal hematoma (SRH) is defined as a retroperitoneal
CE
hemorrhage that is unrelated to trauma, surgery, invasive procedures or any
AC
underlying pathology [1]. It is a rare clinical entity associated with high mortality and morbidity rates [2]. Anticoagulation therapy has been associated with SRH. Sunga et al [1] reported that 66.3% of the patients diagnosed with SRH were anticoagulated. The incidence of SRH has been reported in 0.6-6.6% of the patients receiving anticoagulant therapy [3]. Although the exact etiology and pathogenesis of SRH has not been clearly defined, several hypotheses regarding potential predisposing factors have been proposed such as diffuse occult vasculopathy and arteriosclerosis of small retroperitoneal vessels, anticoagulation-induced immune microangiopathy, forceful muscular strain and unrecognized minor trauma [3,4]. We describe a case of
ACCEPTED MANUSCRIPT enoxaparin-induced massive spontaneous retroperitoneal hematoma with fatal
T
outcome and review the relevant literature.
RI P
A 75-year-old Caucasian female presented with a 12-hour history of gradually worsening left lower abdominal pain and tachycardia. Her medical history was
SC
significant for atrial fibrillation, arterial hypertension, chronic obstructive pulmonary disease and ischemic stroke. She had been on long-term therapy with warfarin which
MA NU
in the last seven days had been switched to bridging anticoagulation with enoxaparin (60mg/12h) due to a scheduled breast cancer surgery. She did not have any history of bleeding disorder or coagulopathy.
ED
Physical examination revealed a large tender mass measuring approximately 15x15cm in the left lower abdomen. The patient was tachycardic with a heart rate of 115
PT
beats/min, blood pressure of 90/70mmHg and an oxygen saturation of 95% on room air. Laboratory investigations revealed a white blood count of 35.1K/mL, hemoglobin
CE
of 8.9g/dl, hematocrit of 25.9%, platelets of 113K/Ml, blood urea nitrogen of 125.1
AC
mg/dl (range 20.0-50.0), creatinine 1.10 mg/dl (range 0.20-1.50), activated-partial thromboplastin time (APTT): 28.2s (range 26.0-38.0) and international normalized ratio (INR): 1.14 (range 0.85-1.15). Urinalysis revealed hematuria. An emergent contrast enhanced CT scan revealed a large retroperitoneal hematoma measuring 17x16cm involving the lower abdomen and pelvis (Fig. 1). The patient was admitted to the intensive care unit for hemodynamic monitoring. Enoxaparin was discontinued and the patient was tranfused with three units of packed red blood cells (PRBC), two units of fresh frozen plasma (FFP) and volume resuscitation with crystalloids.
ACCEPTED MANUSCRIPT Despite aggressive resuscitation the patient was hemodynamically unstable and her clinical status continued to deteriorate. Emergency angiography was obtained but
T
failed to localize any bleeding vessel. Due to the presence of hemodynamic instability
RI P
the patient underwent emergency laparotomy. A huge retroperitoneal hematoma was found displacing the left colon medially. There was no intraperitoneal bleeding. The
SC
retroperitoneal space was not explored because this maneuver was considered of high risk for worsening the bleeding due to the release of the tamponade effect. The
MA NU
abdomen was primarily closed after a pelvic drain was placed. Intraoperatively the patient received four units of RPBC and two units of FFP. Intraoperatively and after surgery the patient’s hemodynamic status stabilized. Unfortunately, twelve hours after
ED
surgery she suffered a cardiac arrest and died despite vigorous resuscitation.
PT
Low-molecular-weight heparins (LMWHs) have proven to be at least as safe and effective as unfractionated heparin for the prophylaxis and treatment of acute
CE
coronary syndrome, non-Q wave myocardial infarction, venus thrombosis and
AC
pulmonary thomboembolism [2,5]. Apart from safety and efficacy LMWH have several advatages over unfractionated heparin because of the decreased laboratory monitoring and the ability for administration in an oupatient setting [2,6]. Enoxaparin is a low molecular weight heparin which was approved by the US Food and Drug administration (FDA) in 1993 for the treatment of deep venous thrombosis and pulmonary embolism [7]. It is one of the mostly commonly prescribed LMWH both in Europe and US [8]. The use however of enoxaparin is not without risks. Several major bleeding events have been reported in patients treated with enoxaparin, such as abdominal wall
ACCEPTED MANUSCRIPT hematoma,
intrahepatic
hemorrhage,
thigh
hematoma,
psoas
hematoma,
retroperitoneal hematoma and spinal or epidural hematoma [8].
