Presentation on theme: "Onchematologic emergencies"— Presentation transcript:
1 Onchematologic emergencies Dr. Demeter JuditSemmelweis Egyetem ÁOK., I.sz. Belgyógyászati Klinika
2 Onkohematologic emergencies Hemodynamic - vena cava superior syndrom NHL - pericardial tamponade lymphomas - hyperviscosity syndrome MM, Wald. - thrombosis myeloprolif.Hematologic - bleeding qualitative-quantitive pathologies of platelets ITP lack of coagulation factors DIC (M3)Nervous system - spinal cord compression NHL, MM immediate MR! - koponyaűri nyomásfokozódás NHLMetabolic - tumorlysis syndrome hyperuricaemia, hyperkalaemia - hypercalcaemia MM, NHL - hypokalaemia AML - hypoglykaemia insulinomaOther - TTP/HUS
3 Incidence:number of patients with hematologic and oncologic malignancies is increasingThe number of patients presenting with hemato-oncologic emergencies is expected to be increasing
4 Prospects:patients cancer no longer should be looked upon as incurable and terminal even not even in the emergency departmentsPatients are to some degree amenable to therapy or interventionFollowing the succcesful treatment of an emergency condition, these patients may lead relatively normal lives.
5 mechanical emergencies 1.neutropenic fever.the most common !mechanical emergenciesairway obstruction,superior vena cava syndromecardiac tamponadespinal cord compression.metabolic emergencies.hyperviscosity syndromehypercalcemiasyndrome of inappropriate antidiuretic hormone secretion (SIADH)acute tumor lysis syndrome.Often missed! superior sulcus lung tumor (Pancoast syndrome).
6 Infectious Emergencies Neutropenic Fever appropriate recognition and management may significantly lessen morbidity and mortality!Neutropeniaabsolute granulocyte count is < 500 cells/µLor < 1000 cells/µL with an anticipated decrease to < 500 cells/µL.nadir mostly between 2-4 weeks after chemotherapyFever if if temperature exceeds >38.3° (101° F) orif the temperature = 38.0° C (100.4° F) for > 1 hour.
7 lack of circulating white blood cells. few of the classic signs and symptoms of bacterial infectionse.g. significant pneumonia without cough or infiltrates on plain film. urinary tract infectionwithout WBC deposition in the urinary tract , lack of dysuria and frequency.meningitis may present without clinical evidence of meningismus or cerebral spinal fluid pleocytosis.Febrile neutropenia: cultures of blood and urinechest x-ray performed (chest CT even better!)if indwelling central line : at least one set of blood culture through it!
8 Immediate empiric antibiotic therapy! ( because progression of infection in neutropenicpatients may be very rapid)Initial antibiotic therapy should be tailored to the suspected offending pathogens.In the not too distant past, neutropenic patients were covered with two antibiotics, typically a third-generation cephalosporin in combination with an aminoglycoside. Traditionally, G-negative bacilli ( Pseudomonas, E coli, and Klebsiella): most common offending pathogens.Nowadays: increase in the rate of infections caused by gram-positive bacteria, (some of them methicillin-resistant) .Staphylococcus aureuscoagulase-negative staphylococci most common causes, particularly in patients with an indwelling catheterRecommended: single agent antimicrobial therapy (monotherapy).third or fourth-generation cephalosporin (ceftazidime or cefipime)or a carbapenem (imipenem-cilastatin or meropenem)
9 clinically-suspected serious catheter-related infections . Include vancomycin in the treatment if:clinically-suspected serious catheter-related infectionsknown colonization with methicillin-resistant Staphylococcus aureuspositive results of blood culture for gram-positive bacteria before final identification and susceptibility are knownhypotension or other clinical evidence of cardiovascular impairmentGrowth factor treatment: filgrastim (Neupogen).stimulates WBC productionreduces the duration of neutropenia and fever,reduces the requirement of parenteral antibioticsreduces the duration of hospitalization.safe even in acute leukemiaGranulocyte transfusion not recommended!
