SMI Summary: Investigation of bone marrow
drsuryabrata@gmail.comBecause it is an invasive procedure, bone marrow biopsy (typically collected from the posterior iliac crest or the sternum) is rarely used. It’s also proposed that it shouldn’t be done on people who are immune-competent.
It may be useful in the diagnosis of infection in immunocompromised patients (HIV, transplant patients, or patients on high-dose steroids), caused by a small number of pathogens (listed below).
Some situations where it can be useful are:
- PUO, when other modalities failed to get a diagnosis.
- Infection is a differential diagnosis of a haematological abnormality.
The advantage of bone marrow examination over blood culture:
- It can be positive in both acute and chronic infections. Blood culture is usually positive in acute infection only.
- It is more likely to be positive in patients who have been treated with antibiotics.
Organisms for which it is useful:
| ORGANISM | NOTE |
|---|---|
| Salmonella typhi, Salmonella paratyphi | – Enteric fever is the only bacterial infection for which bone marrow is routinely recommended. – The culture of bone marrow is considered to be the ‘gold standard’ method for the diagnosis of typhoid fever. It has higher sensitivity than both blood culture and serology. |
| Brucella species | – Usual method of investigation: Culture, NAATs and antibody detection (the presence of antibodies is not always indicative of active brucellosis). Recovery from blood is suboptimal. – Culture of bone marrow (as well as liver tissue and lymph nodes) may improve the recovery rate within a shorter time frame. |
| Mycobacterium species | – Culture is considered the ‘gold standard’ method for laboratory diagnosis, however, incubation times may be long. – Bone marrow culture assists in aiding diagnosis in uncertain cases of disseminated disease, particularly in those with HIV. |
| Fungi | – Bone marrow investigation can be performed for Visceral Leishmaniasis. – Splenic puncture is the most sensitive test, but bone marrow examination is safer and has a sensitivity of around 70 – 80%. Following presumptive identification using Giemsa stain to detect amastigotes, send the sample to ref lab for confirmation. Rapid diagnostic tests are direct agglutination and immunochromatographic tests (ICT). Serological diagnosis is significantly less sensitive in those with advanced HIV coinfection than for HIV-negative individuals. Negative results should not, therefore, be used to rule out a diagnosis in those with HIV. |
| Leishmania species | – Bone marrow investigation can be performed for Visceral Leishmaniasis. – Splenic puncture is the most sensitive test, but bone marrow examination is safer and has a sensitivity of around 70 – 80%. Following presumptive identification using Giemsa stain to detect amastigotes, send the sample to ref lab for confirmation. Rapid diagnostic tests are direct agglutination and immunochromatographic tests (ICT). Serological diagnosis is significantly less sensitive in those with advanced HIV coinfection than for HIV negative individuals. Negative results should not, therefore, be used to rule out a diagnosis in those with HIV. |
| Virus | Viral detection indicates infection but does not necessarily confirm a diagnosis of disease. The clinical significance of a positive bone marrow result is dependent on the immune status of the patient and the disease/illness under investigation; positive results from bone marrow samples must therefore be interpreted with caution. In the immunocompromised, blood serology results may be negative at the onset of clinical disease. If there is a high clinical suspicion of viral infection, but peripheral blood NAATs results are negative, diagnosis may be confirmed by bone marrow examination. |
Specimen
The specimen should be put in blood culture bottles; additional samples can be put in leakproof sterile containers. The sample should be as large as possible but remember – volumes of >3mL are likely to be contaminated with peripheral blood which may have a dilution effect.
Safety
If suspecting hazard group 3 organism process in containment level 3 (TB, Salmonella typhi/paratyphi, dimorphic fungi, Brucella). If not suspecting ACDP category 3 (or 4) organism process at containment level 2 but perform all the procedures inside a safety cabinet. Pay attention to the travel history when processing fungus. Dimorphic fungi may present as yeast in blood culture bottles but @ 28-30 degrees on a subculture plate, they may present as highly infectious mould.
Stain
Giemsa, Gram and AFB stain, as and when appropriate.
Culture
Blood culture bottle – subcultured onto – blood agar, chocolate agar, FAA and SAB (when suspecting fungus). Brucella may need 5 days of incubation – check chocolate agar.
Investigation for TB, parasites and Viruses, as appropriate (as per respective SMI).
Identification
To species level.
Methods like MALDI-ToF or NAAT (PCR) are used.
Notification to public health
Notify if any of the listed organisms are isolated – https://www.gov.uk/guidance/notifiable-diseases-and-causative-organisms-how-to-report