T
Spontaneous retroperitoneal hematoma is a severe complication of enoxaparin therapy
RI P
accounting for 5% of enoxaparin-induced complications [7]. It has been reported to occur within five days of therapy [2]. Less than twenty cases have been reported in
SC
the literature according to a review conducted by Quartey et al [7]. From our literature review we found ten cases of SRH with fatal outcome [6,8-13]. Table 1.
MA NU
The main risk factors for developing SRH are advanced age, impaired renal function, doses of enoxaparin approaching 1mg/kg, and concomitant administration of drugs that alter haemostasis [2,7,10].
ED
Clinical manifestations of SRH are highly variable and may be vague especially in the early stages thus resulting in delayed diagnosis [3]. Sunga et al [1] reported that
PT
10.1% of patients with SRH were misdiagnosed at initial presentation. Clinical signs and symptoms vary from abdominal or back pain to catastrophic hypovolemic shock
CE
[3,4,10]. Most common symptoms and signs of SRH include anterior abdominal pain,
AC
leg pain, hip pain, back pain, neurologic deficiencies hematuria and vomiting [1,6]. Signs of hypovolemic shock may also be present depending on the extent and duration of bleeding. Computed tomography (CT) scan is the diagnostic imaging modality of choice [1,3,6]. It is a rapidly obtainable and highly sensitive examination that can provide detailed information about the site and extent of SRH [3,6]. In addition, if the CT shows active extravasation of the contrast material, an emergency angiography and embolization of the bleeding vessel is indicated [3]. Early diagnosis and aggressive treatment of SRH is of paramount importance [1]. The management is multifactorial and should better be implemented in an intensive care
ACCEPTED MANUSCRIPT setting [2,11]. Basic principles of conservative management include discontinuation of enoxaparin, administration of protamine, PRBC, FFP and volume resuscitation.
T
Serial coagulation and hemoglobin measurements are essential [2,4,10,11].
RI P
Although most patients with SRH can be treated conservatively [3], surgical intervention has its role if conservative treatment fails. Surgery, however, is limited
SC
by the inability to locate the bleeding vessel and the risk of worsening the bleeding due to release of the tamponade effect [3,4]. Abdominal gauze packing may be the
MA NU
only surgical option if no specific arterial but general oozing is present [3,7]. If a diagnosis of abdominal compartment syndrome is made, a decompression laparostomy may be required [7]. Despite aggressive treatment, the mortality rate of
ED
SRH remains high [10].
In conclusion, SRH is a severe and potentially fatal complication of enoxaparin
PT
therapy. The case described here is the eleventh reported in the literature with fatal outcome. Phycisians should be cautious when prescribing enoxaparin in elderly
CE
patients, in patients with impaired renal function and in patients concomitantly
AC
receiving oral anticoagulants or antiplatelet agents. SRH should always be included in the differential diagnosis in patients under enoxaparin treatment presenting with abdominal pain. CT scan is the diagnostic imaging modality of choice. Early diagnosis and aggressive treatment are of paramount importance as SRH is associated with high mortality and morbidity rates.
