Bone marrow aspiration and biopsy: Indications and technique Author: James LZehnder.MD Section Editor: Richard Alarson MD Deputy Editor: Alan G Rosmarin.MD Contributor Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Lite ature review current through:Jan 2020.This topic last updated:Jan 31,2020. INTRODUCTION Bone marrow examination is useful in the diagnosis and staging of hematologic disease,as well as in the assessment of overall bone marrow cellularity.Because of easy accessibility,aspiration, biopsy.and culture of the bone marrow may also play a role in the assessment of patients with fever of undetermined origin as well as in the diagnosis of various storage and infiltrative disorders. The indications,contraindications,technique,and complications of bone marrow aspiration and biopsy will be reviewed here [1].Evaluation of bone marrow aspirates and biopsies is presented separately.(See "Evaluation of bone marrow aspirate smears".) BACKGROUND INFORMATION The bone marrow is one of the most widely distributed organs in the human body.It is the principal site of blood formation beginning at the time of birth,at which time all bone cavities are filled with hematopoietic tissue.(See "Overview of hematopoietic stem cells"section on'Bone marrow anatomy and microenvironment.) By adolescence,active marrow is usually only found in the cavities of axial bones(sternum,ribs,vertebrae,clavicles,scapulae,skull,pelvis,and the proximal ends of the femurs and hu mer i)[23.Overall bone m approximates 100 percent at birth and declines with time,paralleling an age- associated reduction in hematopoietic activity.Accordingly,bone marrow cellularity in the adult is approximately 50 percent,with the remainder of the marrow being composed of adipose tissue(picture 1).(See"Evaluation of
Bone marrow aspiration and biopsy: Indications and technique Author: James L Zehnder, MD Section Editor: Richard A Larson, MD Deputy Editor: Alan G Rosmarin, MD Contributor Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jan 2020. | This topic last updated: Jan 31, 2020. INTRODUCTION Bone marrow examination is useful in the diagnosis and staging of hematologic disease, as well as in the assessment of overall bone marrow cellularity. Because of easy accessibility, aspiration, biopsy, and culture of the bone marrow may also play a role in the assessment of patients with fever of undetermined origin as well as in the diagnosis of various storage and infiltrative disorders. The indications, contraindications, technique, and complications of bone marrow aspiration and biopsy will be reviewed here [1]. Evaluation of bone marrow aspirates and biopsies is presented separately. (See "Evaluation of bone marrow aspirate smears".) BACKGROUND INFORMATION The bone marrow is one of the most widely distributed organs in the human body. It is the principal site of blood formation beginning at the time of birth, at which time all bone cavities are filled with hematopoietic tissue. (See "Overview of hematopoietic stem cells", section on 'Bone marrow anatomy and microenvironment'.) By adolescence, active marrow is usually only found in the cavities of axial bones (sternum, ribs, vertebrae, clavicles, scapulae, skull, pelvis, and the proximal ends of the femurs and humeri) [2,3]. Overall bone marrow cellularity approximates 100 percent at birth and declines with time, paralleling an ageassociated reduction in hematopoietic activity. Accordingly, bone marrow cellularity in the adult is approximately 50 percent, with the remainder of the marrow being composed of adipose tissue (picture 1). (See "Evaluation of
Under physiologic conditions.all sites of hematopoiesis tend to exhibitunifom neralizations can be made regarding overall hematopoiesis from the evaluati of bone ma arrow at a single site.In most hematologic disorders,study of bone marrow at multiple sites has not been shown to improve diagnostic accuracy [2].Exceptions include malignancies that may have patchy marrow involvement(eg,multiple myeloma,lymphoma,metastatic disease),requiring either larger specimens or specim n multiple sites.(See'Adequacy of the biopsy INDICATIONS The decision to perform a bone marrow evaluation must be made after the critical assessment of pertinentinformation available from the history,physical,and laboratory studies,including a review of the unt(CBC)ande eral blood sme e bonemamrow sxamination isausetultoolin theds and staging of various hematologic diseases and in the assessment of bone marrow cellularity,cellular morphology,and maturation.Highly specialized testing,such as cytogenetic,immunophenotypic,and molecular analyses,can be pert rmed on the pecime ns,and hav become critically important in establishing certain diagnoses,especi ally the le kemias and [3,4].(See "Clinical presentation and diagnosis of non-Hodgkin lymphoma". section on 'Studies on excised tissue'and"Clinical manifestations.pathologic features,and diagnosis of acute myeloid leukemia",section on'Diagnosis'.) In addition to accommodating blood cell formation,the bone marrow also houses a complex stromal complex,along with elements of the monocyte- macrophage system.These supporting cellular svstems may also become involved in a number of systemic diseases.Accordingly,aspiration,biopsy and culture of the bone marrow may have value in the assessment of patients with fever of undetermined ongin and in the diagnosis of varous storage and infiltrative diseases,in which the number and/or activity of these stromal cells may be deranged. Most clinical scenarios require both bone marrow aspiration and biopsy for a complete hematologic evaluation.This is especially true when assessing overall bone marrow cellularity.determinina patterns of marrow involvement. sociated with Hodgkin and non bone marrow aspiration is most often accompanied by biopsy [5-8]