10 Management of neutropenic fever 1. initial antibiotic of choice:third or fourth generation cephalosporin or a carbapenem.(single agent therapy)2. Cultures of blood and urine !3. Consider chest CT if pulmonary symptoms present (active pulmonary infections may be present despite normal chest x-rays)4. Vancomycin if indwelling intravenous catheter infection suspected(in addition to gram-negative coverage).5. rapid institution of empiric antibiotic therapy reduces morbidity and mortality.6. reverse isolation room.
11 Mechanical Emergencies: Spinal Cord Compressionany patient who presents with back pain may have spinal cord compression due to malignancy!
12 She developed paralysis and incapacitating pain. disseminated metastatic breast cancer to bone (after both chemotherapy and radiation therapy).She developed paralysis and incapacitating pain.MRI image: extensive bone tumor with collapse of the T10 and T11 vertebrae resulting in spinal cord compression.
13 Epidural spinal cord compression devastating complication of many malignanciesbreastlungprostate cancerAML (chloroma)muItiple myelomaFrequency ca. 5%Importance of early detection in remaining ambulatory!
14 Epidural spinal cord compression Might be the first clinical manifestation of malignancy.Pts with known diagnosis of cancer (breast, lung, prostate, renal) + back painpotentially lethal back pain entitiescancercauda equina syndromeabdominal aortic aneurysm,back pain and a history of malignancy should be assumed to be metastasis to the spine or epidural spinal cord compression until proven otherwise
15 Epidural spinal cord compression Presenting symptomsnumbnesstinglingsensory lossbowel or bladder incontinenceabnormalities of proprioception e.g.loss of vibratory senseback pain worsened by particular maneuvers, such as (coughing or lying in a supine positionpain that is worse at night.New-onset radiculopathy from compression of a spinal root may also be the first manifestation of tumor (DDG: A herniated disc)
16 Epidural spinal cord compression The physical examination may show evidence of spinal cord compression with paralysis or may be completely normal and unrevealing.A detailed motor, sensory, and deep tendon reflex examination should be performed in all patients with suspected spinal cord compression, as well as observation of gait and evaluation of sphincter tone
17 Epidural spinal cord compression think about the diagnosis in patients with back pain!Dg-ic workup: Magnetic resonance imagingepidural spinal cord compression can be subtle, and detection requires a high index of suspicion!Treatment:high dose corticosteroids - decompressive laminectomy - radiation
18 Epidural spinal cord metastasis and/or compression. Pain may be the only finding !Suspicious: Pain worsened by cough or the supine position2. Physical examination:midline bony tenderness (often absent),ataxic gaitweaknessautonomic dysfunction (bowel or bladder incontinence).3. Corticosteroids –iv. immediately!4. Think about the diagnosis!
19 Superior Vena Cava Syndrome becomes an emergency with the development ofcerebral edema (life-threatening cerebral herniation)orlaryngeal edema (leading to airway compromise)Causes: ( tuberculosis, aortic aneurysm, and fibrosing mediastinitis)Nowadays: lung carcinomalymphomacatheter-related superior vena cava thrombosis.
20 Thickening of the prevertebral soft tissue shadow indicates laryngeal edema
21 Superior Vena Cava Syndrome Clinical manifestations:proteandepend on the degree of vena cava obstruction.Fom relatively asymptomatic with only mild facial fullness when bending forward or may have florid symptoms of facial swelling, headache, and airway compromise.
22 A clue to the diagnosis is the presence of asymmetric neck, chest, or upper arm venous distension. One diagnostic tool that has been employed by some is to compare the patient’s appearance to that of a picture of the patient, often a driver’s licenseSubtle and sometimes marked changes in the physical appearance of the patient’s face can be identified.
23 The key to understanding the variability of the clinical presentation is the anatomy of the azygous vein.The azygous vein is a large vessel that enters the proximal superior vena cava and drains blood from the thorax.Obstruction above the level of the azygous entry point may lead to relatively few symptoms due to the ability of the azygous to decompress the upper extremities, head, and neck.If a compressive lesion or thrombus obstructs the SVC below the entry point there is no mechanism for upper torso, head, and neck decompression, and patients may present with marked venous collateral formation and facial swelling on examination .