References 1 Sunga KL, Bellolio MF, Gilmore RM, Cabrera D. Spontaneous retroperitoneal hematoma: etiology, characteristics, management, and outcome. J Emerg Med 2012;43:e157-61
ACCEPTED MANUSCRIPT 2 Ernits M, Mohan PS, Fares LG 2nd, Hardy H 3rd. A retroperitoneal bleed induced by enoxaparin therapy. Am Surg 2005;71:430-3
T
3 Chan YC, Morales JP, Reidy JF, Taylor PR. Management of spontaneous and
RI P
iatrogenic retroperitoneal haemorrhage: conservative management, endovascular
SC
intervention or open surgery? Int J Clin Pract 2008;62:1604-13
4 Won DY, Kim SD, Park SC, Moon IS, Kim JI. Abdominal compartment syndrome to
spontaneous
retroperitoneal
hemorrhage
MA NU
due
in
a
patient
undergoing
anticoagulation.Yonsei Med J 2011;52:358-61
5 Besir FH, Gul M, Ornek T, Ozer T, Ucan B, Kart L. Enoxaparin-associated giant
ED
retroperitoneal hematoma in pulmonary embolism treatment. N Am J Med Sci
PT
2011;3:524-6
CE
6 Lissoway J, Booth A. Fatal retroperitoneal hematoma after enoxaparin administration in a patient with paroxysmal atrial flutter. Am J Health Syst Pharm
AC
2010;67:806-9
7 Quartey B, Nelson J. Massive spontaneous retroperitoneal hemorrhage induced by enoxaparin and subsequent abdominal compartment syndrome requiring surgical decompression. A case report and literature review. IJCRI 2011;2: 14-18
8 Vayá A, Mira Y, Aznar J, Todolí J, Arguedas J, Solá E. Enoxaparin-related fatal spontaneous retroperitoneal hematoma in the elderly. Thromb Res 2003;110:69-71
ACCEPTED MANUSCRIPT 9 Montoya JP, Pokala N, Melde SL. Retroperitoneal hematoma and enoxaparin. Ann
T
Intern Med 1999;131:796-7
RI P
10 Fernández-Ruiz M, Guerra-Vales JM. Enoxaparin-induced retroperitoneal
SC
haematoma in patients with renal insufficiency. Swiss Med Wkly 2010;140:122-3
11 Chan-Tack KM. Fatal spontaneous retroperitoneal hematoma secondary to
MA NU
enoxaparin. South Med J 2003;96:58-60
12 Haq MM, Taimur SDM, Khan SR, Rahman MA. Retroperitoneal hematoma
ED
following enoxaparin treatment in an elderly woman. Cardiovasc J 2010;3:94-7
PT
13 Lee SH, Park JS, Kim W, Hong GR, Shin DG, Kim YJ, Shim BS. Enoxaparin induced fatal retroperitoneal hematoma in elderly patient with acute coronary
AC
CE
syndrome-Case report. Yeungham University J Med 2007;24:Suppl S642-646
Figure legends Figure 1. Contrast enhanced CT scan demostrating a huge retroperitoneal hematoma (stars) measuring 17x16cm involving the lower abdomen (A) and pelvis (B).
SC
RI P
T
ACCEPTED MANUSCRIPT
AC
CE
PT
ED
MA NU
Figure 1
ACCEPTED MANUSCRIPT Table 1. Enoxaparin-induced spontaneous retroperitoneal hematomas with
fatal
outcome. Sex/Age
Enoxaparin indication
Enoxaparin dose
Concomitant medication
1999
M/69
DVT
80mg/12h
Aspirin
Supportive
2003
F/77
DVT
100mg/12h
Acenocoumarol
Supportive
2003
F/B3
MI
1mg/kg/12h
Aspirin
Supportive
Lee
2007
M/83
UA
50mg/12h
Aspirin, Clopidogrel
Surgery
Fernandez10 Ruiz
2010
M/69 M/77 M/71
AF AF AF
80mg/12h 60mg/12h 80mg/12h
--------Aspirin
Supportive Supportive Supportive+ Embolization
AF
60mg/12h
-----
Chan-Tack
11
13
Haq12
PT
M/73
RI P
8
SC
Vaya
9
MA NU
Montoya
T
Year
ED
Author
Management
Supportive
F/66
MI
1mg/kg/12h
Aspirin, Clopidogrel
Supportive
Lissoway
2010
F/63
AF
80mg/12h
Aspirin
Supportive
Salemis
2014
F/75
AF
60mg/12h
--------
Surgery
AC
6
CE
2010
(present case)
Abbreviations: M: male, F: female, AF: atrial fibrillation, DVT: deep vein thrombosis MI: myocardial infarction, UA: unstable angina