bone marrow aspirate smears", section on 'Estimation of cellularity and myeloid to erythroid ratio'.) Under physiologic conditions, all sites of hematopoiesis tend to exhibit uniform cellularity and cell lineage proportions. Thus, generalizations can be made regarding overall hematopoiesis from the evaluation of bone marrow at a single site. In most hematologic disorders, study of bone marrow at multiple sites has not been shown to improve diagnostic accuracy [2]. Exceptions include malignancies that may have patchy marrow involvement (eg, multiple myeloma, lymphoma, metastatic disease), requiring either larger specimens or specimens from multiple sites. (See 'Adequacy of the biopsy specimen' below.) INDICATIONS The decision to perform a bone marrow evaluation must be made after the critical assessment of pertinent information available from the history, physical, and laboratory studies, including a review of the complete blood count (CBC) and examination of the peripheral blood smear. As noted above, bone marrow examination is a useful tool in the diagnosis and staging of various hematologic diseases and in the assessment of bone marrow cellularity, cellular morphology, and maturation. Highly specialized testing, such as cytogenetic, immunophenotypic, and molecular analyses, can be performed on these specimens, and have become critically important in establishing certain diagnoses, especially the leukemias and lymphomas [3,4]. (See "Clinical presentation and diagnosis of non-Hodgkin lymphoma", section on 'Studies on excised tissue' and "Clinical manifestations, pathologic features, and diagnosis of acute myeloid leukemia", section on 'Diagnosis'.) In addition to accommodating blood cell formation, the bone marrow also houses a complex stromal complex, along with elements of the monocytemacrophage system. These supporting cellular systems may also become involved in a number of systemic diseases. Accordingly, aspiration, biopsy, and culture of the bone marrow may have value in the assessment of patients with fever of undetermined origin and in the diagnosis of various storage and infiltrative diseases, in which the number and/or activity of these stromal cells may be deranged. Most clinical scenarios require both bone marrow aspiration and biopsy for a complete hematologic evaluation. This is especially true when assessing overall bone marrow cellularity, determining patterns of marrow involvement, and searching for evidence of infiltration associated with Hodgkin and nonHodgkin lymphoma, solid malignancies, or storage diseases. Accordingly, bone marrow aspiration is most often accompanied by biopsy [5-8]
Exceptions to this rule are circumstances in which a very specific clinical might be in the question.can beanswered via aCMin nle diagnosis and follow-up of chron relies heavily on cytogenetic and molecular findings,as well as morphology. all of which can be obtained by aspiration or by sampling peripheral blood [4] However.even this is controversial.as some cases of CML may be accompanied by fibrosis,which is best assessed on the biopsy specimen e may be ate for the initial diagnosis of acute leukemia(AM )as well as routine surveillance b one marrow ex aminations on these patients [41.(See "Remission criteria in acute mveloid leukemia and monitoring for residual disease".) Indications for bone marrow evaluation fall into several categories(table 1) .Evaluation of unexplained anemia,leukopenia,thrombocytopenia,or pancytopenia.(See"Approach to the adult with anemia"section on 'Bone marrow examination'and"Laboratory evaluation of neutrophil disorders"and"Approach to the adult with unexplained thrombocytopenia"section on 'Hematologist referral/consultation'and"Approach to the adult with pancytopenia") Evaluation of unexplaine elevations in peripheral blood polycythemia,thrombocytosis,leukocytosis).(See"Diagnostic approach to the patient with polycythemia"and"Approach to the patient with thrombocytosis"and"Approach to the patient with neutrophilia".) .Diagnosis and staging of lymphoma or solid tumors.(See "Clinical presentation and diagnosis of non-Hodgkin lymphoma"section on'Bone marrow examination'and"Pathobiology and staging of small cell carcinoma of the lung",section on'Staging workup'.) .Diagnosis and evaluation of plasma cell disorders and leukemias. (See "Multiple myeloma:Clinical features,laboratory manifestations,and diagnosis",section on'Bone marrow examination'and"Clinical manifestations pathologic features.and diagnosis of acute myeloid leukemia",section on'Bone marrow biopsy and aspirate'.) Evaluation of iron metabolism and stores when routine laboratory testing is inadequate .Evaluation of suspected deposition and storage diseases(eg amyloido aucher dis ease ee "Pathogenesis of immunoglobulin light chain (AL)amyloidosis and light and heavy chain deposition diseases",section on 'Pathogenesis'and"Gaucher disease: Pathogenesis,clinical manifestations,and diagnosis"section on Diagnosis') .Evaluation of fever of undetermined origin,suspected mycobacterial fungal,or parasitic infections,or granulomatous diseases [9-13]. (See "Approach to the adult with fever of unknown origin",section on 'Biopsy.)
