Dr Harpreet Sehmi, Dr Sanja Zivanovic
You’re the SHO on the neonatal unit reviewing blood tests for a baby admitted earlier in the day. This full term baby has platelets of 88 – what could be going on?
What is thrombocytopenia?
Thrombocytopenia is a platelet count of less than 150 x 109/L.
Thrombocytopenia can be classified like this:
- Mild thrombocytopenia: platelet count 100-150 x 109/L
- Moderate thrombocytopenia: platelet count 50-99 x 109/L
- Severe thrombocytopenia: platelet count < 50 x 109/L
So this baby has moderate thrombocytopenia… how do figure out the cause?
Thinking about the clinical picture
Firstly, is this early or late onset thrombocytopenia? Early onset thrombocytopenia presents within the first 72 hours after birth, while late onset thrombocytopenia is when the thrombocytopenia presents after 72 hours.
Next, is the baby well or unwell?
As with pretty much everything in neonates, this question is important because, infection/sepsis =should be at the top of your list of differential diagnoses, regardless of the time of onset of the thrombocytopenia.
Also, don’t forget to go through the mum’s history and check her platelet count too.
What can cause EARLY onset thrombocytopenia in a well baby?
Placental insufficiency
This is the most common cause of thrombocytopenia. It usually presents when there has been pregnancy induced hypertension, pre-eclampsia, or intrauterine growth restriction. The thrombocytopenia is usually mild to moderate and it improves by itself within 7-10 days.
Immune mediated thrombocytopenia
Immune mediated thrombocytopenia is usually severe (platelets below 50) and happens because of antibodies passing across the placenta from the mum’s circulation to the fetal circulation.
Immune mediated thrombocytopenia can be either:
- Autoimmune – where the mum also has a low platelet count, or
- Alloimmune – when the mum’s platelet count is normal.
Autoimmune thrombocytopenia
Think about this as a differential diagnosis if there is a maternal history of immune thrombocytopenia purpura (ITP) or an autoimmune disease (with or without thrombocytopenia).
Autoimmune thrombocytopenia is when when mum’s antibodies cross the placenta to the baby. Autoimmune thrombocytopenia happens in around 25% of babies whose mothers have ITP. It’s severe in 9-15% of these babies.
When we know a mother has an autoimmune disease or history of ITP, the baby should have their platelets checked at birth (or soon afterwards). If the baby’s platelet count is normal then nothing else needs to be done. If the platelet count is low then it should be repeated in 2-3 days, as it usually drops to the lowest level between day 2 and 5.
These babies might be thrombocytopenic for weeks or months, so will need to be closely followed up for quite a while.
With maternal ITP, it’s really rare for a baby to bleed in utero, even if the mother has severe ITP – so treatment of ITP during pregnancy is mostly based on the risk of bleeding in the mother.
There isn’t much association between fetal platelet counts and maternal platelet counts, platelet antibody levels or history of maternal splenectomy. IVIG given to mums with ITP hasn’t been shown to improve the baby’s platelet count. The only reliable prediction ofneonatal thrombocytopenia is a history of neonatal thrombocytopenia in a previous pregnancy.
Treatment can include intravenous immunoglobulin (IVIG), and platelet transfusion on top if the baby is bleeding.
Neonatal Alloimmune Thrombocytopenia (NAIT):
If it’s early onset severe thrombocytopenia, NAIT is the most common cause. In NAIT, the mother has antibodies against specific human platelet antigen (HPA) which are present in the baby but not in the mother. These antibodies cross the placenta to the baby, meaning that platelets are attacked and there is also reduced platelet production.
The baby inherits the HPA antigen from their father. There are lots of HPA antigens and they vary with ethnic group, for example in caucasians HPA-1a is a major cause of NAIT, followed by HPA-5. NAIT happens in 0.5-1.5 per 1000 live births – so it’s not uncommon to see if you work in a fairly busy neonatal unit.