28 Superior vena cava syndrome Traditional teaching : most patients present with a sensation of facial fullness, facial swelling, cough, variable arm swelling, and dilated neck and upper chest wall veins, with these it would not be a difficult diagnosis to make.However, this oncologic entity may present with few if any clinical findings.Further frequent symptom:sensation of fullness when bending forwardor a vague, chronic cough.However, if venous decompression is able to occur, there will be no prominent veins or facial swelling the diagnosis may not even be considered.
29 Depiction of the azygous vein (denoted by asterisk) Depiction of the azygous vein (denoted by asterisk). Diagram on the left indicates point at which the azygous enters the SVC and its relationship to intercostal vessels.
30 Treatment aim:alleviating congestive symptoms while simultaneously attempting to make a definitive diagnosis.In cases where suspected or confirmed lung cancer or lymphoma is the cause, institution of radiation therapy may help lessen venous congestion and reduce upper torso, head, and neck venous pressure.Previously, superior vena cava syndrome was considered an emergency. Today, emergent radiation therapy should be reserved for patients with life-threatening laryngeal or cerebral edema.
31 Patients with a confirmed or suspected diagnosis of SVC syndrome based on clinical grounds should undergo CT scanningto define the degree of SVC obstruction andto evaluate for the possibility of thrombotic SVC occlusion (10).If no known tissue diagnosis of cancer has been done,a biopsy is typically performed as an outpatient or inpatient.Adjunctive treatment modalities such as steroids and diuretic therapymay be used, particularly if head and neck edema is a prominent feature.
32 Superior vena cava syndrome caused by lung carcinoma Superior vena cava syndrome caused by lung carcinoma. Notice the ruddy appearance of the patient's face caused by elevation of the arm - Pemberton's sign.
33 Superior vena cava syndrome 1. A complaint of facial swelling should be enough to make the emergency physician consider the diagnosis of SVC syndrome. Partial SVC occlusion or compression above the azygous vein may not lead to any physical exam findings.2. Hoarseness may be a subtle clue when laryngeal edema has developed.3. Stoke’s sign - Face and neck swelling seen in SVC syndrome4. Relatively rare but pathognomonic of SVC syndrome is supine facial cyanosis: development of facial cyanosis when the patient is placed in the supine position.5. Subtle presentations are common and include fatigue (due to poor venous return), dyspnea, chest pain, headache, face and neck swelling, and facial flushing.6. Incidence of thrombotic SVC syndrome is on the rise.7. Symptoms tend to be worse upon awakening secondary to venous pooling.
34 Clinical presentation of a patient with superior vena cava syndrome.
36 Injury/Microorganisms Microcirculatory disturbances DICInjury/MicroorganismsActivation of -PMN -Macrophage -EndotheliumCytokinesSystemic activation of coagulationfibrin formationToxinsMicroclot formationConsumption of coagulation factors and inhibitorsSecondary fibrinolysisMicrocirculatory disturbancesBleedingOrganfailure
37 Thrombotic microangiopathies A THROMBOTIC THROMBOCYTOPENIc PURPURA (TTP) ÉS A HAEMOLYTIC URAEMIC SYNDROM (HUS)Have microvascular platelet aggregation in commonBut.: TTP can be regarded as a systemic dsorder,HUS: is localized to the kidneys.TTP és HUS have very many similarities .Similar starting events :… TTP/HUS complex
38 TTP and HUS consumptive thrombocytopenia microangiopathic haemolytic anaemiaischaemic symptomsTTPHUSTTPHUS
45 Haemolytic uremic syndrome A diagnostic criteria: all the three have to be present)Thrombocytopenia, number megakaryocytes in the BM normal or increased.Fragmentocytic haemolytic anaemia, a direkt Coombs test negatíve (kivéve: neuraminidase infekciókhoz társuló secunder formák).Variable degree of kidney involvement, kidney failureClinical forms:Diarrhoea-asszociated or típical HUS: benign form, mortality less than 10 % .Sporadic or atypical HUS, high mortality, (ca..70 %.) no accurate data on incidence.
