Clinical Guidance. Neonatal Manual Chapter 8: Haematology
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1 Clinical Guidance Neonatal Manual Chapter 8: Haematology Summary This manual contains clinical guidelines developed by the Neonatal Unit multidisciplinary team over recent years. This chapter contains guidelines on haematology. It is linked to and should be used in conjunction with the completed neonatal manual details of which are contained in the introductory chapters. Document Detail Document Type Clinical Guideline Document name Neonatal Manual Chapter 8: Haematology Document location GTi Clinical Guidance Database Version 2.0 Effective from September 2011 Review date September 2013 Owner Clinical Lead, Children s Services Author Timothy Watts, Consultant Neonatologist Approved by, date Neonatal Clinical Governance Group, August 2011 Superseded documents Neonatal Manual Chapter 8: Haematology v1.0 Related documents Neonatal Manual Chapters 1-15 Use of irradiated blood components guideline Blood transfusion for children and neonates guideline Blood Transfusion Policy Keywords Neonatal, Neonatology, Neonatal Unit, Newborn, NNU, NICU, SCBU, anaemia, neutropenia, thrombocytopenia, neonatal alloimmune thrombocytopenia, NAITP, polycythaemia, red cell transfusion, vitamin K, coagulopathy Relevant external law, regulation, standards Change History Date Change details, since approval Approved by
2 CONTENTS 8. Page 8.1 Anaemia and red cell transfusions Polycythaemia Neutropenia Neonatal thrombocytopenia Maternal thrombocytopenia Neonatal clotting abnormalities Vitamin K deficiency bleeding and the administration of vitamin K 16 Page 2 of 17
3 8.1 ANAEMIA AND RED CELL TRANFUSIONS Important causes of anaemia in neonates 1. Blood loss Antepartum haemorrhage (especially placenta praevia) Feto-maternal haemorrhage Feto-fetal haemorrhage Umbilical cord accidents Intraventricular haemorrhage (IVH) Pulmonary haemorrhage 2. Haemolysis if severe anaemia consider exchange transfusion 3. Iatrogenic (blood sampling) - commonest 4. Anaemia of prematurity 5. Bone marrow disorders Normal Hb values: Preterm Term Postnatal term babies weeks 1 day 1 week 2 weeks weeks weeks Hb (g/dl) (14-20) 18.4 (15-23) 17.0 (13-22) 16.8 (13-20) Indications for red cell transfusions are: 1. Significant blood loss 2. Hb < 11 g/dl in a baby 2 weeks old requiring ventilation or NCPAP 3. Hb < 10 g/dl in a baby > 2 weeks old requiring ventilation or NCPAP. Threshold in babies > 28 days old and stable on respiratory support may be lower e.g. 9 g/dl. 4. Hb < 8 g/dl in a stable growing preterm if requiring nasal cannula oxygen, tachycardia of >180, tachypnoea >80 or increasing apnoeas 5. Hb < 7g/dL in any stable, growing preterm baby Thresholds may be higher in any unstable baby (e.g. sepsis, cardiovascular instability, perioperatively etc.). Low reticulocyte count (<100x10 9 /l) may give an indication of likelihood of needing subsequent transfusion in an anaemic preterm baby. Page 3 of 17
4 Crossmatch Except in emergency situations and within the first 12 hours of life, Blood Transfusion requires two blood samples taken at different times from any patient before cross-match will be performed Babies <27 weeks gestation or <800g birth weight should have 6 paediatric packs of red cells allocated at initial crossmatch. At subsequent allocations 3 paediatric packs should be allocated. All other babies should have 3 paediatric packs allocated at each crossmatch/allocation. This will minimise donor exposure. Transfusion Paediatric packs of O RhD negative red cells are available in the blood fridge on Hospital Birth Centre if baby needs emergency transfusion before initial crossmatch has been performed For emergency blood after the immediate newborn period, contact Blood Transfusion (Mon-Fri ext or 80751; all other times bleep 0201) and request a Crash Blood Alert Indications for each transfusion must be documented on the Neonatal Red Cell Transfusion Chart ml/kg (depending on the increment required) or use the formula of desired rise in Hb (g/dl) x weight x 4 - slowly over 4 hours. Consider > 15mL/kg if desired increment > 3g/dL More than 20mL/kg is not usually required except in circumstances such as ongoing blood losses. Furosemide