Exceptions to this rule are circumstances in which a very specific clinical question can be answered via aspiration alone. An example might be in the diagnosis and follow-up of chronic myeloid leukemia (CML), as the diagnosis relies heavily on cytogenetic and molecular findings, as well as morphology, all of which can be obtained by aspiration or by sampling peripheral blood [4]. However, even this is controversial, as some cases of CML may be accompanied by fibrosis, which is best assessed on the biopsy specimen. Aspiration alone may be adequate for the initial diagnosis of acute myeloid leukemia (AML), as well as routine surveillance bone marrow examinations on these patients [4]. (See "Remission criteria in acute myeloid leukemia and monitoring for residual disease".) Indications for bone marrow evaluation fall into several categories (table 1): ●Evaluation of unexplained anemia, leukopenia, thrombocytopenia, or pancytopenia. (See "Approach to the adult with anemia", section on 'Bone marrow examination' and "Laboratory evaluation of neutrophil disorders" and "Approach to the adult with unexplained thrombocytopenia", section on 'Hematologist referral/consultation' and "Approach to the adult with pancytopenia".) ●Evaluation of unexplained elevations in peripheral blood counts (eg, polycythemia, thrombocytosis, leukocytosis). (See "Diagnostic approach to the patient with polycythemia" and "Approach to the patient with thrombocytosis" and "Approach to the patient with neutrophilia".) ●Diagnosis and staging of lymphoma or solid tumors. (See "Clinical presentation and diagnosis of non-Hodgkin lymphoma", section on 'Bone marrow examination' and "Pathobiology and staging of small cell carcinoma of the lung", section on 'Staging workup'.) ●Diagnosis and evaluation of plasma cell disorders and leukemias. (See "Multiple myeloma: Clinical features, laboratory manifestations, and diagnosis", section on 'Bone marrow examination' and "Clinical manifestations, pathologic features, and diagnosis of acute myeloid leukemia", section on 'Bone marrow biopsy and aspirate'.) ●Evaluation of iron metabolism and stores when routine laboratory testing is inadequate. ●Evaluation of suspected deposition and storage diseases (eg, amyloidosis, Gaucher disease). (See "Pathogenesis of immunoglobulin light chain (AL) amyloidosis and light and heavy chain deposition diseases", section on 'Pathogenesis' and "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis", section on 'Diagnosis'.) ●Evaluation of fever of undetermined origin, suspected mycobacterial, fungal, or parasitic infections, or granulomatous diseases [9-13]. (See "Approach to the adult with fever of unknown origin", section on 'Biopsy'.)
.Evaluation of unexplained splenomegaly. .Confirmation tha t the bone marrov vis normal in a potential allogeneic hematopoietic cell donor in selected patients(rarely nee (See "Donor selection for hematopoietic cell transplantation". CONTRAINDICATIONS The only absolute contraindications to performing a bone marrow biopsy are the presence of severe hemophilia severe disseminated intravascular coagulopathy,or other related severe bleeding disorders.Thrombocytopenia,regardless of severity,is not a contraindication [14.15].Howe ver,depending on the circumstances.platelet transfusion to ins e a platelet count 20.00 may be warranted prio to the procedure [16].(See"Clinical and laboratory aspects of platelet transfusion therapy",section on 'Preparation for an invasive procedure'.) Most hematologists do not consider therapeutic anticoagulation to be ar important nsk factor for bleeding following bone marrow biopsy,although practice patterns in this regard vary widely.As an example,an email survey of members of the australasian society of Thrombosis and Haemostasis and the Hematology Society of Australia and New Zealand asked hematologists about their cu oaches to pe ng bone sy among thrombocytopenic or anticoagulated patients.Results of this informal survey included the following [17] .In thrombocytopenic patients,48 percent did nottransfus platelets,49 percent transfused platelets only in selected patients.and 3 percent transfused platelets routinely. .In anticoaqulated patients.13 percent performed the biopsy irrespective of the INR,51 percent performed the biopsy if the INR was not above the therapeutic range .18 percent performed the bi opsy if the e INR was<2.0 and 18 percent stopped warfarin or reversed anticoagulation before performing the biopsy. There is little or noinformation conceming the risk of bleeding following bone marrow aspiration/biopsy in patients who are taking one or more antiplatelet agents.It is the general consensus that bone marrow aspiration/biopsy is a low-risk procedure and that the risk of thrombosis from stopping these agents prior to the biopsy is greater than the risk of bleeding if these agents are not stopped.(See"P erioperative management of patients receiving anticoaqulants",section on Estimating thromboembolic risk'and"Perioperative medication management",section on 'Medications affectina hemostasis') Post-procedural bleeding,if any,is almost always controlled by manual application of pressure to the site.(See 'Bleeding'below.)
●Evaluation of unexplained splenomegaly. ●Confirmation that the bone marrow is normal in a potential allogeneic hematopoietic cell donor in selected patients (rarely needed). (See "Donor selection for hematopoietic cell transplantation".) CONTRAINDICATIONS The only absolute contraindications to performing a bone marrow biopsy are the presence of severe hemophilia, severe disseminated intravascular coagulopathy, or other related severe bleeding disorders. Thrombocytopenia, regardless of severity, is not a contraindication [14,15]. However, depending on the circumstances, platelet transfusion to insure a platelet count >20,000/microL may be warranted prior to the procedure [16]. (See "Clinical and laboratory aspects of platelet transfusion therapy", section on 'Preparation for an invasive procedure'.) Most hematologists do not consider therapeutic anticoagulation to be an important risk factor for bleeding following bone marrow biopsy, although practice patterns in this regard vary widely. As an example, an email survey of members of the Australasian Society of Thrombosis and Haemostasis and the Hematology Society of Australia and New Zealand asked hematologists about their current approaches to performing bone marrow biopsy among thrombocytopenic or anticoagulated patients. Results of this informal survey included the following [17]: ●In thrombocytopenic patients, 48 percent did not transfuse platelets, 49 percent transfused platelets only in selected patients, and 3 percent transfused platelets routinely. ●In anticoagulated patients, 13 percent performed the biopsy irrespective of the INR, 51 percent performed the biopsy if the INR was not above the therapeutic range, 18 percent performed the biopsy if the INR was <2.0, and 18 percent stopped warfarin or reversed anticoagulation before performing the biopsy. There is little or no information concerning the risk of bleeding following bone marrow aspiration/biopsy in patients who are taking one or more antiplatelet agents. It is the general consensus that bone marrow aspiration/biopsy is a low-risk procedure and that the risk of thrombosis from stopping these agents prior to the biopsy is greater than the risk of bleeding if these agents are not stopped. (See "Perioperative management of patients receiving anticoagulants", section on 'Estimating thromboembolic risk' and "Perioperative medication management", section on 'Medications affecting hemostasis'.) Post-procedural bleeding, if any, is almost always controlled by manual application of pressure to the site. (See 'Bleeding' below.)
