A 77 year-old male h/o asthma, HTN, HLD, recently diagnosed CML presents with pain to recent bone marrow biopsy site and right lower extremity pain such that he cannot walk since last night. He also c/o nausea with few episodes of NBNB vomiting. He was prescribed imatinib but has not started it yet. He is having normal stools and passing flatus. He was admitted to the hospital last week for a malignancy workup after presenting with malaise and fever with a WBC of 68,000. An inpatient bone marrow biopsy was performed that confirmed CML with philadelphia chromosome.
ROS: +subjective fevers; otherwise negative
Meds: amlodipine, statin
SH: Emigrated from middle east, no toxic habits
VS: HR 94 RR 20 BP 117/65 T 97.5F SaO2 97% FSG 231
Gen: Ill-appearing man in distress secondary to pain
HEENT: Intact, atraumatic, MMM, PERRLA, no scleral icterus, oropharynx wnl
Neck: No LAD, no thyromegaly or nodules, supple
CV: RRR, no M/R/G
Resp: CTA b/l
Abd: Distended, diffuse mild tenderness, BS present, no CVA tenderness, no spinal tenderness or abnormalities, biopsy site with some induration but no fluctuance or erythema
Skin: Warm, dry, no rash
Extremities: No edema, cyanosis, or clubbing
Neuro: RLE weakness due to pain
EKG: Sinus tachycardia @108/min with normal axis, normal intervals; no ST elevations, isolated T inversion with ST depression in lead III.
iCa 4.46, creatinine 1.57, K+ 5.1, Na 131, Cl 102, Glucose 242, Lactate 1.7
UA: trace ketones, negative nitrite/LE/hemoglobin, 0-5 RBCs, 5-10 WBCs, 20-50 epithelial cells
ED Course: Th presenting symptoms and elevated potassium and creatinine were concerning for tumor lysis syndrome, so crystalloid bolus was given. Morphine was given for pain. FAST revealed air in bowel but no free intraperitoneal fluid. Patient had persistent pain and had an episode of coffee ground emesis, after which he became tachycardic with notable increase in abdominal distension. He was given pantoprazole and ondansetron. A nasogastric tube was placed to intermittent suction. Uric acid and lactate dehydrogenase levels were significantly elevated. Hemoglobin was noted to be 1-2 g/dl lower than previous level a day prior so 2 units of pRBC’s were ordered. CT abdomen/pelvis with IV contrast demonstrated retroperitoneal hematoma with possible active bleeding (“blush”). Hematology, Surgery, Critical Care Medicine, and Interventional Radiology (IR) services were consulted. As per consultant recommendations, allopurinol was given, and the patient was sent to the IR suite for angioembolization. No bleeding vessel was found and he was admitted to the MICU for further management of tumor lysis syndrome and retroperitoneal hematoma.
Creatinine continued to rise until HD2 before it began to improve and return to baseline levels. Rasburicase was initially recommended by Hematology but was never given – the G6PD level took days to return, and the patient’s kidney function had already begun to recover. During his workup, it was noted he had hepatitis B and thus was not started on imatinib. On HD3, he developed increased right hip pain, and a lower extremity venous duplex ultrasound showed no DVT or pseudoaneurysm. He returned to the IR suite, and a bleeding right iliopsoas artery was embolized. He received an additional 2 units of pRBCs. On HD6 he was downgraded to the medical floor and then days later signed out against medical advice.
Retroperitoneal hematoma (RPH) is a hemorrhage contained within the retroperitoneum. It can be life threatening and difficult to diagnose due to its nonspecific presentation. Symptoms can include abdominal pain, back pain, leg or hip pain, neurological deficits, hematuria, or vomiting. Patients may also present with hypovolemic shock depending on the amount of hemorrhage that has occurred. Risk factors for the development of RPH include anticoagulation, invasive procedures involving the abdomen or flanks, trauma, coagulopathies and even simply exercise or coughing (1,2). They can also occur spontaneously, usually associated with antiplatelet or anticoagulant use, advanced age, or impaired renal function (2,3). The retroperitoneum is divided into three anatomical zones that can determine management. Zone I (central RP) includes the area medial to the renal hila encompassing the abdominal aorta, inferior vena cava, proximal renal vasculature, pancreas, and part of the duodenum. Zone II (lateral RP) contains the adrenals, kidneys, and proximal genitourinary tract. Zone III (pelvic RP) contains the rectum, iliac vessels, and their branches (1).