46 Treatment of TTP and HUS aim: curative.Only in hospitals with intensive care unitsTreatment: Plasmaexchange, daily,, substitution with fresh frozen plazma or cryo-supernatant : thus % of patients might be cured.Alternativ therapy: Fresh frozen plasma or infusion of fresh frozen plasma: signifivcatnlyx less effective than plasma exchange,Futher drug therapies Corticosteroids - Thrombocyta aggregácion inhibitors? - Vincristine - Immunosuppressive drugs - potentially high dose iv. Ig
47 Supportív therapy:RBC transfusion,Platelet transfusion is usually contraindicated!Treatment of infectionsDialysisIntensive care unit (ritkán gépi lélegeztetés, parenterális táplálás)Treatment of precipitating cause in the case of secondary forms
48 Hematological indications of apheresis I. HyperleukocytosisLeukostasisHigh peripheral cell counts + chemotherapy causing acute cytolysisHigh peripheral cell counts + organomegaly causing severe compression symptomsExtremely hig cell numbers a. myeloproliferatív sy: WBC > 300 G/l b. lymphoproliferatív sy: WBC > 500 G/lThrombocytosisWith complications (threatening ot manifest thrombosis and/or bleedingplt > 1000 G/l + pregnancyplt > 1000 G/l + before a planned operation or coronarography ( maximally 2 aphereses végezhető)4. thr > 1000 G/l + thrombophilia proven by a laboratory testTTPApheresis shlould be stopped in the case of hematological remission or (brain)death
57 Laboratory abnormalities - 2 Significantly elvated serum-LDH (2-20x)se-kreatininvariable (TTP)increased (HUS)Hemostatic abnormalitiesnormál prothrombin, PTI, fibrinogénUrinehaematuria, proteinuria, cylindersCRP: normal or slightly increasedLiver enzymes: normal or slightly increased
58 Differentialdiagnosis TTP or HUSDIC(pre)eclampsia / HELLP sysystemic vasculitidesthrombocytopenia or haemolysis of other causes
59 Treatment results – empiric plasma therapy Idiopathic TTP/HUScomplete haematological remission: %Relapse within 10 years: %Secundary TTP/HUSVariable, depends on underlying cause
60 Evidence based plasmaexchange since the early 1990-s : plazmaexchange / plasma transfusion: prospektíve randomized controlled studyplasmaexhange or plazma transfusion?- Rock: N Engl J Med 1991;325:393- Henon: Transfus Sci 1992; 13:63PLASMAEXCHANGE!
62 Hematological indications of apheresis – II. HUS1. All adult cases 2. Childhood atypical HUS 3. Childhood therapy resistant HUSApheresis should be stopped at the time of haematoligical remission independent of the renal statusHELLP sythrombocytopenia, haemolysis, SGOT >70 U/l, LDH>600 U/l, if:Symptoms persist hours follwing termiantion of pregnancy resistant to conservative treatmentWith postpartum eclampsiaThe usual gynecologic causes of DIC should be excluded before start of apheresis
63 Hematologial indication of apheresis – III. Gammopathieshyperproteinaemia: total protein > 100 g/2. hyperviscosity sy: blood viscosity is more than 15 % above what is normal for the given HtAcute renal failure caused by paraprotein4. polyneuropathyCryoglobulinaemiakryokrit > 1 %, if 1. Raynaud sy and/or necrotising cutan vasculitis 2. cryoglobulinaemic vasculitisCold type AIHAhaemolytic crisisMasszíve intravasal haemolysisImpending renal failure
64 Hypercalcaemia malignus betegségekben Általános jellemzők
65 Hypercalcaemia non-Hodgkin lymphomákban Gyakorisága: összes NHL 4%-a (9/219) (kifejezett mal. NHL: 30%)Mechanizmusa: calcitriol-mediált (19 esetben egyidejű hypercalcaemia és hypercalcitriolaemia)a növekedett calcitriol szint valószínűleg extrarenalis eredetűnincs jellemző csontváltozás
66 In patients taking salicilates, ticlopidin or clopidogrel, no operation should be performed ( no stomatological procedure!)
67 A calcitriol-mediált hypercalcaemia kezelése corticosteroid önmagában is hatásostovábbi kezelési lehetőségekCsontokból calciummobilizáció gátlása (osteoclastok gátlása: calcitonin, biszfoszfonátok)bélből calciumfelszívódás csökkentése: Ca szegény étrendrenalis calciumürítés csökkentése hypovolaemia korrekció FONTOS TOVÁBBÁ: - UV sugárzás kerülése - D vitamin bevitel kerülése