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(BQ) Part 2 book Oncologic emergencies has contents: Hematologic emergencies, chemotherapy related emergencies, palliative care in the emergency center, psychiatric emergencies, dermatologic emergencies, ophthalmologic emergencies,... and other contents.
© Springer Science+Business Media New York 2016 Ellen F Manzullo, Carmen Esther Gonzalez, Carmen P Escalante and Sai-Ching J Yeung (eds.), Oncologic Emergencies, MD Anderson Cancer Care Series, DOI 10.1007/978-1-4939-3188-0_10 10 Hematologic Emergencies Shuwei Gao1, Khanh Vu1, Francisca Gushiken2 and Khanh Thi Thuy Nguyen1 (1) Department of General Internal Medicine, Unit 428, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA (2) Department of Internal Medicine, South Texas Veterans Health Care System, San Antonio, TX, USA Khanh Thi Thuy Nguyen Email: Ktnguyen1@mdanderson.org Chapter Overview Introduction Acute Deep Venous Thrombosis and Pulmonary Embolism Clinical Manifestations Diagnosis of VTE Treatment of Acute VTE HVS Hyperleukocytosis Thrombocytosis Anemia Hemolytic Anemia Decreased Production of RBCs Thrombocytopenia Acute Hemorrhage Overview Assessment Management Blood Transfusion Reactions Acute Hemolytic Transfusion Reactions TRALI Bacterial Contamination Severe Allergic (Anaphylactic) Reactions Key Practice Points Suggested Readings Keywords Hematologic – Venous thromboembolism – Hyperviscosity – Anemia – Hemorrhage – Transfusion reaction Chapter Overview Hematologic emergencies are acute, life-threatening events Cancer, its treatments, and its baseline comorbidities can independently or collectively lead to hematologic emergencies requiring quick recognition, prompt diagnosis, and swift delivery of therapeutic interventions by frontline clinicians The hematologic emergencies frequently encountered in cancer patients described in this chapter include venous thromboembolism (VTE), hyperviscosity syndrome (HVS), anemia, thrombocytopenia, acute hemorrhage, and transfusion reactions Introduction Hematologic abnormalities are the most common medical issues in patients with all types of cancer Most of these problems are straightforward or chronic, such as chemotherapy-related bone marrow suppression presenting as anemia and thrombocytopenia However, some are acute, complex, and life-threatening, presenting as bona fide emergencies Examples are pulmonary embolism (PE), leukocytosis in patients with acute leukemia, and intracranial hemorrhage Compounding their complexity is the fact that diagnosis and management of hematologic emergencies often involve several specialists, including internal medicine physicians, hematologists, oncologists, procedurebased specialists, and surgeons Not uncommonly, multidiscipline collaborations are required Therefore, providing a practical integrated resource for clinicians in dealing with these emergencies is the goal of this chapter The two extreme pathologic manifestations of hematologic emergencies are thrombosis and bleeding Under the first two topics in this chapter—VTE and HVS—we describe the thrombotic processes and their clinical presentations, diagnosis, and treatments Under the next three topics— anemia, thrombocytopenia, and acute hemorrhage—we discuss the conditions that may lead to or be a consequence of bleeding Clinical descriptions, pathogenesis, differential diagnosis, diagnostic evaluation, and early management are reviewed and summarized in quickly referenced tables As part of the common interventions for hematologic emergencies, transfusion of the affected blood component can involve immunologic and nonimmunologic phenomena that range from benign to catastrophic Under the last topic, we review the spectrum of transfusion reactions and treatments We hope that this chapter provides understanding and early recognition of these common hematologic emergencies in cancer patients, leading to prompt diagnosis, early therapeutic intervention, and, thus, successful outcomes Acute Deep Venous Thrombosis and Pulmonary Embolism VTE, including both deep venous thrombosis (DVT) and PE, is a major complication of cancer Specifically, VTE is the second leading cause of death in patients with cancer (Lyman et al 2007) The risk of VTE in patients with cancer is 4- to 8-fold higher than that in individuals without it Furthermore, the risk of VTE is greatest in the first year, especially the first few months, after the cancer diagnosis (Blom et al 2005; Chew et al 2006) The risk of VTE is very high in patients who present with metastatic cancer Certain malignancies are associated with an increased VTE risk (e.g., pancreatic, gastric, colon, brain, kidney, ovarian, prostate, hematologic, lung) (Chew et al 2006) Use of certain medications to treat cancer, such as tamoxifen, erythropoietin, thalidomide, lenalidomide, and bevacizumab, has been associated with a high rate of VTE (Chew et al 2006) Clinical Manifestations Classical symptoms and signs of DVT are pain, swelling, redness, and warmness in the affected extremity or area Physical examination may reveal a palpable and tender cord, engorged superficial vein, painful and cyanotic limb if acute, and nearly total venous occlusion Common symptoms of acute PE include sudden-onset dyspnea, pleuritic chest pain, cough with or without hemoptysis, wheezing, and syncope in severe cases Common signs include tachypnea, tachycardia, rales or pleural rubs, an accentuated pulmonic component of the second heart sound (P2), jugular venous distension, and hypotension in severe cases Of note is that the diagnosis is proven in less than 25 % of cancer patients who present with a high clinical suspicion for VTE, whereas more than half of cancer patients with proven acute or subacute VTE have no typical symptoms or signs, with many patients having no symptoms at all Laboratory findings are nonspecific and include leukocytosis, an increased erythrocyte sedimentation rate, and an elevated serum lactate dehydrogenase (LDH) level in patients with VTE Brain natriuretic peptide and troponin levels are often increased in patients with significant PE, and these increased levels are associated with adverse outcomes (Meyer et al 2000; Sohne et al 2006) Arterial blood gas analysis usually reveals hypoxemia, hypocapnia, respiratory alkalosis, and elevated A-a gradients in patients with acute PE The level of D-dimer, a degradation product of cross-linked fibrin, is often elevated in cancer patients with or without VTE, limiting its use in the diagnosis of VTE in cancer cases (Carrier et al 2008) Electrocardiographic changes are common but nonspecific in patients with acute PE The most common of these changes are sinus tachycardia and nonspecific ST- and T-wave abnormalities Other electrocardiographic abnormalities are less common and include atrial fibrillation/flutter, right bundle branch block, precordial T-wave inversion, and inferior Q waves Chest X-rays can be normal, but more than 80 % of patients with acute PE have some radiographic changes resembling cardiomegaly, atelectasis, parenchymal abnormalities, hemidiaphragmatic elevation, and pleural effusion (Stein et al 1991) Diagnosis of VTE Because the symptoms and signs of VTE are nonspecific, variable, and common in patients with and without VTE, accurate diagnosis or exclusion of VTE relies on objective imaging studies However, a comprehensive history, a thorough physical examination, routine laboratory testing, electrocardiography, and chest X-rays are useful in suggesting alternative diagnoses, indicating the general severity of the patient’s illness and, most importantly, assessing the clinical probability of VTE Clinical prediction rules (such as the Wells and Geneva scores) (Wells et al 2001; Le Gal et al 2006), which have been used successfully to quantitatively assess the clinical probability of DVT and PE in the general population, should not be used in cancer patients because of a lack of validation Duplex compression ultrasonography (US) is widely recognized as the most cost-effective and the preferred imaging modality for the diagnosis of DVT in both the lower and upper extremities It is most sensitive (greater than 97 %) and specific in detecting symptomatic proximal DVT but markedly less sensitive in detecting distal DVT (53–73 %) and asymptomatic proximal DVT (62 %) Negative US results in patients with a high clinical suspicion for DVT should be interpreted cautiously In such cases, alternative imaging studies or repeat US within a week should be performed Contrast venography, an invasive procedure, is the historic and de facto gold standard for the diagnosis of DVT It has been largely replaced by noninvasive diagnostic modalities such as US, however Contrast venography is now very rarely used and reserved for situations such as when noninvasive studies are not feasible or the results of those studies are equivocal or discordant with clinical suspicion Computed tomography venography (CTV) has greater sensitivity and specificity than US in the evaluation of proximal DVT (Sampson et al 2007; Thomas et al 2008) It has several advantages over US, such as identification of extravascular sources of extrinsic compression that may underlie the cause of DVT as well as better detection of thrombi in pelvic veins (proximal external iliac vein, iliac vein, and inferior vena cava [IVC]) However, it has problems similar to those for contrast venography, such as exposure to ionizing radiation and iodinated contrast media, and it cannot be performed at bedside Magnetic resonance venography (MRV) has not been studied as widely as US or CTV However, several clinical studies have demonstrated that MRV is as sensitive and specific as US or CTV when evaluating proximal DVT (Sampson et al 2007) MRV does not expose