In our case, the patient’s RPH arose from a zone III bleed that was likely secondary to his bone marrow biopsy. Bone marrow biopsy is a relatively safe procedure, with the majority of complications involving pain at the site. Rare, but more serious complications include infections, neuropathy, fractures, needle breaks, retropneumoperitoneum, and RPH (4,5). A 2002 survey, conducted in the UK found an adverse event rate of 0.12%. The most common serious adverse event was hemorrhage which led to three deaths. A follow-up survey in 2004 found similar results and revealed that a diagnosis of myeloproliferative neoplasm was an independent risk factor for serious bleeding after BM biopsy (4).
RPH is difficult to diagnose clinically. CT is the ideal diagnostic modality as it is noninvasive, highly sensitive, and can also demonstrate active extravasation if contrast-enhanced in order to help localize source of bleeding (2,5,6). CT scan also has the benefit of being able to diagnose other possible etiologies of the patient’s symptoms. In a small study of ED patients with non-traumatic, non-iatrogenic, non-aortic cases of RPH, there was 100% sensitivity of CTA for detecting RPH and in 63% of patients demonstrated active contrast extravasation. CT was also able to identify the exact source of bleed in 40% of cases (6). In an observational cohort study by Sunga et al, ultrasound was able to diagnose spontaneous RPH in 12 of 19 cases in which ultrasound was utilized. In my literature search, I was unable to find any studies that evaluated the use of ultrasound specifically for the diagnosis of RPH (2). Theoretically, this diagnosis could readily be made with ultrasound if due to a ruptured abdominal aortic aneurysm. However, other etiologies of RPH may be much more difficult to diagnose, and ultrasound would be unable to localize the source of the bleed. CT is the preferred diagnostic tool.
The tenets of RPH management include addressing inciting factors such as anticoagulation use (reversal as indicated), transfusion of blood products, and supportive care (2,3,7). Patients with RPH should be monitored in an intensive care setting as they are at high risk of decompensation. For active bleeds, angioembolization via interventional radiology may be the preferred treatment strategy; however, there remains a small role for surgical decompression (2,5,8). If the patient fails embolization or there are significant neurological symptoms, abdominal compartment syndrome, or has other concomitant surgical issues, laparotomy may be indicated (2,8). Surgical decompression also carries a risk of worsening hemorrhage since doing so may in fact remove the tamponade effect on the bleeding artery (8). All RPHs due to penetrating trauma and all zone I injuries should be considered for surgical exploration due to risk of injury to vital vascular structures. Zone II and III should only be explored after blunt injury if there is pulsatile or expanding RPH (1).
Tumor Lysis Syndrome (TLS)
Tumor lysis syndrome (TLS) is an uncommon complication of malignancies that can be life-threatening. It often occurs early in the diagnosis and treatment of highly proliferative malignancies and is defined by specific lab abnormalities that result from the destruction of malignant cells. It can occur spontaneously but is most often precipitated by induction of chemotherapy, radiation, or high dose steroid therapy (9,10).
As cancer cells are lysed, intracellular contents are released, such as potassium, phosphorus, proteins, and nucleic acids. Hyperkalemia is the most concerning electrolyte abnormality of TLS as it can lead to neuromuscular weakness, GI distress, cardiac arrhythmia, and death. As the body catabolizes the released purine nucleic acids via xanthine oxidase, serum uric acid levels are increased. Calcium levels are decreased through increased phosphate binding. Uric acid is renally eliminated, but the high uric acid loads can overwhelm the kidney’s clearance rate, resulting in crystal formation, deposition, and renal failure. The risk of developing TLS is further stratified based upon the specific malignancy involved, the choice of chemotherapeutic agents, comorbid medical conditions, and baseline serum uric acid (9,10). The following table groups malignancies by risk for developing TLS.
It is important to distinguish between patients who present with the lab abnormalities of TLS and patients with clinical manifestations of TLS. The Cairo-Bishop definition of laboratory tumor lysis syndrome is defined as at least two of the following alterations of metabolites three days before through seven days after starting anticancer treatment. Lactate dehydrogenase levels will be elevated due to cell lysis, but this is not a diagnostic criteria for TLS. Clinical TLS is defined as laboratory TLS AND either renal failure, cardiac arrhythmias, or seizures (10).