should not be used routinely with blood transfusion. Consider if: - Pre-existing fluid overload (tachycardia, tachypnoea, hepatomegaly, oedema, rise in O 2 requirement) - PDA with evidence of cardiac failure; or other cause of congestive cardiac failure - Chronic lung disease (not an absolute indication) - Renal failure Ensure that all documentation is completed using the Neonatal Red Cell Transfusion Chart Special requirements: neonates may have particular requirements for blood and blood products - CMV negative: all neonates - Irradiated: irradiated blood components should be used to avoid graft versus host disease in the following circumstances Page 4 of 17
5 Babies who have had previous intrauterine transfusions, until 6 months corrected age (top-up transfusions & exchange transfusions); Babies with di George Syndrome; Babies with congenital heart disease <1 month old (including orders for cross match for surgery). This does not include PDA ligations. Exchange transfusions this is recommended unless it is going to significantly delay the exchange Routine top up transfusions do not need to be irradiated. Page 5 of 17
6 8.2 POLYCYTHAEMIA Definition Central venous or arterial PCV >65% Clinical findings May be asymptomatic. Plethora is often present, but is non-specific. Symptoms/signs that should be taken into account when deciding on intervention (see below) are: Lethargy and hypotonia Poor sucking Irritability Convulsions Tachypnoea Hypoglycaemia Complications Cerebrovascular occlusion Renal vein thrombosis Necrotising enterocolitis Myocardial ischaemia Thrombocytopenia Investigations Haemoglobin Arterial or free-flowing venous PCV If twin, check twin s PCV may be anaemic (due to TTTS) Management In all babies at risk, ensure adequate hydration. Treat if: - Central venous or arterial PCV > 70, even if asymptomatic - Central venous or arterial PCV > 65, if symptomatic Hydrate with iv fluids and stop oral feeds If inadequate response to hydration, perform a dilutional exchange transfusion see separate protocol for exchange transfusion. Note: - use 0.9% saline for dilutional exchange (can use 4.5% albumin or FFP) Page 6 of 17
7 - avoid umbilical catheterisation if possible (may increase risk of NEC) - volume needed for exchange (ml) = total blood volume x (observed PCV desired PCV) observed PCV N.B. Neonatal blood volume = 85 ml/kg (approx.) Desired PCV = 55% Aliquots used : 5 20 ml/kg (lower part of range for preterm babies) Page 7 of 17
8 8.3 NEUTROPENIA (neutrophil count <1.5x10 9 /L) Aetiology Infection usually bacterial, don t forget fungal and viral Placental insufficiency IUGR, maternal hypertensive disorders NEC Hypoxia-ischaemia Spurious beware machine differentials as FBC analysers do not always count neutrophils accurately in the newborn period. Always confirm with a manual differential on a blood film Other - Reduced production Fanconi s etc - Immune destruction: neonatal alloimmune neutropenia (NAIN), autoimmune Investigation Request blood film to confirm If baby <5 days old, moderate neutropenia ( x10 9 /L) and significant placental insufficiency no investigations necessary Severe neutropenia (<0.5 x10 9 /L), no previous history of placental insufficiency or 5 days old careful clinical assessment septic screen Treatment No treatment unless neutrophil count <0.5x10 9 /L (severe) and baby very sick Discuss options (eg G-CSF, NAIN investigations) with Paediatric Haematology SpR on Bleep 1621 or Dr Jay Alamelu, Consultant Haematologist Page 8 of 17
9 8.4 NEONATAL THROMBOCYTOPENIA (mild x10 9 /L, moderate x10 9 L, severe <50x10 9 L) Aetiology Preterm (A) Early apparent in first 72 hours of life, usually resolves spontaneously if uncomplicated. 1. Extreme prematurity 2. Placental insufficiency IUGR, maternal PET etc. 3. See also term causes, esp. immune and infection. (B) Late after 72 hours, though may complicate early. 1. Infection usually bacterial, don t forget fungal and viral (esp. CMV, but other congenital infection too). 2. NEC Term 1. Neonatal alloimmune (NAITP) 2. Maternal ITP 3. Infection viral (congenital viral infections e.g. CMV, toxo. etc.), bacterial, fungal 4. Hypoxia-ischaemia 5. Other rarer causes a. Reduced production (e.g Fanconi s, TAR, congenital amegakaryocytic) b. Sequestration (e.g. splenic, Kasabach-Merritt) Page 9 of 17