Patients with suspected multiple myeloma or other disorders associated with bone resorption should not unde 90 mal bone marrow ration due to ar ncre ased of st temnal per foration.Bone marrow biopsy of the sternum should never be attempted in any patient,due to the fragility of the bone at this site as well as its proximity to the heart and great vessels Precautions may need to be taken if there is skin infection oroste omyelitis in the area of proposed aspiration or biopsy,or if the patient is unable to remain still for the procedure.Several complications may accompany bone marrow aspiration or biopsy despite adherence to these precautions (see 'Comp s'below). ADVANCE PREPARATION A number of important issues need to be resolved before the procedure is undertaken,including choice of the biopsy site,use of premedications and the need for an assistant,as well as determining the need and preparation necessary for specialized tests to be performed on the marrow specimens. Deciding which tests are needed-The tests that are obtained depend on the clinical scenario and the diagnoses that are being considered. Before starting the procedure,decisions should be made about whether both an aspirate and biopsy are required.and if special samples are needed for additional tests(eg.cytogenetics,flow cytometry,special stains)(table 2).A discussion with the hematopath logy labo atory should ccur before the procedure is undertaken to make sure that the appropriate samples,sample collection vials,and tests have been agreed upon.As examples,cytogenetic testing requires live cells,ideally in culture medium(not formalin-fixed cells). and special stains may require more slides than are routinely prepared. Signed informed consent must be obtained in advance from the patient, parent.or health care proxy.as appropriate. Timing of the procedure-Obtaining the sample when laboratory personnel are available for discussion and optimal specimen handling is generally preferable.However.in certain cases it may be necessary to obtain the sample in off-hours.Examples may include mple before glucocorticoids are administered to a patient with possible lymphoid malignancy.Importantly,however,treatment of the patient should not be delayed solely to obtain a better sample. It is also preferable to have a complete blood count(CBC)with differential and blood smear that was obtained on the same day as the bone marrow sample
Patients with suspected multiple myeloma or other disorders associated with bone resorption should not undergo sternal bone marrow aspiration due to an increased risk of sternal perforation. Bone marrow biopsy of the sternum should never be attempted in any patient, due to the fragility of the bone at this site as well as its proximity to the heart and great vessels. Precautions may need to be taken if there is skin infection or osteomyelitis in the area of proposed aspiration or biopsy, or if the patient is unable to remain still for the procedure. Several complications may accompany bone marrow aspiration or biopsy despite adherence to these precautions (see 'Complications' below). ADVANCE PREPARATION A number of important issues need to be resolved before the procedure is undertaken, including choice of the biopsy site, use of premedications and the need for an assistant, as well as determining the need and preparation necessary for specialized tests to be performed on the marrow specimens. Deciding which tests are needed — The tests that are obtained depend on the clinical scenario and the diagnoses that are being considered. Before starting the procedure, decisions should be made about whether both an aspirate and biopsy are required, and if special samples are needed for additional tests (eg, cytogenetics, flow cytometry, special stains) (table 2). A discussion with the hematopathology laboratory should occur before the procedure is undertaken to make sure that the appropriate samples, sample collection vials, and tests have been agreed upon. As examples, cytogenetic testing requires live cells, ideally in culture medium (not formalin-fixed cells), and special stains may require more slides than are routinely prepared. Signed informed consent must be obtained in advance from the patient, parent, or health care proxy, as appropriate. Timing of the procedure — Obtaining the sample when laboratory personnel are available for discussion and optimal specimen handling is generally preferable. However, in certain cases it may be necessary to obtain the sample in off-hours. Examples may include obtaining a sample before glucocorticoids are administered to a patient with possible lymphoid malignancy. Importantly, however, treatment of the patient should not be delayed solely to obtain a better sample. It is also preferable to have a complete blood count (CBC) with differential and blood smear that was obtained on the same day as the bone marrow sample
