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