the patient to ionizing radiation or iodinated contrast media Also, like CTV, MRV has the advantages over US of detecting pelvic DVT, delineating extravascular anatomy, and identifying nonthrombotic conditions that may mimic DVT Cost, availability, and use of unsafe devices are among the many limitations of and contraindications for MRV Radionuclide venography is a noninvasive modality that is not as sensitive or specific as US, but it is still a reasonable alternative to US, CTV, and MRV when those studies are not feasible Because radionuclide venography has yet to be validated in comparison with contrast venography or US in large prospective clinical trials, both positive and negative radionuclide venography findings should be confirmed using other diagnostic modalities if these findings are not strongly concordant with clinical suspicion of DVT Computed tomography pulmonary angiography (CTPA) has largely replaced ventilation and perfusion and become the primary modality for diagnosis of PE With improvements in this technology, new multidetector computed tomography scanners have become widely used and exhibited high sensitivity in detecting PE, particularly in the peripheral pulmonary arteries Therefore, a negative result of this sensitive modality is generally accepted as excluding PE without the need for additional imaging Pulmonary angiography, the reference standard for diagnosis of PE, is now used rarely and only when coupled with clot extraction or thrombolytic therapy V/Q scintigraphy (V/Q scan) is much less sensitive and specific than CTPA in detecting PE More than 50 % of patients must undergo additional testing after a V/Q scan because of nondiagnostic results Therefore, V/Q scans should be reserved for patients with contraindications for CTPA, such as uncorrectable contrast medium allergies and significant renal insufficiency A V/Q scan should be used if CTPA is not available or impossible in patients who are severely obese Interpretation of V/Q scan results for cancer patients should be correlated with the clinical probability of PE before testing A high-probability V/Q scan will confirm the diagnosis of PE unless the patient’s clinical probability is low Also, a normal V/Q scan safely excludes acute PE in patients whose clinical probability is not high However, a low-probability V/Q scan cannot be interpreted as negative for PE because 40 % of patients with low-probability scans but high clinical suspicion have PE (PIOPED Investigators 1990) Therefore, when a V/Q scan is nondiagnostic (low or moderate probability), additional testing, such as lower extremity US or CTPA, is necessary to confidently exclude or diagnose VTE Treatment of Acute VTE The goals of VTE treatment are to prevent death and recurrence and minimize long-term morbidity Because most VTE deaths result from recurrent PE within the first few hours after the initial event, effective antithrombotic therapy should be instituted as quickly as possible to decrease the likelihood of death (Carson et al 1992) Therefore, empiric anticoagulant therapy should be started during the diagnostic evaluation if the physician has a high clinical suspicion of VTE and the patient does not have an excessive risk of bleeding Supportive care, such as supplemental oxygen, intravenous (IV) fluid, mechanical ventilation, and vasopressors, should be provided as necessary to stabilize patients to complete their diagnostic evaluations and confirm diagnoses If PE is confirmed, the patients should undergo risk stratification at diagnosis by using readily available validated risk-assessment tools, such as the Pulmonary Embolism Severity Index (PESI) (Table 10.1) (Donze et al 2008) Acute VTE can be safely and effectively treated on an outpatient basis However, because of increased risk of an adverse outcome, initial anticoagulation therapy should be started in the hospital for patients with PESI scores greater than 85 or patients with the following conditions: severe PE or severe symptomatic DVT; a high risk of bleeding; thrombocytopenia; surgery within days; impaired heart, lung, liver, or kidney function; medical noncompliance; or lack of family support Patients with PESI scores greater than 85 also should have their right ventricular sizes and functions checked using echocardiography or reviews of computed tomography angiography Thrombolytic therapy should be considered for patients with massive PE or submassive PE with moderate or severe right ventricular enlargement or dysfunction and without a high risk of bleeding Embolectomy should be considered for patients with hemodynamic instability, a high risk of bleeding, or other contraindications for thrombolytic therapy Table 10.1 PESI Adverse outcome predictor Age in years Outcome point score per year Male sex +10 Cancer +30 Heart failure +10 Chronic lung disease +10 Heart rate ≥110 bpm +20 Systolic blood pressure