to allow identification of specific cells and to correlate the bone marrow cellularity with cytopenias in the peripheral blood Choice of aspiration or biopsy site-The iliac crest is the only site at which both aspiration and biop sy may be safely performed in the adult. .The poste superior ilia cres nd spine(fiqure 1)is the favore ed site of examination in the adult,as well as in the child and in most infants This site also provides the least discomfort to the patient compared with other sites. .The anterior iliac crest(fiqure 2)may be used for bone marrow as n nd biopsy in ad when access the posterior ilia crest is limited (eg,the patient is unable to be moved for proper access to the chosen aspiration site.morbid obesity.skin diseases.or previous radiation)[2.14].An initial attempt to sample the posteror iliac bone may be worthwhile even in neonates b may be rnbs.s8eater obtained fro m the trochanter of th ur,individu vertebral bodies IC procedures,including open bone biopsies,are best obtained through surgical consultation,and may require CT guidance(see 'Surgical iopsy'below). .Obtaining bone marrow fro m a site which has been previously irradiated o yield subopt espe overa cellularity.Another site should be chosen if at all possible. Bone marrow may be aspirated from the stemumin patients over 12 years of age(fiqure 3),although biopsy at this site is contr because of it minimal thickness.Special care needs to be taken if this site is chosen for marrow aspiration,since penetration of the inner table of the stemnum or penetration through a rib interspace may lead to fatal hemorrhage (see 'Complications'below). In premature infants and some full-terminfants,the iliac bone has not completely ossified,and an altemative bone(eg,the anterior portion of the tibia)should be used [18).If the anterior tibia must be entered,it should only b sed for aspiration and limited to infants younger than 18months of age On occasion,it may not be possible to identify an aspiration/biopsy site e cause of t ence of excessive adipose tissue;su rface landmarks s may be difficult to identify and/or the available needle may not reach the bone surface (see 'Technique'below and'Needle selection'below).If these maneuvers have failed,one solution is to perform the procedure using computed tomography (CD quidance [191. In cases in which the landmarks can be identified but the needle is too short, a trephine biopsy needle may be used for both the aspiration and biopsy. (See 'Needle selection'below.)
to allow identification of specific cells and to correlate the bone marrow cellularity with cytopenias in the peripheral blood. Choice of aspiration or biopsy site — The iliac crest is the only site at which both aspiration and biopsy may be safely performed in the adult. ●The posterior superior iliac crest and spine (figure 1) is the favored site of examination in the adult, as well as in the child and in most infants. This site also provides the least discomfort to the patient compared with other sites. ●The anterior iliac crest (figure 2) may be used for bone marrow aspiration and biopsy in adults when access to the posterior iliac crest is limited (eg, the patient is unable to be moved for proper access to the chosen aspiration site, morbid obesity, skin diseases, or previous radiation) [2,14]. An initial attempt to sample the posterior iliac bone may be worthwhile, even in neonates. ●In selected cases, bone marrow may be obtained from the greater trochanter of the femur, individual vertebral bodies, or ribs. Such procedures, including open bone biopsies, are best obtained through surgical consultation, and may require CT guidance (see 'Surgical biopsy' below). ●Obtaining bone marrow from a site which has been previously irradiated is likely to yield suboptimal results, especially in terms of overall cellularity. Another site should be chosen if at all possible. Bone marrow may be aspirated from the sternum in patients over 12 years of age (figure 3), although biopsy at this site is contraindicated because of its minimal thickness. Special care needs to be taken if this site is chosen for marrow aspiration, since penetration of the inner table of the sternum or penetration through a rib interspace may lead to fatal hemorrhage (see 'Complications'below). In premature infants and some full-term infants, the iliac bone has not completely ossified, and an alternative bone (eg, the anterior portion of the tibia) should be used [18]. If the anterior tibia must be entered, it should only be used for aspiration and limited to infants younger than 18 months of age. On occasion, it may not be possible to identify an aspiration/biopsy site because of the presence of excessive adipose tissue; surface landmarks may be difficult to identify and/or the available needle may not reach the bone surface (see 'Technique' below and 'Needle selection' below). If these maneuvers have failed, one solution is to perform the procedure using computed tomography (CT) guidance [19]. In cases in which the landmarks can be identified but the needle is too short, a trephine biopsy needle may be used for both the aspiration and biopsy. (See 'Needle selection' below.)
