Reticulocyte count is 1-2% in childhood, but can be up to 7% at birth, falling within a few days to 1-3%, and below 1% at 7 days. Preterms tend to have higher counts, which persist for longer. Persistence of reticulocytes or nucleated RBCs may indicate haemolysis (but not always, as neonates have excess oxygen carrying capacity so may not stimulate marrow). Neonates have relative hyposplenism, esp prems, so Howell-Jolly bodies, target cells etc commonly seen. Nonetheless, film is still worthwhile as it may be suggestive of sphero/elliptocytosis, alpha thal, microangiopathy. More reliable at 3-4 months.
IM prophylaxis became the standard route because manufacturers never got round to licensing a product for oral use. It also became routine to give a 1 mg injection, even though this was a thousand times more than the dose of menadione needed each day and 10 times the dose used in the only controlled trial of clinical efficacy ever conducted.
There is uncertainty as to just how common the condition really is. The classic early presentation with dark melaena stools, bloody vomit, nose bleed, blood stained urine, or bleeding from the umbilical stump or after circumcision, two to six days after birth occurs perhaps 1-2 per 1000, but these cases are easily recognised. Then there are those older babies where typically no abnormality is suspected until a catastrophic intracerebral bleed two to 10 weeks after birth (the name HDN is of course inaccurate here). The risk of late bleeding is a half to a third of that of early bleeding. It is only seen in breast fed babies who have never had even a few "complementary" feeds of bottle milk, and who have never received intramuscular vitamin K.
There is no case for giving healthy artifically fed babies vitamin K. It has also become clear that oral prophylaxis can be as reliable as intramuscular prophylaxis: what matters here is not so much the total dose given as the need for the dose regime to allow for the fact that natural body stores are low and turnover is rapid (1-2 days); the large intramuscular dose traditionally given at birth perhaps functions as a slow release "depot" store. Bottle fed babies are at almost no risk because almost all these milks are artificially fortified. The risk of cancer has been addressed in a DoH pooled analysis of 6 matched studies which showed no increase in solid tumours but an increased risk of leukaemia of 25%. However, it is difficult to be sure that children offered prophylaxis and those not are identical populations, for whatever reason.
A single 1 mg IM dose is effective at preventing both early and late disease, as are four 1 mg (or three 2 mg) oral doses once weekly. The only babies not protected are those with liver disease. Konakion MM is licensed for oral use but is expensive and cannot be given by parents. There are no convenient formulations for the third world.
(May-Hegglin abnormality gives giant plts like Bernard Soulier but is asymptomatic!)
Diagnosis: low plt count and normal coag! Check Mum for specific antibodies (1a, 5b at least). Can affect 1st pregnancy if there has been 1st trimester sensitization. NB High index of suspicion as risk of bleed highest in first few days, and antibodies not always detectable, so don't wait for serology before starting treatment.
Treatment:
Platelet count returns to normal in 2 weeks! Counsel Mum's sisters!
Classically Rhesus disease, where a Rhesus negative mum has a Rhesus positive baby (inheriting from the Dad). If mum becomes sensitized (eg after a first baby, or after an antepartum haemorrhage) then she begins to generate antibodies which cause fetal haemolysis. If severe this can lead to anaemia, hydrops, jaundice and kernicterus.
Rhesus disease is due to a D antigen, but there are numerous other red blood cell antigens that can cause problems including (little) c, (big) E, Kell and Duffy (Fya). These alloantibodies should be screened for in pregnancy. If a postitive is found, then the level is loosely predictive of fetal problems (although the rate of rise is also important): under 4 U/ml (or 1:16) is safe, above that, amnio can be done to check baby's group, serial scanning can look at fetal MCA doppler velocity (high suggests severe anaemia) and for signs of hydrops (not always present even in severe anaemia). Fetal blood transfusion is possible to prevent hydrops.
The screening test in a baby is the Direct Coombs test, which detects alloimmunization of any cause. Early (in first 24 hours) jaundice is a clue to an undiagnosed haemolytic process. For antenatally suspected cases, phototherapy can be given prophylactically pending serial bilirubin measurements.