10 Investigation Early thrombocytopenia Mild Moderate Severe no lx Preterm Term Term Preterm Clotting? Maternal autoimmune disease (check maternal FBC) Clotting Septic screen,?axr TORCH Blood to haematology for NAITP (baby and parents) Late thrombocytopenia Mild moderate Severe Septic screen ± clotting Clotting Septic screen,?axr Urine CMV / TORCH Consider immune and rarer causes Treatment 1. Assess bleeding i.e. IVH, pulmonary, GIT, petechiae, urine 2. If baby <34 weeks gestation, consider recruitment into PlaNet 2 study of platelet transfusion thresholds if the platelet counts <100x10 9 /L 3. If baby not in PlaNet 2 study, treat if: a. Platelet count < 50x10 9 /L and bleeding and/or sick b. Preterm - platelet count < 50x10 9 /L and < 1 week of age - platelet count < 30x10 9 /L and > 1 week of age Page 10 of 17
11 c. Term and platelet count < 20x10 9 /L 4. If NAITP, treat urgently with HPA1a-negative platelets. 5. If maternal ITP (or NAITP with consumption of HPA1a-negative platelets), give IV immunoglobulin, 0.4g/kg/day over 4 hours for 5 days. If unresponsive or platelet count <20x10 9 /L, consider platelet transfusion +/- steroids after consultation. 6. Platelet transfusion (unmatched) for other indications 7. Remember to check whether platelet count has responded to treatment. 8. Consider prophylactic platelet transfusion at platelet count < 50x10 9 /L for lumbar puncture and ibuprofen treatment for PDA. For surgery, we should discuss prophylactic transfusion with anaesthetist +/- surgeon if the platelet count is < 100x10 9 /L. It may be appropriate to ensure platelets are available in theatre. Page 11 of 17
12 8.5 MATERNAL THROMBOCYTOPENIA Maternal ITP 1. FBC on cord blood (preferably) or baby blood soon after birth if platelets >100, repeat FBC day 3-4 if platelets , daily FBC if platelets < 30, repeat FBC after 12 hours 2. Treat if platelets <30 in preterm and <20 in term babies (unless evidence of bleeding (see above)) IV immunoglobulin platelet transfusion consider steroids if unresponsive to immunoglobulin Maternal thrombocytopenia of unknown aetiology 1. FBC on cord blood or baby blood soon after birth if platelet count >150, no need for further investigation; otherwise treat as for maternal ITP. Page 12 of 17
13 8.6 NEONATAL CLOTTING ABNORMALITIES Newborn babies have relatively low concentrations of coagulation factors compared with adults. A variety of disorders can exacerbate this bleeding tendency and lead to significant haemorrhage. Pathophysiology 1. Prothrombin time (PT) ratio - Assesses fibrinogen (I), prothrombin (II), V (common pathway), VII and X (extrinsic pathway) - Prolonged in multiple deficiencies (single deficiencies of these are rare) such as prematurity, liver failure, vitamin K deficiency and DIC. 2. Activated partial thromboplastin time (APTT) ratio - Assesses I, II, V (common pathway), VIII, IX, XI and XII (intrinsic pathway) - Prolonged in multiple deficiencies (as above), haemophilias and with heparin contamination. 3. Fibrinogen concentration - Reduced in DIC or liver dysfunction 4. Thrombin time (TT) - Assesses fibrinogen (function and concentration) and is very sensitive to heparin contamination - Prolonged in DIC and heparin contamination. 5. Reptilase time (RT) similar to TT (assesses fibrinogen), but unaffected by heparin. Page 13 of 17
14 6. Fibrin degradation products (FDPs)/d-dimers raised in DIC. Aetiology 1. Prematurity coagulation factor concentrations are lower at lower gestations PT, APTT, fibrinogen < 1.5g/L (but abnormal if <1.2). 2. DIC particularly following hypoxia/ischaemia and sepsis. thrombocytopenia, PT, APTT, fibrinogen, TT, RT, FDP/d-dimers. 