The most important intervention for the management of TLS is prevention with close electrolyte monitoring, hydration, and allopurinol. However, when these patients present to the ED, the cornerstone of management will be aggressive fluid hydration with a goal urine output of 80-100 mL per square meter body surface area per hour. This translates to roughly 150-200 mL/hr of urine output for your standard 70 kg patient with normal BMI. Hyperkalemia will be treated as it would normally be treated from other etiologies, except with cautious calcium administration. The hypocalcemia of TLS generally resolves without repletion, especially if the hyperphosphatemia is treated. Phosphate binders can be given, in addition to fluid hydration or hemodialysis, to decrease phosphate levels. Asymptomatic hypocalcemia should not be treated with calcium repletion as the risk of metatstatic calcification from elevated phosphate levels is high. For this reason, caution is advised when administering calcium for hyperkalemia. However, if the patient is peri-arrest or has ECG changes associated with hyperkalemia, calcium must be given and hemodialysis should be considered if other treatments fail. Urine alkalinization is not routinely recommended, as it can precipitate calcium-phosphorus or xanthine crystals, further exacerbating electrolyte abnormalities and increasing risk for clinical TLS (9,10).
For the acute treatment of hyperuricemia, allopurinol is not recommended as it decreases the production of uric acid, but not decrease the already elevated uric acid levels. Furthermore, allopurinol must be renally dosed, may produce xanthine nephropathy and calclui, increases risk for Stevens-Johnson Syndrome, and has a slow onset of action of 24-72 hours. Rasburicase is a recombinant urate-oxidase, produced by Aspergillus flavus, that humans are unable to synthesize. Urate-oxidase converts uric acid to allantoin, which is soluble in urine and allows it to be renally eliminated. Its use is contraindicated in G6PD-deficiency since hydrogen peroxide is a byproduct of the urate-oxidase reaction. Rasburicase is well tolerated and can be given in a single dose of 3 mg or 6 mg, with the latter providing larger decreases in serum uric acid but without clear improvement in patient oriented outcomes (10). Administration of rasburicase in the ED should be strongly considered based on patient presentation and in consultation with hematology/oncology.
Certain factors put the patient in our case at an increased risk for RPH due to a post-procedural complication. He was on daily aspirin and enoxaparin for DVT prophylaxis prior to the bone marrow biopsy, in addition to having philadelphia chromosome-positive CML. CML put our patient at lower risk for TLS, however, he was not started on allopurinol, and the RPH may have reduced renal perfusion and contributed to the development of TLS.
- Characterized by ↑ Postassium ↑ Phosphate ↑ Uric Acid ↓Calcium
- Clinical manifestations: Renal failure, seizures, cardiac arrest
- “B” malignancies are higher risk – B-ALL and Burkitt’s lymphoma
- Treatment: IV hydration, phosphate binders, insulin/D50, rasburicase
- Diagnosis: CTA abdomen/pelvis or CT abdomen/pelvis with IV contrast (contrast is not required to diagnose RPH)
- Consider in patients on anticoagulant/antiplatelet agents, patients s/p invasive abdominal/pelvic procedures, trauma, coagulopathies
- Consult IR
- Kasotakis G. Retroperitoneal and rectus sheath hematomas. Surg CLin N Am (2014);94:71-76
- Sunga KL, Bellolio MF, Gilmore RM, Cabrera D. Spontaneous retroperitoneal hematoma: etiology, characteristics, management, and outcome. The Journal of Emergency Medicine (2012);43(2):157-161
- Salemis NS, Oikonomakis I, Lagoudianakis E, et al. Enoxaparin-induced spontaneous massive retroperitoneal hematoma with fatal outcome. Am J Emerg Med. 2014;32(12):1559e1–1559e3
- Wan Jamaludin W.F. et al. Retroperitoneal hemorrhage associated with bone marrow trephine biopsy. American Journal of Case Reports (2013);14:489-493
- Al Zahrani Y, Peck D. Median sacral artery injury following a bone marrow biopsy successfully treated with selective trans-arterial embolization: a case report. Journal of Medical Case Reports (2016);10(42):1-4
- Caleo, O., Bocchini, G., Paoletta, S. et al. Radiol med (2015) 120: 133. doi:10.1007/s11547-014-0482-0
- Neesse A, Kalinowski M, Walthers EM, Gorg C, Neubauer A. Clinical management of massive retroperitoneal hemorrhage after bone marrow biopsy. Leukemia & Lymphoma. March 2009;50(3):475-477
- Chan Y, Morales J, Reidy J, Taylor P. Management of spontaneous and iatrogenic retroperitoneal haemorrhage: conservative management, endovascular intervention or open surgery?. International Journal Of Clinical Practice [serial online]. October 2008;62(10):1604-1613.
- Pi J, Kang Y, Smith M, Earl M, Norigian Z, McBride A. A review in the treatment of oncologic emergencies. Journal of Oncology Pharmacy Practice. October 2016;22(4):625-638
- Criscuolo, L. Fianchi, G. Dragonetti & L. Pagano. Tumor lysis syndrome: review of pathogenesis, risk factors and management of a medical emergency. Expert Review of Hematology. 2016;9(2):197-208
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