Premedications-the pain perceived by the patientdurina bone marrow biopsy pero ed underlocal anesthesia is lo vto moderate being approx on a 0 to 10 scale in one stu dy [20]and 1.7 on a0 to5 scale in another [21].While premedications,including anxiolytics or opiates. are notusually necessary [221.certain individuals with underlving dense bone structure.pain issues.or those with heightened anxiety may benefit from the use of such agents.It cannot be overstated that the quality of the specimen obtained may be stly superior in cooperativ e and com patient. In children with procedure phobias,the use of lorazepam under carefully dnican be very beneficial.producing bothreax antegrade zepan n or trama may na nilar adults with anxiety [23-26].This can be particularly helpful if the child or anxious adultis likely to require multiple bone marrow evaluations over a period of time,as in the treatment of acute leukemia.A safe conscious sedation policy should be in place prior to using drugs such as benzodiazepines or opioids in patients of any age The use of inhaled nitrous oxide and oxvaen.an established combination used for pain management and sedation in certain gynecologicprocedures well-tole erated and effective for u se during bone marrow aspiration and biopsy:use of this agent may diminish the risk of prolonged sedation associated with benzodiazepine or opioid dosing [27-29]. However,given the limited nature of these studies,further research may be required before the use of nitrous oxide/oxygen is accepted into standard practice Any premedications should be administered in a timely fashion,prior to Use of an assistant-Bone marrow aspirates and biopsies often clot within minutes of being ained.During this time, h n perf the procedure may still be busy performing an aspiration or biopsy at the same or another site,reassuring the patient,or initiating local hemostasis.Ideally, bone marrow aspiration and biopsy be carried out with the help of a trained pare the slides and specimens or who assist tant who can either nepp completion of the procedure. in achieving adequate hemos Needle selection-Disposable aspiration and biopsy needles are preferred in order to guarantee sterility and sharpness,as well as to reduce procedure- and"failure"rat [301 Allc vailable needles are lfor piraion and biopy ofcrestForste the needle should have a guard which screws securely to a selected portion of the needle in order to limit its penetration(see'Stemal aspiration'below)
Premedications — The pain perceived by the patient during bone marrow aspiration and biopsy performed under local anesthesia is low to moderate, being approximately 3 on a 0 to 10 scale in one study [20] and 1.7 on a 0 to 5 scale in another [21]. While premedications, including anxiolytics or opiates, are not usually necessary [22], certain individuals with underlying dense bone structure, pain issues, or those with heightened anxiety may benefit from the use of such agents. It cannot be overstated that the quality of the specimen obtained may be vastly superior in a cooperative and comfortable patient. In children with procedure phobias, the use of lorazepam under carefully controlled conditions can be very beneficial, producing both relaxation and antegrade amnesia; lorazepam or tramadol may have a similar effect in adults with anxiety [23-26]. This can be particularly helpful if the child or anxious adult is likely to require multiple bone marrow evaluations over a period of time, as in the treatment of acute leukemia. A safe conscious sedation policy should be in place prior to using drugs such as benzodiazepines or opioids in patients of any age. The use of inhaled nitrous oxide and oxygen, an established combination used for pain management and sedation in certain gynecologic procedures and in sigmoidoscopy, is both well-tolerated and effective for use during bone marrow aspiration and biopsy; use of this agent may diminish the risk of prolonged sedation associated with benzodiazepine or opioid dosing [27-29]. However, given the limited nature of these studies, further research may be required before the use of nitrous oxide/oxygen is accepted into standard practice. Any premedications should be administered in a timely fashion, prior to performing the procedure, in order to allow for the desired effects [25,26]. (See "Procedural sedation in children outside of the operating room".) Use of an assistant — Bone marrow aspirates and biopsies often clot within minutes of being obtained. During this time, the person performing the procedure may still be busy performing an aspiration or biopsy at the same or another site, reassuring the patient, or initiating local hemostasis. Ideally, bone marrow aspiration and biopsy be carried out with the help of a trained assistant who can either help prepare the slides and specimens or who assist in achieving adequate hemostasis following completion of the procedure. Needle selection — Disposable aspiration and biopsy needles are preferred in order to guarantee sterility and sharpness, as well as to reduce procedurerelated pain and "failure" rates [30]. All commercially available needles are acceptable for aspiration and biopsy of the iliac crest. For sternal aspiration, the needle should have a guard which screws securely to a selected portion of the needle in order to limit its penetration (see 'Sternal aspiration' below)
Occasionally,in obese or large patients,it may be necessary to use a Sequence of aspiration and biops -Althouah the techniques used fo obtaining bon e marrow aspiration and biopsy samples have be nfairly we standardized.there has been some debate as to the sequence of aspiration and biopsy: .Prior studies have demonstrated artifactual reduction in overall cellularity of the bone marrow sample due to acute intramedullary hemorrhage in th when aspiration was foll eRways6moeoenetyo wed by bi psy [31].This ning a longer,deeper specimen which bypasses the aspiration site [32]. .Altemnatively,biopsy followed by aspiration could lead to premature clotting of the aspirated specimen. Despite these issues,it is generally felt that high quality specimens can be obtained,regardless of the order,provided that separate needles and 8ap8ce0e8owocentmeesapanaongheiaces0aeusedio Adequacy of the biopsy specimen-Biopsies consisting mostly of cortical bone.cartilage,or muscle,v are least 5 mm in length.In some cases,more extensive sampling may be required. Obtaining an adequate biopsy from a single site in a patientwith non-Hodgkin ymphoma(NHL)has been deemed inadequate by a number of studies. (See"Clinical presentation and diagnosis of non-Hodgkin lymphoma",section on Bone marrow examination'.) .An early study involving 282 patients with lymphoma and other neoplastic diseases revealed accurate diagnosis with unilateral biopsy in only 22 percent of patients with NHL,43 percent of patients with Hodgkin ympho and 36 pe t of th ewith other neoplastic sses [33]. The investigators concluded that bilateral sampling could yield ar additional 11 to 22 percent of positive biopsies. .Another study,including 170 specimens from 145 patients,found that accurate diagnosis improved 26 percent when bilateral specimens were obtained [341 A third study of 260 patients with NHL revealed that 30 percent of positive marrows had unilateral involvement only,supporting the need for bilateral sampling [35]