3. Haemorrhagic disease of the newborn (vitamin K deficiency) vitamin K dependent factors are II (prothrombin), VII, IX and X PT, APTT, normal fibrinogen, normal platelets, low factors assays II, VII, IX, X. 4. Liver disease impaired production of clotting factors. Screen in conjugated hyperbilirubinaemia. PT, APTT, may have lowish fibrinogen and platelets, all factor assays low. 5. Inherited disorders commonest are the haemophilias i.e. factor VIII and IX deficiencies. normal PT, APTT, normal fibrinogen and platelets, specific factor assay 6. Heparin contamination normal PT, APTT, normal fibrinogen, TT, normal RT. Investigations - see cascade figure above FBC and clotting screen (usually will be given PT, APTT, fibrinogen) will usually be adequate. It is reasonable to take a clotting screen from a heparinised line in small, difficult babies if you take 2 ml of deadspace first and interpret the result accordingly. You can ask the laboratory to correct for heparinisation (e.g. Reptilase time). Treatment always take coagulation screen results in tandem with platelet count (a) Threshold for treatment 1. Mildly deranged (PT and APTT ratios < 1.5, fibrinogen >1.2g/L) - very common, especially in preterm - no treatment 2. Moderately deranged (PT and/or APTT ratios and/or fibrinogen g/L) usually requires treatment only if baby has significant bleeding 3. Markedly deranged (PT and/or APTT ratios > 2.0 and/or fibrinogen < 0.8g/L) requires treatment if Page 14 of 17
15 - bleeding present - baby is unwell - at high risk of bleeding, esp. preterm babies in the first week of life - associated with severe thrombocytopenia (platelet count < 50x10 9 /L) (b) Management 1. Treat underlying problem (sepsis, HIE, acidosis etc.) 2. Vitamin K ensure it has been given, may require repeated doses. 3. Octaplas (FFP-substitute) first line treatment for all babies who are bleeding, start with 15mL/kg. 4. Cryoprecipitate if fibrinogen remains low (<0.8g/L) despite Octaplas 5. Platelet transfusion if indicated (see separate protocol). 6. Fibrinogen concentrate consider in refractory fibrinogen (especially in DIC). D/W Haemostasis / Haematology SpR/consultant 7. There are other blood products available from Blood Bank (eg specific factor concentrate if specific deficiency found). These should not be given without discussion with Haematology or Haemostasis Consultant. Page 15 of 17
16 8.7 VITAMIN K DEFICIENCY BLEEDING AND THE ADMINISTRATION OF VITAMIN K All babies should receive vitamin K at birth Incidence of vitamin K deficiency bleeding (VKDB) without prophylaxis - early: 1 in newborn babies (1-7 days) - late: 5 in 100,000 babies (2 weeks - 6 months) Breast milk is low in vitamin K whereas formula milks are all fortified. VKDB is therefore commoner in breast fed babies. An increased risk of malignancy was reported in the early 1990s to be associated with the administration of IM vitamin K to the newborn. Subsequent studies demonstrated that solid tumours are certainly no more common in children given IM vitamin K, however, it has not been possible to definitely prove that there is no increased risk of leukaemia. If there is a leukaemia risk, it is extremely small and insignificant compared to the dangers of vitamin K deficiency bleeding. Current NICE guidance is that all babies should receive IM vitamin K Route of administration IM vitamin K is recommended in all babies If parents refuse IM dose, they will be offered oral dosage. This is felt to be the less good option, as there may be problems with supply and compliance with 2 nd and 3 rd doses Dose IM Konakion MM only one dose at birth required BWt 2.5 kg 1 mg BWt <2.5 kg 0.4 mg/kg OR Oral Konakion MM 2-3 doses required as follows: All babies 1. Birth 2 mg 2. 1 week 2 mg Breast fed babies only (<2 bottles formula / day) weeks 2 mg Each mother is issued with a 2 ampoule pack at birth and a vitamin K record card (which should be put in the baby s personal child health record book). Page 16 of 17
17 The doses at birth and 1 week are given by the midwife and the 4-6 week dose by the GP, health visitor or local child health clinic. NB it is not recommended to give vitamin K IV routinely as the depot effect of the IM injection is lost. However if an IV dose only is given at birth further doses will be needed (IM or oral). If dose of oral vitamin K is missed Give 2 doses of oral Konakion MM 2mg one week apart and a third dose of 2mg at 4-6 weeks. If the baby is 4 weeks or older give 3 doses one week apart. If parents refuse administration of vitamin K Midwives should inform Neonatologist on bleep Explain the risks of not giving vitamin K and if they still refuse discuss with registrar or consultant. Page 17 of 17
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