Appendix 04 - Haematology Guidance

Neonates with DS have recognised differences in their blood cell morphology and counts, which are usually mild and benign and resolve spontaneously by approximately 3 weeks. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2480572/)

Polycythaemia

Approximately 20% of individuals with DS will develop Polycythaemia (Haematocrit 0.65) as a result of increased intrauterine erythropoiesis. In cases where there is an antenatal diagnosis of DS, avoid delayed cord clamping. For management refer to the local guidelines for ‘Polycythaemia’.

Thrombocytopaenia

50% of babies with DS tend to have a platelet count <150 x 109/L but it is important to consider other causes of thrombocytopaenia e.g. Sepsis and IUGR. This tends to be asymptomatic and other than regular monitoring does not require further intervention.

Transient Abnormal Myelopoiesis (TAM)/ Transient Leukaemia of Down Syndrome (TL-DS)

TAM is a disease entity unique to DS and is defined as the morphological detection of blasts at less than 3 months of age. TAM has been reported to occur in 5-30% of neonates with Down Syndrome.

The pathogenesis of TAM is complex and underpinned by mutations in the haemaopoietic transcription factor gene GATA 1, predisposing the individual to impaired Megakaryocytic differentiation and uncontrolled proliferation of megakaryoblasts. The blasts are prevalent in the peripheral blood as opposed to bone marrow, indicating that they are derived from tissues of fetal haematopoiesis e.g. the fetal liver. 

It is usually asymptomatic and spontaneously resolves by 3 months of age although some can develop severe disease including hydrops fetalis, liver fibrosis, renal disease and cardiopulmonary failure.  Clinical features include hepatosplenomegaly, rash and pleural/ pericardial effusions.  Later development of Acute Myeloid Leukaemia (AML) occurs in some.

A FBC and peripheral blood film should be obtained on day 2-3 of life, with a request for a Haematologist experienced at reviewing neonatal blood films to report the film and comment on the peripheral blast percentage if present.  If the blast percentage is >10% and/or there are clinical features suggestive of TAM, urgently discuss with the Paediatric Haematologist on-call at Great Ormond Street Hospital. Furthermore, a blood sample should be sent for GATA1 mutation (discuss with Haematology at GOSH).  If a peripheral blast cell percentage was not performed in the first 3 days of life or there is significant IUGR (blast cell percentage may be suppressed) the neonate will still be at risk of TAM in the first 4-8 weeks of life and be monitored closely (Discuss this with GOSH so there is a unified plan for monitoring).

If TAM is associated with clinical features, monitor closely until there is resolution of symptoms, thereafter monitor FBC and blood film 3 monthly up until 2 years and 6 monthly until the age of 4 years. Likewise if asymptomatic but diagnosed with TAM, monitor FBC and blood film 3 monthly up until 2 years and 6 monthly until the age of 4 years because 20-23% of those with resolved TAM will develop Myeloid Leukaemia of Down Syndrome (ML-DS) in the first 4 years of life.

Persistent lymphopenia/hypogammaglobulinaemia/recurrent infections:

The question relates to interpretation of lymphocyte subsets in patients with T21.  We all talk about the cohort being 'relatively immunodeficient' however we don’t have specific knowledge about the range of 'normal' Lymphocyte subsets (LSS) and Immunoglobulins (Igs). 

Refer to the local haematology clinic/immunology clinic but also consider referral to GOSH immunology:

Immunologist at GOSH, “We try to see T21 patients at least once here if they have been detected to have lymphopenia/hypogammaglobulinaemia/recurrent infections. We are also happy to see them if they haven't had an LSSMEM/IgGAM/vaccine responses checked and/or history of infections.  We see quite a wide spectrum of immunodeficiency in children with T21.  We have a specific clinic where we see children and young people with syndromes like Down Syndrome.  If they are referred into the Immunology Department - even if, as above, with no LSS/IgGAM/vaccine responses done elsewhere - we will triage them into the most appropriate clinic and see the child.”

For haematology advice at Barnet:

Currently based on other pathways and on the DSMIG guidance, we are not doing annual FBC and blood films.  If these tests are required for a clinical reason, and you are requesting a FBC, it is probably worth asking for a blood film routinely to avoid having to re-bleed later for a film if needed.  For any haematology concerns, discuss with the consultant haematologist about the need for a blood film review and ongoing management.  Barnet hospital also has a paediatric haematology clinic run by Dr Maxene Lissack