Occasionally, in obese or large patients, it may be necessary to use a trephine biopsy needle for both the aspiration and biopsy at the iliac crest, as this needle tends to be longer than a standard aspiration needle. Sequence of aspiration and biopsy — Although the techniques used for obtaining bone marrow aspiration and biopsy samples have been fairly well standardized, there has been some debate as to the sequence of aspiration and biopsy: ●Prior studies have demonstrated artifactual reduction in overall cellularity of the bone marrow sample due to acute intramedullary hemorrhage in the biopsy specimen when aspiration was followed by biopsy [31]. This effect was shown to be overcome by obtaining a longer, deeper specimen which bypasses the aspiration site [32]. ●Alternatively, biopsy followed by aspiration could lead to premature clotting of the aspirated specimen. Despite these issues, it is generally felt that high quality specimens can be obtained, regardless of the order, provided that separate needles and separate sites (one to two centimeters apart along the iliac crest) are used for each procedure [32]. Adequacy of the biopsy specimen — Biopsies consisting mostly of cortical bone, cartilage, or muscle, without sufficient sampling of the medullary cavity are inadequate for proper evaluation. Most laboratories require a sample at least 5 mm in length. In some cases, more extensive sampling may be required. Obtaining an adequate biopsy from a single site in a patient with non -Hodgkin lymphoma (NHL) has been deemed inadequate by a number of studies. (See "Clinical presentation and diagnosis of non-Hodgkin lymphoma", section on 'Bone marrow examination'.) ●An early study involving 282 patients with lymphoma and other neoplastic diseases revealed accurate diagnosis with unilateral biopsy in only 22 percent of patients with NHL, 43 percent of patients with Hodgkin lymphoma, and 36 percent of those with other neoplastic processes [33]. The investigators concluded that bilateral sampling could yield an additional 11 to 22 percent of positive biopsies. ●Another study, including 170 specimens from 145 patients, found that accurate diagnosis improved 26 percent when bilateral specimens were obtained [34]. ●A third study of 260 patients with NHL revealed that 30 percent of positive marrows had unilateral involvement only, supporting the need for bilateral sampling [35]
However,adequate length of a unilateral biopsy may obviate the need for bilateral examination .In one study,a biopsy length of 19.5 mm was the smallest acceptable length,leading to a 50 percent chance of detecting bone marrow stases [36 tudy concluded that one 20 mm-long specimen could obviate the need for bilateral bone marrow sampling in patients being evaluated for the presence of diffuse large B-cell NHL [37]. TECHNIQUE Materials-The supplies necessary for a bone marrow biopsy and aspiration.with the exception of sterile gloves and vials for specific studies on the collected samples,are conventionally packaged in a single tray.The contents should include all of the following: .Povidone-iodine antiseptic solution for cleansing the chosen site,along with the necessary drapes to maintain sterility at the site A1 or 2 percer lidocaine solution for local anesthesia,along with a sterile syringe,a 23-gauge and a 21-gauge needle .A number 11 scalpel blade for making the skin incision prior to inserting the aspiration and biopsy needles .Sufficient quantities of sterile gauze and bandages to clean the biopsy site and to apply local pressure to insure hemostasis wi hen the proced ure has been completed .A large selection of needles used for aspiration is available.a needle with a stylet that can be fixed in place initially and removed later is oreferred.it is important to use a sharp needle.as well as one long enough to penetrate through the subcutaneous tissues and into the marrow cavity.A needle osen for stemal aspiration should be shorte than one used for aspiration at the iliac crest.and should be equipped with a guard to insure controlled entrance into(and not beyond)the stemal marrow cavity (see'Sternal aspiration'below). .Jamshidi biopsy needle with stylet and a device (obturator)for removing the biopsy core from the needle with amage to e specimen Posterior iliac crest-Proper bone marrow aspiration and biopsy requires strict attention to detail.The following items should be completed in the order in which they appear .Administer any necessary premedications(anti-anxiolytics or pain medications)(see 'Premedications'above). .The patient should be placed in either a prone or lateral decubitus position.In heavier patients,a lateral decubitus position with the knees
However, adequate length of a unilateral biopsy may obviate the need for bilateral examination: ●In one study, a biopsy length of 19.5 mm was the smallest acceptable length, leading to a 50 percent chance of detecting bone marrow metastases [36]. ●Another study concluded that one 20 mm-long specimen could obviate the need for bilateral bone marrow sampling in patients being evaluated for the presence of diffuse large B-cell NHL [37]. TECHNIQUE Materials — The supplies necessary for a bone marrow biopsy and aspiration, with the exception of sterile gloves and vials for specific studies on the collected samples, are conventionally packaged in a single tray. The contents should include all of the following: ●Povidone-iodine antiseptic solution for cleansing the chosen site, along with the necessary drapes to maintain sterility at the site ●A 1 or 2 percent lidocaine solution for local anesthesia, along with a sterile syringe, a 23-gauge and a 21-gauge needle ●A number 11 scalpel blade for making the skin incision prior to inserting the aspiration and biopsy needles ●Sufficient quantities of sterile gauze and bandages to clean the biopsy site and to apply local pressure to insure hemostasis when the procedure has been completed ●A large selection of needles used for aspiration is