RCOG/NICE recommend 2 doses of Anti-D for Rhesus negative Mums. This deals with the problem of unrecognized feto-maternal haemorrhages. There are no equivalent anti-antigens for other blood groups.
Haemolytic disease with anti-A or B is unusual because not many antigens expressed in neonates. Maternal titres do not appear to correlate with disease in baby. Transfusing babies with maternal anti-A/B may cause significant haemolysis, and DAT (Coombs) may convert from negative to positive! So if exchange transfusion necessary, use Group O with low titre anti-A/B or Group O cells suspended in AB plasma.
X-linked but over 400 genetic variants, so different clinical characteristics. Since mostly asymptomatic until a crisis occurs, many affected adults are unaware of their diagnosis! Girls can be affected depending on the level of enzyme activity associated with their variant, and the degree of Lyonization; or they can be homozygotes even without a family history, if Dad is asymptomatic and Mum a carrier. Screening tests are unreliable in girls, although you are unlikely to miss a severe case as the enzyme level is predictive of phenotype. Anaemia may also reduce sensitivity of screening tests. Rates in some populations are as high as 20% (related to historical malaria incidence); the rate in girls is about a seventh that in boys, but much less in some studies.
With G6PD deficiency, the rate of hyperbilirubinaemia is about 3 times higher, and the rate of exchange transfusion about 10 times higher. Strangely, the jaundice level does not correlate with enzyme activity, probably due to varying impairment of bilirubin conjugation and excretion.
Haemolytic crisis is precipitated by infection esp pneumonia, URTI, gastroenteritis. The intravascular debris can cause renal failure in adults but this is rare in children. Favism, ie haemolysis after ingestion of fava beans, is worse with fresh beans, and can occur via breast milk. But this and haemolysis after drugs (esp primaquine, sulphonamides, nitrofurantoin, mothballs) are variable between patients.
CMV negative blood is preferred for transfusions in the first year of life. Leucodepleted blood has much lower risk, but bags are not usually tested individually to confirm counts. Highest risk of CMV is in under 1.5kg, immunodeficiency and stem cell recipients.
Irradiation is required for:
Packed cells are usually used for top up transfusion. Plasma reduced red cells are more appropriate for severe anaemia and exchange transfusion (less donor exposure than using whole blood).
Exchange transfusion: single-volume exchange will remove 75% of red cells, while a double-volume exchange (160-200 ml/kg, depending on gestation) removes 90% of the initial red cells. A double-volume exchange can remove 50% of available intravascular bilirubin.
Pedipacks reduce donor exposure. Lifespan is 35 days for red cells, 5 days for platelets.
Top up: little evidence for benefit, beyond volume expansion! Some evidence that oxygen delivery is improved and oxygen consumption decreased in bronchopulmonary dysplasia by maintaining a haematocrit more than 0.40 (Alverson et al, 1988).
Erythropoietin does not seem to offer much benefit when given routinely. Better off changing threshold?
Correction of coagulopathy with Fresh Frozen Plasma (FFP) is unpredictable. 15ml/kg is the standard dose. No benefit vs IVH when given routinely. Similarly, platelet transfusion at levels above 50 does not appear to give benefit. A cut off of 20 for term and 50 for preterm in the first days of life seems reasonable, except in alloimmune ITP where HPA antibody inhibits platelet function, so a higher threshold of 30 is used.
Polycythaemia - viscosity rises exponentially above haematocrit of 0.65, esp over 0.68. But symptoms of hyperviscosity (neurological, respiratory, cardiac) correlate poorly. In symptomatic babies, partially exchange with crystalloid aiming for haematocrit of 0.55 (use 4.5% albumin if hypoalbuminaemic).
T antibody - significance of T activation eg in NEC is unclear. If haemolysis develops in these cases, do Lectin test and consider exchange transfusion. Adult plasma almost always contains anti-T so low titre products difficult to source.
British Journal of Haematology Volume 124, Issue 4, Pages 433-453 BCSH guideline 2004
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