Severe cases of NAIT can lead to intracranial bleeds, as well as stillbirth and neonatal death – both intracranial bleeds and death can happen as early as 14-16 weeks of pregnancy. About 20% of babies with NAIT have intracranial bleeds (both pre- and postnatally). The bleeds tend to be in the brain tissue rather than in the ventricles. When a mother has had a baby with NAIT, it’s likely that subsequent pregnancies will also be affected – there is about an 80% reoccurrence rate.
The clinical course of NAIT is short in most cases – it often completely resolves within two weeks.
Tests to do if you’re thinking about NAIT:
- Full blood count from the baby to check for thrombocytopenia
- Blood should be collected from the mother, father and baby. The blood is sent to specialist labs for antigen screening. If blood can’tbe taken from the parents, the baby’sblood can be checked for the presence of antiplatelet antibodies.
- All babies with suspected NAIT need to have cranial ultrasounds to check for bleeds.
Managing NAIT:
Management of NAIT differs depending on the following:
Suspected NAIT in a baby – unknown in pregnancy. The management for this includes random donor platelet transfusions for low platelets. If the platelets don’t increase with random donor platelets, then antigen negative platelets are given. IVIG can also be used.
Known case of NAIT: when it’s a known case of NAIT, genotypical matched platelets are first line treatment.
Antenatal management when there is a history of baby with NAIT: The recurrence risk is high. These women should be followed up in high risk obstetric clinic (it is important to highlight this to mums for their future pregnancies). Antenatal genetic testing on the baby is usually performed. Treatment during the pregnancy depends on how severe the thrombocytopenia is, and whether there was an intracranial bleed in the previously affected baby. Treatment can include IVIG+/- steroids starting at 12 weeks or at 20-26 weeks of the pregnancy.
Causes of EARLY onset thrombocytopenia in an UNWELL baby:
Think, Sepsis, Congenital viral or parasitic infections (CMV, HIV, Toxoplasma, enterovirus) and Disseminated intravascular coagulopathy (DIC).
Other (less common) causes of EARLY onset thrombocytopenia
- Hypoxic ischemic encephalopathy (HIE)
- Thrombocytopenia absent radii (TAR) syndrome
- Amegakaryocytic thrombocytopenia with radio-ulnar synostosis
- Fanconi Anaemia
- Trisomies – T21, T18, T13
- Other syndromes: Noonan syndrome, Turner syndrome
- Renal vein thrombosis
- Inborn errors of metabolism
EARLY ONSET THROMBOCYTOPENIA – Flow chart
What can cause LATE onset thrombocytopenia?
The most common causes of late onset thrombocytopenia are:
Remember! In both sepsis and NEC, thrombocytopenia may be the first presenting sign – so be aware of this and don’t dismiss an ‘unexplained’ low platelet count.
Other causes of LATE onset thrombocytopenia:
- Viral infections – HSV, CMV, enterovirus (usually accompanied by deranged LFTs)
- Thrombosis – remember to consider if has central access
- Drug induced thrombocytopenia – heparin, antibiotics (penicillin, cephalosporins, metronidazole, vancomycin, rifampicin), phenobarbital, phenytoin.
- Inborn errors of metabolism
- Fanconi anaemia
- Disseminated Intravascular Coagulation (DIC)
LATE ONSET THROMBOCYTOPENIA – Flow chart
Dr Harpreet Sehmi, Paediaitric trainee, and Dr Sanja Zivanovic, Consultant Neonatologist, Imperial College Healthcare NHS Trust
References
Irene Roberts, Barbara J. Bain. Neonatal Haematology: A Practical Guide. 1st ed. Newark: Wiley, 2022. Chapter 4.
Eichenwald, Eric C. et al., eds. Cloherty and Stark’s Manual of Neonatal Care. Ninth edition / editors, Eric C. Eichenwald, MD, Anne R. Hansen, MD, MPH, Camilia R. Martin, MD, MS, Ann R. Stark, MD. Philadelphia: Wolters Kluwer, 2023.
Fernandes CJ, Neonatal Thrombocytopenia: Etiology. In Up to Date: Connor RF (ed), Wolters Kluwer. (Accessed on January 18, 2024.)
Pejaver RJT, Textbook of Clinical Neonatology. Jaypee Brothers Medical P, 2021