available. A needle with a stylet that can be fixed in place initially and removed later is preferred. It is important to use a sharp needle, as well as one long enough to penetrate through the subcutaneous tissues and into the marrow cavity. A needle chosen for sternal aspiration should be shorter than one used for aspiration at the iliac crest, and should be equipped with a guard to insure controlled entrance into (and not beyond) the sternal marrow cavity (see 'Sternal aspiration' below). ●Jamshidi biopsy needle with stylet and a device (obturator) for removing the biopsy core from the needle without damage to the specimen. Posterior iliac crest — Proper bone marrow aspiration and biopsy requires strict attention to detail. The following items should be completed in the order in which they appear: ●Administer any necessary premedications (anti-anxiolytics or pain medications) (see 'Premedications' above). ●The patient should be placed in either a prone or lateral decubitus position. In heavier patients, a lateral decubitus position with the knees
pulled closer to the chest,or a prone position accompanied by pressure over the bone,may help to dentify女 ndmarks by reducing the depth of the fat pad overlying the iliaccrest[38 .Examine the potential site for evidence of infection:palpate the posteno iliac crest and posterior superior iliac spine and locate these landmarks (fiaure 1)1391 The anterior superior iliac spine should also be palpated and located,as the needle will be pointed in this direction once the bone s been entered(fiqure 2) .Maintain a steady dialogue with the patient,explaining each step. alerting the patient to potential discomfort,with reassurance as needed. .In the absence of local skin problems(eg,infection,induration, ulceration).the usual site for aspiration and biopsy is approximately three s from the midline and two finger- widths int or to the iliac crest.Mark the chosen area by making an indentation in the skin with a coin,fingemail,or the end of a ballpoint pen with the writing tip retracted .Using sterile technique,protective clothing and gloves(and eye wear if necessary),the bone marrow tray should be first opened and organized for easy access to needed ito ems.Needi stylets, and plastic (not glass) syringes should be checked to ensure that they are intact and function propeny. .Cleanse the chosen area with povidone-iodine solution and drape a sterile field.Prepare the instruments. .Anesthetize the skin and subcutaneous tissues with a 1 to 2 percent lidocaine sol n using a 23-gauge needle:th en anesthetize the periosteum by repeatedly injecting small amounts of lidocaine solution at different points on the surface of the bone with a 21-gauge needle.It is useful to anesthetize a dime-sized area of the periosteum surrounding the tar nt adjacentsites .While waiting for the anesthetic to produce its effect,extra syringes for special studies(eg,flow cytometry,cytogenetics,and molecular studies) can be appropriately anticoagulated.Specimens for molecular studies should not contain heparin the help of an assistant is invaluable .Once local anesthesia has been achieved,make a small (3 mm)skin incision with a scalpel blade at the site of insertion of the aspiratior needle.in order to facilitate its entry and promote organized healing of the wound. .Hold the bone marrow needle (with stylet in place)perpendicular to the skin at the previously marked point,and gently advance it to the periosteur In order to be ure hat the edle is e ente ectly,the second and third fingers on the hand not being used to insert the needle should be placed on the iliac crest or spine and the needle inserted between them [3].When the needle has been advanced to the periosteum,it should be pointed laterally in the direction of the anterior
pulled closer to the chest, or a prone position accompanied by pressure over the bone, may help to identify the landmarks by reducing the depth of the fat pad overlying the iliac crest [38]. ●Examine the potential site for evidence of infection; palpate the posterior iliac crest and posterior superior iliac spine and locate these landmarks (figure 1) [39]. The anterior superior iliac spine should also be palpated and located, as the needle will be pointed in this direction once the bone has been entered (figure 2). ●Maintain a steady dialogue with the patient, explaining each step, alerting the patient to potential discomfort, with reassurance as needed. ●In the absence of local skin problems (eg, infection, induration, ulceration), the usual site for aspiration and biopsy is approximately three finger-widths from the midline and two finger-widths inferior to the iliac crest. Mark the chosen area by making an indentation in the skin with a coin, fingernail, or the end of a ballpoint pen with the writing tip retracted. ●Using sterile technique, protective clothing and gloves (and eye wear if necessary), the bone marrow tray should be first opened and organized for easy access to needed items. Needles, stylets, and plastic (not glass) syringes should be checked to ensure that they are intact and function properly. ●Cleanse the chosen area with povidone-iodine solution and drape a sterile field. Prepare the instruments. ●Anesthetize the skin and subcutaneous tissues with a 1 to 2 percent lidocaine solution using a 23-gauge needle; then anesthetize the periosteum by repeatedly injecting small amounts of lidocaine solution at different points on the surface of the bone with a 21-gauge needle. It is useful to anesthetize a dime-sized area of the periosteum surrounding the targeted location, as the aspiration and biopsy should be taken from slightly different adjacent sites. ●While waiting for the anesthetic to produce its effect, extra syringes for special studies (eg, flow cytometry, cytogenetics, and molecular studies) can be appropriately anticoagulated. Specimens for molecular studies should not contain heparin. The help of an assistant is invaluable. ●Once local anesthesia has been achieved, make a small (3 mm) skin incision with a scalpel blade at the site of insertion of the aspiration needle, in order to facilitate its entry and promote organized healing of the wound. ●Hold the bone marrow needle (with stylet in place) perpendicular to the skin at the previously marked point, and gently advance it to the periosteum. In order to be sure that the needle is entering correctly, the second and third fingers on the hand not being used to insert the needle should be placed on the iliac crest or spine and the needle inserted between them [3]. When the needle has been advanced to the periosteum, it should be pointed laterally in the direction of the anterior